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Group B streptococcus (GBS) is a gram-positive bacteria that asymptomatically colonizes the vaginal tract. However, during pregnancy maternal GBS colonization greatly predisposes the mother and baby to a wide range of adverse outcomes, including preterm birth (PTB), stillbirth, and neonatal infection. Although many mechanisms involved in GBS pathogenesis are partially elucidated, there is currently no approved GBS vaccine. The development of a safe and effective vaccine that can be administered during or prior to pregnancy remains a principal objective in the field, because current antibiotic-based therapeutic strategies do not eliminate all cases of invasive GBS infections. Herein, we review our understanding of GBS disease pathogenesis at the maternal-fetal interface with a focus on the bacterial virulence factors and host defenses that modulate the outcome of infection. We follow GBS along its path from an asymptomatic colonizer of the vagina to an invasive pathogen at the maternal-fetal interface, noting factors critical for vaginal colonization, ascending infection, and vertical transmission to the fetus. Finally, at each stage of infection we emphasize important host-pathogen interactions, which, if targeted therapeutically, may help to reduce the global burden of GBS.

Preeclampsia (PE) is a hypertensive disorder of pregnancy occurring in approximately 10% of women worldwide. While it is life threatening to both the mother and baby, the only effective treatment is delivery of the placenta and fetus, which is often preterm. Maternal obesity is a risk factor for PE, and the effects of both on offspring are long standing with increased incidence of cardiometabolic disease in adulthood. Obese BPH/5 mice spontaneously exhibit excessive gestational weight gain and late-gestational hypertension, similar to women with PE, along with fetal growth restriction and accelerated compensatory growth in female offspring. We hypothesized that BPH/5 male offspring will demonstrate cardiovascular and metabolic phenotypes similar to BPH/5 females. As previously described, BPH/5 females born to ad libitum-fed dams are overweight with hyperphagia and increased subcutaneous, peri-renal, and peri-gonadal white adipose tissue (WAT) and cardiomegaly compared to age-matched adult female controls. In this study, BPH/5 adult male mice have similar body weights and food intake compared to age-matched control mice but have increased inflammatory subcutaneous and peri-renal WAT and signs of cardiovascular disease: left ventricular hypertrophy and hypertension. Therefore, adult male BPH/5 do not completely phenocopy the cardiometabolic profile of female BPH/5 mice. Future investigations are necessary to understand the differences observed in BPH/5 male and female mice as they age. In conclusion, the impact of fetal programming due to PE has a transgenerational effect on both male and female offspring in the BPH/5 mouse model. The maternal obesogenic environment may play a role in PE pregnancy outcomes, including offspring health as they age.

River water temperatures are increasing globally, particularly in urban systems. In winter, wastewater treatment plant (WWTP) effluent inputs are of particular concern because they increase water temperatures from near freezing to ~7–15 °C. Recent laboratory studies suggest that warm overwinter temperatures impact the reproductive timing of some fishes. To evaluate winter water temperature’s influence in the wild, we sampled Johnny Darter Etheostoma nigrum from three urban South Platte River tributaries in Colorado upstream and downstream of WWTP effluent discharge sites. Fish were collected weekly during the spring spawning season of 2021 and reproductive development was determined from histological analysis of the gonads. Winter water temperatures were approximately 5–10 °C greater ~300 m downstream of the WWTP effluent compared to upstream sites, and approximately 3 °C warmer at sampling sites ~5000 m downstream of the effluent discharge. Females collected downstream of WWTP effluent experienced accelerated reproductive development compared to upstream by 1–2 weeks. Water quality, including total estrogenicity, and spring water temperatures did not appear to explain varying reproductive development. It appears that small increases in winter water temperature influence the reproductive timing in E. nigrum. Further investigations into how shifts in reproductive timing influence other population dynamics are warranted.

