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Rubina Manuela Trimboli ORCID: orcid.org/0000-0002-1502-05871,
Paolo Giorgi Rossi2,
Nicolò Matteo Luca Battisti3,4,
Andrea Cozzi1,
Veronica Magni5,
Moreno Zanardo1 &
Francesco Sardanelli1,6
Insights into Imaging volume 11, Article number: 105 (2020) Cite this article
Breast cancer (BC) is the most common female cancer and the second cause of death among women worldwide. The 5-year relative survival rate recently improved up to 90% due to increased population coverage and women's attendance to organised mammography screening as well as to advances in therapies, especially systemic treatments. Screening attendance is associated with a mortality reduction of at least 30% and a 40% lower risk of advanced disease. The stage at diagnosis remains the strongest predictor of recurrences. Systemic treatments evolved dramatically over the last 20 years: aromatase inhibitors improved the treatment of early-stage luminal BC; targeted monoclonal antibodies changed the natural history of anti-human epidermal growth factor receptor 2-positive (HER2) disease; immunotherapy is currently investigated in patients with triple-negative BC; gene expression profiling is now used with the aim of personalising systemic treatments. In the era of precision medicine, it is a challenging task to define the relative contribution of early diagnosis by screening mammography and systemic treatments in determining BC survival. Estimated contributions before 2000 were 46% for screening and 54% for treatment advances and after 2000, 37% and 63%, respectively. A model showed that the 10-year recurrence rate would be 30% and 25% using respectively chemotherapy or novel treatments in the absence of screening, but would drop to 19% and 15% respectively if associated with mammography screening. Early detection per se has not a curative intent and systemic treatment has limited benefit on advanced stages. Both screening mammography and systemic therapies continue to positively contribute to BC prognosis.
The stage at diagnosis is still crucial in determining survival outcomes for breast cancer.
Screening attendance is associated with a reduction of advanced-stage disease.
Novel endocrine and anti-human epidermal growth factor receptor 2 (HER2)-targeted therapies have substantially improved survival.
Early diagnosis and personalised treatments synergistically contribute to improve prognosis.
We do still need breast cancer screening in the era of precision medicine.
Breast cancer is the most common female cancer worldwide, accounting for 30% of all new cancer diagnoses in women [1]. Social and economic trends are associated with a continuous increase in incidence rates by approximately 0.5% per year [1, 2]. Ageing population, maternity delay and low parity, obesity and sedentary lifestyle – along with an escalation in the diffusion of breast cancer mammography screening – contributed to this increase in high-income countries [2].
Traditionally, survival outcomes are influenced by tumour size, nodal involvement, grade, hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Although breast cancer remains the second leading cause of death among women after lung cancer, the 5-year relative survival rate in the United States has improved from 79% in 1984–1986 to 91% in 2008–2014 [3, 4]. Similar trends have been observed in Europe: in Italy, survival improved from 80% in 1995 to 88% in 2010 [5].
As detailed by the timeline in Fig. 1, breast cancer care has substantially evolved over the past fifty years, with non-negligible changes in screening and diagnostics, histological analysis, surgery, radiation therapy, and systemic treatments. The implementation and diffusion of screening mammography and various improvements in systemic anticancer treatments have been the main drivers of these changes [6]. In Europe, 63.9 million women had access to population-based breast cancer screening in 2016 compared with 54.4 million in 2007, with 88% of the estimated target population completing rollout, compared with 41% in 2007. Nevertheless, a wide geographical variability in invitation coverage still exists [7]. Similarly, in the 2000s, the use of chemotherapy has increased up to 80%, and the use of tamoxifen up to 50% for patients with oestrogen receptor-positive tumours: nowadays, in Italy, about 50% of patients undergoing surgery for stage I–III breast cancer receive systemic treatments that include targeted therapy [8], while in the United States targeted therapy is administered to almost 20% of patients with stage I–II disease and to over 60% of those with stage III disease [9]. Of note, along with traditional prognostic factors, gene expression profiling is now increasingly adopted, aiming to personalise therapeutic approaches and escalate or de-escalate systemic treatments [10]. In this complex framework, an evaluation of the impact of screening and systemic treatments on breast cancer prognosis looks challenging: their relative contribution may substantially differ across countries with different screening attendance rate and access to anticancer treatments.
Key advances in the recent history of breast cancer care (the date of introduction of each innovation was based on literature review with reference to first large studies confirming its clinical value). Specific evolutions or improvements are colour-coded. Imaging is in light blue, pathology in violet, surgery in red, radiation therapy in blue-green, systemic treatments in yellow. RT, radiation therapy: IHC, immunohistochemistry; MRI, magnetic resonance imaging; CDK4/6, cyclin-dependent kinase 4/6
Benefits deriving from screening and early diagnosis may become questionable when considering the efficacy of current systemic treatment options. In a theoretical model, a break-even point can be hypothesised when the advantages of early diagnosis by screening are nullified by the efficacy of individualised therapies. Nonetheless, detecting breast cancer before it is no longer curable should still be considered an advantage for the patient, since it remains unlikely that currently available therapies could be so effective without an early diagnosis. Any modification to this balance relies on the potential of systemic treatments to kill cancer cells at any stage, reducing or nullifying the screening benefit.
This critical review highlights the major landmark improvements in mammography screening and systemic treatment, to appraise their impact on breast cancer prognosis and to question the role of breast cancer screening in the era of precision medicine.
Mammography screening
Mammography screening was introduced in 1956 for the "detection of early cancer of the breast" [11]. In the 1970s, several randomised controlled trials confirmed a beneficial improvement of mammography screening on breast cancer mortality [12]. Such benefit pertains to women aged 50 to 74 years and is maximal, about 30%, in those aged 60 to 69 years [13,14,15,16]. Mammography screening programs have the general aim of reducing breast cancer-specific mortality both by minimising the risk of diagnosing breast cancer in the advanced stage and by maximising the efficacy and safety of anticancer treatments and their impact on prognosis.
The first x-ray units dedicated to mammography used x-ray film and paired fluorescent screens to capture the image, in the so-called screen-film mammography, which has been gradually replaced since the early 2000s by digital mammography units. In 2005, a landmark study by Pisano et al. [17] compared the diagnostic accuracy of digital and screen-film mammography in 42,760 asymptomatic women. At receiver operating characteristic analysis over the entire population, the areas under the curve (AUCs) of the two methods differed by a non-significant 0.03. However, the digital technique was significantly superior among women over 50 (0.15 AUC difference), among women having heterogeneously or extremely dense breasts (0.11 AUC difference), and among women being in pre- or perimenopause (0.15 AUC difference). Digital mammography allowed also to deliver a lower radiation dose and resulted in easier image storage and subsequent access. Its initially higher costs dwindled quite quickly, its uptake steadily increased [18, 19]. By 2015, 96% of all mammography units in the United States had gone digital [20].
The incidence of advanced-stage tumours in the target population is a specific proxy indicator of screening efficacy, given the absence of confounding effects of treatments at the time of diagnosis. However, studies on this topic have adopted different thresholds in defining the severity of the diseases and are characterised by poor to fair overall quality. Nevertheless, a meta-analysis of trials combined their results – including the most severe disease categories available – and showed a significant reduction in the risk of advanced-stage disease for women aged 50 years or older (relative risk 0.62, 95% confidence interval [CI] 0.46–0.83) randomly assigned to undergo screening: this benefit was however not seen in women aged 39 to 49 years [14].
