Direct and indirect effects of risks on service-oriented supply chain: a covid-19 pandemic perspective

Purpose - A solid service-oriented foundation is required to make supply chain management a competitive advantage, especially in this Covid-19 pandemic. A well-established service-oriented supply chain becomes more adaptable to changing client expectations. This study aims at analysing the direct and indirect impact of risks on the service-oriented supply chain from a pandemic perspective. Design/methodology/approach - The Q-sort method is applied with the participation of nine top-level managers to initially review the reliability, validity, and unidimensionality of research concepts. Then a questionnaire containing these measuring variables is developed to obtain the opinions of those who are experienced in logistics and supply chain management. These empirical data are analysed based on Structural Equation Modelling (SEM) to evaluate direct and indirect effects of risks on supply chain performance. Findings - The risk is inherent in service-oriented supply chains, affecting both direct and indirect performance. The proposed risk model explains 33.6 percent of Supplier performance, 46.4 percent of Operational performance, 47.1 percent of Customer satisfaction, and 46.5 percent of Finance variation. We found that service-oriented supply chains effectively monitor demand risk. External risk has the smallest impact on supply chain performance measures, whereas demand risk has the smallest effect. That a service-oriented supply chain is focused on meeting customer demand and managing demand-related risks is reinforced by these findings. Research limitations/implications - In the literature on supply chain risk management, resilience studies and disruption management receive less attention than studies on risk assessment and risk mitigation (Katsaliaki et al., 2021). Future supply chain risk management research should differentiate between risk-as an event and/or risk-as a process since they have different periodic effects on response management and resilience. Originality/value - This is a pioneering study lookingJICA - Japan International Cooperation Agency(undefined)This work was supported by the project of “An Empirical Study on Services Value Chain based on the Experiential and Credibility Values” (Grant-in-Aid for Scientific Research (A) No.25240050), and Japanese Government by Japan International Cooperation Agency (JICA) through AUN/SEED-Net Project: 022674.242.2015/JICA-A

Pharmacological and Toxicological Properties of the Potent Oral γ-Secretase Modulator BPN-15606.

Alzheimer's disease (AD) is characterized neuropathologically by an abundance of 1) neuritic plaques, which are primarily composed of a fibrillar 42-amino-acid amyloid-β peptide (Aβ), as well as 2) neurofibrillary tangles composed of aggregates of hyperphosporylated tau. Elevations in the concentrations of the Aβ42 peptide in the brain, as a result of either increased production or decreased clearance, are postulated to initiate and drive the AD pathologic process. We initially introduced a novel class of bridged aromatics referred tγ-secretase modulatoro as γ-secretase modulators that inhibited the production of the Aβ42 peptide and to a lesser degree the Aβ40 peptide while concomitantly increasing the production of the carboxyl-truncated Aβ38 and Aβ37 peptides. These modulators potently lower Aβ42 levels without inhibiting the γ-secretase-mediated proteolysis of Notch or causing accumulation of carboxyl-terminal fragments of APP. In this study, we report a large number of pharmacological studies and early assessment of toxicology characterizing a highly potent γ-secretase modulator (GSM), (S)-N-(1-(4-fluorophenyl)ethyl)-6-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methylpyridazin-3-amine (BPN-15606). BPN-15606 displayed the ability to significantly lower Aβ42 levels in the central nervous system of rats and mice at doses as low as 5-10 mg/kg, significantly reduce Aβ neuritic plaque load in an AD transgenic mouse model, and significantly reduce levels of insoluble Aβ42 and pThr181 tau in a three-dimensional human neural cell culture model. Results from repeat-dose toxicity studies in rats and dose escalation/repeat-dose toxicity studies in nonhuman primates have designated this GSM for 28-day Investigational New Drug-enabling good laboratory practice studies and positioned it as a candidate for human clinical trials

The Smoking Paradox in the Development of Psoriatic Arthritis among Psoriasis Patients – A Population-Based Study

Objectives: Smoking is strongly associated with an increased risk of psoriatic arthritis (PsA) in the general population, but not among psoriasis patients. We sought to clarify the possible methodologic mechanisms behind this paradox. Methods: Using 1995-2015 data from The Health Improvement Network, we performed survival analysis to examine the association between smoking and incident PsA in the general population and among psoriasis patients. We clarified the paradox using mediation analysis and conducted bias sensitivity analyses to evaluate the potential impact of index event bias and quantify its magnitude from uncontrolled/unmeasured confounders. Results: Of 6.65 million subjects without PsA at baseline, 225,213 participants had psoriasis and 7,057 developed incident PsA. Smoking was associated with an increased risk of PsA in the general population (RR, 1.27; 95% CI, 1.19-1.36), but with a decreased risk among psoriasis patients (RR 0.91; 95% CI, 0.85-0.99). Mediation analysis showed that the effect of smoking on the risk of PsA was mediated almost entirely through its effect on psoriasis. Bias sensitivity analyses indicated that even when the relation of uncontrolled confounders to either smoking or PsA was modest (both RRs = ~1.50), it could reverse the biased estimate of effect of smoking among psoriasis patients (RR=0.9). Conclusions: In this large cohort representative of the UK general population, smoking was positively associated with PsA risk in the general population, but negatively associated among psoriasis patients. Conditioning on a causal intermediate variable (psoriasis) can reverse the association between smoking and PsA, explaining the smoking paradox for the risk of PsA among psoriasis patients

Reference Ranges for Bone Mineral Density and Prevalence of Osteoporosis in Vietnamese Men and Women

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the effect of different reference ranges in bone mineral density on the diagnosis of osteoporosis.</p> <p>Methods</p> <p>This cross-sectional study involved 357 men and 870 women aged between 18 and 89 years, who were randomly sampled from various districts within Ho Chi Minh City, Vietnam. BMD at the femoral neck, lumbar spine and whole body was measured by DXA (Hologic QDR4500). Polynomial regression models and bootstraps method were used to determine peak BMD and standard deviation (<it>SD</it>). Based on the two parameters, we computed T-scores (denoted by <it>T</it>_VN) for each individual in the study. A similar diagnosis was also done based on T-scores provided by the densitometer (<it>T</it>_DXA), which is based on the US White population (NHANES III). We then compared the concordance between <it>T</it>_VNand <it>T</it>_DXAin the classification of osteoporosis. Osteoporosis was defined according to the World Health Organization criteria.</p> <p>Results</p> <p>In post-menopausal women, the prevalence of osteoporosis based on femoral neck <it>T</it>_VNwas 29%, but when the diagnosis was based on <it>T</it>_DXA, the prevalence was 44%. In men aged 50+ years, the <it>T</it>_VN-based prevalence of osteoporosis was 10%, which was lower than <it>T</it>_DXA-based prevalence (30%). Among 177 women who were diagnosed with osteoporosis by <it>T</it>_DXA, 35% were actually osteopenia by <it>T</it>_VN. The kappa-statistic was 0.54 for women and 0.41 for men.</p> <p>Conclusion</p> <p>These data suggest that the <it>T-</it>scores provided by the Hologic QDR4500 over-diagnosed osteoporosis in Vietnamese men and women. This over-diagnosis could lead to over-treatment and influence the decision of recruitment of participants in clinical trials.</p

Advancement of photospheric radius expansion and clocked type-I x-ray burst models with the new 22Mg(α,p)25 Al reaction rate determined at Gamow energy

We report the first (in)elastic scattering measurement of $^{25}\mathrm{Al}+p$ with the capability to select and measure in a broad energy range the proton resonances in $^{26}$Si contributing to the $^{22}$Mg$(\alpha,p)$ reaction at type I x-ray burst energies. We measured spin-parities of four resonances above the $\alpha$ threshold of $^{26}$Si that are found to strongly impact the $^{22}$Mg$(\alpha,p)$ rate. The new rate advances a state-of-the-art model to remarkably reproduce light curves of the GS 1826$-$24 clocked burster with mean deviation $<9$ % and permits us to discover a strong correlation between the He abundance in the accreting envelope of photospheric radius expansion burster and the dominance of $^{22}$Mg$(\alpha,p)$ branch.Comment: accepted by Physical Review Letters on 5 August 2021, published 19 October 202

Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study

Statins are commonly used for reducing cardiovascular disease risk but therapeutic benefit and reductions in levels of low-density lipoprotein cholesterol (LDL-C) vary among individuals. Other effects, including reductions in C-reactive protein (CRP), also contribute to treatment response. Metabolomics provides powerful tools to map pathways implicated in variation in response to statin treatment. This could lead to mechanistic hypotheses that provide insight into the underlying basis for individual variation in drug response. Using a targeted lipidomics platform, we defined lipid changes in blood samples from the upper and lower tails of the LDL-C response distribution in the Cholesterol and Pharmacogenetics study. Metabolic changes in responders are more comprehensive than those seen in non-responders. Baseline cholesterol ester and phospholipid metabolites correlated with LDL-C response to treatment. CRP response to therapy correlated with baseline plasmalogens, lipids involved in inflammation. There was no overlap of lipids whose changes correlated with LDL-C or CRP responses to simvastatin suggesting that distinct metabolic pathways govern statin effects on these two biomarkers. Metabolic signatures could provide insights about variability in response and mechanisms of action of statins

