title: Early introduction and rise of the Omicron SARS-CoV-2 variant in highly vaccinated university populations

abstract: The Omicron variant of SARS-CoV-2 is transmissible in vaccinated and unvaccinated populations. Here, we describe the rapid dominance of Omicron following its introduction to three Massachusetts universities with asymptomatic surveillance programs. We find that Omicron was established and reached fixation earlier on these campuses than in Massachusetts or New England as a whole, rapidly outcompeting Delta despite its association with lower viral loads. These findings highlight the transmissibility of Omicron and its propensity to fixate in small populations, as well as the ability of robust asymptomatic surveillance programs to offer early insights into the dynamics of pathogen arrival and spread.


title: Graph Convolutional Neural Networks for Histological Classification of Pancreatic Cancer

abstract: Pancreatic ductal adenocarcinoma has some of the worst prognostic outcomes among various cancer types. Detection of histologic patterns of pancreatic tumors is essential to predict prognosis and decide about the treatment for patients. This histologic classification can have a large degree of variability even among expert pathologists. This study proposes a graph convolutional network-based deep learning model to detect aggressive adenocarcinoma and less aggressive pancreatic tumors from benign cases. Our model uses a convolutional neural network to extract detailed information from every small region in a whole-slide image. Then, we use a graph architecture to aggregate the extracted features from these regions and their positional information to capture the whole-slide level structure and make the final prediction. We evaluated our model on an independent test set and achieved an F1 score of 0.85 for detecting neoplastic cells and ductal adenocarcinoma, significantly outperforming other baseline methods. If validated in prospective studies, this approach has a great potential to assist pathologists in identifying adenocarcinoma and other types of pancreatic tumors in clinical settings.

category: pathology


title: Systematically omitting indoor air quality: sub-standard guidance for shelters, group homes and long-term care during the COVID-19 pandemic

abstract: Scientific evidence suggests that COVID-19 is transmitted through the air, and can be mitigated using indoor air quality measures such as ventilation and filtration. We set out to explore how Public Health Ontario (PHO) responded to this evidence. PHO is mandated by legislation to share "scientific and technical advice and support" and "contribute to efforts to reduce health inequities" in Ontario, Canada, a jurisdiction of more than 14 million people (Ontario Agency for Health Protection and Promotion Act, 2007). We were particularly interested in how PHO addressed indoor air quality measures in the context of guidance developed for communal facilities such as long-term care homes and congregate settings (e.g. shelters, group homes, detention centres). We reviewed PHOs public, written COVID-19 guidance specifically designed for long-term care and congregate settings, and published or revised between January, 2021 and October, 2021. We also compared PHOs COVID-19 checklists for long-term care and congregate settings to PHOs COVID-19 checklists for schools, camps and doctors offices. We found no references to indoor air quality measures in any guidance documents specifically designed for long-term care and congregate settings, including COVID-19 checklists. We did, however, find references to indoor air quality measures in COVID-19 checklists for schools, summer camps and doctors offices. We conclude that PHO has provided sub-standard COVID-19 guidance to long-term care and congregate settings, putting workers and residents at greater risk of illness and death, and exacerbating health inequities in Ontario.

category: public and global health


title: Questioning the Seasonality of SARS-COV-2: A Fourier Spectral Analysis

abstract:
ObjectivesCOVID-19 recurrent waves have ignited a debate on the role of seasonality in the contagion resurgence. Two opposite positions emerged. Those convinced of a sinusoidal seasonality recurring over one-year period driven by climate. Those believing that a fluctuation of the outbreaks repeats without limits, in the absence of control measures. We studied the series of daily confirmed SARS-CoV-2 cases in 30 different countries (February 2020 - December 2021), investigating the hypothesis of whether seasonal and geographic variations may guide the pandemic trajectory.

MethodsWe chose 30 countries from different geographies and climates. With a discrete Fourier transform, we performed a spectral analysis of the series of the daily SARS-CoV-2 infections, looking for peaks in the frequency spectrum that could correspond to a recurrent cycle of a given length. This analysis allows to question whether COVID-19 outbreaks have an observable seasonal periodicity.

ResultsAll the 30 investigated countries see the recurrence of at least one COVID-19 wave, repeating over a period in the range 3 - 9 months, with a peak of magnitude at least half as large as that of the highest peak ever experienced since the beginning of the pandemic until December 2021. We also computed the distance in days between the two higher peaks in each country, and then we averaged those values over the 30 countries, yielding a mean of 190 days (SD 100). This suggests that outbreaks may repeat with cycles of different lengths, without a precisely predictable seasonality of one year.

ConclusionOur findings suggest that COVID-19 outbreaks are likely to occur worldwide, with cycles of repetition of variable lengths. Our Fourier analysis with 30 different countries has not found evidence in favor of a seasonality that recurs over one-year period, solely or with a precisely fixed periodicity.

DesignNot Applicable

SettingNot Applicable

ParticipantsNot Applicable

InterventionsNot Applicable

Primary and Secondary Outcome MeasuresNot Applicable

Article SummaryO_ST_ABSStrengths and Limitations of this StudyC_ST_ABSO_LIThe use of a discrete Fourier transform offers the advantage of a temporal decomposition of the time series of the daily SARS-COV-2 cases, allowing to explore the temporal relationships among recurrent outbreaks.
C_LIO_LIAnalyzing for each country the various repetition cycles of the outbreaks, along with their magnitudes, represents an appropriate method to question the assumption of a seasonal "rise and fall" structure of COVID-19 assumed to recur, almost exclusively, based on a one-year long period.
C_LIO_LIWe have made inferences about the seasonality of COVID-19 from a purely observational study. The problem has been avoided to quantify, precisely, the role attributable to various climatic factors or control measures, like temperatures or vaccination.
C_LIO_LITo take advantage of a natural experiment, the time series of the number of daily SARS-CoV-2 cases were subjected to a discrete Fourier transform without resorting to any form of correction/normalization. The SARS-CoV-2 outbreak (started in December 2021) has not been included in this study as the progression of this wave is still ongoing.
C_LIO_LIThis analysis presents a natural limitation in time as the pandemic has been in progress so far, for only two years. The Fourier uncertainty principle may render the results at low frequencies somewhat uncertain given this extremely short time domain.
C_LI


title: IRE1α-XBP1 Activation Elicited by Viral Singled Stranded RNA via TLR8 May Modulate Lung Cytokine Induction in SARS-CoV-2 Pneumonia

abstract:
Initial symptoms of COVID-19 infection depend on viral replication, while hyperinflammation is a hallmark of critical illness and may drive severe pneumonia and death. Among the mechanisms potentially involved in the hyperinflammatory state, we focused on the unfolded protein response, because the IRE1-XBP1 branch can be activated as result of the endoplasmic reticulum stress produced by the overwhelming synthesis of viral components and synergizes with Toll-like receptor signaling to induce cytokine expression. Viral RNA may trigger the IRE1-XBP1 branch via TLR7/8 activation and like TLR2 and TLR4 may underpin cytokine expression trough XBP1 splicing (sXBP1). The expression of IL1B, IL6, and TNF mRNA in bronchoalveolar aspirates (BAAs) were higher in COVID-19 patients under mechanical ventilation and intubation who showed sXBP1. The scrutiny of monocytic/macrophagic markers during active infection showed a reduction of those involved in antigen presentation and survival, as well as the IFN stimulated gene MX1. These changes reverted after infection tests turned negative. In contrast, the expression of the mRNA of the serine protease TMPRSS2 involved in S protein priming showed a high expression during active infection. TLR8 mRNA showed an overwhelming expression as compared to TLR7 mRNA, which suggests the presence of monocyte-derived dendritic cells (MDDCs). In vitro experiments in MDDCs activated with ssRNA40, a positive-sense, single-stranded RNA (+ssRNA) like SARS-CoV-2 RNA, induced sXBP1 and the expression of IL-1{beta}, IL-6, and TNF at mRNA and protein levels. These responses were blunted by the IRE1 ribonuclease inhibitor MKC8866. Given the analogies between the results observed in BAAs and the effects induced by +ssRNA in MDDCs, IRE1 ribonuclease inhibition might be a druggable target in severe COVID-19 disease.

O_FIG O_LINKSMALLFIG WIDTH=180 HEIGHT=200 SRC="FIGDIR/small/22269752v1_ufig1.gif" ALT="Figure 1">
View larger version (53K):
org.highwire.dtl.DTLVardef@13b04b3org.highwire.dtl.DTLVardef@1b1af7corg.highwire.dtl.DTLVardef@780104org.highwire.dtl.DTLVardef@8ad0ba_HPS_FORMAT_FIGEXP  M_FIG C_FIG Author summaryCOVID-19 pandemics put an unprecedented pressure on health systems. The need of new therapies urged research on the mechanisms triggered by the interaction of SARS-CoV-2 virus with host cells and the ensuing pathophysiology driving pneumonia and multiorgan failure. Hyperinflammation soon appeared as a mechanism involved in mortality that could even proceed after viral infection comes to an end. Hyperinflammation is supported by an inappropriate production of cytokines, and this explains the use of the term cytokine storm to refer to this phase of the disease. Given that insight into the molecular mechanisms driving cytokine storm should focus on the interaction of viral components with immune cells, experiments addressing the effect of viral components on its cognate receptors were carried out. It was observed that viral RNA induces a cytokine pattern like the one observed in bronchoalveolar aspirates of COVID-19 patients with critical disease. Overall, the study revealed that both cell organelle overload and receptors involved in the recognition of viral RNA may team up to induce proinflammatory cytokines. This mechanism can be exploited to develop new treatments for COVID-19 disease.

category: allergy and immunology


title: IMPACT OF WEEKNIGHT AND WEEKEND CURFEWS USING MOBILITY DATA: A CASE STUDY OF BENGALURU URBAN

abstract: Karnataka imposed weeknight and weekend curfews to mitigate the spread of the Omicron variant of SARS-CoV-2. We attempt to assess the impact of curfew using community mobility reports published by Google. Then, we quantify the impact of such restrictions via a simulation study. The pattern of weeknight and weekend curfew, followed by relaxations during the weekdays, seems, at best, to slow and delay the Omicron spread. The simulation outcomes suggest that Omicron eventually spreads and affects nearly as much of the population as it would have without the restrictions. Further, if Karnataka cases trajectory follows the South African Omicron wave trend and the hospitalisation is similar to that observed in well-vaccinated countries (2% of the confirmed cases), then the healthcare requirement is likely within the capacity of Bengaluru Urban when the caseload peaks, with or without the mobility restrictions. On the other hand, if Karnataka cases trajectory follows both the South African Omicron wave trend and the hospitalisation requirement observed there (6.9%), then the healthcare capacity may be exceeded at peak, with or without the mobility restrictions.

