A Concept of Modeling a Health Manpower Educational System

The paper presents some mathematical concepts of modeling a health manpower educational system. The importance of manpower resources, i.e., doctors, nurses, and other supporting staff, in the health services delivery process is widely recognized. Therefore, the research on resource supply models analyzing health manpower education was undertaken. First, the general structure of the health manpower educational system (HMES) was presented. Next the adapted methodology of modeling was described, followed by mare detailed presentations of: secondary medical school subsystems; medical academy subsystems; and postgraduate courses. Numerical examples from Poland of the application of proposed simulation techniques to medical academies were given. In addition, the forecasts of the number of medical doctors with Ph.D. degrees were presented. Then the utilization of resources in the education process was briefly described. The paper focused its attention on models for simulation purposes, but an optimization approach to the modeling of an educational system was also presented, proceeding naturally from simulation models

Cost-effectiveness of a mobile health-supported lifestyle intervention for pregnant women with an elevated body mass index

Objective To assess the cost-effectiveness of a mobile health-supported lifestyle intervention compared with usual care. Methods We conducted a cost-effectiveness analysis from the perspective of the publicly-funded health care system. We estimated costs associated with the intervention and health care utilisation from first antenatal care appointment through delivery. We used bootstrap methods to quantify the uncertainty around cost‐effectiveness estimates. Health outcomes assessed in this analysis were gestational weight gain (GWG; kg), incidence of excessive GWG, quality-adjusted life years (QALYs), and incidence of large-for-gestational-age (LGA). Incremental cost-effectiveness ratios (ICERs) were calculated as cost per QALY gained, cost per kg of GWG avoided, cost per case of excessive GWG averted, and cost per case of LGA averted. Results Total mean cost including intervention and health care utilisation was €3745 in the intervention group and €3471 in the control group (mean difference €274, P = 0.08). The ICER was €2914 per QALY gained. Assuming a ceiling ratio of €45,000, the probability that the intervention was cost‐effective based on QALYs was 79%. Cost per kg of GWG avoided was €209. The cost-effectiveness acceptability curve (CEAC) for kg of GWG avoided reached a confidence level of 95% at €905, indicating that if one is willing to pay a maximum of an additional €905 per kg of GWG avoided, there is a 95% probability that the intervention is cost-effective. Costs per case of excessive GWG averted and case of LGA averted were €2117 and €5911, respectively. The CEAC for case of excessive GWG averted and for case of LGA averted reached a confidence level of 95% at €7090 and €25,737, respectively. Conclusions Results suggest that a mobile-health lifestyle intervention could be cost-effective; however, a better understanding of the short- and long-term costs of LGA and excessive GWG is necessary to confirm the results

Characterizing and predicting repeat food consumption behavior for just-in-time interventions

National Research Foundation (NRF) Singapore under its International Research Centres in Singapore Funding Initiativ

Identification of the first in Poland CACNA1A gene mutation in familial hemiplegic migraine. Case report

Introduction Migraine is a common neurological disorder characterized by a particular phenotype, complex pathophysiology and a heterogeneous genetic background. Among several heritable forms, familial hemiplegic migraine is the best described one. In the majority of cases it is caused by mutations in one of three different genes. Case report Clinical symptoms of a 47 year old proband (and independently described in his 20 year old son) as well as differential diagnosis are discussed in the presented report. The most characteristic were recurrent attacks of blurred vision, paresthesias and hemiparesis often accompanied by speech disturbances and followed by severe headache with vomiting. Advanced morphological and genetic procedures were required to exclude MELAS, CADASIL and Call-Fleming syndrome. Finally, the definite diagnosis was possible after the application of the whole exome sequencing technique. It confirmed, for the first time in the Polish population, a heterozygous T666M mutation (c.1997C>T; p.Thr666Met) in the CACNA1A gene in the proband, the proband's son and in several other family members. Conclusion The presented report provides clinical and genetic insight into familial hemiplegic migraine 1 resulting from a mutation in the CACNA1A gene

Hyaline fibromatosis syndrome inducing mutations in the ectodomain of anthrax toxin receptor 2 can be rescued by proteasome inhibitors.

