Modeling Iron and Light Controls on the Summer \u3ci\u3ePhaeocystis antarctica\u3c/i\u3e Bloom in the Amundsen Sea Polynya

Of all the Antarctic coastal polynyas, the Amundsen Sea Polynya is the most productive per unit area. Observations from the 2010-2011 Amundsen Sea Polynya International Research Expedition (ASPIRE) revealed that both light and iron can limit the growth of phytoplankton (Phaeocystis antarctica), but how these controls manifest over the bloom season is poorly understood, especially with respect to their climate sensitivity. Using a 1-D biogeochemical model, we examine the influence of light and iron limitation on the phytoplankton bloom and vertical carbon flux at 12 stations representing different bloom stages within the polynya. Model parameters are determined by Bayesian optimization and assimilation of ASPIRE observations. The model-data fit is most sensitive to phytoplankton physiological parameters, which among all model parameters are best constrained by the optimization. We find that the 1-D model captures the basic elements of the bloom observed during ASPIRE, despite some discrepancies between modeled and observed dissolved iron distributions. With this model, we explore the way iron availability, in combination with light availability, controlled the rise, peak, and decline of the bloom at the 12 stations. Modeled light limitation by self-shading is very strong, but iron is drawn down as the bloom rises, becoming limiting in combination with light as the bloom declines. These model results mechanistically confirm the importance of climate-sensitive controls like stratification and meltwater on phytoplankton bloom development and carbon export in this region

Acceptability and Feasibility of the Telehealth Bariatric Behavioral Intervention to Increase Physical Activity: Protocol for a Single-Case Experimental Study

Background: Regular physical activity (PA) is recommended to optimize weight and health outcomes in patients who have undergone metabolic and bariatric surgery (MBS). However, >70% of patients have low PA levels before MBS that persist after MBS. Although behavioral interventions delivered face-to-face have shown promise for increasing PA among patients who have undergone MBS, many may experience barriers, preventing enrollment into and adherence to such interventions. Delivering PA behavior change interventions via telehealth to patients who have undergone MBS may be an effective strategy to increase accessibility and reach, as well as adherence. Objective: This paper reports the protocol for a study that aims to assess the feasibility and acceptability of the protocol or methods and the Telehealth Bariatric Behavioral Intervention (TELE-BariACTIV). The intervention is designed to increase moderate-to-vigorous intensity PA (MVPA) in patients awaiting bariatric surgery and is guided by a multitheory approach and a patient perspective. Another objective is to estimate the effect of the TELE-BariACTIV intervention on presurgical MVPA to determine the appropriate sample size for a multicenter trial. Methods: This study is a multicenter trial using a repeated (ABAB’A) single-case experimental design. The A phases are observational phases without intervention (A1=pre-MBS phase; A2=length personalized according to the MBS date; A3=7 months post-MBS phase). The B phases are interventional phases with PA counseling (B1=6 weekly pre-MBS sessions; B2=3 monthly sessions starting 3 months after MBS). The target sample size is set to 12. Participants are inactive adults awaiting sleeve gastrectomy who have access to a computer with internet and an interface with a camera. The participants are randomly allocated to a 1- or 2-week baseline period (A1). Protocol and intervention feasibility and acceptability (primary outcomes) will be assessed by recording missing data, refusal, recruitment, retention, attendance, and attrition rates, as well as via web-based acceptability questionnaires and semistructured interviews. Data collected via accelerometry (7-14 days) on 8 occasions and via questionnaires on 10 occasions will be analyzed to estimate the effect of the intervention on MVPA. Generalization measures assessing the quality of life, anxiety and depressive symptoms, and theory-based constructs (ie, motivational regulations for PA, self-efficacy to overcome barriers to PA, basic psychological needs satisfaction and frustration, PA enjoyment, and social support for PA; secondary outcomes for a future large-scale trial) will be completed via web-based questionnaires on 6-10 occasions. The institutional review board provided ethics approval for the study in June 2021. Results: Recruitment began in September 2021, and all the participants were enrolled (n=12). Data collection is expected to end in fall 2023, depending on the MBS date of the recruited participants. Conclusions: The TELE-BariACTIV intervention has the potential for implementation across multiple settings owing to its collaborative construction that can be offered remotely

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination

Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio