Search results for: polygenic risk score

Authors: Yelin Zhao, Xinxiu Li, Martin Smelik, Oleg Sysoev, Firoj Mahmud, Dina Mansour Aly, Mikael Benson

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Background: Early diagnosis of pancreatic cancer is clinically challenging due to vague, or no symptoms, and lack of biomarkers. Polygenic risk score (PRS) scores may provide a valuable tool to assess increased or decreased risk of PC. This study aimed to develop such PRS by filtering genetic variants identified by GWAS using transcriptional programs identified by single-cell RNA sequencing (scRNA-seq). Methods: ScRNA-seq data from 24 pancreatic ductal adenocarcinoma (PDAC) tumor samples and 11 normal pancreases were analyzed to identify differentially expressed genes (DEGs) in in tumor and microenvironment cell types compared to healthy tissues. Pathway analysis showed that the DEGs were enriched for hundreds of significant pathways. These were clustered into 40 “programs” based on gene similarity, using the Jaccard index. Published genetic variants associated with PDAC were mapped to each program to generate program PRSs (pPRSs). These pPRSs, along with five previously published PRSs (PGS000083, PGS000725, PGS000663, PGS000159, and PGS002264), were evaluated in a European-origin population from the UK Biobank, consisting of 1,310 PDAC participants and 407,473 non-pancreatic cancer participants. Stepwise Cox regression analysis was performed to determine associations between pPRSs with the development of PC, with adjustments of sex and principal components of genetic ancestry. Results: The PDAC genetic variants were mapped to 23 programs and were used to generate pPRSs for these programs. Four distinct pPRSs (P1, P6, P11, and P16) and two published PRSs (PGS000663 and PGS002264) were significantly associated with an increased risk of developing PC. Among these, P6 exhibited the greatest hazard ratio (adjusted HR[95% CI] = 1.67[1.14-2.45], p = 0.008). In contrast, P10 and P4 were associated with lower risk of developing PC (adjusted HR[95% CI] = 0.58[0.42-0.81], p = 0.001, and adjusted HR[95% CI] = 0.75[0.59-0.96], p = 0.019). By comparison, two of the five published PRS exhibited an association with PDAC onset with HR (PGS000663: adjusted HR[95% CI] = 1.24[1.14-1.35], p < 0.001 and PGS002264: adjusted HR[95% CI] = 1.14[1.07-1.22], p < 0.001). Conclusion: Compared to published PRSs, scRNA-seq-based pPRSs may be used not only to assess increased but also decreased risk of PDAC.

Keywords: cox regression, pancreatic cancer, polygenic risk score, scRNA-seq, UK biobank

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Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh

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Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we  also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.

Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI

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Authors: Abhijitsinh Gohil, Kaushal Wadhvaniya, Kuldipsinh Jadeja

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Road Safety is a multi-sectoral and multi-dimensional issue. An effective model can assess the risk associated with highway safety. A questionnaire survey is very essential to identify the events or activities which are causing unsafe condition for traffic on an urban highway. A questionnaire of standard questions including vehicular, human and infrastructure characteristics can be made. Responses from the age wise group of road users can be taken on field. Each question or an event holds a specific risk weightage, which contributes in creating an inappropriate and unsafe flow of traffic. The probability of occurrence of an event can be calculated from the data collected from the road users. Finally, the risk score can be calculated by considering the risk factor and the probability of occurrence of individual event and addition of all risk score for the individual event will give the total risk score of a particular road. Standards for risk score can be made and total risk score can be compared with the standards. Thus road can be categorized based on risk associated and traffic safety on it. With this model, one can assess the need for traffic safety improvement on a given road, and qualitative data can be analysed.

Keywords: probability of occurrence, questionnaire, risk factor, risk score

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Authors: Louise Moles, Steve Riley, Sarah D. Lichenstein, Marzieh Babaeianjelodar, Robert Kohler, Annie Cheng, Corey Horien Abigail Greene, Wenjing Luo, Jonathan Ahern, Bohan Xu, Yize Zhao, Chun Chieh Fan, R. Todd Constable, Sarah W. Yip

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Background: Risks for depression are myriad and include both genetic and brain-based factors. However, relationships between these systems are poorly understood, limiting understanding of disease etiology, particularly at the developmental level. Methods: We use a data-driven machine learning approach connectome-based predictive modeling (CPM) to identify functional connectivity signatures associated with polygenic risk scores for depression (DEP-PRS) among youth from the Adolescent Brain and Cognitive Development (ABCD) study across diverse brain states, i.e., during resting state, during affective working memory, during response inhibition, during reward processing. Results: Using 10-fold cross-validation with 100 iterations and permutation testing, CPM identified connectivity signatures of DEP-PRS across all examined brain states (rho’s=0.20-0.27, p’s<.001). Across brain states, DEP-PRS was positively predicted by increased connectivity between frontoparietal and salience networks, increased motor-sensory network connectivity, decreased salience to subcortical connectivity, and decreased subcortical to motor-sensory connectivity. Subsampling analyses demonstrated that model accuracies were robust across random subsamples of N’s=1,000, N’s=500, and N’s=250 but became unstable at N’s=100. Conclusions: These data, for the first time, identify neural networks of polygenic depression risk in a large sample of youth before the onset of significant clinical impairment. Identified networks may be considered potential treatment targets or vulnerability markers for depression risk.

Keywords: genetics, functional connectivity, pre-adolescents, depression

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Authors: Shumaila Zeb

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The proposed study aims to investigate insolvency risk of commercial banks of Pakistan. Furthermore, it empirically estimates the effect of already implemented financial regulations on the insolvency risk of banks. To carry out the empirical analysis, a balanced bank-level panel data covering the period 2008-2016 is used. The Z-score is used for calculating the insolvency risk of each bank. The panel regression is used to investigate the relationship between financial regulations and insolvency risk of banks. The empirics reveal that the financial regulations enforced by State Bank of Pakistan have significant impacts on the insolvency risk of banks. The results further indicate that loan ratio and reserve ratio are positively and significantly related to the insolvency risk of banks.

Keywords: insolvency risk, Z-score, financial regulations, banks

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Authors: Umesh Kumar Singh, Chanchala Joshi

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With increasing dependency on IT infrastructure, the main objective of a system administrator is to maintain a stable and secure network, with ensuring that the network is robust enough against malicious network users like attackers and intruders. Security risk management provides a way to manage the growing threats to infrastructures or system. This paper proposes a framework for risk level estimation which uses vulnerability database National Institute of Standards and Technology (NIST) National Vulnerability Database (NVD) and the Common Vulnerability Scoring System (CVSS). The proposed framework measures the frequency of vulnerability exploitation; converges this measured frequency with standard CVSS score and estimates the security risk level which helps in automated and reasonable security management. In this paper equation for the Temporal score calculation with respect to availability of remediation plan is derived and further, frequency of exploitation is calculated with determined temporal score. The frequency of exploitation along with CVSS score is used to calculate the security risk level of the system. The proposed framework uses the CVSS vectors for risk level estimation and measures the security level of specific network environment, which assists system administrator for assessment of security risks and making decision related to mitigation of security risks.

Keywords: CVSS score, risk level, security measurement, vulnerability category

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Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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Authors: Iqbal Pramukti, Mamat Lukman, Hasniatisari Harun, Kusman Ibrahim

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Introduction: People living with HIV had a higher risk of osteoporotic fracture than the general population. The purpose of this study was to predict the 10-year risk of fracture among people living with HIV (PLWH) using FRAX™ and to identify characteristics related to the fracture risk. Methodology: This study consisted of 75 subjects. The ten-year probability of major osteoporotic fractures (MOF) and hip fractures was assessed using the FRAX™ algorithm. A cross-tabulation was used to identify the participant’s characteristics related to fracture risk. Results: The overall mean 10-year probability of fracture was 2.4% (1.7) for MOF and 0.4% (0.3) for hip fractures. For MOF score, participants with parents’ hip fracture history, smoking behavior and glucocorticoid use showed a higher MOF score than those who were not (3.1 vs. 2.5; 4.6 vs 2.5; and 3.4 vs 2.5, respectively). For HF score, participants with parents’ hip fracture history, smoking behavior and glucocorticoid use also showed a higher HF score than those who were not (0.5 vs. 0.3; 0.8 vs. 0.3; and 0.5 vs. 0.3, respectively). Conclusions: The 10-year risk of fracture was higher among PLWH with several factors, including the parent’s hip. Fracture history, smoking behavior and glucocorticoid used. Further analysis on determining factors using multivariate regression analysis with a larger sample size is required to confirm the factors associated with the high fracture risk.

Keywords: HIV, PLWH, osteoporotic fractures, hip fractures, 10-year risk of fracture, FRAX

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Authors: Swathi Sampath, V. Kalaichelvi

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The assessment of the risk posed by a borrower to a lender is one of the common problems that financial institutions have to deal with. Consumers vying for a mortgage are generally compared to each other by the use of a number called the Credit Score, which is generated by applying a mathematical algorithm to information in the applicant’s credit report. The higher the credit score, the lower the risk posed by the candidate, and the better he is to be taken on by the lender. The objective of the present work is to use fuzzy logic and linguistic rules to create a model that generates Credit Scores.

Keywords: credit scoring, fuzzy logic, mortgage, risk assessment

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Authors: Ulas Cinar, Omer Faruk Ugurlu, Selcuk Cebi

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Occupational safety risk management is the most important element of a safe working environment. Effective risk management can only be possible with accurate analysis and evaluations. Scoring-based risk assessment methods offer considerable ease of application as they convert linguistic expressions into numerical results. It can also be easily adapted to any field. Contrary to all these advantages, important problems in scoring-based methods are frequently discussed. Effective measurability is one of the most critical problems. Existing methods allow experts to choose a score equivalent to each parameter. Therefore, experts prefer the score of the most likely outcome for risk. However, all other possible consequences are neglected. Assessments of the existing methods express the most probable level of risk, not the real risk of the enterprises. In this study, it is aimed to develop a method that will present a more comprehensive evaluation compared to the existing methods by evaluating the probability and severity scores, all sub-parameters, and potential results, and a new scoring-based method is proposed in the literature.

