Isolation, purification, and full NMR assignments of cyclopamine from Veratrum californicum

The Hedgehog signaling pathway is essential for embryogenesis and for tissue homeostasis in the adult. However, it may induce malignancies in a number of tissues when constitutively activated, and it may also have a role in other forms of normal and maladaptive growth. Cyclopamine, a naturally occurring steroidal alkaloid, specifically inhibits the Hedgehog pathway by binding directly to Smoothened, an important Hedgehog response element. To use cyclopamine as a tool to explore and/or inhibit the Hedgehog pathway in vivo, a substantial quantity is required, and as a practical matter cyclopamine has been effectively unavailable for usage in animals larger than mice

All-cause hospitalisation according to demographic group in people living with HIV in the current ART era: Recent findings from a cohort study in the UK

OBJECTIVE: We investigated differences in all-cause hospitalisation between key demographic groups among people with HIV in the UK in the current ART era. DESIGN/METHODS: We used data from the Royal Free HIV Cohort study between 2007 and 2018. Individuals were classified into five groups: men who have sex with men (MSM), Black African men who have sex with women (MSW), MSW of other ethnicity, Black African women and women of other ethnicity. We studied hospitalisations during the first year after HIV diagnosis (Analysis-A) separately from those more than one year after diagnosis (Analysis-B). In Analysis-A, time to first hospitalisation was assessed using Cox regression adjusted for age and diagnosis date. In Analysis-B, subsequent hospitalisation rate was assessed using Poisson regression, accounting for repeated hospitalisation within individuals, adjusted for age, calendar year, time since diagnosis. RESULTS: The hospitalisation rate was 30.7/100 person-years in the first year after diagnosis and 2.7/100 person-years subsequently; 52% and 13% hospitalisations respectively were AIDS-related. Compared to MSM, MSW and women were at much higher risk of hospitalisation during the first year [aHR (95%CI): 2.7 (1.7-4.3), 3.0 (2.0-4.4), 2.0 (1.3-2.9), 3.0 (2.0-4.5) for Black African MSW; other ethnicity MSW; Black African women; other ethnicity women respectively, Analysis-A] and remained at increased risk subsequently [corresponding aIRR (95% CI): 1.7 (1.2-2.4), 2.1 (1.5-2.8), 1.5 (1.1-1.9), 1.7 (1.2-2.3), Analysis-B]. CONCLUSIONS: In this setting with universal healthcare, substantial variation exists in hospitalisation risk across demographic groups, both in early and subsequent periods after HIV diagnosis, highlighting the need for targeted interventions

Genetically based adaptive trait shifts at an expanding mangrove range margin

AbstractNeotropical black mangrove (Avicennia germinans) is expanding poleward into temperate salt marsh along Atlantic Florida, USA, with field evidence of trait shifts consistent with greater cold tolerance within range margin populations. However, whether these shifts have a genetic basis remains unanswered. To address this gap, we measured multiple phenotypic traits of twenty A. germinans maternal cohorts from areas in both the Atlantic Florida range core and margin in a 2-year greenhouse common garden with annual temperatures analogous to range margin conditions. Compared to those from the range core, range margin cohorts survived in greater numbers, established (i.e., produced first true leaves) more quickly, and were less stressed under winter temperatures. Range margin cohorts were not taller, but invested more into lateral growth and biomass accumulation that presumably reflects adaptation to their colder and open-canopy environment. Range margin cohorts also exhibited leaf traits consistent with greater resource acquisition that may compensate for a shorter growing season and reduced light quality at higher latitude. Our results suggest that genetically based phenotypic differences better enable these range margin mangroves to thrive within their stressful environment and may facilitate further poleward expansion. An improved understanding of adaptive trait variation within ecologically important mangrove foundation species should also help inform coastal restoration initiatives.</jats:p

Towards a Context-Aware Knowledge Model for Smart Service Systems

The advancement of the Internet of things, big data, and mobile computing leads to the need for smart services that enable the context awareness and the adaptability to their changing contexts. Today, designing a smart service system is a complex task due to the lack of an adequate model support in awareness and pervasive environment. In this paper, we present a context-aware knowledge model for smart service systems that organizes the domain and context-aware knowledge into knowledge components based on the three levels of services: Services, Service system and Network of service systems. The context-aware knowledge model for smart service systems integrates all the information and knowledge related to smart services, knowledge components and context awareness that can play a key role for any framework, infrastructure, or applications deploying smart services. To demonstrate the approach, a case study about a chatbot as a smart service for customer support is presented

Mechanisms of Psychological Distress following War in the Former Yugoslavia: The Role of Interpersonal Sensitivity

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This study was funded by a grant from the European Commission, contract number INCO-CT-2004-509176. AN was supported by a Clinical Early Career Research Fellowship (113295) and a Project Grant (104288

Tariffs

Northern Indiana Public Service Co. (NIPSCO) is collaborating with a group of municipalities to initiate a program to replace all fixtures in its service territory with LED fixtures. In this presentation we discuss this program and its timing, results, and tariff impacts

A multi-centre qualitative study exploring the experiences of UK South Asian and White Diabetic Patients referred for renal care

Background An exploration of renal complications of diabetes from the patient perspective is important for developing quality care through the diabetic renal disease care pathway. Methods Newly referred South Asian and White diabetic renal patients over 16 years were recruited from nephrology outpatient clinics in three UK centres - Luton, West London and Leicester – and their experiences of the diabetes and renal care recorded. A semi-structured qualitative interview was conducted with 48 patients. Interview transcripts were analysed thematically and comparisons made between the White and South Asian groups. Results 23 South Asian patients and 25 White patients were interviewed. Patient experience of diabetes ranged from a few months to 35 years with a mean time since diagnosis of 12.1 years and 17.1 years for the South Asian and White patients respectively. Confusion emerged as a response to referral shared by both groups. This sense of confusion was associated with reported lack of information at the time of referral, but also before referral. Language barriers exacerbated confusion for South Asian patients. Conclusions The diabetic renal patients who have been referred for specialist renal care and found the referral process confusing have poor of awareness of kidney complications of diabetes. Healthcare providers should be more aware of the ongoing information needs of long term diabetics as well as the context of any information exchange including language barriers

Control of crystal size tailors the electrochemical performance of alpha-V2O5 as a Mg2+ intercalation host

α-V2O5 has been extensively explored as a Mg2+ intercalation host with potential as a battery cathode, offering high theoretical capacities and potentials vs. Mg2+/Mg. However, large voltage hysteresis is observed with Mg insertion and extraction, introducing significant and unacceptable round-trip energy losses with cycling. Conventional interpretations suggest that bulk ion transport of Mg2+ within the cathode particles is the major source of this hysteresis. Herein, we demonstrate that nanosizing α-V2O5 gives a measurable reduction to voltage hysteresis on the first cycle that substantially raises energy efficiency, indicating that mechanical formatting of the α-V2O5 particles contributes to hysteresis. However, no measurable improvement in hysteresis is found in the nanosized α-V2O5 in latter cycles despite the much shorter diffusion lengths, suggesting that other factors aside from Mg transport, such as Mg transfer between the electrolyte and electrode, contribute to this hysteresis. This observation is in sharp contrast to the conventional interpretation of Mg electrochemistry. Therefore, this study uncovers critical fundamental underpinning limiting factors in Mg battery electrochemistry, and constitutes a pivotal step towards a high-voltage, high-capacity electrode material suitable for Mg batteries with high energy density

Pralidoxime in Acute Organophosphorus Insecticide Poisoning-A Randomised Controlled Trial

Background: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. Methods and Findings: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio HR] 1.69, 95% confidence interval CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 21.5%], placebo 24/114 21.1%], adjusted HR 1.27 95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. Conclusions: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required

Seeing two faces together: preference formation in humans and rhesus macaques

Humans, great apes and old world monkeys show selective attention to faces depending on conspecificity, familiarity, and social status supporting the view that primates share similar face processing mechanisms. Although many studies have been done on face scanning strategy in monkeys and humans, the mechanisms influencing viewing preference have received little attention. To determine how face categories influence viewing preference in humans and rhesus macaques (Macaca mulatta), we performed two eye-tracking experiments using a visual preference task whereby pairs of faces from different species were presented simultaneously. The results indicated that viewing time was significantly influenced by the pairing of the face categories. Humans showed a strong bias towards an own-race face in an Asian–Caucasian condition. Rhesus macaques directed more attention towards non-human primate faces when they were paired with human faces, regardless of the species. When rhesus faces were paired with faces from Barbary macaques (Macaca sylvanus) or chimpanzees (Pan troglodytes), the novel species’ faces attracted more attention. These results indicate that monkeys’ viewing preferences, as assessed by a visual preference task, are modulated by several factors, species and dominance being the most influential