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Background Rising midlife mortality in the USA has raised concerns, particularly the increase in 'deaths of despair' (due to drugs, alcohol and suicide). Life expectancy is also stalling in other countries such as the UK, but how trends in midlife mortality are evolving outside the USA is less understood. We provide a synthesis of cause-specific mortality trends in midlife (25–64 years of age) for the USA and the UK as well as other high-income and Central and Eastern European (CEE) countries. Methods We document trends in midlife mortality in the USA, UK and a group of 13 high-income countries in Western Europe, Australia, Canada and Japan, as well as seven CEE countries from 1990 to 2019. We use annual mortality data from the World Health Organization Mortality Database to analyse sex- and age-specific (25–44, 45–54 and 55–64 years) age-standardized death rates across 15 major cause-of-death categories. Results US midlife mortality rates have worsened since 1990 for several causes of death including drug-related, alcohol-related, suicide, metabolic diseases, nervous system diseases, respiratory diseases and infectious/parasitic diseases. Deaths due to homicide, transport accidents and cardiovascular diseases have declined since 1990 but saw recent increases or stalling of improvements. Midlife mortality also increased in the UK for people aged 45–54 year and in Canada, Poland and Sweden among for those aged 25–44 years. Conclusions The USA is increasingly falling behind not only high-income, but also CEE countries, some of which were heavily impacted by the post-socialist mortality crisis of the 1990s. Although levels of midlife mortality in the UK are substantially lower than those in the USA overall, there are signs that UK midlife mortality is worsening relative to that in Western Europe. [ABSTRACT FROM AUTHOR]

Background Pertussis is a contagious respiratory disease. Maternal tetanus–diphtheria–acellular pertussis vaccination during pregnancy has been recommended by the United States Centres for Disease Control (US CDC) Advisory Committee on Immunization Practices (ACIP) for unvaccinated pregnant women since October 2011 to prevent infection among infants; in 2012, ACIP extended this recommendation to every pregnancy, regardless of previous vaccination status. The population-level effect of these recommendations on infant pertussis is unknown. This study aimed to examine the impact of the 2011/2012 ACIP pertussis recommendation on pertussis incidence and mortality among US infants. Methods We used monthly data on pertussis deaths among infants aged <1 year between January 2005 and December 2017 in the CDC Death Data and yearly infant pertussis incidence data from the CDC National Notifiable Disease Surveillance System to perform an interrupted time series analysis, accounting for the passage of the Affordable Care Act. Results This study included 156 months of data. A potential decline in trend in infant pertussis incidence was noted during the post-recommendations period. No appreciable differences in trend were found in population-level infant pertussis mortality after the guideline changes in both adjusted and unadjusted models. Results were similar for all mortality sensitivity analyses. Conclusions The 2011/2012 ACIP maternal pertussis vaccination recommendations were not associated with a population-level change in the trend in mortality, but were potentially associated with a decrease in incidence in the USA between 2005 and 2017. [ABSTRACT FROM AUTHOR]

Economic change over the past 20 years has rendered many individuals and territories vulnerable, leading to greater interpersonal and interterritorial inequality. This rising inequality is seen as a root cause of populism. Yet, there is no comparative evidence as to whether this discontent is the consequence of localised interpersonal inequality or stagnant growth in 'left-behind' places. This article assesses the association between levels and changes in local GDP per capita and interpersonal inequality, and the rise of far-right populism in Europe and in the USA. The analysis—conducted at small region level for Europe and county level for the USA—shows that there are both similarities and differences in the factors connected to populist voting on both sides of the Atlantic. In the USA, neither interpersonal inequality nor economic decline can explain populist support on their own. However, these factors gain significance when considered together with the racial composition of the area. Counties with a large share of white population where economic growth has been stagnant and where inequalities have increased supported Donald Trump. Meanwhile, counties with a similar economic trajectory but with a higher share of minorities shunned populism. In Europe, the most significant factor behind the rise of far-right populism is economic decline. This effect is particularly large in areas with a high share of immigration. [ABSTRACT FROM AUTHOR]

Consumer behavior and sociological research have recognized early on the negative externalities of exposure to conspicuous consumption: anxiety, debt and wasteful consumption. This article contributes to political economy by incorporating the costs of exposure to wealth-signaling consumption into the materialist self-interest model of social policy preferences. The argument is that exposure to conspicuous consumption reduces support for social spending and increases demand for lower income taxes. Tax cuts impact purchasing power directly, allowing individuals to keep up with consumption standards and to avoid looking poor by comparison. Two USA-based analyses using fine-grained data on consumption and individual attitudes at the zip code and county level support the argument. Importantly, less-affluent citizens are more likely to prioritize cuts to social spending over tax increases, at higher levels of conspicuous consumption. Additional analyses rule out alternative explanations like upward mobility prospects, local wealth effects and partisan context. [ABSTRACT FROM AUTHOR]

COVID Keynesianism evaluates the USA and UK's economic response to the COVID-19 pandemic and compares it to the previous iterations of the Anglo-American policy response template. The analysis details the morbid character of neoliberal state intervention by tracing the distributional routes of monetary and fiscal measures into global corporations and across the domestic economy. The comparative findings show the degree to which emergency economic relief measures, despite their size and early success, have amplified the fault lines of inequality. The argument is that monetary flows generated windfall wealth gains for the already wealthy, while fiscal flows provided temporary gains and provisions for those on low-incomes and in deprived regions. Neoliberal efforts to protect wealth-holdings are discussed with reference to the structural conditions that generate permanent crises. [ABSTRACT FROM AUTHOR]

This article presents an application of recent management theories concerning the effect of pre-entry experience and knowledge transfer within the context of creative industries. The setting of the empirical research is the television situation comedy (sitcom) industry in the United States between 1949 and 2011. Specifically, we explore the factors that explain the survival rate of sitcoms and their spin-offs. We develop two sets of indicators to explore the effect of pre-entry experience: team similarity and star power based on the character/actor. Our findings show that spin-offs, or sitcoms that inherit character/actors and theme elements from a successful parent sitcom, have a greater likelihood to survive than de novo sitcoms. Even further, the greater the number of team members that not only worked with each other on previous shows but worked together on the same parent show, the better the performance of the spin-off. By contrast, star power, or the fame of the character/actor(s) that passes from the parent to the spin-off, shows no significant correlation with performance. We suggest that these results provide initial evidence that, consistent with the literature on spinouts in manufacturing industries, knowledge endowments represent an important source of performance heterogeneity in project-based industries. [ABSTRACT FROM AUTHOR]

The Defense Advanced Research Projects Agency (DARPA) was formed in 1958 as a research and development (R&D) agency within the US Department of Defense, while the two newer but closely comparable R&D agencies, the Advanced Research Projects Agency-Energy (ARPA-E) and the Intelligence Advanced Research Projects Agency (IARPA), were formed within the Department of Energy (DOE) and the Office of the Director of National Intelligence in 2009 and 2007, respectively. The three share an ambitious innovation organization model, operating as public sector intermediaries between science and industry to pursue mission-oriented, high-risk/high-reward, breakthrough research. They also actively promote the follow-on development and implementation of technologies they support in their mission areas, achieving what has been termed mission innovation. They are therefore much more activist than more standard American R&D agencies, which do not pursue conscious technology strategies oriented to specific mission technology challenges. The three "ARPA" agencies tend to operate as change agents within the often conservative "legacy" sectors they operate within—defense, energy, and intelligence. Within the context of the overall US innovation system, DARPA and IARPA are leading examples of what can be termed the "extended pipeline" model, while ARPA-E is located within a more traditional R&D "pipeline" model agency, the DOE, trying to reach further down the innovation pipeline. All face the types of innovation barriers common to legacy sectors, which further challenge their efforts to implement their innovations. Despite these challenges, this ARPA model has proven quite dynamic; DARPA has an unparalleled record of technological advance, and the other two are rapidly building their own records. ARPA-E and IARPA show that the DARPA model is now a proven one in the innovation space, clearly relevant for consideration in other technology development mission sectors. [ABSTRACT FROM AUTHOR]

Volunteers in the USA have long provided support for refugees being resettled through the UNHCR-based refugee resettlement program, as well as for asylum seekers and other undocumented migrants through local community or faith-based organizations. Individual and collective acts of solidarity on behalf of those seeking sanctuary, asylum seekers, and refugees have recently increased, reflecting public reaction to increasingly restrictive US immigration policies. Based on interviews with community volunteers and leaders, we analyse this activism in terms of whether it constitutes social solidarity, civic solidarity, and/or political solidarity. We find this solidarity action on behalf of forced migrants has been relatively 'low-risk' compared to other countries, where activists have faced imprisonment by engaging in 'high-risk' solidarity action. In the USA, these efforts have emphasized civic and social solidarity, with limited political solidarity actions even when volunteers have been confronted by explicitly racist and exclusionary policies. In addition, this response has yet to develop into a broader political movement in support of refugees, asylum seekers, and immigrants. [ABSTRACT FROM AUTHOR]

Just months after the Mississippi Truth Commission's public launch in 2009, organizers abandoned the Commission despite sufficient funding and growing public support, deciding instead to pursue a statewide oral history project. This study explores why, offering insight into an understudied phenomenon: incomplete truth commissions. Drawing on ethnographic observations, archival documents and interviews with local practitioners, this study highlights several reasons that local organizers changed course. In addition to a shifting cultural context, the Mississippi Truth Commission faced several cognitive challenges. First, local audiences struggled to comprehend the structure and scope of the truth commission model, leading to 'Transitional Justice 101,' a perpetual, and ultimately unsuccessful, public education program. Second, local organizers' visit to South Africa in 2009 cast doubt on the efficacy of truth commissions and caused them to question the metaphoric logic that had constructed Mississippi's history of racial violence as analogous to South Africa's, providing implicit justification for the Commission until that point. Thus, alongside economic and political resources, this research suggests that cognitive resources are a critical, and often overlooked, component of truth commissions' infrastructure. Findings also indicate that incomplete truth commissions can be leveraged to support alternative truth-seeking processes that may be more advantageous in stable democracies. [ABSTRACT FROM AUTHOR]

Objective One in four persons living with HIV in the USA is a woman. While the annual HIV diagnoses for 2019 decreased by approximately 9% when compared with 2015, this decrease was seen in men, while the rates remained stable for women. Pre-exposure prophylaxis (PrEP) is one major biomedical tool that could benefit women at risk of HIV. However, women only account for approximately 5% of PrEP users annually. The objective of this study is to identify and address the gender disparity in PrEP use. Methods This study used epidemiological data from the AIDSVu database to confirm the presence of a gender disparity in PrEP use across the USA. Cross-sectional data from 2019 showed that PrEP use was significantly higher in men, which suggested the existence of a disparity. The PrEP-to-Need ratio was then used to examine the trends in PrEP use relative to the rate of HIV infections, from 2012 to 2019, and to confirm the existence of the gender disparity in PrEP use. Key findings There is a marked gender disparity in PrEP use. This disparity is widening and therefore demands more attention to women at risk of HIV. Some recommendations for addressing the disparity include the following: raising awareness, capacity building for providers, scaling up efforts to better reach women at risk of HIV and additional research to understand the drivers of the disparity. Conclusions Policy makers could therefore prioritize the health outcomes of women by promoting research and education aimed at extending PrEP offerings to effectively reach women. [ABSTRACT FROM AUTHOR]

Background: Tick-borne encephalitis (TBE) is an arboviral disease that is focally endemic in parts of Europe and Asia. TBE cases among US travellers are rare, with previous reports of only six cases among civilian travellers through 2009 and nine military-related cases through 2020. A TBE vaccine was licenced in the USA in August 2021. Understanding TBE epidemiology and risks among US travellers can help with the counselling of travellers going to TBE-endemic areas.Methods: Diagnostic testing for TBE in the USA is typically performed at the Centers for Disease Control and Prevention (CDC) because no commercial testing is available. Diagnostic testing for TBE at CDC since 2010 was reviewed. For individuals with evidence of TBE virus infection, information was gathered on demographics, clinical presentations and risk factors for infection.Results: From 2010-20, six patients with TBE were identified. Cases occurred among both paediatric and adult travellers and all were male. Patients were diagnosed with meningitis (n = 2) or encephalitis (n = 4); none died. Cases had travelled to various countries in Europe or Russia. Three cases reported visiting friends or relatives. Activities reported included hiking, camping, trail running, or working outdoors, and two cases had a recognized tick bite.Conclusions: TBE cases among US travellers are uncommon, with these six cases being the only known TBE cases among civilian travellers during this 11-year period. Nonetheless, given potential disease severity, pre-travel counselling for travellers to TBE-endemic areas should include information on measures to reduce the risk for TBE and other tick-borne diseases, including possible TBE vaccine use if a traveller's itinerary puts them at higher risk for infection. Clinicians should consider the diagnosis of TBE in a patient with a neurologic or febrile illness recently returned from a TBE-endemic country, particularly if a tick bite or possible tick exposure is reported. [ABSTRACT FROM AUTHOR]

In 2000, Robert Putnam forecast that United States (US) democracy was at risk from the twin challenges of declining civic engagement and rising interpersonal inequality. Sixteen years later, his predictions were vindicated by the election of Donald Trump as president of the US. This paper analyses the extent to which the 2016 election of Donald Trump—and his failed re-election bid in 2020—have been related to levels of social capital and interpersonal inequalities. We posit an alternative: that the rise in votes for Trump has been the result of long-term economic and population decline in areas with strong social capital. This hypothesis is confirmed by the econometric analysis conducted for US counties. Long-term declines in employment and population—rather than in earnings, salaries, or wages—in places with relatively strong social capital propelled Donald Trump to the presidency and almost secured his re-election. By contrast, low social capital and high interpersonal inequality were not connected to a surge in support for Trump. These results are robust to the introduction of control variables and different inequality measures. The analysis also shows that the discontent at the base of the Trump margin is not just a consequence of the 2008 crisis but had been brewing for a long time. Places in the US that remained cohesive but witnessed an enduring decline are no longer bowling alone, they have golfed with Trump and will, in all likelihood, continue to golf with Trumpism or other forms of populism. [ABSTRACT FROM AUTHOR]

