Prevalence of, and Resident and Facility Characteristics Associated With Antipsychotic Use in Assisted Living vs. Long-Term Care Facilities: A Cross-Sectional Analysis from Alberta, Canada

BACKGROUND: Potentially inappropriate antipsychotic use in long-term care (LTC) facilities has been the focus of significant policy and clinical attention over the past 20 years. However, most initiatives aimed at reducing the use of these medications have overlooked assisted living (AL) settings. OBJECTIVE: We sought to compare the prevalence of antipsychotic use (including potentially inappropriate use) among older AL and LTC residents and to explore the resident and facility-level factors associated with use in these two populations. METHODS: We performed cross-sectional analyses of 1089 residents (mean age 85 years; 77% female) from 59 AL facilities and 1000 residents (mean age 85 years; 66% female) from 54 LTC facilities, in Alberta, Canada. Research nurses completed comprehensive resident assessments at baseline (2006-2007). Facility-level factors were assessed using standardized administrator interviews. Generalized linear models were used to estimate odds ratios for associations, accounting for clustering by facility. RESULTS: Over a quarter of residents in AL (26.4%) and LTC (31.8%) were using antipsychotics (p = 0.006). Prevalence of potentially inappropriate use was similar in AL and LTC (23.4 vs. 26.8%, p = 0.09). However, among users, the proportion of antipsychotic use deemed potentially inappropriate was significantly higher in AL than LTC (AL: 231/287 = 80.5%; LTC: 224/318 = 70.4%; p = 0.004). In both settings, comparable findings regarding associations between resident characteristics (including dementia, psychiatric disorders, frailty, behavioral symptoms, and antidepressant use) and antipsychotic use were observed. Few facility characteristics were associated with overall antipsychotic use, but having a pharmacist on staff (AL), or an affiliated physician (LTC) was associated with a lower likelihood of potentially inappropriate antipsychotic use. CONCLUSION: Our findings illustrate the importance of including AL settings in clinical and policy initiatives aimed at reducing inappropriate antipsychotic use among older vulnerable residents

Birth cluster simulations of planetary systems with multiple super-Earths : initial conditions for white dwarf pollution drivers

Previous investigations have revealed that eccentric super-Earths represent a class of planets that are particularly effective at transporting minor bodies towards white dwarfs and subsequently polluting their atmospheres with observable chemical signatures. However, the lack of discoveries of these planets beyond a few astronomical units from their host stars prompts a better understanding of their orbital architectures from their nascent birth cluster. Here, we perform stellar cluster simulations of three-planet and seven-planet systems containing super-Earths on initially circular, coplanar orbits. We adopt the typical stellar masses of main-sequence progenitors of white dwarfs (⁠1.5M⊙–2.5M⊙⁠) as host stars and include 8000 main-sequence stars following a Kroupa initial mass function in our clusters. Our results reveal that about 30 per cent of the simulated planets generate eccentricities of at least 0.1 by the time of cluster dissolution, which would aid white dwarf pollution. We provide our output parameters to the community for potential use as initial conditions for subsequent evolution simulations

Relationship between perceived body weight and body mass index based on self- reported height and weight among university students: a cross-sectional study in seven European countries

Mikolajczyk RT, Maxwell AE, El Ansari W, Stock C, Petkeviciene J, Guillen-Grima F. Relationship between perceived body weight and body mass index based on self- reported height and weight among university students: a cross-sectional study in seven European countries. BMC Public Health. 2010;10(1): 40.Background Despite low rates of obesity, many university students perceive themselves as overweight, especially women. This is of concern, because inappropriate weight perceptions can lead to unhealthy behaviours including eating disorders. Methods We used the database from the Cross National Student Health Survey (CNSHS), consisting of 5,900 records of university students from Bulgaria, Denmark, Germany, Lithuania, Poland, Spain and Turkey to analyse differences in perceived weight status based on the question: "Do you consider yourself much too thin, a little too thin, just right, a little too fat or much too fat?". The association between perceived weight and body mass index (BMI) calculated from self-reported weight and height was assessed with generalized non-parametric regression in R library gam. Results Although the majority of students reported a normal BMI (72-84% of males, 65-83% of females), only 32% to 68% of students considered their weight "just right". Around 20% of females with BMI of 20 kg/m2 considered themselves "a little too fat" or "too fat", and the percentages increased to 60% for a BMI of 22.5 kg/m2. Male students rarely felt "a little too fat" or "too fat" below BMI of 22.5 kg/m2, but most felt too thin with a BMI of 20 kg/m2. Conclusions Weight ideals are rather uniform across the European countries, with female students being more likely to perceive themselves as "too fat" at a normal BMI, while male students being more likely to perceive themselves as "too thin". Programs to prevent unhealthy behaviours to achieve ill-advised weight ideals may benefit students

Ex vivo Drug Sensitivity Imaging-based Platform for Primary Acute Lymphoblastic Leukemia Cells

Resistance of acute lymphoblastic leukemia (ALL) cells to chemotherapy, whether present at diagnosis or acquired during treatment, is a major cause of treatment failure. Primary ALL cells are accessible for drug sensitivity testing at the time of new diagnosis or at relapse, but there are major limitations with current methods for determining drug sensitivity ex vivo. Here, we describe a functional precision medicine method using a fluorescence imaging platform to test drug sensitivity profiles of primary ALL cells. Leukemia cells are co-cultured with mesenchymal stromal cells and tested with a panel of 40 anti-leukemia drugs to determine individual patterns of drug resistance and sensitivity ("pharmacotype"). This imaging-based pharmacotyping assay addresses the limitations of prior ex vivo drug sensitivity methods by automating data analysis to produce high-throughput data while requiring fewer cells and significantly decreasing the labor-intensive time required to conduct the assay. The integration of drug sensitivity data with genomic profiling provides a basis for rational genomics-guided precision medicine. Key features Analysis of primary acute lymphoblastic leukemia (ALL) blasts obtained at diagnosis from bone marrow aspirate or peripheral blood. Experiments are performed ex vivo with mesenchymal stromal cell co-culture and require four days to complete. This fluorescence imaging-based protocol enhances previous ex vivo drug sensitivity assays and improves efficiency by requiring fewer primary cells while increasing the number of drugs tested to 40. It takes approximately 2-3 h for sample preparation and processing and a 1.5-hour imaging time. Graphical overview

Programmable Ligand Detection System in Plants through a Synthetic Signal Transduction Pathway

There is an unmet need to monitor human and natural environments for substances that are intentionally or unintentionally introduced. A long-sought goal is to adapt plants to sense and respond to specific substances for use as environmental monitors. Computationally re-designed periplasmic binding proteins (PBPs) provide a means to design highly sensitive and specific ligand sensing capabilities in receptors. Input from these proteins can be linked to gene expression through histidine kinase (HK) mediated signaling. Components of HK signaling systems are evolutionarily conserved between bacteria and plants. We previously reported that in response to cytokinin-mediated HK activation in plants, the bacterial response regulator PhoB translocates to the nucleus and activates transcription. Also, we previously described a plant visual response system, the de-greening circuit, a threshold sensitive reporter system that produces a visual response which is remotely detectable and quantifiable.We describe assembly and function of a complete synthetic signal transduction pathway in plants that links input from computationally re-designed PBPs to a visual response. To sense extracellular ligands, we targeted the computational re-designed PBPs to the apoplast. PBPs bind the ligand and develop affinity for the extracellular domain of a chemotactic protein, Trg. We experimentally developed Trg fusions proteins, which bind the ligand-PBP complex, and activate intracellular PhoR, the HK cognate of PhoB. We then adapted Trg-PhoR fusions for function in plants showing that in the presence of an external ligand PhoB translocates to the nucleus and activates transcription. We linked this input to the de-greening circuit creating a detector plant.Our system is modular and PBPs can theoretically be designed to bind most small molecules. Hence our system, with improvements, may allow plants to serve as a simple and inexpensive means to monitor human surroundings for substances such as pollutants, explosives, or chemical agents

On the Free Energy That Drove Primordial Anabolism

A key problem in understanding the origin of life is to explain the mechanism(s) that led to the spontaneous assembly of molecular building blocks that ultimately resulted in the appearance of macromolecular structures as they are known in modern biochemistry today. An indispensable thermodynamic prerequisite for such a primordial anabolism is the mechanistic coupling to processes that supplied the free energy required. Here I review different sources of free energy and discuss the potential of each form having been involved in the very first anabolic reactions that were fundamental to increase molecular complexity and thus were essential for life

Integrating Life Cycle and Impact Assessments to Map Food's Cumulative Environmental Footprint

Feeding a growing, increasingly affluent population while limiting environmental pressures of food production is a central challenge for society. Understanding the location and magnitude of food production is key to addressing this challenge because pressures vary substantially across food production types. Applying data and models from life cycle assessment with the methodologies for mapping cumulative environmental impacts of human activities (hereafter cumulative impact mapping) provides a powerful approach to spatially map the cumulative environmental pressure of food production in a way that is consistent and comprehensive across food types. However, these methodologies have yet to be combined. By synthesizing life cycle assessment and cumulative impact mapping methodologies, we provide guidance for comprehensively and cumulatively mapping the environmental pressures (e.g., greenhouse gas emissions, spatial occupancy, and freshwater use) associated with food production systems. This spatial approach enables quantification of current and potential future environmental pressures, which is needed for decision makers to create more sustainable food policies and practices

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility