534 research outputs found

    Scheduling MapReduce Jobs under Multi-Round Precedences

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    We consider non-preemptive scheduling of MapReduce jobs with multiple tasks in the practical scenario where each job requires several map-reduce rounds. We seek to minimize the average weighted completion time and consider scheduling on identical and unrelated parallel processors. For identical processors, we present LP-based O(1)-approximation algorithms. For unrelated processors, the approximation ratio naturally depends on the maximum number of rounds of any job. Since the number of rounds per job in typical MapReduce algorithms is a small constant, our scheduling algorithms achieve a small approximation ratio in practice. For the single-round case, we substantially improve on previously best known approximation guarantees for both identical and unrelated processors. Moreover, we conduct an experimental analysis and compare the performance of our algorithms against a fast heuristic and a lower bound on the optimal solution, thus demonstrating their promising practical performance

    Prescribing Renally Inappropriate Medication to Hospitalized Geriatric Patients in Makkah, Saudi Arabia

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    Hamsah S Alqashqri,1 Ahmed Siddiqi,2 Halah T Albar,3 Enas H Alfalogy,1,4 Nahla H Hariri,1 Yosra Z Alhindi,5 Asim M Alshanberi,1 Safaa M Alsanosi,5 Alaa H Falemban5 1Department of Community Medicine and Pilgrims Health Care, Faculty of Medicine, Umm Al Qura University, Makkah, Saudi Arabia; 2Department of Internal Medicine, National Guard Hospital, Jeddah, Saudi Arabia; 3Department of Physiology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 4Family Medicine, Faculty of Medicine, Suez-Canal University, Ismailia, Egypt; 5Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al Qura University, Makkah, Saudi ArabiaCorrespondence: Alaa H Falemban, Email [email protected]: As a result of the physiological decline in renal function that comes with age and the common failure to recognise renal insufficiency, older adults aged 65 and above are at increased risk of receiving medications that are inappropriate for their level of renal function which in turn lead to increased risk of adverse effects. Little is known about how many older adults receive medications that are inappropriate for their level of renal function. This study aimed to determine the prevalence of renally inappropriate medications in elderly adults by reviewing patient files and evaluating the appropriateness of medication doses relative to renal function in patients aged ≥ 65 years at inpatient healthcare departments.Methods: A retrospective cross-sectional study of patients aged ≥ 65 years was conducted, covering cases from 2015 to 2021. Patient’s medical records were reviewed, their renal function and medications lists were evaluated, determined whether they had been prescribed at least one renally inappropriate medication based on drug-dosing recommendations for different degrees of renal function.Results: A total of 317 elderly inpatients were included, 10% of whom had received inappropriate doses relative to their renal function. Glomerular filtration rate was associated with inappropriate dosing in this study. Of the patients CKD stage 5, 36.8% had at least one drug administered at an inappropriate dose, while this figure was 6.5% among the patients at CKD stage 1; this difference was statistically significant (p = 0.001).Conclusion: A notable portion of older adults may be at risk of adverse effects due to inappropriate medication dosing related to their renal function. Further studies with large samples, drug use analyses based on comprehensive geriatric references and a prioritisation of actual outcomes over potential outcomes are needed to further determine elderly adults’ exposure to inappropriate drugs.Keywords: older adults, geriatric, inappropriate medication, healthcare outcomes, elderly inpatients, renally inappropriate medication, physiological decline, healthcare evaluation, insufficienc

    Observer-Based State Feedback for Enhanced Insulin Control of Type ‘I’ Diabetic Patients

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    During the past few decades, biomedical modeling techniques have been applied to improve performance of a wide variety of medical systems that require monitoring and control. Diabetes is one of the most important medical problems. This paper focuses on designing a state feedback controller with observer to improve the performance of the insulin control for type ‘I’ diabetic patients. The dynamic model of glucose levels in diabetic patients is a nonlinear model. The system is a typical fourth-order single-input-single-output state space model. Using a linear time invariant controller based on an operating condition is a common method to simplify control design. On the other hand, adaptive control can potentially improve system performance. But it increases control complexity and may create further stability issues. This paper investigates patient models and presents a simplified control scheme using observer-based feedback controllers. By comparing different control schemes, it shows that a properly designed state feedback controller with observer can eliminate the adaptation strategy that the Proportional-Integral-Derivative (PID) controllers need to improve the control performance. Control strategies are simulated and their performance is evaluated in MATLAB and Simulink

    A Markov chain model for changes in users’ assessment of search results

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    Previous research shows that users tend to change their assessment of search results over time. This is a first study that investigates the factors and reasons for these changes, and describes a stochastic model of user behaviour that may explain these changes. In particular, we hypothesise that most of the changes are local, i.e. between results with similar or close relevance to the query, and thus belong to the same ”coarse” relevance category. According to the theory of coarse beliefs and categorical thinking, humans tend to divide the range of values under consideration into coarse categories, and are thus able to distinguish only between cross-category values but not within them. To test this hypothesis we conducted five experiments with about 120 subjects divided into 3 groups. Each student in every group was asked to rank and assign relevance scores to the same set of search results over two or three rounds, with a period of three to nine weeks between each round. The subjects of the last three-round experiment were then exposed to the differences in their judgements and were asked to explain them. We make use of a Markov chain model to measure change in users’ judgments between the different rounds. The Markov chain demonstrates that the changes converge, and that a majority of the changes are local to a neighbouring relevance category. We found that most of the subjects were satisfied with their changes, and did not perceive them as mistakes but rather as a legitimate phenomenon, since they believe that time has influenced their relevance assessment. Both our quantitative analysis and user comments support the hypothesis of the existence of coarse relevance categories resulting from categorical thinking in the context of user evaluation of search results

    Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk

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    Studies in post-mortem human brain tissue have associated major depressive disorder (MDD) with cortical transcriptomic changes, whose potential in vivo impact remains unexplored. To address this translational gap, we recently developed a transcriptome-based polygenic risk score (T-PRS) based on common functional variants capturing ‘depression-like’ shifts in cortical gene expression. Here, we used a non-clinical sample of young adults (n = 482, Duke Neurogenetics Study: 53% women; aged 19.8 ± 1.2 years) to map T-PRS onto brain morphology measures, including Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index, as well as broad MDD risk, indexed by self-reported family history of depression. We conducted side-by-side comparisons with a PRS independently derived from a Psychiatric Genomics Consortium (PGC) MDD GWAS (PGC-PRS), and sought to link T-PRS with diagnosis and symptom severity directly in PGC-MDD participants (n = 29,340, 59% women; 12,923 MDD cases, 16,417 controls). T-PRS was associated with smaller amygdala volume in women (t = −3.478, p = 0.001) and lower prefrontal gyrification across sexes. In men, T-PRS was associated with hypergyrification in temporal and occipital regions. Prefrontal hypogyrification mediated a male-specific indirect link between T-PRS and familial depression (b = 0.005, p = 0.029). PGC-PRS was similarly associated with lower amygdala volume and cortical gyrification; however, both effects were male-specific and hypogyrification emerged in distinct parietal and temporo-occipital regions, unassociated with familial depression. In PGC-MDD, T-PRS did not predict diagnosis (OR = 1.007, 95% CI = [0.997–1.018]) but correlated with symptom severity in men (rho = 0.175, p = 7.957 × 10−4) in one cohort (N = 762, 48% men). Depression-like shifts in cortical gene expression have sex-specific effects on brain morphology and may contribute to broad depression vulnerability in men

    Oxidative Stress and NF-κB signaling are involved in LPS induced pulmonary dysplasia in chick embryos

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    Inflammation or dysbacteriosis-derived lipopolysaccharides (LPS) adversely influence the embryonic development of respiratory system. However, the precise pathological mechanisms still remain to be elucidated. In this study, we demonstrated that LPS exposure caused lung maldevelopment in chick embryos, including higher embryo mortality, increased thickness of alveolar gas exchange zone, and accumulation of PAS+ immature pulmonary cells, accompanied with reduced expression of alveolar epithelial cell markers and lamellar body count. Upon LPS exposure, pulmonary cell proliferation was significantly altered and cell apoptosis was inhibited as well, indicating a delayed progress of pulmonary development. LPS treatment also resulted in reduced CAV-1 expression and up-regulation of Collagen I, suggesting increased lung fibrosis, which was verified by Masson staining. Moreover, LPS induced enhanced Nrf2 expression in E18 lungs, and the increased reactive oxygen species (ROS) production was confirmed in MLE-12 cells in vitro. Antioxidant vitamin C restored the LPS induced down-regulation of ABCA3, SP-C and GATA-6 in MLE-12 cells. Furthermore, LPS induced activation of NF-κB signaling in MLE-12 cells, and the LPS-induced decrease in SP-C expression was partially abrogated by blocking NF-κB signaling with Bay-11-7082. Bay-11-7082 also inhibited LPS-induced increases of ROS and Nrf2 expression. Taken together, we have demonstrated that oxidative stress and NF-κB signaling are involved in LPS induced disruption of pulmonary cell development in chick embryos

    Cerebrospinal Fluid Concentration of Brain-Derived Neurotrophic Factor and Cognitive Function in Non-Demented Subjects

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    Brain-derived neurotrophic factor (BDNF) is an activity-dependent secreted protein that is critical to organization of neuronal networks and synaptic plasticity, especially in the hippocampus. We tested hypothesis that reduced CSF BDNF is associated with age-related cognitive decline.CSF concentration of BDNF, Abeta(42) and total tau were measured in 128 cognitively normal adults (Normals), 21 patients with Alzheimer's disease (AD), and nine patients with Mild Cognitive Impairment. Apolipoprotein E and BDNF SNP rs6265 genotype were determined. Neuropsychological tests were performed at baseline for all subjects and at follow-up visits in 50 Normals. CSF BDNF level was lower in AD patients compared to age-matched Normals (p = 0.02). CSF BDNF concentration decreased with age among Normals and was higher in women than men (both p<0.001). After adjusting for age, gender, education, CSF Abeta(42) and total tau, and APOE and BDNF genotypes, lower CSF BDNF concentration was associated poorer immediate and delayed recall at baseline (both p<0.05) and in follow up of approximately 3 years duration (both p<0.01).Reduced CSF BDNF was associated with age-related cognitive decline, suggesting a potential mechanism that may contribute in part to cognitive decline in older individuals

    PRKCA Polymorphism Changes the Neural Basis of Episodic Remembering in Healthy Individuals

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    Everyday functioning relies on episodic memory, the conscious retrieval of past experiences, but this crucial cognitive ability declines severely with aging and disease. Vulnerability to memory decline varies across individuals however, producing differences in the time course and severity of memory problems that complicate attempts at diagnosis and treatment. Here we identify a key source of variability, by examining gene dependent changes in the neural basis of episodic remembering in healthy adults, targeting seven polymorphisms previously linked to memory. Scalp recorded Event-Related Potentials (ERPs) were measured while participants remembered words, using an item recognition task that requires discrimination between studied and unstudied stimuli. Significant differences were found as a consequence of a Single Nucleotide Polymorphism (SNP) in just one of the tested genes, PRKCA (rs8074995). Participants with the common G/G variant exhibited left parietal old/new effects, which are typically seen in word recognition studies, reflecting recollection-based remembering. During the same stage of memory retrieval participants carrying a rarer A variant exhibited an atypical pattern of brain activity, a topographically dissociable frontally-distributed old/new effect, even though behavioural performance did not differ between groups. Results replicated in a second independent sample of participants. These findings demonstrate that the PRKCA genotype is important in determining how episodic memories are retrieved, opening a new route towards understanding individual differences in memory

    Evolutionism and genetics of posttraumatic stress disorder

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    The authors discuss, from the evolutionary concept, how flight and fight responses and tonic immobility can lead to a new understanding of posttraumatic stress disorder. Through the analysis of symptom clusters (revivals, avoidance and hyperexcitation), neurobiological and evolutionary findings are correlated. The current discoveries on posttraumatic stress disorder genetics are summarized and analyzed in this evolutionary perspective, using concepts to understand the gene-environment interaction, such as epigenetic. The proposal is that the research of susceptibility factors in posttraumatic stress disorder must be investigated from the factorial point of view, where their interactions increase the risk of developing the disorder, preventing a unique search of the cause of this disorder. The research of candidate genes in posttraumatic stress disorder must take into consideration all the systems associated with processes of stress response, such as the hypothalamus-pituitary-adrenal and sympathetic axes, mechanisms of learning, formation and extinguishing of declarative memories, neurogenesis and apoptosis, which involve many systems of neurotransmitters, neuropeptides and neurohormones.Os autores discutem, a partir do conceito evolutivo, como a resposta de estresse, nas suas possibilidades de fuga e luta e de imobilidade tônica, pode levar a uma nova compreensão etiológica do transtorno de estresse pós-traumático. Através da análise dos agrupamentos de sintomas desse diagnóstico - revivência, evitação e hiperexcitação -, procuram correlacionar os achados neurobiológicos e evolutivos. As descobertas atuais sobre a genética do transtorno de estresse pós-traumático são resumidas e colocadas nessa perspectiva evolutiva, dentro de conceitos que possibilitam o entendimento da interação gene/ambiente, como a epigenética. Propõem que a pesquisa dos fatores de risco do transtorno de estresse pós-traumático deva ser investigada do ponto de vista fatorial, onde a somatória destes aumenta o risco de desenvolvimento do quadro, não sendo possível a procura da causa do transtorno de forma única. A pesquisa de genes candidatos no transtorno de estresse pós-traumático deve levar em consideração todos os sistemas associados aos processos de respostas ao estresse, sistemas dos eixos hipotálamo-hipofisário-adrenal e simpático, mecanismos de aprendizado, formação de memórias declarativas, de extinção e esquecimento, da neurogênese e da apoptose, que envolvem vários sistemas de neurotransmissores, neuropeptídeos e neuro-hormônios.Universidade Federal de São Paulo (UNIFESP)(UNIFESP)UNIFESP Departamento de PsiquiatriaUniversidade de São Paulo Faculdade de Medicin Hospital de ClínicasUNIFESP, Depto. de PsiquiatriaSciEL

    Evidence for biological roots in the transgenerational transmission of intimate partner violence

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    Intimate partner violence is a ubiquitous and devastating phenomenon for which effective interventions and a clear etiological understanding are still lacking. A major risk factor for violence perpetration is childhood exposure to violence, prompting the proposal that social learning is a major contributor to the transgenerational transmission of violence. Using an animal model devoid of human cultural factors, we showed that male rats became highly aggressive against their female partners as adults after exposure to non-social stressful experiences in their youth. Their offspring also showed increased aggression toward females in the absence of postnatal father–offspring interaction or any other exposure to violence. Both the females that cohabited with the stressed males and those that cohabited with their male offspring showed behavioral (including anxiety- and depression-like behaviors), physiological (decreased body weight and basal corticosterone levels) and neurobiological symptoms (increased activity in dorsal raphe serotonergic neurons in response to an unfamiliar male) resembling the alterations described in abused and depressed women. With the caution required when translating animal work to humans, our findings extend current psychosocial explanations of the transgenerational transmission of intimate partner violence by strongly suggesting an important role for biological factors
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