text:
(B) Percentage of voxels used per region averaged across the grou
(B) Percentage of voxels used per region averaged across the group. Error bars show standard error of the mean. Fig. S6. (A) Decoding accuracy as a function of MEK inhibitor TR for feedback and non-feedback condition, and attend-face and attend-place trials that constitute these two conditions. The filled round markers represent significantly above-chance decoding (P < 0.05) whereas the empty markers represent below-chance decoding (P > 0.05). (B) Mean decoding accuracy. Error bars indicate standard error of the mean. Fig. S7. Comparison of percent signal change in feedback and non-feedback
conditions. (A) Percent signal change for attend-face trials in feedback and non-feedback condition. The top plots show percent signal change at every TR during a trial (including the 12 s rest period. The bottom plot shows the percent signal change aggregated over the 12 TRs. (B) Percent signal change for attend-place trials in feedback and non-feedback conditions. Error bars represent standard error of the mean. Fig. S8. Comparison of prediction probablities of the decoder for
feedback and non-feedback conditions. (A) Prediction probability for feedback and non-feedback conditions containing both successful and failed trials. No significant difference was found. (B) Prediction probability for only successful trials in feedback and non-feedback conditions. The prediction probability for feedback trials was significantly higher Lumacaftor datasheet than non-feedback trials (C) Prediction probability for only failed trials in feedback and non-feedback conditions. The prediction probability for failed trials was significantly stronger (lower) for feedback trials compared to non-feedback trials. Error bars represent standar error of the mean. Fig. S9. (A) Average decoding performance for classifiers trained on feedback and non-feedback conditions. The classifier trained on the feedback condition was decoded with significantly higher accuracy than the classifier trained on the non-feedback condition. (B). Anatomical Coproporphyrinogen III oxidase regions recruited by the classifiers trained on feedback and non-feedback conditions "
"The gating behavior of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid (AMPA) and kainate receptors is modulated by association with the auxiliary proteins: transmembrane AMPA receptor regulatory proteins (TARPs) and neuropilin tolloid-like (Netos), respectively. Although the mechanisms underlying receptor modulation differ for both AMPA and kainate receptors, association with these auxiliary subunits results in the appearance of a slow component in the decay of ensemble responses to rapid applications of saturating concentrations of glutamate. We show here that these components arise from distinct gating behaviors, characterized by substantially higher open probability (Popen), which we only observe when core subunits are associated with their respective auxiliary partners.
Bacteria establish copper homeostasis chiefly by exporting excess
Bacteria establish copper homeostasis chiefly by exporting excess copper and by sequestering cytoplasmic copper with copper chaperones for safe delivery to copper exporters and copper-requiring proteins (Solioz et al., 2010). The genes involved in copper homeostasis are regulated by copper-responsive transcriptional regulators. Lactococcus lactis has been used recently as a model organism for the study of bacterial copper homeostasis. It was found that a set selleckchem of widely diverse genes are under the control of the CopR copper-responsive repressor (Magnani et al., 2008). This so-called CopR regulon encompasses 14 genes: two monocistronic genes (lctO, copB) and four operons (ydiDE,
yahCD-yaiAB, ytjDBA and copRZA). Some of the proteins encoded by these genes, such as the CopR repressor, the CopZ copper chaperone and the two copper ATPases, CopA and CopB, play an evident role in copper homeostasis by dealing directly with copper ions (Solioz & Vulpe, 1996; Solioz & Stoyanov,
2003; Solioz et al., 2011). Two more proteins of the CopR regulon have been studied in detail: LctO is a lactate oxidase that converts lactate to pyruvate under the use of molecular oxygen, presumably to reduce oxygen tension and thus oxygen-associated stress (Barréet al., 2007). Ku-0059436 purchase CinD, on the other hand, is a nitroreductase (encoded by ytjD) that can detoxify nitro compounds that exacerbate copper stress (Mermod et al., 2010). In the present study, we investigated the function of another member gene of the CopR regulon, yahD. By sequence comparison, this gene is predicted to encode an α/β serine hydrolase of 206 amino acids. The α/β-hydrolase fold is one of the most versatile and widespread folds known (Nardini & Dijkstra, 1999). Even though all the members of this superfamily have a similar fold and a conserved catalytic triad, they exhibit wide substrate specificity. Serine hydrolases use a nucleophilic serine to hydrolyze amidic, ester and thioester bonds in small molecules or proteins (Simon & Cravatt, 2010). YahD was found to be induced Dipeptidyl peptidase by copper, cadmium and silver, but not by other metals or by oxidative or
nitrosative stress-inducing chemicals. The three-dimensional structure of YahD was resolved by X-ray crystallography to a resolution of 1.88 Å and was found to exhibit an α/β-hydrolase fold with the characteristic Ser-His-Asp catalytic triad. YahD did not catalyze any of the known α/β serine hydrolase reactions and appears to represent a novel subclass of serine hydrolases. Lactococcus lactis IL1403 was grown semi-anaerobically (air-saturated media in sealed bottles), in M17 media (Terzaghi & Sandine, 1975) at 30 °C or on plates containing M17 media with 1.5% agar (AppliChem, Darmstadt, Germany). Escherichia coli DH5α (Stratagene, La Jolla, CA) and ER2566 (Invitrogen life Technologies) cells used for cloning were transformed according to the manufacturer's instructions.
For multiple births, only the first twin or triplet was included
For multiple births, only the first twin or triplet was included in the analysis. Use of prophylaxis for infants born to women diagnosed up to one week after delivery is described
separately within this paper. Year of birth was grouped into two periods (2001–2004 and Selleckchem Epigenetic inhibitor 2005–2008), in line with the publication of new versions of national guidelines [8,9]. Neonatal PEP was categorized as none, single, dual or triple (three or more antiretroviral drugs). Information on timing and duration of neonatal PEP was not available. Maternal antiretroviral therapy in pregnancy was classified as none, monotherapy, dual therapy or highly active antiretroviral therapy (HAART; three or more drugs). Maternal HIV-1 RNA viral load closest to delivery and up to seven days post-partum was selected, and categorized as undetectable (<50 HIV-1 RNA copies/mL), 50–999 copies/mL or ≥1000 copies/mL. Gestational age was categorized as ≤31, 32–34, 35–36 or ≥37 weeks. Mode of delivery was reported by respondents as elective caesarean section, emergency caesarean section, or vaginal delivery (planned or unplanned). PFT�� Infants were classified as uninfected if they had a negative polymerase chain reaction (PCR) test after one month of age or a negative HIV antibody test after 18 months
of age, or infected if they had a positive PCR result at any time or a positive HIV antibody test after 18 months of age. Data were managed BCKDHB with access 2003 (Microsoft Corporation, Redmond, WA, USA) and analysed using stata version 11 (Stata Corporation, College Station, TX, USA). Differences in proportions were analysed using χ2 or Fisher's exact tests. Logistic regression models were fitted to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Analysis of factors associated with receipt of triple PEP was restricted to infants who received single or triple prophylaxis, as only a small proportion of infants received dual PEP, and these differed from the other two groups in terms of maternal and pregnancy characteristics and other interventions. Between 2001 and 2008, 8442 eligible births to diagnosed HIV-infected women were reported to the NSHPC, including 146 first twins or triplets.
Most mothers were Black African, had received antenatal HAART and had undetectable viral load near delivery (Table 1); over half (52.5%; 4398 of 8373) were aware of their HIV status before pregnancy. Information on receipt of neonatal PEP was available for 97.2% of infants (8205 of 8442), almost all of whom (99.4%; 8155 of 8205) received prophylaxis. Most prophylaxis consisted of a single drug, although 2.9% of infants were given two drugs and 11.4% three or more. Single-drug PEP consisted mainly of zidovudine (97.7%; 6733 of 6893), while most triple combinations consisted of zidovudine, lamivudine and nevirapine (79.4%; 731 of 921). The proportion of infants receiving no prophylaxis decreased over time from 0.8% (27 of 3282) in 2001–2004 to 0.
The joint mortality risk score was obtained
from SMART da
from SMART data using a conditional logistic regression model that considered both IL-6 and d-dimer (each log10-transformed) for the outcome of all-cause mortality. The joint mortality risk score was calculated by solving for the logit selleck inhibitor formed with the estimated parameters from SMART and the log10-transformed values of IL-6 and d-dimer from the current study. Higher values of this score were associated with a higher risk of death in SMART. Data were analysed using R statistical software (version 2.8.1; http://www.cran.r-project.org). Characteristics of the 32 HIV-infected participants who were enrolled have been previously reported [2,3]. Mean (standard deviation) age was 40 (9.6) years and body mass index was 26 (5.1) kg/m2. Twenty-eight participants (88%) were male, 19 (59%) were current smokers, 11 (34%) had hepatitis C virus coinfection, two (6%) had diabetes mellitus, and two
(7%) had a prior AIDS clinical event. Mean CD4 count was 391 (182) cells/μL and mean HIV RNA level was 4.15 (0.73) log10 HIV-1 RNA copies/mL. The median (interquartile range) values for IL-6, d-dimer, and the joint mortality risk score were 1.79 (1.34–4.88) pg/mL, 0.39 (0.19–0.60) μg/mL, APO866 solubility dmso and 0.47 (0.33–0.74), respectively. Mean values for each surrogate measure of vessel function (untransformed) and HIV RNA level (log10-transformed) are reported by quartile of IL-6 and d-dimer (Table 1). Higher levels of IL-6 (fourth vs. first quartile, and as a continuous variable in Spearman rank correlations) tended to be associated with impaired Sodium butyrate SAE and higher levels of sICAM-1 and E-selectin. A similar pattern was seen when comparing markers of vascular dysfunction with d-dimer levels. LAE and CD4 cell count (data not shown) did not vary by IL-6 or d-dimer level. For comparisons using the joint (IL-6/d-dimer) mortality risk score, the associations with markers of vascular dysfunction (SAE, sICAM-1 and E-selectin) became more pronounced. In
summary, we have shown that higher IL-6 and d-dimer levels among persons with untreated HIV infection are associated with vascular dysfunction, indicated by higher endothelial biomarkers and impaired SAE – a marker of early vascular disease and future clinical risk. Findings from SMART suggest that non-AIDS-related mortality may be a consequence of greater inflammation (IL-6 levels) and thrombotic activity (d-dimer levels) in persons with HIV infection [1]. Levels of IL-6 and d-dimer and estimates of artery elasticity (LAE and SAE) are being ascertained in a subset of participants in the ongoing Strategic Timing of Antiretroviral Therapy trial, and will provide valuable insight into the mechanisms contributing to early vascular disease in persons with HIV infection. Future research should consider the role of HIV-mediated endothelial injury as a contributor to both CVD- and non-CVD-related mortality in the current era.
from SMART data using a conditional logistic regression model that considered both IL-6 and d-dimer (each log10-transformed) for the outcome of all-cause mortality. The joint mortality risk score was calculated by solving for the logit Gemcitabine nmr formed with the estimated parameters from SMART and the log10-transformed values of IL-6 and d-dimer from the current study. Higher values of this score were associated with a higher risk of death in SMART. Data were analysed using R statistical software (version 2.8.1; http://www.cran.r-project.org). Characteristics of the 32 HIV-infected participants who were enrolled have been previously reported [2,3]. Mean (standard deviation) age was 40 (9.6) years and body mass index was 26 (5.1) kg/m2. Twenty-eight participants (88%) were male, 19 (59%) were current smokers, 11 (34%) had hepatitis C virus coinfection, two (6%) had diabetes mellitus, and two
(7%) had a prior AIDS clinical event. Mean CD4 count was 391 (182) cells/μL and mean HIV RNA level was 4.15 (0.73) log10 HIV-1 RNA copies/mL. The median (interquartile range) values for IL-6, d-dimer, and the joint mortality risk score were 1.79 (1.34–4.88) pg/mL, 0.39 (0.19–0.60) μg/mL, Quizartinib clinical trial and 0.47 (0.33–0.74), respectively. Mean values for each surrogate measure of vessel function (untransformed) and HIV RNA level (log10-transformed) are reported by quartile of IL-6 and d-dimer (Table 1). Higher levels of IL-6 (fourth vs. first quartile, and as a continuous variable in Spearman rank correlations) tended to be associated with impaired Protein kinase N1 SAE and higher levels of sICAM-1 and E-selectin. A similar pattern was seen when comparing markers of vascular dysfunction with d-dimer levels. LAE and CD4 cell count (data not shown) did not vary by IL-6 or d-dimer level. For comparisons using the joint (IL-6/d-dimer) mortality risk score, the associations with markers of vascular dysfunction (SAE, sICAM-1 and E-selectin) became more pronounced. In
Gram reaction was determined using the nonstaining (KOH) method a
Gram reaction was determined using the nonstaining (KOH) method as described by Buck (1982). Cell morphology and motility were studied using phase-contrast microscopy and electron microscopy as described previously by Herrera et al. (2007). NaCl growth tolerance and requirements were investigated using nutrient broth (0.5% peptone from casein, 0.3% meat extract, 0.3% yeast extract, and adjusted to pH 7.2) supplemented with various concentrations of NaCl (0–15% at intervals of 1%). The pH range for growth was determined in nutrient broth that was adjusted to various pH values (pH 2.0–12.5 at intervals of 0.5 pH units). Anaerobic growth was assessed at 20 °C in anaerobic chambers with an H2/CO2 atmosphere (bioMérieux). Catalase
