Explore the vast range of titles available.

Abstract Background Understanding the attack rate of influenza infection and the proportion who become ill by risk group is key to implementing prevention measures. While population-based studies of antihemagglutinin antibody responses have been described previously, studies examining both antihemagglutinin and antineuraminidase antibodies are lacking. Methods In 2015, we conducted a seroepidemiologic cohort study of individuals randomly selected from a population in New Zealand. We tested paired sera for hemagglutination inhibition (HAI) or neuraminidase inhibition (NAI) titers for seroconversion. We followed participants weekly and performed influenza polymerase chain reaction (PCR) for those reporting influenza-like illness (ILI). Results Influenza infection (either HAI or NAI seroconversion) was found in 321 (35% [95% confidence interval, 32%–38%]) of 911 unvaccinated participants, of whom 100 (31%) seroconverted to NAI alone. Young children and Pacific peoples experienced the highest influenza infection attack rates, but overall only a quarter of all infected reported influenza PCR–confirmed ILI, and one-quarter of these sought medical attention. Seroconversion to NAI alone was higher among children aged <5 years vs those aged ≥5 years (14% vs 4%; P < .001) and among those with influenza B vs A(H3N2) virus infections (7% vs 0.3%; P < .001). Conclusions Measurement of antineuraminidase antibodies in addition to antihemagglutinin antibodies may be important in capturing the true influenza infection rates. New Zealand’s seroepidemiological cohort study found that neuraminidase inhibition assay identified more influenza virus infections than hemagglutination inhibition assay. This result highlights the importance to measure serologically defined infections against not just hemagglutinin but also neuraminidase antigens in future seroepidemiologic cohort studies.

T-cell-redirecting bispecific antibodies have emerged as a new class of therapeutic agents designed to simultaneously bind to T cells via CD3 and to tumor cells via tumor-cell-specific antigens (TSA), inducing T-cell-mediated killing of tumor cells. The promising preclinical and clinical efficacy of TSAxCD3 antibodies is often accompanied by toxicities such as cytokine release syndrome due to T-cell activation. How the efficacy and toxicity profile of the TSAxCD3 bispecific antibodies depends on the binding affinity to CD3 remains unclear. Here, we evaluate bispecific antibodies that were engineered to have a range of CD3 affinities, while retaining the same binding affinity for the selected tumor antigen. These agents were tested for their ability to kill tumor cells in vitro, and their biodistribution, serum half-life, and anti-tumor activity in vivo. Remarkably, by altering the binding affinity for CD3 alone, we can generate bispecific antibodies that maintain potent killing of TSA + tumor cells but display differential patterns of cytokine release, pharmacokinetics, and biodistribution. Therefore, tuning CD3 affinity is a promising method to improve the therapeutic index of T-cell-engaging bispecific antibodies.

In this brief report, we evaluate Health Pathfinder, a whole health response to domestic violence and abuse (DVA) in the United Kingdom. We used two national datasets: monitoring data for highrisk cases, and a service-level database used to track the performance of DVA services across the UK. Drawing on a comparative interrupted time series analysis over 2018-2019, we considered the impact of implementation in each of the eight sites on rate of referral of high risk cases standardised by the number of adult women in each area, and on composition of victim-survivors seen by services. Implementation of Health Pathfinder was associated with a 10.9 per cent step change in the rate of high-risk referrals, and growth in subsequent quarters of 10.1 per cent. At the same time, implementation of Health Pathfinder was linked with a 33.6 per cent step change increase in the proportion of victim-survivors seen by services that were judged not to be at highest risk (that is, taking up services earlier). Our findings reflect both underlying system improvements across multiple stakeholders involved in Health Pathfinder as well as improved detection of DVA across a wider spectrum of risks, and provide additional evidence that multilevel interventions to improve DVA victim-survivors' experiences are effective.

INTRODUCTION : Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. METHODS : We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. RESULTS : We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. CONCLUSIONS : This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.

GATA-binding protein 3 (GATA3) is a transcription factor that is crucial to mammary gland morphogenesis and differentiation of progenitor cells, and has been suggested to have a tumor suppressor function. The rs570613 single nucleotide polymorphism (SNP) in intron 4 of GATA3 was previously found to be associated with a reduction in breast cancer risk in the Cancer Genetic Markers of Susceptibility project and in pooled analysis of two case-control studies from Norway and Poland (P trend = 0.004), with some evidence for a stronger association with estrogen receptor (ER) negative tumours [Garcia-Closas M et al. (2007) Cancer Epidemiol Biomarkers Prev 16:2269-2275]. We genotyped GATA3 rs570613 in 6,388 cases and 4,995 controls from the Breast Cancer Association Consortium (BCAC) and 5,617 BRCA1 and BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). We found no association between this SNP and breast cancer risk in BCAC cases overall (ORper₋allele = 1.00, 95% CI 0.94-1.05), in ER negative BCAC cases (ORper₋allele = 1.02, 95% CI 0.91-1.13), in BRCA1 mutation carriers RRper₋allele = 0.99, 95% CI 0.90-1.09) or BRCA2 mutation carriers (RRper₋allele = 0.93, 95% CI 0.80-1.07). We conclude that there is no evidence that either GATA3 rs570613, or any variant in strong linkage disequilibrium with it, is associated with breast cancer risk in women.

Here, two more experts give both sides of the argument. emily.retter@mirror.co.uk Yes Lisa McCrindle NSPCC Policy Manager Children of nursery age should already receive age-appropriate sex education - but of course it doesn't mention sex at this point. [...]if the argument is to reduce teenage pregnancy rates, stop the sexting epidemic, and combat sexual harassment and violence in schools and wider society, simply doing that could never hope to achieve these ends.\\n

Here, two more experts give both sides of the argument. emily.retter@mirror.co.uk Yes Lisa McCrindle NSPCC Policy Manager Children of nursery age should already receive age-appropriate sex education - but of course it doesn't mention sex at this point. [...]if the argument is to reduce teenage pregnancy rates, stop the sexting epidemic, and combat sexual harassment and violence in schools and wider society, simply doing that could never hope to achieve these ends.\\n