Trends in Ages at Key Reproductive Transitions in the United States, 1951–2010

AbstractBackgroundKey sexual and reproductive health milestones typically mark changing life stages with different fertility intentions and family planning needs. Knowing the typical ages at such events contributes to our understanding of changes in family formation and transition to adulthood and helps inform needs for reproductive health services.MethodsWe used data from the 1982–2010 National Surveys of Family Growth and the 1995 National Survey of Adolescent Males and event history methods to examine trends over time for women and men in the median ages at several reproductive and demographic events.FindingsWomen's reports indicate that age at menarche has changed little since 1951. Women's and men's median ages at first sex declined through the 1978 birth cohort, but increased slightly since then, to 17.8 years for women and 18.1 for men. The interval from first sex to first contraceptive use has narrowed, although Hispanic women have a longer interval. Age at first union (defined as the earlier of first marriage or first cohabiting relationship) has remained relatively stable, but the time between median age at first sex and median age at first birth has increased to 9.2 years for women and 11.4 for men. For some women and men born in the late 1970s, median age at first birth was earlier than median age at first marriage for the first time in at least the past several decades.ConclusionThe large majority of the reproductive years are spent sexually active. Thus, women have a lengthy period during which they require effective methods. In particular, the period between first sex and first childbearing has lengthened, but long-acting method use, although increasing, has not kept up with this shift. Moving the contraceptive method mix toward underutilized but highly effective contraceptive methods has the potential to reduce the unintended pregnancy rate

CYP2C19 Genotype Prevalence and Association With Recurrent Myocardial Infarction in British–South Asians Treated With Clopidogrel

BACKGROUND: Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in CYP2C19 and their relationship with clinical efficacy have not included South Asian populations. OBJECTIVES: The objective of this study was to assess prevalence of common CYP2C19 genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel. METHODS: The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. CYP2C19 diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification. RESULTS: Genes & Health cohort participants (N = 44,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function CYP2C19 allele. The prevalence of poor metabolizers carrying 2 CYP2C19 loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; P = 0.019). CONCLUSIONS: A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry

Teamwork and Adherence to Guideline on Newborn Resuscitation-Video Review of Neonatal Interdisciplinary Teams

BACKGROUND: Little is known about the importance of non-technical skills for the adherence to guidelines, when teams of midwives, obstetricians, anesthesiologists, and pediatricians resuscitate and support the transition of newborns. Non-technical skills are competences underpinning successful teamwork in healthcare. These are usually referred to as leadership, situational awareness, communication, teamwork, decision making, and coping with stress and fatigue. OBJECTIVE: By review of videos of teams managing newborns with difficult transition, we aimed to investigate whether the level of the teams' non-technical skills was associated with the degree of adherence to guidelines for newborn resuscitation and transitional support at birth. METHODS: Four expert raters independently assessed 43 real-life videos of teams managing newborns with transitional difficulties, two assessed the non-technical score and two assessed the clinical performance. Exposure was the non-technical score, obtained by the Global Assessment Of Team Performance checklist (GAOTP). GAOTP was rated on a Likert Scale 1–5 (1 = poor, 3 = average and 5 = excellent). The outcome was the clinical performance score of the team assessed according to adherence of the European Resuscitation Counsel (ERC) guideline for neonatal resuscitation and transitional support. The ERC guideline was adapted into the checklist TeamOBS-Newborn to facilitate a structured and simple performance assessment (low score 0–60, average 60–84, high 85–100). Interrater agreement was analyzed by intraclass correlation (ICC), Bland-Altman analysis, and Cohen's kappa weighted. The risk of high and low clinical performance was analyzed on the logit scale to meet the assumptions of normality and constant standard deviation. RESULTS: Teams with an excellent non-technical score had a relative risk 5.5 [95% confidence interval (CI) 2.4–22.5] of high clinical performance score compared to teams with average non-technical score. In addition, we found a dose response like association. The specific non-technical skills associated with the highest degree of adherence to guidelines were leadership and teamwork, coping with stress and fatigue, and communication with parents. Inter-rater agreement was high; raters assessing non-technical skills had an interclass coefficient (ICC) 0.88 (95% CI 0.79–0.94); the neonatologists assessing clinical performance had an ICC of 0.81 (95% CI 0.66–0.89). CONCLUSION: Teams with an excellent non-technical score had five times the chance of high clinical performance compared to teams with average non-technical skills. High performance teams were characterized by good leadership and teamwork, coping with stress, and fatigue and communication with parents

Steps in the bacterial flagellar motor

The bacterial flagellar motor is a highly efficient rotary machine used by many bacteria to propel themselves. It has recently been shown that at low speeds its rotation proceeds in steps [Sowa et al. (2005) Nature 437, 916--919]. Here we propose a simple physical model that accounts for this stepping behavior as a random walk in a tilted corrugated potential that combines torque and contact forces. We argue that the absolute angular position of the rotor is crucial for understanding step properties, and show this hypothesis to be consistent with the available data, in particular the observation that backward steps are smaller on average than forward steps. Our model also predicts a sublinear torque-speed relationship at low torque, and a peak in rotor diffusion as a function of torque

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity

Biological measurement beyond the quantum limit

Quantum noise places a fundamental limit on the per photon sensitivity attainable in optical measurements. This limit is of particular importance in biological measurements, where the optical power must be constrained to avoid damage to the specimen. By using non-classically correlated light, we demonstrated that the quantum limit can be surpassed in biological measurements. Quantum enhanced microrheology was performed within yeast cells by tracking naturally occurring lipid granules with sensitivity 2.4 dB beyond the quantum noise limit. The viscoelastic properties of the cytoplasm could thereby be determined with a 64% improved measurement rate. This demonstration paves the way to apply quantum resources broadly in a biological context

Forty years studying British politics : the decline of Anglo-America

The still present belief some 40 years ago that British politics was both exceptional and superior has been replaced by more theoretically sophisticated analyses based on a wider and more rigorously deployed range of research techniques, although historical analysis appropriately remains important. The American influence on the study of British politics has declined, but the European Union dimension has not been fully integrated. The study of interest groups has been in some respects a fading paradigm, but important questions related to democratic health have still to be addressed. Public administration has been supplanted by public policy, but economic policy remains under-studied. A key challenge for the future is the study of the management of expectations

Force and Motion Generation of Molecular Motors: A Generic Description

We review the properties of biological motor proteins which move along linear filaments that are polar and periodic. The physics of the operation of such motors can be described by simple stochastic models which are coupled to a chemical reaction. We analyze the essential features of force and motion generation and discuss the general properties of single motors in the framework of two-state models. Systems which contain large numbers of motors such as muscles and flagella motivate the study of many interacting motors within the framework of simple models. In this case, collective effects can lead to new types of behaviors such as dynamic instabilities of the steady states and oscillatory motion.Comment: 29 pages, 9 figure