activity was determined by assessing bubble production in 3% v/v H2O2; oxidase activity was determined using 1% w/v tetramethyl-p-phenylenediamine as described by Lim et al. (2008). Some physiological characteristics were determined using GSI-IX datasheet API 20NE, API 50CH and API ZYM (bioMérieux). Cells for inoculation of the strips were grown for 24 h at 20 °C on TSA supplemented with 1.5% NaCl and the results were visually interpreted according to the manufacturer's instructions. Extraction and amplification of genomic DNA for 16S rRNA gene sequence analysis
were carried out as described previously (Balcázar et al., 2009), and the recA gene was amplified and sequenced as described by Thompson et al. (2005). The sequences Galunisertib of these genes were compared against the sequences available in the GenBank, EMBL and DDBJ databases obtained from the National Center for Biotechnology Information using the blastn (Altschul et al., 1990). Phylogenetic analyses were performed using the software mega version 4.0 (Tamura et al., 2007) after multiple alignments of data by clustal x (Thompson et al., 1997). Distances (distance options according to the Kimura two-parameter model)
and clustering with the neighbour-joining (Fig. 1) and maximum-parsimony (Supporting Information, Fig. S1) methods were determined using bootstrap values based on 1000 replications. For base composition analysis, DNA was prepared according to Chun & Goodfellow (1995). The G+C content of the DNA was determined using the thermal denaturation method (Mandel & Marmur, 1968). DNA from Vibrio harveyi DSM 19623T was used as a reference SDHB for determination of the thermal-melting profile (Tm). Whole-cell fatty acids from the isolate were extracted from biomass grown on nutrient agar (0.5% peptone from casein, 0.3% meat extract, 0.3% yeast extract, 1.5% agar, and adjusted to pH 7.2) supplemented with 1.5% NaCl and were analysed according to the standard protocol of the Sherlock Microbial Identification System (MIDI version 4.5). Phenotypically, strain BFLP-4T can be clearly assigned to the genus Vibrio (Noguerola & Blanch, 2008). Cells of strain BFLP-4T were slightly curved rods (Fig. 2), Gram-negative, oxidase- and catalase-positive, motile and facultatively anaerobic.
DNA probes used for EMSAs were prepared by labeling at the 3′ end
DNA probes used for EMSAs were prepared by labeling at the 3′ end with digoxigenin (DIG)-11-ddUTP. The DNA-protein binding reactions were carried out at 20 °C in a final volume of 10 μL mixture containing 3 fmol of DIG-labeled probe, 0.5 µg of salmon sperm DNA, 0.1 µg of poly-(l-lysine), and 50 ng of purified ht-IphR (0.8 pmol dimer) in a binding buffer [20 mM HEPES, 1 mM EDTA, 10 mM (NH4)2SO4, 1 mM dithiothreitol, 0.2% (w/v) Tween 20, and 30 mM KCl, pH 7.6] for 20 min following the same procedure described earlier (Kamimura et al., 2010). When required,
effectors E7080 datasheet including IPA or unlabeled fragments shown in Fig. S1 were added to a final concentration of 1 mM or 3 μM, respectively. Gel electrophoresis and the detection of signals were carried out as described previously (Kamimura et al., 2010). In a previous study, E6 cells harboring a lacZ reporter plasmid, pZSH2 containing a 1794 bp region upstream from the iphA start codon, showed 88-fold higher β-galactosidase activity in the presence of IPA (Fukuhara et al., 2010). To determine the iphA Selleckchem Nutlin-3a promoter region, a set of deletion plasmids of pZSH2 was constructed and used for the promoter assay (Fig. 1a). The inducible expressions of the iphA promoter variants were observed in
IPA-grown E6 cells harboring pZSM1, pZSP08, pZSN06, pZSNE530, and pZSNE347. On the other hand, no promoter activity was shown in E6 cells harboring pZSNE198. These results suggested that the region sufficient for the IPA-dependent induction of the iphA promoter was located within a 160 bp region upstream from the iphA start codon. The transcription start site of iphA was determined by primer extension analyses using total RNA isolated from E6 and the iphR mutant (DEIR) cells. A 159-nucleotides (nt) DNA fragment was observed when using total RNA from E6 cells grown in the presence of IPA (Fig. 1b); however, no significant extension product was seen in the absence of IPA
(data not shown). From these results, the transcription start site of the iph operon was determined to be a cytosine located 49 bp upstream of the iphA start codon (Fig. 1c). Putative −35 and −10 sequences separated by 16 nt were found upstream of the transcription start site. We also found two inverted repeat sequences IR1 Thymidylate synthase and IR2. In the case of DEIR, a 159-nt DNA fragment appeared regardless of the presence of IPA in the cultures (data not shown). These results supported that the iph operon is negatively autoregulated by IphR. To further identify the iphA promoter region, pZ347, pZ284, pZ274, and pZ255 were constructed and used for the promoter assays (Fig. 1c). The inducible expression of the iphA promoter was observed in E6 cells harboring pZ347, pZ284, and pZ274 (Table 1). However, cells harboring pZ255, which lacks the putative −35 sequence, showed no promoter activity.
5819; 95% confidence interval (CI) 03457–09795; P = 00416] Vi
5819; 95% confidence interval (CI) 0.3457–0.9795; P = 0.0416]. Viral load tended to increase with decreasing genetic score in the logistic regression analysis (slope = −0.127 ± 0.076; P = 0.095; r2 = 0.161). The CX3CR1 A allele and lower genetic scores may restrict the switch of HIV-1 tropism from R5 to X4. This effect may be associated with the amount of co-receptor on the cell surface. Chemokine receptor gene polymorphisms influence both disease progression and tropism variability. "
"Inversion of the CD4:CD8 ratio (< 1) has been identified as a hallmark of inmmunosenescence and an independent predictor
of mortality in the general population. We aimed to assess the association between the CD4:CD8 ratio and markers of age-associated disease in treated HIV-infected patients with good immunovirological response. A cross-sectional analysis was TSA HDAC conducted in 132 HIV-infected adults on antiretroviral therapy (ART), with plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 1 year, CD4 count > 350 cells/μL and age < 65 years. We analysed the associations between the CD4:CD8 ratio and subclinical atherosclerosis [assessed using carotid intima-media thickness (IMT)], arterial stiffness [assessed using ABT-199 cost the augmentation index (AIx)], the estimated glomerular filtration rate (eGFR), muscle wasting and sarcopenia [assessed using appendicular lean mass/height2 (ALM) measured by dual-energy X-ray absorptiometry (DEXA)]. CD4:CD8 ratio inversion
was associated with higher IMT, lower eGFR and lower ALM (all values P < 0.05), but not with AIx. In multivariate analyses adjusted for age, sex, hypertriglyceridaemia, tobacco
use and cumulative ART exposure, inversion of the CD4:CD8 ratio was independently associated with higher IMT [odds ratio (OR) 2.9; 95% confidence interval (CI) 1.2–7.1], arterial stiffness (OR 4.8; 95% CI 1.0–23.5) and lower eGFR (OR 5.2; Pregnenolone 95% CI 1.0–64.4), but not sarcopenia (OR 0.7; 95% CI 0.2–2.7). These associations persisted when models were applied to subjects with nadir CD4 counts > 200 cells/μL and those with CD4 counts > 500 cells/μL. The CD4:CD8 ratio in treated HIV-infected subjects with good immunovirological response is independently associated with markers of age-associated disease. Hence, it might be a clinically useful predictor of non-AIDS-defining conditions. "
"Pregnancy results in physiological changes altering the pharmacokinetics of drugs metabolized by cytochrome P450 3A4 (CYP3A4). The urinary ratio of 6-β hydroxycortisol to cortisol (6βHF : F) is a marker of CYP3A4 induction. We sought to evaluate its change in antiretroviral (ARV)-treated HIV-1-infected women and to relate this change to ARV pharmacokinetics. Women receiving various ARVs had pharmacokinetic evaluations during the third trimester of pregnancy (> 30 weeks) and postpartum with determination of 6βHF : F carried out on the same days. The Wilcoxon signed rank test was used to compare the ratio antepartum to postpartum.
Laboratory investigations may reveal thrombocytopenia, anaemia, h
Laboratory investigations may reveal thrombocytopenia, anaemia, hypoalbuminaemia and hypergammaglobulinaemia. Haemophagocytic lymphohistiocytosis selleckchem may be also be present and confirmed by bone marrow examination [6]. Patients may also present with pancytopenia, renal or respiratory failure. Other less common complications include polyneuropathy and leptomeningeal and
central nervous system (CNS) infiltration with central pontine myelinolysis [7] as well as myasthenia gravis [8]. The polyneuropathy is a chronic, inflammatory demyelinating neuropathy and may be present as part of the rare POEMS syndrome (Crow–Fukase disease) [9]. Primary effusion lymphoma (PEL), also driven by HHV8, can develop in the presence of MCD [10], demonstrating an association between these conditions, although a definite clonal relationship has not been demonstrated. A study by Chadburn et al. [11] indicated that, although both PEL and MCD originate from HHV8-infected
pre-terminally differentiated B cells, HIV-positive MCD arises from extrafollicular B cells, whereas PELs Staurosporine originate from cells that have traversed the germinal centre. MCD is a relapsing and remitting disease and the definition of an 'attack' has recently been proposed as a combination of fever and a raised serum C-reactive protein plus three of the following symptoms: peripheral lymphadenopathy, splenomegaly, oedema, pleural effusion, ascites, cough, nasal obstruction, xerostomia, mTOR inhibitor rash, central neurological symptoms, jaundice or autoimmune haemolytic anaemia [12]. There is an association between MCD and AIDS-associated Kaposi sarcoma
(KS) [13]. In 1994, Chang and Moore isolated a new human gamma-2 herpesvirus from AIDS-KS lesions using differential representational analysis [14]. This virus, known as human herpesvirus 8 (HHV8) or Kaposi sarcoma herpesvirus (KSHV), was later found to be present in all cases of HIV-associated MCD [15]. The role of combination antiretroviral therapy (cART) and CD4 level in preventing the emergence of MCD, in treatment or in preventing relapse remains unclear. Powles et al. [16] showed that the risk of MCD was related to a nadir CD4 cell count greater than 200 cells/μL, older age, no previous cART and a non-Caucasian background. In one small series, seven of eight patients who were receiving cART at the time of presentation of MCD, had a median CD4 cell count of 385 (140–950) cells/μL [17]. Therefore MCD can present in the context of a well-preserved immune system. Westrop et al. [18] suggested that the 2–4-fold higher incidence of MCD in patients of African ancestry presenting with HHV8-related malignancies might be due to the three-times higher frequency of the A299G single nucleotide polymorphism.
8/100 PY (95% CI 665, 934/100 PY) For responders, the crude ho
8/100 PY (95% CI 66.5, 93.4/100 PY). For responders, the crude hospitalization rate declined statistically significantly during the 46 to 90-day time period, with a relative rate (RR) vs. the first 45 days of 0.71 (95% CI 0.51, 0.98). From 90 days to the end of the year, the hospitalization rate for responders stabilized at near 45/100 PY (RR for days 91–180 vs. the first 45 days, 0.56; 95% CI 0.40, 0.78). For nonresponders, there was no statistically significant change in all-cause
hospitalization rates across time periods, with the point estimates ranging from 78.7 to 99.7/100 PY (Fig. 1). Fewer than half of all subjects (34% of responders and 46% of nonresponders; P<0.001) were ever hospitalized over the entire period beginning 180 days before HAART initiation to 365 days afterwards. In multivariate analysis (Table 2), responders' hospitalization rates retained an identical http://www.selleckchem.com/products/AG-014699.html pattern of statistically significant decrease in later time periods vs. earlier periods (RR 0.59; 95% CI 0.42, 0.82 for responders in days 91–180 vs. days 1–45). Having an increase in CD4 count of at least 101 cells/μL (the median increase in CD4 count in virological responders) had a borderline association with a decreased risk of hospitalization (RR 0.83; 95% CI 0.67, 1.03). Additional factors significantly associated with hospitalization included being a nonresponder in the 91–180 day
(RR vs. responders 2.14; 95% CI 1.41, 3.25) and 181–365 day (RR vs. responders 1.43; 95% CI 1.00, 2.04) time periods; female gender; African American race; IDU; and lower CD4 cell count at HAART initiation. GSK126 cell line Hospitalization rates for the seven diagnostic categories with the highest
rates are shown in Fig. 2. Non-ADI infections (the three most frequent individual diagnoses being pneumonia, unspecified organism; lower limb cellulitis; and acute/subacute Glycogen branching enzyme bacterial endocarditis) and ADIs (pneumocystosis, cryptococcosis and candidal esophagitis) were consistently the most common reasons for admission across all time periods for both responders and nonresponders. Psychiatric illness [major depression, recurrent episode; depressive disorder, not elsewhere classified (NEC); and drug-induced mood disorder] was the third most common category and was followed by gastrointestinal and hepatic disease (acute pancreatitis; chronic pancreatitis; and cirrhosis of the liver, NEC); cardiovascular disease (hypertensive end-stage chronic kidney disease; venous thrombosis, NEC; and cerebral artery occlusion with infarct); endocrine, nutritional, metabolic or immune disease (hypovolaemia, cachexia, and hypercalcaemia); and renal disease (acute renal failure, NEC; chronic renal failure; and lower nephron nephrosis). For responders, hospitalizations as a result of ADI and non-ADI infections revealed statistically significant decreases by the period starting 90 days after HAART initiation (Fig. 2a). In the 1–45 day period, IRIS hospitalizations (rate 10.9/100 PY; 95% CI 5.6, 21.


text:
United Way of Miami County announced Thursday, December 31, 2015, it officially closed its campaign.
The organization's goal was to raise at least $195,000. The official total came to $202,662, which is 103.9% of goal. "It's a message of confidence that the community has in us; they trust us to be good stewards of what they're giving. It's exciting to see how far we have come and also to look ahead and see what we will be able to do because of the funds we raise," says Executive Director, Debi Wallick.
"Thank you to every individual and company who gave to the United Way Campaign. The residents of our community realized that many friends and neighbors are struggling. Because of your generosity, hungry families will receive food, abused children and adults can find shelter. You gave so others could have a better life. I am very proud to live in Miami County where people care about each other," said Wallick.
"Making our campaign goal means that the eight United Way Partner Agencies, 19 programs and the five initiatives United Way supports will receive allocation funding this year. The agencies will also be able to provide essential health and human services to the community. Although the economy has improved, there are still many families, children, and elderly who continue to struggle in our community. By exceeding the goal, United Way supported programs and initiatives will be able to continue their services and make sure that people in our community receive the help they need," Wallick continued.
"I'm always just blown away by how generous our community is," said Wallick. "They went above and beyond the call. They gave us more than we had expected two weeks ago." The United Way provides leadership and oversight by addressing and prioritizing community needs, collectively distributing funds, and ensuring agency accountability. "The newly adopted mission statement is to provide direction and accountability to promote education, health, and financial independence for the good of all Miami County."
Again, United Way of Miami County is grateful to every volunteer and donor who helped us surpass this year's campaign goal. Thank you for making a difference. The United Way spends four months collecting money for the campaign. Next year's campaign will start around the middle of August. For more information call United Way at 765-473-4240, drop in the office at 13 E. Main St. Peru between 8:00 – 4:00 p.m. Monday – Friday, or contact us through our website at www.uwmiamip.org.

redpajama_set_name: RedPajamaCommonCrawl


Every time UserFrosting is booted up to handle a request, it goes through its application lifecycle. This process includes loading the resources and services in your Sprinkles, setting up the Slim application, registering middleware, and setting up your routes.
At each stage in this process, events are triggered that you can hook into via a Bootstrapper class in your Sprinkle.
Create the dependency injection container.
Register basic system services, such as the locator service, Sprinkle manager, and the lifecycle event dispatcher.
Load the list of Sprinkles from sprinkles.json, and register each Sprinkle's bootstrapper class (if it exists) with the event dispatcher.
Add each Sprinkle's resources (assets, config, templates, routes, etc) to the locator service.
Register each Sprinkle's service provider (if it exists).
Fire the onSprinklesRegisterServices event. Note that this is the point where the core Sprinkle sets values for PHP settings such as log_errors, display_errors, error_reporting, and timezone from the UF configuration files, and where the custom ShutdownHandler is set up.
Load the Slim application settings from the config service, and create the Slim application instance.
Load the route definitions in each Sprinkle's routes/ directory.
Fire the onAddGlobalMiddleware event. This is where the core Sprinkle sets up the global CSRF middleware.
Invoke the run method on the Slim application.
At the base level of each Sprinkle, you may optionally define a bootstrapper class. This is a class where you can hook into any of the five events mentioned above: onSprinklesInitialized, onSprinklesAddResources, onSprinklesRegisterServices, onAppInitialize, and onAddGlobalMiddleware. The name of the class must be the same as the name of the Sprinkle directory, but in StudlyCaps. The class itself must extend the base UserFrosting\System\Sprinkle\Sprinkle class.
Bootstrapper classes are basically implementations of Symfony's EventSubscriberInterface, and they subscribe to the event dispatcher that is created in step 2 of the application lifecycle.
To add a listener for an event, simply create a method of the same name as the event in your bootstrapper class. The method should take one parameter - an Event object that contains any additional information the dispatcher chooses to include with the event. In the case of the onAppInitialize and onAddGlobalMiddleware events, this object will contain a reference to the Slim application that can be accessed from the Event's getApp method.
You should also add your listener to a static getSubscribedEvents method, which returns a list of events mapped to a list containing the listener method and the associated priority integer. You can control the order in which listeners in each bootstrapper class are executed, by setting this integer to a higher number. For each event, Sprinkles that assign a higher number to the corresponding listener method will cause that method to be executed earlier than Sprinkles that assigned a lower number to the event.
* Defines which events in the UF lifecycle our Sprinkle should hook into.
* Add custom global middleware.
// and that you have defined this in your Sprinkle's service provider.
* Set static references to DI container in necessary classes.
Notice that the base Sprinkle class has access to the application dependency injection container via $this->ci. This allows you to invoke other services, or even use the entire container, in your listener methods.
For more information on event dispatching, subscribing, and listening, check out the Symfony documentation.


Twitter said on Tuesday that President Trump is not immune from being kicked off the platform if his tweets "cross a line" with abusive behavior, reports Politico.
The social media giant has previously said that vitriolic tweets from world leaders with newsworthy statements would be allowed some leeway, however it's "not a blanket exception for the president or anyone else," according to comments made to Politico by legal and policy chief Vijaya Gadde, alongside CEO Jack Dorsey.
Dorsey, who is set to testify before two congressional committees Wednesday about censorship and other corporate policies, says he receives notifications to his phone when Trump tweets – however he declined to get into specifics when asked if he would weigh in personally to remove Trump from the platform.
"We have to balance it with the context that it's in," he said. "So my role is to ask questions and make sure we're being impartial, and we're upholding consistently our terms of service, including public interest.".
Twitter and Facebook have both been under intense pressure from legislators over how the companies decide to censor content, as well as which advertisements they allow to run on their platforms. Dorsey is testifying on Capitol Hill on Wednesday, first before the Senate Intelligence Committee – where he will discuss foreign use of social media for election meddling, and later to the House regarding allegations of bias against conservatives.
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one is the loneliest number: gender in tony abbott's cabinet
Emma Koehn
The cast of Gilmore Girls, the cast of 7th Heaven, the Afghani national cabinet and, if you think about it, most Lynx commercials have more of the lady folk in them than Tony Abbott's new cabinet.
PM Abbott is 'very disappointed' that his new line up includes only one female MP. Anyway, that woman, Julie Bishop, will become the lone 'female influence' in the top tier of the Coalition government as she takes on the portfolio of Foreign Affairs.
It's an odd look for a guy that's played up his closeness to women people (standing next to his daughters, smiling, encouraging the sex appeal of his candidates, that sort of thing). But there are less women in parliament than men on all sides of politics. How surprising is it that few are in high up positions?
Does gender imbalance matter?
When it comes down to it, our parliament is supposed to be vaguely representative of the groups that make up the nation. Which is awks, sure, because lots and lots of groups are underrepresented. But Australia's population is roughly 50/50 ladies and men, and the numbers in parliament should be as close to that as possible to ensure that a variety of points of view are considered in law making. Liberal Senator Sue Boyce was vocal in her disappointment at the choices for cabinet positions. She went as far as to say that the Liberal Party needs to look at their structural arrangements and how these may be affecting recruitment of women into the party in the first place. Having balance, to her it seems, means a stronger government.
Abbott did have more than one woman to choose from. He placed Bronwyn Bishop in the Speaker's Chair, demoted Brisbane MP Teresa Gambaro and placed another four ladies in his outer ministry. What's lacking is representation at the top of the tree. This is why people are up in arms–the big wigs make big decisions, and it doesn't seem balanced for only one lady to be in on that party.
What do the parties do about gender generally?
The Liberal Party don't have any formal measures for ensuring that women are represented at any particular level of parliament, though they do have a policy of employing 50% women in their administrative arm. As such, there's nothing really stopping all future Liberal candidates from being men. This is something that pops up every time we talk gender representation in parliament–if there's no encouragement for women to enter the field, it's argued the 'depth of experience' of female parliamentarians won't ever be properly realised.
The Labor Party, on the other hand, has an affirmative action policy of 40:40:20, in which at least 40% of candidates for seats must be women. This is a fact that Labor MPs are keen to spruik, because they have had consistently higher levels of women in cabinet (six women were in KRudd's before the election).
Neither of the major parties reaches that 50/50 gender split, and if they did there would still be a chance that women could end up on the back bench. But some voices in the Liberal Party have been connecting this lack of quota with the shortage of cabinet ministers, and it's something that has been spoken on and investigated well before the election campaign properly kicked off.
Is meritocracy even a thing?
So there's an argument that the Liberal National Party Coalition is more progressive than Labor because they place ultimate emphasis on the talent of candidates rather than whether or not they're male or female. This is an argument that is used to rebut gender quotas in a lot of situations. If we follow that lead, you finally reach the conclusion that there aren't that many talented women in the Liberal or National parties. If there were, maybe they would have 'matched the skills' of their male counterparts readily, and then more would have been admitted into cabinet. The idea that politics has been dominated by men for so long because they were the 'best' candidates seems a touch problematic.
It seems improbable in light of there being more women in high up roles in Labor and the Greens. Are they fighting it out against less able men, or are women in the Liberal Party just slightly more crap at their jobs overall?
Here's the thing: Abbott didn't have a whole lot of women to choose from, because there aren't that many there to start with. But in terms of the faces of our new government, it's a lotta men in ties and one lady with impeccable taste in brooches (seriously, look for them in Question Time). Does that represent the average citizen of Australia?
Let us know your thoughts.
This entry was posted in featured, News and tagged News, politics, tony abbott. Bookmark the permalink.


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Logo Idea for Copywriter — Quick logo draft for a friend of mine that is a talented copywriter.
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You may read for fun, out of curiosity or to learn new things. As you read, sometimes you'll come across life changing books in unexpected places. These books may teach you a lesson. Sometimes they may articulate your own feelings with surprising accuracy. When you're in a dark place, some books can point you in a different direction. Here are ten of the best life-changing books that you might want to pick up this weekend.
This novel is old, recommended again and again, and the only book of fiction on this list. But we had to include it among the best life-changing books, because Atticus Finch is one of the noblest characters that any novelist has ever created. No other pretentious exploration on how to be a good person can match the effect that this book may have had on millions of people around the world. You can buy the paperback from Amazon at $5.89.
This book is a manual for business leaders and among the world's best life-changing books. But really, anyone can learn from Stephen Covey's advice on getting things done. The book was a mega-hit when it came out. Millions of young entrepreneurs around the world, lost and hungry to give a framework to their dreams, have thumbed its pages.
Today, it may seem a little dated: Covey is essentially telling you to get off Facebook and take steps towards your goals. But one tool I carry with me even today is the 2X2 matrix to prioritize tasks to organize each week around. You can buy the paperback on Amazon for $10.57.
This is a fascinating book that confirms something that you may have suspected all along. That the optimal experiences of our lives don't come from weekends and vacations. Those are only pauses for recharge. It's only when we are are giving our all in pursuing meaningful goals we've set ourselves, that we are in the 'flow'. It is also when we are happiest. But it's not always easy maintaining that flow. This book teaches you how you can channel it, and makes it one of the best life-changing books to read. The classic is available on Amazon for a steal of $2.99.
Happier is a book of stories, anecdotes, wisdom and research by a psychologist from Harvard. If you want to learn practical tips to find happiness in everyday life, this is one of the life changing books that will help you. It doesn't teach you impractical philosophies, but about little changes that you can make in your life to be happier. Amazon is offering the paperback for $6.81.
Have you ever wondered how the prisoners in concentration camps got through each day? How do they reconcile to their situation in their minds? The author gives us a first-hand account of such an experience. What makes the book one among the top life changing books is the questions that Frankl explores. What kind of a person does a prisoner become? This book was written more than fifty years ago. But it's brilliant because it's still relevant (it has sold 10 million copies). It will tell you things about humanity and survival that may change the way you think. You can buy the beautiful hardcover gift edition on Amazon starting at $14.35.
This is not an easy book to read. Nor is it a classic (it was recently released), or without flaws. It is inspired by a classic – James Baldwin's The Fire Next Time. Like the inspiration, it starts with a letter to a young black boy. But Coates' view of the present black position in America is bleak. He tells his son plainly that in America, it is heritage to destroy the black body. Yet like Baldwin, he urges his son to struggle against it.
In a way, the book is powerful because it is a rare book about racism that is not written for white people. If you read it open-mindedly, and ask yourself the tough questions that Coates raises, the book may change your perspective on how you see other people. You can get the paperback on Amazon for $9.59.
This short work is profound and powerful, and deserves to feature along with other life changing books. You'll be able to read through it in a couple of hours, and come away with simple but important ideas on the power of thought to change your life. Get the 21st century edition of the book for $5.99 on Amazon.
This excellent book is written as a letter to a friend on how to bring up her daughter a feminist. But anyone can read this book – fathers, sons, daughters too. The best-selling novelist has the right idea of equality in the 21st century between men and women. The points she makes are easy to follow, if we can only follow them. And if we do, this book can become one of the life changing books we treasure forever. The hardcover format is available on Amazon for $10.53.
The Bright Hour is one of those witty, moving and bittersweet books that will change your life. It is the autobiography of a dying mum, after she has learned that she is dying of breast cancer. The 'cancer' book could clearly have become a tearjerker – and it does draw tears though never gratuitously. But it's a beautiful, pragmatic, humorously written meditation on life and death. Riggs' language is poetic and evocative. She was a poet after all, and a direct descendant of Ralph Waldo Emerson. You can read the hardcover from Amazon at $15.72.
This is another of those books that will change your life, if you let it. It is a book about ordinary people who achieve success. It will make you think about your own situation. Hopefully, it will inspire you to keep going! Get it on Amazon for $10.29.
We hope you find something that you enjoy on this list. Some are modern classics. But we've also slipped in a few recent releases that we think have the potential to become books that will change your life.


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Home » Zika Virus Reported to be Sexually Transmitted in Texas
Zika Virus Reported to be Sexually Transmitted in Texas
CDC confirms Zika transmitted by sex, not mosquito in Dallas
Matt O'Connor
Shortly after the World Health Organization announced the Zika virus an international public health emergency on Monday, a case of Zika virus infection transmitted by sex, as opposed to a mosquito bite, was confirmed in Texas on Tuesday. Today in Florida, Governor Rick Scott declared a public health emergency in four Florida counties due to a total of nine travel-associated Zika cases.
The Centers for Disease Control and Prevention has since confirmed the case in Dallas, according to The New York Times. Health officials there say the person infected during sex had not left the United States, and there was no documented transmission of the virus by mosquitos in the city. The case involved a patient who had had sex with an infected traveler who recently returned from Venezuela.
"America's hospitals are working closely with their local public health officials and with the CDC. Important steps are being taken now by public health agencies to identify and share effective strategies for reducing the likelihood that the virus will spread to the United States and to prepare hospitals to correctly diagnose and treat any who may have become infected," said John Combes, M.D., chief medical officer of the American Hospital Association, in a statement.
"Hospitals will continue to partner with public health officials to spread the word about the dangers of this virus and to share strategies individuals, particularly pregnant women, can use to avoid becoming infected."
Parkland Health & Hospital System announced that it had assembled multidisciplinary teams comprising specialists in infectious diseases, infection prevention, pathology, obstetrics, pediatrics, nursing, patient safety and risk, and offered reassurance that the risk of infection in this country is currently low. "There is no concern for Zika virus in individuals who have not traveled to, or in those who have not had sexual contact with an individual who has traveled to a Zika virus-affected country," said Pranavi Sreeramoju, M.D., Parkland's chief of infection prevention and associate professor in medicine–infectious diseases at the University of Texas Southwestern Medical Center, in a news release.
The CDC said that it will provide guidance on sexual transmission soon, telling Medscape Medical News that "sexual partners can protect themselves by using condoms to prevent spreading sexually transmitted infections."
However, it is important to note that the majority of transmission involves a bite from a mosquito, but sexual transmission adds a new challenge for detecting and preventing Zika from spreading.
Patient CareClinical ManagementZika Update
The Latest on the Zika Virus
As the Zika virus continues to spread throughout the Americas, patients with the virus are showing up throughout the continental U.S. Two Illinois residents and an Arkansas resident are among the latest to test positive for the virus.
Virus Spreading 'Explosively'; Latest Zika News
The World Health Organization estimates three to four million cases of Zika over the next year.
Working Toward a Zika Vaccine Before it Hits the U.S. Mainland
The Zika virus has been confirmed in more than 20 countries in South and Central America, including cases in Puerto Rico and the U.S. Virgin Islands. The Centers for Disease Control and Prevention yesterday described measures being taken to understand and treat the continuous spread of the Zika virus before it can become prevalent in the United States.
The Role of the Pathologist in Diagnosis, Quality, and Patient Safety


My guest tonight is Earphones award-winning narrator Jim Seybert!
Jim and I reminisce for awhile about L.A. radio stations in the 70s and 80s. Then Jim tells me how he went from the radio world to marketing to audiobook narration, about winning an Earphones award for narrating a book that felt like it was written just for him, and how important it is to have confidence and to pursue excellence as an audiobook narrator. All this over some cask strength Booker's bourbon and a rye flight!
You can find Jim online at http://jimseybert.com, on Facebook at TheJimSeybertCompany, on Twitter at @jimseybert, and on Instagram at @jimseybertnarrator.