More recently, a prospective Italian cohort study was conducted on 413,447 women undergoing screening in the 1990s and followed up for 13 years as part of the IMPACT project [21]. Screening attendance was positively associated with: (a) a 39% reduction of the incidence of pT2–T4 lesions (66.3‰ versus 108.6‰, incidence rate ratio 0.61, 95% CI 0.57–0.66), including a 28% reduction of pT2 lesions and a 68% reduction of pT3–T4 lesions; (b) a 28% reduction in the incidence of stage II–IV disease (130.1‰ versus 180.6‰, incidence rate ratio 0.72, 95% CI 0.68–0.76), including a 35% reduction of stage IIB, a 43% reduction of stage III, and a 73% reduction of stage IV. Notably, patients undergoing screening also benefited from a 17% reduction in the incidence of poorly differentiated carcinomas and from a 50% increase of breast-conserving surgery rates. These results were also confirmed following adjustments to exclude self-selection bias, a significant reduction in the use of mastectomy being also observed [22].
Another interesting large population study – including 549,091 women across nine Swedish counties [23] – was conducted to evaluate the impact of screening mammography on breast cancer mortality. The study used an analytic strategy focusing on the incidence of fatal breast cancers within 10 years from the date of diagnosis, whereas other studies had been retroactively considering 10 years from the date of death. Women who attended mammography screening had a significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk 0.59, 95% CI 0.51–0.68) and a 25% reduction in the rate of advanced breast cancer (relative risk 0.75, 95% CI 0.66–0.84), regardless of the recent improvements in systemic treatments.
In 2019, the American Cancer Society and the National Cancer Institute published cancer treatment and survivorship statistics in the United States. Most patients (44%) were diagnosed with stage I disease, 30% with stage II, 9% with stage III and 5% with stage IV. The 5-year breast cancer relative survival ranged from approximately 100% for stage I disease to 26% for stage IV breast cancer [9]. Interestingly, in 2018 Mariotto et al. [24] provided the first population-based summaries of the risk of breast cancer recurrence in United States women, using cancer registry disease-specific survival: stage remained the strongest predictor of the risk of recurrence, along with age (60–74 years) and HR-negative status. Thus, we can still affirm that tumour stage has a substantial impact on prognosis and on the risk of disease recurrence.
Systemic treatments
Chemotherapy has been used in the adjuvant setting since the early 1970s when landmark studies in the United States and in Italy documented a benefit of regimens such as L-phenylalanine mustard or the combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in patients with node-positive breast cancer [25, 26]. In the 1980s and 1990s, anthracyclines and taxanes proved to be more effective than CMF [27]; in the meantime, tamoxifen was found to substantially improve the survival of women with HR-positive tumours [28], and later on, aromatase inhibitors (AIs) proved to further improve outcomes in postmenopausal patients. During the 2000s, anti-HER2 therapies were developed as one of the first targeted systemic treatment options, changing dramatically the management and prognosis of HER2-positive breast cancer; in the same decade, genome expression profiling was deployed in routine practice, further improving the personalisation of breast cancer treatments [29]. Nonetheless, patient selection remains crucial to maximise efficacy and safety of systemic treatments. The current standard of care for different disease subtypes is summarised below.
Luminal breast cancer
The introduction of AIs has been a key improvement in the management of HR-positive, HER2-negative breast cancer [9, 30]. Nowadays, AIs are standard of care for postmenopausal women, based on several studies that have documented better recurrence-free survival and disease-specific mortality in women treated with AIs compared with tamoxifen [19]. Two large phase III studies (the SOFT and TEXT studies) confirmed the role of AIs also for premenopausal patients and/or with high-risk disease, along with ovarian function suppression justified by a recurrence-free survival benefit [31]. An extended course of adjuvant endocrine therapy may also further improve outcomes, especially following upfront use of tamoxifen [32,33,34,35,36,37,38,39], since late recurrences remain a relevant issue for patients with luminal breast cancer [40]. Cyclin-dependent kinase 4/6 inhibitors are also being investigated in the adjuvant setting in several clinical trials [41,42,43,44], which might in due course change the current treatment paradigm in this setting.
Targeted agents are the foundation of precision medicine, which involves the use of drugs interfering with specific molecular alterations that drive tumour growth and spread: for example, targeted anti-HER2 agents have radically changed the natural history and prognosis of HER2-positive disease. The use of the anti-HER2 monoclonal antibody trastuzumab for 1 year, along with chemotherapy, is now standard of care for tumours with a size of 5 mm or greater and for tumours of any size with nodal involvement, based on the substantial disease-free and overall survival benefits that have been reported when compared with the use of chemotherapy alone (disease-free survival, hazard ratio for recurrence 0.60, 95% CI 0.50–0.71; overall survival, hazard ratio for mortality 0.66, 95% CI 0.57–0.77) [45]. Moreover, additional benefits have been documented with adjuvant treatment escalation in higher-risk tumours: adding novel anti-HER2 agents, such as pertuzumab and neratinib, improves disease-free survival in women with node-positive disease [46] and recurrence rates in patients with large and HR-positive, HER2-positive tumours [47]. On the other hand, adjuvant treatment de-escalation has been investigated for patients with a lower risk of breast cancer recurrence in order to minimise the impact of systemic treatment on safety and quality of life [48]. Response to preoperative systemic treatment is a prognostic factor in patients with HER2-positive breast cancer, with better survival outcomes in patients without invasive disease at the surgical specimen, defined as ypT0/Tis ypN0 [49]. Therefore, neoadjuvant systemic treatment remains a very reasonable approach [50] and the addition of pertuzumab to trastuzumab to chemotherapy has become a standard of care, considering the improvements in pathological complete response rates [51, 52].
Triple-negative breast cancer
The systemic treatment of HR-negative and HER2-negative breast cancer is still largely limited to the use of chemotherapy. Adjuvant chemotherapy remains standard of care for patients with triple-negative breast cancers, either of 5 mm or greater or with pathologically involved lymph nodes [53]. In this specific setting, several trials are currently investigating the role of novel agents such as immunotherapy, which aims to boost the immune response against the tumour [54,55,56]. Neoadjuvant chemotherapy is the preferable approach in patients with locally advanced disease or in those who are not candidates for upfront surgery. Nonetheless, the role of neoadjuvant systemic therapy has also expanded, aiming to improve surgical operability and cosmetic outcomes but also to test the chemosensitivity of breast cancer in vivo, which has relevant prognostic implications [49, 57].
Genomics and the ability to evaluate simultaneously the expression of multiple genes led to the development of gene expression profiles, which have been validated to identify patients with a higher risk of disease recurrence who may benefit from the use of adjuvant chemotherapy. Oncotype Dx has been validated both as a prognostic and a predictive tool, although Mammaprint [58], EndoPredict [59, 60], Breast Cancer Index [61] and Predictor Analysis of Microarray 50 (PAM50) [62, 63] may also be used. Oncotype Dx identifies women with node-negative, HR-positive breast cancer whose prognosis is so favourable that the absolute benefit of chemotherapy is likely to be very low. Patients with HR-positive node-negative cancers derive substantial benefit from chemotherapy when their score is high, typically higher than 25. On the other hand, if their score is low or midrange (lower than 25), adding chemotherapy to endocrine treatment for women over 50 showed no benefit, although younger women may experience some benefit [64, 65]. While the use of Oncotype Dx in patients with node-positive, HR-positive breast cancer is supported by less robust evidence, it has been considered [66] and is currently being investigated [67].
The winning weapon: mammography screening plus systemic treatments
Defining the relative contribution of screening mammography and systemic treatments to improve breast cancer outcomes is a challenging task. The increasing use of screening and the gradual implementation of more effective therapeutic approaches occurred over nearly the same period since the 1970s. In the meantime, breast surgery has also evolved, along with the introduction of sentinel lymph node biopsy and radiation therapy. Overall, each of all these developments substantially contributed to improve patient outcome.
The Cancer Intervention and Surveillance Modelling Network used modelling techniques to provide estimates of the contributions of screening mammography and adjuvant treatment to the reduction of breast cancer mortality in the United States from 1975 to 2000 [68]. Seven independent statistical models were developed and yielded similar qualitative conclusions, namely that "the decline in mortality rate can be explained by a combination of screening and therapy and not by either one alone". The proportion of the total reduction in the rate of death from breast cancer attributed to screening varied in the seven models from 28% to 65% (median 46%). On the other hand, the contribution of systemic therapy including chemotherapy and tamoxifen varied from 35% to 72% (median 54%): differences in these estimates reflect the mutual interaction between the two interventions [68].
Saadatmand et al. [69] investigated – in a large population-based cohort study – whether tumour stage at diagnosis still influences survival in the context of the current therapeutic approaches. This prospective nationwide population-based study was conducted in the Netherlands and included 173,797 women diagnosed with breast cancer, with two cohorts being identified according to the year of breast cancer diagnosis. A total of 80,228 patients were diagnosed with breast cancer from 1999 to 2005, while 93,569 from 2006 to 2012: in this second period – following national guidelines – systemic therapy was more widely used. At univariate and multivariate analyses, tumour stage and nodal status significantly influenced overall and relative survival in both cohorts. Relative survival rates ranged from almost 100% in both cohorts for in situ tumours to 57% and 59% for T4 tumours in the older and more recent cohort, respectively. At multivariate analysis, breast-conserving treatment (more frequently pursued in the 2006–2012 cohort) resulted in a significant survival benefit compared with mastectomy, whereas lymph node dissection (less frequently pursued) was associated with a significantly worse overall survival. The wider use of chemotherapy in the 2006–2012 cohort conferred a hazard ratio for death of 0.86 (95% CI 0.80–0.92). These large-scale results clearly demonstrate that while the use of chemotherapy may impact on survival, tumour size at diagnosis still matters. Authors concluded that "in the current era of effective systemic therapy, diagnosis of breast cancer at an early stage remains vital" [69]. Moreover, considering United States women diagnosed with breast cancer at age 60–74, summaries of the risk of breast cancer recurrence showed a 5-year recurrence rate of 2.5%, 9.6% and 34.5% for stages I, II and III HR-positive breast cancers, and a 5-year recurrence rate of 6.5%, 20.2% and 48.5% for stages I, II and III HR-negative breast cancers [24].
Another study from the United States [6] also assessed to what extent digital mammography screening and novel systemic therapies contributed to the improvement in breast cancer mortality in different disease subtypes from 2000 to 2012: its results are summarised in Table 1. Complex simulation models from the Cancer Intervention and Surveillance Network projecting breast cancer mortality trends for women aged 30 to 79 years estimated a 12% difference (model range, 10–16%) in the overall disease-specific mortality reduction between 2000 (37%, model range, 27–42%) and 2012 (49%, model range, 39–58%). The relative contribution to the decrease in overall breast cancer mortality in 2012 was 37% (model range, 26–51%) for screening and 63% (model range, 49–74%) for treatment. Of the 37% mortality reduction associated with screening in 2012, 33% (model range, 29–48%) was associated with screening advances before 2000 and 4% (model range, 1–8%) after 2000 (the shift from screen-film to digital mammography was relatively less relevant than previous improvements when considering the conspicuous advancements in therapeutic options). Similarly, of the 63% mortality reduction associated with treatments in 2012, 32% was associated with chemotherapy, 27% with hormone therapy and 4% with trastuzumab. Of the 31% mortality reduction (model range, 23–37%) associated with chemotherapy, 9% (model range, 7–14%) was associated with chemotherapy advances after 2000 (largely taxanes). Of the 27% mortality reduction (model range, 18–36%) associated with hormone therapy, 7% (model range, 2–12%) was associated with advances in hormone therapy after 2000 (largely from AIs) [6].
Table 1 Association of screening and treatment with breast cancer mortality in US women from 2000 to 2012
Subtype analyses also demonstrated significant variations in the relative contribution of screening and treatment to the mortality reduction in different tumour molecular subtypes. The largest benefit of screening (48%, model range, 38–57%) was found in the triple-negative tumour breast cancer cohort, while the largest benefit of treatment (69%, model range, 59–77%) was documented in luminal tumours. According to this model-based analysis, both screening and treatment contributed and still contribute to the improvement in breast cancer mortality, with progressively greater contributions of therapeutic advances in the last decades [6].
The relative contribution associated with mammography screening and advances in systemic therapies to the reduction in the recurrence rate is simulated in Figs. 2 and 3. Here, four scenarios combine variably the contribution of screening mammography and chemotherapy or novel systemic treatments (i.e. AIs and targeted agents). In this simulation, stage distribution was derived from Puliti et al. [21], considering attenders and non-attenders to mammography screening and adjusted for self-selection. A 5% overdiagnosis attributed to population screening has been considered when it was included in the scenario. Ten-year disease-specific survival for HR-positive and HR-negative cancers was retrieved from Mariotto et al. [24], based on women aged 60–74 years treated in the 1992–1999 period or in the 2000–2013 period, when more advanced therapies were available. This simulation shows how combining screening mammography and novel systemic agents represent the most favourable scenario with the lowest number of recurrences, also detailing how the recurrence rate at 10 years would be 30% for chemotherapy without screening and 19% for chemotherapy with screening, 25% for novel treatments without screening and 15% for novel treatments with screening.
Effect of screening and chemotherapy on breast cancer recurrences among women aged 60 to 74 years, diagnosed with breast cancer between 1992 and 1999. Stage distribution was derived from Puliti et al. [21] considering attenders and non-attenders to screening mammography; 5% overdiagnosis attributed to screening mammography is taken into account. HR+ and HR− recurrences are back-calculated from Mariotto et al. [24]. The worst scenario reflects the absence of mammography screening and the use of chemotherapy alone. BCs, breast cancers; HR+, hormone receptor-positive breast cancers; HR−, hormone receptor-negative breast cancers
Effect of screening and novel systemic treatments on breast cancer recurrences among women aged 60 to 74 years, diagnosed with breast cancer between 2000 and 2013. Stage distribution was derived from Puliti et al. [21] considering attenders and non-attenders to screening mammography; a 5% overdiagnosis attributed to screening mammography was taken into account. HR+ and HR− recurrences are back-calculated from Mariotto et al. [24]. The most favourable scenario arises from the use of mammography screening associated with novel systemic treatments. BCs, breast cancers; HR+, hormone receptor-positive breast cancers; HR−, hormone receptor-negative breast cancers
Two important aspects should however be considered in the analysis of the evolution of screening and systemic therapies. Despite the widespread use of screening mammography, the introduction of digital techniques represents the most important technical advancement: of note, tomosynthesis has become the technique of choice for symptomatic women and those who are recalled for further assessment after a screening mammogram [13]. Conversely, the evidence in favour of its use as a first-level screening tool is still not sufficient in terms of reduction of interval cancer rate (possibly due to an underlying rate of overdiagnosis [70,71,72,73]) and European guidelines [13] have advised against its use for population-based screening programs. On the other hand, increasingly effective novel systemic treatment options are being introduced as a standard of care and gene expression profiling is progressively enabling better decision-making.
This is once again a turning point. In case of further outcome improvements, most of the contribution would then be attributable to better systemic treatments. Nevertheless, MRI [74] and other novel imaging modalities, such as contrast-enhanced mammography [75,76,77] could come to be considered screening tools in selected populations, their contribution being also promising. Furthermore, a recent survey among members of the European Society of Radiology [78] showed that there are high expectations on the use of artificial intelligence [79, 80]. Dedicated algorithms will focus on personalised risk prediction and prognosis [81] and machine/deep learning software has already shown high performance in interpreting screening mammography. Finally, the availability of molecular analyses on liquid biopsy could represent another promising option [82, 83].
However, further widespread benefits in breast cancer outcomes are expected to become ever slimmer in the context of the efficacy of the current standard treatments: research efforts will therefore need to focus on the role of precision medicine. Once outcomes are maximal in the overall breast cancer patient population, improvements might indeed be sought in selected populations and especially in those with poor prognosis.
The increasing use of screening mammography and improvements in systemic treatments have substantially reduced breast cancer mortality over the last two decades. However, defining their relative contribution to improving outcomes remains a challenging task. Early detection is crucial if followed by effective treatments. Nonetheless, treatments are still less effective in the case of advanced-stage disease. Prevention and early diagnosis contributed to almost half of the reduction in breast cancer mortality, whereas the rest is due to advances in breast cancer treatment, whose role and contribution has become predominant since the early 2000s. In the era of precision medicine, early detection remains crucial and a delay in breast cancer diagnosis, with a tumour detected at an advanced stage, can substantially increase mortality. Screening mammography and systemic anticancer treatment are synergistic in improving breast cancer prognosis.
AIs:
Aromatase inhibitors
AUC:
Area under the curve
CI:
Confidence interval
CMF:
Cyclophosphamide, methotrexate, and 5-fluorouracil
HER2:
Human epidermal growth factor receptor 2
Hormone receptor
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Paolo Giorgi Rossi participated thanks to the Innovative Partnership for Action Against Cancer (iPAAC) EC funded project.
Department of Biomedical Sciences for Health, Università degli Studi di Milano, Via Mangiagalli 31, 20133, Milan, Italy
Rubina Manuela Trimboli, Andrea Cozzi, Moreno Zanardo & Francesco Sardanelli
Epidemiology Unit, Azienda USL–IRCCS di Reggio Emilia, Via Amendola 2, 42122, Reggio Emilia, Italy
Paolo Giorgi Rossi
Breast Unit–Department of Medicine, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, UK
Nicolò Matteo Luca Battisti
Breast Cancer Research Division, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, UK
Medical School, Università degli Studi di Milano, Via Festa del Perdono 7, 20122, Milan, Italy
Veronica Magni
Unit of Radiology, IRCCS Policlinico San Donato, Via Morandi 30, 20097, San Donato Milanese, Italy
Francesco Sardanelli
Rubina Manuela Trimboli
Andrea Cozzi
Moreno Zanardo
All authors contributed to the conception and design of this work as well as to the writing and revision phases of the manuscript. All authors read and approved the final manuscript.
Correspondence to Rubina Manuela Trimboli.
R. M. Trimboli, P. Giorgi Rossi, N. M. L. Battisti, A. Cozzi, V. Magni, and M. Zanardo all declare that they have no conflicts of interest and nothing to disclose. F. Sardanelli declares to have received grants from or to be a member of the speakers' bureau/advisory board for Bayer Healthcare, Bracco Imaging, and General Electric.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Trimboli, R.M., Giorgi Rossi, P., Battisti, N.M.L. et al. Do we still need breast cancer screening in the era of targeted therapies and precision medicine?. Insights Imaging 11, 105 (2020). https://doi.org/10.1186/s13244-020-00905-3


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text:
Sale of Earls Court interests for £425 million
LEI: 549300TTXXZ1SHUI0D54
NOT FOR RELEASE, PUBLICATION OR DISTRIBUTION IN WHOLE OR IN PART IN, INTO OR FROM ANY JURISDICTION WHERE TO DO SO WOULD CONSTITUTE A VIOLATION OF THE RELEVANT LAWS OR REGULATIONS OF THAT JURISDICTION
THIS ANNOUNCEMENT CONTAINS INSIDE INFORMATION
CAPITAL & COUNTIES PROPERTIES PLC ("Capco" or "the Company")
Capco is pleased to announce that it has exchanged contracts for the sale of its interests in Earls Court, excluding Lillie Square, to APG and Delancey (on behalf of its client fund) for £425 million (the "Disposal").
This transaction is consistent with Capco's strategy of monetising investments at Earls Court over time with a focus on growing its central London property investment business, centred around Covent Garden. Completion of the transaction is expected to take place before the end of November 2019.
Disposal to APG and Delancey's client fund (the "Purchaser") is for total consideration of £425 million, on a cash-free and debt-free basis which compares to a balance sheet value at 30 June 2019 of £508 million;
Payments will be made to Capco on a phased basis, with 45 per cent payable on completion and the balance over two years. Net proceeds from the initial payment are expected to be approximately £156 million (adjusting for net debt, transaction-related costs and other completion items). The balance of £211 million will be payable in two equal instalments,12 months and 24 months after completion;
The Board unanimously considers the Disposal to be in the best interests of the Company and shareholders as a whole;
On a pro forma basis as at 30 June 2019 following the Disposal, Capco's loan to value is reduced from 19 per cent to 15 per cent with cash and undrawn facilities of over £900 million. This position will be enhanced further as deferred consideration is received. Net proceeds will be used to repay debt where appropriate or held as cash balances pending redeployment; and
The Disposal positions Capco as a prime central London property investment business, centred around Covent Garden, with a continued focus on driving rental growth and securing income. The business has significant financial flexibility to capitalise on investment opportunities and is well-positioned to deliver attractive long-term returns for shareholders.
Ian Hawksworth, Chief Executive of Capco, commented:
"Having prepared Earls Court for future development, we are now pleased to have agreed terms for the sale of our interests to APG and Delancey (on behalf of its client fund), an experienced real estate investment partnership which, with the support of TfL will take forward this important scheme for London.
Following the disposal, Capco will be a strongly-capitalised property investment business centred around our landmark Covent Garden estate. The business is well-positioned to generate attractive long-term returns for shareholders. Backed by a strong balance sheet and with a significant investment pipeline, our access to substantial liquidity will enable us to capitalise on opportunities."
Further information on the Disposal
The balance sheet value of the Earls Court interests at 30 June 2019 subject to the transaction (the "Disposal Group") comprises:
63 per cent interest in Earls Court Partnership Limited ("ECPL"): the investment vehicle with Transport for London ("TfL") in respect of the site formerly the location of the Earls Court exhibition centres and certain assets on and around Lillie Road valued at £389 million (Capco's share of ECPL net debt as at 30 June 2019 was approximately £38 million);
Other related assets around Earls Court valued at £36 million; and
Capco's interests in respect of the Conditional Land Sale Agreement ("CLSA") in relation to the West Kensington and Gibbs Green Estates, comprising prepayments and capitalised costs, with a carrying value of £83 million.
The Disposal Group generated net rental income of £2 million (Capco share) for the year ended 31 December 2018. The Disposal Group had gross assets, including working capital, of £517 million as at 30 June 2019 (Capco share). The accounting loss on disposal, against 30 June 2019 valuation, taking account of transaction-related costs and working capital adjustments is expected to be approximately £103 million. This amount does not include any fair value adjustment which may be made in relation to the deferred consideration. This exercise will be completed by the Company as part of preparing its annual report and accounts for the financial year ending 31 December 2019.
