The peripheral blood transcriptome in septic cardiomyopathy: an observational, pilot study.

BACKGROUND:Septic cardiomyopathy (SCM) is common in sepsis and associated with increased morbidity and mortality. Left ventricular global longitudinal strain (LV GLS), measured by speckle tracking echocardiography, allows improved identification of impaired cardiac contractility. The peripheral blood transcriptome may be an important window into SCM pathophysiology. We therefore studied the peripheral blood transcriptome and LV GLS in a prospective cohort of patients with sepsis. RESULTS:In this single-center observational pilot study, we enrolled adult patients (age > 18) with sepsis within 48 h of admission to the ICU. SCM was defined as LV GLS > - 17% based on echocardiograms performed within 72 h of admission. We enrolled 27 patients, 24 of whom had high-quality RNA results; 18 (75%) of 24 had SCM. The group was 50% female and had a median (IQR) age of 59.5 (48.5-67.0) years and admission APACHE II score of 21.0 (16.0-32.3). Forty-six percent had septic shock. After filtering for low-expression and non-coding genes, 15,418 protein coding genes were expressed and 73 had significantly different expression between patients with vs. without SCM. In patients with SCM, 43 genes were upregulated and 30 were downregulated. Pathway analysis identified enrichment in type 1 interferon signaling (adjusted p < 10-5). CONCLUSIONS:In this hypothesis-generating study, SCM was associated with upregulation of genes in the type 1 interferon signaling pathway. Interferons are cytokines that stimulate the innate and adaptive immune response and are implicated in the early proinflammatory and delayed immunosuppression phases of sepsis. While type 1 interferons have not been implicated previously in SCM, interferon therapy (for viral hepatitis and Kaposi sarcoma) has been associated with reversible cardiomyopathy, perhaps suggesting a role for interferon signaling in SCM

Association of left ventricular longitudinal strain with central venous oxygen saturation and serum lactate in patients with early severe sepsis and septic shock

Syftet med denna studie är att synliggöra pedagogers syn på föräldrasamverkan i förskolan. Vi har även intresserat oss på samverkan mellan pedagogerna och föräldrar med annat modersmål än svenska. Vår studie grundar sig på observationer kring bemötande av föräldrar på förskolan. Vi undersökte hur pedagogerna såg på föräldrasamverkan och hur de arbetar kring samverkan med föräldrar, för att kunna få en bredare syn i vår studie om hur samverkan fungerar på de aktuella förskolorna. Som metod använde vi kvalitativ intervju då detta lämpade sig väl för oss för att vi skulle kunna få en bredare syn om hur samverkan fungerar på de aktuella förskolorna. Intervjuer ger mer exakta svar och det underlättar för oss som intervjuar att ställa följdfrågor. Resultatet visar att samverkan med föräldrar har ökat i förskolan och blivit en stor del av verksamheten. Pedagogerna försöker engagera sig mycket i arbetet med föräldrasamverkan och letar efter möjligheter för att skapa en bra kommunikation med föräldrar som har annat modersmål än svenska. Resultaten visar även att pedagogerna menar att oavsett om föräldrarna behärskar det svenska språket eller inte så anstränger de sig för att visa föräldrarna att de är viktiga i verksamheten

Why Aboriginal and Torres Strait Islander Australians fall and fracture: the codesigned Study of Indigenous Muscle and Bone Ageing (SIMBA) protocol

OBJECTIVES: Aboriginal and Torres Strait Islander Australians have a substantially greater fracture risk, where men are 50% and women are 26% more likely to experience a hip fracture compared with non-Indigenous Australians. Fall-related injuries in this population have also increased by 10%/year compared with 4.3%/year in non-Indigenous Australians. This study aims to determine why falls and fracture risk are higher in Aboriginal and Torres Strait Islander Australians. SETTING: All clinical assessments will be performed at one centre in Melbourne, Australia. At baseline, participants will have clinical assessments, including questionnaires, anthropometry, bone structure, body composition and physical performance tests. These assessments will be repeated at follow-up 1 and follow-up 2, with an interval of 12 months between each clinical visit. PARTICIPANTS: This codesigned prospective observational study aims to recruit a total of 298 adults who identify as Aboriginal and Torres Strait Islander and reside within Victoria, Australia. Stratified sampling by age and sex will be used to ensure equitable distribution of men and women across four age-bands (35-44, 45-54, 55-64 and 65+ years). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is within-individual yearly change in areal bone mineral density at the total hip, femoral neck and lumbar spine assessed by dual energy X-ray absorptiometry. Within-individual change in cortical and trabecular volumetric bone mineral density at the radius and tibia using high-resolution peripheral quantitative computed tomography will be determined. Secondary outcomes include yearly differences in physical performance and body composition. ETHICAL APPROVAL: Ethics approval for this study has been granted by the Monash Health Human Research Ethics Committee (project number: RES-19-0000374A). TRIAL REGISTRATION NUMBER: ACTRN12620000161921

Zircon U-Pb Geochronology Links the End-Triassic Extinction with the Central Atlantic Magmatic Province

The end-Triassic extinction is characterized by major losses in both terrestrial and marine diversity, setting the stage for dinosaurs to dominate Earth for the next 136 million years. Despite the approximate coincidence between this extinction and flood basalt volcanism, existing geochronologic dates have insufficient resolution to confirm eruptive rates required to induce major climate perturbations. Here, we present new zircon uranium-lead (U-Pb) geochronologic constraints on the age and duration of flood basalt volcanism within the Central Atlantic Magmatic Province. This chronology demonstrates synchroneity between the earliest volcanism and extinction, tests and corroborates the existing astrochronologic time scale, and shows that the release of magma and associated atmospheric flux occurred in four pulses over about 600,000 years, indicating expansive volcanism even as the biologic recovery was under way

The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels

Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a similar to 10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heartderived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity

Body size in early life and risk of epithelial ovarian cancer: results from the Nurses' Health Studies

Adult body mass index (BMI) has been associated with ovarian cancer risk, but few studies have examined body size earlier in life. We prospectively examined associations of body fatness at ages 5 and 10, BMI at age 18, height, and birthweight with risk of epithelial ovarian cancer in the Nurses' Health Study (NHS: 110 311 women, 735 cases) and Nurses' Health Study II (NHSII: 113 059 women, 137 cases). Cox proportional hazards regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs). There was a weak inverse association between average body fatness at ages 5 and 10 and risk in the NHS (RR for heaviest vs most lean=0.81, 95% CI: 0.53–1.24, P for trend=0.04) and a nonsignificant positive association in the NHSII (RR=2.09, 95% CI: 0.98–4.48, P for trend=0.10), possibly due to differences in age and menopausal status. Height was positively associated with risk in both cohorts (RR for ⩾1.75 vs <1.6 m=1.43, 95% CI: 1.05–1.96, P for trend=0.001). Body mass index at the age of 18 years and birthweight were not associated with risk. Further research should examine the biological mechanisms underlying the observed associations

Consensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand

Background: Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. Methods: A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at >80%, and five multiple-choice questions. Statements with moderate agreement (70%–80%) were revised and re-introduced in Phase 3, and statements with low agreement (80%) were confirmed by the Task Force in Phase 4. Conclusions: The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia

Consensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand

Background: Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. Methods: A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at \u3e 80 %, and five multiple-choice questions. Statements with moderate agreement (70 % – 80 %) were revised and re-introduced in Phase 3, and statements with low agreement ( \u3c 70 %) were rejected. In Phase 3, topic experts responded to six revised statements and three additional questions, incorporating results from a parallel Consumer Expert Delphi study. Phase 4 involved finalization of consensus statements. Results: Topic experts from Australia (n = 62, 92.5 %) and New Zealand (n = 5, 7.5 %) with a mean ± SD age of 45.7 ± 11.8 years participated in Phase 2; 38 (56.7 %) were women, 38 (56.7 %) were health professionals and 27 (40.3 % ) were researchers/academics. In Phase 2, 15 of 18 (83.3 %) statements on sarcopenia prevention, screening, assessment, management and future research were accepted with strong agreement. The strongest agreement related to encouraging a healthy lifestyle (100 %) and offering tailored resistance training to people with sarcopenia (92.5 %). Forty-seven experts participated in Phase 3; 5/6 (83.3 %) revised statements on prevention, assessment and management were accepted with strong agreement. A majority of experts (87.9 %) preferred the revised European Working Group for Sarcopenia in Older Persons (EWGSOP2) definition. Seventeen statements with strong agreement ( \u3e 80 %) were confirmed by the Task Force in Phase 4. Conclusions: The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia

The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) sarcopenia diagnosis and management task force: Findings from the consumer expert Delphi process

Objectives: To develop guidelines, informed by health-care consumer values and preferences, for sarcopenia prevention, assessment and management for use by clinicians and researchers in Australia and New Zealand. Methods: A three-phase Consumer Expert Delphi process was undertaken between July 2020 and August 2021. Consumer experts included adults with lived experience of sarcopenia or health-care utilisation. Phase 1 involved a structured meeting of the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force and consumer representatives from which the Phase 2 survey was developed. In Phase 2, consumers from Australia and New Zealand were surveyed online with opinions sought on sarcopenia outcome priorities, consultation preferences and interventions. Findings were confirmed and disseminated in Phase 3. Descriptive statistical analyses were performed. Results: Twenty-four consumers (mean ± standard deviation age 67.5 ± 12.8 years, 18 women) participated in Phase 2. Ten (42%) identified as being interested in sarcopenia, 7 (29%) were health-care consumers and 6 (25%) self-reported having/believing they have sarcopenia. Consumers identified physical performance, living circumstances, morale, quality of life and social connectedness as the most important outcomes related to sarcopenia. Consumers either had no preference (46%) or preferred their doctor (40%) to diagnose sarcopenia and preferred to undergo assessments at least yearly (54%). For prevention and treatment, 46% of consumers preferred resistance exercise, 2–3 times per week (54%). Conclusions: Consumer preferences reported in this study can inform the implementation of sarcopenia guidelines into clinical practice at local, state and national levels across Australia and New Zealand

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis