We present cosmological constraints from the analysis of angular power spectra of cosmic shear maps based on data from the first three years of observations by the Dark Energy Survey (DES Y3). Our ...measurements are based on the pseudo-\(C_\ell\) method and offer a view complementary to that of the two-point correlation functions in real space, as the two estimators are known to compress and select Gaussian information in different ways, due to scale cuts. They may also be differently affected by systematic effects and theoretical uncertainties, such as baryons and intrinsic alignments (IA), making this analysis an important cross-check. In the context of \(\Lambda\)CDM, and using the same fiducial model as in the DES Y3 real space analysis, we find \({S_8 \equiv \sigma_8 \sqrt{\Omega_{\rm m}/0.3} = 0.793^{+0.038}_{-0.025}}\), which further improves to \({S_8 = 0.784\pm 0.026 }\) when including shear ratios. This constraint is within expected statistical fluctuations from the real space analysis, and in agreement with DES~Y3 analyses of non-Gaussian statistics, but favors a slightly higher value of \(S_8\), which reduces the tension with the Planck cosmic microwave background 2018 results from \(2.3\sigma\) in the real space analysis to \(1.5\sigma\) in this work. We explore less conservative IA models than the one adopted in our fiducial analysis, finding no clear preference for a more complex model. We also include small scales, using an increased Fourier mode cut-off up to \(k_{\rm max}={5}{h{\rm Mpc}^{-1}}\), which allows to constrain baryonic feedback while leaving cosmological constraints essentially unchanged. Finally, we present an approximate reconstruction of the linear matter power spectrum at present time, which is found to be about 20\% lower than predicted by Planck 2018, as reflected by the \(1.5\sigma\) lower \(S_8\) value.
Charged lepton flavor violation (CLFV) is a clear signal of new physics; it directly addresses the physics of flavor and of generations. The search for CLFV has continued from the early 1940s, when ...the muon was identified as a separate particle, until today. Certainly in the LHC era the motivations for continued searches are clear and have been covered in many reviews. This review is focused on the experimental history with a view toward how these searches might progress. We examine the status of searches for charged lepton flavor violation in the muon, tau, and other channels, and then examine the prospects for new efforts over the next decade. Finally, we examine what paths might be taken after the conclusion of upcoming experiments and what facilities might be required.
Sexual transmission chains of Ebola virus (EBOV) have been verified and linked to EBOV RNA persistence in semen, post-recovery. The rate of semen persistence over time, including the average duration ...of persistence among Ebola virus disease (EVD) survivors, is not well known. This cohort study aimed to analyze population estimates of EBOV RNA persistence rates in semen over time, and associated risk factors in a population of survivors from Sierra Leone.
In this cohort study from May 2015 to April 2017 in Sierra Leone, recruitment was conducted in 2 phases; the first enrolled 100 male participants from the Western Area District in the capital of Freetown, and the second enrolled 120 men from the Western Area District and from Lungi, Port Loko District. Mean age of participants was 31 years. The men provided semen for testing, analyzed by quantitative reverse transcription PCR (qRT-PCR) for the presence of EBOV RNA. Follow-up occurred every 2 weeks until the endpoint, defined as 2 consecutive negative qRT-PCR results of semen specimen testing for EBOV RNA. Participants were matched with the Sierra Leone EVD case database to retrieve cycle threshold (Ct) values from the qRT-PCR analysis done in blood during acute disease. A purposive sampling strategy was used, and the included sample composition was compared to the national EVD survivor database to understand deviations from the general male survivor population. At 180 days (6 months) after Ebola treatment unit (ETU) discharge, the EBOV RNA semen positive rate was 75.4% (95% CI 66.9%-82.0%). The median persistence duration was 204 days, with 50% of men having cleared their semen of EBOV RNA after this time. At 270 days, persistence was 26.8% (95% CI 20.0%-34.2%), and at 360 days, 6.0% (95% CI 3.1%-10.2%). Longer persistence was significantly associated with severe acute disease, with probability of persistence in this population at 1 year at 10.1% (95% CI 4.6%-19.8%) compared to the probability approaching 0% for those with mild acute disease. Age showed a dose-response pattern, where the youngest men (≤25 years) were 3.17 (95% CI 1.60, 6.29) times more likely to be EBOV RNA negative in semen, and men aged 26-35 years were 1.85 (95% CI 1.04, 3.28) times more likely to be negative, than men aged >35 years. Among participants with both severe acute EVD and a higher age (>35 years), persistence remained above 20% (95% CI 6.0%-50.6%) at 1 year. Uptake of safe sex recommendations 3 months after ETU discharge was low among a third of survivors. The sample was largely representative of male survivors in Sierra Leone. A limitation of this study is the lack of knowledge about infectiousness.
In this study we observed that EBOV RNA persistence in semen was a frequent phenomenon, with high population rates over time. This finding will inform forthcoming updated recommendations on risk reduction strategies relating to sexual transmission of EBOV. Our findings support implementation of a semen testing program as part of epidemic preparedness and response. Further, the results will enable planning of the magnitude of testing and targeted counseling needs over time.
Abstract Chronic wound infections are responsible for considerable morbidity and significantly contribute to the escalation in the cost of health care. Wound infection may initially be manifest as ...bacterial colonization, and it is only when colonization is combined with other factors, such as decreased vascular supply, intrinsic virulence of specific bacteria (eg, Staphylococcus aureus ), and host immune factors, that true infection occurs. The microbiology of chronic wounds is complex, and it is difficult to discern which bacteria are culpable. Deep cultures or quantitative biopsies of wound tissue may be necessary. In some instances, such as in the presence of certain mycobacteria, isolation of specific organisms confirms causation. In many instances, it is appropriate to treat these wounds empirically with a combination of topical antiseptics and systemic antibiotics, especially in the presence of invasive infections.
Mutations at codon 641 of EZH2 are recurrent in germinal center B cell lymphomas, and the most common variants lead to altered EZH2 enzymatic activity and enhanced tri-methylation of histone H3 at ...lysine 27, a repressive chromatin modification. As an initial step toward screening patients for cancer genotype-directed therapy, we developed a screening assay for EZH2 codon 641 mutations amenable for testing formalin-fixed clinical specimens, based on the sensitive SNaPshot single nucleotide extension technology. We detected EZH2 mutations in 12/55 (22%) follicular lymphomas (FL), 5/35 (14%) diffuse large B cell lymphomas with a germinal center immunophenotype (GCB-DLBCL), and 2/11 (18%) high grade B cell lymphomas with concurrent rearrangements of BCL2 and MYC. No EZH2 mutations were detected in cases of Burkitt lymphoma (0/23). EZH2 mutations were frequently associated with the presence of BCL2 rearrangement (BCL2-R) in both the FL (28% of BCL-R cases versus 0% of BCL2-WT cases, p<0.05) and GCB-DLBCL groups (33% of BCL2-R cases versus 4% of BCL2-WT cases, p<0.04), and across all lymphoma types excluding BL (27% of BCL2-R cases versus 3% of BCL2-WT cases, p<0.003). We confirmed gain-of-function activity for all previously reported EZH2 codon 641 mutation variants. Our findings suggest that EZH2 mutations constitute an additional genetic "hit" in many BCL2-rearranged germinal center B cell lymphomas. Our work may be helpful in the selection of lymphoma patients for future trials of pharmacologic agents targeting EZH2 and EZH2-regulated pathways.
We aimed to determine whether any of the nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, infections, and stress trigger symptomatic flares of inflammatory bowel diseases (IBDs).
...Participants drawn from a population-based IBD research registry were surveyed every 3 months for 1 year. They simultaneously tracked the use of NSAIDs, antibiotics, infections, major life events, mood, and perceived stress. Social networks, childhood socioeconomic status, and smoking were assessed at baseline. Disease flare was identified using the Manitoba Inflammatory Bowel Disease Index, a validated disease activity index. Across any two consecutive survey periods, participants were categorized as having a flare (inactive/active), having no flare (inactive/inactive), or remaining active (active/active). Potential triggers were evaluated for the first 3-month period to determine predictive rather than concurrent relationships. Data from only one pair of 3-month periods from an individual were analyzed.
A total of 704 participants completed the baseline survey; 552 (78.3%) returned all 5 surveys. In all, 174 participants who had a flare were compared with 209 who had no flare. Perceived stress, negative affect (mood), and major life events were the only trigger variables significantly associated with flares. There were no differences between those who flared and those who did not, in the use of NSAIDs, antibiotics, or in the presence of infections. Multivariate logistic regression analyses indicated that only high-perceived stress (adjusted odds ratio=2.40 (1.35, 4.26)) was associated with an increased risk of flare.
This study adds to the growing evidence that psychological factors contribute to IBD symptom flares. There was no support for differential rates of use of NSAIDS, antibiotics, or for the occurrence of (non-enteric) infections related to IBD flares.
The human genome is folded into regulatory units termed 'topologically-associated domains' (TADs). Genome-wide studies support a global role for the insulator protein CTCF in mediating chromosomal ...looping and the topological constraint of TAD boundaries. However, the impact of individual insulators on enhancer-gene interactions and transcription remains poorly understood. Here, we investigate epigenome editing strategies for perturbing individual CTCF insulators and evaluating consequent effects on genome topology and transcription. We show that fusions of catalytically-inactive Cas9 (dCas9) to transcriptional repressors (dCas9-KRAB) and DNA methyltransferases (dCas9-DNMT3A, dCas9-DNMT3A3L) can selectively displace CTCF from specific insulators, but only when precisely targeted to the cognate motif. We further demonstrate that stable, partially-heritable insulator disruption can be achieved through combinatorial hit-and-run epigenome editing. Finally, we apply these strategies to simulate an insulator loss mechanism implicated in brain tumorigenesis. Our study provides strategies for stably modifying genome organization and gene activity without altering the underlying DNA sequence.
A number of recommendations for policy and program interventions to limit excess free sugar consumption have emerged, however there are a lack of data describing the amounts and types of sugar in ...foods. This study presents an assessment of sugar in Canadian prepackaged foods including: (a) the first systematic calculation of free sugar contents; (b) a comprehensive assessment of total sugar and free sugar levels; and (c) sweetener and free sugar ingredient use, using the University of Toronto's Food Label Information Program (FLIP) database 2013 (
= 15,342). Food groups with the highest proportion of foods containing free sugar ingredients also had the highest median total sugar and free sugar contents (per 100 g/mL): desserts (94%, 15 g, and 12 g), sugars and sweets (91%, 50 g, and 50 g), and bakery products (83%, 16 g, and 14 g, proportion with free sugar ingredients, median total sugar and free sugar content in Canadian foods, respectively). Free sugar accounted for 64% of total sugar content. Eight of 17 food groups had ≥75% of the total sugar derived from free sugar. Free sugar contributed 20% of calories overall in prepackaged foods and beverages, with the highest at 70% in beverages. These data can be used to inform interventions aimed at limiting free sugar consumption.
These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and ...Immunology; and the Joint Council of Allergy, Asthma and Immunology. The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing “The diagnosis and Management of Rhinitis: An Updated Practice Parameter.” This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.
PDF