Keywords: occupational health and safety, risk assessment, scoring based risk assessment method, underground mining, weighted risk scores

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Authors: Eva Kirzner

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Based on outcome studies published over the past two decades, in 2018, the ACC/AHA published new guidelines for the management of hypercholesterolemia that incorporate the use of coronary artery calcium (CAC) scanning as a decision tool for ascertaining which patients may benefit from statin therapy. This use is based on the recognition that the absence of calcium on CAC scanning (i.e., a CAC score of zero) usually signifies the absence of significant atherosclerotic deposits in the coronary arteries. Specifically, in patients with a high risk for atherosclerotic cardiovascular disease (ASCVD), initiation of statin therapy is generally recommended to decrease ASCVD risk. However, among patients with intermediate ASCVD risk, the need for statin therapy is less certain. However, there is a need for new outcome studies that provide evidence that the management of hypercholesterolemia based on these new ACC/AHA recommendations is safe for patients. Based on a Pub-Med and Google Scholar literature search, four relevant population-based or patient-based cohort studies that studied the relationship between CAC scanning, risk assessment or mortality, and statin therapy that were published between 2017 and 2021 were identified (see references). In each of these studies, patients were assessed for their baseline risk for atherosclerotic cardiovascular disease (ASCVD) using the Pooled Cohorts Equation (PCE), an ACC/AHA calculator for determining patient risk based on assessment of patient age, gender, ethnicity, and coronary artery disease risk factors. The combined findings of these four studies provided concordant evidence that a zero CAC score defines patients who remain at low clinical risk despite the non-use of statin therapy. Thus, these new studies confirm the use of CAC scanning as a safe tool for reducing the potential overuse of statin therapy among patients with zero CAC scores. Incorporating these new data suggest the following best practice: (1) ascertain ASCVD risk according to the PCE in all patients; (2) following an initial attempt trial to lower ASCVD risk with optimal diet among patients with elevated ASCVD risk, initiate statin therapy for patients who have a high ASCVD risk score; (3) if the ASCVD score is intermediate, refer patients for CAC scanning; and (4) and if the CAC score is zero among the intermediate risk ASCVD patients, statin therapy can be safely withheld despite the presence of an elevated serum cholesterol level.

Keywords: cholesterol, cardiovascular disease, statin therapy, coronary calcium

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Authors: Carl van Walraven, Meltem Tuna

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Background: Network meta-analysis (NMA) quantifies the relative efficacy of 3 or more interventions from studies containing a subgroup of interventions. This study applied the analytical approach of NMA to quantify the relative accuracy of prediction models with distinct inclusion criteria that are evaluated on a common population (‘concurrent external validation’). Methods: We simulated binary events in 5000 patients using a known risk function. We biased the risk function and modified its precision by pre-specified amounts to create 15 prediction models with varying accuracy and distinct patient applicability. Prediction model accuracy was measured using the Scaled Brier Score (SBS). Overall prediction model accuracy was measured using fixed-effects methods that accounted for model applicability patterns. Prediction model accuracy was summarized as the Network Relative Model Accuracy (NeRMA) Score which ranges from -∞ through 0 (accuracy of random guessing) to 1 (accuracy of most accurate model in concurrent external validation). Results: The unbiased prediction model had the highest SBS. The NeRMA score correctly ranked all simulated prediction models by the extent of bias from the known risk function. A SAS macro and R-function was created to implement the NeRMA Score. Conclusions: The NeRMA Score makes it possible to quantify the accuracy of binomial prediction models having distinct inclusion criteria in a concurrent external validation.

Keywords: prediction model accuracy, scaled brier score, fixed effects methods, concurrent external validation

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Authors: Mohamed Hamada Abdelkader Fayed

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Background: To evaluate the diagnostic accuracy of (ADD-RS) with D-dimer as a screening test to exclude AAS. Methods: We conducted research for the studies examining the diagnostic accuracy of (ADD- RS)+ D-dimer to exclude the diagnosis of AAS, We searched MEDLINE, Embase, and Cochrane of Trials up to 31 December 2020. Results: We identified 3 studies using (ADD-RS) with D-dimer as a diagnostic tool for AAS, involving 3261 patients were AAS was diagnosed in 559(17.14%) patients. Overall results showed that the pooled sensitivities were 97.6 (95% CI 0.95.6, 99.6) at (ADD-RS)≤1(low risk group) with D-dimer and 97.4(95% CI 0.95.4,, 99.4) at (ADD-RS)>1(High risk group) with D-dimer., the failure rate was 0.48% at low risk group and 4.3% at high risk group respectively. Conclusions: (ADD-RS) with D-dimer was a useful screening test with high sensitivity to exclude Acute Aortic Syndrome.

Keywords: aortic dissection detection risk score, D-dimer, acute aortic syndrome, diagnostic accuracy

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Authors: Thidathit Prachanukool, Chaiyaporn Yuksen, Welawat Tienpratarn, Sorravit Savatmongkorngul, Panvilai Tangkulpanich, Chetsadakon Jenpanitpong, Yuranan Phootothum, Malivan Phontabtim, Promphet Nuanprom

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Background: Ruptured appendicitis has a high morbidity and mortality and requires immediate surgery. The Alvarado Score is used as a tool to predict the risk of acute appendicitis, but there is no such score for predicting rupture. This study aimed to developed the prediction score to determine the likelihood of ruptured appendicitis in an Asian population. Methods: This study was diagnostic, retrospectively cross-sectional and exploratory model at the Emergency Medicine Department in Ramathibodi Hospital between March 2016 and March 2018. The inclusion criteria were age >15 years and an available pathology report after appendectomy. Clinical factors included gender, age>60 years, right lower quadrant pain, migratory pain, nausea and/or vomiting, diarrhea, anorexia, fever>37.3°C, rebound tenderness, guarding, white blood cell count, polymorphonuclear white blood cells (PMN)>75%, and the pain duration before presentation. The predictive model and prediction score for ruptured appendicitis was developed by multivariable logistic regression analysis. Result: During the study period, 480 patients met the inclusion criteria; of these, 77 (16%) had ruptured appendicitis. Five independent factors were predictive of rupture, age>60 years, fever>37.3°C, guarding, PMN>75%, and duration of pain>24 hours to presentation. A score > 6 increased the likelihood ratio of ruptured appendicitis by 3.88 times. Conclusion: Using the Ramathibodi Welawat Ruptured Appendicitis Score. (RAMA WeRA Score) developed in this study, a score of > 6 was associated with ruptured appendicitis.

Keywords: predictive model, risk score, ruptured appendicitis, emergency room

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Authors: Yusra Pintaningrum, Ilma Fahira Basyir, Sony Hilal Wicaksono, Vito A. Damay

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Background: Coronary artery calcium (CAC) scores play an important role in improving prognostic accuracy and can be selectively used to guide the allocation of statin therapy for atherosclerotic cardiovascular disease outcomes and potentially associated with the occurrence of MACE (Major Adverse Cardiovascular Event) and MI (Myocardial Infarction). Objective: This systematic review and meta-analysis aim to analyze the findings of a study about CAC Score and statin treatment effect on MI and MACE risk. Methods: Search for published scientific articles using the PRISMA (Preferred Reporting, Items for Systematic Reviews and Meta-Analysis) method conducted on PubMed, Cochrane Library, and Medline databases published in the last 20 years on “coronary artery calcium” AND “statin” AND “cardiovascular disease” Further systematic review and meta-analysis using RevMan version 5.4 were performed based on the included published scientific articles. Results: Based on 11 studies included with a total of 1055 participants, we performed a meta-analysis and found that individuals with CAC score > 0 increased risk ratio of MI 8.48 (RR = 9.48: 95% CI: 6.22 – 14.45) times and MACE 2.48 (RR = 3.48: 95% CI: 2.98 – 4.05) times higher than CAC score 0 individual. Statin compared against non-statin treatment showed a statistically insignificant overall effect on the risk of MI (P = 0.81) and MACE (P = 0.89) in an individual with elevated CAC score 1 – 100 (P = 0.65) and > 100 (P = 0.11). Conclusions: This study found that an elevated CAC scores individual has a higher risk of MI and MACE than a non-elevated CAC score individual. There is no significant effect of statin compared against non-statin treatment to reduce MI and MACE in elevated CAC score individuals of 1 – 100 or > 100.

Keywords: coronary artery calcium, statin, cardiovascular disease, myocardial infarction, MACE

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Authors: A. Shirazibeheshti, T. Radwan, A. Ettefaghian, G. Wilson, C. Luca, Farbod Khanizadeh

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Anticholinergic medication has been associated with events such as falls, delirium, and cognitive impairment in older patients. To further assess this, anticholinergic burden scores have been developed to quantify risk. A risk model based on clustering was deployed in a healthcare management system to cluster patients into multiple risk groups according to anticholinergic burden scores of multiple medicines prescribed to patients to facilitate clinical decision-making. To do so, anticholinergic burden scores of drugs were extracted from the literature, which categorizes the risk on a scale of 1 to 3. Given the patients’ prescription data on the healthcare database, a weighted anticholinergic risk score was derived per patient based on the prescription of multiple anticholinergic drugs. This study was conducted on over 300,000 records of patients currently registered with a major regional UK-based healthcare provider. The weighted risk scores were used as inputs to an unsupervised learning algorithm (mean-shift clustering) that groups patients into clusters that represent different levels of anticholinergic risk. To further evaluate the performance of the model, any association between the average risk score within each group and other factors such as socioeconomic status (i.e., Index of Multiple Deprivation) and an index of health and disability were investigated. The clustering identifies a group of 15 patients at the highest risk from multiple anticholinergic medication. Our findings also show that this group of patients is located within more deprived areas of London compared to the population of other risk groups. Furthermore, the prescription of anticholinergic medicines is more skewed to female than male patients, indicating that females are more at risk from this kind of multiple medications. The risk may be monitored and controlled in well artificial intelligence-equipped healthcare management systems.

Keywords: anticholinergic medicines, clustering, deprivation, socioeconomic status

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Authors: Hongmeng Su, Luyu Zhao, Yanyan Qian, Hong Fan

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Aim: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors that endanger human health seriously. RNA methylation, especially N6-methyladenosine (m⁶A) and 5-methylcytosine (m⁵C), a crucial epigenetic transcriptional regulatory mechanism, plays an important role in tumorigenesis, progression and prognosis. This research aims to systematically evaluate the prognostic value of m⁶A and m⁵C modulators in HCC patients. Methods: Twenty-four modulators of m⁶A and m⁵C were candidates to analyze their expression level and their contribution to predict the prognosis of HCC. Consensus clustering analysis was applied to classify HCC patients. Cox and LASSO regression were used to construct the risk model. According to the risk score, HCC patients were divided into high-risk and low/medium-risk groups. The clinical pathology factors of HCC patients were analyzed by univariate and multivariate Cox regression analysis. Results: The HCC patients were classified into 2 clusters with significant differences in overall survival and clinical characteristics. Nine-gene risk model was constructed including METTL3, VIRMA, YTHDF1, YTHDF2, NOP2, NSUN4, NSUN5, DNMT3A and ALYREF. It was indicated that the risk score could serve as an independent prognostic factor for patients with HCC. Conclusion: This study constructed a Nine-gene risk model by modulators of m⁶A and m⁵C and investigated its effect on the clinical prognosis of HCC. This model may provide important consideration for the therapeutic strategy and prognosis evaluation analysis of patients with HCC.

Keywords: hepatocellular carcinoma, m⁶A, m⁵C, prognosis, RNA methylation

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Authors: Pubudu K. Hitigala Kaluarachchilage, Champike Attanayake, Sasith Rajasooriya, Chris P. Tsokos

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Operating system (OS) security is a key component of computer security. Assessing and improving OSs strength to resist against vulnerabilities and attacks is a mandatory requirement given the rate of new vulnerabilities discovered and attacks occurring. Frequency and the number of different kinds of vulnerabilities found in an OS can be considered an index of its information security level. In the present study five mostly used OSs, Microsoft Windows (windows 7, windows 8 and windows 10), Apple’s Mac and Linux are assessed for their discovered vulnerabilities and the risk associated with each. Each discovered and reported vulnerability has an exploitability score assigned in CVSS score of the national vulnerability database. In this study the risk from vulnerabilities in each of the five Operating Systems is compared. Risk Indexes used are developed based on the Markov model to evaluate the risk of each vulnerability. Statistical methodology and underlying mathematical approach is described. Initially, parametric procedures are conducted and measured. There were, however, violations of some statistical assumptions observed. Therefore the need for non-parametric approaches was recognized. 6838 vulnerabilities recorded were considered in the analysis. According to the risk associated with all the vulnerabilities considered, it was found that there is a statistically significant difference among average risk levels for some operating systems, indicating that according to our method some operating systems have been more risk vulnerable than others given the assumptions and limitations. Relevant test results revealing a statistically significant difference in the Risk levels of different OSs are presented.

Keywords: cybersecurity, Markov chain, non-parametric analysis, vulnerability, operating system

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Authors: Ahmet Parlak, Celalettin Bilgen

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In order to create an effective early warning system, Identification of the risks, preparation and carrying out risk modeling of risk scenarios, taking into account the shortcomings of the old disaster scenarios should be used to improve the system. In the light of this, the importance of risk modeling in creating an effective early warning system is understood. In the scope of TAFRISK project risk modeling trend analysis report on risk modeling developed and a demonstration was conducted for Risk Modeling for flood and mass movements. For risk modeling R&D, studies have been conducted to determine the information, and source of the information, to be gathered, to develop algorithms and to adapt the current algorithms to Turkey’s conditions for determining the risk score in the high disaster risk areas. For each type of the disaster; Disaster Deficit Index (DDI), Local Disaster Index (LDI), Prevalent Vulnerability Index (PVI), Risk Management Index (RMI) have been developed as disaster indices taking danger, sensitivity, fragility, and vulnerability, the physical and economic damage into account in the appropriate scale of the respective type.

Keywords: disaster, hazard, risk modeling, sensor

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Authors: Yu-Chuan Huang

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Introduction: There is a higher mortality rate for unplanned transfer to intensive care units. It also needs a longer length of stay and makes the intensive care unit beds cannot be effectively used. It affects the immediate medical treatment of critically ill patients, resulting in a drop in the quality of medical care. Purpose: The purpose of this study was using SOFA and APACHEII score to analyze the mortality rate of the cases transferred from ED to ICU. According to the score that should be provide an appropriate care as early as possible. Methods: This study was a descriptive experimental design. The sample size was estimated at 220 to reach a power of 0.8 for detecting a medium effect size of 0.30, with a 0.05 significance level, using G-power. Considering an estimated follow-up loss, the required sample size was estimated as 242 participants. Data were calculated by medical system of SOFA and APACHEII score that cases transferred from ED to ICU in 2016. Results: There were 233 participants meet the study. The medical records showed 33 participants’ mortality. Age and sex with QSOFA , SOFA and sex with APACHEII showed p>0.05. Age with APCHHII in ED and ICU showed r=0.150, 0,268 (p < 0.001**). The score with mortality risk showed: ED QSOFA is r=0.235 (p < 0.001**), exp(B)=1.685(p = 0.007); ICU SOFA 0.78 (p < 0.001**), exp(B)=1.205(p < 0.001). APACHII in ED and ICU showed r= 0.253, 0.286 (p < 0.001**), exp(B) = 1.041,1.073(p = 0.017,0.001). For SOFA, a cutoff score of above 15 points was identified as a predictor of the 95% mortality risk. Conclusions: The SOFA and APACHE II were calculated based on initial laboratory data in the Emergency Department, and during the first 24 hours of ICU admission. In conclusion, the SOFA and APACHII score is significantly associated with mortality and strongly predicting mortality. Early predictors of morbidity and mortality, which we can according the predicting score, and provide patients with a detail assessment and proper care, thereby reducing mortality and length of stay.

Keywords: SOFA, APACHEII, mortality, ICU

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Authors: Issam M Hajjaji, Adel Tajoury, Salah R Benhamid

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The MENA region has the highest prevalence of diabetes in the world. Various risk scores were developed, not all appropriate locally. The objective of this study is to apply the FINDRISC Score to adult Libyan males to determine its significance, sensitivity, specificity and Positive Predictive Values as an initial screening tool for type 2 diabetes, and suggest a cut-off point. Methods: 600 subjects answered the questionnaire at their place of work, and their waist, weight, height & BP were measured. Thereafter, after excluding those with known diabetes, an Oral Glucose Tolerance Test was done. Results: 414 subjects aged 19-78 completed the questionnaire and tests. 35 (8.4%) had impaired glucose tolerance (IGT) and 13 (3.1%) had diabetes (DM). The AUC-ROC for IGT was 0.614 (95% CI: 0.527-0.701), for DM 0.810 (95% CI: 0.709-0.911) and for both 0.689 (95% CI: 0.609-0.769). The Positive Predictive Value for a cut-off score of 5 were 15.5%, 11.7% & 5.7% for both conditions combined, prediabetes & diabetes respectively. The equivalent values for a cut-off score of 8 were 16.1%, 9.0% & 7.7%. The Negative Predictive Values were uniformly above 90%. Conclusions & Recommendations: The FINDRISC Score had a low predictive value for dysglycaemia in this sample and performed at a level of significance for IGT that is similar to other MENA countries, but did better for DM. A larger sample that included women is suggested, with a view of adjusting the Score to suit the local population.

Keywords: diabetes, FINDRISK, Libya, prediabetes

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Authors: Swati Srivastava, Ashish Kumar Upadhyay

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Using longitudinal data from three waves of Young Lives Study and Ordinary Least Square methods, study has investigated the effect of birth order and arrival of younger siblings on child development in India. Study used child’s height for age z-score, weight for age z-score, BMI for age z-score, Peabody Picture Vocabulary Test (PPVT-Score)c, maths score, Early Grade Reading Assessment Test (ERGA) score, and memory score to measure the physical and cognitive development of child during wave-3. Findings suggest that having a high birth order is detrimental for child development and the gap between adjacent siblings is larger for children late in the birth sequences than early in the birth sequences. Study also reported that not only older siblings but arrival of younger siblings before assessment of test also reduces the development of a child. The effects become stronger in case of female children than male children.

Keywords: height for age z-score, weight for age z-score, BMI for z-score, PPVT score, math score, EGRA score, memory score, birth order, siblings, Young Lives Study, India

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Authors: Philippe Dillien, Patrice Forget, Harald Engel, Olivier Cornu, Marc De Kock, Jean Cyr Yombi

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Introduction: Hip fracture precedes commonly death in elderly people. Identification of high-risk patients may contribute to target patients in whom optimal management, resource allocation and trials efficiency is needed. The aim of this study is to construct a predictive score of mortality after hip fracture on the basis of the objective prognostic factors available: Neutrophil-to-lymphocyte ratio (NLR), age, and sex. C-Reactive Protein (CRP), is also considered as an alternative to the NLR. Patients and methods: After the IRB approval, we analyzed our prospective database including 286 consecutive patients with hip fracture. A score was constructed combining age (1 point per decade above 74 years), sex (1 point for males), and NLR at postoperative day+5 (1 point if >5). A receiver-operating curve (ROC) curve analysis was performed. Results: From the 286 patients included, 235 were analyzed (72 males and 163 females, 30.6%/69.4%), with a median age of 84 (range: 65 to 102) years, mean NLR values of 6.47+/-6.07. At one year, 82/280 patients died (29.3%). Graphical analysis and log-rank test confirm a highly statistically significant difference (P<0.001). Performance analysis shows an AUC of 0.72 [95%CI 0.65-0.79]. CRP shows no advantage on NLR. Conclusion: We have developed a score based on age, sex and the NLR to predict the risk of mortality at one year in elderly patients after surgery for a hip fracture. After external validation, it may be included in clinical practice as in clinical research to stratify the risk of postoperative mortality.

Keywords: neutrophil-to-lymphocyte ratio, hip fracture, postoperative mortality, medical and health sciences

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Authors: Mohammad Aziz Shah Mohamed Arip, Aslina Ahmad, Fauziah Mohd Sa'ad, Samsiah Mohd Jais, Syed Sofian Syed Salim

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This experimental study evaluates the effect of using Cognitive-Behavioral Therapy (CBT) and Multidimensional Self-Concept Model (MSCM) in a drug prevention programme to increase resiliency and reduce aggression among at-risk youth in Malaysia. A number of 60 (N=60) university students who were at-risk of taking drugs were involved in this study. Participants were identified with self-rating scales, Adolescent Resilience Attitude Scale (ARAS) and Aggression Questionnaire. Based on the mean score of these instruments, the participants were divided into the treatment group, and the control group. Data were analyzed using t-test. The finding showed that the mean score of resiliency was increased in the treatment group compared to the control group. It also shows that the mean score of aggression was reduced in the treatment group compared to the control group. Drug Prevention Programme was found to help in enhancing resiliency and reducing aggression among participants in the treatment group compared to the controlled group. Implications were given regarding the preventive actions on drug abuse among youth in Malaysia.

Keywords: drug prevention programme, cognitive-behavioral therapy (CBT), multidimensional self concept model (MSCM), resiliency, aggression, at-risk youth

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Authors: Zehra Buyuktuncer, Aylin H. Büyükkaragöz, Tuğçe N. Balcı, Nevin Ergun

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Background: Undergoing rigid dietary habits for enhancing athletic performance could lead to eating disorders. High prevalence of eating disorders among female athletes has been already reported. However, the risk of disordered eating among disabled athletes is not known. A better knowledge of the different eating behaviors and their prevalence in disabled athletes would be helpful to understand interactions between eating and health. This study aimed to examine the cognitive restraint, uncontrolled eating and emotional eating behaviors in a disabled athlete population. Method: A total of 70 disabled Turkish national athletes (33 female, 37 male) from 5 sport branches (soccer, weight lifting, shooting, table tennis and basketball) were involved in the study. The cognitive restraint, uncontrolled eating and emotional eating behaviors were assessed using the revised version of Three Factor Eating Questionnaire-R18 (TFEQ-R18). The questionnaires were conducted by dietitian during the preparation camps of athletes. Body weight, height and waist circumference (WC) were measured; and body composition was analyzed by bioelectrical impedance analysis method. Results: The TFEQ scales showed a cognitive dietary restraint score of 13.9±4.2, uncontrolled eating score of 17.7±5.8 and emotional eating score of 4.9±2.5. The mean score of total TFEQ-R18 was 36.5±8.62. Neither total TFEQ-R18 score nor subscale scores differed significantly by gender or sport branches (p>0.05, for each). The scores were also similar in BMI groups (n=63; p>0.05). Total TFEQ, uncontrolled eating and emotional eating scores were significantly higher among the athletes with congenital disabilities compared to the scores of the athletes with acquired disabilities (p<0.05, for each). Moreover, the cognitive dietary restraint score was significantly high in athletes who would like to lose weight (p=0.009). Conclusion: Disabled athletes might have a risk of disordered eating. The different eating behaviors among disabled athletes should be assessed using validated tools to develop personalized nutritional strategies for those athletes.

Keywords: disabled athletes, eating behaviour, three-factor eating questionnaire-r18, body composition

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Authors: M. V. Shivaani, P. K. Jain, Surendra S. Yadav

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Risk management has been gaining extensive focus from international organizations like Committee of Sponsoring Organizations and Financial Stability Board, and, the foundation of such an effective and efficient risk management system lies in a strong risk governance structure. In view of this, an attempt (perhaps a first of its kind) has been made to develop a risk governance index, which could be used as proxy for quality of risk governance structures. The index (normative framework) is based on eleven variables, namely, size of board, board diversity in terms of gender, proportion of executive directors, executive/non-executive status of chairperson, proportion of independent directors, CEO duality, chief risk officer (CRO), risk management committee, mandatory committees, voluntary committees and existence/non-existence of whistle blower policy. These variables are scored on a scale of 1 to 5 with the exception of the variables, namely, status of chairperson and CEO duality (which have been scored on a dichotomous scale with the score of 3 or 5). In case there is a legal/statutory requirement in respect of above-mentioned variables and there is a non-compliance with such requirement a score of one has been envisaged. Though there is no legal requirement, for the larger part of study, in context of CRO, risk management committee and whistle blower policy, still a score of 1 has been assigned in the event of their non-existence. Recognizing the importance of these variables in context of risk governance structure and the fact that the study basically focuses on risk governance, the absence of these variables has been equated to non-compliance with a legal/statutory requirement. Therefore, based on this the minimum score is 15 and the maximum possible is 55. In addition, an attempt has been made to explore the determinants of this index. For this purpose, the sample consists of non-financial companies (429) that constitute S&P CNX500 index. The study covers a 10 years period from April 1, 2005 to March 31, 2015. Given the panel nature of data, Hausman test was applied, and it suggested that fixed effects regression would be appropriate. The results indicate that age and size of firms have significant positive impact on its risk governance structures. Further, post-recession period (2009-2015) has witnessed significant improvement in quality of governance structures. In contrast, profitability (positive relationship), leverage (negative relationship) and growth (negative relationship) do not have significant impact on quality of risk governance structures. The value of rho indicates that about 77.74% variation in risk governance structures is due to firm specific factors. Given the fact that each firm is unique in terms of its risk exposure, risk culture, risk appetite, and risk tolerance levels, it appears reasonable to assume that the specific conditions and circumstances that a company is beset with, could be the biggest determinants of its risk governance structures. Given the recommendations put forth in the paper (particularly for regulators and companies), the study is expected to be of immense utility in an important yet neglected aspect of risk management.

