Reproductive Suicide: Similar Mechanisms of Aging in C. elegans and Pacific Salmon

In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in C. elegans and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in C. elegans, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those that involve costly resource reallocation, and exhibit endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in C. elegans can teach us about some mechanisms of senescence that are operative in iteroparous organisms

Assessing the impact of different penalty factors of the Bayesian reconstruction algorithm Q.Clear on in vivo low count kinetic analysis of [11C]PHNO brain PET-MR studies

Introduction: Q.Clear is a Bayesian penalised likelihood (BPL) reconstruction algorithm available on General Electric (GE) Positron Emission Tomography (PET)-Computed Tomography (CT) and PET-Magnetic Resonance (MR) scanners. This algorithm is regulated by a β value which acts as a noise penalisation factor and yields improvements in signal to noise ratio (SNR) in clinical scans, and in contrast recovery and spatial resolution in phantom studies. However, its performance in human brain imaging studies remains to be evaluated in depth. This pilot study aims to investigate the impact of Q.Clear reconstruction methods using different β value versus ordered subset expectation maximization (OSEM) on brain kinetic modelling analysis of low count brain images acquired in the PET-MR. Methods: Six [11C]PHNO PET-MR brain datasets were reconstructed with Q.Clear with β100–1000 (in increments of 100) and OSEM. The binding potential relative to non-displaceable volume (BPND) were obtained for the Substantia Nigra (SN), Striatum (St), Globus Pallidus (GP), Thalamus (Th), Caudate (Cd) and Putamen (Pt), using the MIAKAT™ software. Intraclass correlation coefficients (ICC), repeatability coefficients (RC), coefficients of variation (CV) and bias from Bland–Altman plots were reported. Statistical analysis was conducted using a 2-way ANOVA model with correction for multiple comparisons. Results: When comparing a standard OSEM reconstruction of 6 iterations/16 subsets and 5 mm filter with Q.Clear with different β values under low counts, the bias and RC were lower for Q.Clear with β100 for the SN (RC = 2.17), Th (RC = 0.08) and GP (RC = 0.22) and with β200 for the St (RC = 0.14), Cd (RC = 0.18)and Pt (RC = 0.10). The p-values in the 2-way ANOVA model corroborate these findings. ICC values obtained for Th, St, GP, Pt and Cd demonstrate good reliability (0.87, 0.99, 0.96, 0.99 and 0.96, respectively). For the SN, ICC values demonstrate poor reliability (0.43). Conclusion: BPND results obtained from quantitative low count brain PET studies using [11C]PHNO and reconstructed with Q.Clear with β < 400, which is the value used for clinical [18F]FDG whole-body studies, demonstrate the lowest bias versus the typical iterative reconstruction method OSEM

Self-assembly of ClAlPc molecules on moiré-patterned graphene grown on Pt(111)

Phthalocyanines are promising molecules for the development of organic electronic devices, for instance, molecular heterojunctions in organic solar cells or organic field-effect transistors. For an optimum performance of these devices, the molecular ordering on the substrate and the molecular electronic level alignment have been shown as crucial factors. In this work, the self-assembled structure and the electronic structure of chloroaluminum phthalocyanines (ClAlPc) on graphene grown on Pt(111) surfaces have been studied by scanning tunneling microscopy (STM) under ultrahigh vacuum (UHV) and low-temperature conditions. Graphene grown on Pt(111) exhibits multiple moiré patterns with different periodicities, offering a benchmark to investigate the influence of the graphene and the moiré patterns in the ClAlPc ordering. This surface allows to extend previous works performed on graphite and graphene on Cu(100), where no moiré patterns are found. Well-ordered molecular islands exhibiting rotational domains have been observed in the submonolayer regime. The orientation of individual ClAlPc molecules within the structure unit cell has been characterized pointing out to a Cl-Up configuration adopted by the molecules. Our measurements show a correlation between the molecular lattice orientation and the graphene directions, whereas no influence of the underlying moiré patterns has been found. Finally, the ClAlPc electronic structure has been characterized indicating a weak graphene-molecule interactionFinancial support from the Spanish Ministerio de Economía y Competitividad (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER) under grant No. MAT2016-77852-C2-2-R and from the Spanish Ministerio de Ciencia e Innovación, through the “María de Maeztu” Programme for Units of Excellence in R&D (grant No. CEX2018-000805- M) is gratefully acknowledge

Using Knowledge Management To Gain Competitve Advantage In Jordanian Pharmaceutical Industrial Organization

The ability to store, capture, and disseminate knowledge within and across pharmaceutical organizational boundaries has challenged manager for many years. However, as product lifecycles have decreased and environmental complexity and volatility have increase, the need tom manage knowledge is intensifying, particularly across the value chain. Firm view knowledge and knowledge management as part of their strategic orientation. The difficulties of managing knowledge of are faced by pharmaceutical firms of all size. Low – cost strategies may emphasize knowledge that can be used to cut costs, lower prices, and short cycle times whereas differentiation strategies may emphasize, knowledge that adds value to a product giving it unique characteristics that serve to differentiate it from the competition. This research examines the process of acquisition, retention, maintenance, and retrieval of knowledge both within the firm through organizational memory and across the value chain through knowledge management and compares these practices for small and large firms(Chang, Ching-Hsun,2011) This study focused on the relationship between knowledge management and competitive advantages in pharmaceutical firm, it also reviewed in the research  objectives, and its problems to find out solutions and to write down recommendations and suggestion that may be helpful for others. The study has reviewed some of the assumptions associated with this matter and the theories that worked out for the collection of information is a questionnaire which was adopted in the analysis the final, after collecting the information analyzed used SPSS program and reviewed and discussed the results and explaining them in tables and figures, at the end, results and recommendations reached. Key words: knowledge management, competitive advantage, pharmaceutical organizationa

