MACHINE-LEARNING AND STATISTICAL SUBGROUP ANALYSES OF VASOPRESSOR CHOICE FOR THE TREATMENT OF NON-TRAUMATIC SUBARACHNOID HEMORRHAGE USING ELECTRONIC HEALTH RECORDS

Abstract: Subarachnoid hemorrhage (SAH) is a life-threatening stroke caused by bleeding in the subarachnoid space. Delayed cerebral ischemia, a risk factor for death during non-traumatic SAH treatment, is often prevented by inducing hemodynamic augmentation through the administration of vasopressors. The three common vasopressors administrated to SAH patients are dopamine, phenylephrine, and norepinephrine. A recent study using Electronic Health Records (EHR) of nontraumatic SAH patients identified that the administration of phenylephrine is associated with lower hospital mortality; however, this study did not consider heterogeneity in treatment effects. Therefore, the goal of this paper is to study the heterogeneity in vasopressor treatment effects by exploratory subgroup analyses. The subgroups were identified by studying the vasopressor and pretreatment covariates interaction effects. We employed a machine learning and a generalized linear model approach to study the interaction effects. We also employed propensity scoring and inverse probability weighting to minimize the confounding and selection biases in treatment effect estimates due to inherent pretreatment group differences in the data. Our results showed that dopamine had the highest mortality among those who did not have ondansetron ( a pretreatment medication used to prevent nausea) compared to phenylephrine and norepinephrine; whereas norepinephrine has the highest mortality among those who had ondansetron compared to phenylephrine and dopamine. However, for the subgroup who did not have ondansetron but had fentanyl and lidocaine, there was no significant difference in the mortality rate between vasopressor treatment group. Overall, those who had ondansetron had better survival compared to those who did not have ondansetron with respect to all the three vasopressors

Role of Long Noncoding RNAs in Diabetic Complications

LncRNAs, recently found to be pervasively transcribed in the genome, can play key roles in epigenetic modifications during gene transcription. Their role in diabetic complications are however not clear. Using array analysis, we identified alterations of two lncRNAs in high glucose (25mM/L,HG) treated retinal endothelial cells (HRECs). ANRIL expressions were further measured with or without siRNA knockdown in ECs. ANRIL knockout (KO) mice with or without streptozotocin (STZ)-induced diabetes were also investigated for mRNA and protein expression of VEGF and ECM proteins FN and Col1α4. ANRIL knockdown prevented glucose-induced increased VEGF, FN and Col1α4 levels. Comparable results were observed in the retina, heart and kidneys of diabetic ANRILKO mice compared to wildtype controls. We further showed that these alterations under ANRIL’s regulation are mediated by p300 and enhancer of zeste 2 (EZH2) of the PRC2 complex. We also investigated the role of H19 in diabetes by silencing or overexpressing H19 in ECs exposed to various glucose levels. We extended our study to H19 knockout (KO) mice and vitreous samples from patients with proliferative DR. In both instances, diabetes caused downregulation of H19 expression. H19 overexpression prevented glucose-induced endothelial-mesenchymal transition (EndMT) through TGF-β in a Smad-independent pathway. Additional experiments showed a regulatory relationship between ANRIL and H19. These data suggest that glucose and diabetes cause alteration of specific lncRNAs in ECs and mouse tissues respectively. Identification of such mechanisms help in a better understanding of the pathologies in diabetes and consequent development of RNA based therapies

