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Purpose: Rural hospitals are closing at unprecedented rates, with hundreds more at risk of closure in the coming 2 years. Multiple federal policies are being developed and implemented without a salient understanding of the emerging literature evaluating rural hospital closures and its impacts. We conducted a scoping review to understand the impacts of rural hospital closure to inform ongoing policy debates and research. Methods: A comprehensive search strategy was devised by library faculty to collate publications using the PRISMA extension for scoping reviews. Two coauthors then independently performed title and abstract screening, full text review, and study extraction. Findings: We identified 5054 unique citations and assessed 236 full texts for possible inclusion in our narrative synthesis of the literature on the impacts of rural hospital closure. Twenty total original studies were included in our narrative synthesis. Key domains of adverse impacts related to rural hospital closure included emergency medical service transport, local economies, availability and utilization of emergency care and hospital services, availability of outpatient services, changes in quality of care, and workforce and community members. However, significant heterogeneity existed within these findings. Conclusions: Given the significant heterogeneity within our findings across multiple domains of impact, we advocate for a tailored approach to mitigating the impacts of rural hospital closures for policymakers. We also discuss crucial knowledge gaps in the evidence base—especially with respect to quality measures beyond mortality. The synthesis of these findings will permit policymakers and researchers to understand, and mitigate, the harms of rural hospital closure. [ABSTRACT FROM AUTHOR]

The current dosing strategy of immune globulin products for the treatment of primary immunodeficiency diseases (PIDDs) in the USA is based on total body weight (BW). The aim of our study was to assess the relationship between dose and trough level, and to determine whether an alternative dosing strategy should be considered for patients who are overweight or obese. We analyzed data in a total of 533 patients from 11 studies. We modeled the relationship between trough level and dose per week using a linear mixed model. We used an over‐dispersed Poisson model to model the relationship between infection and trough level. In these analyses, we then combined the study‐specific treatment effects using a random‐effect or fixed‐effect model. The mean administered dose per week was 9.77, 14.00, or 18.17 g in patients who were normal weight, overweight, or obese, respectively. Compared with a patient of normal weight, a 1 g increase in dose per week in a patient who was overweight was associated with a smaller increase in the trough level, 0.08 g/L less (95%CI –0.14 to –0.03 g/L), and a 1 g increase in dose per week in a patient who was obese was associated with a much smaller increase in trough level, 0.01 g/L less (95% CI –0.07 to 0.06 g/L). Last, for a 1 unit (g/L) increase in trough level, the expected number of infections remained the same, with a multiplicative factor of 1.01 (95%CI 0.98‐1.04). Overall, we found no compelling evidence to justify a reconsideration of the current dosing strategy based on total BW for patients with PIDDs who are overweight or obese. [ABSTRACT FROM AUTHOR]

Ferroelectrics, due to their polar nature and reversible switching, can be used to dynamically control surface chemistry for catalysis, chemical switching, and other applications such as water splitting. However, this is a complex phenomenon where ferroelectric domain orientation and switching are intimately linked to surface charges. In this work, the temperature-induced domain behavior of ferroelectric-ferroelastic domains in free-standing BaTiO3 films under different gas environments, including vacuum and oxygen-rich, is studied by in situ scanning transmission electron microscopy (STEM). An automated pathway to statistically disentangle and detect domain structure transformations using deep autoencoders, providing a pathway towards real-time analysis is also established. These results show a clear difference in the temperature at which phase transition occurs and the domain behavior between various environments, with a peculiar domain reconfiguration at low temperatures, from a-c to a-a at ≈60 °C. The vacuum environment exhibits a rich domain structure, while under the oxidizing environment, the domain structure is largely suppressed. The direct visualization provided by in situ gas and heating STEM allows to investigate the influence of external variables such as gas, pressure, and temperature, on oxide surfaces in a dynamic manner, providing invaluable insights into the intricate surface-screening mechanisms in ferroelectrics. [ABSTRACT FROM AUTHOR]

Purpose: Americans who reside in health professional shortage areas currently have less than half of the needed physician workforce. While the shortage designation has been associated with poor outcomes for chronic medical conditions, far less is known about outcomes after high‐risk surgical procedures. Methods: We performed a retrospective review of Medicare beneficiaries living in health professional shortage areas and nonshortage areas who underwent abdominal aortic aneurysm repair, coronary artery bypass graft, esophagectomy, liver resection, pancreatectomy, or rectal resection between 2014 and 2018. Risk‐adjusted multivariable logistic regression was used to determine whether rates of postoperative complications and 30‐day mortality differed between patient cohorts. Beneficiary and hospital ZIP codes were used to quantify travel time to obtain care. Findings: Compared with patients living in nonshortage areas, patients living in health professional shortage areas traveled longer (median 60.0 vs 28.0 minutes, P<.001). There were no differences in risk‐adjusted rates of complications (28.5% vs 28.6%, OR = 1.00, 95% CI 1.00‐1.00, P =.59) and small differences in rates of 30‐day mortality (4.2% vs 4.4%, OR = 0.95, 95% CI 0.95‐0.95, P<.001) between beneficiaries living in shortage areas versus those not in shortage areas, respectively. Conclusions: Patients living in health professional shortage area undergoing high‐risk surgery traveled more than 2 times longer for their care to obtain similar outcomes. While reassuring for clinical outcomes, additional efforts may be needed to mitigate the travel burden experienced by shortage area patients. [ABSTRACT FROM AUTHOR]

Protein phosphorylation is a fundamental element of cell signaling. First discovered as a biochemical switch in glycogen metabolism, we now know that this posttranslational modification permeates all aspects of cellular behavior. In humans, over 540 protein kinases attach phosphate to acceptor amino acids, whereas around 160 phosphoprotein phosphatases remove phosphate to terminate signaling. Aberrant phosphorylation underlies disease, and kinase inhibitor drugs are increasingly used clinically as targeted therapies. Specificity in protein phosphorylation is achieved in part because kinases and phosphatases are spatially organized inside cells. A prototypic example is compartmentalization of the cyclic adenosine 3′,5′‐monophosphate (cAMP)‐dependent protein kinase A through association with A‐kinase anchoring proteins. This configuration creates autonomous signaling islands where the anchored kinase is constrained in proximity to activators, effectors, and selected substates. This article primarily focuses on A kinase anchoring protein (AKAP) signaling in the heart with an emphasis on anchoring proteins that spatiotemporally coordinate excitation‐contraction coupling and hypertrophic responses. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the safety and efficacy of Chitogel, with and without Deferiprone (Def) and Gallium Protoporphyrin (GaPP), as a promoter of wound healing to improve surgical outcomes after endoscopic sinus susgery. Design: A double‐blinded, randomised control human clinical trial was conducted in patients undergoing ESS as a treatment for chronic rhinosinusitis. Participants underwent functional ESS or FESS with drill out as required and were randomised to receive test product Chitogel, Chitogel in combination with Def or Def‐GaPP versus no packing (control). Setting: Ostial stenosis and persistent inflammation are the main reasons for revision endoscopic sinus surgery (ESS). Post‐operative (PO) dressings can improve PO wound healing and patient outcomes after ESS. Participants: Eighty two patients were included in this study with 79 patients completing the study with 40 undergoing full house FESS and 39 FESS plus frontal drillout. Main Outcome Measures: Patients were followed up at 2, 6 and 12 weeks PO, and outcome scores such as SNOT‐22, VAS and LKS, pre and post‐surgery (12 weeks) were compared. Results: Seventy nine patients completed the study, there was a significant reduction in SNOT‐22 score and improvement of VAS at 12 weeks in patients treated with Chitogel compared to control (p <.05). In those patients, the mean ostium area for the Chitogel and the Chitogel + Def + GaPP groups was higher across all three sinuses compared to the no‐treatment control group, without statistical significance. Sphenoid sinus ostium was significantly more patent in patients treated with Chitogel compared to the control at the 12‐week time point (p <.05). Conclusion: Chitogel as a PO dressing after ESS results in the best patient‐reported symptom scores and objective measurements. The combination of Def and GaPP to Chitogel though proving safe, had no effect on the ostium patency or mucosal healing. [ABSTRACT FROM AUTHOR]

Many plants exchanged in the global redistribution of species in the last 200 years, particularly between South Africa and Australia, have become threatening invasive species in their introduced range. Refining our understanding of the genetic diversity and population structure of native and alien populations, introduction pathways, propagule pressure, naturalization, and initial spread, can transform the effectiveness of management and prevention of further introductions. We used 20,221 single nucleotide polymorphisms to reconstruct the invasion of a coastal shrub, Chrysanthemoides monilifera ssp. rotundata (bitou bush) from South Africa, into eastern Australia (EAU), and Western Australia (WAU). We determined genetic diversity and population structure across the native and introduced ranges and compared hypothesized invasion scenarios using Bayesian modeling. We detected considerable genetic structure in the native range, as well as differentiation between populations in the native and introduced range. Phylogenetic analysis showed the introduced samples to be most closely related to the southern‐most native populations, although Bayesian analysis inferred introduction from a ghost population. We detected strong genetic bottlenecks during the founding of both the EAU and WAU populations. It is likely that the WAU population was introduced from EAU, possibly involving an unsampled ghost population. The number of private alleles and polymorphic SNPs successively decreased from South Africa to EAU to WAU, although heterozygosity remained high. That bitou bush remains an invasion threat in EAU, despite reduced genetic diversity, provides a cautionary biosecurity message regarding the risk of introduction of potentially invasive species via shipping routes. [ABSTRACT FROM AUTHOR]

Background: Delays in diagnosis of peripartum cardiomyopathy (PPCM) are common and are associated with worse outcomes; however, few studies have addressed methods for improving early detection. Hypothesis: We hypothesized that easily accessible data (heart rate [HR] and electrocardiograms [ECGs]) could identify women with more severe PPCM and at increased risk of adverse outcomes. Methods: Clinical data, including HR and ECG, from patients diagnosed with PPCM between January 1998 and July 2016 at our institution were collected and analyzed. Linear and logistic regression were used to analyze the relationship between HR at diagnosis and the left ventricular ejection fraction (LVEF) at diagnosis. Outcomes included overall mortality, recovery status, and major adverse cardiac events. Results: Among 82 patients meeting inclusion criteria, the overall mean LVEF at diagnosis was 26 ± 11.1%. Sinus tachycardia (HR > 100) was present in a total of 50 patients (60.9%) at the time of diagnosis. In linear regression, HR significantly predicted lower LVEF (F = 30.00, p <.0001). With age‐adjusted logistic regression, elevated HR at diagnosis was associated with a fivefold higher risk of overall mortality when initial HR was >110 beats per minute (adjusted odds ratio 5.35, confidence interval 1.23–23.28), p =.025). Conclusion: In this study, sinus tachycardia in women with PPCM was associated with lower LVEF at the time of diagnosis. Tachycardia in the peripartum period should raise concern for cardiomyopathy and may be an early indicator of adverse prognosis. [ABSTRACT FROM AUTHOR]

SUMMARY: Clinical trials are primarily conducted to understand the average effects treatments have on patients. However, patients are heterogeneous in the severity of the condition and in ways that affect what treatment effect they can expect. It is therefore important to understand and characterize how treatment effects vary. The design and analysis of clinical studies play critical roles in evaluating and characterizing heterogeneous treatment effects. This panel discussed considerations in design and analysis under the recognition that there are heterogeneous treatment effects across subgroups of patients. Panel members discussed many questions including: What is a good estimate of the treatment effect in me, a 65‐year‐old, bald, Caucasian‐American, male patient? What magnitude of heterogeneity of treatment effects (HTE) is sufficiently large to merit attention? What role can prior evidence about HTE play in confirmatory trial design and analysis? Is there anything described in the 21st Century Cures Act that would benefit from greater attention to HTE? An example of a Bayesian approach addressing multiplicity when testing for treatment effects in subgroups will be provided. We can do more or better at understanding heterogeneous treatment effects and providing the best information on heterogeneous treatment effects. [ABSTRACT FROM AUTHOR]

Background: WHO recommends training lay first responders (LFRs) as the first step toward formal emergency medical services development, yet no tool exists to evaluate LFR programs. Methods: We developed Prehospital Emergency Trauma Care Assessment Tool (PETCAT), a seven-question survey administered to first-line hospital-based healthcare providers, to independently assess LFR prehospital intervention frequency and quality. PETCAT surveys were administered one month pre-LFR program launch (June 2019) in Makeni, Sierra Leone and again 14 months post-launch (August 2020). Using a difference-in-differences approach, PETCAT was also administered in a control city (Kenema) with no LFR training intervention during the study period at the same intervals to control for secular trends. PETCAT measured change in both the experimental and control locations. Cronbach's alpha, point bi-serial correlation, and inter-rater reliability using Cohen's Kappa assessed PETCAT reliability. Results: PETCAT administration to 90 first-line, hospital-based healthcare providers found baseline prehospital intervention were rare in Makeni and Kenema prior to LFR program launch (1.2/10 vs. 1.8/10). Fourteen months post-LFR program implementation, PETCAT demonstrated prehospital interventions increased in Makeni with LFRs (5.2/10, p < 0.0001) and not in Kenema (1.2/10) by an adjusted difference of + 4.6 points/10 (p < 0.0001) ("never/rarely" to "half the time"), indicating negligible change due to secular trends. PETCAT demonstrated high reliability (Cronbach's α = 0.93, Cohen's K = 0.62). Conclusions: PETCAT measures changes in rates of prehospital care delivery by LFRs in a resource-limited African setting and may serve as a robust tool for independent EMS quality assessment. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to develop a simple and practical guide for discussing and managing obesity in primary care settings.Methods: This study convened representatives from 12 primary care and obesity specialty organizations for a series of roundtable meetings to discuss the key components of obesity treatment in primary care. Attendees identified the need for a guide for primary care providers that outlined the key steps for discussing obesity with patients and managing their care while recognizing the significant time constraints on such provider/patient encounters.Results: Prevailing themes from the roundtable sessions suggested that the key components of addressing obesity in primary care settings are obtaining patient permission, addressing weight bias, providing a diagnosis, and emphasizing shared decision-making. A modified "6A" framework with the steps "Ask," "Assess," "Advise," "Agree," "Assist," and "Arrange" was deemed appropriate to organize the process of weight management in primary care. An algorithm was developed to provide a script for the patient/provider encounter.Conclusions: The expert panel developed a short, accessible, practical, and informative guide for obesity management by primary care clinicians. Efforts are under way to disseminate the guide to primary care providers through the 11 participating organizations that have endorsed it. [ABSTRACT FROM AUTHOR]

The Cape York Welfare Reform (CYWR) initiative aims to reduce 'passive dependence' on welfare and restore 'positive social norms' to revitalise cultural and social networks and support economic engagement in Indigenous communities in the Cape York Region of Australia. Critics of the initiative and, in particular, its income management (IM) policies have associated it with a broader neoliberal reform agenda that delineates social 'problems' from their historical and structural context. This paper discusses key qualitative findings from a strategic review of CYWR, paying particular attention to the ways in which Cape York IM (CYIM) straddles both Indigenous and settler social norms, while perpetuating neoliberal conceptualisations of welfare 'dependency'. We situate these findings within the existing literature on Australia's other IM models and also consider them in relation to subsequent government responses to the review and associated policies. We argue that CYIM represents a unique initiative, the subtle nuances of which have been largely ignored or misunderstood by critics. Further, we conclude that any extension or revision of this initiative should be considered with respect to deep and wide‐ranging consultation of the Indigenous communities subject to CYWR. However, such consultation has not been the standard practice in Australian contexts. The paper presents the qualitative findings of a Federal Government review of Cape York Income Management (CYIM). We argue that although CYIM shares a common ideological foundation with Australia's other IM policies, it is also distinct from these alternative forms of IM, particularly in terms of its evolution, high‐level of targeting, and delivery mechanism. [ABSTRACT FROM AUTHOR]

In the article, the authors leverage a public opinion survey to assess the differences between emergency department (ED) and urgent care (UC) users for low-acuity health needs. Also cited are how UC centers or retail clinics are better alternatives for low-acuity complaints than EDs, as well as the independent variables on the use of ED or UC like household income, health insurance, and chronic illnesses.

In response to the coronavirus pandemic in the fall of 2020, we created hybrid–virtual or fully virtual field trips to replace in‐person field trips in two courses. For an introductory soil science course with 178 students enrolled, we used a narrative format supported by 360° ground‐level and drone photos, newspaper articles, videos, websites, and landscape diagrams. After reading the narratives, the students took a quiz and then visited the sites (public parks near campus) on their own. For the advanced pedology course with seven students enrolled, a virtual trip replaced an all‐day field trip that travels a 100‐mile route from West Lafayette to Michigan City, IN. The virtual trip was created within the Soil Explorer platform and consists of >50 points of interest (POIs) overlayed on detailed soil maps. Each POI includes relevant information about the soils, agriculture, geology, geomorphology, or history at that point. At two POIs students examined four or five soils along two transects by filling in worksheets using the official series descriptions. Learning was facilitated by a study guide. Effectiveness was assessed by anonymous surveys. Students found the hybrid–virtual or fully virtual field trips informative, interesting, enjoyable, and appropriate given the pandemic. For the introductory class, 42% preferred a virtual field trip format, 39% preferred an in‐person format, and 19% were neutral. In the advanced class there was with a clear preference for in‐person field trips.Core Ideas: Hybrid–virtual field trips were created for introductory and advanced soil science courses.Students found the hybrid–virtual field trips informative, interesting, and enjoyable.Students liked the flexibility of the virtual format.A total of 42% of students preferred virtual field trips, whereas 39% preferred in‐person field trips. [ABSTRACT FROM AUTHOR]

Our objective was to assess the effect of nitric oxide added to the sweep gas of the oxygenator during cardiopulmonary bypass (CPB) in infants on platelet count, platelet function, clinical outcomes, and safety. A randomized, double‐blinded, placebo‐controlled clinical trial in infants less than a year of age undergoing cardiac surgery requiring CPB was undertaken. Nitric oxide at a dose of 20 ppm was added to the sweep gas in the treatment group. Blood was collected at baseline and prior to separation from CPB to measure platelet count and function as determined by responsiveness to specific agonists. Clinical outcomes were observed through hospital discharge. Methemoglobin levels were measured preoperatively, at the conclusion of CPB, and upon admission to the ICU. Forty patients consented and were randomized in the trial. Eighteen patients were randomized to the treatment group and 22 were included in the placebo group. The groups were similar in terms of age, weight, gender, and surgical complexity. No significant differences were found in measures of platelet count, platelet response to agonist, or clinical outcomes. Patients in the treatment group had higher methemoglobin levels after receiving nitric oxide, but no levels approached toxicity (maximum 2.4%). Nitric oxide added to the sweep gas of the oxygenator during CPB in infants did not have an appreciable effect on the preservation of platelet count, platelet responsiveness to agonist, or clinical outcomes. Methemoglobin levels were increased after receiving nitric oxide but were far below a toxic level of 15%. [ABSTRACT FROM AUTHOR]

Solid organ transplant recipients are considered at high risk for COVID‐19 infection due to chronic immune suppression; little data currently exists on the manifestations and outcomes of COVID‐19 infection in lung transplant recipients. Here we report 8 cases of COVID‐19 identified in patients with a history of lung transplant. We describe the clinical course of disease as well as preexisting characteristics of these patients. [ABSTRACT FROM AUTHOR]