category: epidemiology


title: A model-based approach to improve intranasal sprays for respiratory viral infections

abstract: Drug delivery for viral respiratory infections, such as SARS-CoV-2, can be enhanced significantly by targeting the nasopharynx, which is the dominant initial infection site in the upper airway, for example by nasal sprays. However, under the standard recommended spray usage protocol ("Current Use", or CU), the nozzle enters the nose almost vertically, resulting in sub-optimal deposition of drug droplets at the nasopharynx. Using computational fluid dynamics simulations in two anatomic nasal geometries, along with experimental validation of the generic findings in a different third subject, we have identified a new "Improved Use" (or, IU) spray protocol. It entails pointing the spray bottle at a shallower angle (almost horizontally), aiming slightly toward the cheeks. We have simulated the performance of this protocol for conically injected spray droplet sizes of 1 - 24 m, at two breathing rates: 15 and 30 L/min. The lower flowrate corresponds to resting breathing and follows a viscous-laminar model; the higher rate, standing in for moderate breathing conditions, is turbulent and is tracked via Large Eddy Simulation. The results show that (a) droplets sized between [~] 6 - 14 m are most efficient at direct landing over the nasopharyngeal viral infection hot-spot; and (b) targeted drug delivery via IU outperforms CU by approximately 2 orders-of-magnitude, under the two tested inhalation conditions. Also quite importantly, the improved delivery strategy, facilitated by the IU protocol, is found to be robust to small perturbations in spray direction, underlining the practical utility of this simple change in nasal spray administration protocol.

category: respiratory medicine


title: Using quantitative MRI to track cerebral damage in multiple sclerosis: a longitudinal study

abstract:
Quantitative MRI quantifies tissue microstructural properties and improves the characterization of cerebral tissue damages. With an MPM protocol, 4 parameter maps are constructed: MTsat, PD, R1 and R2*, reflecting tissue physical properties associated with iron and myelin contents. Here, we used qMRI to investigate the microstructural longitudinal changes in MS.

Seventeen MS patients (age 25-65, 11 RRMS) were scanned on a 3T MRI, in two sessions separated with a median of 30 months, and the parameters evolution was evaluated within several tissue classes: NAWM, NACGM and NADGM, as well as focal WM lesions. Tissue segmentation was performed using US-with-Lesion, an adapted version of the Unified Segmentation (US) algorithm accounting for lesions. An individual annual rate of change for each qMRI parameter was computed, and its correlation to clinical status was evaluated. For WM plaques, three areas were defined, and a GLMM tested the effect of area, time points, and their interaction on each median qMRI parameter value.

Patients with a better clinical evolution, i.e., clinically stable or improving state, showed positive annual rate of change in MT and R2* within NAWM and NACGM, suggesting repair mechanisms in terms of increased myelin content and/or axonal density as well as edema/inflammation resorption. When examining WM lesions, qMRI parameters within surrounding NAWM showed microstructural modifications, even before any focal lesion is visible on conventional FLAIR MRI.

The results illustrate the benefit of multiple qMRI data in monitoring subtle changes within normal appearing brain tissues and plaque dynamics in relation with tissue repair or disease progression.

Key pointsO_LIPatients with a better clinical evolution showed microstructural improvement in term of MT and R2* increase in their normal appearing tissue, suggesting repair mechanisms.
C_LIO_LIUsing qMRI allows to detect modifications in tissue microstructure in normal appearing tissues surrounding lesions several months before they are visible on conventional MRI.
C_LI

category: neurology


title: Using quantitative magnetic resonance imaging to track cerebral damage in multiple sclerosis: a longitudinal study


title: INCIDENCE OF HEPATITIS B AND C VIRUSES AMONG THE SCAVENGERS IN KWARA STATE, NIGERIA

abstract:
BackgroundPoor economic situations in developing nations had made scavenging a means of livelihood for millions of youth and women across the globe. Lack of proper source segregation of wastes in developing countries has increased the potential for the transmission of pathogens like Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV).

ObjectivesThis study addressed issues relating to waste scavenging, the potential risk in waste scavenging work and seroprevalence of Hepatitis B and C Virus and its relationship with wastes scavenging among wastes scavengers in Kwara State.

MethodsA cross-sectional study was conducted among the scavengers working for major scrap dealers in the three senatorial districts of Kwara State. Consequently, to accomplish the objectives, both primary and secondary data sources were used. The primary data were collected via questionnaires, interviews, blood test and field observations. Whereas the secondary data were extracted from different published and unpublished materials. 240 respondents were administered with questionnaires and undergone hepatitis surface antigen test for both hepatitis B and C in nine of the sixteen local government area in the state. The data were analyzed using statistical package for social science (SPSS version 23) for descriptive and inferential at 5% level of significance. The prevalence of an HBV and HCV infection biological markers (HBsAg and HCsAg) and their associations with exposure to bio-medical waste, socio-demographic factors, and history of occupational injuries was examined.

ResultsThe seroprevalence of HBV and HCV infection among the scavengers were found to be 8.3% and 5% respectively indicating that scavengers are at risk of HBV and HCV infection.

ConclusionsIt was discovered that there are incidences of Hepatitis B and C virus co-infection among scavengers. Also, awareness and compliance to the usage of PPE was found to be an important factor for protection scavengers against the virus. Therefore, vaccination against HBV, enforcement of usage of PPE, good hygiene practices, regular trainings on occupational safety, proper monitoring by regulatory agency and inclusion of scavengers in mandatory health insurance scheme will help to control risk of HBV and HCV infection among scavengers.

category: occupational and environmental health


title: Sex differences, cross-ancestry generalizability, and noise-smoking interactions in the polygenic architecture of hearing loss in adults

abstract: We conducted a comprehensive genome-wide investigation of hearing loss (HL) in 748,668 adult participants of the UK Biobank, the Nurses Health Studies (I and II), the Health Professionals Follow-up Study, and the Million Veteran Program. We identified 54 risk loci and characterized HL polygenic architecture, exploring sex differences, polygenic risk across ancestries, tissue-specific transcriptomic regulation, cause-effect relationships with genetically-correlated traits, and gene interactions with HL environmental risk factors. Our transcriptomic regulation analysis highlighted the potential role of the central nervous system in HL pathogenesis. This was supported by the multivariate interaction analysis that showed how genes involved in brain development interact with sex, noise pollution, and tobacco smoking in relation to their HL associations. Additionally, the genetically-informed causal inference analysis showed that HL is linked to many physical and mental health outcomes. These results provide many novel insights into the complex biology and epidemiology of HL in adults.

category: genetic and genomic medicine


title: General practitioner wellbeing during the COVID-19 pandemic: a qualitative interview study

abstract:
BackgroundWorkload pressures and poor job satisfaction have been reported by UK general practitioners (GPs) for some time. The COVID-19 pandemic presented new challenges, with growing international evidence of its negative impact on GPs mental health and wellbeing. While there has been wide commentary on this topic, UK research evidence is lacking. Developing greater understanding of these lived experiences and subgroup differences is important as doctor wellbeing may affect the sustainability of health care systems and quality of patient care.

ObjectivesTo explore the lived experience of UK GPs during COVID-19, and the pandemics impact on their psychological wellbeing.

Design and SettingIn-depth qualitative interviews, conducted remotely by telephone or video call, with NHS GPs.

ParticipantsGPs were sampled purposively across three career stages (early career, established and late career or retired GPs) with variation in other key demographics. A comprehensive recruitment strategy used multiple channels. Data were analysed thematically using Framework Analysis.

ResultsWe interviewed 40 GPs; most described generally negative sentiment and many displayed signs of psychological distress and burnout. Causes of stress and anxiety related to personal risk, workload, practice changes, public perceptions and leadership, teamworking and wider collaboration and personal challenges. GPs described facilitators of their wellbeing, including sources of support and plans to reduce clinical hours or change career path.

ConclusionsA range of factors detrimentally affected the wellbeing of GPs during the pandemic and we highlight the potential impact of this on workforce retention and quality of care. As the pandemic progresses and general practice faces continued challenges, urgent policy measures are now needed.

Strengths and limitations of this studyO_LIWhile there is growing international evidence base demonstrating the impact of the COVID-19 pandemic on GPs wellbeing and much UK media coverage, this qualitative interview study provides much-needed research evidence of UK GPs lived experiences and wellbeing during COVID-19.
C_LIO_LI40 GPs were sampled purposively to include GPs with different demographic and practice characteristics.
C_LIO_LIWhile there are no easy solutions to the problems highlighted, this research provides increased contextualised understanding of how these experiences may impact future workforce retention and the sustainability of health systems longer-term.
C_LIO_LISub-group differences by gender and age are reported; highlighting a potential need for further research and support targeted at specific groups.
C_LIO_LIFindings are necessarily limited to the time of data collection (Spring/Summer 2021); further tensions in general practice have since arisen, particularly regarding negative and misleading media portrayal.
C_LI

category: health policy


title: Antibody and T cell responses to SARS-CoV-2 mRNA vaccines during maintenance therapy for immune-mediated inflammatory diseases

abstract:
BackgroundLimited information is available on the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID).

MethodsThis observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, or psoriatic disease, with or without maintenance immunosuppressive therapies. Antibody and T cell responses to SARS-COV-2, including neutralization against SARS-CoV-2 variants were determined before and after 1 and 2 vaccine doses.

ResultsWe prospectively followed 150 subjects, 26 healthy controls, 9 IMID patients on no treatment, 44 on anti-TNF, 16 on anti-TNF with methotrexate/azathioprine (MTX/AZA), 10 on anti-IL-23, 28 on anti-IL-12/23, 9 on anti-IL-17, and 8 on MTX/AZA. Antibody and T cell responses to SARS-CoV-2 were detected in all participants, increasing from dose 1 to dose 2 and declining 3 months later, with greater attrition in IMID patients compared to healthy controls. Antibody levels and neutralization efficacy against variants of concern were substantially lower in anti-TNF treated patients than in healthy controls and were undetectable against Omicron by 3 months after dose 2.

ConclusionsOur findings support the need for a third dose of mRNA vaccine and for continued monitoring of immunity in these patient groups.

FundingFunded by a donation from Juan and Stefania Speck and by Canadian Institutes of Health (CIHR) /COVID-Immunity Task Force (CITF) grants VR-1 172711 and VS1-175545 (T.H.W. and A.C.G); CIHR FDN-143250 (T.H.W.), GA2-177716 (V.C., A.C.G., T.W.), GA1-177703 (A.C.G.) and the CIHR rapid response network to SARS-CoV-2 variants, CoVaRR-Net (to A.C.G.).

category: infectious diseases


title: Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune mediated inflammatory diseases


title: Interventions designed to improve vaccination uptake: Scoping review of systematic reviews and meta-analyses - (version 1)

abstract:
BackgroundResources to ensure high vaccination uptake differ widely across countries, but the best use of these precious resources is unclear. To better meet immunization programmes a pressing need to understand what works, particularly in low-resource settings, the World Health Organization commissioned a scoping view.

MethodsWe conducted a scoping review of interventions designed to increase vaccination uptake, including systematic reviews and meta-analyses of interventional studies. We searched the following electronic databases: MEDLINE, Cochrane Database of Systematic Reviews, EMBASE, Epistemonikos, Google Scholar, LILACs and TRIP database until 01 July 2021 and hand-searched the reference lists of included articles. We included systematic reviews if they summarized studies with quantitative data on the impact on vaccine uptake for any age group. To assess review quality, we used a modified AMSTAR score. To evaluate the quality of the evidence in included reviews, we used the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

ResultsThe final analysis set included 107 full-text reviews. Publication of reviews increased markedly over time, from seven reviews in 2010 to 38 reviews filtered in 2021. We conducted quality assessments for 72 reviews (132 outcomes). Based on the AMSTAR criteria, 40 included reviews (56%) received a quality rating of good, while the remaining 32 (44%) were of moderate quality. Only 13 reviews summarized data primarily for low- and middle-income countries (LMIC). The interventions were commonly multi-component, educational or reminder interventions; the description of intervention components was suboptimal and heterogeneous across most reviews. Effect estimates were available for 73 outcomes; in 52 (71%) of these, interventions led to statistically significant higher vaccine uptake compared with controls.

ConclusionsThe literature has a large number of relevant systematic reviews on interventions to increase vaccine uptake, with an increased publication rate over time. However, problems with the definitions and the current reporting of vaccine uptake evidence make it difficult to determine what works best in low-resource settings.


title: SARS-CoV-2 in schools: genome analysis shows that concurrent cases in the second and third wave were often unconnected

abstract:
BackgroundThe risk of SARS-CoV-2 (SCoV2) infection in schools and student households is typically assessed using classical epidemiology whereby transmission is based on time of symptom onset and contact tracing data. Using such methodologies may be imprecise regarding transmission events of different, simultaneous SCoV2 variants spreading with different rates and directions in a given population. We analysed with high resolution the transmission among different communities, social networks, and educational institutions and the extent of outbreaks using whole genome sequencing (WGS).

Methods and FindingsWe combined WGS and contact tracing spanning two pandemic waves from October 2020 to May 2021 in the Canton of Basel-City, Switzerland and performed an in-depth analysis of 235 cases relating to 22 educational institutions. We describe the caseload in educational institutions and the public health measures taken and delineate the WGS-supported outbreak surveillance.

During the study period, 1,573 of 24,557 (6.4%) children and 410 of 3,726 (11%) staff members from educational institutions were reported SCoV2 positive. Thereof, WGS data from 83 children, 35 adult staff in 22 educational institutions and their 117 contacts (social network, families) was available and analysed. 353 contextual sequences from residents of the Canton of Basel-City sequenced through surveillance were identified to be related to cases in the educational institutions. In total, we identified 55 clusters and found that coinciding SCoV2-cases in individual educational institutions were mostly introduced from different sources such as social networks or the larger community. More transmission chains started in the community and were brought into the educational institutions than vice versa (31 vs. 13). Adolescents (12-19 years old) had the highest case prevalence over both waves compared to younger children or adults, especially for the emerging Alpha variant.

ConclusionsIntroduction of SCoV2 into schools accounts for most events and reflects transmission closely related to social activity, whereby teenagers and young adults contribute to significant parallel activity. Combining WGS with contact tracing is pivotal to properly inform authorities about SCoV2 infection clusters and transmission directions in educational settings and the effectiveness of enacted public health measures. The gathered data showing more clusters to seed in the community than vice versa as well as few subsequent in-school transmissions indicate that the agilely employed health measures for educational institutions helped to prevent outbreaks among staff and children.

The clinical trial accession number is NCT04351503 (clinicaltrials.gov).


title: Analysis of Fatality Impact and Seroprevalence Surveys in a Community Sustaining a SARS-CoV-2 Superspreading Event

abstract: There is ongoing debate on the COVID-19 infection fatality rate (IFR) and the impact of COVID-19 on overall population mortality. Here, we addressed these issues in a community in Germany with a major superspreader event analyzing deaths over time as well as auditing death certificates in the community.18 deaths that occurred within the first 6 months of the pandemic in the community had a positive test for SARS-CoV-2. Six out of 18 SARS-CoV-2+ deaths had non-COVID-19 related causes of death (COD). Individuals with confirmed infection and COVID-19 COD typically died of respiratory failure (75%) and tended to have fewer reported comorbidities (p=0.029). Duration between first confirmed infection and death was negatively associated to COVID-19 being COD (p=0.04). Repeated seroprevalence essays on an original sample of 587 individuals in three visits showed modest increases in seroprevalence over time, and substantial seroreversion (30% [27/90] (95% CI: [20.5%; 39.5%])). IFR estimates accordingly varied depending on COVID-19 death attribution and seroprevalence caveats. Careful ascertainment and audit of COVID-19 deaths are important in understanding the impact of the pandemic.


title: Causal Effects Contributing to Elevated Metabolic Power During Walking in Children Diagnosed with Cerebral Palsy

abstract:
Metabolic power (net energy consumed while walking per unit time) is, on average, two-to-three times greater in children with cerebral palsy (CP) than their typically developing peers, contributing to greater physical fatigue, lower levels of physical activity and greater risk of cardiovascular disease. The goal of this project was to identify the total causal effects of clinical factors that may contribute to high metabolic power demand in children with CP.

We included children who 1) visited Gillette Childrens Specialty Healthcare for a quantitative gait assessment after the year 2000, 2) were formally diagnosed with CP, 3) were classified as level I-III under the Gross Motor Function Classification System and 4) were 18 years old or younger. We created a structural causal model that specified the assumed relationships of a childs gait pattern (i.e., gait deviation index, GDI) and common impairments (i.e., dynamic and selective motor control, strength, and spasticity) with metabolic power. We estimated causal effects using Bayesian additive regression trees, adjusting for factors identified by the causal model.

There were 2157 children who met our criteria. We found that a childs gait pattern, as summarized by the GDI, affected metabolic power approximately twice as much as the next largest contributor. Selective motor control, dynamic motor control, and spasticity had the next largest effects. Among the factors we considered, strength had the smallest effect on metabolic power.

Our results suggest that children with CP may benefit more from treatments that improve their gait pattern and motor control than treatments that improve spasticity or strength.

category: pediatrics


title: Brain network mechanisms of visual perceptual organization in schizophrenia and bipolar disorder

abstract: Visual shape completion is a canonical perceptual organization process that integrates spatially distributed edge information into unified representations of objects. People with schizophrenia show difficulty in discriminating completed shapes but the brain networks and functional connections underlying this perceptual difference remain poorly understood. Also unclear is whether similar neural differences arise in bipolar disorder or vary across the schizo-bipolar spectrum. To address these topics, we scanned (fMRI) people with schizophrenia, bipolar disorder, or no psychiatric illness during rest and during a task in which they discriminated configurations that formed or failed to form completed shapes (illusory and fragmented condition, respectively). Multivariate pattern differences were identified on the cortical surface using 360 predefined parcels and 12 functional networks composed of such parcels. Brain activity flow mapping was used to evaluate the likely involvement of resting-state connections for shape completion. Illusory/fragmented task activation differences ("modulations") in the dorsal attention network (DAN) could distinguish people with schizophrenia (AUCs>.85) and could trans-diagnostically predict cognitive disorganization severity. Activity flow over functional connections from the DAN could predict secondary visual network modulations in each group, except among those with schizophrenia. The secondary visual network was strongly and similarly modulated in each subject group. Task modulations were dispersed over a larger number of networks in patients compared to controls. In summary, abnormal DAN activity emerges during perceptual organization in schizophrenia and may be related to improper attention-related feedback into secondary visual areas. Patients with either disorder may compensate for abnormal perception by relying upon non-visual networks.

category: psychiatry and clinical psychology


title: Mentalizing abilities mediate the impact of the low-level social cognitive processes on negative symptoms.

abstract: Social cognitive deficits are currently considered as one of the main predictors of clinical symptoms and functional outcome in patients with schizophrenia. Multiple studies have suggested that two-factor solution (low-level vs. high-level) best describes the structure of social cognitive processes in patients. While higher-order processes have been repeatedly linked to negative symptoms, no such association was found for lower-level processes. Thus, the aim of the current study is to examine whether the association between low-level socio-perceptual processes and symptoms in patients with schizophrenia is mediated by higher-order socio-inferential abilities. One hundred thirty-nine patients have completed basic communicative interactions processing (CID-12) and mind reading (Reading the Mind in the Eyes task) tasks. In line with our hypothesis, we have observed full mediation of the effects of basic social perception abilities on negative symptoms via mentalizing abilities in patients. This effect suggests that, similarly as in the case of positive symptoms, a hierarchical nature of social cognitive processes should be considered while investigating negative symptoms of schizophrenia.


title: Water Insecurity, Water Borrowing, and Psychosocial Stress Among Daasanach Pastoralists in Northern Kenya

abstract: This article quantifies Daasanach water insecurity experiences in Northern Kenya, examines how water insecurity is associated with water borrowing and psychosocial stress, and evaluates if water borrowing mitigates the stress from water insecurity. Of 133 households interviewed in 7 communities, 95% were water insecure and 74.4% borrowed water three or more times in the prior month. Regression analyses demonstrate water borrowing frequency moderates the relationship between water insecurity and psychosocial stress. Only those who rarely or never borrowed water reported greater stress with higher water insecurity. The coping mechanism of water borrowing may help blunt water insecurity-related stress.


title: The effect of reactive balance training on falls in daily life: an updated systematic review and meta-analysis

abstract:
ObjectiveReactive balance training is an emerging approach to reduce falls risk in people with balance impairments. The purpose of this study was to determine the effect of reactive balance training on falls in daily life among individuals at increased risk of falls, and to document associated adverse events.

Data sourcesDatabases searched were Ovid MEDLINE (1946-November 2020), Embase Classic and Embase (1947-November 2020), Cochrane Central Register of Controlled Trials (2014-November 2020), Physiotherapy Evidence Database (PEDro; searched on 9 November 2020).

Study selectionRandomized controlled trials of reactive balance training were included. The literature search was limited to English language. Records were screened by two investigators separately.

Data extractionOutcome measures were number of participants who reported falls after training, number of falls reported after training, and the nature, frequency, and severity of adverse events. Authors of included studies were contacted to obtain additional information.

Data synthesisTwenty-five trials were included, of which 14 reported falls and 19 monitored adverse events. Participants assigned to reactive balance training groups were less likely to fall compared to control groups (fall risk ratio: 0.75, 95% confidence interval=[0.60, 0.92]; p=0.006, I2=37%) and reported fewer falls than control groups (rate ratio: 0.60, 95% confidence interval=[0.42, 0.86]; p=0.005, I2=83%). Prevalence of adverse events was higher in reactive balance training (29%) compared to control groups (19%; p=0.018).

ConclusionRBT reduces the likelihood of falls in daily life for older adults and people with balance impairments. More adverse events were reported for reactive balance training than control groups.

ImpactBalance training that evokes balance reactions can reduce falls among people at increased risk of falls.

category: rehabilitation medicine and physical therapy


title: Persistently reduced humoral and cellular immune response following third SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients

abstract:
ObjectiveTo examine humoral and cellular response in multiple sclerosis patients on anti-CD20 therapy after third BNT162b2 mRNA SARS-CoV-2 vaccination.

MethodsA prospective longitudinal study design from first throughout third vaccination in Danish and American MS centers. All participants were treated with ocrelizumab. Antibody (Ab) levels were assessed before and after third vaccination using SARS-CoV-2 IgG II Quant assay (Abbott Laboratories). B- and T-lymphocytes enumeration was done with BD Multitest6-color TBNK reagent. Spike-specific T-cell responses were measured through PBMC stimulation with spike peptide pools (JPT Peptide Technologies).

ResultsWe found that 14.0%, 37.7%, and 33.3% were seropositive after first, second and third vaccination. The median Ab-levels were 74.2 BAU/mL (range: 8.5-2427), 43.7 BAU/ml (range: 7.8-366.1) and 31.3 BAU/mL (range: 7.9-507.0) after first, second and third vaccination, respectively. No difference was found in levels after second and third vaccination (p=0.1475). Seropositivity dropped to 25.0% of participants before the third vaccination, a relative reduction of 33.3% (p=0.0020). No difference was found between frequencies of spike reactive CD4+ and CD8+ T-cells after second (0.65 {+/-} 0.08% and 0.95 {+/-} 0.20%, respectively) and third vaccination (0.99 {+/-} 0.22% and 1.3 {+/-} 0.34%), respectively.

ConclusionIn this longitudinal cohort we found no significant increased humoral or cellular response with administration of a third SARS-CoV-2 mRNA vaccination. These findings suggest the need for clinical strategies to include allowance of B cell reconstitution before repeat vaccination and/or provision of pre-exposure prophylactic monoclonal antibodies.

Key PointsO_ST_ABSWhat is already known on this topicC_ST_ABSStudies have described decreased humoral response and sustained T-cell reactivity after standard two-dose SARS-CoV-2 mRNA vaccination during anti-CD20 therapy in multiple sclerosis participants.

What this study addsPersistently decreased humoral, but stable cellular reactivity following a third SARS-CoV-2 mRNA vaccination.

How this study might affect research, practice or policyThe findings suggest the need for clinical strategies to include allowance of B cell reconstitution before repeat vaccination and/or provision of pre-exposure prophylactic monoclonal antibodies.


title: Identifying the regional substrates predictive of Alzheimer's disease progression through a convolutional neural network model and occlusion

abstract: Progressive brain atrophy is a key neuropathological hallmark of Alzheimers disease (AD). However, atrophy patterns along the progression of AD are diffuse and variable. Consequently, identifying the major regional atrophy patterns underlying AD progression is challenging. In the current study, we propose a method that evaluates the degree to which specific regional atrophy are predictive of AD progression, while holding all other atrophy changes constant. We first trained a dense convolutional neural network model to differentiate individuals with mild cognitive impairment (MCI) who progress to AD vs. those with a stable MCI diagnosis. Then, we retested the model multiple times, each time occluding major regions from the models testing sets input. This revealed that the hippocampus, fusiform, and inferior temporal gyri, were the strongest predictors of AD progression, in agreement with established staging models. These results shed light on the major regional patterns of atrophy predictive of AD progression.


title: African-Ancestry Associated Gene Expression Signatures and Pathways in Triple Negative Breast Cancer, a Comparison Across Women of African Descent

abstract:
Women of sub-Saharan African ancestry have disproportionately higher incidence of aggressive, early-onset Triple Negative Breast Cancer (TNBC), and TNBC mortality across all race groups. Population-based comparative studies show racial differences in TNBC tumor biology, with higher prevalence of basal-like and Quadruple-Negative subtypes in African Americans (AA). However, most investigations relied on self-reported race (SRR) of primarily United States (US) populations. However, given that genetic admixture in AAs is extremely heterogenous, and race-correlated social determinants can translate into biological differences, the true association of African ancestry with TNBC biology and gene expression is currently unclear. To address this, we conducted RNAseq on an international cohort of AAs, west and east Africans with TNBC. Using genetic ancestry estimation in this African-enriched cohort, we identified 613 genes associated with African ancestry and more than 2200 genes associated with regional-level African ancestry. Functional enrichment and deconvolution revealed tumor-associated immune cell infiltration and activity.

STATEMENT OF SIGNIFICANCEUsing a rigorous ancestry quantification process, we show that TNBC has ancestry-associated gene expression profiles, linked to immunological landscapes, which may contribute to racial differences in clinical outcomes. This is the first study to show the definitive link to tumor immunological landscape, associated with African ancestry, using a multiethnic African-enriched cohort.

category: oncology


title: An interdisciplinary outpatient therapy program for children and adolescents with headache - real world data

abstract:
Background/ ObjectiveMore than 2/3 of children and adolescents in Germany regularly suffer from headaches. Headache-related limitations in everyday life, school drop-out and educational impairment are common. Structured therapy programs for young headache patients are widely missing. We investigate the effects of an outpatient interdisciplinary headache program for children, adolescents and their parents.

Methods91 patients suffering from frequent headaches were treated in a 15 hour group program. Parents received 7 hours of therapy. At the beginning of the therapy program (T0), 6 (T1) and 12 months (T2) after completion, data on headache related disability (PedMidas), headache frequency, intensity, and pediatric pain disability score (PPDI) were collected. The primary endpoint was reduction in headache frequency, secondary endpoint reduction in PedMidas.

Results75 children and adolescents (9-18 years, median = 14; 66.7% female) and their parents provided prospective patient reported outcome measures. Patients were diagnosed with any form of migraine or tension type headache or a combination of both. 6 and 12 months after completion of the therapy program patients reported reduced headache frequency (headache days in the last three months median at baseline: 30; T1: 18 days; T2: 13 days). Linear mixed models revealed significant reduction over time (T0/T1 p = 0,002; T0/T2 p = 0,001). In addition, reduced headache disability has been reported 6 and 12 months after therapy (PedMidas median T0= 30, T1=15, T2=7; p<0,001 and p<0,001 respectively).

ConclusionsThe interdisciplinary headache therapy program for children and adolescents, reported here, reduces headache frequency and headache related disability significantly in a period of 6-12 month following its completion. Comparative studies of children and adolescents with headaches in general outpatient treatment are needed to further describe the therapeutic gains of the program.

category: pain medicine


title: Screening for SARS-CoV-2 in close contacts of individuals with confirmed infection: performance and operational considerations

abstract:
BackgroundPoint-of-care and decentralized testing for SARS-CoV-2 is critical to inform public health responses. Performance evaluations in priority use cases such as contact tracing can highlight trade-offs in test selection and testing strategies.

MethodsA prospective diagnostic accuracy study was conducted among close contacts of COVID-19 cases in Brazil. Two anterior nares swabs (ANS), a nasopharyngeal swab (NPS), and saliva were collected at all visits. Vaccination history and symptoms were assessed. Household contacts were followed longitudinally. Three rapid antigen tests and one molecular method were evaluated for usability and performance against reference RT-PCR on NPS.

ResultsFifty index cases and 214 contacts (64 household) were enrolled. Sixty-five contacts were RT-PCR positive during at least one visit. Vaccination did not influence viral load. Gamma variants were most prevalent; Delta emerged increasingly during implementation. Overall sensitivity of evaluated tests ranged from 33%-76%. Performance was higher among symptomatic cases and cases with Ct<34 and lower among oligo/asymptomatic cases. Assuming a 24-hour time-to-result for RT-PCR, the cumulative sensitivity of an ANS rapid antigen test was >70% and almost 90% after four days.

ConclusionsThe near immediate time-to-result for antigen tests significantly offsets lower analytical sensitivity in settings where RT-PCR results are delayed or unavailable.


title: Evaluation of the CD4+ T cell response to SARS-CoV-2 infection and cross reactivity to beta variant in children of all ages

abstract:
SARS-CoV-2 is still a major burden for global health despite effective vaccines. With the reduction of social distancing measures, infection rates are increasing in children, while data on the pediatric immune response to SARS-CoV-2 infection is still lacking. Although the typical disease course in children has been mild, emerging variants may present new challenges in this age group.

Peripheral blood mononuclear cells (PBMC) from 51 convalescent children, 24 seronegative siblings from early 2020, and 51 unexposed controls were stimulated with SARS-CoV-2-derived peptide MegaPools from the ancestral and beta variants. Flow cytometric determination of activation-induced markers and secreted cytokines were used to quantify the CD4+ T cell response.

The average time after infection was over 80 days. CD4+ T cell responses were detected in 61% of convalescent children and were markedly reduced in preschool children. Cross-reactive T cells for the SARS-CoV-2 beta variant were identified in 45% of cases after infection with an ancestral SARS-CoV-2 variant. The CD4+ T cell response was accompanied most predominantly by IFN-{gamma} and Granzyme B secretion.

An antiviral CD4+ T cell response was present in children after ancestral SARS-CoV-2 infection, which was reduced in the youngest age group. We detected significant cross-reactivity of CD4+ T cell responses to the more recently evolved immune-escaping beta variant. Our findings have epidemiologic relevance for children regarding novel viral variants of concern and vaccination efforts.


title: Diabetes mellitus, hypertension, and HbA1c, as risk factors for arterial stiffness

abstract: Studies in a healthy and diabetic population have shown that there is a correlation between the disease and arterial stiffness, and consequently an increase in Pulse Wave Velocity (PWV). We investigate predictors laboratory and clinical associated with arterial stiffness, validated by the increase in PWV. Our findings showed that the predictor for diabetes mellitus, hypertension, glycated hemoglobin [≥]5.7, confirmed the significant association for increased arterial stiffness, validated by the increase in PWV.

category: cardiovascular medicine


title: Regional connectivity drove bidirectional transmission of SARS-CoV-2 in the Middle East during travel restrictions

abstract:
Regional connectivity and land-based travel have been identified as important drivers of SARS-CoV-2 transmission. However, the generalizability of this finding is understudied outside of well-sampled, highly connected regions such as Europe. In this study, we investigated the relative contributions of regional and intercontinental connectivity to the source-sink dynamics of SARS-CoV-2 for Jordan and the wider Middle East. By integrating genomic, epidemiological and travel data we show that the source of introductions into Jordan was dynamic across 2020, shifting from intercontinental seeding from Europe in the early pandemic to more regional seeding for the period travel restrictions were in place. We show that land-based travel, particularly freight transport, drove introduction risk during the period of travel restrictions. Consistently, high regional connectivity and land-based travel also disproportionately drove Jordans export risk to other Middle Eastern countries. Our findings emphasize regional connectedness and land-based travel as drivers of viral transmission in the Middle East. This demonstrates that strategies aiming to stop or slow the spread of viral introductions (including new variants) with travel restrictions need to prioritize risk from land-based travel alongside intercontinental air travel to be effective.

HighlightsO_LIRegional connectivity drove SARS-CoV-2 introduction risk in Jordan during the period travel restrictions were in place in genomic and travel data.
C_LIO_LILand-based travel rather than air travel disproportionately drove introduction risk during travel restrictions.
C_LIO_LIHigh regional connectivity disproportionately drove Jordans export risk, with significant contribution from land-based travel.
C_LIO_LIRegional transmission dynamics were underestimated in genomic data due to unrepresentative sampling.
C_LI


title: Predicting Substance Use Disorders: A Multifactorial Risk Index Combining Clinical, Environmental, and Genetic Risk Factors

abstract:
ImportanceSubstance use disorders (SUDs) incur serious social and personal costs. Screening techniques that identify persons at risk before problems develop can improve prevention efforts.

ObjectiveTo examine whether models that include polygenic scores (PGS) and a clinical/ environmental/risk index (CERI) are able to identify individuals as having a lifetime SUD.

DesignWe tested the predictive power of PGS and CERI for lifetime diagnosis of DSM-IV substance dependence using four longitudinal cohorts.

SettingThe study included four samples: 1) the National Longitudinal Study of Adolescent to Adult Health (Add Health); 2) the Avon Longitudinal Study of Parents and Children (ALSPAC); 3) the Collaborative Study on the Genetics of Alcoholism (COGA); and 4) the Finnish Twin Cohort Study (FinnTwin12) for a combined sample of N = 15,134.

ParticipantsParticipants in Add Health (NEUR = 4,855; NAFR = 1,605) and COGA (NEUR = 1,878; NAFR = 870) included individuals of both European and African ancestries. Participants in ALSPAC (NEUR = 4,733) and FinnTwin12 (NEUR = 1,193) were limited to individuals of European ancestries.

ExposuresA clinical/environmental risk index (CERI) composed of ten items and PGS for phenotypes with strong genetic overlap with SUDs (drinks per week, problematic alcohol use, externalizing problems, major depressive disorder, and schizophrenia).

Main OutcomesMeeting lifetime criteria for DSM-IV: 1) alcohol dependence, 2) drug dependence, and 3) any substance dependence (alcohol, other drug, or nicotine).

ResultsIn the models containing the five PGS and CERI, the CERI was associated with all three outcomes (ORs = 1.35 - 1.64). PGS for problematic alcohol use was associated with alcohol dependence (OR = 1.14), PGS for externalizing was associated with drug dependence (OR = 1.14) and both were associated with any substance dependence (ORs = 1.11 - 1.19). Including the five PGS, CERI, and covariates explained 6% - 13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.82 - 9.13 for each SUD relative to the bottom 90%.

Conclusions and RelevanceMeasures of clinical, environmental, and genetic, risk demonstrate modest ability to distinguish between affected and unaffected individuals for alcohol, drug, and any substance use disorders in young adulthood. These tools will continue to advance as we identify additional risk factors that can be incorporated into clinical practice and deliver on the goal of precision medicine.


title: Who was wearing a mask in 2021? Update on gender-, age-, and location-related differences during the COVID-19 pandemic

abstract: Previous observational work from 2020 demonstrated gender-, age-, and location-related differences in mask-wearing behavior, despite the efficacy and public health messaging that emphasized face coverings in combatting the spread of COVID-19. In 2021, COVID-19 vaccinations and a corresponding change in public health policy became new considerations in deciding personal protective behaviors. To provide an update on mask wearers and resistors approximately one year after our initial study, we observed shoppers (n = 6,118) entering retail stores using the same experimental methodology. Approximately 26% of individuals wore a mask. Mask wearing has decreased across demographic groups compared to 2020. Aligning with previous findings, females were [~]1.5x more likely to be observed wearing a mask than males, and the odds of observing a shopper wearing a mask in a suburban or urban area was far greater than at rural stores ([~]5.7x and [~]3.3x, respectively). Gender and location are confirmed to be significant and stable factors that impact mask-wearing behavior in the United States during the COVID-19 pandemic. The impact of age on mask wearing was heavily reduced compared to 2020, potentially due to the availability of COVID-19 vaccines and change in mask guidance for vaccinated individuals.


title: A non-systematic signal-correction error in a commercial multiple-breath washout device significantly impacts outcomes in children and adults

abstract:
BackgroundMultiple-breath nitrogen washout is an established and sensitive technique to assess functional residual capacity and ventilation inhomogeneity in the lung. Indirect calculation of nitrogen concentration requires precise calibration and accurate measurement of gas concentrations.

AimWe investigated the accuracy of the carbon dioxide gas concentration used for the indirect calculation of nitrogen concentration in a commercial multiple-breath washout (MBW) device (EasyOne Pro LAB, ndd Medizintechnik AG, Zurich, Switzerland) and its impact on outcomes.

MethodsA high-precision calibration gas mixture was used to evaluate sensor output and calculated carbon dioxide concentration. We assessed the impact of a corrected CO2 signal on MBW outcomes in a dataset of healthy children and adults and children with lung disease.

ResultsThe EasyOne device uses a respiratory quotient-based adjustment to correct the measured carbon dioxide signal for potential long-term changes in sensor output. In the majority of measurements (89%), this resulted in an overestimation of expired nitrogen concentrations (range -0.7 to 1.7%), and consequently MBW outcomes. Correction of the CO2 signal reduced the mean (range) cumulative expired volume by 27.1% (-58.1%; 1.0%), functional residual capacity by 11.1% (-21.6%; 1.2%), and lung clearance index by 18.3% (-44.0%; -0.3%). Additionally, within-visit variability was substantially reduced with the corrected signals.

ConclusionInadequate signal-correction of the measured CO2 concentration in the EasyOne Pro LAB device leads to a non-systematic error in expired nitrogen concentrations and overestimation of test outcomes. Two-point calibration of the CO2 sensor may maintain accurate measurement of gas concentrations and overcome this error.


title: Estimation of the Lifetime Quality-Adjusted Life Years (QALYs) Lost Due to Syphilis acquired in the United States in 2018

abstract:
BackgroundThe purpose of this study was to estimate the health impact of syphilis in the United States in terms of the number of quality-adjusted life years (QALYs) lost attributable to infections in 2018.

MethodsWe developed a Markov model which simulates the natural history and long-term sequelae of syphilis. The model was parameterized by sex (men and women), sexual orientation (women who have sex with men, men who have sex with women [MSW], and men who have sex with men [MSM]), and by age at primary infection. We developed a separate decision tree model to account for health losses due to congenital syphilis. We estimated the average lifetime number of QALYs lost per infection, and the total expected lifetime number of QALYs lost due to syphilis acquired in 2018. We performed probabilistic sensitivity analysis to account for uncertainty in the models estimates.

FindingsWe estimated the average number of discounted lifetime QALYs lost per infection as 0.09 [0.03-0.19 95% uncertainty interval (UI)]. The QALY loss per infection was lower among MSM (0.06) than among MSW (0.15) and women (0.10). The total expected number of QALYs lost due to syphilis acquired in 2018 was 13,349 (5,071-31,360 95%UI). MSM account for 6,373 (47.7%) of the overall burden, compared to MSW (32.1%) and women (20.2%). For each case of congenital syphilis, we estimated 1.79 (1.43-2.16 95%UI) QALYs lost for the child and 0.06 (0.01-0.14 95%UI) QALYs lost for the mother. These per-case estimates correspond to 2,332 (1,871-2,825 95%UI) and 79 (17-177 95%UI) QALYs lost for children and mothers, respectively, due to congenital syphilis in 2018.

ConclusionSyphilis causes substantial health losses in adults and children. Quantifying these health losses in terms of QALYs can inform cost-effectiveness analyses and can facilitate comparisons of the burden of syphilis to that of other diseases.

category: sexual and reproductive health


title: Deep Sequence Learning for Assessing Hypertension in Pregnancy from Doppler Signals

abstract:
Measuring blood pressure during pregnancy is an essential component of antenatal care, and is critical for detecting adverse conditions such as pre-eclampsia. The standard approach for measuring blood pressure is via manual auscultation by a trained expert or via an oscillometric self-inflating cuff. While both methods can provide reasonably accurate blood pressure measurements when used correctly, non-expert use can lead to significant error. Moreover, such techniques are uncomfortable and can cause bruising, pain and consequential resistance to use / low compliance. In this work, we propose a low-cost onedimensional Doppler-based method for the detection of hypertension in pregnancy.

Using a sample of 653 pregnant women of Mayan descent in highland Guatemala, we recorded up to 10 minutes of 1D Doppler data of the fetus, and blood pressure from both arms using an Omron M7 oscillometric cuff. A hierarchical LSTM network with attention mechanism was trained to classify hypertension in pregnancy, producing an area under the receiveroperator curve of 0.94. A projection of the data into lower dimensions indicates hypertensive cases are located at the periphery of the distribution of the output of the distribution.

This work presents the first demonstration that blood pressure can be measured using Doppler (without occlusion) and may lead to a novel class of blood pressure monitors which allow rapid blood pressure estimation from multiple body locations. Moreover, the association of the predictor with the fetal blood flow indicates that hypertension in the mother has a significant effect on the fetal blood flow.

category: obstetrics and gynecology


title: Explainable deep transfer learning model for disease risk prediction using high-dimensional genomic data

abstract:
Building an accurate disease risk prediction model is an essential step in the modern quest for precision medicine. While high-dimensional genomic data provides valuable data resources for the investigations of disease risk, their huge amount of noise and complex relationships between predictors and outcomes have brought tremendous analytical challenges. Deep learning model is the state-of-the-art methods for many prediction tasks, and it is a promising framework for the analysis of genomic data. However, deep learning models generally suffer from the curse of dimensionality and the lack of biological interpretability, both of which have greatly limited their applications. In this work, we have developed a deep neural network (DNN) based prediction modeling framework. We first proposed a group-wise feature importance score for feature selection, where genes harboring genetic variants with both linear and non-linear effects are efficiently detected. We then designed an explainable transfer-learning based DNN method, which can directly incorporate information from feature selection and accurately capture complex predictive effects. The proposed DNN-framework is biologically interpretable, as it is built based on the selected predictive genes. It is also computationally efficient and can be applied to genome-wide data. Through extensive simulations and real data analyses, we have demonstrated that our proposed method can not only efficiently detect predictive features, but also accurately predict disease risk, as compared to many existing methods.

Author summaryAccurate disease risk prediction is an essential step towards precision medicine. Deep learning models have achieved the state-of-the-art performance for many prediction tasks. However, they generally suffer from the curse of dimensionality and lack of biological interpretability, both of which have greatly limited their applications to the prediction analysis of whole-genome sequencing data. We present here an explainable deep transfer learning model for the analysis of high-dimensional genomic data. Our proposed method can detect predictive genes that harbor genetic variants with both linear and non-linear effects via the proposed group-wise feature importance score. It can also efficiently and accurately model disease risk based on the detected predictive genes using the proposed transfer-learning based network architecture. Our proposed method is built at the gene level, and thus is much more biologically interpretable. It is also computationally efficiently and can be applied to whole-genome sequencing data that have millions of potential predictors. Through both simulation studies and the analysis of whole-genome sequencing data obtained from the Alzheimers Disease Neuroimaging Initiative, we have demonstrated that our method can efficiently detect predictive genes and it has better prediction performance than many existing methods.


title: Whole Exome Sequencing (WES) identifies Homozygous mutation in g.37429732G>A in GRHPR gene is responsible for early onset of nephrolithiasis in the population of West Bengal, India

abstract: Kidney stone disease (KSD) or nephrolithiasis (NL), is a serious clinical concern that gradually poses threat to global health and economy. The frequency of KSD is rapidly increasing and about 12% of the Indian population are suffering from this disease. In this scenario, we studied the incidence and age group stratification of KSD in the eastern part of India. Furthermore, patients with GRHPR mutation were highly predominant. Furthermore, real time quantitative PCR expression and protein expression through immunoblotting along with protein activity & computational analysis were carried out in patients with GRHPR mutation. Our findings revealed that the candidates of the early age group are prone to hyperoxaluria moreover a potent and frequent mutation in the GRHPR gene is widely present in this age group. Further, biochemical tests such as serum creatine, serum urea, serum and urinary calcium were carried out for the patients along with age matched controls. Moreover, the actual underlying cause of nephrolithiasis for lower age groups still remains unclear. The study revealed that mutations were more often found in GRHPR, AGXT, and HOGA1 genes in the study cohort.


title: Enhancing the BOADICEA cancer risk prediction model to incorporate new data on RAD51C, RAD51D, BARD1, updates to tumour pathology and cancer incidences.

abstract:
BackgroundBOADICEA for breast cancer and the epithelial ovarian cancer (EOC) models included in the CanRisk tool (www.canrisk.org) provide future cancer risks based on rare pathogenic variants in cancer-susceptibility genes, polygenic risk scores, breast-density, questionnaire-based risk factors and family history. Here, we extend the models to include the effects of pathogenic variants in recently established breast cancer and EOC susceptibility genes, up-to-date age-specific pathology distributions and continuous risk factors.

MethodsBOADICEA was extended to further incorporate the associations of pathogenic variants in BARD1, RAD51C and RAD51D with breast cancer risk. The EOC model was extended to include the association of PALB2 pathogenic variants with EOC risk. Age-specific distributions of oestrogen-receptor-negative and triple-negative breast cancer status for pathogenic variant carriers in these genes and CHEK2 and ATM were also incorporated. A novel method to include continuous risk factors was developed, exemplified by including adult-height as continuous.

ResultsBARD1, RAD51C and RAD51D explain 0.31% of the breast cancer polygenic variance. When incorporated into the multifactorial model, 34-44% of these carriers would be reclassified to the near-population and 15-22% to the high-risk categories based on the UK NICE guidelines. Including height as continuous, increased the BC relative-risk variance from 0.002 to 0.010.

ConclusionsThese extensions will allow for better personalised risks for BARD1, RAD51C, RAD51D and PALB2 pathogenic variant carriers and more informed choices on screening, prevention, risk factor modification or other risk-reducing options.


title: Long-term and low-level envelope C2V3 stimulation from highly diverse virus isolates leads to frequent development of broad and elite antibody neutralization in HIV-1 infected individuals

abstract: Elicitation of potent neutralizing antibodies against genetically diverse HIV-1 isolates is important for an effective HIV-1 vaccine. Some HIV-1 infected patients produce such broadly neutralizing antibodies (bNAbs). Identification of host and viral correlates of bNAb production may help develop the next generation of HIV-1 vaccines. We carried out the first detailed characterization of the neutralizing antibody response and identify viral and host factors associated with the development of bNAbs in HIV-1 infected patients from Angola, one of the oldest, more dynamic, and diverse HIV-1 epidemics in the world. Plasma samples from 322 HIV-1 infected patients were collected in 2001, 2009 and 2014. Phylogenetic analysis of C2V3C3 envelope sequences identified a diverse array of subtypes including A1, A2, B, C, D, F1, G, H, J, untypable strains, and recombinant forms which prevailed over pure subtypes. Notably, 56% of the patients developed cross, broad, or elite neutralizing responses against a reference panel of tier 2 Env-pseudoviruses far exceeding results obtained elsewhere in the world. The frequency of elite neutralizers was higher in 2014, when patients were on ART and had low viremia, than in 2009 when patients were drug naive. In drug naive patients, broad neutralization was associated with subtype C infection, lower CD4+ T cell counts, higher age, or higher titer of C2V3C3-specific antibodies relative to patients that did not develop bNAbs. Neutralizing antibodies targeted the V3-glycan supersite in most patients but antibodies specific for the V2 apex, the CD4 binding site, the gp41 membrane-proximal external region (MPER) and unknown epitopes were also found in some patients. V3 and C3 regions were significantly less variable and less subject to positive selection in elite neutralizers compared to weak or no neutralizers suggesting an active role of bNabs directed against these regions in controlling HIV-1 replication and diversification. Hence, development of broad and elite antibody neutralization against HIV-1 requires long-term and low-level envelope V3C3 stimulation from highly diverse subtype C isolates. These results have direct implications for the design of a new generation of HIV-1 vaccines.

category: hiv aids


title: Sputnik-V reactogenicity and immunogenicity in the blood and mucosa: a prospective cohort study.

abstract:
BackgroundSputnik-V (Gam-COVID-Vac) is a heterologous, recombinant adenoviral (rAdv) vector-based, COVID-19 vaccine now used in >70 countries. Yet there is a shortage of data on this vaccines performance in diverse populations. Here, we performed a prospective cohort study to assess the reactogenicity and immunologic outcomes of Sputnik-V vaccination in a multiethnic cohort from Kazakhstan.

MethodsCOVID-19-free participants (n=82 at baseline) were followed at day 21 after Sputnik-V dose 1 (rAd5) and dose 2 (rAd26). Self-reported local and systemic adverse events were captured using questionnaires. Blood and nasopharyngeal swabs were collected to perform SARS-CoV-2 diagnostic and immunologic assays.

FindingsOf the 73 and 70 participants retained post-dose 1 and 2, respectively, most (>50%) reported mild-to-moderate injection site or systemic reactions to vaccination; no severe or potentially life-threatening conditions were reported. dose 1 appeared to be more reactogenic than dose 2, with fatigue and headache more frequent in participants with prior COVID-19 exposure. After dose 2 nausea was more common in subjects without prior COVID-19. The combined S-IgG and S-IgA seroconversion rate was 97% post-dose 1, remaining the same post-dose 2. The proportion of participants with detectable virus neutralization titers was 83% post-dose 1, and increased to 98% post-dose 2, with the largest relative increase observed in participants without prior COVID-19 exposure. Nasal S-IgG and S-IgA increased post-dose 1, while the boosting effect of dose 2 on mucosal S-IgG, but not S-IgA, was only observed in subjects without prior COVID-19. Systemically, vaccination reduced serum levels of growth regulated oncogene (GRO), which correlated with an elevation in blood platelet count.

InterpretationSputnik-V dose 1 elicited both blood and mucosal SARS-CoV-2 immunity, while the immune boosting effect of dose 2 was minimal, suggesting that adjustments to the current vaccine dosing regimen may be necessary to optimize immunization efficacy and cost-effectiveness. Although Sputnik-V appears to have a reactogenicity profile similar to that of other COVID-19 vaccines, the observed alterations to the GRO/platelet axis call for further investigation of Sputnik V effects on systemic immunology.

FundingMinistry of Education and Science of the Republic of Kazakhstan.


title: A Micronized Electrostatic Precipitator Respirator Effectively Removes Ambient SARS-CoV-2 Bioaerosols

abstract:
RationaleInhalation of ambient SARS-CoV-2-containing bioaerosols leads to infection and pandemic airborne transmission in susceptible populations. Filter-based respirators effectively reduce exposure but complicate normal respiration through breathing zone pressure differential and are therefore impractical for long-term use.

ObjectivesWe tested the comparative effectiveness of a prototyped micronized electrostatic precipitator (mEP) to a filter-based respirator (N95) in the removal of viral bioaerosols from a simulated inspired air stream.

MethodsEach respirator was tested within a 16-liter environmental chamber housed within a Class III biological safety cabinet within biosafety level 3 containment. SARS-CoV-2 containing bioaerosols were generated into the chamber, drawn by vacuum through each respirator, and physical particle removal and viral genomic RNA were measured distal to the breathing zone of each device.

Measurement and Main ResultsThe mEP respirator removed particles (96.5{+/-}0.4%) approximating efficiencies of the N95 (96.9{+/-}0.6%). The mEP respirator similarly decreased SARS-CoV-2 viral RNA (99.792%) when compared to N95 removal (99.942%) as a function of particle removal from the airstream distal to the breathing zone of each respirator.

ConclusionsThe mEP respirator approximated performance of a filter-based N95 respirator for particle removal and viral RNA as a constituent of the SARS-CoV-2 bioaerosols generated for this evaluation. In practice, the mEP respirator would provide equivalent protection from ambient infectious bioaerosols as the N95 respirator without undue pressure drop to the wearer, thereby facilitating long-term use in an unobstructed breathing configuration.


title: Neutralizing Activities against the Omicron Variant after a Heterologous Booster in Healthy Adults Receiving Two Doses of CoronaVac Vaccination

abstract:
BackgroundThe use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) against SARS-CoV-2 is implemented worldwide. However, waning immunity and breakthrough infections have been observed. Therefore, we hypothesized that the heterologous booster might improve the protection against the delta and omicron variants.

MethodsA total of 224 individuals who completed the two-dose CoronaVac for six months were included. We studied reactogenicity and immunogenicity following a heterologous booster with the inactivated vaccine (BBIBP), the viral vector vaccine (AZD1222), and the mRNA vaccine (both BNT162B2 and mRNA-1273). We also determined immunogenicity at 3- and 6-months boosting intervals.

ResultsThe solicited adverse events (AEs) were mild to moderate and well-tolerated. Total RBD immunoglobulin (Ig), anti-RBD IgG, focus reduction neutralization test (FRNT50) against delta and omicron variants, and T cell response were highest in the mRNA-1273 group followed by the BNT162b2, AZD1222 and BBIBP groups, respectively. We also witnessed a higher total Ig anti-RBD in the long-interval than in the short-interval groups.

ConclusionsAll four booster vaccines significantly increased binding and NAbs in individuals immunized with two doses of CoronaVac. The present evidence may benefit vaccine strategies development to thwart variants of concern, including the omicron variant.

category: allergy and immunology


title: Comparative effectiveness of COVID-19 vaccination against death and severe disease in an ongoing nationwide mass vaccination campaign

abstract:
BackgroundAs national COVID-19 mass vaccination campaigns are rolled out, it is important to demonstrate and measure their public health benefit. We aimed to estimate COVID-19 Vaccine Effectiveness (VE) against severe disease and death in the Greek population, for all vaccines in use.

MethodsNationwide active surveillance and vaccination registry data during January-December 2021 were used to estimate VE via quasi-Poisson regression, as one minus the Incidence Rate Ratio, adjusted for age and calendar time. Interaction terms were included to assess VE by age group, against the "delta" SARS-CoV-2 variant and waning of VE over time.

ResultsTwo doses of BNT162b2, mRNA-1273 or ChAdOx1 nCov-19 vaccines offered very high (>90%) VE against both intubation and death across all age groups, similar against both "delta" and previous variants, with one-dose Ad26.COV2.S slightly lower. There was some waning over time but VE remained >80% at six months, and three doses increased VE again to near 100%. Vaccination prevented an estimated 19,691 COVID-19 deaths (95% CI: 18,890-20,788) over the study period.

ConclusionsAll approved vaccines were very highly effective in preventing COVID-19 severe disease and death. Every effort should be made to vaccinate the population with at least two doses, in order to reduce the mortality and morbidity impact of the pandemic.

category: epidemiology


title: A mixed methods analysis of participation in social contact surveys

abstract:
BackgroundSocial contact survey data forms a core component of modern epidemic models: however, there has been little assessment of the potential biases in such data.

MethodsWe conducted focus groups with university students who had (n=13) and had not (n=14) completed a social contact survey during the COVID-19 pandemic. Qualitative findings were explored quantitatively by analysing participation data.

ResultsThe opportunity to contribute to COVID-19 research, to be heard and feel useful were frequently reported motivators for participating in the contact survey. Reductions in survey engagement following lifting of COVID-19 restrictions may have occurred because the research was perceived to be less critical and/ or because the participants were busier and had more contacts. Having a high number of contacts to report, uncertainty around how to report each contact, and concerns around confidentiality were identified as factors leading to inaccurate reporting. Focus groups participants thought that financial incentives or provision of study results would encourage participation.

ConclusionsIncentives could improve engagement with social contact surveys. Qualitative research can inform the format, timing, and wording of surveys to optimise completion and accuracy.

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title: The effect of maternal BMI, smoking and alcohol on congenital heart diseases: a Mendelian randomization study

abstract:
BackgroundCongenital heart diseases (CHDs) remain a significant cause of infant morbidity and mortality. Epidemiological studies have explored maternal risk factors for offspring CHDs, but few have used genetic epidemiology methods to improve causal inference.

MethodsThree birth cohorts, including 38,662 mother/offspring pairs (N = 319 CHD cases) were included. We used Mendelian randomization (MR) analyses to explore the effects of genetically predicted maternal body mass index (BMI), smoking and alcohol on offspring CHDs. We generated genetic risk scores (GRS) using summary data from large scale genome-wide association studies and validated the strength of the genetic instrument for exposure levels during pregnancy. Logistic regression was used to estimate the odds ratio (OR) of CHD per 1 standard deviation (SD) change in GRS. Results for the three cohorts were combined using random-effects meta-analyses. We performed several sensitivity analyses including multivariable MR to check the robustness of our findings.

ResultsThe GRSs associated with the exposures during pregnancy in all three cohorts. The associations of the GRS for maternal BMI with offspring CHD (pooled OR (95% confidence interval) per 1SD higher GRS: 1.01 (0.90, 1.13)) and lifetime smoking (pooled OR: 0.97 (0.87, 1.08)) were close to the null, though with wide confidence intervals. We observed weak evidence of an increased odds of offspring CHDs with increase in the maternal GRS for alcoholic drinks per week (pooled OR: 1.09 (0.98, 1.22)). Sensitivity analyses yielded similar results.

ConclusionsOur results do not provide robust evidence of an effect of maternal BMI or smoking on offspring CHDs. However, results were imprecise. Our findings, including the potential effect of maternal alcohol intake on offspring CHD need to be replicated, and highlight the need for more and larger studies with maternal and offspring genotype and offspring CHD data.


title: Outbreak.info genomic reports: scalable and dynamic surveillance of SARS-CoV-2 variants and mutations

abstract: The emergence of SARS-CoV-2 variants has prompted the need for near real-time genomic surveillance to inform public health interventions. In response to this need, the global scientific community, through unprecedented effort, has sequenced over 7 million genomes as of December 2021. The extraordinarily high sampling rate provides a unique opportunity to track the evolution of the virus in near real-time. Here, we present outbreak.info, a platform that can be used to track over 40 million combinations of PANGO lineages and individual mutations, across over 7,000 locations, to provide insights for researchers, public health officials, and the general public. We describe the data pipelines that enable the scalable ingestion and standardization of heterogeneous data on SARS-CoV-2 variants, the server infrastructure that enables the dissemination of the processed data, and the client-side applications that provide intuitive visualizations of the underlying data.


title: COVID-19 self-testing in Nigeria: Stakeholders opinions and perspective on its value for case detection

abstract:
BackgroundCOVID-19 testing coverage is limited in Nigeria. Access to SARS-CoV-2 self-testing kits may help improve the detection of asymptomatic and mildly symptomatic cases and increase the currently low rate of COVID-19 testing in the country. Before implementing SARS-CoV-2 self-testing in Nigeria, it is imperative to assess the populations perceptions regarding this innovation. We therefore conducted a qualitative study to investigate peoples values and preferences for SARS-CoV-2 self-testing in Nigeria.

MethodsWe used semi-structured interviews and focus group discussions among healthcare workers, community representatives, and public health implementors to explore values and perceptions around various aspects of COVID-19 testing, including conventional COVID-19 testing, SARS-CoV-2 self-testing, the safe and effective use of SARS-CoV-2 self-testing, actions upon receiving a positive SARS-CoV-2 self-test result, and future prospects for SARS-CoV-2 self-testing.

ResultsRespondents reported that there is limited availability of conventional SARS-CoV-2 testing in Nigeria. While just a few respondents were familiar with SARS-CoV-2 testing, respondents generally supported the use of SARS-CoV-2 self-testing as they felt it could assist with early case detection and improve access to testing. Concerns relating to the use of SARS-CoV-2 self-testing were majorly about the ability among low literacy populations to use and interpret the test, the affordability of tests, equity of access, and the availability of healthcare system support for those who test positive.