Ultimate Order Statistics-Based Prototype Reduction Schemes

The objective of Prototype Reduction Schemes (PRSs) and Border Identification (BI) algorithms is to reduce the number of training vectors, while simultaneously attempting to guarantee that the classifier built on the reduced design set performs as well, or nearly as well, as the classifier built on the original design set. In this paper, we shall push the limit on the field of PRSs to see if we can obtain a classification accuracy comparable to the optimal, by condensing the information in the data set into a single training point. We, indeed, demonstrate that such PRSs exist and are attainable, and show that the design and implementation of such schemes work with the recently-introduced paradigm of Order Statistics (OS)-based classifiers. These classifiers, referred to as Classification by Moments of Order Statistics (CMOS) is essentially anti-Bayesian in its modus operandus. In this paper, we demonstrate the power and potential of CMOS to yield single-element PRSs which are either “selective” or “creative”, where in each case we resort to a non-parametric or a parametric paradigm respectively. We also report a single-feature single-element creative PRS. All of these solutions have been used to achieve classification for real-life data sets from the UCI Machine Learning Repository, where we have followed an approach that is similar to the Naïve-Bayes’ (NB) strategy although it is essentially of an anti-Naïve-Bayes’ paradigm. The amazing facet of this approach is that the training set can be reduced to a single pattern from each of the classes which is, in turn, determined by the CMOS features. It is even more fascinating to see that the scheme can be rendered operational by using the information in a single feature of such a single data point. In each of these cases, the accuracy of the proposed PRS-based approach is very close to the optimal Bayes’ bound and is almost comparable to that of the SVM

Pathogenesis of Cholera: Recent Prospectives in Rapid Detection and Prevention of Cholera

Cholera, also known as “blue death” is a potentially epidemic and life-threatening secretory diarrhea characterized by numerous voluminous watery stools, often accompanied by vomiting and resulting in hypovolemic shock and acidosis. The causative agent of this water-borne disease belongs to certain members of the species Vibrio cholerae (V. cholerae) which can also cause mild or unapparent infections. V. cholerae is a facultative anaerobic, Gram-negative bacilli, which possess the characteristic feature of darting motility under wet-mound preparations. Other members of the species may occasionally cause isolated outbreaks of milder diarrhea, whereas others—the vast majority—are free-living and not associated with disease. The emergence of new, virulent, drug-resistant strains of Vibrio is the main cause of protracted outbreaks leading to high fatality rates. The subsequent loss of fluid volume causes a drop in blood pressure and circulatory shock. If the patient remains untreated, they become progressively weaker, sometimes to the point of death, within 12–24 h of the onset of symptoms. The severity and fatality of the disease depend on the strain of Vibrio. The cholera toxin-producing (CT-producing) V. cholerae manifests the most fatal disease known as cholera gravis. Throughout most of the twentieth century, cholera was caused by V. cholerae of the O1 serogroup, and the disease was largely confined to Asia and Africa. The emergence of a pandemic in 1992 was caused by an unknown serogroup of V. cholerae (O139) wherein the targets were India and Bangladesh. The pathogenesis and virulence of the bacteria are due to an enterotoxin it produces—cholera toxin (CT). The mechanism of action of CT is discussed in this chapter at a later stage. Attempts have been made to produce vaccines through a number of trial-and-error methods, and still the possibility of an effective vaccine which gives a good prophylactic measure is under consideration. The identification of the bacteria as well as toxin detection is one of the main elements in the clinical microbiology field. The identification and confirmation of this epidemic disease commend from the morphological identification of Vibrio and end with serotyping and biotyping in addition to toxin detection by various means of assays—both in vitro and in vivo. This chapter will cover all of the mentioned areas of clinical microbiology with respect to cholera infection in addition to the recent outbreaks and epidemics which occurred across the globe

The Measure of Success: Evaluating Corporate Citizenship Performance

This is the second publication resulting from the Measure of Success research project, designed to explore the current corporate perspective on and practices in measuring corporate citizenship performance. It presents a discussion of the evolution of corporate citizenship and how the political debates have influenced measurement practice; and a discussion of measurement as a management tool in the design and implementation of corporate citizenship programmes

Growing population segments and their impact on future transport

The European population is facing enormous demographic changes. Based on data from the Danish National Travel Survey (NTS), this paper focuses on three major societal trends – changing family structures, ageing, and urbanisation – and the impact of these trends on future car use in Denmark. We compared the mode choice of single parents and people in single person households (both in “family age” and after retirement) with the choice of people in more traditional household forms. Additionally, we looked into differences within these groups related to gender and urban from. The relevance of these variables for car use as driver, as passenger, and in total was estimated in linear regression analyses. Persons living alone showed the lowest car use; living with a partner and having kids increased driving. While gender differences in older people’s car use could partly be explained with women’s lower car availability and driving licence rates, this was not the case for younger people. Thus, gender roles and different travel preferences are expected to play a role here. Living in a large urban area significantly decreased car use of younger people, whereas it increased older people’s car use as passenger. The lower driving rates of singles and single parents compared to couples with children could be explained with differences in car availability. When this was controlled for, single parents used the car as often as couples with children. To what extent the mobility needs of single parents are met satisfactorily without a car and whether they could serve as a model for car-free living are among the questions that cannot be answered based on the NTS data but should be addressed in future research

Lower vaccine uptake amongst older individuals living alone: A systematic review and meta-analysis of social determinants of vaccine uptake.

INTRODUCTION: Vaccination is a key intervention to reduce infectious disease mortality and morbidity amongst older individuals. Identifying social factors for vaccine uptake enables targeted interventions to reduce health inequalities. OBJECTIVE: To systematically appraise and quantify social factors associated with vaccine uptake amongst individuals aged ?60years from Europe. METHODS: We searched Medline and Embase from inception to 24/02/2016. The association of vaccine uptake was examined for social factors relevant at an individual level, to provide insight into individuals' environment and enable development of targeted interventions by healthcare providers to deliver equitable healthcare. Factors included: living alone, marital status, education, income, vaccination costs, area-level deprivation, social class, urban versus rural residence, immigration status and religion. Between-study heterogeneity for each factor was identified using I2-statistics and Q-statistics, and investigated by stratification and meta-regression analysis. Meta-analysis was conducted, when appropriate, using fixed- or random-effects models. RESULTS: From 11,754 titles, 35 eligible studies were identified (uptake of: seasonal influenza vaccine (SIV) only (n=27) or including pneumococcal vaccine (PV) (n=5); herpes zoster vaccine (n=1); pandemic influenza vaccine (n=1); PV only (n=1)). Higher SIV uptake was reported for individuals not living alone (summary odds ratios (OR)=1.39 (95% confidence interval (CI): 1.16-1.68). Lower SIV uptake was observed in immigrants and in more deprived areas: summary OR=0.57 (95%CI: 0.47-0.68) and risk ratio=0.93 (95%CI: 0.92-0.94) respectively. Higher SIV uptake was associated with higher income (OR=1.26 (95%CI: 1.08-1.47)) and higher education (OR=1.05 (95%CI: 1-1.11)) in adequately adjusted studies. Between-study heterogeneity did not appear to result from variation in categorisation of social factors, but for education was partly explained by varying vaccination costs (meta-regression analysis p=<0.0001); individuals with higher education had higher vaccine uptake in countries without free vaccination. CONCLUSIONS: Quantification of associations between social factors and lower vaccine uptake, and notably living alone (an overlooked factor in vaccination programmes), should enable health professionals target specific social groups to tackle vaccine-related inequalities

Risk factors for developing acute kidney injury in older people with diabetes and community-acquired pneumonia: a population-based UK cohort study.

BACKGROUND: Acute kidney injury (AKI) is being increasingly recognised in ageing populations. There are a paucity of data about AKI risk factors among older individuals with diabetes and infections, who are at particularly high risk of AKI. The objective of this study was to evaluate the risk factors for developing acute kidney injury (AKI) amongst older patients with diabetes and community-acquired pneumonia (CAP) in England, and whether the impact of underlying kidney function varied with age. METHODS: This was a population-based retrospective cohort study over 7 years (01/04/2004-31/3/2011) using electronic health records from the Clinical Practice Research Datalink linked to Hospital Episode Statistics. The study population comprised individuals with diabetes aged ≥65 years with CAP. Associations between demographic, lifestyle factors, co-morbidities and medications and development of AKI within 28 days of CAP were explored in a logistic regression model. RESULTS: Among 3471 patients with CAP and complete covariate data, 298 patients developed subsequent AKI. In multivariable analyses, factors found to be independently associated with AKI included: male sex (adjusted odds ratio, aOR: 1.56 95% confidence interval (CI): 1.20-2.04), hypertension (aOR1.36 95% CI 1.01-1.85), being prescribed either angiotensin-converting-enzyme inhibitors or angiotensin-II-receptor-blockers (aOR: 1.59 95% CI: 1.19-2.13), or insulin (aOR: 2.27 95% CI: 1.27-4.05), presence of proteinuria (aOR 1.27 95% CI 0.98-1.63), and low estimated glomerular filtration rate (eGFR). The odds of AKI were more graded amongst older participants aged ≥80 years compared to those of younger age: for eGFR of ≤29 mL/min/1.73m2 (vs 60 ml/min/1.73m2) aOR: 5.51 95% CI 3.28-9.27 and for eGFR 30-59 mL/min/1.73m2 1.96 95% CI 1.30-2.96, whilst any eGFR < 60 ml/min/1.73m2 was associated with approximately 3-fold increase in the odds of AKI amongst younger individuals (p-value for interaction = 0.007). CONCLUSIONS: The identified risk factors should help primary care and hospital providers identify high risk patients in need of urgent management including more intensive monitoring, and prevention of AKI following pneumonia

The provenance of late Cenozoic East Asian Red Clay : Tectonic-metamorphic history of potential source regions and a novel combined zircon-rutile approach

Constraining the provenance of aeolian mineral dust is critical in understanding past climate changes, atmospheric dust activity, circulation, and sediment generation. On the Chinese Loess Plateau (CLP), use of detrital zircon U-Pb age data as source tracers for the dust has seen a huge growth and lead to breakthroughs in understanding dust provenance. However, significant ambiguities remain especially regarding the provenance of the aeolian Neogene Red Clay (RC). To address this, here we review the state of the art of understanding of Neogene RC provenance, with a focus on single-grain analyses, and introduce detrital rutile geochemistry as a tool to complement zircon U-Pb dating. Furthermore, to better utilise the link between the detrital minerals and their primary origin, we compile primary source region geologic background and single-grain data relevant for use of geochronological and metamorphic provenance proxy minerals. We discuss four major tectonic divisions in northern China and southern Mongolia: North China Craton (NCC), Tarim Craton (TC), Central China Orogen (CCO), parts of the Central Asian Orogenic Belt (CAOB), and briefly summarize the Tibetan-Himalayan orogen. Many of these regions have been tectonically active during the same time periods in the Earth's history, and our analysis demonstrates how use of zircon age data alone has limitations in differentiating between a number of key potential dust sources to the CLP. Addition of a metamorphic source tracer such as rutile allows some of these possible source areas to be distinguished. For example, the proximal northern NCC regions that show high-/ ultrahigh-temperature metamorphic conditions can potentially be diagnostic of a northerly source component to CLP dust. Our combined zircon-rutile data analysis of ca. 4 Ma Nihewan RC in northern CLP verifies the utility of the novel rutile provenance proxy in sourcing CLP sediments. The zircon and rutile data suggest similar dust provenance: the dominant sources are proximal areas on the NCC, while contributions from the dry areas in parts of the CAOB, central deserts, and the Yellow River are also likely. Our results also hint at a minor source component deriving from distal western source regions in the TC, and/or in the central parts of the CCO, but rutile data from potential secondary source areas are needed to verify this possibility. We also conclude that multi-proxy single-grain provenance analyses are needed for more reliable provenance analyses.Peer reviewe

Factors Influencing Construction Labour Productivity: An Indian Case Study

Construction productivity is of interest to researchers and practitioners because of its impact on the performance of construction projects. Despite various studies to identify factors influencing productivity in other countries, no study has addressed productivity issues in India. This paper reports the results of a questionnaire survey of project managers, site engineers, supervisors and craftsmen, in the state of Kerala in India, to identify the factors influencing construction labour productivity. The top five factors identified as having a significant impact on productivity: (1) timely availability of materials at the worksite, (2) delayed material delivery by the supplier, (3) strikes called by political parties or hartals, (4) frequent revisions of drawings/design, resulting in additional work/rework and (5) timely availability of drawings at the worksite. The findings provide a better understanding of the factors influencing productivity in the Indian context and will aid construction practitioners in making effective plans for productivity improvement