Hyaline Fibromatosis Syndrome (HFS) is a human genetic disease caused by mutations in the anthrax toxin receptor 2 (or cmg2) gene, which encodes a membrane protein thought to be involved in the homeostasis of the extracellular matrix. Little is known about the structure and function of the protein or the genotype-phenotype relationship of the disease. Through the analysis of four patients, we identify three novel mutants and determine their effects at the cellular level. Altogether, we show that missense mutations that map to the extracellular von Willebrand domain or the here characterized Ig-like domain of CMG2 lead to folding defects and thereby to retention of the mutated protein in the endoplasmic reticulum (ER). Mutations in the Ig-like domain prevent proper disulphide bond formation and are more efficiently targeted to ER-associated degradation. Finally, we show that mutant CMG2 can be rescued in fibroblasts of some patients by treatment with proteasome inhibitors and that CMG2 is then properly transported to the plasma membrane and signalling competent, identifying the ER folding and degradation pathway components as promising drug targets for HFS

An evolutionary timeline of the oxytocin signaling pathway.

Oxytocin is a neuropeptide associated with both psychological and somatic processes like parturition and social bonding. Although oxytocin homologs have been identified in many species, the evolutionary timeline of the entire oxytocin signaling gene pathway has yet to be described. Using protein sequence similarity searches, microsynteny, and phylostratigraphy, we assigned the genes supporting the oxytocin pathway to different phylostrata based on when we found they likely arose in evolution. We show that the majority (64%) of genes in the pathway are 'modern'. Most of the modern genes evolved around the emergence of vertebrates or jawed vertebrates (540 - 530 million years ago, 'mya'), including OXTR, OXT and CD38. Of those, 45% were under positive selection at some point during vertebrate evolution. We also found that 18% of the genes in the oxytocin pathway are 'ancient', meaning their emergence dates back to cellular organisms and opisthokonta (3500-1100 mya). The remaining genes (18%) that evolved after ancient and before modern genes were classified as 'medium-aged'. Functional analyses revealed that, in humans, medium-aged oxytocin pathway genes are highly expressed in contractile organs, while modern genes in the oxytocin pathway are primarily expressed in the brain and muscle tissue

A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer's disease

Brain perfusion and blood-brain barrier (BBB) integrity are reduced early in Alzheimer's disease (AD). We performed single nucleus RNA sequencing of vascular cells isolated from AD and non-diseased control brains to characterise pathological transcriptional signatures responsible for this. We show that endothelial cells (EC) are enriched for expression of genes associated with susceptibility to AD. Increased β-amyloid is associated with BBB impairment and a dysfunctional angiogenic response related to a failure of increased pro-angiogenic HIF1A to increased VEGFA signalling to EC. This is associated with vascular inflammatory activation, EC senescence and apoptosis. Our genomic dissection of vascular cell risk gene enrichment provides evidence for a role of EC pathology in AD and suggests that reducing vascular inflammatory activation and restoring effective angiogenesis could reduce vascular dysfunction contributing to the genesis or progression of early AD.</p

Ti alloy with enhanced machinability in UAT turning

Metastable β-titanium alloys such as Ti 15V 3Al 3Cr 3Sn are of great technological interest thanks to their high fatigue strength-to-density ratio. However, their high hardness and poor machinability increase machining costs. Additionally, formation of undesirable long chips increases the machining time. To address those issues, a metastable β-titanium alloy (Ti 15V 3Al 3Cr 2Zr 0.9La) with enhanced machinability was developed to produce short chips even at low cutting speeds. A hybrid ultrasonically assisted machining technique, known to reduce cutting forces, was employed in this study. Cutting force components and surface quality of the finished work-pieces were analyzed for a range of cutting speeds in comparison with those for more traditional Ti 15V 3Al 3Cr 3Sn. The novel alloy demonstrated slightly improved machining characteristics at higher cutting speeds and is now ready for industrial applications