South African healthcare provider perspectives on transitioning adolescents into adult HIV care

Background. The first generation of South African (SA) children perinatally infected with HIV is entering adulthood, and there is now a pressing need for systematised transfer of these patients from paediatric to adult care.Objectives. Previous research has investigated the HIV healthcare transition in North America and Europe, yet none has been conducted in SA. Our study is the first to describe the perspectives of healthcare providers overseeing the transition in resource-limited settings.Methods. We approached healthcare providers working in government paediatric HIV clinics and hospitals in the Western Cape Province, SA. Seven physicians and counsellors in adolescent/paediatric care, representing five clinics, were  interviewed, and 43 completed a written survey. Interviews addressed the current state of the transition, barriers and facilitators, and model components. Interviews were assessed for major themes using framework analysis, while logistic regression was applied to survey responses to identify associations with measured covariates.Results. Analysis of interview transcripts revealed several overarching perspectives that were corroborated by survey responses. One barrier identified was the  healthcare providers’ difficulty in letting go of their relationships with the adolescent patients. Since healthcare providers regarded their patients as particularly  vulnerable, they felt a strong and protective attachment towards them. A second barrier identified was a lack of structure and effective communication between adult and paediatric providers; accordingly, healthcare providers feared that they were transferring their adolescents unprepared, to a judgemental, depersonalised and overburdened environment. All interviewees and a majority of survey respondents (>80%) agreed that the formation of adolescent support groups in adult care clinics as well as a later transition age would improve the transition process.Conclusion. This study highlights the need for a systematic healthcare transition for HIV-positive adolescents cared for in the Western Cape, while acknowledging the limitations of the current healthcare infrastructure. Several feasible   recommendations have been identified, including forming support groups and greater involvement of adolescent healthcare providers to facilitate the transition

Dendritic Spine Shape Analysis: A Clustering Perspective

Functional properties of neurons are strongly coupled with their morphology. Changes in neuronal activity alter morphological characteristics of dendritic spines. First step towards understanding the structure-function relationship is to group spines into main spine classes reported in the literature. Shape analysis of dendritic spines can help neuroscientists understand the underlying relationships. Due to unavailability of reliable automated tools, this analysis is currently performed manually which is a time-intensive and subjective task. Several studies on spine shape classification have been reported in the literature, however, there is an on-going debate on whether distinct spine shape classes exist or whether spines should be modeled through a continuum of shape variations. Another challenge is the subjectivity and bias that is introduced due to the supervised nature of classification approaches. In this paper, we aim to address these issues by presenting a clustering perspective. In this context, clustering may serve both confirmation of known patterns and discovery of new ones. We perform cluster analysis on two-photon microscopic images of spines using morphological, shape, and appearance based features and gain insights into the spine shape analysis problem. We use histogram of oriented gradients (HOG), disjunctive normal shape models (DNSM), morphological features, and intensity profile based features for cluster analysis. We use x-means to perform cluster analysis that selects the number of clusters automatically using the Bayesian information criterion (BIC). For all features, this analysis produces 4 clusters and we observe the formation of at least one cluster consisting of spines which are difficult to be assigned to a known class. This observation supports the argument of intermediate shape types.Comment: Accepted for BioImageComputing workshop at ECCV 201

BPIFB1 (LPLUNC1) is upregulated in cystic fibrosis lung disease

Although the biology the PLUNC (recently renamed BPI fold, BPIF) family of secreted proteins is poorly understood, multiple array based studies have suggested that some are differentially expressed in lung diseases. We have examined the expression of BPIFB1 (LPLUNC1), the prototypic two-domain containing family member, in lungs from CF patients and in mouse models of CF lung disease. BPIFB1 was localized in CF lung samples along with BPIFA1, MUC5AC, CD68 and NE and directly compared to histologically normal lung tissues and that of bacterial pneumonia. We generated novel antibodies to mouse BPIF proteins to conduct similar studies on ENaC transgenic (ENaC-Tg) mice, a model for CF-like lung disease. Small airways in CF demonstrated marked epithelial staining of BPIFB1 in goblet cells but staining was absent from alveolar regions. BPIFA1 and BPIFB1 were not co-localised in the diseased lungs. In ENaC-Tg mice there was strong staining of both proteins in the airways and luminal contents. This was most marked for BPIFB1 and was noted within 2 weeks of birth. The two proteins were present in distinct cells within epithelium. BPIFB1 was readily detected in BAL from ENaC-Tg mice but was absent from wild-type mice. Alterations in the expression of BPIF proteins is associated with CF lung disease in humans and mice. It is unclear if this elevation of protein production, which results from phenotypic alteration of the cells within the diseased epithelium, plays a role in the pathogenesis of the disease

