Miracle-dz/UniFAR-FTUs huggingface dataset:
Burnout and patient care in junior doctors in Mexico City.

BACKGROUND Burnout is known to occur in public service workers leading to a reduction in effectiveness at work. AIM To estimate the prevalence of burnout in junior doctors and its impact on patient care. METHODS A cross-sectional study of junior doctors at three hospitals in Mexico City was conducted. Measures used included the Maslach Burnout Inventory (MBI), measuring depersonalization (DP), emotional exhaustion (EE) and personal achievement (PA), a questionnaire about patient care practices and attitudes and one on sociodemographic characteristics. Logistic regression analysis was used to assess the association between burnout and suspected risk factors. RESULTS A total of 312 junior doctors participated (response rate 65%). In total, 57% were male and the average age was 28. Average scores in MBI subscales were EE: 18.2, DP: 6.9 and PA: 37.6. Burnout prevalence was 40% (126). Junior doctors with burnout were more likely to report suboptimal patient care practices occurring monthly (OR 5.5; 95% CI 2.7-11.2) and weekly (OR 5.2; 95% CI 1.6-16.3). The logistic regression model for burnout included shifts lasting >12 h, current depression, former major depression, first- or second-year junior doctors, male gender and single status. CONCLUSIONS Burnout was most strongly associated with shifts >12 h and with both current and previous depression. Reported suboptimal patient care was also associated with working shifts of >or=12 h. Burnout may be adversely affecting junior doctors' health and their patients' care.
Combining static and dynamic views for architecture reconstruction

Static analysis aims at recovering the structure of a software system, while dynamic analysis focuses on its run time behaviour. We propose a technique for combining the analysis of static and dynamic architectural information to support the task of architecture reconstruction. The approach emphasises the correct choice of architecturally significant concepts for the reconstruction process and relies on abstraction techniques for their manipulation. The technique allows the software architect to create a set of architectural views valuable for the architecture description of the system. To support our technique, we outline an environment that relies on hierarchical typed directed graphs to show the system's structure and message sequence charts for its behaviour. The main features of the environment are: visualisation of static and dynamic views, synchronisation of abstractions performed on the views, scripting support and management of the use cases. The approach and the environment are demonstrated with an example.
Signal Integration during T Lymphocyte Activation and Function: Lessons from the Wiskott–Aldrich Syndrome

Over the last decades, research dedicated to the molecular and cellular mechanisms underlying primary immunodeficiencies (PID) has helped to understand the etiology of many of these diseases and to develop novel therapeutic approaches. Beyond these aspects, PID are also studied because they offer invaluable natural genetic tools to dissect the human immune system. In this review, we highlight the research that has focused over the last 20 years on T lymphocytes from Wiskott–Aldrich syndrome (WAS) patients. WAS T lymphocytes are defective for the WAS protein (WASP), a regulator of actin cytoskeleton remodeling. Therefore, study of WAS T lymphocytes has helped to grasp that many steps of T lymphocyte activation and function depend on the crosstalk between membrane receptors and the actin cytoskeleton. These steps include motility, immunological synapse assembly, and signaling, as well as the implementation of helper, regulatory, or cytotoxic effector functions. The recent concept that WASP also works as a regulator of transcription within the nucleus is an illustration of the complexity of signal integration in T lymphocytes. Finally, this review will discuss how further study of WAS may contribute to solve novel challenges of T lymphocyte biology.
Validation of the English version of the Five-Factor Self-Concept Questionnaire.

BACKGROUND The Spanish Five-Factor Self-Concept Questionnaire (AF5) is one of the most widely used instruments assessing self-concept with Spanish-speaking samples. It is also one of the few psychometrically sound instruments assessing self-concept from a multidimensional perspective. The availability of the AF5 in both languages (Spanish and English) would expand its potential, and would facilitate cross-cultural research. METHOD To validate the English version of the AF5, we used multi-sample confirmatory factor analysis. The sample was 624 USA respondents, 301 males (48%) and 323 females, ranging in age from 14 to 18 (M = 16.21, SD = 1.08). RESULTS The English version of the AF5 does not change the original factor weights, the variances and covariances of the factors, or the error variances of items, with regard to the original Spanish five-factor model. The five factors proposed -academic, social, emotional, family, and physical- satisfactorily reproduce the inter-item relationships of the original Spanish version. The reliability for all items and dimensions of the English version was also good, with similar results as the original version. CONCLUSIONS This preliminary validation study of the English version of the AF5 showed that it is an acceptable measure to be used with English-speaking adolescents.
Streptococcus suis serotype 2 strains isolated in Argentina (South America) are different from those recovered in North America and present a higher risk for humans

Introduction: Streptococcus suis serotype 2 is an important swine pathogen and emerging zoonotic agent causing meningitis and septicemia/septic shock. Strains are usually virulent (Eurasia) or of intermediate/low virulence (North America). Very few data regarding human and swine isolates from South America are available. Case presentation: Seventeen new human S. suis cases in Argentina (16 serotype 2 strains and a serotype 5 strain) are reported. Alongside, 14 isolates from pigs are analyzed: 12 from systemic disease, one from lungs and one from tonsils of a healthy animal. All human serotype 2 strains and most swine isolates are sequence type (ST) 1, as determined by multilocus sequence typing and present a mrp+/epf+/sly+ genotype typical of virulent Eurasian ST1 strains. The remaining two strains (recovered from swine lungs and tonsils) are ST28 and possess a mrp+/epf−/sly− genotype typical of low virulence North American strains. Representative human ST1 strains as well as one swine ST28 strain were analyzed by whole-genome sequencing and compared with genomes from GenBank. ST1 strains clustered together with three strains from Vietnam and this cluster is close to another one composed of 11 strains from the United Kingdom. Conclusion: Close contact with pigs/pork products, a good surveillance system, and the presence of potentially virulent Eurasian-like serotype 2 strains in Argentina may be an important factor contributing to the higher number of human cases observed. In fact, Argentina is now fifth among Western countries regarding the number of reported human cases after the Netherlands, France, the UK and Poland.
Prevalence of atopy, asthma symptoms and diagnosis, and the management of asthma: comparison of an affluent and a non-affluent country

BACKGROUND The prevalence of childhood asthma and of atopy varies widely between countries. However, few studies have compared the pattern of diagnosis and management of asthma, or the role of atopy in predisposing to asthma between a less affluent country and a more affluent country. The aim of this study was to compare the prevalence of symptoms, diagnosis, and management of asthma, and the prevalence of atopy as measured by skin prick tests in Nigeria and Australia using a standardised methodology. METHODS Respiratory history was collected using a validated questionnaire administered to parents, and atopy was measured with skin prick tests in 654 Australian and 566 Nigerian children aged 8–11 years (70% consent rate in Australia, 60% in Nigeria). RESULTS Wheeze and persistent cough were less prevalent in Nigeria (10.2% and 5.1%, respectively) than in Australia (21.9% and 9.6%, respectively), caused less morbidity, and were less likely to be labelled or treated as asthma than in Australia. There was no significant difference in the overall prevalence of atopy between the two countries (Australia 32.5%, Nigeria 28.2%). Atopy was a strong risk for wheeze in both countries (odds ratio (OR) 3.4 (95% CI 2.3 to 5.1) in Australia, 1.8 (95% CI 1.0 to 3.3) in Nigeria), especially atopy to house dust mites (OR 3.1 (95% CI 2.1 to 4.7) in Australia, 2.4 (95% CI 1.3 to 4.3) in Nigeria). CONCLUSION Although there was a similar prevalence of atopy in both countries, Australian children had a higher prevalence of asthma symptoms. Further studies are needed to determine why atopic children in Australia are more at risk of developing asthma. Such studies will have important implications for the prevention of asthma.
Suppression of HER2/HER3-Mediated Growth of Breast Cancer Cells with Combinations of GDC-0941 PI3K Inhibitor, Trastuzumab, and Pertuzumab

Purpose: Oncogenic activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is prevalent in breast cancer and has been associated with resistance to HER2 inhibitors in the clinic. We therefore investigated the combinatorial activity of GDC-0941, a novel class I PI3K inhibitor, with standard-of-care therapies for HER2-amplified breast cancer. Experimental Design: Three-dimensional laminin-rich extracellular matrix cultures of human breast cancer cells were utilized to provide a physiologically relevant approach to analyze the efficacy and molecular mechanism of combination therapies ex vivo. Combination studies were done using GDC-0941 with trastuzumab (Herceptin), pertuzumab, lapatinib (Tykerb), and docetaxel, the principal therapeutic agents that are either approved or being evaluated for treatment of early HER2-positive breast cancer. Results: Significant GDC-0941 activity (EC50 <1 μmol/L) was observed for >70% of breast cancer cell lines that were examined in three-dimensional laminin-rich extracellular matrix culture. Differential responsiveness to GDC-0941 as a single agent was observed for luminal breast cancer cells upon stimulation with the HER3 ligand, heregulin. Combined treatment of GDC-0941, trastuzumab, and pertuzumab resulted in growth inhibition, altered acinar morphology, and suppression of AKT mitogen-activated protein kinase (MAPK) / extracellular signed-regulated kinase (ERK) kinase and MEK effector signaling pathways for HER2-amplified cells in both normal and heregulin-supplemented media. The GDC-0941 and lapatinib combination further showed that inhibition of HER2 activity was essential for maximum combinatorial efficacy. PI3K inhibition also rendered HER2-amplified BT-474M1 cells and tumor xenografts more sensitive to docetaxel. Conclusions: GDC-0941 is efficacious in preclinical models of breast cancer. The addition of GDC-0941 to HER2-directed treatment could augment clinical benefit in breast cancer patients.
MICAL-1 Is a Negative Regulator of MST-NDR Kinase Signaling and Apoptosis

ABSTRACT MICALs (molecules interacting with CasL) are atypical multidomain flavoenzymes with diverse cellular functions. The molecular pathways employed by MICAL proteins to exert their cellular effects remain largely uncharacterized. Via an unbiased proteomics approach, we identify MICAL-1 as a binding partner of NDR (nuclear Dbf2-related) kinases. NDR1/2 kinases are known to mediate apoptosis downstream of the mammalian Ste-20-like kinase MST1, and ablation of NDR1 in mice predisposes the mice to cancer as a result of compromised apoptosis. MST1 phosphorylates NDR1/2 kinases at their hydrophobic motif, thereby facilitating full NDR kinase activity and function. However, if and how this key phosphorylation event is regulated are unknown. Here we show that MICAL-1 interacts with the hydrophobic motif of NDR1/2 and that overexpression or knockdown of MICAL-1 reduces or augments NDR kinase activation or activity, respectively. Surprisingly, MICAL-1 is a phosphoprotein but not an NDR or MST1 substrate. Rather, MICAL-1 competes with MST1 for NDR binding and thereby antagonizes MST1-induced NDR activation. In line with this inhibitory effect, overexpression or knockdown of MICAL-1 inhibits or enhances, respectively, NDR-dependent proapoptotic signaling induced by extrinsic stimuli. Our findings unveil a previously unknown biological role for MICAL-1 in apoptosis and define a novel negative regulatory mechanism of MST-NDR signaling.
Chronic Lung Function Decline in Cotton Textile Workers: Roles of Historical and Recent Exposures to Endotoxin

Background Long-term occupational exposure to cotton dust that contains endotoxin is associated with chronic respiratory symptoms and excessive decline in forced expiratory volume in 1 sec (FEV1), but the mechanisms of endotoxin-related chronic airflow obstruction remain unclear. Objective In the current study, we examined temporal aspects of the exposure–response relationship between airborne endotoxin exposure, longitudinal change in FEV1, and respiratory symptoms in a cohort of Chinese cotton textile workers. Methods This prospective cohort study followed 447 cotton textile workers from 1981 to 2006.at approximately 5-year intervals. We used a generalized estimating equations approach to model FEV1 level and respiratory symptoms as a function of past exposure (cumulative exposure up to the start of the most recent 5-year survey interval) and cumulative exposure (within the most recent interval) to endotoxins, after adjusting for other covariates. Models were stratified by active versus retired work status and by years employed before the baseline survey (< 5 and ≥ 5 years). Results and conclusions Past exposure to endotoxin was associated with reduced FEV1 level among retired cotton workers. Among all cotton workers, past exposure was more strongly associated with reduced FEV1 for those hired < 5 years before baseline than for those who were hired ≥ 5 years after baseline. Recent endotoxin exposure was significantly associated with byssinosis, chronic bronchitis, and chronic cough.
Evaluation of the Effect of Axial Wall Modification and Coping Design on the Retention of Cement-retained Implant-supported Crowns

Background and aims. Because of compromised angulations of implants, the abutments are sometimes prepared. The purpose of this study was to investigate the effect of removing one wall of the implant abutment on the retention of cement-retained crowns. Materials and methods. Four prefabricated abutments were attached to analogues and embedded in acrylic resin blocks. The first abutment was left intact. Axial walls were partially removed from the remaining abutments to produce abutments with three walls. The screw access channel for the first and second abutments were completely filled with composite resin. For the third and fourth abutments, only partial filling was done. Wax-up models were made by CAD/CAM. Ten cast copings were fabricated for each abutment. The copings of fourth abutment had an extension into the screw access channel. Copings were cemented with Temp Bond. The castings were removed from the abutment using an Instron machine, and the peak removal force was recorded. A one-way ANOVA was used to test for a significant difference followed by the pairwise comparisons. Results. The abutments with opened screw access channel had a significantly higher retention than the two other abutments. The abutment with removed wall and no engagement into the hole by the castings exhibited the highest retention. Conclusion. Preserving the opening of screw access channel significantly increases the retention where one of the axial walls of implant abutments for cement-retained restorations is removed during preparation.
Model selection as a tool for phylogeographic inference: an example from the willow Salix melanopsis

Phylogeographic inference has typically relied on analyses of data from one or a few genes to provide estimates of demography and population histories. While much has been learned from these studies, all phylogeographic analysis is conditioned on the data, and thus, inferences derived from data that represent a small sample of the genome are unavoidably tenuous. Here, we demonstrate one approach for moving beyond classic phylogeographic research. We use sequence capture probes and Illumina sequencing to generate data from >400 loci in order to infer the phylogeographic history of Salix melanopsis, a riparian willow with a disjunct distribution in coastal and the inland Pacific Northwest. We evaluate a priori phylogeographic hypotheses using coalescent models for parameter estimation, and the results support earlier findings that identified post‐Pleistocene dispersal as the cause of the disjunction in S. melanopsis. We also conduct a series of model selection exercises using IMa2, Migrate‐n and ∂a∂i. The resulting ranking of models indicates that refugial dynamics were complex, with multiple regions in the inland regions serving as the source for postglacial colonization. Our results demonstrate that new sources of data and new approaches to data analysis can rejuvenate phylogeographic research by allowing for the identification of complex models that enable researchers to both identify and estimate the most relevant parameters for a given system.
Study of Metabolic Enzyme-Efflux Transporter Relations with in Silico Devices

order to study the complex interactions and positional relations between metabolic enzymes such as CYP and efflux transporters such as PGP, we constructed an In Silico Transwell Device (ISTD) and an In Silico Intestine Device (ISID) to represent in vitro cell culture systems and human small intestines. Both are 3-dimentional, discrete event, discrete space, agent-based models. An ISID is a modification of an ISTD. To study CYP–PGP interactions, we completed 5 simulated cases using both devices. Simulation results showed: 1) with the ISTD under certain circumstances, either synergistic or antagonistic, or no effects occurred; 2) backflow occurring in the ISTD led to CYP–PGP interactions for the drugs whose CYP reaction rates are slow; whereas 3) backflow occurring in the ISTD is not an essential condition for the drugs which react quickly with CYP; and 4) CYP–PGP interactions do not occur in the ISID, suggesting that they are unlikely in human intestines. We also simulated the effect of proximity between CYP and PGP using the ISTD. The simulation results showed: (1) under the same PGP condition, transport is determined dominantly by the closeness of CYP to the membranes (either the apical membrane or the basal membrane); (2) unexpectedly, the asymmetric localization of PGP on the apical membrane does not facilitate more transport, but it slightly enhances metabolism.
Epistemic logic: a survey

