Distribution patterns of terrestrial mammals in KwaZulu-Natal

Distribution patterns, plotted by eighth-degree squares (7.5' x 7.5'), of the 162 mammal species recorded in the province of KwaZulu-Natal, South Africa were examined in relation to the combined factors of vegetation type, climate, and altitude (= bioregions); and in relation to protected areas within the nine bioregions. Highest species richness was recorded in the warmest most heterogeneous (vegetation) bioregions, and lowest in a cool montane region. Species richness was intermediate in relatively homogeneous, predominantly grassland bioregions. Mammalian biodiversity in KwaZulu-Natal is concentrated in the savanna regions in the north-east of the province, although further species-rich areas are found in the north-west and south-west for carnivores, and in the central region for many of the smaller mammals (Insectívora, Chiroptera, Rodentia). Analysis of taxonomic resemblances between bioregions distinguished taxonomically distinct ‘savanna’ and ‘grassland’ groups. Taxonomic resemblances between bioregions were generally lowest in bats (i.e. greatest bioregion specificity) and highest in carnivores (i.e. lowest specificity). In total, 92% of the mammal species occur in one or more protected areas. The percentages of species within protected areas in each of the bioregions are generally high (68-100%). In four of the bioregions the amount of land occupied by protected areas is adequate (6-96%) and protected areas are large, but in the other five bioregions the opposite holds (< 2% protected) and populations within them may not be viable

Concurrent validity and test-retest reliability of the Polhemus Liberty for the measurement of spinal range

This paper discusses concurrent validity and test-retest reliability of the Polhemus Liberty for the measurement of spinal range.It was presented at the International Society of Biomechanics, XXII World Congress, in 2009

Measuring movement fluency during the sit-to-walk task

Restoring movement fluency is a key focus for physical rehabilitation; it's measurement, however, lacks objectivity. The purpose of this study was to find whether measurable movement fluency variables differed between groups of adults with different movement abilities whilst performing the sit-to-walk (STW) movement. The movement fluency variables were: (1) hesitation during movement (reduction in forward velocity of the centre of mass; CoM), (2) coordination (percentage of temporal overlap of joint rotations) and (3) smoothness (number of inflections in the CoM jerk signal)

Executive function in Williams and Down syndromes

Williams (WS) and Down (DS) syndromes are characterised by roughly opposing ability profiles. Relative verbal strengths and visuospatial difficulties have been reported in those with WS, while expressive language difficulties have been observed in individuals with DS. Few investigations into the executive function (EF) skills of these groups have examined the effect of verbal/visuospatial task type on performance. Analogous verbal and visuospatial measures were administered to these populations within four EF domains: executive-loaded working memory (ELWM), inhibition, fluency and set-shifting. Performance in both groups was compared to that of typically developing (TD) children using regression techniques controlling for potentially influential cognitive/developmental factors. Individuals with WS showed the expected relative visuospatial difficulties, as indicated by poorer performance than TD individuals, on tests of ELWM and fluency. Individuals with DS displayed the expected relative verbal difficulty in the domain of set-shifting. In addition, each population showed pervasive deficits across modality in one domain; ELWM for individuals with DS, and inhibition for individuals with WS. Individuals with WS and DS showed EF difficulties in comparison to a TD group, but, their executive performance was affected by EF task type (verbal/visuospatial) and EF domain in different ways. While the findings indicated that EF in these populations is characterised by a range of specific strengths and weaknesses, it was also suggested that the relative verbal/visuospatial strengths associated with each population do not consistently manifest across EF domains. Lastly, syndrome specificity was indicated by the differences in groups’ performance patterns

Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR

BACKGROUND: The ability to restore cystic fibrosis transmembrane regulator (CFTR) function with effective small molecule modulators in patients with cystic fibrosis provides an opportunity to study relationships between CFTR ion channel function, organ level physiology, and clinical outcomes. METHODS: We performed a multisite, prospective, observational study of ivacaftor, prescribed in patients with the G551D-CFTR mutation. Measurements of lung mucociliary clearance (MCC) were performed before and after treatment initiation (1 and 3 months), in parallel with clinical outcome measures. RESULTS: Marked acceleration in whole lung, central lung, and peripheral lung MCC was observed 1 month after beginning ivacaftor and was sustained at 3 months. Improvements in MCC correlated with improvements in forced expiratory volume in the first second (FEV1) but not sweat chloride or symptom scores. CONCLUSIONS: Restoration of CFTR activity with ivacaftor led to significant improvements in MCC. This physiologic assessment provides a means to characterize future CFTR modulator therapies and may help to predict improvements in lung function. TRIAL REGISTRATION: ClinicialTrials.gov, NCT01521338. FUNDING: CFF Therapeutics (GOAL11K1)

Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor

Using developmental trajectories to examine verbal and visuospatial short-term memory development in children and adolescents with Williams and Down syndromes

Williams (WS) and Down (DS) syndromes have been associated with specifically compromised short-term memory (STM) subsystems. Individuals with WS have shown impairments in visuospatial STM, while individuals with DS have often shown problems with the recall of verbal material. However, studies have not usually compared the development of STM skills in these domains, in these populations. The present study employed a cross sectional developmental trajectories approach, plotting verbal and visuospatial STM performance against more general cognitive and chronological development, to investigate how the domain-specific skills of individuals with WS and DS may change as development progresses, as well as whether the difference between STM skill domains increases, in either group, as development progresses. Typically developing children, of broadly similar cognitive ability to the clinical groups, were also included. Planned between- and within group comparisons were carried out. Individuals with WS and DS both showed the domain specific STM weaknesses in overall performance that were expected based on the respective cognitive profiles. However, skills in both groups developed, according to general cognitive development, at similar rates to those of the TD group. In addition, no significant developmental divergence between STM domains was observed in either clinical group according to mental age or chronological age, although the general pattern of findings indicated that the influence of the latter variable across STM domains, particularly in WS, might merit further investigation

Characteristics of subjective cognitive decline associated with amyloid positivity

Introduction: The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. Methods: In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) ε4 carriership, and neuropsychiatric symptoms with amyloid positivity. Results: Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE ε4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages. Discussion: Next to age, setting, and APOE ε4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals

Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum

Falciparum malaria is clinically heterogeneous and the relative contribution of parasite and host in shaping disease severity remains unclear. We explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection (CHMI). We uncovered marked heterogeneity in the host response to blood challenge; some volunteers remained quiescent, others triggered interferon-stimulated inflammation and some showed transcriptional evidence of myeloid cell suppression. Significantly, only inflammatory volunteers experienced hallmark symptoms of malaria. When we tracked temporal changes in parasite VSA expression to ask whether variants associated with severe disease rapidly expand in naive hosts, we found no transcriptional evidence to support this hypothesis. These data indicate that parasite variants that dominate severe malaria do not have an intrinsic growth or survival advantage; instead, they presumably rely upon infection-induced changes in their within-host environment for selection

Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1 beta, IL-8, and IL-1 beta. Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.Peer reviewe