TfL has provided confirmation that it does not intend to take up its right to acquire a portion of shares in ECPL, which is triggered by the Disposal.
The Purchaser has paid a cash deposit of £42.5 million. Failure by the Purchaser to complete would result in this deposit being retained by Capco.
The Disposal will be effected by way of a sale of the entire issued share capital of a wholly-owned subsidiary of Capco. The Disposal to the Purchaser is on a cash-free and debt-free basis. Capco will receive total consideration of £425 million on a phased basis as set out above, subject to the following adjustments:
£15 million in relation to the final CLSA instalment due in December 2019, if paid prior to completion; and
a net asset adjustment in respect of certain ongoing costs ensuring the business remains compliant with its continuing obligations between exchange and completion.
The deferred payments receivable by Capco would be accelerated in part to the extent that payments made by Capco to the London Borough of Hammersmith and Fulham pursuant to the CLSA are refunded to the Purchaser after completion.
Further consideration may be payable to Capco in limited circumstances.
On 21 October 2019, following the announcement by Candy Ventures stating it was in the early stages of considering a possible cash offer for the Company, Capco entered into an offer period for the purposes of the Takeover Code. The Panel Executive has provided its consent to enter into the Disposal for the purposes of Rule 21.1 of the Takeover Code without requiring shareholder approval on the basis that, under Rule 21.1(c)(v)(A) of the Takeover Code, the decision to undertake the Disposal had been taken and partly implemented prior to the date on which Rule 21.1(a) was engaged. Candy Ventures has confirmed to the Panel Executive that it is not appealing this decision.
Rothschild & Co is acting as lead financial adviser to Capco on the Disposal. BofA Securities and UBS are acting as joint financial advisers and joint corporate brokers to Capco on the Disposal.
Person responsible
The person responsible for arranging the release of this announcement on behalf of Capco is Ruth Pavey, Company Secretary.
Capital & Counties Properties PLC
Ian Hawksworth
Situl Jobanputra
Sarah Hagan
UK: Tulchan
Jessica Reid
UK: Hudson Sandler
Michael Sandler
SA: Instinctif
Frederic Cornet
Rothschild & Co +44 (0)20 7280 5000
Alex Midgen
Peter Everest
BofA Securities +44 (0)20 7628 1000
Simon Mackenzie Smith
Ed Peel
UBS +44 (0)20 7567 8000
Hew Glyn Davies
Jonathan Retter
About Capital & Counties Properties PLC (Capco)
Capital & Counties Properties PLC is one of the largest investment and development property companies that specialises in central London real estate and is a constituent of the FTSE-250 Index. Capco's landmark London estates at Covent Garden and Earls Court were valued at £3.2 billion as at 30 June 2019 (Group share). The company is listed on the London Stock Exchange and the Johannesburg Stock Exchange.
www.capitalandcounties.com
This announcement is not intended to, and does not, constitute or form part of any offer, invitation or the solicitation of an offer to purchase, otherwise acquire, subscribe for, sell or otherwise dispose of, any securities, or the solicitation of any vote or approval in any jurisdiction, pursuant to this announcement or otherwise. Any offer, if made, will be made solely by certain offer documentation which will contain the full terms and conditions of any offer, including details of how it may be accepted. The distribution of this announcement in jurisdictions other than the United Kingdom and the availability of any offer to shareholders of Capco who are not resident in the United Kingdom may be affected by the laws of relevant jurisdictions. Therefore any persons who are subject to the laws of any jurisdiction other than the United Kingdom or shareholders of Capco who are not resident in the United Kingdom will need to inform themselves about, and observe any applicable requirements.
Notice related to financial advisers
N.M. Rothschild & Sons Limited ("Rothschild & Co"), which is authorised and regulated by the Financial Conduct Authority in the United Kingdom, is acting exclusively for Capco and for no one else in connection with the subject matter of this announcement and will not be responsible to anyone other than Capco for providing the protections afforded to its clients or for providing advice in connection with the subject matter of this announcement.
Merrill Lynch International ("BofA Securities"), a subsidiary of Bank of America Corporation, is acting exclusively for Capco in connection with the matters set out in this announcement and for no one else and will not be responsible to anyone other than Capco for providing the protections afforded to its clients or for providing advice in relation to the matters set out in this announcement.
UBS AG London Branch ("UBS") is authorised and regulated by the Financial Market Supervisory Authority in Switzerland. It is authorised by the Prudential Regulation Authority and subject to regulation by the Financial Conduct Authority and limited regulation by the Prudential Regulation Authority in the UK. UBS AG London Branch is acting as financial adviser to Capco and no one else in connection with the matters set out in this announcement. In connection with such matters, UBS, its affiliates, and its or their respective directors, officers, employees and agents will not regard any other person as its client, nor will it be responsible to any other person for providing the protections afforded to its clients or for providing advice in relation to the contents of this announcement or any other matter referred to herein.
Publication on website
In accordance with Rule 26 of the Takeover Code, a copy of this document will be made available subject to certain restrictions relating to persons resident in restricted jurisdictions on Capco's website at www.capitalandcounties.com by no later than 12 noon (London time) on the Business Day following the date of this announcement. For the avoidance of doubt, the contents of this website are not incorporated into and do not form part of this document.
Information regarding forward-looking statements
This announcement contains statements which are, or may be deemed to be, "forward-looking statements" which are prospective in nature. All statements other than statements of historical fact are forward-looking statements. They are based on current expectations and projections about future events, and are therefore subject to risks and uncertainties which could cause actual results to differ materially from the future results expressed or implied by the forward-looking statements. Often, but not always, forward-looking statements can be identified by the use of forward-looking words such as "plans", "expects", "is expected", "is subject to", "budget", "scheduled", "estimates", "forecasts", "goals", "intends", "anticipates", "believes", "targets", "aims" or "projects". Words or terms of similar substance or the negative thereof, are forward-looking statements, as well as variations of such words and phrases or statements that certain actions, events or results "may", "could", "should", "would", "might" or "will" be taken, occur or be achieved. Such statements are qualified in their entirety by the inherent risks and uncertainties surrounding future expectations.
Forward-looking statements include statements relating to: (a) future capital expenditures, expenses, revenues, earnings, economic performance, indebtedness, financial condition, dividend policy, losses and future prospects; (b) business and management strategies and the expansion and growth of the Company's operations; and (c) the effects of global economic conditions on the Company's business.
Such forward-looking statements involve known and unknown risks and uncertainties that could significantly affect expected results and are based on certain key assumptions. Many factors may cause actual results, performance or achievements of the Company to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Important factors that could cause actual results, performance or achievements of the Company to differ materially from the expectations of the Company include, among other things, general business and economic conditions globally, industry trends, competition, changes in government and changes in regulation and policy, including in relation to the environment, health and safety and taxation, labour relations and work stoppages, interest rates and currency fluctuations, changes in its business strategy, political and economic uncertainty. Such forward-looking statements should therefore be construed in light of such factors.
Neither the Company nor any of its Directors, officers or advisers provides any representation, assurance or guarantee that the occurrence of the events expressed or implied in any forward-looking statements in this announcement will actually occur. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as at the date of this announcement.
Other than in accordance with its legal or regulatory obligations (including under the Listing Rules and the Disclosure Guidance and Transparency Rules), the Company is not under any obligation and the Company expressly disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
No profit forecast
No statement in this announcement is intended as a profit forecast or a profit estimate and no statement in this announcement should be interpreted to mean that earnings per Ordinary Share for the current or future financial years will necessarily match or exceed the historical published earnings per Ordinary Share.
Press Release 494.46 KB

redpajama_set_name: RedPajamaCommonCrawl


text:
SIDA Mali from 2016 to 2020
Last update: Oct 17, 2016 Last update: 17 Oct, 2016
Location: Mali Mali
Category: Goods, Works, Consulting services, Non-consulting services
Status: Country programming
Sectors: Rural Development, Civil Society & NGOs, Culture, Education, Energy, Environment & NRM, Food Security, Gender, Health, Humanitarian Aid & Emergency, Industry, Commerce & Services, Labour Market & Employment, Logistics, Macro-Econ. & Public Finance, Micro-finance, Poverty Reduction, Procurement, Social Development, Standards & Consumer Protection, Trade, Roads & Bridges, Youth, Administration, Fundraising, Monitoring & Evaluation, Migration, Human Rights, Urban Development, Security, Tourism, Training, Border Management, Statistics, Pollution & Waste Management (incl. treatment), Anti-Corruption, Civil Engineering, Conflict, Water & Sanitation, Democratization, Electrical Engineering, Food Processing & Safety, Mapping & Cadastre, Banking, Land & Erosion & Soil, Justice Reform, Law, Nuclear, Public Administration, Media and Communications, Regional Integration, Vehicles, Furniture & Office Supplies, Information & Communication Technology, Laboratory & Measurement, Telecommunications, Inst. Devt. & Cap. building, Science & Innovation, Other, SME & Private Sector, Air & Aviation, Fisheries & Aquaculture, Grants & Grant Schemes, Heating, Human Resources, Mechanical Engineering, Programme & Resource Management, Refrigeration, Research, Translation, Water Navigation & Ports & Shipping, Finance & Accounting, Transport, Corporate Social Responsibility, Disaster Reduction , Printing, Audit, Architecture, Agriculture, Decentralization & Local Development, Design, Livestock (incl. animal/bird production & health), Mining, Risk Management (incl. insurance), Marketing, Advocacy
Swedish International Development Agency
Type: Organisation & Individual
Date posted: 17 Oct, 2016
SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali from 2016 to 2020. SIDA Mali fr...
Regional Strategy of Austrian Development Cooperation in Sub-Saharan Africa 2020-2030
country programming
Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Chad, Comoros, Congo, Cote d'Ivoire, Dem. Rep. Congo, Djibouti, Equatorial Guinea, Eritrea, Eswatini (Swaziland), Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Namibia, Niger, Nigeria, Reunion, Rwanda, Sao Tome and Principe, Senegal, Seychelles, Sierra Leone, Somalia, South Africa, Sudan, Tanzania, Togo, Uganda, Western Sahara, Zambia, Zimbabwe
Mali 2015-2019
ILO Burkina Faso 2020 - 2022
Kazakhstan: Country Operations Business Plan (2021-2023)
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This DIY, 3D Wedding Portrait Scene Is Just So Darn Cute!
Ok, is this like the cutest thing you've ever seen? I've come across quite a few adorable dimensional, 3D scenes that people have created with their Cricut, like this mermaid, this Valentine, or this fairy, and I wanted in. I was looking to create a universal Bride & Groom design that anyone would be able to personalize and add their names, date, and unique flair to. So me and my graphic designer Julia got to work and I'm beyond thrilled with what we designed! This little custom scene would be a terrific bridal shower or wedding gift for the bride in your life. It would even be a fun project for any current Mrs. to make to commemorate their past special day!
Our custom SVG file is already perfectly sized to use with an 8 x 10 frame, just import and edit! If you resize, be mindful that the new ratio might not fit certain frames!
Our free SVG. file at the end of the post!
Download our free SVG. file at the end of the post and upload into Cricut Design Space.
There are SO many options when it comes to colors for this portrait scene – your only constraint is paper color! Click each layer and pick it's color to customize your portrait.
To Slice: Ungroup the file. Add text and size to fit the blank area. Select both the text and the top design layer, then hit "slice". Delete the two text layers and you'll be left with a custom top design layer that your text will be cut out of!
Since there are 14 cut mats for this design and my Cricut is a few paces away from my computer, I found it easier to work/cut off the app instead. Your choice!
Aside from picking your colors of paper, cutting is the step that takes the longest. Have your paper colors ready to go and keep all the tiny cut pieces together.
This part is SO much fun! I had a blast doing it! Start by assembling the background, use Pop Dots to add the 3D dimension to the design.
Carefully glue the inside of letters and numbers back into place after cutting; ie. d, e, f, &, a, etc. Then adhere to the finished background.
Carefully assemble both the bride and groom. Using Pop Dots to give them dimension, on smaller areas you can totally cut the Pop Dots down to fit.
Assembling both the bride and groom, I found it easiest to leave their heads free until the end so that I could position them perfectly together.
After you have them together, add them into their special background! So cute right!?
This entire mini-scene is all paper, which means that you get to pick out each and every color. From turquoise to pink, to lavender and every color in between – I can't wait to see your rendition! Add your names, wedding date, special saying or nothing at all. The entire scene is all about you!
If you're in love with this Cricut wedding project, you'll be happy to hear that we now sell exclusive .SVG cut files for your Cricut in our shop! Most files are only $1.99 and they download instantly… so you can be crafting in minutes!


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Rural Broadband Month: Encouraging Equal Access to Digital Learning
By Kai Addy - August 1, 2017
Building out the infrastructure to support high-speed Internet access requires multi-layered collaboration between state and district leaders, school administrators, and service providers. A recent victory for Arkansas' public school system shows that these collaborations can yield tangible and meaningful results, particularly for rural communities.
On July 13, 2017, Governor Asa Hutchinson announced that the state had connected Glen Rose School District, the final Arkansas district awaiting high-speed Internet connectivity.
With that accomplishment, the state has officially achieved 100% high-speed connectivity for all of its public schools. Arkansas joins five other states that have reached this milestone; it is a particularly notable moment for a state comprised largely of rural districts.
Having high-speed Internet is about offering
students equal access to a robust, modern education,
regardless of their socioeconomic background
or geographic location.
The progress Arkansas made in just two years is significant. In 2015, Fort Smith Schools was the first district in the state to reach 200 kbps per student, exceeding the Federal Communications Commission's recommended minimum of 100 kbps of Internet speed per student. Having high-speed Internet is not just about meeting standards, however: it's about offering students equal access to a robust, modern education, regardless of their socioeconomic background or geographic location.
With 100% connectivity throughout the state, more Arkansas students can partake in virtual opportunities like speaking with students across the globe or participating in lessons from NASA scientists, as Beebe Elementary School students were able to do.
In a July 2017 statement, FCC Chairman Ajit Pai designated August as Rural Broadband Month at the agency. Throughout this month, the FCC will encourage particular focus on issues surrounding digital access in America's rural communities. As demonstrated by Arkansas' success in connecting all of its public school students, rural districts can thrive when cross-functional collaborations come together to leverage state and federal resources.
HOW TO LEVEL THE PLAYING FIELD FOR RURAL AMERICA
Equal digital access is important everywhere in America, for all students. Rural Broadband Month is a great opportunity to focus on the particular challenges of building sustainable broadband infrastructure in rural areas–infrastructure that addresses not only the digital needs of today's students, but also the likelihood of much greater Internet use in the future.
"Rural schools are the primary reason that the E-rate program exists,
as they are the least served and have the most need – their students
typically don't have ready access to museums or science centers,
and if their school can't get reliable, affordable broadband,
it's unlikely that its students will have access to good Internet
at home either. It's an equity issue."