For over a decade, the New Vaccine Surveillance Network (NVSN) has conducted active rotavirus (RVA) strain surveillance in the USA. The evolution of RVA in the post-vaccine introduction era and the possible effects of vaccine pressure on contemporary circulating strains in the USA are still under investigation. Here, we report the whole-gene characterization (eleven ORFs) for 157 RVA strains collected at seven NVSN sites during the 2014 through 2016 seasons. The sequenced strains included 52 G1P[8], 47 G12P[8], 18 G9P[8], 24 G2P[4], 5 G3P[6], as well as 7 vaccine strains, a single mixed strain (G9G12P[8]), and 3 less common strains. The majority of the single and mixed strains possessed a Wa-like backbone with consensus genotype constellation of G1/G3/G9/G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, while the G2P[4], G3P[6], and G2P[8] strains displayed a DS-1-like genetic backbone with consensus constellation of G2/G3-P[4]/P[6]/P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Two intergenogroup reassortant G1P[8] strains were detected that appear to be progenies of reassortment events between Wa-like G1P[8] and DS-1-like G2P[4] strains. Two Rotarix® vaccine (RV1) and two RV5 derived (vd) reassortant strains were detected. Phylogenetic and similarity matrices analysis revealed 2–11 sub-genotypic allelic clusters among the genes of Wa- and DS-1-like strains. Most study strains clustered into previously defined alleles. Amino acid (AA) substitutions occurring in the neutralization epitopes of the VP7 and VP4 proteins characterized in this study were mostly neutral in nature, suggesting that these RVA proteins were possibly under strong negative or purifying selection in order to maintain competent and actual functionality, but fourteen radical (AA changes that occur between groups) AA substitutions were noted that may allow RVA strains to gain a selective advantage through immune escape. The tracking of RVA strains at the sub-genotypic allele constellation level will enhance our understanding of RVA evolution under vaccine pressure, help identify possible mechanisms of immune escape, and provide valuable information for formulation of future RVA vaccines. [ABSTRACT FROM AUTHOR]

Study Question: Has the number of preimplantation genetic testing (PGT) cycles in the UK and USA changed between 2014 and 2016?Summary Answer: From 2014 to 2016, the number of PGT cycles in the UK has remained the same at just under 2% but in the USA has increased from 13% to 27%.What Is Known Already: PGT was introduced as a treatment option for couples at risk of transmitting a known genetic or chromosomal abnormality to their child. This technology has also been applied as an embryo selection tool in the hope of increasing live birth rates per transfer. ART cycles are monitored in the UK by the Human Fertilisation and Embryology Authority (HFEA) and in the USA by the Society for Assisted Reproductive Technology (SART). Globally, data are monitored via the ESHRE PGT Consortium.Study Design, Size, Duration: This cross-sectional study used the HFEA and SART databases to analyse PGT cycle data and make comparisons with IVF data to examine the success of and changes in patient treatment pathways. Both data sets were analysed from 2014 to 2016. The UK data included 3385 PGT cycles and the USA data included 94 935 PGT cycles.Participants/materials, Setting, Methods: Following an extensive review of both databases, filters were applied to analyse the data. An assessment of limitations of each database was also undertaken, taking into account data collection by the ESHRE PGT Consortium. In the UK and USA, the publicly available information from these datasets cannot be separated into different indications.Main Results and the Role Of Chance: The proportion of PGT cycles as a total of ART procedures has remained the same in the UK but increased annually in the USA from 13% to 27%. Between 2014 and 2016 inclusive, 3385 PGT cycles have been performed in the UK, resulting in 1074 PGT babies being born. In the USA 94 935 PGT cycles have been performed, resulting in 26 822 babies being born. This gave a success rate per egg collection for PGT of 32% for the UK and 28% for the USA. Analysis of the data by maternal age shows very different patient populations between the UK and USA. These differences may be related to the way PGT is funded in the UK and USA and the lack of HFEA support for PGT for aneuploidy.Limitations, Reasons For Caution: Data reported by the HFEA and SART have different limitations. As undertaken by the ESHRE PGT Consortium, both data sets should separate PGT data by indication. Although the HFEA collects data from all IVF clinics in the UK, SART data only represent 83% of clinics in the USA.Wider Implications Of the Findings: Worldwide, a consistent reporting scheme is required in which success rates can convey the effectiveness of PGT approaches for all indications.Study Funding/competing Interest(s): No specific funding was obtained and there are no competing interests to declare that are directly related to this project. Joyce Harper is the director of the Embryology and PGD Academy, which offers education in these fields. [ABSTRACT FROM AUTHOR]

In this paper, we argue that the relationship between shareholder conflicts and corporate assets can generate multiple equilibrium configurations that can be helpful to understand how corporate governance systems may change under different historical models of capitalism. These relationships can be modeled as 'meta-complementarities' existing among two different sets of institutional complementarity. The first institutional complementarity arises in realm of the conflicts among different stakeholders and generates multiple equilibria that define different systems of rights on corporate assets. The second institutional complementarity arises between corporate rights and assets. Dispersed shareholders and non-unionized workers are complementary organizational forms and generate a form of corporate governance interacting with complementary corporate assets. A similar set of institutional meta-complementarities characterizes the relation between concentrated ownership, unionized workers and corporate assets. [ABSTRACT FROM AUTHOR]

I draw on the findings of a recently completed comparative research project to address the question: how did intergenerational social mobility change over cohorts of men and women born in the first two-thirds of the twentieth century, and what role, if any, did education play in this? The countries studied are the US, France, Germany, the Netherlands, and Sweden. Notwithstanding the differences between them, by and large they present the same picture. Rates of upward mobility increased among cohorts born in the second quarter of the century and then declined among those born later. Among earlier born cohorts, social fluidity increased (that is, the association between the class a person was born into and the class he or she came to occupy as an adult declined) and then remained unchanged for those born after mid-century. The association between class origins and educational attainment followed much the same trend as social fluidity. This suggests that growing equalization in education may have contributed to the increase in social fluidity. In our analyses we find that this is so, but educational expansion also led to greater fluidity in some countries. There is also a strong link between upward mobility and social fluidity. Upward mobility was mostly driven by the expansion of higher-level white-collar jobs, especially in the 30 years after the end of the Second World War. This facilitated social fluidity because people from working class and farming origins could move into the service or salariat classes without reducing the rate at which children born into those classes could remain there. Educational expansion, educational equalization, and rapid structural change in the economies of the US and Europe all contributed to greater social fluidity among people born in the second quarter of the twentieth century. For people born after mid-century, rates of downward mobility have increased: however, despite the lack of further educational equalization and less pronounced structural change, social fluidity has remained unchanged. [ABSTRACT FROM AUTHOR]

The current debate about taxing financial transactions is often presented as a brand new one. It is not. At the turn of the 19th century, a similar tax was debated in France and the US Financial actors fought the tax mightily. Those actors were very powerful. Yet, they lost. A tax on stock transfers (STT) was established. Why? Through a comparative analysis of France and the State of New York, this article argues that the tax was adopted because politicians interested in capitalizing on public discontent endeavored to publicize and frame the STT in simple and antagonizing terms. Strong but heterogeneous public hostility against finance got focused on the explicitly politicized issue of the tax. Political salience disrupted the logics of 'quiet politics' and momentarily undermined the privileged position of finance. Despite intense lobbying and threats to relocate from financiers, elected officials chose to vote for the STT. [ABSTRACT FROM AUTHOR]

Background: The USA ranks last in life expectancy among high-income countries. Since 2000, excess US mortality has been particularly concentrated in the working ages, which are also the ages hardest hit by the increase in drug deaths. This study measures the effect of drug-related mortality on the gap in life expectancy between the USA and other countries.Methods: Data from the Human Mortality Database and the World Health Organization were combined to construct age-standardized mortality rates for 2000-14 in 12 high-income countries and the USA for seven broad causes of death, including drug use. The contribution of each cause to the difference in life expectancy between the USA and the other 12 countries was estimated.Results: In 2014, the increase in drug-related deaths accounted for 10-15% of the US disadvantage in mortality, but with marked differences by age group. For working-age men, the increase in drug-related deaths accounted for up to 38% of the difference. Overall, American mortality is higher than the comparison countries across a wide range of causes.Conclusions: The severity of the drug epidemic appears to be specific to the USA, but it only partly contributes to the American shortfall in mortality. [ABSTRACT FROM AUTHOR]