Epistemic logic is the logic of knowledge: how do you reason about the question whether your silent admirer knows that you know that (s)he sent you an anonymous Valentine card? Is it harmful if, at a literature-exam you don't know the contents of a chapter? No, as long as you know that the examiner does not know that you do not know it. Knowing whether your neighbor knows that he regularly plays his radio so loudly that you wake up during the night, may help you to solve the problem in an appropriate way. In negotiations, it will harm you to let the other party know your `bottom-line', but it may be helpful to disclose other information about yourself, for example about some of your values. In this article, we will use examples and puzzles to give some avor of the eld and to demonstrate that the notion \it is known that" is meaningful and interesting for researchers in theoretical computer science, arti cial intelligence and game theory. The rst person who wrote about epistemic logic was the Swedish-Finnish philosopher G.H. von Wright in his book \An Essay in Modal Logic" [53]. His treatment is completely axiomatic, with no mention of possible semantics. Most philosophical work on epistemic logic following up on Von Wright's work has concentrated on defending certain axioms and denouncing others. However, the subject of epistemic logic only started to ourish after Kripke's invention of a semantics for modal logic in the early sixties. Kripke introduced a possible worlds semantics for modal logics. The name \possible world" is somewhat misleading, because, according to Hintikka [30], \applications to entire universes are scarcely found outside philosophers' speculations. The primary intended applications are to scenarios covering relatively small pieces of spacetime". In the context of epistemic logic, one can view worlds that are possible for a certain agent in a world as epistemic alternatives, that are compatible with the agent's information in that world. The precise de nitions will be given in Section 2. The rst full-length book about epistemic logic, Hintikka's \Knowledge and Belief" [29], applies these semantical ideas, although his de nitions are
Varieties and the Transfer Problem: The Extensive Margin of Current Account Adjustment

Most analyses of the macroeconomic adjustment required to correct global imbalances ignore net exports of new varieties of goods and services and do not account for firms' entry in the product market. In this paper we revisit the macroeconomics of trade adjustment in the context of the classic 'transfer problem,' using a model where the set of exportables, importables and nontraded goods is endogenous. We show that exchange rate movements associated with adjustment are dramatically lower when the above features are accounted for, relative to traditional macromodels. We also find that, for reasonable parameterizations, consumption and employment (hence welfare) are not highly sensitive to product differentiation, and change little regardless of whether adjustment occurs through movements in relative prices or quantities. This result warns against interpreting the size of real depreciation associated with trade rebalancing as an index of macroeconomic distress.
Boosting sensor network calculus by thoroughly bounding cross-traffic

Sensor Network Calculus (SensorNC) provides a framework for worst-case analysis of wireless sensor networks. The analysis proceeds in two steps: For a given flow, (1) the network is reduced to a tandem of nodes by computing the arrival bounds of cross-traffic; (2) the flow is separated from the cross-traffic by subtracting cross-flows and concatenating nodes on its path. While the second step has seen much treatment, the first step has not at all. This is in sharp contrast to the fact that arrival bounding takes roughly 80% of the total analysis time and is equally crucial for the tightness of the bounds. Therefore, we turn our attention to this first SensorNC analysis step with the goal to boost the performance and applicability of the overall framework. The main technical contribution is a generalized version of the concatenation theorem within the SensorNC setting. This generalization is instrumental in simplifying and streamlining the cross-traffic arrival bound computations such that run times can be reduced by more than a factor of 5. Even more important, it enables a localization of the information necessary to execute the calculations at the node level, thus enabling a distribution of the SensorNC analysis within a self-modeling WSN.