364 research outputs found
flexiMAP: a regression-based method for discovering differential alternative polyadenylation events in standard RNA-seq data
Motivation: We present flexible Modeling of Alternative PolyAdenylation (flexiMAP), a newbeta-regression-based method implemented in R, for discovering differential alternative polyadenylation events in standard RNA-seq data.
Results: We show, using both simulated and real data, that flexiMAP exhibits a good balance between specificity and sensitivity and compares favourably to existing methods, especially at low fold changes. In addition, the tests on simulated data reveal some hitherto unrecognized caveats of existing methods. Importantly, flexiMAP allows modeling of multiple known covariates that often confound the results of RNA-seq data analysis.
Availability and implementation: The flexiMAPR package is available at:https://github.com/kszkop/flexiMAP. Scripts and data to reproduce the analysis in this paper are available at: https://doi.org/10.5281/zenodo.3689788
Characteristics of revisits of children at risk for serious infections in pediatric emergency care
In this study, we aimed to identify characteristics of (unscheduled) revisits and its optimal time frame after Emergency Department (ED) discharge. Children with fever, dyspnea, or vomiting/diarrhea (1 monthâ16 years) who attended the ED of Erasmus MC-Sophia, Rotterdam (2010â2013), the Netherlands, were prospectively included. Three days after ED discharge, we applied standardized telephonic questionnaires on disease course and revisits. Multivariable logistic regression analysis was used to identify independent characteristics of revisits. Young age, parental concern, and alarming signs and symptoms (chest wall retractions, ill appearance, clinical signs of dehydration, and tachypnea) were associated with revisits (nâ=â527) in children at risk for serious infections discharged from the ED (nâ=â1765). Children revisited the ED within a median of 2 days (IQR 1.0â3.0), but this was proven to be shorter in children with vomiting/diarrhea (1.0 day (IQR 1.0â2.0)) compared to children with fever or dyspnea (2.0 (IQR 1.0â3.0)).
CONCLUSION: Young age, parental concern, and alarming signs and symptoms (chest wall retractions, ill appearance, clinical signs of dehydration, and tachypnea) were associated with emergency health care revisits in children with fever, dyspnea, and vomiting/diarrhea. These characteristics could help to define targeted review of children during post-discharge period. We observed a disease specific and differential timing of control revisits after ED discharge
Inflammatory Polyarthritis in a Patient with Psoriasis: Is It Psoriatic Arthritis or Rheumatoid Arthrirtis?
Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. There are no generally accepted diagnostic criteria for PsA. Indeed, the diagnosis of this inflammatory arthritis is made by exclusion of other possible diseases and based upon immunologic, radiologic, and clinical features which are consistent with the diagnosis. Inflammatory arthritis in a patient with psoriasis can be an important clue for the diagnosis of PsA, but the possibility for diagnosis of other inflammatory arthritides ever remains. Herein we report a case of a female patient who was not diagnosed with PsA, but with rheumatoid arthritis, even though she had psoriasis
Warfarin-Induced Penile Necrosis in a Patient with Heparin-Induced Thrombocytopenia
A 56-yr-old man with lung adenocarcinoma presented with subsegmental pulmonary thrombosis. Platelet count on presentation was 531Ă109/L. The patient was anticoagulated with subcutaneous low molecular weight heparin (LMWH). Next day, oral anticoagulation was initiated with 5 mg of warfarin once daily with LMWH and LMWH was discontinued at third hospital day. On the third day of oral anticoagulation therapy, he complained of left leg swelling and prolonged painful penile erection of 24 hr-duration. His platelet count reached a nadir 164Ă109/L at that time, and the patient had a deficiency of protein C and S, with an activity level of 16% and 20% of normal value. Warfarin was stopped and he underwent penile aspiration. The next day, left leg edema and penile erection was disappeared, but penile and glans penis necrosis was started. This case illustrates that processes underlying heparin-induced thrombocytopenia (HIT) may also underlie warfarin-induced skin necrosis
Parentsâ experiences with a sick or injured child during the COVID-19 lockdown: an online survey in the Netherlands
ObjectiveTo assess the impact of the COVID-19 lockdown on parentsâ health-seeking behaviour and care for a sick or injured child in the Netherlands.Design and settingAn online survey on parentsâ experiences with a sick or injured child during the COVID-19 lockdown periods was disseminated through social media.ParticipantsParents living in the Netherlands with a sick or injured child during the lockdown periods from March to June 2020 and from December 2020 to February 2021 were eligible to participate.Outcome measuresDescriptive statistics and thematic analysis were used to analyse family and childrenâs characteristics, parentsâ response to a sick or injured child, and the perceived impact of the lockdown on childâs severity of illness and treatment reported by parents. Analyses were stratified for children with and without chronic conditions.ResultsOf the 105 parents who completed the survey, 83% reported they would have sought medical help before lockdown compared with 88% who did seek help during lockdown for the same specific medical problem. Parents reported that changes in health services affected their childâs severity of illness (31%) and their treatment (39%), especially for children with chronic conditions. These changes included less availability of healthcare services and long waiting lists, which mostly led to worsening of the childâs illness. During lockdown, there was no change in health-seeking behaviour by parents of children with a chronic condition (N=51) compared with parents of children without a chronic condition.ConclusionParents in the Netherlands who completed the survey were not deterred from seeking medical help for their sick or injured child during the COVID-19 lockdown periods. However, changes in health services affected childâs severity of illness and treatment, especially for children with chronic conditions.</jats:sec
Parental help-seeking behaviour for, and care of, a sick or injured child during the COVID-19 pandemic: a European online survey
Background
Globally, the COVID-19 pandemic had a huge impact on patients and healthcare systems. A decline in paediatric visits to healthcare settings was observed, which might have been due to lower incidence of injury and infectious illness, changes in healthcare services and parental concern. The aim of our study was to examine parental experiences of help-seeking for, and care of, a sick or injured child during COVID-19 lockdown periods in five European countries with different healthcare systems in place.