Abstract The purpose of this consensus document was to develop feasible, evidence‐based occupational heat safety recommendations to protect the US workers that experience heat stress. Heat safety recommendations were created to protect worker health and to avoid productivity losses associated with occupational heat stress. Recommendations were tailored to be utilized by safety managers, industrial hygienists, and the employers who bear responsibility for implementing heat safety plans. An interdisciplinary roundtable comprised of 51 experts was assembled to create a narrative review summarizing current data and gaps in knowledge within eight heat safety topics: (a) heat hygiene, (b) hydration, (c) heat acclimatization, (d) environmental monitoring, (e) physiological monitoring, (f) body cooling, (g) textiles and personal protective gear, and (h) emergency action plan implementation. The consensus‐based recommendations for each topic were created using the Delphi method and evaluated based on scientific evidence, feasibility, and clarity. The current document presents 40 occupational heat safety recommendations across all eight topics. Establishing these recommendations will help organizations and employers create effective heat safety plans for their workplaces, address factors that limit the implementation of heat safety best‐practices and protect worker health and productivity.

The geochemical behavior of Pb in terrestrial and coastal water systems significantly influences Pb biogeochemical cycling and pollutant exchange at the land-sea continuum. An ideal case study of Pb environmental geochemistry is Galveston Bay, an anthropogenic estuary exposed to industrial runoff, wastewater and shipping vessel spills but also fed by natural rivers. Here, sediments from Galveston Bay were measured for Pb isotope ratios and abundances to constrain Pb sources and fluxes and understand Pb pollution history in the bay. Lead isotopes have been established as source tracers of environmental pollution and allow Pb sources to be reliably fingerprinted and identified. Sediments were leached to distinguish authigenic sediment coatings from lithogenic residual sediments, in addition to bulk sediment digestions. Total Pb concentrations ranged from 1.76 µg/g–29.19 µg/g in bulk digests, which are below federal toxicity thresholds and aligns well with prior measurements of Pb in Galveston Bay sediments in the 20th century. Lead concentrations are spatially constrained by flocculation in eastern bay areas where the Trinity River enters the bay and positively temporally correlated to freshwater discharge. Sediment 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb ratios range between 18.338–19.777±0.002, 15.557–15.755±0.002 and 37.913–43.340±0.005, respectively, and were used in an advanced Bayesian isotope mixing model to identify Pb sources in the Galveston Bay sediment fractions analyzed. Anthropogenic sources supply approximately 83.8%, 16.6% and 25.5% of Pb to the leachates, residues and bulk sediments, respectively. This study showcases the importance of estuaries in moderating terrestrial and marine Pb distribution and provides insight for future contaminant studies in Galveston Bay and other estuarine systems around the world.MAIN FINDINGS Pb isotope ratio and abundance measurements of Galveston Bay sediments demonstrate significant anthropogenic Pb inputs to the estuary despite low Pb levels.

A wide array of pathogens has the potential to injure the fetus and induce teratogenesis, the process by which mutations in fetal somatic cells lead to congenital malformations. Rubella virus was the first infectious disease to be linked to congenital malformations due to an infection in pregnancy, which can include congenital cataracts, microcephaly, hearing impairment and congenital heart disease. Currently, human cytomegalovirus (HCMV) is the leading infectious cause of congenital malformations globally, affecting 1 in every 200 infants. However, our knowledge of teratogenic viruses and pathogens is far from complete. New emerging infectious diseases may induce teratogenesis, similar to Zika virus (ZIKV) that caused a global pandemic in 2016–2017; thousands of neonates were born with congenital microcephaly due to ZIKV exposure in utero, which also included a spectrum of injuries to the brain, eyes and spinal cord. In addition to congenital anomalies, permanent injury to fetal and neonatal organs, preterm birth, stillbirth and spontaneous abortion are known consequences of a broader group of infectious diseases including group B streptococcus (GBS), Listeria monocytogenes, Influenza A virus (IAV), and Human Immunodeficiency Virus (HIV). Animal models are crucial for determining the mechanism of how these various infectious diseases induce teratogenesis or organ injury, as well as testing novel therapeutics for fetal or neonatal protection. Other mammalian models differ in many respects from human pregnancy including placentation, labor physiology, reproductive tract anatomy, timeline of fetal development and reproductive toxicology. In contrast, non-human primates (NHP) most closely resemble human pregnancy and exhibit key similarities that make them ideal for research to discover the mechanisms of injury and for testing vaccines and therapeutics to prevent teratogenesis, fetal and neonatal injury and adverse pregnancy outcomes (e.g., stillbirth or spontaneous abortion). In this review, we emphasize key contributions of the NHP model pre-clinical research for ZIKV, HCMV, HIV, IAV, L. monocytogenes, Ureaplasma species, and GBS. This work represents the foundation for development and testing of preventative and therapeutic strategies to inhibit infectious injury of human fetuses and neonates.

In the context of global warming, changes in phytoplankton-associated bacterial communities have the potential to change biogeochemical cycling and food webs in marine ecosystems. Skeletonema is a cosmopolitan diatom genus in coastal waters worldwide. Here, we grew a Skeletonema strain with its native bacterial assemblage at different temperatures and examined cell concentrations of Skeletonema sp. and free-living bacteria, dissolved organic carbon (DOC) concentrations of cultures, and the community structure of both free-living and attached bacteria at different culture stages. The results showed that elevated temperature increased the specific growth rates of both Skeletonema and free-living bacteria. Different growth stages had a more pronounced effect on community structure compared with temperatures and different physical states of bacteria. The effects of temperature on the structure of the free-living bacterial community were more pronounced compared with diatom-attached bacteria. Carbon metabolism genes and those for some specific amino acid pathways were found to be positively correlated with elevated temperature, which may have profound implications on the oceanic carbon cycle and the marine microbial loop. Network analysis revealed evidence of enhanced cooperation with an increase in positive interactions among different bacteria at elevated temperature. This may help the whole community to overcome the stress of elevated temperature. We speculate that different bacterial species may build more integrated networks with a modified functional profile of the whole community to cope with elevated temperature. This study contributes to an improved understanding of the response of diatom-associated bacterial communities to elevated temperature.

With the power to unite or divide a nation, patriotism is an integral component of the many attitudes, beliefs, and behaviors which collectively influence the nature and direction of society. In its extreme forms, patriotism can lead to systematic social disorganization, foster intolerance and fear, or give rise to fascist or neo-fascist movements. Given the diverse and potentially problematic roles patriotism can play, identifying determinants for patriotism represents an important line of inquiry. Although several studies have explored the origins of patriotism in society, prior research has yet to examine the influence of birth cohort effects on patriotic self-identification the United States. This study examines generational birth cohort effects on a subjective measure of American patriotism. Data for this research were collected from the Pew Research Center 2014 Political Survey. Results from our analysis suggest that younger cohorts are significantly less patriotic than preceding generations. Cohort effects on patriotism were significant with and without controls. To our knowledge, this is the first study to identify a systematic link between birth cohort and patriotism within the context of a multivariate examination. We also found evidence of a significant interaction between religiosity and birth cohort. Specifically, the positive effect of religiosity on patriotism is considerably more pronounced among Millennials than Baby Boomers. In addition to identifying a new source of variation in American patriotism, this study demonstrates the continued relevance and utility of birth cohort research for identifying and describing broad patterns of variation in society.

Abstract TRIM32 is a E3 ubiquitin -ligase containing RING, B-box, coiled-coil and six C-terminal NHL domains. Mutations involving NHL and coiled-coil domains result in a pure myopathy (LGMD2H/STM) while the only described mutation in the B-box domain is associated with a multisystemic disorder without myopathy (Bardet-Biedl syndrome type11), suggesting that these domains are involved in distinct processes. Knock-out (T32KO) and knock-in mice carrying the c.1465G > A (p.D489N) involving the NHL domain (T32KI) show alterations in muscle regrowth after atrophy and satellite cells senescence. Here, we present phenotypical description and functional characterization of mutations in the RING, coiled-coil and NHL domains of TRIM32 causing a muscle dystrophy. Reduced levels of TRIM32 protein was observed in all patient muscle studied, regardless of the type of mutation (missense, single amino acid deletion, and frameshift) or the mutated domain. The affected patients presented with variable phenotypes but predominantly proximal weakness. Two patients had symptoms of both muscular dystrophy and Bardet-Biedl syndrome. The muscle magnetic resonance imaging (MRI) pattern is highly variable among patients and families. Primary myoblast culture from these patients demonstrated common findings consistent with reduced proliferation and differentiation, diminished satellite cell pool, accelerated senescence of muscle, and signs of autophagy activation.

Abstract Background The deltopectoral approach is a well-described surgical approach to the proximal humerus and glenohumeral joint. One of the structures at risk during this approach is the axillary nerve. Typically, the axillary nerve arises off the posterior cord of the brachial plexus and courses lateral to the proximal humerus and inferior to the glenohumeral joint, exiting the axilla through the quadrangular space. We describe a case of an aberrant axillary nerve, coursing anteriorly across the glenohumeral joint within the deltopectoral groove encountered during a reverse total shoulder arthroplasty. Case presentation A 73-year-old female presented complaining of atraumatic progressive right shoulder pain of several months duration. Clinical and radiographic findings were consistent with advanced rotator cuff arthropathy. After failing appropriate non-operative treatment, the patient elected to undergo reverse total shoulder arthroplasty. During the deltopectoral approach to the glenohumeral joint, the axillary nerve was found to be coursing deep to the cephalic vein within the deltopectoral interval. The nerve was isolated and protected, and the glenohumeral joint was accessed via a small window in the anterior deltoid muscle. The remainder of the procedure was performed without complication. The patient was found to be healing well and with normal axillary nerve function at 4-month follow-up. Conclusions Neurologic lesions are well-documented complications of reverse total shoulder arthroplasty. The integrity of the axillary nerve is of particular importance to reverse total shoulder arthroplasty as it innervates the deltoid and post-operative function of the extremity is dependent upon a functioning deltoid muscle. Extreme care must be taken to avoid insult to the axillary nerve and any aberrant paths it may course around the glenohumeral joint.

Objective: Life-threatening hypoglycemia is a major limiting factor in the management of diabetes. While it is known that counterregulatory responses to hypoglycemia are impaired in diabetes, molecular mechanisms underlying the reduced responses remain unclear. Given the established roles of the hypothalamic proopiomelanocortin (POMC)/melanocortin 4 receptor (MC4R) circuit in regulating sympathetic nervous system (SNS) activity and the SNS in stimulating counterregulatory responses to hypoglycemia, we hypothesized that hypothalamic POMC as well as MC4R, a receptor for POMC derived melanocyte stimulating hormones, is required for normal hypoglycemia counterregulation. Methods: To test the hypothesis, we induced hypoglycemia or glucopenia in separate cohorts of mice deficient in either POMC or MC4R in the arcuate nucleus (ARC) or the paraventricular nucleus of the hypothalamus (PVH), respectively, and measured their circulating counterregulatory hormones. In addition, we performed a hyperinsulinemic-hypoglycemic clamp study to further validate the function of MC4R in hypoglycemia counterregulation. We also measured Pomc and Mc4r mRNA levels in the ARC and PVH, respectively, in the streptozotocin-induced type 1 diabetes mouse model and non-obese diabetic (NOD) mice to delineate molecular mechanisms by which diabetes deteriorates the defense systems against hypoglycemia. Finally, we treated diabetic mice with the MC4R agonist MTII, administered stereotaxically into the PVH, to determine its potential for restoring the counterregulatory response to hypoglycemia in diabetes. Results: Stimulation of epinephrine and glucagon release in response to hypoglycemia or glucopenia was diminished in both POMC- and MC4R-deficient mice, relative to their littermate controls. Similarly, the counterregulatory response was impaired in association with decreased hypothalamic Pomc and Mc4r expression in the diabetic mice, a phenotype that was not reversed by insulin treatment which normalized glycemia. In contrast, infusion of an MC4R agonist in the PVH restored the counterregulatory response in diabetic mice. Conclusion: In conclusion, hypothalamic Pomc as well as Mc4r, both of which are reduced in type 1 diabetic mice, are required for normal counterregulatory responses to hypoglycemia. Therefore, enhancing MC4R function may improve hypoglycemia counterregulation in diabetes. Keywords: Hypothalamus, Pro-opiomelanocortin (POMC), Melanocortin 4 receptor (MC4R), Hypoglycemia counterregulation, Diabetes

The present study assesses the global distribution of marginal accessory tubercles of the maxillary premolars. This trait, despite constituting one of the variables standardized by Turner and colleagues (1991), has received little attention in morphological studies. Frequencies were calculated from data sheets collected by Christy G. Turner II for mesial, distal, and mesial + distal grades. Different geographic patterns were identified for both types of expression on the upper premolars. The patterned geographic distribution of these traits indicates their utility in biodistance investigations. In addition, the distinction between mesial and distal accessory tubercles specified by Scott and Irish (2017) is recommended, as these two traits exhibit different geographic patterns.

Key concepts and theories that are taught in order to develop cultural competency skills are often introduced to medical students throughout behavioral and social science (BSS) learning content. BSS represents a core component of medical education in the United Kingdom. In this paper, we examine, through (auto)ethnographic data and reflections, the experiences of BSS in medical education. The empirical data and insights have been collected in two ways: (1) through long-term ethnographic fieldwork among medical students and (2) via autoethnographic reflexive practice undertaken by the co-authors who studied, worked, examined, and collaborated with colleagues at different UK medical schools. Our findings indicate that despite BSS constituting a mandatory, essential component of the medical curriculum, medical students did not always perceive BSS as useful for their future practice as doctors, nor did they find it to be clinically relevant, in comparison to the biomedical learning content. We suggest that it is paramount for all stakeholders to commit to cultivating and developing cultural competency skills in medical education, through robustly embedding BSS learning content across the undergraduate medical curriculum. We conclude with recommendations for a wide range of educational practices that would ensure a full integration of BSS in the medical curriculum.

The effect of an inoculant, [triethylamine (TEA)] on the corrosion behavior of multilayered mild steel/Al-Cr plates in guava leaf extract was investigated in 0.5M HCl solution using gravimetric based mass-loss test and potentiodynamic polarization techniques. The mild steel plates were sectioned into coupons of 4 and then pickled, after which they were coated at 750 with an Al-Cr alloy. The gravimetric-based mass loss test was carried out at room temperature for different concentrations and time intervals of 2.0, 4.0, 6.0, 8.0%v/v and 24, 48, 72, 96 hours respectively. The result showed that triethylamine (TEA) decreased the corrosion rate at the various concentrations indicating protection efficiency up to 59.02% in the gravimetric-based-mass-loss technique. Equally the potentiodynamic polarization technique indicates higher corrosion resistance of 98.49%. The two methods used for the evaluation of the degradation of multilayered mild steel/Al-Cr plates in 0.5M HCl/guava leaf extract medium were in agreement.

Adrenergic stimulation of brown adipocytes alters mitochondrial dynamics, including the mitochondrial fusion protein optic atrophy 1 (OPA1). However, direct mechanisms linking OPA1 to brown adipose tissue (BAT) physiology are incompletely understood. We utilized a mouse model of selective OPA1 deletion in BAT (OPA1 BAT KO) to investigate the role of OPA1 in thermogenesis. OPA1 is required for cold-induced activation of thermogenic genes in BAT. Unexpectedly, OPA1 deficiency induced fibroblast growth factor 21 (FGF21) as a BATokine in an activating transcription factor 4 (ATF4)-dependent manner. BAT-derived FGF21 mediates an adaptive response by inducing browning of white adipose tissue, increasing resting metabolic rates, and improving thermoregulation. However, mechanisms independent of FGF21, but dependent on ATF4 induction, promote resistance to diet-induced obesity in OPA1 BAT KO mice. These findings uncover a homeostatic mechanism of BAT-mediated metabolic protection governed in part by an ATF4-FGF21 axis, which is activated independently of BAT thermogenic function.

States in the Northeast United States have the ambitious goal of producing more than 22 GW of offshore wind energy in the coming decades. The infrastructure associated with offshore wind energy development is expected to modify marine habitats and potentially alter the ecosystem services. Species distribution models were constructed for a group of fish and macroinvertebrate taxa resident in the Northeast US Continental Shelf marine ecosystem. These models were analyzed to provide baseline context for impact assessment of lease areas in the Middle Atlantic Bight designated for renewable wind energy installations. Using random forest machine learning, models based on occurrence and biomass were constructed for 93 species providing seasonal depictions of their habitat distributions. We developed a scoring index to characterize lease area habitat use for each species. Subsequently, groups of species were identified that reflect varying levels of lease area habitat use ranging across high, moderate, low, and no reliance on the lease area habitats. Among the species with high to moderate reliance were black sea bass (Centropristis striata), summer flounder (Paralichthys dentatus), and Atlantic menhaden (Brevoortia tyrannus), which are important fisheries species in the region. Potential for impact was characterized by the number of species with habitat dependencies associated with lease areas and these varied with a number of continuous gradients. Habitats that support high biomass were distributed more to the northeast, while high occupancy habitats appeared to be further from the coast. There was no obvious effect of the size of the lease area on the importance of associated habitats. Model results indicated that physical drivers and lower trophic level indicators might strongly control the habitat distribution of ecologically and commercially important species in the wind lease areas. Therefore, physical and biological oceanography on the continental shelf proximate to wind energy infrastructure development should be monitored for changes in water column structure and the productivity of phytoplankton and zooplankton and the effects of these changes on the trophic system.

