Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome

Loss of function in the Scn1a gene leads to a severe epileptic encephalopathy called Dravet syndrome (DS). Reduced excitability in cortical inhibitory neurons is thought to be the major cause of DS seizures. Here, in contrast, we show enhanced excitability in thalamic inhibitory neurons that promotes the non-convulsive seizures that are a prominent yet poorly understood feature of DS. In a mouse model of DS with a loss of function in Scn1a, reticular thalamic cells exhibited abnormally long bursts of firing caused by the downregulation of calcium-activated potassium SK channels. Our study supports a mechanism in which loss of SK activity causes the reticular thalamic neurons to become hyperexcitable and promote non-convulsive seizures in DS. We propose that reduced excitability of inhibitory neurons is not global in DS and that non-GABAergic mechanisms such as SK channels may be important targets for treatment

Search for Exotic Strange Quark Matter in High Energy Nuclear Reactions

We report on a search for metastable positively and negatively charged states of strange quark matter in Au+Pb reactions at 11.6 A GeV/c in experiment E864. We have sampled approximately six billion 10% most central Au+Pb interactions and have observed no strangelet states (baryon number A < 100 droplets of strange quark matter). We thus set upper limits on the production of these exotic states at the level of 1-6 x 10^{-8} per central collision. These limits are the best and most model independent for this colliding system. We discuss the implications of our results on strangelet production mechanisms, and also on the stability question of strange quark matter.Comment: 21 pages, 9 figures, to be published in Nuclear Physics A (Carl Dover memorial edition

The incidence of myocardial injury following post-operative Goal Directed Therapy.

BACKGROUND: Studies suggest that Goal Directed Therapy (GDT) results in improved outcome following major surgery. However, there is concern that pre-emptive use of inotropic therapy may lead to an increased incidence of myocardial ischaemia and infarction. METHODS: Post hoc analysis of data collected prospectively during a randomised controlled trial of the effects of post-operative GDT in high-risk general surgical patients. Serum troponin T concentrations were measured at baseline and on day 1 and day 2 following surgery. Continuous ECG monitoring was performed during the eight hour intervention period. Patients were followed up for predefined cardiac complications. A univariate analysis was performed to identify any associations between potential risk factors for myocardial injury and elevated troponin T concentrations. RESULTS: GDT was associated with fewer complications, and a reduced duration of hospital stay. Troponin T concentrations above 0.01 microg l-1 were identified in eight patients in the GDT group and six in the control group. Values increased above 0.05 microg l-1 in four patients in the GDT group and two patients in the control group. There were no overall differences in the incidence of elevated troponin T concentrations. The incidence of cardiovascular complications was also similar. None of the patients, in whom troponin T concentrations were elevated, developed ECG changes indicating myocardial ischaemia during the intervention period. The only factor to be associated with elevated troponin T concentrations following surgery was end-stage renal failure. CONCLUSION: The use of post-operative GDT does not result in an increased incidence of myocardial injury

Metabolic analysis of the interaction between plants and herbivores

Insect herbivores by necessity have to deal with a large arsenal of plant defence metabolites. The levels of defence compounds may be increased by insect damage. These induced plant responses may also affect the metabolism and performance of successive insect herbivores. As the chemical nature of induced responses is largely unknown, global metabolomic analyses are a valuable tool to gain more insight into the metabolites possibly involved in such interactions. This study analyzed the interaction between feral cabbage (Brassica oleracea) and small cabbage white caterpillars (Pieris rapae) and how previous attacks to the plant affect the caterpillar metabolism. Because plants may be induced by shoot and root herbivory, we compared shoot and root induction by treating the plants on either plant part with jasmonic acid. Extracts of the plants and the caterpillars were chemically analysed using Ultra Performance Liquid Chromatography/Time of Flight Mass Spectrometry (UPLCT/MS). The study revealed that the levels of three structurally related coumaroylquinic acids were elevated in plants treated on the shoot. The levels of these compounds in plants and caterpillars were highly correlated: these compounds were defined as the ‘metabolic interface’. The role of these metabolites could only be discovered using simultaneous analysis of the plant and caterpillar metabolomes. We conclude that a metabolomics approach is useful in discovering unexpected bioactive compounds involved in ecological interactions between plants and their herbivores and higher trophic levels.

Foot pain and foot health in an educated population of adults: results from the Glasgow Caledonian University Alumni Foot Health Survey