ConclusionThough the public perceive multiple benefits associated with access to SARS-CoV-2 self-testing, the efficiency of the national health service delivery system may limit access of the users of the kits to psychosocial and clinical support. In Nigeria, where COVID-19 vaccine coverage is low and the risk of further waves of COVID-19 is high, self-testing may assist in the prompt detection of cases and contribute to halting the spread of the virus.

category: public and global health


title: Critical success factors for high routine immunization performance: A case study of Nepal

abstract:
IntroductionThe essential components of a vaccine delivery system are well-documented, but robust evidence on how and why the related processes and implementation strategies drive catalytic improvements in vaccination coverage are not well established. To address this gap, we identified critical success factors that may have led to substantial improvements in routine childhood immunization coverage in Nepal from 2000 through 2019.

MethodsWe identified Nepal as an exemplar in the delivery of early childhood vaccines through analysis of DTP1 and DTP3 coverage data. Through interviews and focus group discussions at the national, regional, district, health post, and community level, we investigated factors that contributed to high and sustained vaccine coverage. We conducted a thematic analysis through application of implementation science frameworks to determine critical success factors. We triangulated these findings with quantitative analyses using publicly available data.

ResultsThe following success factors emerged: 1) Codification of health as a human right, along with other vaccine-specific legislation, ensured the stability of vaccination programming; 2) National and multi-national partnerships supported information sharing, division of labor, and mutual capacity building; 3) Pro-vaccine messaging through various mediums, which was tailored to local needs, generated public awareness; 4) Female Community Health Volunteers educated community members as trusted and compassionate neighbors; and 5) Cultural values fostered collective responsibility and community ownership of vaccine coverage.

ConclusionThis case study of Nepal suggests that the success of its national immunization program relied on the engagement and understanding of the beneficiaries. The immunization program was supported by consistent and reliable commitment, collaboration, awareness, and collective responsibility between the government, community, and partners. These networks are strengthened through a collective dedication to vaccination programming and a universal belief in health as a human right.


title: The progressive loss of brain network fingerprints in Amyotrophic Lateral Sclerosis predicts clinical impairment

abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by functional connectivity alterations in both motor and extra-motor brain regions. In network analysis, fingerprint represent a valid approach able to assess the subject-specific connectivity features of a given population. Here, we applied the Clinical Connectome Fingerprint (CCF) analysis to source-reconstructed magnetoencephalography (MEG) signals in a cohort of seventy-eight subjects: thirty-nine ALS patients and thirty-nine healthy controls. We set out to develop an identifiability matrix to assess the extent to which each subject was recognisable based on his/her connectome. The analysis was performed in all five canonical frequency bands. Then we built a multilinear regression model to test the ability of "clinical fingerprint" to predict the clinical evolution of disease assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-r), the Kings disease staging system and the Milano-Torino Staging (MiToS) disease staging system. We found a drop in patients identifiability in the alpha band compared to the healthy controls. Furthermore, the "clinical fingerprint" was predictive of ALSFRS-r (p=0.0397; {beta}=32.8), Kings (p=0.0001; {beta}= -7.40) and MiToS (p=0.0025; {beta}= -4.9) scores and negatively correlated with Kings and MiToS scales according to Spearmans correlation. Our results demonstrated the ability of the CCF approach in assessing the individual motor condition and its relationship with ALS disease. Thanks to the subject-specific characteristic of this approach, we hope that further exploration related to its clinical application may help improve the management of disease.

category: neurology


title: Maternal Disrespect and Abuse by Health Care Providers among postpartum women attending Mizan-Tepi University Teaching Hospital, South West Ethiopia

abstract:
BackgroundIn Ethiopia, only 48% of all births occur at health facilities. Maternal disrespect and abuse by health care providers during child birth is one of the main reasons that affect health care seeking behaviors from health facilities. Thus, this study aims to assess magnitude of maternal disrespect and abuse during institutional delivery among postpartum women at Mizan -Tepi University Teaching Hospital (MTUTH), Bench Sheko Zone, South west Ethiopia

MethodsInstitution-based cross-sectional study design was employed. A total of 409 postpartum women were enrolled using systematic random sampling technique between Augusts to September, in 2021. Pre-tested and structured questionnaire used for face-to-face interview. Data were coded, edited, and analyzed using SPSS version 25. Bivariate and multivariable logistic regression analyses were done. The presence and strength of association were determined using AOR with its 95% CI. Variables with P value of less than 0.05 were considered as statistically significant

ResultsAbout half (52.1%) of the postpartum women experienced at least one category of maternal disrespect and abuse during institutional delivery. No formal education status during labor [AOR=2.216; 95% CI:1.266, 3.879], delivery during night shifts [(AOR=2.2; 95% CI: 1.306, 3.772], living in rural area [AOR=3.014;95% CI:1.630,5.572], number of health provider 2-3[AOR=4.101; 95%CI:2.70,6.23] and number of health provider above three[AOR=8.13; 95%CI:2.12,5.62] were found to be strongly associated with reporting maternal disrespect and abuse.

ConclusionsThe study highlights that large proportion of mothers are experiencing maternal disrespect and abuse during institutional delivery in this study setting. Thus, appropriate interventions should be designed, focusing on supervision during night shifts, empowering childbearing women about their rights at health facilities and providing training for health care providers about respectful maternity care need to be emphatise.

category: nursing


title: Factors associated with secondhand smoke exposure among non-smoking employees in the workplace: A cross-sectional study in Qingdao, China

abstract:
ObjectiveThe study was designed to describe secondhand smoke (SHS) exposure among non-smoking employees in the workplace and identify factors that related exposure in Qingdao.

MethodsThe study subjects covered the key non-smoking places stipulated in the "Qingdao City Smoking Control Regulations". Airborne nicotine concentration in the workplace and saliva cotinine concentration of employees were measured. Questionnaire included employees demographics factors, smoke-free measures in the workplace, the employers tobacco hazard knowledge and attitudes towards smoke-free policy.

ResultsA total of 222 non-smoking employees and 46 employees were included in the study. The median concentrations of airborne nicotine and salivary cotinine were 0.389 g/m3 and 0.575 ng/ml. Educational status, average number of smokers per day and exposure time of SHS in the workplace, whether to divide smoking and non-smoking areas were related to the airborne nicotine concentration significantly. Age, educational status, exposure time of SHS in the workplace, tobacco control training and publicity and whether the employers support the "Qingdao Tobacco Control Regulation" were related to the salivary cotinine concentration significantly.

ConclusionsExposure to SHS is highly prevalent among non-smoking employees in the workplace. Interventions to reduce SHS exposure in the workplace are urgently needed.

category: occupational and environmental health


title: Agility and sustainability: A qualitative evaluation of COVID-19 Non-pharmaceutical Interventions (NPIs) in the UK logistics sector

abstract:
BackgroundThe emergence of SARS-CoV-2 triggered a chain of public health responses that radically changed our way of living and working. Non-healthcare sectors, such as the logistics sector, play a key role in such responses. This research aims to qualitatively evaluate the non-pharmaceutical interventions (NPIs) implemented in the UK logistics sector during the COVID-19 pandemic.

MethodsWe conducted nine semi-structured interviews in July-August 2020 and May-June 2021. In total 11 interviewees represented six companies occupying a range of positions in the UKs logistics sector, including takeaway food delivery, large and small goods delivery and home appliance installation, and logistics technology providers. Inductive thematic analysis was completed using NVivo12 to generate emerging themes and subthemes. Themes/subthemes relevant to interventions were mapped deductively onto an adapted Hierarchy of Control (HoC) framework, focusing on delivery workers. Themes/subthemes relevant to the process of implementation were analyzed to understand the barriers and facilitators of rapid responses.

ResultsHoC analysis suggests the sector has implemented a wide range of risk mitigation measures, with each company developing their own portfolio of measures. Contact-free delivery was the most commonly implemented measure and perceived effective. In addition, a broad range of measures were implemented, including social distancing, internal contact tracing, communication and collaboration with other key stakeholders of the sector. Process evaluation identified facilitators of rapid responses including capacity to develop interventions internally, localized government support, overwhelming external mandates, effective communication, leadership support and financial support for self-isolation, while barriers included unclear government guidance, shortage of testing capacity and supply, high costs and diversified language and cultural backgrounds. Main sustainability issues included compliance fatigue, and the possible mental health impacts of a prolonged rapid response.

ConclusionsThis research identified drivers and obstacles of rapid implementation of NPIs in response to a respiratory infection pandemic. Existing implementation process models do not consider speed to respond and the absence or lack of guidance in emergency situations such as the COVID-19. We recommend the development of a rapid response model to inform the design of effective and sustainable infection prevention and control policies and to focus future research priorities.

Contributions to the fieldO_LIThe study offered important insights into the process of the UK logistics sectors response to the COVID-19 pandemic.
C_LIO_LIThe Hierarchy of Control (HoC) framework was adapted for the evaluation of a collection of non-pharmaceutical interventions (NPIs) implemented in a non-healthcare sector.
C_LIO_LIThematic analysis of qualitative data generated themes that were relevant to the process of rapid implementation of NPIs during a public health emergency.
C_LIO_LIBarriers, facilitators and sustainability issues of the sectors rapid response to the COVID-19 pandemic have been highlighted to inform future research on implementation strategies.
C_LI


title: Investigating the Characteristics of Genes and Variants Associated with Self-Reported Hearing Loss in Older Adults in the UK Biobank

abstract: Age-related hearing loss is a common, heterogeneous disease with a strong genetic component, but to date most of the genes underlying human adult-onset hearing loss remain unknown. Most genetic studies have focussed on very rare variants (such as family studies and patient cohort screens) or very common variants (genome-wide association studies). Here we present a study based on exome sequencing and self-reported hearing loss in the UK Biobank, a large-scale biomedical database. We have carried out variant load analyses and compared the resulting gene lists to a manually-curated list of nearly 700 genes known to be involved in hearing in humans and/or mice. Our results suggest that relatively common as well as rare variants with a high predicted impact contribute to age-related hearing loss, and that the genetic contributions to age-related hearing loss may differ between the sexes. Our manually-curated list of deafness genes is a useful resource for candidate gene prioritisation in hearing loss.

category: genetic and genomic medicine