Thermal modeling of lesion growth with radiofrequency ablation devices

BACKGROUND: Temperature is a frequently used parameter to describe the predicted size of lesions computed by computational models. In many cases, however, temperature correlates poorly with lesion size. Although many studies have been conducted to characterize the relationship between time-temperature exposure of tissue heating to cell damage, to date these relationships have not been employed in a finite element model. METHODS: We present an axisymmetric two-dimensional finite element model that calculates cell damage in tissues and compare lesion sizes using common tissue damage and iso-temperature contour definitions. The model accounts for both temperature-dependent changes in the electrical conductivity of tissue as well as tissue damage-dependent changes in local tissue perfusion. The data is validated using excised porcine liver tissues. RESULTS: The data demonstrate the size of thermal lesions is grossly overestimated when calculated using traditional temperature isocontours of 42°C and 47°C. The computational model results predicted lesion dimensions that were within 5% of the experimental measurements. CONCLUSION: When modeling radiofrequency ablation problems, temperature isotherms may not be representative of actual tissue damage patterns

Enteric Microbiome Metabolites Correlate with Response to Simvastatin Treatment

Although statins are widely prescribed medications, there remains considerable variability in therapeutic response. Genetics can explain only part of this variability. Metabolomics is a global biochemical approach that provides powerful tools for mapping pathways implicated in disease and in response to treatment. Metabolomics captures net interactions between genome, microbiome and the environment. In this study, we used a targeted GC-MS metabolomics platform to measure a panel of metabolites within cholesterol synthesis, dietary sterol absorption, and bile acid formation to determine metabolite signatures that may predict variation in statin LDL-C lowering efficacy. Measurements were performed in two subsets of the total study population in the Cholesterol and Pharmacogenetics (CAP) study: Full Range of Response (FR), and Good and Poor Responders (GPR) were 100 individuals randomly selected from across the entire range of LDL-C responses in CAP. GPR were 48 individuals, 24 each from the top and bottom 10% of the LDL-C response distribution matched for body mass index, race, and gender. We identified three secondary, bacterial-derived bile acids that contribute to predicting the magnitude of statin-induced LDL-C lowering in good responders. Bile acids and statins share transporters in the liver and intestine; we observed that increased plasma concentration of simvastatin positively correlates with higher levels of several secondary bile acids. Genetic analysis of these subjects identified associations between levels of seven bile acids and a single nucleotide polymorphism (SNP), rs4149056, in the gene encoding the organic anion transporter SLCO1B1. These findings, along with recently published results that the gut microbiome plays an important role in cardiovascular disease, indicate that interactions between genome, gut microbiome and environmental influences should be considered in the study and management of cardiovascular disease. Metabolic profiles could provide valuable information about treatment outcomes and could contribute to a more personalized approach to therapy

The Role of Medical Interpretation on Breast and Cervical Cancer Screening Among Asian American and Pacific Islander Women

We examined whether the impact of medical interpretation services was associated with the receipt of a mammogram, clinical breast exam, and Pap smear. We conducted a large cross-sectional study involving four Asian American and Pacific Islander (AAPI) communities with high proportions of individuals with limited English proficiency (LEP). Participants were recruited from community clinics, churches and temples, supermarkets, and other community gathering sites in Northern and Southern California. Among those that responded, 98% completed the survey rendering a total of 1,708 AAPI women. In a series of multivariate logistic regression models, it was found that women who typically used a medical interpreter had a greater odds of having received a mammogram (odds ratio [OR] = 1.85; 95% confidence interval [CI] = 1.21, 2.83), clinical breast exam (OR = 3.03; 95% CI = 1.82, 5.03), and a Pap smear (OR = 2.34; 95% CI = 1.38, 3.97) than those who did not usually use an interpreter. The study provides support for increasing language access in healthcare settings. In particular, medical interpreters may help increase the utilization of breast and cervical cancer screening among LEP AAPI women