Time-to-birth prediction models and the influence of expert opinions

Preterm birth is the leading cause of death among children under five years old. The pathophysiology and etiology of preterm labor are not yet fully understood. This causes a large number of unnecessary hospitalizations due to high--sensitivity clinical policies, which has a significant psychological and economic impact. In this study, we present a predictive model, based on a new dataset containing information of 1,243 admissions, that predicts whether a patient will give birth within a given time after admission. Such a model could provide support in the clinical decision-making process. Predictions for birth within 48 h or 7 days after admission yield an Area Under the Curve of the Receiver Operating Characteristic (AUC) of 0.72 for both tasks. Furthermore, we show that by incorporating predictions made by experts at admission, which introduces a potential bias, the prediction effectiveness increases to an AUC score of 0.83 and 0.81 for these respective tasks

Reversible Random Sequential Adsorption of Dimers on a Triangular Lattice

We report on simulations of reversible random sequential adsorption of dimers on three different lattices: a one-dimensional lattice, a two-dimensional triangular lattice, and a two-dimensional triangular lattice with the nearest neighbors excluded. In addition to the adsorption of particles at a rate K+, we allow particles to leave the surface at a rate K-. The results from the one-dimensional lattice model agree with previous results for the continuous parking lot model. In particular, the long-time behavior is dominated by collective events involving two particles. We were able to directly confirm the importance of two-particle events in the simple two-dimensional triangular lattice. For the two-dimensional triangular lattice with the nearest neighbors excluded, the observed dynamics are consistent with this picture. The two-dimensional simulations were motivated by measurements of Ca++ binding to Langmuir monolayers. The two cases were chosen to model the effects of changing pH in the experimental system.Comment: 9 pages, 10 figure

Toward a conceptual framework of the acceptability of tuberculosis treatment in children using a theory generative approach

To describe an early-stage holistic framework towards evaluating factors that impact the overall acceptability of TB treatment along the TB care cascade in children. We developed a conceptual framework utilising a theory generative approach. Domains were developed through review of existing definitions and analysis of existing qualitative data undertaken in acceptability studies of TB treatment in children. Clarity of domain definitions was achieved through iterative refinement among the research team. Three domains, each comprising several dimensions, were identified to holistically evaluate treatment acceptability: (1) usability, which involves the alignment between the requirements of treatment use and caregivers’ and children’s ability to integrate TB treatment into their everyday routines, (2) receptivity, which describes the end-user’s perception and expectations of treatment and its actual use, and (3) integration, which describes the relationship between available health services and caregivers/children’s capacity to make use of those services. Our framework addresses the gaps in current research which do not account for the influence of caregivers’ and children’s contexts on TB treatment uptake and overall acceptability. This approach may support the development of more standard, holistic measures to improve TB treatment delivery and experiences and future research in children

Clinical presentation and outcome of Tuberculosis in Human Immunodeficiency Virus infected children on anti-retroviral therapy

<p>Abstract</p> <p>Background</p> <p>The tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics are poorly controlled in sub-Saharan Africa, where highly active antiretroviral treatment (HAART) has become more freely available. Little is known about the clinical presentation and outcome of TB in HIV-infected children on HAART.</p> <p>Methods</p> <p>We performed a comprehensive file review of all children who commenced HAART at Tygerberg Children's Hospital from January 2003 through December 2005.</p> <p>Results</p> <p>Data from 290 children were analyzed; 137 TB episodes were recorded in 136 children; 116 episodes occurred before and 21 after HAART initiation; 10 episodes were probably related to immune reconstitution inflammatory syndrome (IRIS). The number of TB cases per 100 patient years were 53.3 during the 9 months prior to HAART initiation, and 6.4 during post HAART follow-up [odds ratio (OR) 16.6; 95% confidence interval (CI) 12.5–22.4]. A positive outcome was achieved in 97/137 (71%) episodes, 6 (4%) cases experienced no improvement, 16 (12%) died and the outcome could not be established in 18 (13%). Mortality was less in children on HAART (1/21; 4.8%) compared to those not on HAART (15/116; 12.9%).</p> <p>Conclusion</p> <p>We recorded an extremely high incidence of TB among HIV-infected children, especially prior to HAART initiation. Starting HAART at an earlier stage is likely to reduce morbidity and mortality related to TB, particularly in TB-endemic areas. Management frequently deviated from standard guidelines, but outcomes in general were good.</p

Characteristics and Programme-Defined Treatment Outcomes among Childhood Tuberculosis (TB) Patients under the National TB Programme in Delhi

Childhood tuberculosis (TB) patients under India's Revised National TB Control Programme (RNTCP) are managed using diagnostic algorithms and directly observed treatment with intermittent thrice-weekly short-course treatment regimens for 6–8 months. The assignment into pre-treatment weight bands leads to drug doses (milligram per kilogram) that are lower than current World Health Organization (WHO) guidelines for some patients.The main aim of our study was to describe the baseline characteristics and treatment outcomes reported under RNTCP for registered childhood (age <15 years) TB patients in Delhi. Additionally, we compared the reported programmatic treatment completion rates between children treated as per WHO recommended anti-TB drug doses with those children treated with anti-TB drug doses below that recommended in WHO guidelines.For this cross-sectional retrospective study, we reviewed programme records of all 1089 TB patients aged <15 years registered for TB treatment from January to June, 2008 in 6 randomly selected districts of Delhi. WHO disease classification and treatment outcome definitions are used by RNTCP, and these were extracted as reported in programme records.Among 1074 patients with records available, 651 (61%) were females, 122 (11%) were <5 years of age, 1000 (93%) were new cases, and 680 (63%) had extra-pulmonary TB (EP-TB)—most commonly peripheral lymph node disease [310 (46%)]. Among 394 pulmonary TB (PTB) cases, 165 (42%) were sputum smear-positive. The overall reported treatment completion rate was 95%. Similar reported treatment completion rates were found in all subgroups assessed, including those patients whose drug dosages were lower than that currently recommended by WHO. Further studies are needed to assess the reasons for the low proportion of under-5 years of age TB case notifications, address challenges in reaching all childhood TB patients by RNTCP, the accuracy of diagnosis, and the clinical validity of reported programme defined treatment completion

Prognostic value of myocardial perfusion scintigraphy in type 2 diabetic patients with mild, stable angina pectoris

Aim: To determine the prognostic value of reversible myocardial perfusion defects on myocardial perfusion scintigraphy (MPS) in patients with type 2 diabetes mellitus and mild anginal complaints. Methods and results: In the MERIDIAN trial, patients with diabetes mellitus type 2, stable, mild anginal symptoms (Canadian Cardiovascular Society classification (CCS) I-II/IV) and reversible perfusion defects were randomized to either continued pharmacological treatment or early invasive treatment. In this sub analysis, the severity of the myocardial perfusion defect was related to the occurrence of cardiac death and non-fatal myocardial infarction, in 319 patients (63% male, 65 ± 9 years). During follow-up (2.2 ± 0.6 years), 14 patients had a cardiac event: 3 in 171 patients without myocardial ischemia and 11 in 148 patients with myocardial ischemia. Annual event rates rose from 0.8% to 5.8% with increasing severity of myocardial ischemia. Multivariable analysis identified the presence of severe myocardial ischemia (hazard ratio (HR) 5.45, 95%CI 1.89-15.71) and insulin use (HR 4.00, 95%CI 1.25-12.75) as independent predictors of cardiac events. Conclusions: Type 2 diabetics with mild anginal symptoms with no or moderate myocardial ischemia have a low annual cardiac event rate. In patients with severe myocardial ischemia event rate increased 3-6 fold

How Sensory Experiences Affect Adolescents with an Autistic Spectrum Condition within the Classroom

Sensory processing difficulties are consistently reported amongst individuals with an autistic spectrum condition (ASC); these have a significant impact on daily functioning. Evidence in this area comes from observer reports and first-hand accounts; both have limitations. The current study used the Adolescent/Adult Sensory Profile (AASP; Brown and Dunn in The Adolescent/Adult Sensory Profile: self questionnaire. Pearson, 2002a), and a qualitative questionnaire to investigate sensory issues in school children with ASC. The AASP found that the participants’ mean scores were outside normal parameters. Participants reported difficulties in at least one sensory domain, with hearing affecting them the most. Content analysis revealed sensory sensitivity to affect the participant’s learning and that sensory experiences were largely negative. Results suggest that schools need to create sensory profiles for each individual with ASC

