Miracle-dz/UniFAR-FTUs huggingface dataset:
Multivariate Markov Process Models for the Transmission of Methicillin‐Resistant Staphylococcus Aureus in a Hospital Ward

Summary Methicillin‐resistant Staphylococcus Aureus (MRSA) is a pathogen that continues to be of major concern in hospitals. We develop models and computational schemes based on observed weekly incidence data to estimate MRSA transmission parameters. We extend the deterministic model of McBryde, Pettitt, and McElwain (2007, Journal of Theoretical Biology245, 470–481) involving an underlying population of MRSA colonized patients and health‐care workers that describes, among other processes, transmission between uncolonized patients and colonized health‐care workers and vice versa. We develop new bivariate and trivariate Markov models to include incidence so that estimated transmission rates can be based directly on new colonizations rather than indirectly on prevalence. Imperfect sensitivity of pathogen detection is modeled using a hidden Markov process. The advantages of our approach include (i) a discrete valued assumption for the number of colonized health‐care workers, (ii) two transmission parameters can be incorporated into the likelihood, (iii) the likelihood depends on the number of new cases to improve precision of inference, (iv) individual patient records are not required, and (v) the possibility of imperfect detection of colonization is incorporated. We compare our approach with that used by McBryde et al. (2007) based on an approximation that eliminates the health‐care workers from the model, uses Markov chain Monte Carlo and individual patient data. We apply these models to MRSA colonization data collected in a small intensive care unit at the Princess Alexandra Hospital, Brisbane, Australia.
Brain Penetration of WEB 2086 (Apafant) and Dantrolene in Mdr1a (P-Glycoprotein) and Bcrp Knockout Rats

Transporter gene knockout rat models are attracting increasing interest for mechanistic studies of new drugs as transporter substrates or inhibitors in vivo. However, limited data are available on the functional validity of such models at the blood-brain barrier. Therefore, the present study evaluated Mdr1a [P-glycoprotein (P-gp)], Bcrp, and combined Mdr1a/Bcrp knockout rat strains for the influence of P-gp and breast cancer resistance protein (BCRP) transport proteins on brain penetration of the selective test substrates [14C]WEB 2086 (3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo-[4,3-a][1,4]-diazepin-2-yl]-1-(4-morpholinyl)-1-propanon) for P-gp and dantrolene for BCRP. Brain-to-plasma concentration ratios (BPR) were measured after intravenous coinfusions of 5.5 µmol/kg per hour [14C]WEB 2086 and 2 µmol/kg per hour dantrolene for 2 hours in groups of knockout or wild-type rats. Compared with wild-type controls, mean BPR of [14C]WEB 2086 increased 8-fold in Mdr1a knockouts, 9.5-fold in double Mdr1a/Bcrp knockouts, and 7.3-fold in zosuquidar-treated wild-type rats, but was unchanged in Bcrp knockout rats. Mean BPR of dantrolene increased 3.3-fold in Bcrp knockouts and 3.9-fold in double Mdr1a/Bcrp knockouts compared with wild type, but was unchanged in the Mdr1a knockouts. The human intestinal CaCo-2 cell bidirectional transport system in vitro confirmed the in vivo finding that [14C]WEB 2086 is a substrate of P-gp but not of BCRP. Therefore, Mdr1a, Bcrp, and combined Mdr1a/Bcrp knockout rats provide functional absence of these efflux transporters at the blood-brain barrier and are a suitable model for mechanistic studies on the brain penetration of drug candidates.
Principal component analysis of MCG–06-30-15 with XMM–Newton

We analyse the spectral variability of MCG–06-30-15 with 600 k s of XMM–Newton data, including 300 k s of new data from the joint XMM–Newton and NuSTAR 2013 observational campaign. We use principal component analysis to find high-resolution, model-independent spectra of the different variable components of the spectrum. We find that over 99 per cent of the variability can be described by just three components, which are consistent with variations in the normalization of the power-law continuum (∼97 per cent), the photon index (∼2 per cent) and the normalization of a relativistically blurred reflection spectrum (∼0.5 per cent). We also find a fourth significant component but this is heavily diluted by noise, and we can attribute all the remaining spectral variability to noise. All three components are found to be variable on time-scales from 20 down to 1 k s, which corresponds to a distance from the central black hole of less than 70 gravitational radii. We compare these results with those derived from spectral fitting, and find them to be in very good agreement with our interpretation of the principal components. We conclude that the observed relatively weak variability in the reflected component of the spectrum of MCG–06-30-15 is due to the effects of light-bending close to the event horizon of the black hole, and demonstrate that principal component analysis is an effective tool for analysing spectral variability in this regime.
Electrocardiographic diagnosis of acute myocardial infarction: Current concepts for the clinician.