Abstract Background Foot pain is common amongst the general population and impacts negatively on physical function and quality of life. Associations between personal health characteristics, lifestyle/behaviour factors and foot pain have been studied; however, the role of wider determinants of health on foot pain have received relatively little attention. Objectives of this study are i) to describe foot pain and foot health characteristics in an educated population of adults; ii) to explore associations between moderate-to-severe foot pain and a variety of factors including gender, age, medical conditions/co-morbidity/multi-morbidity, key indicators of general health, foot pathologies, and social determinants of health; and iii) to evaluate associations between moderate-to-severe foot pain and foot function, foot health and health-related quality-of-life. Methods Between February and March 2018, Glasgow Caledonian University Alumni with a working email address were invited to participate in the cross-sectional electronic survey (anonymously) by email via the Glasgow Caledonian University Alumni Office. The survey was constructed using the REDCap secure web online survey application and sought information on presence/absence of moderate-to-severe foot pain, patient characteristics (age, body mass index, socioeconomic status, occupation class, comorbidities, and foot pathologies). Prevalence data were expressed as absolute frequencies and percentages. Multivariate logistic and linear regressions were undertaken to identify associations 1) between independent variables and moderate-to-severe foot pain, and 2) between moderate-to-severe foot pain and foot function, foot health and health-related quality of life. Results Of 50,228 invitations distributed, there were 7707 unique views and 593 valid completions (median age [inter-quartile range] 42 [31–52], 67.3% female) of the survey (7.7% response rate). The sample was comprised predominantly of white Scottish/British (89.4%) working age adults (95%), the majority of whom were overweight or obese (57.9%), and in either full-time or part-time employment (82.5%) as professionals (72.5%). Over two-thirds (68.5%) of the sample were classified in the highest 6 deciles (most affluent) of social deprivation. Moderate-to-severe foot pain affected 236/593 respondents (39.8%). High body mass index, presence of bunions, back pain, rheumatoid arthritis, hip pain and lower occupation class were included in the final multivariate model and all were significantly and independently associated with moderate-to-severe foot pain (p < 0.05), except for rheumatoid arthritis (p = 0.057). Moderate-to-severe foot pain was significantly and independently associated lower foot function, foot health and health-related quality of life scores following adjustment for age, gender and body mass index (p < 0.05). Conclusions Moderate-to-severe foot pain was highly prevalent in a university-educated population and was independently associated with female gender, high body mass index, bunions, back pain, hip pain and lower occupational class. Presence of moderate-to-severe foot pain was associated with worse scores for foot function, foot health and health-related quality-of-life. Education attainment does not appear to be protective against moderate-to-severe foot pain

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography

A toolkit for incorporating genetics into mainstream medical services: Learning from service development pilots in England

Background: As advances in genetics are becoming increasingly relevant to mainstream healthcare, a major challenge is to ensure that these are integrated appropriately into mainstream medical services. In 2003, the Department of Health for England announced the availability of start-up funding for ten 'Mainstreaming Genetics' pilot services to develop models to achieve this. Methods: Multiple methods were used to explore the pilots' experiences of incorporating genetics which might inform the development of new services in the future. A workshop with project staff, an email questionnaire, interviews and a thematic analysis of pilot final reports were carried out. Results: Seven themes relating to the integration of genetics into mainstream medical services were identified: planning services to incorporate genetics; the involvement of genetics departments; the establishment of roles incorporating genetic activities; identifying and involving stakeholders; the challenges of working across specialty boundaries; working with multiple healthcare organisations; and the importance of cultural awareness of genetic conditions. Pilots found that the planning phase often included the need to raise awareness of genetic conditions and services and that early consideration of organisational issues such as clinic location was essential. The formal involvement of genetics departments was crucial to success; benefits included provision of clinical and educational support for staff in new roles. Recruitment and retention for new roles outside usual career pathways sometimes proved difficult. Differences in specialties' working practices and working with multiple healthcare organisations also brought challenges such as the 'genetic approach' of working with families, incompatible record systems and different approaches to health professionals' autonomous practice. 'Practice points' have been collated into a Toolkit which includes resources from the pilots, including job descriptions and clinical tools. These can be customised for reuse by other services. Conclusions: Healthcare services need to translate advances in genetics into benefits for patients. Consideration of the issues presented here when incorporating genetics into mainstream medical services will help ensure that new service developments build on the body of experience gained by the pilots, to provide high quality services for patients with or at risk of genetic conditions

DNA repair: Clamping down on copy errors

Repair enzymes must communicate across hundreds of nucleotides to undo errors made during DNA replication. Imaging reveals that the enzymes do this by forming a series of ring-like clamps that diffuse along the DNA

Normative perspectives on journalism studies: Stock-taking and future directions

Journalism has advanced greatly as a field in its own right in recent decades. As well as a cause for celebration, however, this may give rise to concerns – in particular that scholars may pay increasing attention to the inner workings of journalistic institutions at the expense of their external ties, impact and significance, including their normative ones. It is true that important normative analyses have appeared in the literature, six of which the article defines and exemplifies. So far, however, these ideas have had relatively little influence on the thought or practice of journalists. The article concludes by suggesting a way in which a closer and more constructive dialogue could be achieved between journalism scholars and practitioners, centring on the normative challenges faced by both sides

Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis.

Biomarkers are needed for predicting the effectiveness of disease modifying antirheumatic drugs (DMARDs). Here, using functional lipid mediator profiling and deeply phenotyped patients with early rheumatoid arthritis (RA), we observe that peripheral blood  specialized pro-resolving mediator (SPM) concentrations are linked with both DMARD responsiveness and disease pathotype. Machine learning analysis demonstrates that baseline plasma concentrations of resolvin D4, 10S, 17S-dihydroxy-docosapentaenoic acid, 15R-Lipoxin (LX)A4 and n-3 docosapentaenoic-derived Maresin 1 are predictive of DMARD responsiveness at 6 months. Assessment of circulating SPM concentrations 6-months after treatment initiation establishes that differences between responders and non-responders are maintained, with a decrease in SPM concentrations in patients resistant to DMARD therapy. These findings elucidate the potential utility of  plasma SPM concentrations as biomarkers of DMARD responsiveness in RA