Grey matter sublayer thickness estimation in the mouse cerebellum

The cerebellar grey matter morphology is an important feature to study neurodegenerative diseases such as Alzheimer’s disease or Down’s syndrome. Its volume or thickness is commonly used as a surrogate imaging biomarker for such diseases. Most studies about grey matter thickness estimation focused on the cortex, and little attention has been drawn on the morphology of the cerebellum. Using ex vivo highresolution MRI, it is now possible to visualise the different cell layers in the mouse cerebellum. In this work, we introduce a framework to extract the Purkinje layer within the grey matter, enabling the estimation of the thickness of the cerebellar grey matter, the granular layer and molecular layer from gadolinium-enhanced ex vivo mouse brain MRI. Application to mouse model of Down’s syndrome found reduced cortical and layer thicknesses in the transchromosomic group

Substantially thinner internal granular layer and reduced molecular layer surface in the cerebellum of the Tc1 mouse model of Down Syndrome - a comprehensive morphometric analysis with active staining contrast-enhanced MRI

Down Syndrome is a chromosomal disorder that affects the development of cerebellar cortical lobules. Impaired neurogenesis in the cerebellum varies among different types of neuronal cells and neuronal layers. In this study, we developed an imaging analysis framework that utilizes gadolinium-enhanced ex vivo mouse brain MRI. We extracted the middle Purkinje layer of the mouse cerebellar cortex, enabling the estimation of the volume, thickness, and surface area of the entire cerebellar cortex, the internal granular layer, and the molecular layer in the Tc1 mouse model of Down Syndrome. The morphometric analysis of our method revealed that a larger proportion of the cerebellar thinning in this model of Down Syndrome resided in the inner granule cell layer, while a larger proportion of the surface area shrinkage was in the molecular layer

Alcohol Production as an Adaptive Livelihood Strategy for Women Farmers in Tanzania and Its Potential for Unintended Consequences on Women's Reproductive Health.

Although women occupy a central position in agriculture in many developing countries, they face numerous constraints to achieving their full potential including unequal access to assets and limited decision-making authority. We explore the intersection of agricultural livelihoods, food and economic security, and women's sexual and reproductive health in Iringa Region, Tanzania. Our goal was to understand whether the benefits of supporting women in the agricultural sector might also extend to more distal outcomes, including sexual and reproductive health. Using the Sustainable Livelihoods Framework to guide data collection, we conducted 13 focus group discussions (FGD) with female (n = 11) and male farmers (n = 2) and 20 in-depth interviews with agricultural extension officers (n = 10) and village agro-dealers (n = 10). Despite providing the majority of agricultural labor, women have limited control over land and earned income and have little bargaining power. In response to these constraints, women adopt adaptive livelihood strategies, such as alcohol production, that allow them to retain control over income and support their households. However, women's central role in alcohol production, in concert with the ubiquitous nature of alcohol consumption, places them at risk by enhancing their vulnerability to unsafe or transactional sex. This represents a dangerous confluence of risk for female farmers, in which alcohol plays an important role in income generation and also facilitates high-risk sexual behavior. Alcohol production and consumption has the potential to both directly and indirectly place women at risk for undesirable sexual and reproductive health outcomes. Group formation, better access to finance, and engaging with agricultural extension officers were identified as potential interventions for supporting women farmers and challenging harmful gender norms. In addition, joint, multi-sectoral approaches from health and agriculture and alternative income-generating strategies for women might better address the complexities of achieving safe and sustainable livelihoods for women in this context

Metal-insulator transition in vanadium dioxide nanobeams: probing sub-domain properties of strongly correlated materials

Many strongly correlated electronic materials, including high-temperature superconductors, colossal magnetoresistance and metal-insulator-transition (MIT) materials, are inhomogeneous on a microscopic scale as a result of domain structure or compositional variations. An important potential advantage of nanoscale samples is that they exhibit the homogeneous properties, which can differ greatly from those of the bulk. We demonstrate this principle using vanadium dioxide, which has domain structure associated with its dramatic MIT at 68 degrees C. Our studies of single-domain vanadium dioxide nanobeams reveal new aspects of this famous MIT, including supercooling of the metallic phase by 50 degrees C; an activation energy in the insulating phase consistent with the optical gap; and a connection between the transition and the equilibrium carrier density in the insulating phase. Our devices also provide a nanomechanical method of determining the transition temperature, enable measurements on individual metal-insulator interphase walls, and allow general investigations of a phase transition in quasi-one-dimensional geometry.Comment: 9 pages, 3 figures, original submitted in June 200

