Brain Mechanisms and Social Problems

Knowledge with regard to the Central Nervous System (C.N.S.) is increasing so quickly that it is difficult to adjust one's ideas to the ever-changing scene. When we turn for help to the ideas of great thinkers in the past, it becomes apparent that these are now of limited importance for the simple reason that they were building castles with bricks which are now known to be inadequate. It seems desirable therefore that we should from time to time stand back and view the whole problem of how we use our brains or of how our brains use us.The neurologist is constantly studying the effect of lesions of the C.N.S. on functions and behaviour, so that he is forced to consider the physiological mechanisms involved

Smallest Anopheles farauti occur during the peak transmission season in the Solomon Islands

Background: Malaria transmission varies in intensity amongst Solomon Island villages where Anopheles farauti is the only vector. This variation in transmission intensity might be explained by density-dependent processes during An. farauti larval development, as density dependence can impact adult size with associated fitness costs and daily survivorship. Methods: Adult anophelines were sampled from six villages in Western and Central Provinces, Solomon Islands between March 2014 and February 2017. The size of females was estimated by measuring wing lengths, and then analysed for associations with biting densities and rainfall. Results: In the Solomon Islands, three anopheline species, An. farauti, Anopheles hinesorum and Anopheles lungae, differed in size. The primary malaria vector, An. farauti, varied significantly in size among villages. Greater rainfall was directly associated with higher densities of An. farauti biting rates, but inversely associated with body size with the smallest mean sized mosquitoes present during the peak transmission period. A measurable association between body size and survivorship was not found. Conclusions: Density dependent effects are likely impacting the size of adult An. farauti emerging from a range of larval habitats. The data suggest that rainfall increases An. farauti numbers and that these more abundant mosquitoes are significantly smaller in size, but without any reduced survivorship being associated with smaller size. The higher malaria transmission rate in a high malaria focus village appears to be determined more by vector numbers than size or survivorship of the vectors

Res Medica, Summer 1960, Volume II, Number 2

TABLE OF CONTENTSBRAIN MECHANISMS AND SOCIAL PROBLEMS: W. Ritchie Russell, C.B.E., M.D., D.Sc., F .R.C .P.PORTAL HYPERTENSION: J. G. ClarkRES MEDICA  AUSCULTATION OF THE HEART: R. W. D. Turner, O .B.E., M.A., M.D., F.R .C.P. CONGENITAL MALDEVELOPMENTS AS A CAUSE OF HYDROCEPHALUS : David Doyle THE BIOLOGICAL BASIS OF INDIVIDUALITY: M. F. A. Woodruff, M.D., M.S., F.R.C.S.ANTI-EMETICS IN PREGNANCY AND TRAVEL SICKNESS: R. F. Rintoul BRIGHT AND BRIGHT'S DISEASE: E. A. W. Slater  CONSUMER RESEARCHHOSPITAL ARCHITECTURE IN BRITAI

A genome-wide investigation of adaptive signatures in protein-coding genes related to tool behaviour in New Caledonian and Hawaiian crows

Funding: A David Phillips Fellowship to C.R. from the UK’s Biotechnology and Biological Sciences Research Council (BBSRC; grant BB/G023913/2). Further funding for personnel and data generation of the remaining species was provided by the European Research Council (ERCStG-336536 FuncSpecGen to J.B.W.W.), the Swedish Research Council Vetenskapsrådet (621-2013-4510 to J.B.W.W.), the Knut and Alice Wallenberg Foundation (to J.B.W.W.), the Lawski foundation (to V.E.K. and J.B.W.W.) and the German Research Foundation (KU 3402/1-1 to V.E.K.). A Marsden Fund Grant to G.R.H., R.D.G. and N.J.G. from the Royal Society of New Zealand (UOA1208), a Japanese Society for Promotion of Science Postdoctoral Fellowship (H.A.), together with funding from University of Auckland (G.R.H. and R.D.G.), the Department of Linguistic and Cultural Evolution at the Max Planck Institute for the Science of Human History, and University of Otago (N.J.G.). N.D. acknowledges funding from the Swiss National Science Foundation (P2SKP3_165031 and P300PA_177845) and the Carl Tryggers Foundation.Very few animals habitually manufacture and use tools. It has been suggested that advanced tool behaviour co-evolves with a suite of behavioural, morphological and life-history traits. In fact, there are indications for such an adaptive complex in tool-using crows (genus Corvus species). Here, we sequenced the genomes of two habitually tool-using and ten non-tool-using crow species to search for genomic signatures associated with a tool-using lifestyle. Using comparative genomic and population genetic approaches, we screened for signals of selection in protein-coding genes in the tool-using New Caledonian and Hawaiian crows. While we detected signals of recent selection in New Caledonian crows near genes associated with bill morphology, our data indicate that genetic changes in these two lineages are surprisingly subtle, with little evidence at present for convergence. We explore the biological explanations for these findings, such as the relative roles of gene regulation and protein-coding changes, as well as the possibility that statistical power to detect selection in recently diverged lineages may have been insufficient. Our study contributes to a growing body of literature aiming to decipher the genetic basis of recently evolved complex behaviour.PostprintPeer reviewe

Flexible trial design in practice – dropping and adding arms in STAMPEDE: a multi-arm multi-stage randomised controlled trial

The trial recruits men with locally advanced or metastatic prostate cancer starting standard long-term hormone therapy. There are 5 research arms and 1 control arm. The trial has a pilot stage assessing safety and feasibility, 3 intermediate “activity” stages (I-III) where the outcome measure is failure-free survival (FFS) and one final “efficacy” stage (IV) with overall survival as primary outcome measure. At the end of each stage, each research arm is formally compared pairwise to the control arm. Accrual of further patients is discontinued early for any research arm either not showing sufficient evidence of activity or with adverse safety considerations; accrual continues to arms showing activity with acceptable safety. The stopping guideline compares the treatment effect against a pre-defined cut-off value using the hazard ratio when the hazards are proportional and restricted-mean survival time otherwise. This interim hurdle becomes increasingly stringent stage-by-stage. The addition of new research arm(s) can be actively considered when sufficiently interesting agents emerge. New research arms are compared only to contemporaneously-recruited control arm patients using the same intermediate guidelines in a time-delayed manner. The addition of new research arms is independent of any of the original research arms stopping accrual early subject to adequate recruitment to support the overall trial aims

Using a New Odour-Baited Device to Explore Options for Luring and Killing Outdoor-Biting Malaria Vectors: A Report on Design and Field Evaluation of the Mosquito Landing Box.

Mosquitoes that bite people outdoors can sustain malaria transmission even where effective indoor interventions such as bednets or indoor residual spraying are already widely used. Outdoor tools may therefore complement current indoor measures and improve control. We developed and evaluated a prototype mosquito control device, the 'Mosquito Landing Box' (MLB), which is baited with human odours and treated with mosquitocidal agents. The findings are used to explore technical options and challenges relevant to luring and killing outdoor-biting malaria vectors in endemic settings. Field experiments were conducted in Tanzania to assess if wild host-seeking mosquitoes 1) visited the MLBs, 2) stayed long or left shortly after arrival at the device, 3) visited the devices at times when humans were also outdoors, and 4) could be killed by contaminants applied on the devices. Odours suctioned from volunteer-occupied tents were also evaluated as a potential low-cost bait, by comparing baited and unbaited MLBs. There were significantly more Anopheles arabiensis, An. funestus, Culex and Mansonia mosquitoes visiting baited MLB than unbaited controls (P<=0.028). Increasing sampling frequency from every 120 min to 60 and 30 min led to an increase in vector catches of up to 3.6 fold (P<=0.002), indicating that many mosquitoes visited the device but left shortly afterwards. Outdoor host-seeking activity of malaria vectors peaked between 7:30 and 10:30pm, and between 4:30 and 6:00am, matching durations when locals were also outdoors. Maximum mortality of mosquitoes visiting MLBs sprayed or painted with formulations of candidate mosquitocidal agent (pirimiphos-methyl) was 51%. Odours from volunteer occupied tents attracted significantly more mosquitoes to MLBs than controls (P<0.001). While odour-baited devices such as the MLBs clearly have potential against outdoor-biting mosquitoes in communities where LLINs are used, candidate contaminants must be those that are effective at ultra-low doses even after short contact periods, since important vector species such as An. arabiensis make only brief visits to such devices. Natural human odours suctioned from occupied dwellings could constitute affordable sources of attractants to supplement odour baits for the devices. The killing agents used should be environmentally safe, long lasting, and have different modes of action (other than pyrethroids as used on LLINs), to curb the risk of physiological insecticide resistance

Murray Valley encephalitis virus surveillance and control initiatives in Australia.

Mechanisms for monitoring Murray Valley encephalitis (MVE) virus activity include surveillance of human cases, surveillance for activity in sentinel animals, monitoring of mosquito vectors and monitoring of weather conditions. The monitoring of human cases is only one possible trigger for public health action and the additional surveillance systems are used in concert to signal the risk of human disease, often before the appearance of human cases. Mosquito vector surveillance includes mosquito trapping for speciation and enumeration of mosquitoes to monitor population sizes and relative composition. Virus isolation from mosquitoes can also be undertaken. Monitoring of weather conditions and vector surveillance determines whether there is a potential for MVE activity to occur. Virus isolation from trapped mosquitoes is necessary to define whether MVE is actually present, but is difficult to deliver in a timely fashion in some jurisdictions. Monitoring of sentinel animals indicates whether MVE transmission to vertebrates is actually occurring. Meteorological surveillance can assist in the prediction of potential MVE virus activity by signalling conditions that have been associated with outbreaks of Murray Valley encephalitis in humans in the past. Predictive models of MVE virus activity for south-eastern Australia have been developed, but due to the infrequency of outbreaks, are yet to be demonstrated as useful for the forecasting of major outbreaks. Surveillance mechanisms vary across the jurisdictions. Surveillance of human disease occurs in all States and Territories by reporting of cases to health authorities. Sentinel flocks of chickens are maintained in 4 jurisdictions (Western Australia, the Northern Territory, Victoria and New South Wales) with collaborations between Western Australia and the Northern Territory. Mosquito monitoring complements the surveillance of sentinel animals in these jurisdictions. In addition, other mosquito monitoring programs exist in other States (including South Australia and Queensland). Public health control measures may include advice to the general public and mosquito management programs to reduce the numbers of both mosquito larvae and adult vectors. Strategic plans for public health action in the event of MVE virus activity are currently developed or being developed in New South Wales, the Northern Territory, South Australia, Western Australia and Victoria. A southern tri-State agreement exists between health departments of New South Wales, Victoria and South Australia and the Commonwealth Department of Health and Aged Care. All partners have agreed to co-operate and provide assistance in predicting and combatting outbreaks of mosquito-borne disease in south-eastern Australia. The newly formed National Arbovirus Advisory Committee is a working party providing advice to the Communicable Diseases Network Australia on arbovirus surveillance and control. Recommendations for further enhancement of national surveillance for Murray Valley encephalitis are described

Combining Enzalutamide with Abiraterone, Prednisone, and Androgen Deprivation Therapy in the STAMPEDE Trial

There are compelling reasons to study the addition of both enzalutamide and abiraterone, in combination, to standard-of-care for hormone-naïve prostate cancer. Through a protocol amendment, this will be assessed in the STAMPEDE trial, with overall survival as primary outcome measure. © 2014 European Association of Urology

Counting the bodies: Estimating the numbers and spatial variation of Australian reptiles, birds and mammals killed by two invasive mesopredators

Aim Introduced predators negatively impact biodiversity globally, with insular fauna often most severely affected. Here, we assess spatial variation in the number of terrestrial vertebrates (excluding amphibians) killed by two mammalian mesopredators introduced to Australia, the red fox (Vulpes vulpes) and feral cat (Felis catus). We aim to identify prey groups that suffer especially high rates of predation, and regions where losses to foxes and/or cats are most substantial. Location Australia. Methods We draw information on the spatial variation in tallies of reptiles, birds and mammals killed by cats in Australia from published studies. We derive tallies for fox predation by (i) modelling continental-scale spatial variation in fox density, (ii) modelling spatial variation in the frequency of occurrence of prey groups in fox diet, (iii) analysing the number of prey individuals within dietary samples and (iv) discounting animals taken as carrion. We derive point estimates of the numbers of individuals killed annually by foxes and by cats and map spatial variation in these tallies. Results Foxes kill more reptiles, birds and mammals (peaking at 1071 km−2 year−1) than cats (55 km−2 year−1) across most of the unmodified temperate and forested areas of mainland Australia, reflecting the generally higher density of foxes than cats in these environments. However, across most of the continent – mainly the arid central and tropical northern regions (and on most Australian islands) – cats kill more animals than foxes. We estimate that foxes and cats together kill 697 million reptiles annually in Australia, 510 million birds and 1435 million mammals. Main conclusions This continental-scale analysis demonstrates that predation by two introduced species takes a substantial and ongoing toll on Australian reptiles, birds and mammals. Continuing population declines and potential extinctions of some of these species threatens to further compound Australia's poor contemporary conservation record