BACKGROUND Over the past 2 decades, the 12-lead electrocardiogram has attained special significance for the diagnosis and triage of patients with chest pain because timely detection of myocardial injury and a rapid assessment of myocardium at risk proved pivotal to implementing effective reperfusion therapies during acute myocardial infarction. However, this wealth of information could still be underutilized by clinicians who may restrict their diagnostic quest in patients with chest pain to the more classic electrocardiographic signs. METHODS The medical literature on electrocardiographic manifestations of acute myocardial infarction was extensively reviewed. RESULTS The widespread utilization of both coronary angiography and methods to determine myocardial function and metabolism in patients with acute myocardial infarction over the last 10 years has provided the means for rigorous comparisons with electrocardiographic information. We summarize these electrocardiographic signs and patterns in terms of their relevance to the clinician to help reduce the incidence of "nondiagnostic electrocardiograms" and improve timely decision-making. CONCLUSIONS The electrocardiogram continues to be an invaluable tool in the initial evaluation of patients with chest pain. The plethora of data currently available on electrocardiographic changes correlating with myocardial injury allows clinicians to make faster and better decisions than ever before.
Commentary Aberrant DNA Methylation: Have We Entered the Era of More Than One Type of Colorectal Cancer?

It has been known for over two decades that DNA from colorectal cancer (CRC) is hypomethylated compared to that from normal colonic epithelia. More recently it has also been recognized that specific CpG dinucleotide islands are often hypermethylated in this tumor type, giving rise to the term CpG island methylator phenotype, or CIMP . Hypomethylation may contribute to the activation of oncogenes, whereas CpG-island specific hypermethylation has been linked to the transcriptional silencing of tumor suppressor genes. The relationship between these two epigenetic phenomena has not been examined, however, in CRC. Intuitively one might expect that tumors with severe global DNA hypomethylation might also show a lower frequency of CpG island hypermethylation due to a lower overall content of methyl groups. The meticulous study by Bariol et al in this issue of The American Journal of Pathology reveals this not to be the case. No association was apparent between global 5-methyl cytosine content and the number of methylated CpG sites in a relatively large and representative series of 97 premalignant and malignant lesions. With only one exception, all of the 22 CRCs investigated showed a lower 5-methyl cytosine content compared to normal mucosa from the same patient. Moreover, approximately 30 to 40% of hyperplastic polyps, adenomas, and CRCs showed no methylation at any of the five CpG sites examined. This most recent study by the Ward laboratory follows on from their previous work in characterizing CIMP CRCs. It is also relevant to the notion put forward by these and other workers that CIMP and the closely related tumor subgroup with microsatellite instability (MSI ) originate in large hyperplastic polyps and serrated adenomas. Increasingly, it is becoming recognized that tumors with widespread DNA hypermethylation have distinctive clinicopathological and molecular features. Although the study by Bariol et al emphasizes and probably serves to justify the current interest in hypermethylation as opposed to hypomethylation, there is clearly much more to be learned about the general role of aberrant DNA methylation in the development and progression of CRC. Technical Issues in the Study of Aberrant DNA Methylation
Antioxidant Supplements and Risk of Breast Cancer Recurrence and Breast Cancer-Related Mortality Among Postmenopausal Women

Despite widespread use, only a few clinical or epidemiological studies have examined the relationship between antioxidant supplements and risk of breast cancer recurrence or breast cancer-related mortality. We used proportional hazards and logistic regression modeling to estimate rate ratios and odds ratios (ORs) for recurrence and mortality among 385 postmenopausal women diagnosed with breast cancer between 1986 and 1988 enrolled into a case-control study on diet and cancer. Women were recontacted with a single questionnaire to ascertain the use of nutritional supplements during 12-14 yr of follow-up time. In multivariable models, antioxidant supplement users compared with nonusers were less likely to have a breast cancer recurrence or breast cancer-related death (OR = 0.54, 95% CI = 0.27-1.04). Vitamin E supplements showed a modest protective effect when used for more than 3 yr (OR = 0.33, 95% CI = 0.10-1.07). Premorbid dietary intake of vitamins C or E from diet, supplements, or both showed no relationship with risk. Risks of recurrence and disease-related mortality were reduced among women using vitamin C and vitamin E supplements for more than 3 yr. Recall bias among proxy respondents for women who died during follow-up may have contributed to these findings. This study provides limited support for the hypothesis that antioxidant supplements may reduce the risk of breast cancer recurrence or breast cancer-related mortality.
Prevalence of Anaemia and Its Epidemiological Determinants in Pregnant Women

Background: Nutritional anaemia in pregnant women is one of the India’s major public health problems, despite the fact that this problem is largely preventable & easily treatable. Objectives: 1.To determine the prevalence of anaemia in pregnant women. 2. To assess the epidemiological determinants of anaemia in pregnancy. Methodology: A descriptive case series study was conducted among the pregnant women from second trimester onwards from urban field practice area from 1 st March 2010 to 31 st July 2010 by using pre-designed, pre-tested, structured schedule. Haemoglobin estimation was done by Sahli’s method & anaemia was graded according to WHO criteria. Statistical analyses were done by percentages and proportions, Mean and Standard Deviation (S.D), Chi-square test. Results: A high prevalence (82.9%) of anaemia (Haemoglobin < 11.0gm/dl) was observed among 228 pregnant women. Majority (50.4%) had moderate degree of anaemia (Haemoglobin 7.0 to 10.0 gm/dl) and 7.0% had severe anaemia (Haemoglobin < 7.0 gm/dl). Severity of anaemia was more in 26 years of age, from nuclear families, educated upto secondary level, having vegetarian diet, parity two or more & those in third trimester with two or more abortions, although statistically not significant. However, anaemia prevalence was significantly higher among those subjects from below Class IV socioeconomic status, those with less than two years of spacing between previous and index pregnancies & with less than two months IFA tablet consumption. Conclusion: A very high prevalence of anaemia in pregnancy needs mandatory regular supply of IFA tablets to adolescent and pregnant women from 4 th month onwards till 3-6 months post-partum along with correction of other nutritional deficiencies and timely intervention for reducing the burden of related diseases.
Knowledge to Action: Implementing a Guideline for Second Stage Labor

PurposeTo quantify practice changes associated with implementing a clinical practice guideline for the second stage of labor in term nulliparous women with epidural anesthesia and to describe the lessons learned about knowledge translation. The main clinical practice guideline recommendation was waiting up to 2 hours before pushing after full dilatation. Design and MethodsPre- and post-evaluation of clinical outcomes and knowledge translation strategies associated with implementing the second stage of labor clinical practice guideline at two birthing units within a large teaching hospital. ResultsThe implementation of the clinical practice guideline resulted in a significant increase in median waiting time before pushing of 33 minutes at Site 1. This change was also reflected in the twofold increase in the proportion of women waiting longer than 120 minutes before pushing at this site. There was no change in waiting time at Site 2. The duration of the second stage did not change significantly at either site. The median pushing time decreased at both sites but was only statistically significant at Site 1. Clinical ImplicationsBringing about practice change in obstetrics is complex. The measured change in this study was less than we expected. Greater success might have been achieved by enhancing feedback to care providers and more frequent audits of practice. We need to better understand the subtle influences in attitude and culture that prevented successful implementation in one site. For units considering a similar process, we recommend a commensurately greater level of presence in the units to encourage compliance with the clinical practice guideline in order to achieve the desired level of practice change.
Soluble Programmed Death 1 (PD-1) Is Decreased in Patients With Immune Thrombocytopenia (ITP)