Climatic changes and anthropogenic pressures affect biodiversity and community composition. These biodiversity shifts are recognized in marine ecosystems, but the underlying processes are barely understood so far. Importantly, human well-being highly relies on oceanic services, which are affected by anthropogenic pressures. Here, we review how interdisciplinary research approaches, with the incorporation of eDNA (environmental DNA) analyses, can help increase the understanding of complex ecosystem processes and dynamics, and how they affect ecosystem services. We discuss marine conservation issues in the light of life cycle aspects and conclude that eDNA can improve our ecological knowledge in some instances, for example, in tracking migration patterns. We also illustrate and discuss the application of eDNA analysis within the context of population genetics, epigenetics, geochemistry and oceanography. Embedded into an interdisciplinary context, eDNA can be exploited by a huge variety of methodological techniques, and can resolve spatio-temporal patterns of diversity, species, or even populations within ecological, evolutionary, and management frameworks.

Purpose: To establish a quantitative relationship between the Blackburne–Peel index and posterior tibial slope in both skeletally mature and skeletally immature individuals and to evaluate the rate at which variation in tibial slope influences changes in patellar height categorization as normal, patella alta, and patella baja. Methods: A consecutive series of lateral knee radiographs were retrospectively reviewed. Radiographs were excluded for rotation, inadequate visible proximal tibia length, and obstructive hardware/pathology. Modified tibial slopes of 0°, 5°, 10°, and 15° were projected anteriorly from the medial tibial plateau as described by Blackburne–Peel. The Blackburne–Peel index was determined at each modified tibial slope interval. Caton–Deschamps and Insall–Salvati indices also were measured for comparison. The rate of Blackburne–Peel index change with increase in posterior tibial slope was quantitatively analyzed. Results: Fifty skeletally mature and 50 skeletally immature radiographs were included. In the skeletally mature, Blackburne–Peel indices decreased on average by 0.037, 0.044, and 0.049 as posterior tibial slope increased from 0-5°, 5-10°, and 10-15°, respectively. In the skeletally immature, Blackburne–Peel indices decreased on average by 0.045, 0.053, and 0.059 as posterior tibial slope increased from 0-5°, 5-10°, and 10-15°, respectively. Overall, 29 individuals with 0° of tibial slope were categorized as patella alta by the Blackburne–Peel index, and only 16 (55%) remained categorized as patella alta after increasing their posterior tibial slope to 15°. Conclusions: This study quantitatively demonstrates the relationship between posterior tibial slope and the Blackburne–Peel index. As expected, as posterior tibial slope increases, the Blackburne–Peel index decreases. While the change in the Blackburne–Peel index per 5° change in tibial slope appears to be small, nearly half (45%) of individuals categorized as patella alta with 0° of tibial slope were categorized as normal when their posterior tibial slope was systematically increased from 0° to 15°. When evaluating patellar height, it is important to understand how tibial slope affects the Blackburne-Peel Index measurement. Clinical Relevance: As posterior tibial slope increases, the numerator of the Blackburne-Peel ratio decreases, and vice versa. This relationship can lead to incorrect assessment of patellar height. Objectively placing individuals into patella alta and baja categories may influence patient care and decision making.

Abstract Systematic conservation planning identifies priority areas to cost‐effectively meet conservation targets. Yet, these tools rarely guide wholesale declaration of reserve systems in a single time step due to financial and implementation constraints. Rather, incremental scheduling of actions to progressively build reserve networks is required. To ensure this incremental action is guided by the original plan, and thus builds a reserve network that meets all conservation targets, strategic scheduling, and iterative planning is needed. We explore the issue of scheduling conservation actions using the national scale conservation plan for Papua New Guinea (PNG), commissioned by the PNG Conservation and Environment Protection Authority that identifies a comprehensive set of priority areas that meet conservation targets in both the land and sea. As part of the planning process a subset of areas were identified in collaboration as priorities for immediate action—termed areas of interest (AOIs). However, the extent to which targets are met if action stopped after implementing the AOIs is unknown. We test three possible implementation scenarios based on these priority areas to measure target achievement and shortfalls. We then consider how iterative planning would interact with scheduling actions to identify new long‐term priorities that will meet missing targets. Our results show that while a large number of conservation targets are met within the AOIs there are shortfalls for protecting threatened and range restricted endemic species. Meeting targets for these would require an updated set of national priorities and an additional 13% of land area compared with if all areas identified in the original assessment were protected in a single time step. This provides important insights into the benefits of strategic scheduling of implementation, as well as the need for capacity to monitor action and update priorities as implementation proceeds.