Methods
An online survey for parents with a child with any kind or illness of injury during COVID-19 lockdowns was circulated through social media in five European countries: Italy, Spain, Sweden, the Netherlands, and the United Kingdom. Parents living in one of these countries with self-identification of a sick or injured child during COVID-19 lockdown periods were eligible to fill in the survey. Descriptive statistics were used for the level of restrictions per country, childrenâs characteristics, family characteristics and reported help-seeking behaviour of parents prior to the lockdown and their real experience during the lockdown. The free text data was subjected to thematic analysis.
Results
The survey was fully completed by 598 parents, ranging from 50 to 198 parents per country, during varying lockdown periods from March 2020 until May 2022. Parents who completed the survey were not deterred from seeking medical help for their sick or injured child during the COVID-19 pandemic. This finding was comparable in five European countries with different healthcare systems in place. Thematic analysis identified three main areas: parental experiences of access to healthcare, changes in parentsâ help-seeking behaviours for a sick or injured child during lockdowns, and the impact of caring for a sick or injured child during the lockdowns. Parents reported limited access to non-urgent care services and were anxious about either their child or themselves catching COVID-19.
Conclusion
This insight into parental perspectives of help-seeking behaviour and care for a sick or injured child during COVID-19 lockdowns could inform future strategies to improve access to healthcare, and to provide parents with adequate information concerning when and where to seek help and support during pandemics
Game theory of mind
This paper introduces a model of âtheory of mindâ, namely, how we represent the intentions and goals of others to optimise our mutual interactions. We draw on ideas from optimum control and game theory to provide a âgame theory of mindâ. First, we consider the representations of goals in terms of value functions that are prescribed by utility or rewards. Critically, the joint value functions and ensuing behaviour are optimised recursively, under the assumption that I represent your value function, your representation of mine, your representation of my representation of yours, and so on ad infinitum. However, if we assume that the degree of recursion is bounded, then players need to estimate the opponent's degree of recursion (i.e., sophistication) to respond optimally. This induces a problem of inferring the opponent's sophistication, given behavioural exchanges. We show it is possible to deduce whether players make inferences about each other and quantify their sophistication on the basis of choices in sequential games. This rests on comparing generative models of choices with, and without, inference. Model comparison is demonstrated using simulated and real data from a âstag-huntâ. Finally, we note that exactly the same sophisticated behaviour can be achieved by optimising the utility function itself (through prosocial utility), producing unsophisticated but apparently altruistic agents. This may be relevant ethologically in hierarchal game theory and coevolution
Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study
In a historical cohort study of all singleton live births in Northern Ireland from 1971â86 (n=434â933) associations between early life factors and childhood acute lymphoblastic leukaemia were investigated. Multivariable analyses showed a positive association between high paternal age (â©Ÿ35 years) and acute lymphoblastic leukaemia (relative risk=1.49; 95% confidence interval (CI)=0.96â2.31) but no association with maternal age. High birth weight (â©Ÿ3500âg) was positively associated with acute lymphoblastic leukaemia (relative risk=1.66; 95% CI=1.18â2.33). Children of mothers with a previous miscarriage or increased gestation (â©Ÿ40 weeks) had reduced risks of ALL (respective relative risks=0.49; 95% CI=0.29â0.80, and 0.67; 95% CI=0.48â0.94). Children born into more crowded households (â©Ÿ1 person per room) had substantially lower risks than children born into less crowded homes with also some evidence of a lower risk for children born into homes with three adults (relative risks=0.56; 95% CI=0.35â0.91 and 0.58; 95% CI=0.21â1.61 respectively). These findings indicate that several early life factors, including living conditions in childhood and maternal miscarriage history, influence risk of acute lymphoblastic leukaemia in childhood
The p63 Protein Isoform ÎNp63α Modulates Y-box Binding Protein 1 in Its Subcellular Distribution and Regulation of Cell Survival and Motility Genes
The Y-box binding protein 1 (YB-1) belongs to the cold-shock domain protein superfamily, one of the most evolutionarily conserved nucleic acid-binding proteins currently known. YB-1 performs a wide variety of cellular functions, including transcriptional and translational regulation, DNA repair, drug resistance, and stress responses to extracellular signals. Inasmuch as the level of YB-1 drastically increases in tumor cells, this protein is considered to be one of the most indicative markers of malignant tumors. Here, we present evidence that ÎNp63α, the predominant p63 protein isoform in squamous epithelia and YB-1, can physically interact. Into the nucleus, ÎNp63α and YB-1 cooperate in PI3KCA gene promoter activation. Moreover, ÎNp63α promotes YB-1 nuclear accumulation thereby reducing the amount of YB-1 bound to its target transcripts such as that encoding the SNAIL1 protein. Accordingly, ÎNp63α enforced expression was associated with a reduction of the level of SNAIL1, a potent inducer of epithelial to mesenchymal transition. Furthermore, ÎNp63α depletion causes morphological change and enhanced formation of actin stress fibers in squamous cancer cells. Mechanistic studies indicate that ÎNp63α affects cell movement and can reverse the increase of cell motility induced by YB-1 overexpression. These data thus suggest that ÎNp63α provides inhibitory signals for cell motility. Deficiency of ÎNp63α gene expression promotes cell mobilization, at least partially, through a YB-1-dependent mechanism
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