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by dysregulation of T cells. Programmed death (PD) 1 and programmed death 1 ligand 1 (PD-L1) are cosignaling molecules, and the major role of the PD-1 pathway is the inhibition of self-reactive T cells and to protect against autoimmune diseases. We measured levels of serum soluble PD 1 (sPD-1) and serum soluble PD-L1 (sPD-L1) in 67 patients with ITP (24 newly diagnosed ITP [ndITP], 43 chronic ITP [cITP]) and 21 healthy controls (HCs). We determined decreased serum sPD-1 levels both in patients with ndITP and in patients with cITP when compared to HC. Moreover, there was a positive correlation between sPD-1 levels and platelet counts. The sPD-L1 levels were decreased in patients with ndITP when compared to patients with cITP. This is the first study investigating PD-1 signaling pathway in ITP. Decreased sPD-1 levels may have a role in ITP pathogenesis as without the inhibitory regulation of PD-1, sustained activation of T cells may cause inflammatory responses which is the case in ITP.
Alcohol acutely increases vascular reactivity together with insulin sensitivity in type 2 diabetic men.

Moderate alcohol consumption is associated with increased insulin sensitivity and reduced cardiovascular risk. We hypothesized that this relates to a direct effect of alcohol and therefore investigated whether acute alcohol intake altered insulin sensitivity or endothelial function in patients with type 2 diabetes. In an open-label two period design, the effect of a single oral dose of 40 g of alcohol (168 ml 40% vodka) on an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT) and on endothelium-dependent (flow mediated, FMD) or endothelium-independent (glyceroltrinitrate (GTN)-induced) vasodilation of the brachial artery measured by ultrasound was studied. Experiments were carried out in twelve male patients with type 2 diabetes mellitus (64+/-6 years, body mass index 28.4+/-5.7 kg/m (2)). Baseline insulin sensitivity index (S (I)) was 1.10+/-0.34 min (-1). microU (-1). ml, baseline FMD was +4.1+/-3.0%, and GTN-induced vasodilation +7.4+/-2.3% from resting brachial artery diameter. Acute alcohol intake increased alcohol plasma levels to 0.33+/-0.04 per thousand, S (I) to 1.86+/-0.45 min (-1). microU (-1). ml (p<0.05), and FMD to +8.2+/-2.8% (p<0.05), while GTN-induced dilation remained unchanged. No relationship was detectable between the observed changes. We conclude that alcohol intake acutely increases endothelium-dependent brachial artery vasodilation in patients with type 2 diabetes together with insulin sensitivity. This acute effect might explain some beneficial effects of low alcohol consumption in epidemiological observations.
Age-related physiological responses to emotion anticipation and exposure

Although there is accumulating evidence for physiological and behavioral changes in response to emotion with age, little is known about developmental changes in response to emotion anticipation. Here, we investigated brain activations related to emotion anticipation and exposure, in participants aged between 19 and 54 years. During the anticipation of negative stimuli, a linear decrease of activation with age was detected in the rostral anterior cingulate cortex and brainstem; whereas exposure to negative stimuli revealed decreasing activation in a network of regions implicated in emotion processing and salience detection. The observed results might reflect reduced focusing on negative future events with age, and are in line with an age-related shift of motivational priorities for the pursuit of emotional satisfaction and well being.
Evidence for the aetiological role of blood‐borne virus infections in causing reduced lectin‐induced T‐cell proliferation in haemophilic boys

Summary T‐lymphocyte function, as expressed by polyclonal proliferation to lectin mitogens phytohaemagglutinin and concanavalin A, has been studied in a normal control population and three groups of haemophilic boys: group 1, HIV and HCV seronegative and treated only with a single heat‐treated factor VILT (FVITI) concentrate; group 2, HIV seronegative but HCV seropositive; group 3, all HIV and HCV seropositive. Groups 2 and 3 have been previously treated with unheated and heated FVIII concentrate. Group 1 boys (HIV/HCV uninfected) showed no significant reduction in lymphocyte proliferation when compared with a control population. Group 2 and 3 boys showed an impaired response to these mitogens compared to group 1 boys and the control group. There was no relationship between FVIII concentrate received and proliferative response. The absence of immune modulation in haemophilic boys who have not acquired HIV and HCV infection implicates chronic blood‐borne virus infections as the major contributory factors to impaired lymphocyte proliferative responses seen in haemophiliacs treated with large‐pool concentrates. The presence of virus infections, such as HCV, may account for similar lymphocyte function abnormalities observed in previously described cohorts.
Anticonvulsant Activity of Phenobarbital and Valproate Against Maximal Electroshock in Mice During Chronic Treatment with Caffeine and Caffeine Discontinuation

We evaluated the protective activity (expressed as ED50, values in mg/kg) of phenobarbital (PB, 120 min before testing) and valproate (30 min) alone or combined with caffeine in male mice with seizures induced by maximal electroshock (MES). Both antiepilep‐tic drugs (AEDs) were administered by intraperitoneal (i.p.) injection in a single dose to mice receiving intraperitoneal caffeine either in a single dose 30 min before the test or as pretreatment every 12 h for 3 and 14 days. In addition, we determined the ED50, values of the AEDs 24 and 72 h after 14–day treatment with caffeine. Finally, we studied the influence of a challenge dose of caffeine, injected in mice 24 and 72 h after 14 days of treatment with caffeine, on the protective activity of PB or VPA. Caffeine in a single dose of 23.1 mg/kg reduced the anticonvulsant effect of PB. Its protective activity was further impaired after 3 and 14 days of caffeine treatment. The ED50, for VPA was significantly increased both by the single dose of caffeine and by chronic treatment. The anticonvulsant activity of PB and VPA measured 24 and 72 h after 14–day treatment with caffeine did not differ from control values, but a challenge dose of caffeine injected 24 or 72 h after daily injections for 14 days resulted in a significant reduction in the protective activity of both AEDs. Measurement of the total plasma levels of caffeine, VPA, and PB did not suggest pharmacokinetic interactions as an explanation for our results. Our results indicate that chronic caffeine exposure may progressively reduce the antiepileptic potency of VPA and PB.
Activity Profiles in International Women's Team Handball Using PlayerLoad.

Team handball matches place diverse physical demands on players, which may result in fatigue and decreased activity levels. However, previous speed-based methods of quantifying player activity may not be sensitive for capturing short-lasting team-handball-specific movements. PURPOSE To examine activity profiles of a women's team handball team and individual player profiles, using inertial measurement units. METHODS Match data were obtained from 1 women's national team in 9 international matches (N = 85 individual player samples), using the Catapult OptimEye S5. PlayerLoad/min was used as a measure of intensity in 5- and 10-min periods. Team profiles were presented as relative to the player's match means, and individual profiles were presented as relative to the mean of the 5-min periods with >60% field time. RESULTS A high initial intensity was observed for team profiles and for players with ≥2 consecutive periods of play. Substantial declines in PlayerLoad/min were observed throughout matches for the team and for players with several consecutive periods of field time. These trends were found for all positional categories. Intensity increased substantially in the final 5 min of the first half for team profiles. Activity levels were substantially lower in the 5 min after a player's most intense period and were partly restored in the subsequent 5-min period. DISCUSSION Possible explanations for the observed declines in activity profiles for the team and individual players include fatigue, situational factors, and pacing. However, underlying mechanisms were not accounted for, and these assumptions are therefore based on previous team-sport studies.
Air Pollutants Emissions from Waste Treatment and Disposal Facilities

This study examined the atmospheric pollution created by some waste treatment and disposal facilities in the State of Kuwait. Air monitoring was conducted in a municipal wastewater treatment plant, an industrial wastewater treatment plant established in a petroleum refinery, and at a landfill site used for disposal of solid wastes. Such plants were selected as models for waste treatment and disposal facilities in the Arabian Gulf region and elsewhere. Air measurements were made over a period of 6 months and included levels of gaseous emissions as well as concentrations of volatile organic compounds (VOCs). Samples of gas and bioaerosols were collected from ambient air surrounding the treatment facilities. The results obtained from this study have indicated the presence of VOCs and other gaseous pollutants such as methane, ammonia, and hydrogen sulphide in air surrounding the waste treatment and disposal facilities. In some cases the levels exceeded the concentration limits specified by the air quality standards. Offensive odors were also detected. The study revealed that adverse environmental impact of air pollutants is a major concern in the industrial more than in the municipal waste treatment facilities but sitting of municipal waste treatment and disposal facilities nearby the urban areas poses a threat to the public health.