Abstract Perpetual conservation easements are a popular method in some countries for addressing conservation goals. Landowner participation plays a key role in the development of these agreements. Despite the importance of involvement by landowners, no recent efforts have been made to synthesize information about the motivations for participation in perpetual easement programs. As a result, the literature lacks a framework to guide future case studies that would facilitate comparisons and generalizations. To this end, we reviewed 43 studies that investigated individual motivations to participate in perpetual conservation easements, and categorized motivations using Ostrom's social–ecological framework. We identified a strong tendency among studies to focus only on local‐scale processes involving landowners, with little consideration of broader‐scale influences. We also highlight several cross‐study trends and gaps in the literature where future research would prove valuable.

Introduction Direct-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE.Methods Several design features accommodate a direct-to-family approach. Participants meeting eligibility criteria from across the USA were identified a priori through a disease registry, and all outcome data are collected remotely. The primary outcome (medication adherence) is evaluated using electronic medication event-monitoring, plasma drug levels, patient questionnaires and pill counts. Secondary and exploratory endpoints include (1) lupus disease activity measured by a remote SLE Disease Activity Index examination and the Systemic Lupus Activity Questionnaire; and (2) hydroxychloroquine pharmacokinetics and pharmacodynamics. Recruitment of the initial target of 20 participants was achieved within 10 days. Due to initial recruitment success, enrolment was increased to 26 participants. Additional participants who were interested were placed on a waiting list in case of dropouts during the study.Discussion and dissemination Direct-to-family trials offer several advantages but present unique challenges. Lessons learnt from the protocol development, design, and implementation of this trial will inform future direct-to-family trials for children and adults with rheumatic diseases. Additionally, the data collected remotely in this trial will provide critical information regarding the accuracy of teleresearch in lupus, the impact of adherence to hydroxychloroquine on disease activity and a pharmacokinetic analysis to inform paediatric-specific dosing of hydroxychloroquine.Trial registration number ClinicalTrials.gov Registry (NCT04358302).

Group B streptococci (GBS) are bacteria that commonly reside in the female lower genital tract as asymptomatic members of the microbiota. However, during pregnancy, GBS can infect tissues at the maternal-fetal interface, leading to preterm birth, stillbirth, or fetal injury.

A 68-year-old woman with a medical history significant for psoriatic arthritis was found to have an enlarged, painful lump on her left hip 15 months after intramedullary rod placement for a left subtrochanteric femur fracture sustained in a fall. Histopathological findings showed rice body formation (RBF) with concurrent H. parainfluenza. RBF is a relatively rare arthropathy of a subset of chronic inflammatory disease such as rheumatoid arthritis or tuberculous arthropathy. RBF associated with psoriatic arthritis or orthopedic hardware placement has been reported in a handful of cases in the literature but there has not been any definitive evidence for RBF as a result of Haemophilus parainfluenza infections and is a rather unusual characteristic of this case.