At the meeting of the commission for modernisation on 30 March, President Dmitri Medvedev announced a list of recommendations for the government and the President's Administration aimed at improving the investment climate. On the level of specific instructions, the crucial is that the deputy prime ministers and ministers sitting on the supervisory boards of the state-owned enterprises in their respective industries should resign by 1 July this year. Implementing this order will lead to the departure of several important representatives of the ruling team from state companies, including the influential deputy prime minister Igor Sechin. This action will weaken these officials' means for direct control over the companies, but it does not mean they will lose their influence on the economy, as the practice of governing via informal contacts is of essential importance. The general significance of the President's recommendations comes down to a call to reform the existing economic model, and is another sign of his public criticism of how power is wielded in Russia. By this action, Medvedev is giving up demonstrating his loyalty to the ruling elite; this may lend credence to the thesis that he is not seeking re-election, and is now focusing on strengthening his image as a moderniser and reformer.
A list of 10 recommendations, with deadlines for their implementation, was handed to the Government and the President's Administration on 2 April (presidential recommendations are not binding legal instruments, and are rather seen as political documents). Among other measures, the President has called for a reduced role for officials in regulating economic processes, increased public supervision of the activities of state organs, and the building of mechanisms for dialogue and consultation with business. The most important recommendation appears to be that the deputy prime ministers and ministers sitting on the supervisory boards of the state-owned enterprises in their respective industries be dismissed by 1 July (as should all representatives of the government and the President's Administration, by 1 October), and that independent directors or delegates of the government should be appointed to those positions. Interestingly, this recommendation does not apply to the Prime Minister (Vladimir Putin is head of the supervisory board of the state bank Vneshekonombank). Currently, representatives of the government and the President's Administration serve on many boards of directors in state-owned companies, often several at a time. This reinforces their control over these particular sectors, and they often exploit this role to build up their private economic power bases.
Who will lose from these changes?
Most of the recommendations contained in the document are not very specific in nature. Some of them accord with government policy (such as the elaboration of a specific timetable for privatisation over the period from 2011 to 2013; the government has already accepted a general programme for privatisation by 2015). We may also expect the implementation of the President's plan to lower the social insurance rates, which had been raised during the economic crisis.
In turn, implementing the most important recommendation – namely, removing the deputy prime ministers and ministers from the supervisory boards of state-owned enterprises – may lead to changes in the government's mechanism for supervising these firms, and limit the influence of certain officials on how these businesses operate. However, formal membership of the supervisory boards is not their sole and most important tool for affecting the economy, especially regarding important members of Putin's elite (most of whom have no government positions). Most important is the informal influence and exploitation of social contacts they use to promote decisions which benefit them, most often with the Prime Minister and leader of the ruling team, Vladimir Putin. It is likely that the members of the elite are now using their influence to keep control over the state companies, for example, by getting trusted associates appointed to their old positions.
The most important case here seems to be that of the deputy prime minister Igor Sechin, the interim chairman of Rosneft's supervisory board, and the person at whom President Medvedev's recommendations will strike hardest. Sechin is one of the most influential members of Putin's elite, and the best example of how Putin's inner circle has used informal mechanisms to take control of the economy. The launch of the 'Yukos case' in 2003, which resulted in the state-owned Rosneft taking over its most important assets, is attributed to Sechin, although he himself had no formal instruments of control over the petroleum sector at that time. Sechin was only named deputy prime minister for the energy sector in Putin's government in 2008, when his informal influence in this sector was already firmly established. Now, as directed by the President, Sechin must leave Rosneft, which formally removes him from any decision-making on the company's policies. On the other hand, Sechin's strong position in the elite and his crucial impact on the petroleum sector leads one to believe that he will seek to maintain his interests in the company via his associates. From media reports, it appears that the government's representative in Rosneft may turn out to be Sechin's close colleague Vladimir Milovidov. Previously head of the government's Federal Financial Markets Service, Milovidov resigned from this position on 30 March. The case of Sechin shows that even the formal implementation of the President's recommendations does not mean that the declared objective, of reducing the role of the state in the economy, will be achieved.
An analysis of the possible consequences of Medvedev's recommendations shows that the President's aim is not so much to limit the influence of the ruling elite as a whole, but rather to temporarily weaken the position of certain members of the elite, especially Sechin. This can be explained by the poor relationship between the two politicians (before the choice of Medvedev as President, Sechin was said to have opposed his nomination); nor can it be ruled out that the move to put certain limits on the influential and increasingly self-reliant Sechin may have the tacit support of the leader of the ruling team, Vladimir Putin.
At the same time, the general significance of the President's recommendations and their accompanying rhetoric (such as his strong criticism of the state's excessive role in the economy) confirm that during the run-up to the election, the President is allowing himself to criticise Russia's economic and political model with increasing vigour, ceasing his demonstrations of loyalty to Putin's elite. This may lend credence to the thesis that Medvedev is not seeking re-election, which at the same time would suggest that Vladimir Putin has made the decision to return to the Kremlin. In this context, President Medvedev's liberal declarations of the last month would be part of his strategy of strengthening his image as a moderniser and reformer. In his declarations, Medvedev seems to be drawing on the mood of the country's business and intellectual elites, who are appealing increasingly vocally for adjustments to the ruling team's policies, including an end to the latter's monopoly on political and economic decisions. The most interesting voice to be heard in this discussion comes from a report issued at the end of March by the Centre for Strategic Studies, a think-tank close to Putin, which warns the government against losing its legitimacy, and states that a political crisis might erupt if the current policies, including tight control over the political sphere, are maintained.


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'Privileged' Mike Williams signed Leicester Tigers contract extension without hesitation
"I didn't even have to think about it," says forward after putting pen to paper on two-year deal
martin Crowson
Mike Williams "didn't even have to think about" signing his new Leicester Tigers contract (Image: Henry Browne/Getty Images)
Forward Mike Williams says he was so happy to be offered an extended contract at Leicester Tigers that he "didn't even have to think about it" before putting pen to paper.
The 26-year-old comes to the end of his current deal next summer and Tigers have acted quickly to tie him down for another two years.
The hard-hitting Zimbabwean has been terribly unlucky with injuries since joining the club from Worcester in 2015, suffering three broken arms in the process.
But with those problems hopefully behind him, Leicester know just the level of physical presence that he brings to the team. With head coach Matt O'Connor especially keen for his sides to win the gain-line battle, a player of Williams' presence is crucial to that aim.
Leicester Tigers' Tom Croft announces his immediate retirement from rugby
The flanker/lock says he agreed to stay on because he feels the club is heading is just the right direction under O'Connor's leadership.
"I didn't even have to think about it when I was offered an extension," he said. "I feel very privileged to be offered to stay for another two seasons.
"Tigers have been very good to me throughout the time I have been here, especially with all of my arm injuries. It was an easy decision to make and I am happy to be here.
"I heard a lot of good things about Matty from those boys who had worked with him before and you can see with regards to our performances in the Premiership before the Anglo-Welsh kicked off, that we are all on the same page now and heading in the right direction with how Matt wants to play.
Mike Williams feels "very privileged" to have signed a new Tigers contract
"These are promising times and it is going to be a challenging time, especially with a tough block over Christmas and with the international boys being away now.
"If you look at the performance against Bath though, with ten teenagers out there, it is very good to see the depth of the squad that is coming through. It creates competition on the pitch and makes all of the boys work hard for starting jerseys at the weekend."
Williams could be part of the squad that faces Sale Sharks when the clubs return to Aviva Premiership action on Sunday. Tigers face Sale (10th) and Worcester (12th) during a six-day spell and two wins will be a minimum requirement for a side with pretentions of a top-two finish.
Leicester will be without a host of international but Williams says there will still be some fierce competition for shirts this week.
Tom Croft's top five career highlights and his injury setbacks
"Sale are a very tough team with a strong pack and good line-out, drive and scrum," he said. "But if we can bring it to them up front, I am sure we will be okay.
"It's always a difficult block for the bigger squads when you lose international boys but, luckily enough, we have loads of young boys coming through and they have shown over the past two weekends that they are capable of that step-up and can put in a performance.
"We saw in the Anglo Welsh Cup how much the young boys are coming through and are putting their hand up for selection."
Leicester City FCLeicester City continue under-23s recruitment drive by signing former Aston Villa defenderSteve Beaglehole's development side will have plenty of new faces ahead of next season


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8 young de...
8 young designers pen letter for future fur-free fashion
Vivian Hendriksz
Tuesday, October 25 2016
8 young and talented designers have penned a letter to students at Central Saint Martins, urging them to explore the ethical side of the fashion industry and not use fur in their collection.
The letter, which encourages students to embrace vegan materials and reject any offers from fur companies to use their skins or pelts in exchange for collection sponsorship, is signed by none other than Hannah Weiland, founder of Shrimps and London fashion week designer. Her signature is joined by Marta Jakubowski, Faustine Steinmetz, JH Zane, Molly Goddard, Felder Felder, Renli Su and Vika Gazinskaya.
"As future fashion designers, students at Central Saint Martins have a unique opportunity to influence the next generation of consumers by embracing the trend towards cruelty-free fashion," reads the letter. "Humane fabrics have never been more in demand, and the growing number of fur-free designs on international catwalks is a clear indication that you can be daring as well as innovative and rule the runways without harming animals."
"Fur farming is deeply cruel, bad for the environment, and completely contrary to the spirit of fashion, which should be fun, forward-looking, and innovative. Animals killed for their skins usually spend their entire lives in tiny wire cages before being gassed or anally electrocuted," concludes the letter.
Eighty-six per cent of the Autumn-Winter 2016 collections shown during London Fashion Week excluded fur according to research carried out by PETA and recent studies confirm that 95 per cent of the British public refuse to wear the cruelly produced material.
Undercover exposes have consistently shown how animals such as foxes, weasels and minks are kept confined in cramped, filthy cages without adequate space to exhibit natural behaviours before being beaten, electrocuted or drown for their fur - even at "Origin Assured" farms.
Photo 1: By Copyright © University of the Arts London (Copyright © University of the Arts London) [CC BY-SA 4.0 ( http://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons
Photo 2: JMcArthur / The Ghosts in Our Machine


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Q: Why does the Android Instrumented Test example from the official docs not work? Following the docs at https://developer.android.com/training/testing/unit-testing/instrumented-unit-tests, I have created the following build.gradle file for my app module:
buildscript {
    repositories {
        mavenCentral()
        maven { url 'https://maven.fabric.io/public' }
    }

    dependencies {
        classpath 'io.fabric.tools:gradle:1.25.3'
    }
}
apply plugin: 'com.android.application'
apply plugin: 'io.fabric'

repositories {
    maven { url 'https://maven.fabric.io/public' }
}

android {

    compileSdkVersion 27
    buildToolsVersion '27.0.3'
    useLibrary 'org.apache.http.legacy'
    defaultConfig {
        applicationId "com.myapp"
        minSdkVersion 19
        targetSdkVersion 19
        versionCode 7
        versionName "1.3.0"
        ndk {
            abiFilters "armeabi", "armeabi-v7a", "x86", "mips"
        }

        testInstrumentationRunner "android.support.test.runner.AndroidJUnitRunner"
    }

    sourceSets {
        main {
            jniLibs.srcDirs = ['libs']
        }
    }
    lintOptions {
        checkReleaseBuilds false
        abortOnError false
    }
    dexOptions {
        javaMaxHeapSize "4g"
    }
}

dependencies {
    // Required -- JUnit 4 framework
    testImplementation 'junit:junit:4.12'
    // Optional -- Mockito framework
    testImplementation 'org.mockito:mockito-core:1.10.19'
    androidTestImplementation 'com.android.support:support-annotations:27.1.1'
    androidTestImplementation 'com.android.support.test:runner:1.0.2'
    androidTestImplementation 'com.android.support.test:rules:1.0.2'
    androidTestImplementation 'org.hamcrest:hamcrest-library:1.3'
    androidTestImplementation 'com.android.support.test.espresso:espresso-core:3.0.2'
    androidTestImplementation 'com.android.support.test.espresso:espresso-contrib:3.0.2'
    androidTestImplementation 'com.android.support.test.espresso:espresso-intents:3.0.2'
    androidTestImplementation 'com.android.support.test.espresso:espresso-accessibility:3.0.2'
    androidTestImplementation 'com.android.support.test.espresso:espresso-web:3.0.2'
    androidTestImplementation 'com.android.support.test.espresso.idling:idling-concurrent:3.0.2'

    implementation fileTree(include: ['*.jar'], dir: 'libs')
    implementation project(':deviceprint-lib-2.0.1')
    implementation files('libs/gson-2.2.4.jar')
    implementation files('libs/activation.jar')
    implementation files('libs/additionnal.jar')
    implementation files('libs/mail.jar')

    implementation 'com.android.support:support-v4:27.1.1'

}

and the following project level build.gradle:
buildscript {
    repositories {
        jcenter()
        google()
    }
    dependencies {
        classpath 'com.android.tools.build:gradle:3.1.2'
    }
}

allprojects {
    repositories {
        jcenter()
        google()
    }
}

I created a directory at app/src/androidTest/java/com/mypackage and added the following file:
package com.mypackage;

import android.support.test.runner.AndroidJUnit4;
import org.junit.Test;
import static org.hamcrest.Matchers.is;
import static org.junit.Assert.assertThat;

public class ApplicationTest
{
    public ApplicationTest()
    {

    }

    @Test public void failingTest()
    {
        assertThat(false, is(true));
    }
}

All of the import statements, and the @Test annotation are marked as errors, with the message, "cannot resolve symbol" and If I right click on the file in the project window, I do not have the option to "Run".  Why?

A: The example started to work correctly after I restarted Android Studio.  :facepalm:
Edit:
another note, as I recently experienced these same symptoms for a different reason: the build variant must be set to "debug" (or you must set testBuildType inside the android {} block of your module's build.gradle file to the variant you want to test)

redpajama_set_name: RedPajamaStackExchange


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Yuki Kawauchi Runs Seventh Sub-2:10 Marathon
The Japanese marathoner is fresh off a 2:09:36 at the Hamburg Marathon, his fifth of 2014.
By Cathal Dennehy
Victor Sailer/PhotoRun
Yuki Kawauchi, the Japanese marathoner who is a sporting hero in his native country, has never been one to do things conventionally.
The 27-year-old, who has 35 marathons under his belt and a PR of 2:08:14, raced the Hamburg Marathon on Sunday, his fifth this year, finishing ninth in 2:09:36. By the end of 2014, he hopes to have raced at least 10 high-level marathons.
Kawauchi, who has run below 2:10 on seven occasions, has gained a cult following in distance running circles around the world for his unorthodox approach. He shuns the professional athlete lifestyle, preferring to work full-time, and races almost weekly.
It is in his native Japan, of course, that he is most revered. "In the history of Japanese marathoning, Kawauchi is one of the three most influential people," says his representative Brett Larner. "He has close to 200 outstanding invitations to run races in Japan at the moment and if he does show up and run, those races will have tens of thousands more than usual out on the course to see him run."
Kawauchi sat down with Running Times in Hamburg last weekend and explained through a translator why he races so often, how he combines high-level training with full-time employment, and why he's shooting for a medal at the next Olympics.
Running Times: Were you happy with your performance in Hamburg (2:09:36)?
Yuki Kawauchi: Yes. I had never broken 2:12 before when racing with jet lag, and my goal here was to break 2:10, so I'm very happy.
RT: It's virtually unheard of for an elite athlete to run high-level marathons so frequently. Why do you do it?
YK: At this point my training cycle is worked out to a one month cycle, so from my regular training I'm able to build up to a peak performance within one month. Because of this, I'm able to plan my schedule so I'm able to race very often. Compared to other athletes at my level, from Monday to Friday, I'm not able to do serious training because I work, so in the morning I do relatively low-intensity running. That allows me to put more into my weekend performances. A lot of the races are serving as workouts, even the marathons. Japanese athletes place a big importance on how many hard long runs you have done before a major marathon. It just happens that I like to do my hard long runs in public, as races, whereas most other athletes do them alone in training
RT: How do you combine full-time employment with elite marathon training?
YK: It's true that it's difficult to balance the two. It creates new challenges. I work 40 hours a week in the administration office of a high school, just regular office work. I can only train once a day during the week. In some respects, it's a restricted schedule, but compared to a lot of elite athletes, I have freedom. I don't have a coach telling me what I'm trying to do is crazy. If I want to run 10 marathons a year there's no one telling me not to do it. Being financially independent gives me freedom to do what I want to do and be the athlete I want to be.
RT: What does your typical training week look like?
YK: I run about 140K [86 miles] per week. Monday and Tuesday are just jogging. On Wednesday I do intervals or a tempo run. The intervals might be 10 x 1,000m in about three minutes or just under. I'll also do interval workouts like 20 x 400m, and that'll be at a slightly faster pace. Thursday and Friday are just jogging, and if I don't have a race on Sunday, I'll do something serious on Saturday like a long tempo run. When I do have a race on Sunday, Saturday will be relatively easy.
RT: Considering you have such a high profile in Japan and such potential with sponsorship and appearance fees, why do you choose to work a full-time job?
YK: On a practical level, government employees are not allowed accept money for outside employment, so I'm not allowed accept sponsorship, sponsor bonuses or appearance fees. On another level, though, I choose that lifestyle because for me, running is not about making money; it's about having freedom. If I'm running for money, it creates certain needs and requirements that limit my options about where I can race. I'm running for myself, my own goals and my own freedom. I have my own ambitions.
RT: What are your main goals for the year and looking further ahead, your long-term goals?
YK: My aim is to win a gold medal in the marathon at the Asian Games in October. Long-term, I'm targeting the Rio Olympics and the London World Championships in 2017. I'll be around 30 for those, my peak years. I want to win major medals then, and work towards running 2:06 and show the world that not only Africans can run those times.
RT: Will you keep going until the Tokyo Olympics in 2020?
YK: After the age of 30, you never know what's going to happen, so we'll see how that goes. I have other motivations. I want to do little local races in obscure countries. I can see my motivation shifting at some point away from making Olympic and World teams, so I'll see how that plays out after Rio.
RT: In the marathon and half-marathon, Japan has a massive depth of talent. What is it about the system there that creates so many good distance runners?
YK: It's all because of the existence of the Ekiden Relays, especially the Hakone Ekiden, which is the University Road Relay Championships. That is so prestigious in Japan. The average stage length is about a half-marathon, so you have hundreds of guys putting all their best years into running that kind of distance, and there's nobody targeting track. Nobody cares about track. The focus is entirely on the half-marathon as collegiates, and that sets people up to run 2:09, 2:10, when they leave.
RT: What are your racing plans for the rest of the year?
YK: I'm doing a trail marathon in June, then a 50K, and I'm doing the Gold Coast Marathon in Australia in July. I might do the Perth Marathon too. I'll have the Asian Games in October, and maybe two or three more marathons after that.
RT: Of all the races you've run, which one stands out as your favorite?
YK: The single greatest experience so far in my career was at the World Championships in Daegu in 2011 when I was part of the Japanese team that won the silver medal. In terms of a race itself: running the New York Marathon last year. It was eye-opening to see the top level of the sport, and they cheered me like I was one of the big boys. It was really special to be part of that world, so I want to go back there and run up to the level I can.
RT: Any other races you'd really like to do in the future?
YK: Either the Paris or London Marathon.
RT: You're a hero to many runners, but who are your heroes?
YK: I really respect people who are able to do it over a long career, like Chema Martinez from Spain, Lee Troop from Australia, and Haile Gebrselassie. My goal is to do this for the long haul, so I admire those who had that kind of career. I hope to reach my peak around the age 30, so everything I'm doing now is to reach my peak then.
Believe It: A Sub-2 Marathon Is Coming
A Primer on the Sub-2-Hour Marathon
When Will We See a Sub-2 Marathon, Really?
After a Near Sub-2 Marathon, What's Next?
Hobie Call, Would-Be Sub-2:00 Marathoner
Sub-2:00 Marathon Project Launches