Keywords: corporate governance, ERM, risk governance, risk management

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Authors: Rohin Rameswarapu, Sameer Valsangkar

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Background: Globally, musculoskeletal disorders are the largest single cause of work-related illnesses accounting for over 33% of all newly reported occupational illnesses. Risk factors for MSD need to be delineated to suggest means for amelioration. Material and methods: In this current cross-sectional study, the prevalence of MSDs among workers in an electrical company assembly line, the socio-demographic and job characteristics associated with MSD were obtained through a semi-structured questionnaire. A quantitative assessment of the physical risk factors through the Rapid Upper Limb Assessment (RULA) tool, and measurement of psychosocial risk factors through a Likert scale was obtained. Statistical analysis was conducted using Epi-info software and descriptive and inferential statistics including chi-square and unpaired t test were obtained. Results: A total of 263 workers consented and participated in the study. Among these workers, 200 (76%) suffered from MSD. Most of the workers were aged between 18–27 years and majority of the workers were women with 198 (75.2%) of the 263 workers being women. A chi square test was significant for association between male gender and MSD with a P value of 0.007. Among the MSD positive group, 4 (2%) had a grand score of 5, 10 (5%) had a grand score of 6 and 186 (93%) had a grand score of 7 on RULA. There were significant differences between the non-MSD and MSD group on five out of the seven psychosocial domains, namely job demand, job monotony, co-worker support, decision control and family and environment domains. Discussion: The current cross-sectional study demonstrates a high prevalence of MSD among assembly line works with inherent physical and psychosocial risk factors and recommends that not only physical risk factors, addressing psychosocial risk factors through proper ergonomic means is also essential to the well-being of the employee.

Keywords: musculoskeletal disorders, India, occupational health, Rapid Upper Limb Assessment (RULA)

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Authors: Thitaporn Thoopputra, Tipaporn Pongmesa, Shuchuen Li

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Aims: To evaluate the application of non-invasive diabetes risk assessment tool in community pharmacy setting. Methods: Thai diabetes risk score was applied to assess individuals at risk of developing type 2 diabetes. Interactive computer-based risk screening (IT) and paper-based risk screening (PT) tools were applied. Participants aged over 25 years with no known diabetes were recruited in six participating pharmacies. Results: A total of 187 clients, mean aged (+SD) was 48.6 (+10.9) years. 35% were at high risk. The mean value of willingness-to-pay for the service fee in IT group was significantly higher than PT group (p=0.013). No significant difference observed for the satisfaction between groups. Conclusions: Non-invasive risk assessment tool, whether paper-based or computerized-based can be applied in community pharmacy to support the enhancing role of pharmacists in chronic disease management. Long term follow up is needed to determine the impact of its application in clinical, humanistic and economic outcomes.

Keywords: community pharmacy, intervention, prevention, risk assessment, type 2 diabetes

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Authors: Ahmad Shahfarhat, Ashraf Mohammadzade, Reza Saeedi, Hadi Hesari

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Background: Mothers of infants admitted at NICU are vulnerable to depression (affecting 10 to 20% of mothers during the first year after delivery) As you know, about half of women with prominent postpartum depression (PPD) symptoms are not diagnosed. The Edinburgh Postnatal Depression Scale (EPDS) is the most widely used screening instrument for PPD. In this study, we checked EPDS score of 12 or more on the second day (D2), discharge, day 28(D28), and day42 (D42) postpartum to determine the risk factors as well as the prevalence of PPD in a sample of mothers of NICU admitted neonates. Methods: A sample of 682 women used the EPDS on admission and at discharge. An assessment for PPD was performed on D28 and D42 by a telephone interview. Results: On admission, the average score on EPDS was 9.72 (SD = 4.4), and 27.4% of women (187) had an EPDS score ≥12. On Discharge, 4weeks and 6weeks postpartum the average score was ordinary 9.34 (SD = 3.8), 9.12 (SD = 3.7), 8.52(SD = 3.36), and (173)25.4 %,( 141)23.3 %,( 88)15.3% of women presented with PPD. a positive correlation was found between scores on EPDS on admission and D42 (P = 0.001). An analysis shows that mothers of twins (P = 0.001) and higher age mothers (P=0.001) are significantly associated with PPD. Conclusion: Women with EPDS score more than 12 and/or older will benefit from a closer follow-up during the rest of the post-partum period, and it is better to be under psychological support.

Keywords: NICU, depression, pregnancy, mothers

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Authors: Yuki Irie, Shota Ogawa, Hitomi Kosugi, Hiromitsu Shinozaki

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Background: Dropout from higher educational institutions is a major problem both for students and institutions, and poor mental health is one of the risk factors. Medical college students are at higher risk of poor mental health than general students because of their hard academic schedules. On the other hand, food insecurity has negative impacts on mental health. The healthcare college of the project site is located heavily snowy area. The students without own vehicles may be at higher risk of food insecurity, especially in the winter season. Therefore, they have many risks to mental health. The aim of the study is to clarify the relationship between mental health and its risk factors to promote students’ mental well-being. Method: A cross-sectional design was used to investigate the relationship between mental health status and lifestyle, including diet and food security among the students (n=421, 147 male, 274 females; 20.7 ± 2.8 years old). Participants were required to answer 3 questionnaires which consisted of diet, lifestyle, food security, and mental health. The survey was conducted during the snowy season from Dec. 2022 to Jan. 2023. Results: Mean mental score was 6.7±4.6 (max. score 27, a higher score means worse mental health). Significant risk factors in mental health were breakfast habit (p=0.02), subjective dietary habit (p=0.00), subjective health (p=0.00), exercise habit (p=0.02), food insecurity in the winter season (p=0.01), and vitamin A intakes (p=0.03). Conclusions: Nutrients intakes are not associated with mental health except vitamin A; however, some other lifestyle factors are significantly associated with mental health. Nutrition doesn’t lead to poor mental health directly; however, the promotion of a healthy lifestyle and improved food security in winter may be effective in better mental health.

Keywords: mental health, winter, lifestyle, students

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