Objectives: Loss‐of‐function mutations in the gene encoding the calcium‐calmodulin (Ca2+‐CaM)‐dependent protein kinase kinase‐2 (CaMKK2) enzyme are linked to bipolar disorder. Recently, a de novo arginine to cysteine (R311C) mutation in CaMKK2 was identified from a whole exome sequencing study of bipolar patients and their unaffected parents. The aim of the present study was to determine the functional consequences of the R311C mutation on CaMKK2 activity and regulation by Ca2+‐CaM. Methods: The effects of the R311C mutation on CaMKK2 activity and Ca2+‐CaM activation were examined using a radiolabeled adenosine triphosphate (ATP) kinase assay. We performed immunoblot analysis to determine whether the R311C mutation impacts threonine‐85 (T85) autophosphorylation, an activating phosphorylation site on CaMKK2 that has also been implicated in bipolar disorder. We also expressed the R311C mutant in CaMKK2 knockout HAP1 cells and used immunoblot analysis and an MTS reduction assay to study its effects on Ca2+‐dependent downstream signaling and cell viability, respectively. Results: The R311C mutation maps to the conserved HRD motif within the catalytic loop of CaMKK2 and caused a marked reduction in kinase activity and Ca2+‐CaM activation. The R311C mutation virtually abolished T85 autophosphorylation in response to Ca2+‐CaM and exerted a dominant‐negative effect in cells as it impaired the ability of wild‐type CaMKK2 to initiate downstream signaling and maintain cell viability. Conclusions: The highly disruptive, loss‐of‐function impact of the de novo R311C mutation in human CaMKK2 provides a compelling functional rationale for being considered a potential rare monogenic cause of bipolar disorder. [ABSTRACT FROM AUTHOR]

Molecular nitrogen (N2) constitutes the majority of Earth's modern atmosphere, contributing ~0.79 bar of partial pressure (pN2). However, fluctuations in pN2 may have occurred on 107–109 year timescales in Earth's past, perhaps altering the isotopic composition of atmospheric nitrogen. Here, we explore an archive that may record the isotopic composition of atmospheric N2 in deep time: the foliage of cycads. Cycads are ancient gymnosperms that host symbiotic N2‐fixing cyanobacteria in modified root structures known as coralloid roots. All extant species of cycads are known to host symbionts, suggesting that this N2‐fixing capacity is perhaps ancestral, reaching back to the early history of cycads in the late Paleozoic. Therefore, if the process of microbial N2 fixation records the δ15N value of atmospheric N2 in cycad foliage, the fossil record of cycads may provide an archive of atmospheric δ15N values. To explore this potential proxy, we conducted a survey of wild cycads growing in a range of modern environments to determine whether cycad foliage reliably records the isotopic composition of atmospheric N2. We find that neither biological nor environmental factors significantly influence the δ15N values of cycad foliage, suggesting that they provide a reasonably robust record of the δ15N of atmospheric N2. Application of this proxy to the record of carbonaceous cycad fossils may not only help to constrain changes in atmospheric nitrogen isotope ratios since the late Paleozoic, but also could shed light on the antiquity of the N2‐fixing symbiosis between cycads and cyanobacteria. [ABSTRACT FROM AUTHOR]

Immobilizing the photocatalyst in a water treatment process design is essential; however, the immobilization method may affect the photoactivity of the photocatalyst. In this work, photocatalyst powders were successfully coated on 316 L stainless steel plates by a novel brush coating method. Three combinations of photocatalyst mixtures (pure TiO2 anatase, anatase doped with WO3, or TiO2 rutile) were and annealed at different temperatures between 460‐540°C. The ~ 10 μm thick coatings demonstrated full plate coverage and strong adhesion and adequate durability. Surface roughness increased with annealing temperature. The doping and annealing process enabled band gap reduction to the visible light spectrum for all coatings, with the smallest band gap being 2.48 eV (1 eV = 1.6 × 10−19 J). Subsequent methylene blue degradation tests under UV‐C showed that the coatings annealed in 460°C exhibited the best performance and with the highest degradation rate constant of 5.59 hours−1. [ABSTRACT FROM AUTHOR]

This article examines the gaps between research and practice in the areas of rater accuracy and goal setting. Prior research has shown that human resource managers may incorrectly believe that training raters to recognize errors will increase rater accuracy and that employee participation in goal setting is more effective than assigning goals. Theory-based research suggests ways to help raters recognize expected performance and enable employees to self-regulate their pursuit of goals. We describe applications of these findings to performance management programs and suggest methods for evaluating their effectiveness once implemented. [ABSTRACT FROM AUTHOR]

Readers of Rousseau are aware of his professed admiration for the ancients and his appeal to ancient examples throughout his works. The model of the citizen is exemplified by the Spartans, or rather Rousseau's imagination of them, for, according to Shklar (1968), Rousseau was not much interested in history. While many interpreters privilege Sparta in interpreting Rousseau, often either seeing his evocation of Lacedaemon as elegiac or taking it as evidence of his totalitarian tendencies, Champy's attention to Rome, which Rousseau himself called "that model of all free peoples", reveals a more practical side of Rousseau than is often appreciated. [Extracted from the article]

A UV‐C/titanium dioxide (TiO2) plate coated photocatalytic reactor using a corrugated frame system was designed for water borne organic contaminant degradation. The anticipated advantages of using the corrugated layout include a larger photocatalytic surface area per unit volume and improved photocatalytic activity. The water distribution system was designed to assist effective interactions among the water pollutant, photocatalyst, and photons. The degradation of a methylene blue solution, as a model water contaminant, was carried out at room temperature (22 °C) at different concentrations and flowrates. With an 11 mg/L methylene blue solution, 70 % was degraded within the first 10 min using TiO2 coated corrugated plates, whereas under the same conditions the degradation rate was only 12 % for a corrugated reactor without a catalyst coating, and 4 % for a no‐plate reactor. The methylene blue degradation was described by the Langmuir‐Hinshelwood model, and the apparent photonic efficiency of the corrugated arrangement was found to be in the range of 1.53–2.83 % when half the initial concentration was degraded. The local area specific rate of energy absorption (LASREA) profile over the plates was determined from a model developed based on UV‐C light irradiation distribution and plate configuration. Light intensity measurements were carried out and were found to correlate with this model. A set of corrugated plate photocatalytic reactors with different geometries, but with the same coated area, were then analyzed and absorbed UV light intensities were integrated to determine the best geometry. [ABSTRACT FROM AUTHOR]

SUMMARY: Microalgae have been investigated for their ability to produce metabolites that exhibit antibacterial activity. However, as research on antibacterial activity progresses, the effect of microalgal extracts on mammalian cells needs to be also assessed. The in vitro effect of microalgal extracts with demonstrated antibacterial activity against the human opportunistic pathogen Staphylococcus aureus was examined on the viability of non‐malignant (MCF10A and 184B5 cells) and malignant human cell lines (A2780 and MCF7). Direct cell counts indicated that the MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) proliferation assay was found to under/overestimate cell viability when specific microalgal extracts and/or concentrations were tested. From direct cell counts, the viability of non‐malignant cells was not reduced after exposure to the extracts, whereas the viability of malignant cells was affected by specific microalgal extracts and concentrations. The results suggest that green microalgae are worthy of further investigation as potential sources of antibiotics, since they did not show a negative effect on the non‐malignant cell lines, MCF10A and 184B5. Additional studies should evaluate the compounds responsible for the anti‐proliferative activity of specific microalgal extracts observed on the malignant cells A2780 and MCF7. [ABSTRACT FROM AUTHOR]

Objective: Identify, diagnose, and document oral clinical and radiographic evidence associated with the genetic condition known as special AT-rich sequence-binding protein 2 (SATB2)-associated syndrome. Through identifying and publishing these common dental and behavioral findings, we hope to educate oral and medical healthcare providers to identify this condition in an attempt to develop meaningful comprehensive care to this patient population.Methods: A total of 37 patients (19 female), ranging from ages 2 to 20 were evaluated at Arkansas Children's Hospital in Little Rock, Arkansas. Patient geographic distribution included: the United States, Canada, Portugal, Spain, and the Netherlands. Patients were clinically and radiographically examined for oral findings. Panoramic radiographs were obtained when patient's behavior allowed. Patient's parents or guardians were also interviewed concerning dental, medical, and behavioral histories.Results: Clinical findings included delayed tooth eruption, bruxism, sialorrhea, larger than normal teeth with an increased propensity for maxillary anterior tooth trauma due to unsteady ambulation. Radiographic findings included delayed permanent root formation, significantly delayed or missing second bicuspids, malformed teeth, and taurodontism. Medical and behavioral issues included: insomnia, hyperphagia, cognitive delays, and an extremely high pain threshold.Conclusion: Patients with SATB2-associated syndrome have shown to have a consistent and unique set of dental findings both clinically and radiographically. A thorough health and dental history along with the aforementioned results of the study may facilitate a diagnosis of this syndrome. Due to the complexity of the patient's dental needs and behavior, a health practitioner with special needs care experience on a comprehensive craniofacial team would be optimal. [ABSTRACT FROM AUTHOR]

Groundwater in karst aquifers constitutes about 25% of drinking water sources globally. Karst aquifers are open systems, susceptible to contamination by surface‐borne pollutants. In this study, springs and wells from two karst aquifers in Illinois, USA, were found to contain microplastics and other anthropogenic contaminants. All microplastics were fibers, with a maximum concentration of 15.2 particles/L. The presence of microplastic was consistent with other parameters, including phosphate, chloride and triclosan, suggesting septic effluent as a source. More studies are needed on microplastic sources, abundance, and impacts on karst ecosystems. Article impact statement: Plastics present a serious worldwide environmental problem. This article provides evidence that microplastics are present in karst groundwater. [ABSTRACT FROM AUTHOR]

Background: Laparoscopy has proven to be feasible and effective at reducing surgical morbidity and mortality in low resource settings. In Rwanda, the demand for and perceived challenges to laparoscopy use remain unclear.Methods: A mixed-methods study was performed at the four Rwandan national referral teaching hospitals. Retrospective logbook reviews (July 2014-June 2015) assessed procedure volume and staff involvement. Web-based surveys and semi-structured interviews investigated barriers to laparoscopy expansion.Results: During the study period, 209 laparoscopic procedures were completed: 57 (27.3%) general surgery cases; 152 (72.7%) ob/gyn cases. The majority (58.9%, 125/209) occurred at the private hospital, which performed 82.6% of cholecystectomies laparoscopically (38/46). The three public hospitals, respectively, performed 25% (7/28), 15% (12/80), and 0% (denominator indeterminate) of cholecystectomies laparoscopically. Notably, the two hospitals with the highest laparoscopy volume relied on a single surgeon for more than 85% of cases. The four ob/gyn departments performed between 4 and 87 laparoscopic cases (mostly diagnostic). Survey respondents at all sites listed a dearth of trainers as the most significant barrier to performing laparoscopy (65.7%; 23/35). Other obstacles included limited access to training equipment and courses. Equipment and material costs, equipment functionality, and material supply were perceived as lesser barriers. Twenty-two interviews revealed widespread interest in laparoscopy, insufficient laparoscopy exposure, and a need for trainers.Conclusion: While many studies identify cost as the most prohibitive barrier to laparoscopy utilization in low resource settings, logbook review and workforce perception indicate that a paucity of trainers is currently the greatest obstacle in Rwanda. [ABSTRACT FROM AUTHOR]

Despite continued advancements in perioperative care for pediatric liver transplant (LT), graft- threatening vascular occlusion events including hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) remain a source of significant morbidity and mortality. Perioperative anticoagulation is commonly used for the prevention of HAT and PVT, but evidence-based guidelines are lacking. The goals of this survey were to determine the frequency of use of an anticoagulation protocol and to describe variation in anticoagulation practices among pediatric LT centers. The study consisted of an online survey distributed to members of SPLIT. The survey focused on institutional anticoagulation practices employed to reduce the incidence of graft and lifethreatening vascular occlusion events. Responses were received from 31 of 39 SPLIT centers. All respondents report using anticoagulation after pediatric LT, and approximately 90% have institutional anticoagulation protocols. Subgroup analysis of high volume pediatric LT centers revealed similar variability in anticoagulation patterns. All participating SPLIT centers reported the use of post-transplant anticoagulation and nearly all use a protocol. However, there is marked variability in the type and dose of anticoagulation as well as the timing of initiation and duration of therapy across centers. [ABSTRACT FROM AUTHOR]

Background: Influenza immune globulin, manufactured from plasma of convalescent or vaccinated donors has been proposed as a potential therapy for severe influenza. In 2009, a program was initiated to collect plasma from donors who self-identified as having had H1N1 influenza or having received the H1N1 pandemic vaccine. The goal of this study was to determine the efficiency of donor screening by self-identification without antibody testing, and to evaluate demographic predictors of high-titer donations.Study Design and Methods: Plasma samples from self-identified or control donors were randomly selected to evaluate hemagglutination inhibition (HAI) antibody responses. HAI titers were correlated with donor age, gender, location, and influenza exposure history.Results: Both self-identified vaccinated and convalescent donor groups had higher geometric mean titers (GMTs) against A/California/07/2009 (H1N1) virus compared to the control donors (39.9, 24, and 8.5, respectively). The proportion of samples with titers ≥64 in vaccinated, convalescent, and control donors were 54%, 37%, and 10%, respectively. Donations with titers ≤16 were predominant in control donors (80%) and substantial in convalescent (47%) and vaccinated (40%) donors. Titers did not correlate with donor age, gender, or geographical location. GMTs for vaccinated donors were significantly higher than for convalescent donors and in both groups significantly higher than in the control.Conclusion: Targeted collection of plasma containing high levels of anti-influenza antibodies from self-identified donors was effective, but could be further improved by reducing the number of low-titer donations. More selective donor screening and/or testing for influenza antibodies could increase the potency of an influenza antibody-rich immune globulin (FLUIGIV). [ABSTRACT FROM AUTHOR]

Objective To compare number of infections and health care utilization in children insured by TRICARE with recurrent acute otitis media (RAOM) managed surgically with tympanostomy tube (TT) placement compared with those managed medically. Study Design Retrospective matched cohort study. Setting TRICARE claims database from 2006 to 2010. Subjects and Methods We matched TRICARE beneficiaries ≤5 years of age diagnosed with RAOM who underwent TT placement with those managed medically using 1:1 coarsened-exact matching on age, sex, race, sponsor rank, and region. We used multivariable negative binomial regression to compare number of infections and health care utilization at 1 and 2 years. Outcomes were adjusted for rate of infection before treatment for RAOM, season of either TT placement or establishment of candidacy for TT placement, and comorbidities. Results Among 6659 pairs identified at 1-year follow-up, the TT group had fewer infections (1.96 vs 2.18, P < .001) and oral antibiotic prescriptions (1.52 vs 1.67, P < .001) but more visits to primary care physicians (4.36 vs 4.06, P < .0001) and otolaryngologists (1.21 vs 0.44, P < .0001) compared with the medically managed group. At 2-year follow-up, the benefits of TT placement were no longer seen. Conclusion TT placement for RAOM is associated with fewer infections and oral antibiotic prescriptions in the first year after surgery but more doctor visits. Benefits of TT placement do not appear to extend through the second year. Future research should investigate costs associated with TT placement vs medical management, as well as real-time health care utilization with impact on patient symptoms and quality of life. [ABSTRACT FROM AUTHOR]

Background/Objectives: Skin conditions are commonly encountered in general practice but dermatology is underrepresented in undergraduate medical courses. Australian and international studies have shown that the dermatological diagnostic ability of general practitioners (GPs) is suboptimal, contributing to increased dermatology outpatient referrals. Dermatological experience in GP vocational training is thus of particular importance. We aimed to document the prevalence of skin disease presentations and the range of skin diseases encountered by GP trainees. We also sought to establish associations of GP trainee’s skin disease experience, including their personal characteristics, consultation factors, and the actions arising from the consultation. Methods: This study took place in the Registrars Clinical Encounters in Training (ReCEnT) study. ReCEnT is an ongoing, prospective, multi-site cohort study of Australian GP trainees’ consultations. A descriptive cross-sectional analysis was performed on trainees’ consultation data. Results: In total, 645 individual trainees contributed data from 84 615 consultations. Altogether, 11% of all problems managed were skin problems. Infections, dermatitis, injury and wounds were the most common presentations. Associations of consultations for skin problems (compared with all other problems) included seeking in-consultation advice, planning patient follow up and generating learning goals. Conclusions: These findings suggest GP trainees find skin problems challenging and may indicate a need for more and better targeted undergraduate and GP trainee education. [ABSTRACT FROM AUTHOR]

After decades on the margins of primary health care, surgical and anaesthesia care is gaining increasing priority within the global development arena. The 2015 publications of the Disease Control Priorities third edition on Essential Surgery and the Lancet Commission on Global Surgery created a compelling evidenced-based argument for the fundamental role of surgery and anaesthesia within cost-effective health systems strengthening global strategy. The launch of the Global Alliance for Surgical, Obstetric, Trauma, and Anaesthesia Care in 2015 has further coordinated efforts to build priority for surgical care and anaesthesia. These combined efforts culminated in the approval of a World Health Assembly resolution recognizing the role of surgical care and anaesthesia as part of universal health coverage. Momentum gained from these milestones highlights the need to identify consensus goals, targets and indicators to guide policy implementation and track progress at the national level. Through an open consultative process that incorporated input from stakeholders from around the globe, a global target calling for safe surgical and anaesthesia care for 80% of the world by 2030 was proposed. In order to achieve this target, we also propose 15 consensus indicators that build on existing surgical systems metrics and expand the ability to prioritize surgical systems strengthening around the world. [ABSTRACT FROM AUTHOR]

Nerve growth factor ( NGF), a member of the neurotrophin family, is known to regulate the development and survival of a select population of neurons through the binding and activation of the TrkA receptor. Elevated levels of NGF have been associated with painful pathologies such as diabetic neuropathy and fibromyalgia. However, completely inhibiting the NGF signal could hold significant side effects, such as those observed in a genetic condition called congenital insensitivity to pain and anhidrosis ( CIPA). Previous methods of screening for NGF-inhibitors used labeling techniques which have the potential to alter molecular interactions. SPR spectroscopy and NGF-dependent cellular assays were utilized to identify a novel NGF-inhibitor, BVNP-0197 ( IC50 = 90 nmol/L), the first NGF-inhibitor described with a high nanomolar NGF inhibition efficiency. The present study utilizes molecular modeling flexible docking to identify a novel binding domain in the loop II/ IV cleft of NGF. [ABSTRACT FROM AUTHOR]

Background: Although pneumonia is a leading cause of inpatient mortality, deaths may also occur after discharge from hospital. However, prior studies have been small, in selected groups or did not fully evaluate risk factors, particularly malnutrition and HIV. We determined 1-year post-discharge mortality and risk factors among children diagnosed with severe pneumonia.Methods: A cohort study of children aged 1-59 months admitted to Kilifi County Hospital with severe pneumonia (2007-12). The primary outcome was death <1 year after discharge, determined through Kilifi Health and Demographic Surveillance System (KHDSS) quarterly census rounds.Results: Of 4184 children (median age 9 months) admitted with severe pneumonia, 1041 (25%) had severe acute malnutrition (SAM), 267 (6.4%) had a positive HIV antibody test, and 364 (8.7%) died in hospital. After discharge, 2279 KHDSS-resident children were followed up; 70 (3.1%) died during 2163 child-years: 32 (95% confidence interval (CI) 26, 41) deaths per 1000 child years. Post-discharge mortality was greater after admission for severe pneumonia than for other diagnoses, hazard ratio 2.5 (95% CI 1.2, 5.3). Malnutrition, HIV status, age and prolonged hospitalisation, but not signs of pneumonia severity, were associated with post-discharge mortality. Fifty-two per cent (95% CI 37%, 63%) of post-discharge deaths were attributable to low mid-upper arm circumference and 11% (95% CI 3.3%, 18%) to a positive HIV test.Conclusions: Admission with severe pneumonia is an important marker of vulnerability. Risk stratification and better understanding of the mechanisms underlying post-discharge mortality, especially for undernourished children, are needed to reduce mortality after treatment for pneumonia. [ABSTRACT FROM AUTHOR]

Globally, Phytophthora cinnamomi is listed as one of the 100 worst invasive alien species and active management is required to reduce impact and prevent spread in both horticulture and natural ecosystems. Conversely, there are regions thought to be suitable for the pathogen where no disease is observed. We developed a climex model for the global distribution of P. cinnamomi based on the pathogen's response to temperature and moisture and by incorporating extensive empirical evidence on the presence and absence of the pathogen. The climex model captured areas of climatic suitability where P. cinnamomi occurs that is congruent with all available records. The model was validated by the collection of soil samples from asymptomatic vegetation in areas projected to be suitable by the model for which there were few records. DNA was extracted, and the presence or absence of P. cinnamomi was determined by high-throughput sequencing ( HTS). While not detected using traditional isolation methods, HTS detected P. cinnamomi at higher elevations in eastern Australia and central Tasmania as projected by the climex model. Further support for the climex model was obtained using the large data set from south-west Australia where the proportion of positive records in an area is related to the Ecoclimatic Index value for the same area. We provide for the first time a comprehensive global map of the current P. cinnamomi distribution, an improved climex model of the distribution, and a projection to 2080 of the distribution with predicted climate change. This information provides the basis for more detailed regional-scale modelling and supports risk assessment for governments to plan management of this important soil-borne plant pathogen. [ABSTRACT FROM AUTHOR]

The ecological dynamics of microplastic (<5 mm) are well documented in marine ecosystems, but the sources, abundance, and ecological role of microplastic in rivers are unknown and likely to be substantial. Microplastic fibers (e.g., synthetic fabrics) and pellets (e.g., abrasives in personal care products) are abundant in wastewater treatment plant (WWTP) effluent, and can serve as a point source of microplastic in rivers. The buoyancy, hydrophobic surface, and long transport distance of microplastic make it a novel substrate for the selection and dispersal of unique microbial assemblages. We measured microplastic concentration and bacterial assemblage composition on microplastic and natural surfaces upstream and downstream of WWTP effluent sites at nine rivers in Illinois, United States. Microplastic concentration was higher downstream of WWTP effluent outfall sites in all but two rivers. Pellets, fibers, and fragments were the dominant microplastic types, and polymers were identified as polypropylene, polyethylene, and polystyrene. Mean microplastic flux was 1,338,757 pieces per day, although the flux was highly variable among nine sites (min = 15,520 per day, max = 4,721,709 per day). High-throughput sequencing of 16S rRNA genes showed bacterial assemblage composition was significantly different among microplastic, seston, and water column substrates. Microplastic bacterial assemblages had lower taxon richness, diversity, and evenness than those on other substrates, and microplastic selected for taxa that may degrade plastic polymers (e.g., Pseudomonas) and those representing common human intestinal pathogens (e.g., Arcobacter). Effluent from WWTPs in rivers is an important component of the global plastic "life cycle," and microplastic serves as a novel substrate that selects and transports distinct bacterial assemblages in urban rivers. Rates of microplastic deposition, consumption by stream biota, and the metabolic capacity of microplastic biofilms in rivers are unknown and merit further research. [ABSTRACT FROM AUTHOR]

A-kinase anchoring proteins (AKAPs) are a family of proteins that provide spatiotemporal resolution of protein kinase A (PKA) phosphorylation. In the myocardium, PKA and AKAP18γ/δ are found in complex with sarcoendoplasmic reticulum Ca2+-ATPase 2 (SERCA2) and phospholamban (PLB). This macromolecular complex provides a means by which anchored PKA can dynamically regulate cytoplasmic Ca2+ release and re-uptake. For this reason, AKAP18γ/δ presents an interesting drug target with therapeutic potential in cardiovascular disease. The crystal structure of the central domain of human AKAP18γ has been determined at the atomic resolution of 1.25 Å. This first structure of human AKAP18γ is trapped in a novel conformation by a malonate molecule bridging the important R-loop with the 2H phosphoesterase motif. Although the physiological substrate of AKAP18γ is currently unknown, a potential proton wire deep in the central binding crevice has been indentified, leading to bulk solvent below the R-loop. Malonate complexed with AKAP18γ at atomic resolution provides an excellent starting point for structure-guided drug design. [ABSTRACT FROM AUTHOR]

Context Health care workers must possess high levels of medical knowledge, technical skills and also non-technical skills ( NTS) in order to provide safe, effective and patient-centred care. Although there has been a recent proliferation of NTS assessment and training tools developed in high-income countries, little is known about NTS in low- and middle-income countries ( LMICs), which face a variety of provider-level and system-level challenges. The aim of this study was to identify the NTS used by providers in LMICs that have been studied, describe how they are assessed and taught, and explain the contextual factors in LMICs that affect their use. Methods We conducted a systematic literature review in accordance with preferred reporting items for systematic reviews and meta-analyses guidelines for primary research publications from January 1994 to December 2013 on evaluation or teaching of NTS used by health care workers in LMICs using MEDLINE, Embase, CIHHAL and Web of Science. Bibliographies of relevant manuscripts were also hand-searched to identify all potentially eligible manuscripts. Results We identified 21 manuscripts from 17 LMICs involving eight types of health care providers and trainees. These studies covered five NTS categories: decision making, communication, teamwork, leadership and stress management. The most commonly used methods were questionnaires, interviews and observations, and 43% ( n = 9) scored > 10 points using the Medical Education Research Study Quality Instrument. Although many studies highlighted the ways in which overburdened health care systems, lack of provider empowerment and deficiencies in provider training had an impact on providers' use of these NTS, no context-specific assessment or educational tools were identified. Conclusion There is growing worldwide interest in understanding and teaching critical non-technical skills to health care providers. This review highlights several studies describing a variety of important non-technical skills. However, these skills must be further characterised in order to develop context-specific tools for assessing and teaching NTS that are sensitive to the local challenges that are common across a variety of LMIC contexts. [ABSTRACT FROM AUTHOR]

Objectives To systematically review the current literature on mortality and functional outcomes after emergency major abdominal surgery in older adults. Design Systematic literature search and standardized data collection of primary research publications from January 1994 through December 2013 on mortality or functional outcome in adults aged 65 and older after emergency major abdominal surgery using PubMed, EMBASE, Web of Science, Cochrane, and CINAHL. Bibliographies of relevant reports were also hand-searched to identify all potentially eligible studies. Setting Systematic review of retrospective and cohort studies using Preferred Reporting Items for Systematic reviews and Meta-Analyses, Meta-analysis Of Observational Studies in Epidemiology, Strengthening the Reporting of Observational Studies in Epidemiology, and A Measurement Tool to Assess Systematic Reviews guidelines. Participants Older adults. Measurements Articles were assessed using a standardized quality scoring system based on study design, measurement of exposures, measurement of outcomes, and control for confounding. Results Of 1,459 articles screened, 93 underwent full-text review, and 20 were systematically reviewed. In-hospital and 30-day mortality of all older adults exceeded 15% in 14 of 16 studies, where reported. Older adults undergoing emergency major abdominal surgery consistently had higher mortality across study settings and procedure types than younger individuals undergoing emergency procedures and older adults undergoing elective procedures. In studies that stratified older adults, odds of death increased with age. None of these studies examined postoperative functional status, which precluded including functional outcomes in this review. Differences in exposures, outcomes, and data presented in the studies did not allow for quantification of association using metaanalysis. Conclusion Age independently predicts mortality after emergency major abdominal surgery. Data on changes in functional status of older adults who undergo these procedures are lacking. [ABSTRACT FROM AUTHOR]

Transition interventions aim to improve care and reduce hospital readmissions but evaluations of these interventions have reported inconsistent results. We report on the evaluation of an intervention implemented in Auckland, New Zealand. Participants were people over the age of 65 who had an acute medical admission and were at high risk of readmission. The intervention included an improved discharge process and nurse telephone follow-up soon after discharge. Outcomes were 28 day readmission rates and emergency attendances. The study is observational, using both interrupted times series and regression discontinuity designs. 5239 patients were treated over a one year period. There was no change in readmission rates or ED attendances or secondary outcomes. Not all patients received all components of the intervention. This transition intervention was not successful. Possible reasons for this and implications are discussed. Although non-experimental methods were used, we believe the results are robust. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives Indiscriminate health screening is increasingly seen as being problematic. In particular, vitamin D testing rates are increasing rapidly despite recommendations against population screening. The purpose of this study was to determine the level of vitamin D testing among family practice/general practitioner ( GP) trainees and to establish associations of this testing. Methods Cross-sectional analysis of data from the ReCEnT ( Registrars Clinical Encounters in Training) cohort study. The setting was GP practices in four Australian states. Data from 60 consecutive consultations per trainee were recorded each 6-month training term (up to four terms). Results Vitamin D tests were ordered in 726 (1.0%) of encounters ( n = 69 412). Vitamin D test ordering was significantly associated with patients being older, female and non- English speaking. Trainees were more likely to test if they worked in a completely bulk-billing practice (i.e. a practice without any patient payment), if more problems were dealt with, more pathology tests were ordered in the consultation and if a lipid profile was ordered. They were less likely to test if they sought in-consultation advice or information. The most common reasons for testing were 'check-up' and 'health maintenance'. Conclusions In this first report of associations of vitamin D testing in the GP setting, we found that non-targeted vitamin D testing (testing inconsistent with current guidelines) is widespread in GP trainees' practice. Adoption of more rational testing approaches is needed. [ABSTRACT FROM AUTHOR]

Purpose Spontaneous adverse event reporting systems are critical tools for monitoring the safety of licensed medical products. Commonly used signal detection algorithms identify disproportionate product-adverse event pairs and may not be sensitive to more complex potential signals. We sought to develop a computationally tractable multivariate data-mining approach to identify product-multiple adverse event associations. Methods We describe an application of stepwise association rule mining (Step-ARM) to detect potential vaccine-symptom group associations in the US Vaccine Adverse Event Reporting System. Step-ARM identifies strong associations between one vaccine and one or more adverse events. To reduce the number of redundant association rules found by Step-ARM, we also propose a clustering method for the post-processing of association rules. Results In sample applications to a trivalent intradermal inactivated influenza virus vaccine and to measles, mumps, rubella, and varicella (MMRV) vaccine and in simulation studies, we find that Step-ARM can detect a variety of medically coherent potential vaccine-symptom group signals efficiently. In the MMRV example, Step-ARM appears to outperform univariate methods in detecting a known safety signal. Conclusions Our approach is sensitive to potentially complex signals, which may be particularly important when monitoring novel medical countermeasure products such as pandemic influenza vaccines. The post-processing clustering algorithm improves the applicability of the approach as a screening method to identify patterns that may merit further investigation. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

SNF1-related protein kinase 1 (SnRK1) is the plant orthologue of the evolutionarily-conserved SNF1/ AMPK/Sn RK1 protein kinase family that contributes to cellular energy homeostasis. Functional as heterotrimers, family members comprise a catalytic α subunit and non-catalytic β and γ subunits; multiple isoforms of each subunit type exist, giving rise to various isoenzymes. The Arabidopsis thaliana genome contains homologues of each subunit type, and, in addition, two atypical subunits, β3 and βγ, with unique domain architecture, that are found only amongst plants, suggesting atypical heterotrimers. The AtSn RK1 subunit structure was determined using recombinant protein expression and endogenous co-immunoprecipitation, and six unique isoenzyme combinations were identified. Each heterotrimeric isoenzyme comprises a catalytic α subunit together with the unique βγ subunit and one of three non-catalytic β subunits: β1, β2 or the plant-specific β3 isoform. Thus, the AtSn RK1 heterotrimers contain the atypical βγ subunit rather than a conventional γ subunit. Mammalian AMPK heterotrimers are phosphorylated on the T-loop ( pThr175/176) within both catalytic a subunits. However, AtSn RK1 is insensitive to AMP and ADP, and is resistant to T-loop dephosphorylation by protein phosphatases, a process that inactivates other SNF1/ AMPK family members. In addition, we show that Sn RK1 is inhibited by a heat-labile, >30 kDa, soluble proteinaceous factor that is present in the lysate of young rosette leaves. Finally, none of the three Sn RK1 carbohydrate-binding modules, located in the β1, β2 and βγ subunits, associate with various carbohydrates, including starch, the plant analogue of glycogen to which AMPK binds in vitro. These data clearly demonstrate that AtSn RK1 is an atypical member of the SNF1/ AMPK/Sn RK1 family. [ABSTRACT FROM AUTHOR]

ABSTRACT Seed persistence is the survival of seeds in the environment once they have reached maturity. Seed persistence allows a species, population or genotype to survive long after the death of parent plants, thus distributing genetic diversity through time. The ability to predict seed persistence accurately is critical to inform long-term weed management and flora rehabilitation programs, as well as to allow a greater understanding of plant community dynamics. Indeed, each of the 420000 seed-bearing plant species has a unique set of seed characteristics that determine its propensity to develop a persistent soil seed bank. The duration of seed persistence varies among species and populations, and depends on the physical and physiological characteristics of seeds and how they are affected by the biotic and abiotic environment. An integrated understanding of the ecophysiological mechanisms of seed persistence is essential if we are to improve our ability to predict how long seeds can survive in soils, both now and under future climatic conditions. In this review we present an holistic overview of the seed, species, climate, soil, and other site factors that contribute mechanistically to seed persistence, incorporating physiological, biochemical and ecological perspectives. We focus on current knowledge of the seed and species traits that influence seed longevity under ex situ controlled storage conditions, and explore how this inherent longevity is moderated by changeable biotic and abiotic conditions in situ, both before and after seeds are dispersed. We argue that the persistence of a given seed population in any environment depends on its resistance to exiting the seed bank via germination or death, and on its exposure to environmental conditions that are conducive to those fates. By synthesising knowledge of how the environment affects seeds to determine when and how they leave the soil seed bank into a resistance-exposure model, we provide a new framework for developing experimental and modelling approaches to predict how long seeds will persist in a range of environments. [ABSTRACT FROM AUTHOR]

A correction to the article "Development of a Unifying Target and Consensus Indicators for Global Surgical Systems Strengthening: Proposed by the Global Alliance for Surgery, Obstetric, Trauma, and Anaesthesia Care," published in a previous issue of the journal is presented.