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Discover Madrid with our free app 🎒
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Temple Madrid, Spain
Ancient Egyptian temple Templo de Debod
The Temple of Debod (Templo de Debod) is an ancient Egyptian temple that was dismantled and rebuilt in Madrid.
The shrine was originally erected 15 kilometres (9.3 mi) south of Aswan in Upper Egypt, very close to the first cataract of the Nile and to the great religious center in Philae dedicated to the goddess Isis. In the early 2nd century BC, Adikhalamani (Tabriqo), the Kushite king of Meroë, started its construction by building a small single-room chapel dedicated to the god Amun. It was built and decorated in a similar design to the later Meroitic chapel on which the Temple of Dakka is based. Later, during the reigns of Ptolemy VI, Ptolemy VIII, and Ptolemy XII of the Ptolemaic dynasty, it was extended on all four sides to form a small temple, 12 by 15 metres (39 ft × 49 ft), which was dedicated to Isis of Philae. The Roman emperors Augustus and Tiberius completed its decorations.From the quay, there is a long processional way leading to the stone-built enclosure wall, through three stone pylon gateways, and finally to the temple itself. The pronaos, which had four columns with composite capitals, collapsed in 1868 and is now lost. Behind it lay the original sanctuary of Amun, the offering table room and a later sanctuary with several side-rooms and stairs to the roof. In 1960, due to the construction of the Aswan High Dam and the consequent threat posed by its reservoir to numerous monuments and archeological sites, UNESCO made an international call to save this rich historical legacy. As a sign of gratitude for the help provided by Spain in saving the Abu Simbel temples, the Egyptian state donated the temple of Debod to Spain in 1968. The temple was rebuilt in one of Madrid's parks, the Parque del Oeste, near the Royal Palace of Madrid, and opened to the public in 1972. The reassembled gateways have been placed in a different order than when originally erected. Compared to a photo of the original site, the gateway topped by a serpent-flanked sun was not the closest gateway to the temple proper. It constitutes one of the few works of ancient Egyptian architecture that can be seen outside Egypt and the only one of its kind in Spain.
Tuesday: 10:00 am – 2:00 pm, 6:00 – 8:00 pm
Wednesday: 10:00 am – 2:00 pm, 6:00 – 8:00 pm
Thursday: 10:00 am – 2:00 pm, 6:00 – 8:00 pm
Friday: 10:00 am – 2:00 pm, 6:00 – 8:00 pm
Calle Ferraz, 1, 28008 Madrid, Spain


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Home / Store / Rock / Kiss – Destroyer original Japan LP with obi
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Kiss – Destroyer original Japan LP with obi
An original Japanese pressing of Destroyer by Kiss, complete with Japan-only gatefold cover and obi.
SKU: SKU-2316 Categories: 1970s, Audiophile and Quad, Hard Rock and Heavy Metal, Items, Japanese, Rock Tags: 1970s, audiophile, hard rock, Japan, Kiss, rock
Offered for sale is an original Japanese pressing of Destroyer by Kiss, including the obi, insert, and gatefold cover.
About this copy: This copy of Destroyer is an original 1976 Japanese pressing, featuring a gatefold cover and the original obi and lyric insert. This version features the then-current dark blue Casablanca label and the album includes the short instrumental track "Rock and Roll Party" which was untitled on original pressings an deleted from some later ones.
The cover is VG++, with just traces of wear at the corners. The disc is M-. No poster.
A nice copy of a hard to find Japanese Kiss album.
Background: Released as their fourth studio album, Destroyer, released in 1976, was the album that finally got Kiss their first hit. Granted, it was "Beth," a ballad, rather than the hard rock for which the band was known, but the album sold well and received a fair amount of airplay.
Allmusic.com gave Destroyer 4 1/2 stars:
The pressure was on Kiss for their fifth release, and the band knew it. Their breakthrough, Alive!, was going to be hard to top, so instead of trying to recreate a concert setting in the studio, they went the opposite route. Destroyer is one of Kiss' most experimental studio albums, but also one of their strongest and most interesting. Alice Cooper/Pink Floyd producer Bob Ezrin was on hand, and he strongly encouraged the band to experiment — there's extensive use of sound effects (the album's untitled closing track), the appearance of a boy's choir ("Great Expectations"), and an orchestra-laden, heartfelt ballad ("Beth"). But there's plenty of Kiss' heavy thunder rock to go around, such as the demonic "God of Thunder" and the sing-along anthems "Flaming Youth," "Shout It Out Loud," "King of the Night Time World," and "Detroit Rock City" (the latter a tale of a doomed concert-goer, complete with violent car-crash sound effects). But it was the aforementioned Peter Criss ballad, "Beth," that made Destroyer such a success; the song was a surprise Top Ten hit (it was originally released as a B-side to "Detroit Rock City"). Also included is a song that Nirvana would later cover ("Do You Love Me?"), as well as an ode to the pleasures of S&M, "Sweet Pain." Destroyer also marked the first time that a comic-book illustration of the band appeared on the cover, confirming that the band was transforming from hard rockers to superheroes.
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Got the album yesterday. You were correct. Perfect condition. Thanks!!!!!!!!!
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shrinkage due to increasing demands, overexploitation and biodiversity erosion.
environment policy, and to generate strategies for environmental conflict management.
promoters of change in their society.
skills to address challenges and needs of global development.
and a maximum period of twenty four72. months. All candidates enrolled for the Ph.D.
with the rules established in Egerton University Statutes.
undertake supervised independent research submit a thesis pass an oral examination.
The Ph.D. in Natural Resources and Peace is not classified.


At times it can be hard to know if a particular project that Lutheran World Relief supports continues to have an impact even after our portion has ended. That's why it was fun to hear an update from our Regional Communications Officer for Latin America, Annalise Romoser.
Annalise recently visited one of our partners in Colombia, MINGA, at an event at the Centro de Memoria Historica, in Bogotá. A few years ago we partnered with MINGA to document the experiences of victims of the ongoing violence in Colombia. Out of this documentation we created two Memory Galleries: one that toured the United States (including a display in the U.S. Congress), and one that was displayed in Colombia itself, thanks to an award we won from the United States Institute for Peace.
I was glad to hear the gallery (both galleries actually) are still going strong. They have been displayed in over 20 barrios in Bogotá and now are showing in 20 high schools. The showings and tours and affiliated pedagogy are funded in part by the mayor's office and recently the secretary of education said he wants the gallery shown in all 350 public high schools in Bogotá.
I just wanted to share this because I think it is an awesome example of how initial and relatively small investments by INGOs [International Non-Governmental Organizations] can grow into more sustainable national or local initiatives. I remember when MINGA approached us five years ago. I thought they were nuts (to be honest) and that there was no space in [Colombia] for a museum, and that a gallery was maybe off the mark. I love seeing how wrong I was. The Centro de Memoria Historica is now built and the gallery is totally relevant to where the country is at now in terms of national dialogue. I like to think the gallery helped to get to get the country there!
We love seeing this continued impact. It means that our lasting promise to the communities where we work really is sustainable!