A SELEX-Screened Aptamer of Human Hepatitis B Virus RNA Encapsidation Signal Suppresses Viral Replication

Background: The specific interaction between hepatitis B virus (HBV) polymerase (P protein) and the e RNA stem-loop on pregenomic (pg) RNA is crucial for viral replication. It triggers both pgRNA packaging and reverse transcription and thus represents an attractive antiviral target. RNA decoys mimicking e in P protein binding but not supporting replication might represent novel HBV inhibitors. However, because generation of recombinant enzymatically active HBV polymerase is notoriously difficult, such decoys have as yet not been identified. Methodology/Principal Findings: Here we used a SELEX approach, based on a new in vitro reconstitution system exploiting a recombinant truncated HBV P protein (miniP), to identify potential e decoys in two large e RNA pools with randomized upper stem. Selection of strongly P protein binding RNAs correlated with an unexpected strong enrichment of A residues. Two aptamers, S6 and S9, displayed particularly high affinity and specificity for miniP in vitro, yet did not support viral replication when part of a complete HBV genome. Introducing S9 RNA into transiently HBV producing HepG2 cells strongly suppressed pgRNA packaging and DNA synthesis, indicating the S9 RNA can indeed act as an e decoy that competitively inhibits P protein binding to the authentic e signal on pgRNA. Conclusions/Significance: This study demonstrates the first successful identification of human HBV e aptamers by an in vitro SELEX approach. Effective suppression of HBV replication by the S9 aptamer provides proof-of-principle for the abilit

The Tetraspanin Protein CD37 Regulates IgA Responses and Anti-Fungal Immunity

Immunoglobulin A (IgA) secretion by plasma cells in the immune system is critical for protecting the host from environmental and microbial infections. However, the molecular mechanisms underlying the generation of IgA+ plasma cells remain poorly understood. Here, we report that the B cell–expressed tetraspanin CD37 inhibits IgA immune responses in vivo. CD37-deficient (CD37−/−) mice exhibit a 15-fold increased level of IgA in serum and significantly elevated numbers of IgA+ plasma cells in spleen, mucosal-associated lymphoid tissue, as well as bone marrow. Analyses of bone marrow chimeric mice revealed that CD37–deficiency on B cells was directly responsible for the increased IgA production. We identified high local interleukin-6 (IL-6) production in germinal centers of CD37−/− mice after immunization. Notably, neutralizing IL-6 in vivo reversed the increased IgA response in CD37−/− mice. To demonstrate the importance of CD37—which can associate with the pattern-recognition receptor dectin-1—in immunity to infection, CD37−/− mice were exposed to Candida albicans. We report that CD37−/− mice are evidently better protected from infection than wild-type (WT) mice, which was accompanied by increased IL-6 levels and C. albicans–specific IgA antibodies. Importantly, adoptive transfer of CD37−/− serum mediated protection in WT mice and the underlying mechanism involved direct neutralization of fungal cells by IgA. Taken together, tetraspanin protein CD37 inhibits IgA responses and regulates the anti-fungal immune response

Somatosensory processing in neurodevelopmental disorders

The purpose of this article is to review the role of somatosensory perception in typical development, its aberration in a range of neurodevelopmental disorders, and the potential relations between tactile processing abnormalities and central features of each disorder such as motor, communication, and social development. Neurodevelopmental disorders that represent a range of symptoms and etiologies, and for which multiple peer-reviewed articles on somatosensory differences have been published, were chosen to include in the review. Relevant studies in animal models, as well as conditions of early sensory deprivation, are also included. Somatosensory processing plays an important, yet often overlooked, role in typical development and is aberrant in various neurodevelopmental disorders. This is demonstrated in studies of behavior, sensory thresholds, neuroanatomy, and neurophysiology in samples of children with Fragile X syndrome, autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and cerebral palsy (CP). Impaired somatosensory processing is found in a range of neurodevelopmental disorders and is associated with deficits in communication, motor ability, and social skills in these disorders. Given the central role of touch in early development, both experimental and clinical approaches should take into consideration the role of somatosensory processing in the etiology and treatment of neurodevelopmental disorders