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AbstractHow does protest affect political speech? Protest is an important form of political claim-making, yet our understanding of its influence on how individual legislators communicate remains limited. Our paper thus extends a theoretical framework on protests as information about voter preferences, and evaluates it using crowd-sourced protest data from the 2017–2019 Fridays for Future protests in the UK. We combine these data with ~2.4m tweets from 553 legislators over this period and text data from ~150k parliamentary speech records. We find that local protests prompted MPs to speak more about the climate, but only online. These results demonstrate that protest can shape the timing and substance of political communication by individual elected representatives. They also highlight an important difference between legislators' offline and online speech, suggesting that more work is needed to understand how political strategies differ across these arenas.

AbstractHow do cabinet reshuffles affect the parliamentary opposition's use of no-confidence motions in the government? Opposition parties employ no-confidence motions as electoral signals to highlight government incompetence and to position themselves as a government in waiting. We argue that cabinet reshuffles – which prime ministers use to respond to policy failures, scandals, poor ministerial performance and disloyalty – present an opportunity for the opposition to deploy no-confidence motions to this end. The incentives to deploy this strategy, however, are contingent on the nature of the party system and are greatest where party-system concentration positions a single opposition party as the alternative to the government and sole beneficiary of a no-confidence vote. We test this expectation using a multilevel modelling approach applied to data on reshuffles in 316 governments and 16 parliamentary democracies, and find support for our expectation: cabinet reshuffles raise the probability of no-confidence motions conditional on party-system concentration.

Recent research has shown an increasing interest in the historical evolution of legislative institutions. The development of the UK Parliament has received particularly extensive attention. In this article, we contribute to this literature in three important ways. First, we introduce a complete, machine‐readable data set of all the Standing Orders of the UK House of Commons between 1811 and 2015. Second, we demonstrate how this data set can be used to construct innovative measures of procedural change. Third, we illustrate a potential empirical application of the data set, offering an exploratory test of several expectations drawn from recent theories of formal rule change in parliamentary democracies. We conclude that the new data set has the potential to substantially advance our understanding of legislative reforms in the United Kingdom and beyond.

Study question: does advanced maternal age (AMA) in mice affect cardiometabolic health during post-natal life in offspring derived from an assisted reproduction technology (ART) procedure? Summary answer: offspring derived from blastocysts collected from aged female mice displayed impaired body weight gain, blood pressure, glucose metabolism and organ allometry during post-natal life compared with offspring derived from blastocysts from young females; since all blastocysts were transferred to normalized young mothers, this effect is independent of maternal pregnancy conditions. What is known already: although studies in mice have shown that AMA can affect body weight and behaviour of offspring derived from natural reproduction, data on the effects of AMA on offspring cardiometabolic health during post-natal development are not available. Given the increasing use of ART to alleviate infertility in women of AMA, it is pivotal to develop ART–AMA models addressing the effects of maternal aging on offspring health. Study design, size, duration: blastocysts from old (34–39 weeks) or young (8–9 weeks) C57BL/6 females mated with young CBA males (13–15 weeks) were either subjected to differential cell staining (inner cell mass and trophectoderm) or underwent embryo transfer (ET) into young MF1 surrogates (8–9 weeks) to produce young (Young-ET, 9 litters) and old (Old-ET, 10 litters) embryo-derived offspring. Offspring health monitoring was carried out for 30 weeks. Participants/materials, setting, methods: all animals were fed with standard chow. Blood pressure was measured at post-natal Weeks 9, 15 and 21, and at post-natal Week 30 a glucose tolerance test (GTT) was performed. Two days after the GTT mice were killed for organ allometry. Blastocyst cell allocation variables were evaluated by T-test and developmental data were analysed with a multilevel random effects regression model. Main results and the role of chance: the total number of cells in blastocysts from aged mice was decreased (P < 0.05) relative to young mice due to a lower number of cells in the trophectoderm (mean ± SEM: 34.5 ± 2.1 versus 29.6 ± 1.0). Weekly body weight did not differ in male offspring, but an increase in body weight from Week 13 onwards was observed in Old-ET females (final body weight at post-natal Week 30: 38.5 ± 0.8 versus 33.4 ± 0.8 g, P < 0.05). Blood pressure was increased in Old-ET offspring at Weeks 9–15 in males (Week 9: 108.5 ± 3.13 versus 100.8 ± 1.5 mmHg, Week 15: 112.9 ± 3.2 versus 103.4 ± 2.1 mmHg) and Week 15 in females (115.9 ± 3.7 versus 102.8 ± 0.7 mmHg; all P < 0.05 versus Young-ET). The GTT results and organ allometry were not affected in male offspring. In contrast, Old-ET females displayed a greater (P < 0.05) peak glucose concentration at 30 min during the GTT (21.1 ± 0.4 versus 17.8 ± 1.16 mmol/l) and their spleen weight (88.2 ± 2.6 ± 105.1 ± 4.6 mg) and several organ:body weight ratios (g/g × 103) were decreased (P < 0.05 versus Young-ET), including the heart (3.7 ± 0.06 versus 4.4 ± 0.08), lungs (4.4 ± 0.1 versus 5.0 ± 0.1), spleen (2.4 ± 0.06 versus 3.2 ± 0.1) and liver (36.4 ± 0.6 versus 39.1 ± 0.9). Limitations, reasons for caution: results from experimental animal models cannot be extrapolated to humans. Nevertheless, they are valuable to develop conceptual models that can produce hypotheses for eventual testing in the target species (i.e. humans). Wider implications of the findings: our data show that offspring from mouse embryos from aged mothers can develop altered phenotypes during post-natal development compared with embryos from young mothers. Because all embryos were transferred into young mothers for the duration of pregnancy to normalize the maternal in vivo environment, our findings indicate that adverse programming via AMA is already established at the blastocyst stage. Whilst human embryos display increased aneuploidy compared with mouse, we believe our data have implications for women of AMA undergoing assisted reproduction, including surrogacy programmes. Study funding/competeing interest(s): this work was supported through the European Union FP7-CP-FP Epihealth programme (278418) to T.P.F. and the BBSRC (BB/F007450/1) to T.P.F. The authors have no conflicts of interest to declare

Abstract
Secretogranin 2 (Scg2) is a member of the secretogranin/chromogranin family of proteins that is involved in neuropeptide and hormone packaging to secretory granules and serves as a precursor for several secreted pleiotropic peptides. A recent study in zebrafish showed that the teleost Scg2 orthologs, scg2a and scg2b, play an important role in mating behavior, but its modes of action and regulatory mechanisms remain unclear. In this study, we identify scg2a in another teleost species, medaka, by transcriptomic analysis as a gene that is expressed in an ovarian secretion-dependent manner in a group of neurons relevant to female sexual receptivity, termed FeSP neurons. Investigation of scg2a expression in the FeSP neurons of estrogen receptor (Esr)-deficient medaka revealed that it is dependent on estrogen signaling through Esr2b, the major determinant of female-typical mating behavior. Generation and characterization of scg2a-deficient medaka showed no overt changes in secretory granule packaging in FeSP neurons. This, along with the observation that Scg2a and neuropeptide B, a major neuropeptide produced by FeSP neurons, colocalize in a majority of secretory granules, suggests that Scg2a mainly serves as a precursor for secreted peptides that act in conjunction with neuropeptide B. Further, scg2a showed sexually biased expression in several brain nuclei implicated in mating behavior. However, we found no significant impact of scg2a deficiency on the performance of mating behavior in either sex. Collectively, our results indicate that, although perhaps not essential for mating behavior, scg2a acts in an estrogen/Esr2b signaling-dependent manner in neurons that are relevant to female sexual receptivity.

Data Monitoring Committees (DMCs) are responsible for safeguarding the interests of study participants and assuring the integrity and credibility of clinical trials. The independence of DMCs from sponsors and investigators is essential to achieving this mission. Creative approaches are needed to address ongoing and emerging challenges that potentially threaten DMCs' independence and effectiveness. An expert panel of representatives from academia, industry and government sponsors, and regulatory agencies discussed these challenges and proposed best practices and operating principles for effective functioning of contemporary DMCs.

IMPORTANCE The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce. OBJECTIVE To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged < 5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study. EVIDENCE REVIEW Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates. FINDINGS Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia. CONCLUSIONS AND RELEVANCE Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.