Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

Effect of pre-milking teat preparation procedures on the microbial count on teats prior to cluster application

A study was carried out to investigate the effect of six pre-milking teat preparation procedures on lowering the staphylococal, streptococcal and coliform microbial count on teat skin prior to cluster application. The teat preparations included 'Iodine', 'Chlorhexidine' teat foam, 'Washing and drying' with paper, 'No preparation', 'Chlorine' teat foam, and disinfectant 'Wipes'. Teat preparations were applied for five days to 10 cows for each treatment during two herd management periods (indoors and outdoors). Teats were swabbed on day four and five before teat preparation and repeated after teat preparation. The swabs were plated on three selective agars: Baird Parker (Staphylococcus spp.), Edwards (Streptococcus spp.), and MacConkey (coliform). Following incubation, microbial counts for each pathogen type were manually counted and assigned to one of six categories depending on the microbial counts measured. The results were analysed by logistic regression using SAS [28]. The main analysis was conducted on binary improvement scores for the swabbing outcomes. There were no differences for staphylococcal, streptococcal and coliform bacterial counts between treatments, measured 'before' teat preparation. Treatments containing 'Chlorhexidine' teat foam (OR = 4.46) and 'Wipes' (OR = 4.46) resulted in a significant reduction (P < 0.01) in the staphylococcal count on teats compared to 'Washing and drying' or 'No preparation'. 'Chlorine' teat foam (OR = 3.45) and 'Wipes' (3.45) had the highest probability (P < 0.01) of reducing streptococcal counts compared to 'Washing and drying' or 'No preparation'. There was no statistical difference between any of the disinfectant treatments applied in reducing coliforms. Thus, the use of some disinfectant products for pre-milking teat preparation can have beneficial effects on reducing the levels of staphylococcal and streptococcal pathogens on teat skin

How to juggle priorities? An interactive tool to provide quantitative support for strategic patient-mix decisions: an ophthalmology case

An interactive tool was developed for the ophthalmology department of the Academic Medical Center to quantitatively support management with strategic patient-mix decisions. The tool enables management to alter the number of patients in various patient groups and to see the consequences in terms of key performance indicators. In our case study, we focused on the bottleneck: the operating room. First, we performed a literature review to identify all factors that influence an operating room's utilization rate. Next, we decided which factors were relevant to our study. For these relevant factors, two quantitative methods were applied to quantify the impact of an individual factor: regression analysis and computer simulation. Finally, the average duration of an operation, the number of cancellations due to overrun of previous surgeries, and the waiting time target for elective patients all turned out to have significant impact. Accordingly, for the case study, the interactive tool was shown to offer management quantitative decision support to act proactively to expected alterations in patient-mix. Hence, management can anticipate the future situation, and either alter the expected patient-mix or expand capacity to ensure that the key performance indicators will be met in the future

"Half plate of rice to a male casual sexual partner, full plate belongs to the husband": Findings from a qualitative study on sexual behaviour in relation to HIV and AIDS in northern Tanzania

A thorough understanding of the contexts of sexual behaviour of the people who are vulnerable to HIV infection is an important component in the battle against AIDS epidemic. We conducted a qualitative study to investigate perceptions, attitudes and practices of sexually active people in three districts of northern Tanzania with the view of collecting data to inform the formulation of appropriate complementary interventions against HIV and AIDS in the study communities. We conducted 96 semi-structured interviews and 48 focus group discussions with sexually active participants (18-60 years of age) who were selected purposively in two fishing and one non-fishing communities. The study revealed a number of socio-economic and cultural factors which act as structural drivers of HIV epidemic. Mobility and migration were mentioned to be associated with the risk of HIV acquisition and transmission. Sexual promiscuous behaviour was common in all study communities. Chomolea, (a quick transactional sex) was reported to exist in fishing communities, whereas extramarital sex in the bush was reported in non-fishing community which was predominantly Christian and polygamous. Traditional practices such as Kusomboka (death cleansing through unprotected sex) was reported to exist. Other risky sexual behaviour and traditional practices together with their socio-economic and cultural contexts are presented in details and discussed. Knowledge of condom was low as some people mistook them for balloons to play with and as decorations for their living rooms. Acute scarcity of condoms in some remote areas such as vizingani (fishing islands) push some people to make their own condoms locally known as kondomu za pepsi using polythene bags. HIV prevention efforts can succeed by addressing sexual behaviour and its socio-economic and cultural contexts. More innovative, interdisciplinary and productive structural approaches to HIV prevention need to be developed in close collaboration with affected communities and be closely related to policy-making and implementation; to go beyond the limited success of traditional behavioural and biomedical interventions to particularly address the underlying social and structural drivers of HIV risk and vulnerability in the study communities

Modeling dynamic interactions between pre-exposure prophylaxis interventions & treatment programs: predicting HIV transmission & resistance

Clinical trials have recently demonstrated the effectiveness of Pre-Exposure Prophylaxis (PrEP) in preventing HIV infection. Consequently, PrEP may soon be used for epidemic control. We model the dynamic interactions that will occur between treatment programs and potential PrEP interventions in resource-constrained countries. We determine the consequences for HIV transmission and drug resistance. We use response hypersurface modeling to predict the effect of PrEP on decreasing transmission as a function of effectiveness, adherence and coverage. We predict PrEP will increase need for second-line therapies (SLT) for treatment-naïve individuals, but could significantly decrease need for SLT for treatment-experienced individuals. If the rollout of PrEP is carefully planned it could increase the sustainability of treatment programs. If not, need for SLT could increase and the sustainability of treatment programs could be compromised. Our results show the optimal strategy for rolling out PrEP in resource-constrained countries is to begin around the “worst” treatment programs

Chromosome microarray analysis as first-line test in pregnancies with a priori low risk for detection of submicroscopic chromosomal abnormalities

n this study, we aimed to explore the utility of chromosomal microarray analysis (CMA) in groups of pregnancies with a priori low risk for detection of submicroscopic chromosome abnormalities, usually not considered an indication for testing, in order to assess whether CMA improves the detection rate of prenatal chromosomal aberrations. A total of 3000 prenatal samples were processed in parallel using both whole-genome CMA and conventional karyotyping. The indications for prenatal testing included: advanced maternal age, maternal serum screening test abnormality, abnormal ultrasound findings, known abnormal fetal karyotype, parental anxiety, family history of a genetic condition and cell culture failure. The use of CMA resulted in an increased detection rate regardless of the indication for analysis. This was evident in high risk groups (abnormal ultrasound findings and abnormal fetal karyotype), in which the percentage of detection was 5.8% (7/120), and also in low risk groups, such as advanced maternal age (6/1118, 0.5%), and parental anxiety (11/1674, 0.7%). A total of 24 (0.8%) fetal conditions would have remained undiagnosed if only a standard karyotype had been performed. Importantly, 17 (0.6%) of such findings would have otherwise been overlooked if CMA was offered only to high risk pregnancies.The results of this study suggest that more widespread CMA testing of fetuses would result in a higher detection of clinically relevant chromosome abnormalities, even in low risk pregnancies. Our findings provide substantial evidence for the introduction of CMA as a first-line diagnostic test for all pregnant women undergoing invasive prenatal testing, regardless of risk factors

A Simple Method for Analyzing Exome Sequencing Data Shows Distinct Levels of Nonsynonymous Variation for Human Immune and Nervous System Genes

To measure the strength of natural selection that acts upon single nucleotide variants (SNVs) in a set of human genes, we calculate the ratio between nonsynonymous SNVs (nsSNVs) per nonsynonymous site and synonymous SNVs (sSNVs) per synonymous site. We transform this ratio with a respective factor f that corrects for the bias of synonymous sites towards transitions in the genetic code and different mutation rates for transitions and transversions. This method approximates the relative density of nsSNVs (rdnsv) in comparison with the neutral expectation as inferred from the density of sSNVs. Using SNVs from a diploid genome and 200 exomes, we apply our method to immune system genes (ISGs), nervous system genes (NSGs), randomly sampled genes (RSGs), and gene ontology annotated genes. The estimate of rdnsv in an individual exome is around 20% for NSGs and 30–40% for ISGs and RSGs. This smaller rdnsv of NSGs indicates overall stronger purifying selection. To quantify the relative shift of nsSNVs towards rare variants, we next fit a linear regression model to the estimates of rdnsv over different SNV allele frequency bins. The obtained regression models show a negative slope for NSGs, ISGs and RSGs, supporting an influence of purifying selection on the frequency spectrum of segregating nsSNVs. The y-intercept of the model predicts rdnsv for an allele frequency close to 0. This parameter can be interpreted as the proportion of nonsynonymous sites where mutations are tolerated to segregate with an allele frequency notably greater than 0 in the population, given the performed normalization of the observed nsSNV to sSNV ratio. A smaller y-intercept is displayed by NSGs, indicating more nonsynonymous sites under strong negative selection. This predicts more monogenically inherited or de-novo mutation diseases that affect the nervous system