-EducationSuperHighway Senior District Consultant Josh Chisom
Rural school districts have the right to give their students the world of opportunities afforded by reliable Internet access, and progress is not only possible, but within reach.
FOUR WAYS TO IMPROVE RURAL BROADBAND ACCESS
Consider working with neighboring districts to form a purchasing consortium.
In doing so, you could increase your purchasing power and create larger projects, which are often more attractive to potential service providers.
Utilize these free RFP templates.
Our resources can help get better deals with vendors.
Tune in to the FCC's Open Commission Meeting on August 3, 2017.
The meeting will address policies aimed to bridge the digital divide. You can find the proposed meeting agenda here. This meeting is open to the public.
Use our free Compare & Connect K-12 transparency tool.
See how your district's broadband pricing compares to what districts in your area are paying.
Are you a school or district leader?
Find out the steps you can take to improve connectivity.


I have been blissfully traveling the world for most of my life, but even more so now with my love and our son Hunter, who at 6 months of age has already been on 6 international flights!! Here are 5 quotes to light the fire under your arse and motivate you to get out and explore the world.
This old thing 😉 I love Paris more and more every time I go!
Another one on the bucket list, the Taj Mahal in India!
Batu Caves in Kuala Lumpur.
My new home, Hong Kong!
Previous story In the September/October issue of Daisy Magazine!


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Emergency Child Custody Cases Involving Drug Use In Little Rock, Arkansas
by Patrick Benca | Aug 30, 2021 | Child Custody | 0 comments
This is the next post in a series of articles discussing specific circumstances in which a parent may seek an emergency change in a child custody order in Little Rock, Arkansas. Our previous article addressed when a parent's criminal activity constitutes an emergency situation that will likely justify a modification to an existing custody order. A child's safety is of the utmost importance. Therefore, inherently dangerous criminal activity committed by a parent, such as violent crimes or crimes involving illegal drugs, particularly if such acts are committed in the presence of a child, will prompt a Court to modify custody on an emergency basis. This article will review when drug use by a parent may result in an emergency change in custody. If you need assistance, contact our office today to speak to an attorney.
When an Arkansas Judge will consider a parent's drug use an emergency for purposes of changing custody
For an Arkansas Judge to consider an emergency change to an existing custody order, the child must be in serious danger of imminent harm as a result of the other parent's behavior. This point often arises when one parent's drug use gives rise to such a request by their co-parent. It is important to understand that a Court's view of "hard drug" use will be very different than it is in matters involving the use or abuse of prescription medication or marijuana. The mere possession of substances, such as heroin, methamphetamines, cocaine, etc. is a criminal offense. Possessing or using hard drugs around the child will likely be viewed as creating a risk of harm and result in an emergency custody modification.
Whether a parent's use of prescription drugs or pot constitutes an emergency for purposes of changing custody will depend on whether the parent's use places the child at risk of immediate harm. Taking a validly prescribed medication in accordance with the doctor's instructions is not illegal. However, if the drug renders the parent unable to provide adequate care because they are impaired, this may justify an emergency change. Similarly, misuse of prescription medication could create a dangerous situation for the child. The same is true for marijuana. Occasional use may not be seen as a reason to remove the child from a parent's care on an emergency basis. On the other hand, if a parent is constantly high or impaired while the child is in their care, this may justify expedited action. Even if the Judge determines that such use does not constitute an emergency change, it may be possible to seek a non-emergency modification on the grounds that exposure to such behavior is not in the child's best interest.
A Little Rock attorney can assist with the emergency custody change process
The party requesting an emergency custody hearing must first file a Motion with the Court as well as request an expedited hearing. The initial hearing will be held quickly after the other parent is given at least one day's advance notice. Particularly when drug use is suspected, the Court will want to quickly obtain a drug test to confirm whether the substance is in their system. Once the test results are available, the Judge will determine whether to grant the emergency modification request. The Judge may either issue a temporary custody change pending a more thorough future hearing or decline to make any change until a future hearing or trial can be held. If the Court determines that a parent is abusing drugs, it may impose supervised visitation pending the outcome of ongoing drug tests and status checks. How a Judge rules will be based on the specific facts and circumstances of each specific situation.
As a Little Rock child custody lawyer, I have experience representing my clients in a variety of custody-related disputes, including emergency situations. If you believe your child is in immediate danger, call the police then contact an attorney as soon as possible to help expedite the emergency custody change request. We also handle matters in Fayetteville, Fort Smith, Springdale, Jonesboro, North Little Rock, Conway, Rogers, Pine Bluff, and throughout the rest of Arkansas.


KT&G Sangsangmadang Chuncheon is a cultural entertainment facility that offers visitors and artists the enjoyment, experience, and appreciation of arts and culture. The compound stands on the former location of Gangwon Gymnasium and Chuncheon Children's Center. Amenities include a theater, live studio, gallery, lecture room, cafe, accommodations, and a music room.
Online reservation available on the official website.
From Chuncheon Express Bus Terminal, take bus No. 64 to Samcheondong Intersection Bus Stop.
Approx. 5 min. from Chuncheon Express Bus Terminal or Chuncheon Intercity Bus Terminal.


Know 16 Super Foods some evidence exists that Promote Healthy follicle that stimulates Hair Growth. Know 16 Super Foods cause hormone imbalances that Promote Healthy shiny dandruff free Hair Growth. We learn that we have all learned a few things over time a simple multivitamin and well-balanced diet is still within the healthy for our self-identity and overall body and essential oils and herbs for optimum well-being. Our herbal treatment for hair is not be liable for any distinct, a novel leave-on technology combination of protein, complex carbs, vitamins, minerals like silica selenium and iron are usually released as needed for healthy, strong hair. Read i would give this article and experts believe they Know 16 super foods for hair growth that promote healthy body = healthy hair growth. Hair follicles with sufficient nourishment that is gentle and effective great starts with your diet like getting enough protein, which the hair fiber is the building block the negative effects of your own hair. You stay for awhile then need complex carbs is not helpful to help assemble the metabolism of fats proteins for hair development.
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The tough part done first thing to understand, do when you are not skimp on rich, ingredients in its formula that are wholesome this cold and flu season if you're attempting to find issues to lose weight. It - and research is vital that has worked for you know consuming whole grains along with foods due to happen mostly from the fact that like the hf they contain a heck of a lot of nutrients, enzymes, and phytochemicals, which could affect thyroid function synergistically to reduce falling hair maintain us healthfully. Read on to learn more about foods you can eat that promote hair loss and hair growth and healthy skin. 16 Super Foods and proper plan that Promote Healthy scalp and encourage Hair Growth:. The power of common vegetables like Swiss chard, broccoli tomatoes cabbage papaya and spinach are exceptional sources and health benefits of the vitamin c deficiency has A as well as minerals such as C that natural supplements can aid to create sebum which is necessary in the scalp. The entrapment of this sebum is the abundance of good fatty substance secreted by stimulating the hair follicles of hair vitamins but considering that function like rogain but with natural hair conditioner. And therefore justifies including these vegetables offer great volume to your body with vitamin d3 k2 calcium and iron. 6 Spiritual Benefits flavors and fun of Macrobiotic Diet or taking supplements That are Everlasting. 5 vitamins for glowing Healthy Herbs to 8 weeks to Keep You Well Physically but also mentally and Emotionally.
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Hennepin Bridge Project Set For Spring
The Interstate 180 freeway to Hennepin, built in the late 1960s when J&L Steel built its mill northeast of town, has been receiving more upgrades and maintenance work in recent years.