Curtailment of turbine operations during low wind conditions has become an operational minimization tactic to reduce bat mortality at terrestrial wind energy facilities. Site-specific studies have demonstrated that bat activity is higher during lower wind speeds and that operational curtailment can effectively reduce fatalities. However, the exact nature of the relationship between curtailment cut-in speed and bat fatality reduction remains unclear. To evaluate the efficacy of differing curtailment regimes in reducing bat fatalities, we examined data from turbine curtailment experiments in the United States and Canada in a meta-analysis framework. We used multiple statistical models to explore possible linear and non-linear relationships between turbine cut-in speed and bat fatality. Because the overall sample size for this meta-analysis was small (n = 36 control-treatment studies from 17 wind farms), we conducted a power analysis to assess the number of control-treatment curtailment studies needed to understand the relationship between fatality reduction and change in cut-in speed. We also identified the characteristics of individual curtailment field studies that may influence their power to detect fatality reductions, and in turn, contribute to future meta-analyses. We found strong evidence that implementing turbine curtailment reduces fatality rates of bats at wind farms; the estimated fatality ratio across all studies was 0.37 (p < 0.001), or a 63% decrease in fatalities. However, the nature of the relationship between the magnitude of treatment and reduction in fatalities was more difficult to assess. Models that represented the response ratio as a continuous variable (e.g., with a linear relationship between the change in cut-in speed and fatalities) and a categorical variable (to allow for possible non-linearity in this relationship) both had substantial support when compared using AICc. The linear model represented the best fit, likely due to model simplicity, but the non-linear model was the most likely without accounting for parsimony and suggested fatality rates decreased when the difference in curtailment cut-in speeds was 2m/s or larger. The power analyses showed that the power to detect effects in the meta-analysis was low if fatality reductions were less than 50%, which suggests that smaller increases in cut-in speed (i.e., between different treatment categories) may not be easily detectable with the current dataset. While curtailment is an effective operational mitigation measure overall, additional well-designed curtailment studies are needed to determine precisely whether higher cut-in speeds can further reduce bat fatalities.

BackgroundAdolescence is the last opportunity to reverse any growth faltering accumulated from fetal life through childhood and it is considered a crucial period to optimize human development. In Bangladesh, a growing double burden of underweight and obesity in adolescents is recognized, yet limited data exists on how, when, and where to intervene. This study assesses the dynamics of growth among adolescent girls in Bangladesh, providing insight about critical junctures where faltering occurs and where immediate interventions are warranted.MethodsWe pooled data from Bangladesh's Food Security and Nutrition Surveillance Project collected between 2011 and 2014 to document the age dynamics of weight and linear growth. 20,572 adolescent girls were measured for height and 19,345 for weight. We constructed growth curves for height, weight, stunting, and underweight. We also stratified growth dynamics by wealth quintile to assess socioeconomic inequities in adolescent trajectories.ResultsHeight-for-age z-score (HAZ) in Bangladeshi girls deteriorates throughout adolescence and especially during the early years. Mean HAZ decreases by 0.20 standard deviations (sd) per year in early adolescence (10-14 years) vs 0.06 sd/year during late adolescence (15-19 years), while stunting increases by 16 percentage points (pp) vs 6.7 pp, respectively. Conversely, BMI-for-age z-score (BAZ) increases by 0.13 sd/year in early adolescence vs 0.02 sd/year in late adolescence, and underweight decreases by 12.8 pp vs 3.2 pp. Adolescent girls in all socioeconomic groups show a similar pattern of HAZ and BAZ dynamics, but the curve for the richest quintile stays above that of the poorest across all ages.ConclusionsTrends and levels of stunting and underweight among adolescent girls in Bangladesh are worrisome, suggesting substantial linear growth faltering in early adolescence, with improving weight-for-age occurring only as linear growth slows and stops. Given the rising burden of non-communicable diseases (NCDs) in Bangladesh and emerging evidence of the link between stunting and later chronic diseases, greater attention to adolescent growth and development is needed. Our findings suggest that, to address stunting, interventions in early adolescence would have the greatest benefits. School-based interventions could be a way to target this population.

The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)–1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC–HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growth in vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC–HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies.

UDP-glucose:glycoprotein glucosyltransferase (UGGT) 1 and 2 are central hubs in the chaperone network of the endoplasmic reticulum (ER), acting as gatekeepers to the early secretory pathway, yet little is known about their cellular clients. These two quality control sensors control lectin chaperone binding and glycoprotein egress from the ER. A quantitative glycoproteomics strategy was deployed to identify cellular substrates of the UGGTs at endogenous levels in CRISPR-edited HEK293 cells. The 71 UGGT substrates identified were mainly large multidomain and heavily glycosylated proteins when compared to the general N-glycoproteome. UGGT1 was the dominant glucosyltransferase with a preference toward large plasma membrane proteins whereas UGGT2 favored the modification of smaller, soluble lysosomal proteins. This study sheds light on differential specificities and roles of UGGT1 and UGGT2 and provides insight into the cellular reliance on the carbohydrate-dependent chaperone system to facilitate proper folding and maturation of the cellular N-glycoproteome.