Host-parasite relationships between Western Burrowing Owls (Athene cunicularia hypugaea) and the fleas (Pulex irritans, Siphonaptera:Pulicidae) they harbor were studied to understand the extent to which migratory Burrowing Owls translocated fleas from wintering grounds to breeding grounds. This has implications for host-parasite relationships in Burrowing Owls and also potentially for the dynamics of plague, as Burrowing Owl distributions overlap plague foci, owls inhabit fossorial mammal colonies where epizootic outbreaks of plague occur, and owls may harbor species of flea that are competent plague vectors. We used hydrogen stable isotope analysis to help elucidate geographic origins of fleas collected from adults and nestlings in 2 migratory populations of Burrowing Owls in Idaho and Oregon, USA. For adults, we posited that bird-mediated dispersal would impart flea isotopic compositions representative of southern latitudes and be similar to owl toenail tissue recently grown on wintering grounds, but they would differ from contour feathers presumably grown on breeding grounds the previous year. We assumed nestling feathers and toenails would have isotopic compositions representative of the breeding grounds. We analyzed contour feathers and toenails from adults collected shortly after they arrived in breeding grounds following spring migration and from nestlings later in the breeding season, to which we compared isotopic compositions in fleas collected from individuals of both age classes. Fleas on nestlings in both populations had isotopic compositions that did not differ from nestling feathers and toenails, suggesting that nestling fleas had breeding ground origins. Fleas on adults in one population (Oregon) had breeding ground isotopic signatures, as flea compositions did not differ from nestling feathers or toenails. Adult owls in Idaho had fleas that similarly did not express a wintering ground signature, but they were enriched in the heavy isotope (deuterium) relative to nestling feathers and toenails. Therefore, we discuss the possibility that adult owls in Idaho acquired fleas at migratory stopover sites. While the latter indicates that Burrowing Owls have the potential to disperse fleas, there was no evidence of continent-wide movement of fleas by owls from wintering grounds to breeding grounds. [ABSTRACT FROM AUTHOR]

Background: Many lines of evidence point to HIV-1 subtype-specific differences in the development of drug resistance mutations. While variation between subtype C and others has been extensively explored, there has been less emphasis on subtypes common to West Africa. We examined a previously described national survey of pretreatment drug resistance in HIV-1-infected Nigerian children aged <18 months, to explore the association between subtypes and patterns of resistance.Methods: Five hundred and forty-nine dried blood spots, from 15 early infant diagnostic facilities in Nigeria, were amplified and HIV-1 polymerase was sequenced. Four hundred and twenty-four were analysed for surveillance drug resistance mutations (SDRMs). Associations between subtype and SDRMs were evaluated by Fisher's exact test and logistic regression analysis, controlling for geographical region and exposure.Results: Using the sub-subtypes of HIV-1 G defined by Delatorre et al. (PLoS One 2014.9: e98908) the most common subtypes were CRF02_AG (174, 41.0%), GWA-I (128, 30.2%), GWA-II (24, 5.7%), GCA (11, 2.6%), A (21, 5.0%) and CRF06_cpx (18, 4.2%). One hundred and ninety infants (44.8%) had ≥1 NNRTI mutation, 92 infants (21.7%) had ≥1 NRTI mutation and 6 infants (1.4%) had ≥1 PI mutation. By logistic regression, 67N was more common in GWA-II/GCA than CRF02_AG (OR 12.0, P = 0.006), as was 70R (OR 23.1, P = 0.007), 184I/V (OR 2.92, P = 0.020), the presence of ≥1 thymidine analogue mutation (TAM) (OR 3.87, P = 0.014), ≥1 type 2 TAM (OR 7.61, P = 0.001) and ≥1 NRTI mutation (OR 3.26, P = 0.005).Conclusions: This dataset reveals differences among SDRMs by subtype; in particular, between the GWA-II and GCA subclades, compared with CRF02_AG and GWA-I. [ABSTRACT FROM AUTHOR]

Objectives: The neutropenic murine thigh infection model and a dose-fractionation approach were used to determine the pharmacokinetic/pharmacodynamic (PK/PD) relationship of LYS228, a novel monobactam antibiotic with activity against Enterobacteriaceae including carbapenem-resistant strains.Methods: Mice (n = 4 per group) were inoculated with Enterobacteriaceae strains via intramuscular injection. Two hours post-bacterial inoculation, treatment with LYS228 was initiated. Animals were euthanized with CO2 24 h after the start of therapy and bacterial counts (log10 cfu) per thigh were determined. PK parameters were calculated using free (f) plasma drug levels.Results: Following a dose-fractionation study, non-linear regression analysis determined that the predominant PK/PD parameter associated with antibacterial efficacy of LYS228 was the percentage of the dosing interval that free drug concentrations remained above the MIC (%fT>MIC). In a dose-dependent manner, LYS228 reduced the thigh bacterial burden in models established with Enterobacteriaceae producing β-lactamase enzymes of all classes (e.g. ESBLs, NDM-1, KPC, CMY-2 and OXA-48). The range of the calculated static dose was 86-649 mg/kg/day for the isolates tested, and the magnitude of the driver of efficacy was 37-83 %fT>MIC. %fT>MIC was confirmed as the parameter predominantly driving efficacy as evidenced by a strong coefficient of determination (r2 = 0.68). Neutrophils had minimal impact on the effect of LYS228 in the murine thigh infection model.Conclusions: LYS228 is efficacious in murine thigh infection models using β-lactamase-producing strains of Enterobacteriaceae, including those expressing metallo-β-lactamases, ESBLs and serine carbapenemases, with the PK/PD driver of efficacy identified as %T>MIC. [ABSTRACT FROM AUTHOR]

Background: Current inhaled polymyxin therapy is empirical and often large doses are administered, which can lead to pulmonary adverse effects. There is a dearth of information on the mechanisms of polymyxin-induced lung toxicity and their intracellular localization in lung epithelial cells.Objectives: To investigate the intracellular localization of polymyxins in human lung epithelial A549 cells.Methods: A549 cells were treated with polymyxin B and intracellular organelles (early and late endosomes, endoplasmic reticulum, mitochondria, lysosomes and autophagosomes), ubiquitin protein and polymyxin B were visualized using immunostaining and confocal microscopy. Fluorescence intensities of the organelles and polymyxin B were quantified and correlated for co-localization using ImageJ and Imaris platforms.Results: Polymyxin B co-localized with early endosomes, lysosomes and ubiquitin at 24 h. Significantly increased lysosomal activity and the autophagic protein LC3A were observed after 0.5 and 1.0 mM polymyxin B treatment at 24 h. Polymyxin B also significantly co-localized with mitochondria (Pearson's R = 0.45) and led to the alteration of mitochondrial morphology from filamentous to fragmented form (n = 3, P < 0.001). These results are in line with the polymyxin-induced activation of the mitochondrial apoptotic pathway observed in A549 cells.Conclusions: Accumulation of polymyxins on mitochondria probably caused mitochondrial toxicity, resulting in increased oxidative stress and cell death. The formation of autophagosomes and lysosomes was likely a cellular response to the polymyxin-induced stress and played a defensive role by disassembling dysfunctional organelles and proteins. Our study provides new mechanistic information on polymyxin-induced lung toxicity, which is vital for optimizing inhaled polymyxins in the clinic. [ABSTRACT FROM AUTHOR]

In this study, we used age–crime statistics from India to investigate the two core tenets of Hirschi and Gottfredson's (HG) invariance thesis that the age distribution of crime is always and everywhere adolescent spiked and thereafter declines continuously into elder ages. Besides comparisons to the inverted J-shaped distribution projected by HG, we further compared Indian age–crime patterns with those in United States (Western nation; main evidential source for HG invariance projection) and Taiwan (like India, a non-Western collectivist society). Findings suggest considerable divergence in India's age–crime patterns compared with HG invariance norm and US age–crime distributions, but overall similarity with Taiwan's age–crime schedules. Implications for research and theory on the age–crime relation more broadly are discussed. [ABSTRACT FROM AUTHOR]

Many research studies aim to draw causal inferences using data from large, nationally representative survey samples, and many of these studies use propensity score matching to make those causal inferences as rigorous as possible given the non-experimental nature of the data. However, very few applied studies are careful about incorporating the survey design with the propensity score analysis, which may mean that the results do not generate population inferences. This may be because few methodological studies examine how to best combine these methods. Furthermore, even fewer of them investigate different non-response mechanisms. This study examines methods for handling survey weights in propensity score matching analyses of survey data under different non-response mechanisms. Our main conclusions are: (i) whether the survey weights are incorporated in the estimation of the propensity score does not impact estimation of the population treatment effect, as long as good population treated-comparison balance is achieved on confounders, (ii) survey weights must be used in the outcome analysis, and (iii) the transferring of survey weights (i.e., assigning the weights of the treated units to the comparison units matched to them) can be beneficial under certain non-response mechanisms. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are characterized by highly specific immune responses against molecules in self-tissues. Different autoimmune diseases are characterized by distinct immune responses, making autoantibodies useful for diagnosis and prediction. In many diseases, the targets of autoantibodies are incompletely defined. Although the technologies for autoantibody discovery have advanced dramatically over the past decade, each of these techniques generates hundreds of possibilities, which are onerous and expensive to validate. We set out to establish a method to greatly simplify autoantibody discovery, using a pre-filtering step to define subgroups with similar specificities based on migration of radiolabeled, immunoprecipitated proteins on sodium dodecyl sulfate (SDS) gels and autoradiography [Gel Electrophoresis and band detection on Autoradiograms (GEA)]. Human recognition of patterns is not optimal when the patterns are complex or scattered across many samples. Multiple sources of errors-including irrelevant intensity differences and warping of gels-have challenged automation of pattern discovery from autoradiograms.In this article, we address these limitations using a Bayesian hierarchical model with shrinkage priors for pattern alignment and spatial dewarping. The Bayesian model combines information from multiple gel sets and corrects spatial warping for coherent estimation of autoantibody signatures defined by presence or absence of a grid of landmark proteins. We show the pre-processing creates more clearly separated clusters and improves the accuracy of autoantibody subset detection via hierarchical clustering. Finally, we demonstrate the utility of the proposed methods with GEA data from scleroderma patients. [ABSTRACT FROM AUTHOR]

The effects of media exposure differ when people are given the opportunity to choose content compared to when they are forced to view it. Contemporary explanations propose that differences between forced and selected exposure occur because of between-subject differences. We propose that differences also result from within-subject psychological reactions. Using a novel experimental design, a representative sample of U.S. adults (N = 1,967) provided their content preferences in a first session and then, in a second session, were randomly assigned to choose content or to view randomly-assigned content. Results confirm that forced exposure yields different psychological reactions than selected exposure, even in some cases among participants forced to view their preferred content. [ABSTRACT FROM AUTHOR]

Arctic cod (Boreogadus saida) is an ecologically significant species that is uniquely adapted to occupy ice edges, but warming and loss of sea ice are hypothesized to favour more facultative gadids, such as walleye pollock (Gadus chalcogrammus). To test this hypothesis, we experimentally measured the growth and survival of Arctic cod and walleye pollock at two larval stages across a range of temperature and food conditions in the laboratory. Results indicated early and late-stage Arctic cod larvae have a competitive growth and survival advantage over walleye pollock at low temperatures. However, these advantages are lost under warmer, food-productive conditions where walleye pollock larvae survived and experienced accelerated growth rates. Growth models developed from this study emphasize the need to account for both species- and stage-specific differences in the thermal response of closely related marine fish larvae. More broadly, these new vital rate data provide a mechanistic framework to forecast spatial-temporal shifts of gadids at the Arctic-boreal interface resulting from climatic warming and altered productivity regimes. [ABSTRACT FROM AUTHOR]

The Arctic marine environment is rapidly changing with rising sea surface temperatures, declining sea ice habitat and projected increases in boreal species invasions. The success of resident Arctic fish will depend on both their thermal tolerance and their ability to cope with changing trophic interactions. Larval fish energetic condition is closely associated with mortality rates and therefore provides an indicator of overall well-being or fitness. In this study, we experimentally determined larval morphometric and lipid-based condition in an Arctic gadid (Arctic cod, Boreogadus saida) and a boreal gadid (walleye pollock, Gadus chalcogrammus) in response to different temperatures and food rations. Our results suggest that larval condition is highly sensitive to both factors but varies in a species- and ontogenetic-dependent manner. Results indicated that condition metrics based on length–weight relationships were not as sensitive as those based on lipid storage. Further, condition metrics changed with ontogeny and were best used within a developmental stage rather than across developmental stages. As expected, larval condition in first-feeding Arctic cod was higher at colder temperatures (2–5°C) than in the boreal gadid (5–12°C). However, at more developed larval stages the peak condition for Arctic cod was at warmer temperatures (7°C), while walleye pollock had the same thermal optimum as during earlier stages. Arctic cod were more sensitive to food ration at first feeding than walleye pollock, however; at later larval stages both species had a negative condition response to low food ration, especially at elevated temperatures (5 vs. 7°C). The lower thermal tolerance of Arctic cod, coupled with a higher sensitivity to food availability indicates that Arctic cod are particularly vulnerable to on-going environmental change. Arctic cod is a lipid-rich keystone species and therefore a reduction in their energetic condition during summer has the potential to affect the health of higher trophic levels throughout the Alaskan Arctic. [ABSTRACT FROM AUTHOR]

One in seven American adults takes medication to alter or to prevent unwanted experience or behavior. But, the prescription and use of psychiatric medication raises practically important theological and ethical questions for practitioners, for clergy, for scholars, and for people who take medication. How does the prescription and use of psychiatric medication shape imagination and belief about what it means to be human and about the relationship of the body to the acting person? To what extent does medication facilitate technological interpretation and engagement of human life and experience? How does medication use reflect and form modern individualism? How does medication affect human experiences and perceptions of God and of God's action? In this special issue of Christian Bioethics, five scholars from different disciplines—Jeffrey Bishop, M. Therese Lysaught, Warren Kinghorn, Susan Eastman, and John Swinton—engage the meaning of psychiatric medication for Christian bioethics and for faithful Christian practice. [ABSTRACT FROM AUTHOR]

People often take psychiatric medication in order to obtain both freedom from painful experience and freedom for relationships and vocation. Thomas Aquinas' account of agency and freedom offers resources for using medications wisely. For Aquinas, bodily health is only the beginning of freedom. True freedom—always realized imperfectly in this life and perfected only with the assistance of grace—emerges when the acting person consistently pursues life-giving ends and develops habits to act for these ends with ease and pleasure. Psychiatric medications can encourage agency and freedom by correcting pathological processes, by relieving incapacitating suffering, and perhaps by lowering barriers to habituation in virtue, but they can also discourage agency and freedom by inhibiting morally salient emotional responses, by facilitating avoidance of pathological social contexts, and by reinforcing biological determinism. Psychiatric medications must be used only in ways that attend to social context and that encourage the cultivation of healthy agency. [ABSTRACT FROM AUTHOR]

Using focus groups and grounded-theory methods, this study builds a situation-specific theory describing the transitional responses of 18 former South Sudanese refugees resettled in a Midwestern US city. 'Reaching for a better life' emerged as the dominant process following resettlement. Findings revealed beliefs, abilities and expectations collide with new realities in 'The Clash' zone on arrival, encompassing varied social and cultural domains while reaching for a better life. Processes of 'understanding' and 'being understood' are mediated by resources from others and perceived losses and gains, with challenges evolving unpredictably and persisting over time. Participants identified that formal resettlement programme shortcomings include neglect of their human capital, prior knowledge and abilities, and failure to consider the most pressing needs identified by former refugees themselves. Findings contribute to understanding of the refugee journey and situational life transitions among resettled South Sudan refugees, with implications for social and health service design and community participatory research. [ABSTRACT FROM AUTHOR]

Numerous tectonic scenarios have been proposed for terrane growth and accretion within the Archean Dharwar Craton, southern Peninsular India. Previously accepted interpretations involving a two-terrane model—comprising a Western Dharwar Craton (WDC) and Eastern Dharwar Craton (EDC) block—have invoked west-dipping subduction and ocean closure, leading to arc magmatism and accretionary orogeny in the WDC, followed by metamorphic overprinting and collisional orogeny in the EDC. However, recent field investigations have revealed the existence of a previously unrecognized 'central' block (Central Dharwar Craton; CDC) within the craton, which requires revision of this model and reinterpretation of metamorphic and magmatic age data. Five samples of high-pressure, upper amphibolite- and granulite-facies meta-igneous and metasedimentary rocks from the southern portion of the Chitradurga Suture Zone, which divides the WDC and CDC, record minimum peak metamorphic conditions of ∼820–875°C at ∼10 kbar, indicating equilibration at the base of thickened continental crust. U–Pb zircon and Pb–Pb monazite geochronology indicates crystallization of parent mafic magmas at c. 2·61–2·51 Ga and subsequent regional metamorphism of these intrusions to garnet-amphibolite and garnet-granulite facies at c. 2·48–2·44 Ga, bracketing the timing of microblock accretion to the Archean–Proterozoic boundary. Light rare earth element enrichment within these zircon grains indicates magma generation in a suprasubduction-zone environment. In addition, detrital magmatic zircon grains with ages of c. 3·10–3·03 Ga and c. 2·97–2·86 Ga imply contamination of these magmas with Mesoarchean material sourced from the Western Dharwar Craton continental nucleus. Comparison of these metamorphic and magmatic age data with those recorded in the EDC shows that westward-directed subduction is implausible, and that all three terranes (the WDC, CDC, and EDC) must have accreted synchronously, driven by two separate eastward-dipping ocean–continent convergent plate margins. These data further support a recent abundance of observations from the geological record supporting the hypothesis that subduction-driven plate tectonics had initiated on Earth before c. 2·5 Ga, as opposed to a Neoproterozoic onset (c. 0·8–0·9 Ga) reported by numerous studies. [ABSTRACT FROM AUTHOR]

Prediction is often the primary goal of data analysis. In this work, we propose a novel model averaging approach to the prediction of a functional response variable. We develop a crossvalidation model averaging estimator based on functional linear regression models in which the response and the covariate are both treated as random functions. We show that the weights chosen by the method are asymptotically optimal in the sense that the squared error loss of the predicted function is as small as that of the infeasible best possible averaged function. When the true regression relationship belongs to the set of candidate functional linear regression models, the averaged estimator converges to the true model and can estimate the regression parameter functions at the same rate as under the true model. Monte Carlo studies and a data example indicate that in most cases the approach performs better than model selection. [ABSTRACT FROM AUTHOR]

Sliced inverse regression is a popular tool for sufficient dimension reduction, which replaces covariates with a minimal set of their linear combinations without loss of information on the conditional distribution of the response given the covariates. The estimated linear combinations include all covariates, making results difficult to interpret and perhaps unnecessarily variable, particularly when the number of covariates is large. In this paper, we propose a convex formulation for fitting sparse sliced inverse regression in high dimensions. Our proposal estimates the subspace of the linear combinations of the covariates directly and performs variable selection simultaneously. We solve the resulting convex optimization problem via the linearized alternating direction methods of multiplier algorithm, and establish an upper bound on the subspace distance between the estimated and the true subspaces. Through numerical studies, we show that our proposal is able to identify the correct covariates in the high-dimensional setting. [ABSTRACT FROM AUTHOR]

Multiple types of data measured on a common set of subjects arise in many areas. Numerous empirical studies have found that integrative analysis of such data can result in better statistical performance in terms of prediction and feature selection. However, the advantages of integrative analysis have mostly been demonstrated empirically. In the context of two-class classification, we propose an integrative linear discriminant analysis method and establish a theoretical guarantee that it achieves a smaller classification error than running linear discriminant analysis on each data type individually. We address the issues of outliers and missing values, frequently encountered in integrative analysis, and illustrate our method through simulations and a neuroimaging study of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

We consider a heteroscedastic regression model in which some of the regression coefficients are zero but it is not known which ones. Penalized quantile regression is a useful approach for analysing such data. By allowing different covariates to be relevant for modelling conditional quantile functions at different quantile levels, it provides a more complete picture of the conditional distribution of a response variable than mean regression. Existing work on penalized quantile regression has been mostly focused on point estimation. Although bootstrap procedures have recently been shown to be effective for inference for penalized mean regression, they are not directly applicable to penalized quantile regression with heteroscedastic errors. We prove that a wild residual bootstrap procedure for unpenalized quantile regression is asymptotically valid for approximating the distribution of a penalized quantile regression estimator with an adaptive |$L_1$| penalty and that a modified version can be used to approximate the distribution of a |$L_1$| -penalized quantile regression estimator. The new methods do not require estimation of the unknown error density function. We establish consistency, demonstrate finite-sample performance, and illustrate the applications on a real data example. [ABSTRACT FROM AUTHOR]

Uncertainty in the estimation of daytime ecosystem carbon cycling due to the light inhibition of leaf respiration and photorespiration, and how these small fluxes vary through the growing season in the field, remains a confounding element in calculations of gross primary productivity and ecosystem respiration. Our study focuses on how phenology, short-term temperature changes and canopy position influence leaf-level carbon exchange in Quercus rubra L. (red oak) at Harvard Forest in central Massachusetts, USA. Using leaf measurements and eddy covariance, we also quantify the effect of light inhibition on estimates of daytime respiration at leaf and ecosystem scales. Measured rates of leaf respiration in the light and dark were highest in the early growing season and declined in response to 10-day prior air temperatures (P < 0.01), evidence of within-season thermal acclimation. Leaf respiration was significantly inhibited by light (27.1 ± 2.82% inhibited across all measurements), and this inhibition varied with the month of measurement; greater inhibition was observed in mid-summer leaves compared with early- and late-season leaves. Increases in measurement temperature led to higher rates of respiration and photorespiration, though with a less pronounced positive effect on photosynthesis; as a result, carbon-use efficiency declined with increasing leaf temperature. Over the growing season when we account for seasonally variable light inhibition and basal respiration rates, our modeling approaches found a cumulative 12.9% reduction of leaf-level respiration and a 12.8% reduction of canopy leaf respiration, resulting in a 3.7% decrease in total ecosystem respiration compared with estimates that do not account for light inhibition in leaves. Our study sheds light on the environmental controls of the light inhibition of daytime leaf respiration and how integrating this phenomenon and other small fluxes can reduce uncertainty in current and future projections of terrestrial carbon cycling. [ABSTRACT FROM AUTHOR]

We derive solutions describing longitudinal shear flow in the Cassie state over a superhydrophic surface textured with a periodic array of equally spaced parallel grooves for arbitrary solid fraction (between |$0$| and |$1$|⁠) and arbitrary protrusion angle (between |$-\pi $| and |$\pi $|⁠) of the liquid–gas interfaces. The latter are assumed to be circular in cross section. These results provide a natural extension of those recently derived by Crowdy (2015a, IMA J. Appl. Math. 80, 1902–1931) for a similar problem but with the protrusion angle restricted to just |$\pi /2$|⁠. As in the latter, we obtain our solutions for the corresponding velocity field in a quasi-analytical form using a novel transform method. However, additional complications arise in the analysis required to perform the extension to a range of protrusion angles, as we do here, notably for protrusion angles that are negative, for which we must split the flow domain. In the process of deriving these solutions, we compute the effective slip length of the surface. As a check on our results, we compare our values for this slip length against those found by full numerical simulations, as well as against those given by analytical formulae (for the special cases for which these hold). [ABSTRACT FROM AUTHOR]

Background: Vancomycin-resistant Enterococcus faecium (VREfm) represent a major source of nosocomial infection worldwide. In Australia, there has been a recent concerning increase in bacteraemia associated with the vanA genotype, prompting investigation into the genomic epidemiology of VREfm.Methods: A population-level study of VREfm (10 November-9 December 2015) was conducted. A total of 321 VREfm isolates (from 286 patients) across Victoria State were collected and sequenced with Illumina NextSeq. SNPs were used to assess relatedness. STs and genes associated with resistance and virulence were identified. The vanA-harbouring plasmid from an isolate from each ST was assembled using long-read data. Illumina reads from remaining isolates were then mapped to these assemblies to identify their probable vanA-harbouring plasmid.Results: vanA-VREfm comprised 17.8% of isolates. ST203, ST80 and a pstS(-) clade, ST1421, predominated (30.5%, 30.5% and 37.2%, respectively). Most vanB-VREfm were ST796 (77.7%). vanA-VREfm were more closely related within hospitals versus between them [core SNPs 10 (IQR 1-357) versus 356 (179-416), respectively], suggesting discrete introductions of vanA-VREfm, with subsequent intra-hospital transmission. In contrast, vanB-VREfm had similar core SNP distributions within versus between hospitals, due to widespread dissemination of ST796. Different vanA-harbouring plasmids were found across STs. With the exception of ST78 and ST796, Tn1546 transposons also varied. Phylogenetic analysis revealed Australian strains were often interspersed with those from other countries, suggesting ongoing cross-continental transmission.Conclusions: Emerging vanA-VREfm in Australia is polyclonal, indicating repeat introductions of vanA-VREfm into hospitals and subsequent dissemination. The close relationship to global strains reinforces the need for ongoing screening and control of VREfm in Australia and abroad. [ABSTRACT FROM AUTHOR]

Objectives To sequence the genomes and determine the genetic mechanisms for linezolid resistance identified in three strains of Enterococcus isolated from cattle and swine caecal contents as part of the US National Antimicrobial Resistance Monitoring System (NARMS) surveillance programme. Methods Broth microdilution was used for in vitro antimicrobial susceptibility testing to assess linezolid resistance. Resistance mechanisms and plasmid types were identified from data generated by WGS on Illumina®and PacBio®platforms. Conjugation experiments were performed to determine whether identified mechanisms were transmissible. Results Linezolid resistance plasmids containing optrA were identified in two Enterococcus faecalis isolates and one Enterococcus faecium. The E. faecium isolate also carried the linezolid resistance gene cfr on the same plasmid as optrA. The linezolid resistance plasmids had various combinations of additional resistance genes conferring resistance to phenicols (fexA), aminoglycosides [ spc and aph(3′)-III ] and macrolides [ erm (A) and erm (B)]. One of the plasmids was confirmed to be transmissible by conjugation, resulting in linezolid resistance in the transconjugant. Conclusions To the best of our knowledge, this is the first identification of linezolid resistance in the USA in bacteria isolated from food animals. The oxazolidinone class of antibiotics is not used in food animals in the USA, but the genes responsible for resistance were identified on plasmids with other resistance markers, indicating that there may be co-selection for these plasmids due to the use of different antimicrobials. The transmissibility of one of the plasmids demonstrated the potential for linezolid resistance to spread horizontally. Additional surveillance is necessary to determine whether similar plasmids are present in human strains of Enterococcus. [ABSTRACT FROM AUTHOR]

Objectives: Extremely premature infants are at high risk of developing invasive candidiasis; fluconazole prophylaxis is safe and effective for reducing invasive candidiasis in this population but further study is needed. We sought to better understand the effect of prophylactic fluconazole on a selection of fluconazole-resistant Candida species.Methods: We evaluated the susceptibility to fluconazole of Candida isolates from premature infants (<750 g birth weight) enrolled in a multicentre, randomized, placebo-controlled trial of fluconazole prophylaxis. Candida species were isolated through surveillance cultures at baseline (study day 0-7), period 1 (study day 8-28) and period 2 (study day 29-49). Fluconazole MICs were determined for all Candida isolates.Results: Three hundred and sixty-one infants received fluconazole (n = 188) or placebo (n = 173). After the baseline period, Candida colonization was significantly lower in the fluconazole group compared with placebo during periods 1 (5% versus 27%; P < 0.001) and 2 (3% versus 27%; P < 0.001). After the baseline period, two infants (1%) were colonized with at least one fluconazole-resistant Candida in each group. Median fluconazole MIC was similar in both treatment groups at baseline and period 1. However, in period 2, median MIC was higher in the fluconazole group compared with placebo (1.00 versus 0.50 mg/L, P = 0.01). There was no emergence of resistance observed and no patients developed invasive candidiasis with a resistant Candida isolate.Conclusions: Fluconazole prophylaxis decreased Candida albicans and 'non-albicans' Candida colonization and was associated with a slightly higher fluconazole MIC for colonizing Candida isolates. [ABSTRACT FROM AUTHOR]

This article examines the role of religion in shaping environmental action by bringing contemporary arguments in cultural sociology to bear on longstanding debates about the role of religion in environmental care. Drawing on 169 in-depth interviews from 22 Christian, Muslim, and Jewish congregations in Houston and Chicago, we examine conditions under which religion enables and constrains environmental action. Findings reveal that religious institutions can motivate members' environmental actions when they cultivate not only declarative environmental beliefs but also nondeclarative environmental practices. Religion may inhibit environmental concern when respondents believe environmental commitment undermines their religious beliefs, but such justifications are disconnected from the actual environmental practices they nevertheless engage in. We also find that religious individuals largely attribute motivations for their environmental action to institutions other rather than religion. Our findings shed new theoretical light on the mixed results that characterize research on religion and the environment. [ABSTRACT FROM AUTHOR]

Background There is still significant uncertainty as to whether market competition raises or lowers clinical quality in publicly funded healthcare systems. We attempted to assess the effects of market competition on inpatient care quality of stroke patients in a retrospective study of the universal single-payer health insurance system in Taiwan. Methods In this 11-year population-based study, we conducted a pooled time-series cross-sectional analysis with a fixed-effects model and the Hausman test approach by utilizing two nationwide datasets: the National Health Insurance Research Database and the National Hospital and Services Survey in Taiwan. Patients who were admitted to a hospital for ischemic or hemorrhagic stroke were enrolled. After excluding patients with a previous history of stroke and those with different types of stroke, 247 379 ischemic and 79 741 hemorrhagic stroke patients were included in our analysis. Four outcome indicators were applied: the in-hospital mortality rate, 30-day post-operative complication rate, 14-day re-admission rate and 30-day re-admission rate. Results Market competition exerted a negative or negligible effect on the medical care quality of stroke patients. Compared to hospitals located in a highly competitive market, in-hospital mortality rates for hemorrhagic stroke patients were significantly lower in moderately (β = –0.05, P < 0.01) and less competitive markets (β = –0.05, P < 0.01). Conversely, the impact of market competition on the quality of care of ischemic stroke patients was insignificant. Conclusions Simply fostering market competition might not achieve the objective of improving the quality of health care. Other health policy actions need to be contemplated. [ABSTRACT FROM AUTHOR]

Background Determinants of hypertension diagnosis and/or awareness and control among older adults are understudied in Albania, a former communist country in South Eastern Europe, which is experiencing rapid demographic, socioeconomic and epidemiological transition. This paper examines the association of individual, interpersonal, organizational and community factors with hypertension awareness and control among older adults in Tirana, the Albanian capital. Methods Using 2012 International Mobility in Aging Study data on older adults from Albania's capital city (n = 393) and the socioecological model as a conceptual framework, multinomial regression models identified factors associated with controlled, uncontrolled and undiagnosed hypertension. Results For hypertension, 17.3% participants had none, 23.4% were controlled, 48.4% were uncontrolled and 10.9% were undiagnosed/unaware. Compared to those with controlled hypertension, in multivariable models, a high level of friend support was negatively associated with uncontrolled (OR: 0.4; 95% CI: 0.2–0.9) and undiagnosed (OR: 0.2; 95% CI: 0.1–0.6) hypertension. A high level of perceived neighbourhood safety was negatively associated with uncontrolled (OR: 0.6; 95% CI: 0.3–1.0) and undiagnosed (OR: 0.4; 95% CI: 0.2–1.0) hypertension. Compared to those with no hypertension, children's social support was positively associated with uncontrolled (OR: 2.2; 95% CI: 1.1–4.3) and undiagnosed (OR: 3.6; 95% CI: 1.3–9.6) hypertension. Conclusion This study provides new insights about distinct risk factors for inadequate hypertension management in Albania. It highlights the importance of community-level factors (safety) and interpersonal factors (family and friend ties) to hypertension diagnosis/awareness and control, which may provide novel intervention opportunities for hypertension programs. [ABSTRACT FROM AUTHOR]

Circulating insulin-like growth factor-1 (IGF-1) is consistently associated with prostate cancer risk. IGF-1 binds to IGF-1 receptor (IGF1R) and insulin receptor (IR), activating cancer hallmark pathways. Experimental evidence suggests that TMPRSS2:ERG may interact with IGF/insulin signaling to influence progression. We investigated IGF1R and IR expression and its association with lethal prostate cancer among 769 men. Protein expression of IGF1R, IR and ERG (i.e. a surrogate of ERG fusion genes) were assayed by immunohistochemistry. Cox models estimated hazard ratios (HR) and 95% confidence intervals (CI) adjusted for clinical characteristics. Among patients, 29% had strong tumor IGF1R expression and 10% had strong IR expression. During a mean follow-up of 13.2 years through 2012, 80 men (11%) developed lethal disease. Tumors with strong IGF1R or IR expression showed increased cell proliferation, decreased apoptosis and a higher prevalence of ERG. In multivariable models, strong IGF1R was associated with a borderline increased risk of lethal prostate cancer (HR 1.7; 95% CI 0.9–3.1). The association appeared greater in ERG-positive tumors (HR 2.8; 95% CI 0.9–8.4) than in ERG-negative tumors (HR 1.3; 95% CI 0.6–3.0, p-heterogeneity 0.08). There was no association between IR and lethal prostate cancer (HR 0.8; 95% CI 0.4–1.9). These results suggest that tumor IGF1R expression may play a role in prostate cancer progression to a lethal phenotype and that ERG-positive tumors may be more sensitive to IGF signaling. These data may improve our understanding of IGF signaling in prostate cancer and suggest therapeutic options for disease subtypes. [ABSTRACT FROM AUTHOR]

Millions of dollars have been spent on the design and dissemination of educational materials to improve handwashing to prevent infectious diseases. School-age children have been the focus of many of these efforts; yet little is known about the content of these materials. This study uses content analysis to examine the theoretical and motivational trends as well as the communication approach used in a sample of hand hygiene intervention materials targeting elementary-age children. Two trained coders analyzed 144 communication materials. Study results indicate that educational materials infrequently exhibit information consistent with theories of communication for behavior change, commonly use fear-based messaging, and rarely recommend using technology in the design of the interventions. Implications for future research and the design of more strategic, child-focused hand hygiene interventions are discussed. [ABSTRACT FROM AUTHOR]

The landscape for patenting products and processes tied to the natural world has changed dramatically in recent times as a result of a series of decisions of the US Supreme Court, particularly Mayo Collaborative Services v Prometheus Laboratories 566 U.S. 66 (2012) and Association for Molecular Pathology v Myriad Genetics, Inc. 569 U.S. 576 (2013) (Myriad). This article critically analyses these decisions and the multitude of lower court decisions that have followed them. This analysis provides support for the growing concern in the United States that it will be increasingly difficult to use the patent system to encourage the development of therapies and research intermediates useful in developing new therapeutic interventions. One option being posited in the industry to deal with this problem is to lobby Congress to reform the threshold patent eligibility standard in US patent law. It is argued in this paper that a more nuanced approach is preferable. Using the experience in Australia as a case study, this paper argues that such an approach is feasible. Australia has been chosen for analysis because the threshold patent eligibility standard is similar in both countries, much more so that with the European Union, and because the highest court in Australia has ruled on essentially the same patent as in Myriad, in D'Arcy v Myriad Genetics, Inc [2015] HCA 35. In addition to the nuanced approach to eligibility currently exercised by the Australian courts and patent office, Australia also has a number of post-grant options for addressing the dynamics of patent monopolies. These include experimental use, compulsory licensing, and government use. It is concluded that, while it would be impractical to attempt to replicate the Australian environment in the United States, there is no reason why some lessons can't be learned from the Australian experience with patenting nature. [ABSTRACT FROM AUTHOR]

In the past three decades the European eel Anguilla anguilla experienced up to 99% decline in recruitment in some parts of its distribution range. In addition to this long-term trend, glass eel recruitment exhibits significant inter-annual variability partially explained by large-scale oceanographic processes as well as local-scale meteorological and hydrological variables. A 40-year long time series of glass eel fishery catch in the Minho estuary, Portugal, was used to assess (a) whether local recruitment followed the general pattern of decline of A. anguilla observed elsewhere, and (b) whether environmental variables may explain inter-annual fluctuations in glass eel recruitment in the Minho estuary. The analysis shows that, in contrast to the majority of coastal systems in northern Europe and the Mediterranean, CPUE of glass eel in the Minho estuary did not exhibit a marked decline between 1974–2015 and never dropped below 20% of the 10-year mean (1974–1983), taken as baseline. The difference between the recruitment trend observed in the Minho river and that reported by WGEEL for wider European geographical scales highlights the need to calculate recruitment indices with a higher geographic resolution to better support the assessment of the status of the European eel population. [ABSTRACT FROM AUTHOR]