Primary Teacher Education in Malawi: Insights Into Practice and Policy: Multi-Site Teacher Education Research Project (MUSTER), Country Report Three

Teaching/Communication/Extension/Profession,

Transcranial Magnetic Stimulation and Neuroimaging Coregistration

The development of neuroimaging techniques is one of the most impressive advancements in neuroscience. The main reason for the widespread use of these instruments lies in their capacity to provide an accurate description of neural activity during a cognitive process or during rest. This important advancement is related to the possibility to selectively detect changes of neuronal activity in space and time by means of different biological markers. Specifically, functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and nearinfrared spectroscopy (NIRS) use metabolic markers of ongoing neuronal activity to provide an accurate description of the activation of specific brain areas with high spatial resolution. Similarly, electroencephalography (EEG) is able to detect electric markers of neuronal activity, providing an accurate description of brain activation with high temporal resolution. The application of these techniques during a cognitive task allows important inferences regarding the relation between the detected neural activity, the cognitive process involved in an ongoing task, and behaviour: this is known as a \u201ccorrelational approach\u201d

The role of body fat in multiple sclerosis susceptibility and severity: A Mendelian randomisation study

Objective: The objective of this study was to explore the potential causal associations of body mass index, height, weight, fat mass, fat percentage and non-fat mass in the whole body, arms, legs and trunk (henceforth, ‘anthropometric measures’) with multiple sclerosis (MS) risk and severity. We also investigated the potential for reverse causation between anthropometric measures and MS risk. Methods: We conducted a two-sample univariable, multivariable and bidirectional Mendelian randomisation (MR) analysis. Results: A range of features linked to obesity (body mass index, weight, fat mass and fat percentage) were risk factors for MS development and worsened the disease’s severity in MS patients. Interestingly, we were able to demonstrate that height and non-fat mass have no association with MS risk or MS severity. We demonstrated that the association between anthropometric measures and MS is not subject to bias from reverse causation. Conclusions: Our findings provide evidence from human genetics that a range of features linked to obesity is an important contributor to MS development and MS severity, but height and non-fat mass are not. Importantly, these findings also identify a potentially modifiable factor that may reduce the accumulation of further disability and ameliorate MS severity

Debugging of Web Applications with Web-TLR

Web-TLR is a Web verification engine that is based on the well-established Rewriting Logic--Maude/LTLR tandem for Web system specification and model-checking. In Web-TLR, Web applications are expressed as rewrite theories that can be formally verified by using the Maude built-in LTLR model-checker. Whenever a property is refuted, a counterexample trace is delivered that reveals an undesired, erroneous navigation sequence. Unfortunately, the analysis (or even the simple inspection) of such counterexamples may be unfeasible because of the size and complexity of the traces under examination. In this paper, we endow Web-TLR with a new Web debugging facility that supports the efficient manipulation of counterexample traces. This facility is based on a backward trace-slicing technique for rewriting logic theories that allows the pieces of information that we are interested to be traced back through inverse rewrite sequences. The slicing process drastically simplifies the computation trace by dropping useless data that do not influence the final result. By using this facility, the Web engineer can focus on the relevant fragments of the failing application, which greatly reduces the manual debugging effort and also decreases the number of iterative verifications.Comment: In Proceedings WWV 2011, arXiv:1108.208

Exploring the Role of Plasma Lipids and Statins Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study

BACKGROUND: There has been considerable interest in statins due to their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity. METHOD: We employed two-sample Mendelian randomization (MR) to investigate: (1) the causal role of genetically mimic both cholesterol-dependent (via low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (via Rho GTPases) effects of statins on MS risk and MS severity, (2) the causal link between lipids (high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)) levels and MS risk and severity; and (3) the reverse causation between lipid fractions and MS risk. We used summary statistics from the Global Lipids Genetics Consortium (GLGC), eQTLGen Consortium and the International MS Genetics Consortium (IMSGC) for lipids, expression quantitative trait loci and MS, respectively (GLGC: n = 188,577; eQTLGen: n = 31,684; IMSGC (MS risk): n = 41,505; IMSGC (MS severity): n =7,069). RESULTS: The results of MR using the inverse variance weighted method show that genetically predicted RAC2, a member of cholesterol-independent pathway, (OR 0.86 (95% CI 0.78 to 0.95), p-value 3.80E-03) is implicated causally in reducing MS risk. We found no evidence for the causal role of LDL-C and the member of cholesterol biosynthesis pathway on MS risk. MR results also show that lifelong higher HDL-C (OR 1.14 (95% CI 1.04 to1.26), p-value 7.94E-03) increase MS risk but TG was not. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids. CONCLUSION: Evidence from this study suggests that RAC2 is a genetic modifier of MS risk. Since RAC2 has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk via a cholesterol-independent pathway (i.e., RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk

Finding genetically-supported drug targets for Parkinson's disease using Mendelian randomization of the druggable genome

There is currently no disease-modifying treatment for Parkinson's disease, a common neurodegenerative disorder. Here, the authors use genetic variation associated with gene and protein expression to find putative drug targets for Parkinson's disease using Mendelian randomization of the druggable genome. Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson's disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson's disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson's disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson's disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson's disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson's disease drug development.Peer reviewe

Finding genetically-supported drug targets for Parkinson's disease using Mendelian randomization of the druggable genome

There is currently no disease-modifying treatment for Parkinson's disease, a common neurodegenerative disorder. Here, the authors use genetic variation associated with gene and protein expression to find putative drug targets for Parkinson's disease using Mendelian randomization of the druggable genome. Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson's disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson's disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson's disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson's disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson's disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson's disease drug development.Peer reviewe

The ventilation of buildings and other mitigating measures for COVID-19: a focus on wintertime.

The year 2020 has seen the emergence of a global pandemic as a result of the disease COVID-19. This report reviews knowledge of the transmission of COVID-19 indoors, examines the evidence for mitigating measures, and considers the implications for wintertime with a focus on ventilation.This work was undertaken as a contribution to the Rapid Assistance in Modelling the Pandemic (RAMP) initiative, coordinated by the Royal Society

The ventilation of buildings and other mitigating measures for COVID-19: a focus on wintertime.

The year 2020 has seen the emergence of a global pandemic as a result of the disease COVID-19. This report reviews knowledge of the transmission of COVID-19 indoors, examines the evidence for mitigating measures, and considers the implications for wintertime with a focus on ventilation.This work was undertaken as a contribution to the Rapid Assistance in Modelling the Pandemic (RAMP) initiative, coordinated by the Royal Society