Optimising quantisation noise in energy measurement

We give a model of parallel distributed genetic improvement. With modern low cost power monitors; high speed Ethernet LAN latency and network jitter have little effect. The model calculates a minimum usable mutation effect based on the analogue to digital converter (ADC)’s resolution and shows the optimal test duration is inversely proportional to smallest impact we wish to detect. Using the example of a 1 kHz 12 bit 0.4095 Amp ADC optimising software energy consumption we find: it will be difficult to detect mutations which an average effect less than 58 μA, and typically experiments should last well under a second

Genetic Improvement @ ICSE 2020

Following Prof. Mark Harman of Facebook's keynote and formal presentations (which are recorded in the proceedings) there was a wide ranging discussion at the eighth international Genetic Improvement workshop, GI-2020 @ ICSE (held as part of the 42nd ACM/IEEE International Conference on Software Engineering on Friday 3rd July 2020). Topics included industry take up, human factors, explainabiloity (explainability, justifyability, exploitability) and GI benchmarks. We also contrast various recent online approaches (e.g. SBST 2020) to holding virtual computer science conferences and workshops via the WWW on the Internet without face-2-face interaction. Finally we speculate on how the Coronavirus Covid-19 Pandemic will affect research next year and into the future

Heat shock factor 2 is a stress‐responsive mediator of neuronal migration defects in models of fetal alcohol syndrome

Fetal alcohol spectrum disorder (FASD) is a frequent cause of mental retardation. However, the molecular mechanisms underlying brain development defects induced by maternal alcohol consumption during pregnancy are unclear. We used normal andHsf2‐deficient mice and cell systems to uncover a pivotal role for heat shock factor 2 (HSF2) in radial neuronal migration defects in the cortex, a hallmark of fetal alcohol exposure. Upon fetal alcohol exposure, HSF2 is essential for the triggering of HSF1 activation, which is accompanied by distinctive post‐translational modifications, and HSF2 steers the formation of atypical alcohol‐specific HSF1–HSF2 heterocomplexes. This perturbs the in vivo binding of HSF2 to heat shock elements (HSEs) in genes that control neuronal migration in normal conditions, such as p35 or the MAPs(microtubule‐associated proteins, such as Dclk1 and Dcx), and alters their expression. In the absence of HSF2, migration defects as well as alterations in gene expression are reduced. Thus, HSF2, as a sensor for alcohol stress in the fetal brain, acts as a mediator of the neuronal migration defects associated with FASD

Braving difficult choices alone: children's and adolescents' medical decision making.

OBJECTIVE: What role should minors play in making medical decisions? The authors examined children's and adolescents' desire to be involved in serious medical decisions and the emotional consequences associated with them. METHODS: Sixty-three children and 76 adolescents were presented with a cover story about a difficult medical choice. Participants were tested in one of four conditions: (1) own informed choice; (2) informed parents' choice to amputate; (3) informed parents' choice to continue a treatment; and (4) uninformed parents' choice to amputate. In a questionnaire, participants were asked about their choices, preference for autonomy, confidence, and emotional reactions when faced with a difficult hypothetical medical choice. RESULTS: Children and adolescents made different choices and participants, especially adolescents, preferred to make the difficult choice themselves, rather than having a parent make it. Children expressed fewer negative emotions than adolescents. Providing information about the alternatives did not affect participants' responses. CONCLUSIONS: Minors, especially adolescents, want to be responsible for their own medical decisions, even when the choice is a difficult one. For the adolescents, results suggest that the decision to be made, instead of the agent making the decision, is the main element influencing their emotional responses and decision confidence. For children, results suggest that they might be less able than adolescents to project how they would feel. The results, overall, draw attention to the need to further investigate how we can better involve minors in the medical decision-making process

Reporting quality of randomized trials in the diet and exercise literature for weight loss