Fully-automated μMRI morphometric phenotyping of the Tc1 mouse model of Down Syndrome

We describe a fully automated pipeline for the morphometric phenotyping of mouse brains from μMRI data, and show its application to the Tc1 mouse model of Down syndrome, to identify new morphological phenotypes in the brain of this first transchromosomic animal carrying human chromosome 21. We incorporate an accessible approach for simultaneously scanning multiple ex vivo brains, requiring only a 3D-printed brain holder, and novel image processing steps for their separation and orientation. We employ clinically established multi-atlas techniques-superior to single-atlas methods-together with publicly-available atlas databases for automatic skull-stripping and tissue segmentation, providing high-quality, subject-specific tissue maps. We follow these steps with group-wise registration, structural parcellation and both Voxel- and Tensor-Based Morphometry-advantageous for their ability to highlight morphological differences without the laborious delineation of regions of interest. We show the application of freely available open-source software developed for clinical MRI analysis to mouse brain data: NiftySeg for segmentation and NiftyReg for registration, and discuss atlases and parameters suitable for the preclinical paradigm. We used this pipeline to compare 29 Tc1 brains with 26 wild-type littermate controls, imaged ex vivo at 9.4T. We show an unexpected increase in Tc1 total intracranial volume and, controlling for this, local volume and grey matter density reductions in the Tc1 brain compared to the wild-types, most prominently in the cerebellum, in agreement with human DS and previous histological findings

Targeted prevention of common mental health disorders in university students: randomised controlled trial of a transdiagnostic trait-focused web-based intervention

Background: A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders.<p></p> Aims: To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students.<p></p> Method: Students were recruited online (n = 1047, age: M = 21.8, SD = 4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n = 519) or a control intervention (n = 528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes.<p></p> Results: Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p<.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p = .018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered eating.<p></p> Conclusions This study suggests that a transdiagnostic web-based intervention for university students targeting underlying personality risk factors may be a promising way of preventing common mental disorders with a low-intensity intervention

The WACMOS-ET project, part 2 : evaluation of global terrestrial evaporation data sets

The WAter Cycle Multi-mission Observation Strategy - EvapoTranspiration (WACMOS-ET) project aims to advance the development of land evaporation estimates on global and regional scales. Its main objective is the derivation, validation, and intercomparison of a group of existing evaporation retrieval algorithms driven by a common forcing data set. Three commonly used process-based evaporation methodologies are evaluated: the Penman-Monteith algorithm behind the official Moderate Resolution Imaging Spectroradiometer (MODIS) evaporation product (PM-MOD), the Global Land Evaporation Amsterdam Model (GLEAM), and the Priestley-Taylor Jet Propulsion Laboratory model (PT-JPL). The resulting global spatiotemporal variability of evaporation, the closure of regional water budgets, and the discrete estimation of land evaporation components or sources (i.e. transpiration, interception loss, and direct soil evaporation) are investigated using river discharge data, independent global evaporation data sets and results from previous studies. In a companion article (Part 1), Michel et al. (2016) inspect the performance of these three models at local scales using measurements from eddy-covariance towers and include in the assessment the Surface Energy Balance System (SEBS) model. In agreement with Part 1, our results indicate that the Priestley and Taylor products (PT-JPL and GLEAM) perform best overall for most ecosystems and climate regimes. While all three evaporation products adequately represent the expected average geographical patterns and seasonality, there is a tendency in PM-MOD to underestimate the flux in the tropics and subtropics. Overall, results from GLEAM and PT-JPL appear more realistic when compared to surface water balances from 837 globally distributed catchments and to separate evaporation estimates from ERA-Interim and the model tree ensemble (MTE). Nonetheless, all products show large dissimilarities during conditions of water stress and drought and deficiencies in the way evaporation is partitioned into its different components. This observed inter-product variability, even when common forcing is used, suggests that caution is necessary in applying a single data set for large-scale studies in isolation. A general finding that different models perform better under different conditions highlights the potential for considering biome- or climate-specific composites of models. Nevertheless, the generation of a multi-product ensemble, with weighting based on validation analyses and uncertainty assessments, is proposed as the best way forward in our long-term goal to develop a robust observational benchmark data set of continental evaporation

Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation

Astrocytes play crucial and diverse roles in brain health and disease. The ability to selectively control astrocytes provides a valuable tool for understanding their function and has the therapeutic potential to correct dysfunction. Existing technologies such as optogenetics and chemogenetics require the introduction of foreign proteins, which adds a layer of complication and hinders their clinical translation. A novel technique, magnetomechanical stimulation (MMS), that enables remote and selective control of astrocytes without genetic modification is described here. MMS exploits the mechanosensitivity of astrocytes and triggers mechanogated Ca2+ and adenosine triphosphate (ATP) signaling by applying a magnetic field to antibody-functionalized magnetic particles that are targeted to astrocytes. Using purpose-built magnetic devices, the mechanosensory threshold of astrocytes is determined, a sub-micrometer particle for effective MMS is identified, the in vivo fate of the particles is established, and cardiovascular responses are induced in rats after particles are delivered to specific brainstem astrocytes. By eliminating the need for device implantation and genetic modification, MMS is a method for controlling astroglial activity with an improved prospect for clinical application than existing technologies

Tissue magnetic susceptibility mapping as a marker of tau pathology in Alzheimer's disease.

Alzheimer's disease is connected to a number of other neurodegenerative conditions, known collectively as 'tauopathies', by the presence of aggregated tau protein in the brain. Neuroinflammation and oxidative stress in AD are associated with tau pathology and both the breakdown of axonal sheaths in white matter tracts and excess iron accumulation grey matter brain regions. Despite the identification of myelin and iron concentration as major sources of contrast in quantitative susceptibility maps of the brain, the sensitivity of this technique to tau pathology has yet to be explored. In this study, we perform Quantitative Susceptibility Mapping (QSM) and T2* mapping in the rTg4510, a mouse model of tauopathy, both in vivo and ex vivo. Significant correlations were observed between histological measures of myelin content and both mean regional magnetic susceptibility and T2* values. These results suggest that magnetic susceptibility is sensitive to tissue myelin concentrations across different regions of the brain. Differences in magnetic susceptibility were detected in the corpus callosum, striatum, hippocampus and thalamus of the rTg4510 mice relative to wild type controls. The concentration of neurofibrillary tangles was found to be low to intermediate in these brain regions indicating that QSM may be a useful biomarker for early stage detection of tau pathology in neurodegenerative diseases

Use of AUDIT, and measures of drinking frequency and patterns to detect associations between alcohol and sexual behaviour in male sex workers in Kenya

Background: Previous research has linked alcohol use with an increased number of sexual partners, inconsistent condom use and a raised incidence of sexually transmitted infections (STIs). However, alcohol measures have been poorly standardised, with many ill-suited to eliciting, with adequate precision, the relationship between alcohol use and sexual risk behaviour. This study investigates which alcohol indicator - single-item measures of frequency and patterns of drinking (> = 6 drinks on 1 occasion), or the Alcohol Use Disorders Identification Test (AUDIT) - can detect associations between alcohol use and unsafe sexual behaviour among male sex workers. Methods: A cross-sectional survey in 2008 recruited male sex workers who sell sex to men from 65 venues in Mombasa district, Kenya, similar to a 2006 survey. Information was collected on socio-demographics, substance use, sexual behaviour, violence and STI symptoms. Multivariate models examined associations between the three measures of alcohol use and condom use, sexual violence, and penile or anal discharge. Results: The 442 participants reported a median 2 clients/week (IQR = 1-3), with half using condoms consistently in the last 30 days. Of the approximately 70% of men who drink alcohol, half (50.5%) drink two or more times a week. Binge drinking was common (38.9%). As defined by AUDIT, 35% of participants who drink had hazardous drinking, 15% harmful drinking and 21% alcohol dependence. Compared with abstinence, alcohol dependence was associated with inconsistent condom use (AOR = 2.5, 95% CI = 1.3-4.6), penile or anal discharge (AOR = 1.9, 95% CI = 1.0-3.8), and two-fold higher odds of sexual violence (AOR = 2.0, 95% CI = 0.9-4.9). Frequent drinking was associated with inconsistent condom use (AOR = 1.8, 95% CI = 1.1-3.0) and partner number, while binge drinking was only linked with inconsistent condom use (AOR = 1.6, 95% CI = 1.0-2.5). Conclusions: Male sex workers have high levels of hazardous and harmful drinking, and require alcohol-reduction interventions. Compared with indicators of drinking frequency or pattern, the AUDIT measure has stronger associations with inconsistent condom use, STI symptoms and sexual violence. Increased use of the AUDIT tool in future studies may assist in delineating with greater precision the explanatory mechanisms which link alcohol use, drinking contexts, sexual behaviours and HIV transmission