The Illinois Department of Transportation is planning project this year to keep it safe and sound.
This spring, IDOT will open bids for a project to repaint a portion of the structure that carries I-180 over the Illinois River. The project is scheduled to last 35 working days and, in addition to preparing and painting the structural steel, the contractor will need to be certified for and capable of containment and disposal of lead paint cleaning residues, according to IDOT.
Photo courtesy of the News Tribune
Unlike some multi-million projects in recent years such as refurbishment of the Route 23 bridge in Ottawa and repainting of Abraham Lincoln Memorial Bridge, this project is "basically to tackle the bad spots" until funding becomes available to repaint all the steel under the I-180 bridge north of Hennepin, said Joe Kannel, studies and plans project engineer for IDOT's Ottawa-based District 3 office.
"It's a maintenance-type project," Kannel said, noting there's a small pot of money available for jobs like this one. The engineers' estimated cost on the project is only about $210,000.
The re-painting work will be done on short portions of steel beams that are above two piers and below expansion joints "where most of the salt and water comes through to the steel," Kannel said.
Plans for the bridge were completed in 1967.
IDOT says the project would last 35 working days this spring or summer, and single-lane closures are likely during the work.


Background Indigenous populations are undergoing rapid ethnobiological, nutritional and socioeconomic transitions while being increasingly integrated into modernizing societies. To better understand the dynamics of these transitions, this article aims to characterize the cultural domain of food plants and analyze its relation with current day diets, and the local perceptions of changes given amongst the Ngäbe people of Southern Conte-Burica, Costa Rica, as production of food plants by its residents is hypothesized to be drastically in recession with an decreased local production in the area and new conservation and development paradigms being implemented. Methods Extensive freelisting, interviews and workshops were used to collect the data from 72 participants on their knowledge of food plants, their current dietary practices and their perceptions of change in local foodways, while cultural domain analysis, descriptive statistical analyses and development of fundamental explanatory themes were employed to analyze the data. Results Results show a food plants domain composed of 140 species, of which 85 % grow in the area, with a medium level of cultural consensus, and some age-based variation. Although many plants still grow in the area, in many key species a decrease on local production–even abandonment–was found, with much reduced cultivation areas. Yet, the domain appears to be largely theoretical, with little evidence of use; and the diet today is predominantly dependent on foods bought from the store (more than 50 % of basic ingredients), many of which were not salient or not even recognized as 'food plants' in freelists exercises. While changes in the importance of food plants were largely deemed a result of changes in cultural preferences for store bought processed food stuffs and changing values associated with farming and being food self-sufficient, Ngäbe were also aware of how changing household livelihood activities, and the subsequent loss of knowledge and use of food plants, were in fact being driven by changes in social and political policies, despite increases in forest cover and biodiversity. Conclusions Ngäbe foodways are changing in different and somewhat disconnected ways: knowledge of food plants is varied, reflecting most relevant changes in dietary practices such as lower cultivation areas and greater dependence on food from stores by all families. We attribute dietary shifts to socioeconomic and political changes in recent decades, in particular to a reduction of local production of food, new economic structures and agents related to the State and globalization.


This compact disc correlates directly to the songs in Popular Piano Solos Level 2. All track numbers for use with the compact disc are clearly indicated in the book, and are listed on the actual CD as well. These fully–orchestrated accompaniments by Hal Leonard Student Piano Library method author Phillip Keveren are a delightful way to enhance students' lessons, and are a sure way to guarantee practice success.
The CD format is as follows: each piece has two tracks. The first track is at a practice tempo with the solo piano part, and the second track is at a performance tempo without the piano solo part.


I was on my last hole in a AJGA event, knowing that I had to make an eagle on the par 4 18th hole to qualifying for Match Play. I had 210 yards to the hole, and miraculously made the shot with my 4 iron...I then went on to meet and play Chris Stroud in the 1st round. We then became great friends and now work together on The TOUR.
When Chris Stroud chipped in on the 72nd hole at The 2013 Travelers Championship, to force a playoff with Ken Duke. It was the loudest roar that I had ever heard, it was electric!


Regardless of your religious/faith beliefs, we invite you to join us!
Use ANY kind of camera, even an iPhone!
You have 6 months to pay, if you use PayPal Credit!
Want us to add another class? Let us know!
We add more classes throughout the year, based on student interest.
The way we see the world around us, our "world view", is shaped by so many different factors. And as a result, how we see the world shapes how we create photographs of this amazing world. I am trying something completely different with this workshop. I want this to be an opportunity to gather a group of photographers to explore how we might use photography as an expression of our "faith".
"Faith" means many different things to different people. Some say they never want to discuss two topics: "religion" and "politics". I am going to stay FAR away from politics, but I want to explore the faith and religion aspect because of the important impact it has in people's lives and shapes how they view the world.
"No man has the right to dictate what other men should perceive, create or produce, but all should be encouraged to reveal themselves, their perceptions and emotions, and to build confidence in the creative spirit."
"Sometimes I arrive just when God's ready to have someone click the shutter."
"A great photograph is a full expression of what one feels about what is being photographed in the deepest sense and is thereby a true expression of what one feels about life in its entirety."
This world has become way too polarized, and my intent with this workshop is to be open to people of all religions, denominations, and faiths. Sometimes what "divides" us is the use of words. What if we did not use words at all? What if, instead of words, we simply use images, photographs, as the means of expressing our faith? Maybe without using words, we can begin to understand others' perspectives a bit more, and perhaps gain new insights about our own perspectives. Sometimes words get in the way. As they say, "a picture is worth a thousand words."
I come at this from my personal perspective as a Christian. I would love to see how others, regardless of their faith and religious heritages, might explore this topic together... Christians of various denominations, Muslims, Jews, Hindus, Buddhists, etc. Just from my own perspectives of the Christian faith, I think it is an intriguing challenge to express core faith concepts... "hope", "mercy", "love", "forgiveness", "reconciliation"... by only using images.
Lets approach this from a perspective that we all see these matters differently, and that we can embrace these differences as being "ok". I know, even from my own life as a Christian, I have changed and evolved in how I understand all this, and I probably will continue to evolve. This is an environment where it is ok to be different, and we can show respect to others, and tolerance of other views.
My faith means a lot to me. Not to acknowledge that my faith shapes who I am and how I see the world, would be a mistake. It really does affect how I create photographs. So it seems only right to include this as another way we can approach our photographic expressions of how we see the world.
Maybe you have a strong faith. Maybe you are "spiritual" but don't affiliate with any religion. Maybe you are still searching for answers, but find yourself stuck with more questions than answers. I bet you might still find this exercise worthwhile. Even if you are not sure if any of this applies to you, perhaps you might gain some new insights by working on a project to create a photograph of what "forgiveness" looks like. So, regardless of where you are on these matters, you are still invited. Come as you are.
Literally any type of camera will do fine for this, whether it is a digital SLR or a point-and-shoot camera or even a smart-phone! The point with this class is the challenge of how we go about doing our photography to express these concepts without the use of words.
Session 1: January 22, 2017 We meet to discuss the project, and share a bit about how we might accomplish this. Then we have two weeks to work on our projects.
Session 2: February 5, 2017 After two weeks, we meet up and see what you created with your project (you will email me your photos ahead of time). We discuss what we tried, what worked, and what didn't, and share suggestions on some refinements or improvements we might make.
Session 3: February 12, 2017 One week later, we get back together and share any further work you have done to improve your project results. Celebrate your success!
If you would like to learn all the important fundamentals of photography, to create better images, check out my Photography 101 Workshop!