BACKGROUND: To adequately assess individual studies and synthesize quantitative research on weight loss studies, transparent reporting of data is required. The authors examined the reporting quality of randomized trials in the weight loss literature, focusing exclusively on subject characteristics as they relate to enrollment, allocation, and follow-up. METHODS: An extensive literature review, which included a computerized search of the MEDLINE database, manual searches of bibliographic references, and cross-referencing of 92 review articles was conducted. A checklist, based on CONSORT recommendations, was used to collect information on whether or not authors reported age, gender, co-morbid disease, medication use, race/ethnicity, and postmenopausal status. Also tracked was whether or not initial and final sample size was reported and stratified by gender. RESULTS: Of 604 possible articles, 231 articles met eligibility criteria. Important subject characteristics were not reported as the following breakdown indicates: age (11%), gender (4%), race/ethnicity (86%), co-morbid disease states (34%), and medication use (92%). Additionally, 21% of articles failed to report initial sample size by gender while 69% neglected to report final sample size by gender. CONCLUSION: Inadequate reporting can create difficulties with interpretation and can lead to biased results receiving false credibility. The quality of reporting for weight loss studies needs considerable improvement

Physical inactivity is associated with chronic musculoskeletal complaints 11 years later: results from the Nord-Trøndelag Health Study

Background Physical inactivity is associated with several diseases, but studies evaluating the association between chronic musculoskeletal complaints (MSCs) and physical exercise have shown conflicting results. The aim of this large-scale prospective population-based study was to investigate the association between self-reported physical exercise at baseline and the prevalence of chronic musculoskeletal complaints (MSCs) 11 years later. Methods The results are based upon two consecutive public health studies conducted within the county of Nord-Trøndelag, Norway (The HUNT studies). A total of 39,520 (83%) out of 47,556 adults who participated in HUNT 1 and HUNT 2 responded to questions about physical exercise at baseline in 1984–86, and to questions about musculoskeletal complaints 11 years later (1995–97). Chronic MSCs was defined as MSCs ≥ 3 months during the past year, and chronic widespread MSCs such as pain ≥ 15 days during the last month from the axial region, above the waist, and below the waist. Associations were assessed using multiple logistic regression, estimating prevalence odds ratio (OR) with 95% confidence intervals (CIs). All the final analyses were adjusted for age, gender, body mass index, smoking and education level. Results At follow-up 20,223 (51%) reported chronic MSCs, and among these 2,318 (5.9%) reported chronic widespread MSCs. Individuals who exercised at baseline were less likely to report chronic MSCs 11 years later (OR 0.91, 95% CI 0.85–0.97) than inactive persons. Among individuals who exercised more than three times per week, chronic widespread MSCs were 28% less common (OR 0.72, 95% CI 0.59–0.88) compared to inactive individuals. Conclusion In this large-scale population-based study, physical exercise was associated with lower prevalence of chronic MSCs, in particular chronic widespread MSCs. Future studies should try to clarify whether chronic MSCs are a cause or a consequence of inactivity

Morpholino Gene Knockdown in Adult Fundulus heteroclitus: Role of SGK1 in Seawater Acclimation

The Atlantic killifish (Fundulus heteroclitus) is an environmental sentinel organism used extensively for studies on environmental toxicants and salt (NaCl) homeostasis. Previous research in our laboratory has shown that rapid acclimation of killifish to seawater is mediated by trafficking of CFTR chloride channels from intracellular vesicles to the plasma membrane in the opercular membrane within the first hour in seawater, which enhances chloride secretion into seawater, thereby contributing to salt homeostasis. Acute transition to seawater is also marked by an increase in both mRNA and protein levels of serum glucocorticoid kinase 1 (SGK1) within 15 minutes of transfer. Although the rise in SGK1 in gill and its functional analog, the opercular membrane, after seawater transfer precedes the increase in membrane CFTR, a direct role of SGK1 in elevating membrane CFTR has not been established in vivo. To test the hypothesis that SGK1 mediates the increase in plasma membrane CFTR we designed two functionally different vivo-morpholinos to knock down SGK1 in gill, and developed and validated a vivo-morpholino knock down technique for adult killifish. Injection (intraperitoneal, IP) of the splice blocking SGK1 vivo-morpholino reduced SGK1 mRNA in the gill after transition from fresh to seawater by 66%. The IP injection of the translational blocking and splice blocking vivo-morpholinos reduced gill SGK1 protein abundance in fish transferred from fresh to seawater by 64% and 53%, respectively. Moreover, knock down of SGK1 completely eliminated the seawater induced rise in plasma membrane CFTR, demonstrating that the increase in SGK1 protein is required for the trafficking of CFTR from intracellular vesicles in mitochondrion rich cells to the plasma membrane in the gill during acclimation to seawater. This is the first report of the use of vivo-morpholinos in adult killifish and demonstrates that vivo-morpholinos are a valuable genetic tool for this environmentally relevant model organism

NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury

BACKGROUND: A major class of axon growth-repulsive molecules associated with CNS scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs). Experimental spinal cord injury (SCI) has demonstrated rapid re-expression of CSPGs at and around the lesion site. The pharmacological digestion of CSPGs in such lesion models results in substantially enhanced axonal regeneration and a significant functional recovery. The potential therapeutic relevance of interfering with CSPG expression or function following experimental injuries seems clear, however, the spatio-temporal pattern of expression of individual members of the CSPG family following human spinal cord injury is only poorly defined. In the present correlative investigation, the expression pattern of CSPG family members NG2, neurocan, versican and phosphacan was studied in the human spinal cord. METHODS: An immunohistochemical investigation in post mortem samples of control and lesioned human spinal cords was performed. All patients with traumatic SCI had been clinically diagnosed as having "complete" injuries and presented lesions of the maceration type. RESULTS: In sections from control spinal cord, NG2 immunoreactivity was restricted to stellate-shaped cells corresponding to oligodendrocyte precursor cells. The distribution patterns of phosphacan, neurocan and versican in control human spinal cord parenchyma were similar, with a fine reticular pattern being observed in white matter (but also located in gray matter for phosphacan). Neurocan staining was also associated with blood vessel walls. Furthermore, phosphacan, neurocan and versican were present in the myelin sheaths of ventral and dorsal nerve roots axons. After human SCI, NG2 and phosphacan were both detected in the evolving astroglial scar. Neurocan and versican were detected exclusively in the lesion epicentre, being associated with infiltrating Schwann cells in the myelin sheaths of invading peripheral nerve fibres from lesioned dorsal roots. CONCLUSION: NG2 and phosphacan were both present in the evolving astroglial scar and, therefore, might play an important role in the blockade of successful CNS regeneration. Neurocan and versican, however, were located at the lesion epicentre, associated with Schwann cell myelin on regenerating peripheral nerve fibres, a distribution that was unlikely to contribute to failed CNS axon regeneration. The present data points to the importance of such correlative investigations for demonstrating the clinical relevance of experimental data

Emergence of the Asian 1 Genotype of Dengue Virus Serotype 2 in Viet Nam: In Vivo Fitness Advantage and Lineage Replacement in South-East Asia

A better description of the extent and structure of genetic diversity in dengue virus (DENV) in endemic settings is central to its eventual control. To this end we determined the complete coding region sequence of 187 DENV-2 genomes and 68 E genes from viruses sampled from Vietnamese patients between 1995 and 2009. Strikingly, an episode of genotype replacement was observed, with Asian 1 lineage viruses entirely displacing the previously dominant Asian/American lineage viruses. This genotype replacement event also seems to have occurred within DENV-2 in Thailand and Cambodia, suggestive of a major difference in viral fitness. To determine the cause of this major evolutionary event we compared both the infectivity of the Asian 1 and Asian/American genotypes in mosquitoes and their viraemia levels in humans. Although there was little difference in infectivity in mosquitoes, we observed significantly higher plasma viraemia levels in paediatric patients infected with Asian 1 lineage viruses relative to Asian/American viruses, a phenotype that is predicted to result in a higher probability of human-to-mosquito transmission. These results provide a mechanistic basis to a marked change in the genetic structure of DENV-2 and more broadly underscore that an understanding of DENV evolutionary dynamics can inform the development of vaccines and anti-viral drugs