Descriptive epidemiology of cleft lip and cleft palate in Western Australia

BACKGROUND: Most national and provincial commissions on healthcare services in Canada over the past decade have recommended that primary care services be strengthened in order to guarantee each citizen access to a family physician. Despite these recommendations, finding a family physician continues to be problematic. The issue of enrollment with a family physician is worrying in Canada, where nearly 21% of the country's population reported not having a family physician in the last Commonwealth Fund survey.To respond to this important need, centralized waiting lists have been implemented in four Canadian provinces to help 'orphan,' or unaffiliated, patients find a family physician. These organizational mechanisms are intended to better coordinate the demand for and supply of family physicians. The objectives of this study are: to assess the effects of centralized waiting lists for orphan patients (GACOs) implemented in the province of Quebec and to explain the variation among their effects by analyzing factors influencing implementation process. METHODS: This study is based on two complementary and sequential research strategies. The first (objective 1) is a quantitative longitudinal design to assess the effects of all the GACOs (n = 93) in Quebec using clinical-administrative data. The second (objective 2) involves using four case studies to explain variations in effects through in-depth analysis of the various factors contributing to the observed effects. The primary source of data will be key actors involved in the GACOs. We expect to conduct around 40 semi-structured interviews. DISCUSSION: This will be the first study in Canada to evaluate the implementation of this innovation. It will provide an exhaustive picture of the effects of GACO implementation in Quebec and to assess their potential for generalization elsewhere in Canada. At the theoretical level, this study will produce new knowledge on the factors having the greatest influence on the implementation of primary care innovations in professional environments

Impact of 2009 American Recovery and Reinvestment Act (ARRA) health center investments on disadvantaged neighborhoods after recession

Background: Federally qualified health centers (FQHCs) are integral to the U.S. healthcare safety net and uniquely situated in disadvantaged neighborhoods. The 2009 American Recovery and Reinvestment Act (ARRA) invested $2 billion in FQHC stimulus during the Great Recession; but it remains unknown whether this investment was associated with extended benefits for disadvantaged neighborhoods. Methods: We used a propensity-score matched longitudinal design (2008-2012) to examine whether the 2009 ARRA FQHC investment was associated with local jobs and establishments recovery in FQHC neighborhoods. Job change data were obtained from the Longitudinal Employer-Household Dynamics (LEHD) survey and calculated as an annual rate per 1,000 population. Establishment change data were obtained from the National Neighborhood Data Archive (NaNDA) and calculated as an annual rate per 10,000 population. Establishment data included 4 establishment types: healthcare services, eating/drinking places, retail establishments, and grocery stores. Fixed effects were used to compare annual rates of jobs and establishments recovery between ARRA-funded FQHC census tracts and a matched control group. Results: Of 50,381 tracts, 2,223 contained ≥ 1 FQHC that received ARRA funding. A higher proportion of FQHC tracts had an extreme poverty designation (11.6% vs. 5.4%), high unemployment rate (45.4% vs. 30.3%), and > 50% minority racial/ethnic composition (48.1% vs. 36.3%). On average, jobs grew at an annual rate of 3.84 jobs per 1,000 population (95% CI: 3.62,4.06). In propensity-score weighted models, jobs in ARRA-funded tracts grew at a higher annual rate of 4.34 per 1,000 (95% CI: 2.56,6.12) relative to those with similar social vulnerability. We observed persistent decline in non-healthcare establishments (-1.35 per 10,000; 95% CI: -1.68,-1.02); but did not observe decline in healthcare establishments. Conclusions: Direct funding to HCs may be an effective strategy to support healthcare establishments and some jobs recovery in disadvantaged neighborhoods during recession, reinforcing the important multidimensional roles HCs play in these communities. However, HCs may benefit from additional investments that target upstream determinants of health to mitigate uneven recovery and neighborhood decline.</p

Interleukin-1β Disruption Protects Male Mice From Heart Failure With Preserved Ejection Fraction Pathogenesis

Background: Heart failure with preserved ejection fraction (HFpEF) is a significant unmet need in cardiovascular medicine and remains an untreatable cardiovascular disease. The role and mechanism of interleukin-1β in HFpEF pathogenesis are poorly understood. Methods and Results: C57/Bl6J and interleukin-1β(-/-) male mice were randomly divided into 4 groups. Groups 1 and 2: C57/Bl6J and interleukin-1β(-/-) mice were fed a regular diet for 4 months and considered controls. Groups 3 and 4: C57/Bl6 and interleukin-1β(-/-) mice were fed a high-fat diet with N[w]-nitro-l-arginine methyl ester (endothelial nitric oxide synthase inhibitor, 0.5 g/L) in the drinking water for 4 months. We measured body weight, blood pressure, diabetes status, cardiac function/hypertrophy/inflammation, fibrosis, vascular endothelial function, and signaling. C57/Bl6 fed a high-fat diet and N[w]-nitro-l-arginine methyl ester in the drinking water for 4 months developed HFpEF pathogenesis characterized by obesity, diabetes, hypertension, cardiac hypertrophy, lung edema, low running performance, macrovascular and microvascular endothelial dysfunction, and diastolic cardiac dysfunction but no change in cardiac ejection fraction compared with control mice. Interestingly, the genetic disruption of interleukin-1β protected mice from HFpEF pathogenesis through the modulation of the inflammation and endoplasmic reticulum stress mechanisms. Conclusions: Our data suggest that interleukin-1β is a critical driver in the development of HFpEF pathogenesis, likely through regulating inflammation and endoplasmic reticulum stress pathways. Our findings provide a potential therapeutic target for HFpEF treatment