Exploration of infectious disease transmission dynamics using the relative probability of direct transmission between patients

The question “who infected whom” is a perennial one in the study of infectious disease dynamics. To understand characteristics of infectious diseases such as how many people will one case produce over the course of infection (the reproductive number), how much time between the infection of two connected cases (the generation interval), and what factors are associated with transmission, one must ascertain who infected whom. The current best practices for linking cases are contact investigations and pathogen whole genome sequencing (WGS). However, these data sources cannot perfectly link cases, are expensive to obtain, and are often not available for all cases in a study. This lack of discriminatory data limits the use of established methods in many existing infectious disease datasets. We developed a method to estimate the relative probability of direct transmission between any two infectious disease cases. We used a subset of cases that have pathogen WGS or contact investigation data to train a model and then used demographic, spatial, clinical, and temporal data to predict the relative transmission probabilities for all case-pairs using a simple machine learning algorithm called naive Bayes. We adapted existing methods to estimate the reproductive number and generation interval to use these probabilities. Finally, we explored the associations between various covariates and transmission and how they related to the associations between covariates and pathogen genetic relatedness. We applied these methods to a tuberculosis outbreak in Hamburg, Germany and to surveillance data in Massachusetts, USA. Through simulations we found that our estimated transmission probabilities accurately classified pairs as links and nonlinks and were able to accurately estimate the reproductive number and the generation interval. We also found that the association between covariates and genetic relatedness captures the direction but not absolute magnitude of the association between covariates and transmission, but the bias was improved by using effect estimates from the naive Bayes algorithm. The methods developed in this dissertation can be used to explore transmission dynamics and estimate infectious disease parameters in established datasets where this was not previously feasible because of a lack of highly discriminatory information, and therefore expand our understanding of many infectious diseases

Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington's disease patients.

Quantification of disease-associated proteins in the cerebrospinal fluid (CSF) has been critical for the study and treatment of several neurodegenerative disorders; however, mutant huntingtin protein (mHTT), the cause of Huntington's disease (HD), is at very low levels in CSF and, to our knowledge, has never been measured previously

Freedom from Violence: Tools for Working with Trauma, Mental Health and Substance Use: Resource Tool Kit

First paragraph: The aim of this tool kit is to actively engage readers in applying a feminist analysis to women's experiences of mental health, substance use and past and current experiences of violence. The tool kit contains a wide variety of voices that speak to these issues by drawing on a range of sources: the experience of providing services to women, theory, research, feminist activism and scholarship and, naturally, by the writers' own experiences of substance use, mental health problems and violence

HIT-COVID, a global database tracking public health interventions to COVID-19

The COVID-19 pandemic has sparked unprecedented public health and social measures (PHSM) by national and local governments, including border restrictions, school closures, mandatory facemask use and stay at home orders. Quantifying the effectiveness of these interventions in reducing disease transmission is key to rational policy making in response to the current and future pandemics. In order to estimate the effectiveness of these interventions, detailed descriptions of their timelines, scale and scope are needed. The Health Intervention Tracking for COVID-19 (HIT-COVID) is a curated and standardized global database that catalogues the implementation and relaxation of COVID-19 related PHSM. With a team of over 200 volunteer contributors, we assembled policy timelines for a range of key PHSM aimed at reducing COVID-19 risk for the national and first administrative levels (e.g. provinces and states) globally, including details such as the degree of implementation and targeted populations. We continue to maintain and adapt this database to the changing COVID-19 landscape so it can serve as a resource for researchers and policymakers alike

Visuospatial Processing Deficits Linked to Posterior Brain Regions in Premanifest and Early Stage Huntington's Disease.

OBJECTIVES: Visuospatial processing deficits have been reported in Huntington's disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. METHODS: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. RESULTS: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation ("same") was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. CONCLUSIONS: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595-608)

Progressive alterations in white matter microstructure across the timecourse of Huntington's disease

BACKGROUND: Whole-brain longitudinal diffusion studies are crucial to examine changes in structural connectivity in neurodegeneration. Here, we investigated the longitudinal alterations in white matter (WM) microstructure across the timecourse of Huntington's disease (HD). METHODS: We examined changes in WM microstructure from premanifest to early manifest disease, using data from two cohorts with different disease burden. The TrackOn-HD study included 67 controls, 67 premanifest, and 10 early manifest HD (baseline and 24-month data); the PADDINGTON study included 33 controls and 49 early manifest HD (baseline and 15-month data). Longitudinal changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity from baseline to last study visit were investigated for each cohort using tract-based spatial statistics. An optimized pipeline was employed to generate participant-specific templates to which diffusion tensor imaging maps were registered and change maps were calculated. We examined longitudinal differences between HD expansion-carriers and controls, and correlations with clinical scores, including the composite UHDRS (cUHDRS). RESULTS: HD expansion-carriers from TrackOn-HD, with lower disease burden, showed a significant longitudinal decline in FA in the left superior longitudinal fasciculus and an increase in MD across subcortical WM tracts compared to controls, while in manifest HD participants from PADDINGTON, there were significant widespread longitudinal increases in diffusivity compared to controls. Baseline scores in clinical scales including the cUHDRS predicted WM microstructural change in HD expansion-carriers. CONCLUSION: The present study showed significant longitudinal changes in WM microstructure across the HD timecourse. Changes were evident in larger WM areas and across more metrics as the disease advanced, suggesting a progressive alteration of WM microstructure with disease evolution

Nantucket Shellfish Management Plan

Nantucket’s shellfisheries are significant both locally and nationally. Locally, commercial and recreational shellfishing are critical to the Island’s history, culture, and economy. Nationally, the Island’s largest commercial shellfishery — the Nantucket bay scallop fishery is one of the last wild-harvest bay scallop fisheries in the country, but there is growing concern over the health of the overall population and the sustainability of the fishery. Given the importance of the shellfisheries on Nantucket and the drastic decline of bay scallop populations elsewhere along the Atlantic coast, there is a compelling interest in ensuring that the Town’s shellfish are managed to sustain both the shellfishing industry and the resources. This is the first official management plan for commercially and recreationally harvested shellfish in Nantucket waters. The Plan addresses bay scallops, quahogs, oysters, mussels, soft‐shell clams, and conchs

Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease

BACKGROUND: Deterioration of cognitive functioning is a debilitating symptom in many neurodegenerative diseases, such as Huntington's disease (HD). To date, there are no effective treatments for the cognitive problems associated with HD. Cognitive assessment outcomes will have a central role in the efforts to develop treatments to delay onset or slow the progression of the disease. The TRACK-HD study was designed to build a rational basis for the selection of cognitive outcomes for HD clinical trials. METHODS: There were a total of 349 participants, including controls (n=116), premanifest HD (n=117) and early HD (n=116). A standardised cognitive assessment battery (including nine cognitive tests comprising 12 outcome measures) was administered at baseline, and at 12 and 24 months, and consisted of a combination of paper and pencil and computerised tasks selected to be sensitive to cortical-striatal damage or HD. Each cognitive outcome was analysed separately using a generalised least squares regression model. Results are expressed as effect sizes to permit comparisons between tasks. RESULTS: 10 of the 12 cognitive outcomes showed evidence of deterioration in the early HD group, relative to controls, over 24 months, with greatest sensitivity in Symbol Digit, Circle Tracing direct and indirect, and Stroop word reading. In contrast, there was very little evidence of deterioration in the premanifest HD group relative to controls. CONCLUSIONS: The findings describe tests that are sensitive to longitudinal cognitive change in HD and elucidate important considerations for selecting cognitive outcomes for clinical trials of compounds aimed at ameliorating cognitive decline in HD