Improvement in medication education in a pediatric subspecialty practice

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to measure the impact of an educational intervention on parents of children taking methotrexate (MTX) for juvenile idiopathic arthritis (JIA).</p> <p>Methods</p> <p>This study was conducted using a pre- and postsurvey design. The parents of 100 children with JIA taking MTX for at least 2 months were surveyed during a routine office visit. The parents completed an initial questionnaire regarding the safe use, adverse effects, and guidelines for monitoring the toxicity of MTX. An educational intervention was then administered, and an identical follow-up questionnaire was given during the next office visit. Statistical analysis using a paired <it>t</it>-test (critical <it>P </it>value < 0.05) was performed on individuals who answered both questionnaires.</p> <p>Results</p> <p>There were 100 responses to the initial questionnaire and 67 responses to the follow-up questionnaire. The mean length of time between surveys was 2.9 ± 0.9 months. In those who completed both questionnaires, the overall correct score increased significantly from 75.8% to 93.4%, respectively (<it>P </it>< 0.0001). Individuals scored the lowest (49%) on the question that addressed MTX's impact on pregnancy and fertility.</p> <p>Conclusions</p> <p>MTX knowledge may be less than expected in the parents of children with JIA. Brief educational interventions in the pediatric subspecialty practice can significantly affect a family's understanding of their child's medications.</p

Control over phase separation and nucleation using a laser-tweezing potential

Control over the nucleation of new phases is highly desirable but elusive. Even though there is a long history of crystallization engineering by varying physicochemical parameters, controlling which polymorph crystallizes or whether a molecule crystallizes or forms an amorphous precipitate is still a poorly understood practice. Although there are now numerous examples of control using laser-induced nucleation, the absence of physical understanding is preventing progress. Here we show that the proximity of a liquid–liquid critical point or the corresponding binodal line can be used by a laser-tweezing potential to induce concentration gradients. A simple theoretical model shows that the stored electromagnetic energy of the laser beam produces a free-energy potential that forces phase separation or triggers the nucleation of a new phase. Experiments in a liquid mixture using a low-power laser diode confirm the effect. Phase separation and nucleation using a laser-tweezing potential explains the physics behind non-photochemical laser-induced nucleation and suggests new ways of manipulating matter

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses

Alignment of Biological Sequences with Jalview

In this chapter, we introduce core functionality of the Jalview interactive platform for the creation, analysis, and publication of multiple sequence alignments. A workflow is described based on Jalview's core functions: from data import to figure generation, including import of alignment reliability scores from T-Coffee and use of Jalview from the command line. The accompanying notes provide background information on the underlying methods and discuss additional options for working with Jalview to perform multiple sequence alignment, functional site analysis, and publication of alignments on the web

Machine learning algorithms for systematic review: reducing workload in a preclinical review of animal studies and reducing human screening error

BACKGROUND: Here, we outline a method of applying existing machine learning (ML) approaches to aid citation screening in an on-going broad and shallow systematic review of preclinical animal studies. The aim is to achieve a high-performing algorithm comparable to human screening that can reduce human resources required for carrying out this step of a systematic review. METHODS: We applied ML approaches to a broad systematic review of animal models of depression at the citation screening stage. We tested two independently developed ML approaches which used different classification models and feature sets. We recorded the performance of the ML approaches on an unseen validation set of papers using sensitivity, specificity and accuracy. We aimed to achieve 95% sensitivity and to maximise specificity. The classification model providing the most accurate predictions was applied to the remaining unseen records in the dataset and will be used in the next stage of the preclinical biomedical sciences systematic review. We used a cross-validation technique to assign ML inclusion likelihood scores to the human screened records, to identify potential errors made during the human screening process (error analysis). RESULTS: ML approaches reached 98.7% sensitivity based on learning from a training set of 5749 records, with an inclusion prevalence of 13.2%. The highest level of specificity reached was 86%. Performance was assessed on an independent validation dataset. Human errors in the training and validation sets were successfully identified using the assigned inclusion likelihood from the ML model to highlight discrepancies. Training the ML algorithm on the corrected dataset improved the specificity of the algorithm without compromising sensitivity. Error analysis correction leads to a 3% improvement in sensitivity and specificity, which increases precision and accuracy of the ML algorithm. CONCLUSIONS: This work has confirmed the performance and application of ML algorithms for screening in systematic reviews of preclinical animal studies. It has highlighted the novel use of ML algorithms to identify human error. This needs to be confirmed in other reviews with different inclusion prevalence levels, but represents a promising approach to integrating human decisions and automation in systematic review methodology