The use of genetic markers to reveal dynamic processes in a common toad (Bufo Bufo) population

In contrast to birds and mammals for example, amphibian population studies only rarely capture information based on genealogical relationships among individuals. As a consequence, we only have very limited knowledge about individual fitness measures such as lifetime reproductive success and the consequences of such variation on the linkage between generations of amphibians in the wild. The present thesis makes use of an existing long-term study on the common toad (Bufo bufo) in southern England (Dorset) to genetically identify parent-offspring relationships among approximately 850 individual toads, representing two successive generations (2004/2005/2006 and 2008/2009). The dataset enabled the comparison of measures of effective population size as well as effective breeding size, revealing ratios between 0.07 and 0.26. These data also showed an increasing trend with time and were (by some estimators) confirmed by the cross-generational parentage analysis which revealed a high reproductive skew among individuals. Forty-five percent of offspring could be assigned to a least one parent; in total, 6% of male parents and 30% of female parents were inferred. The pedigree information was also used to identify a possible hereditary basis for an observed decrease in female body condition and fecundity correlated to increased environmental temperatures. There was no indication for heritability of body size, body weight and body condition, suggesting that the documented decrease is based on phenotypic plasticity rather than evolutionary adaptation. However, kinship data that shows the population is less inbred with time coupled with the effective breeding number estimates showing an increasing trend with time suggest that despite the absence of evolutionary change, this population may still be able to circumvent the adverse effects associated with decreased body condition

Linking effective population size dynamics to phenotypic traits in the common toad (Bufo bufo)

The effective size of a population (Ne) determines the retention of neutral genetic variation in isolated populations, and is therefore a key parameter in conservation genetics. However, while our knowledge on the genetic properties of endangered populations has vastly improved in recent decades, rather little is known about the drivers of variation in Ne/Nc (the ratio between Ne and the population census size Nc) within given species. In the present study, we used eight microsatellite markers to genotype 898 adult common toads (Bufo bufo) obtained over five reproductive seasons from a single population (2004–2006 and 2008–2009), and related annual measures of Ne to cohort-specific population attributes. Consistent with the hypothesis that shifts in fitness-related traits can alter reproductive shares, we observed an increase in annual Ne and Ne/Nc ratios in parallel with a decline in body size in both sexes, and in parallel with an increase in body condition in males. The obtained Ne values also corresponded well with parentage inferences across the 6-year study period, which assigned 46.3% of individuals recorded in 2008 and 2009 to at least one putative parent from the 2004–2006 cohorts. Our study highlights a possible causative link between phenotypic traits such as body size and Ne/Nc, which has the potential to influence the amount of genetic erosion through drift. Keywords:Amphibians; Anurans; Genetic compensation; Genetic monitoring; Microsatellite

The use of genetic markers to reveal dynamic processes in a common toad (Bufo Bufo) population

In contrast to birds and mammals for example, amphibian population studies only rarely capture information based on genealogical relationships among individuals. As a consequence, we only have very limited knowledge about individual fitness measures such as lifetime reproductive success and the consequences of such variation on the linkage between generations of amphibians in the wild. The present thesis makes use of an existing long-term study on the common toad (Bufo bufo) in southern England (Dorset) to genetically identify parent-offspring relationships among approximately 850 individual toads, representing two successive generations (2004/2005/2006 and 2008/2009). The dataset enabled the comparison of measures of effective population size as well as effective breeding size, revealing ratios between 0.07 and 0.26. These data also showed an increasing trend with time and were (by some estimators) confirmed by the cross-generational parentage analysis which revealed a high reproductive skew among individuals. Forty-five percent of offspring could be assigned to a least one parent; in total, 6% of male parents and 30% of female parents were inferred. The pedigree information was also used to identify a possible hereditary basis for an observed decrease in female body condition and fecundity correlated to increased environmental temperatures. There was no indication for heritability of body size, body weight and body condition, suggesting that the documented decrease is based on phenotypic plasticity rather than evolutionary adaptation. However, kinship data that shows the population is less inbred with time coupled with the effective breeding number estimates showing an increasing trend with time suggest that despite the absence of evolutionary change, this population may still be able to circumvent the adverse effects associated with decreased body condition

The parameter space of graphene chemical vapor deposition on polycrystalline Cu

A systematic study on the parameter space of graphene CVD on polycrystalline Cu foils is presented, aiming at a more fundamental process rationale in particular regarding the choice of carbon precursor and mitigation of Cu sublimation. CH4 as precursor requires H2 dilution and temperatures ≥1000°C to keep the Cu surface reduced and yield a high quality, complete monolayer graphene coverage. The H2 atmosphere etches as-grown graphene, hence maintaining a balanced CH4/H2 ratio is critical. Such balance is more easily achieved at low pressure conditions, at which however Cu sublimation reaches deleterious levels. In contrast, C6H6 as precursor requires no reactive diluent and consistently gives similar graphene quality at 100-150°C lower temperatures. The lower process temperature and more robust processing conditions allow the problem of Cu sublimation to be effectively addressed. Graphene formation is not inherently self-limited to a monolayer for any of the precursors. Rather, the higher the supplied carbon chemical potential the higher the likelihood of film inhomogeneity and primary and secondary multilayer graphene nucleation. For the latter, domain boundaries of the inherently polycrystalline CVD graphene offer pathways for a continued carbon supply to the catalyst. Graphene formation is significantly affected by the Cu crystallography, i.e. the evolution of microstructure and texture of the catalyst template form an integral part of the CVD process.S.H. acknowledges funding from ERC grant InsituNANO (n°279342) and from EPSRC (Grant Nr. EP/H047565/1). P.R.K. acknowledges funding from the Cambridge Commonwealth Trust and C.D. acknowledges funding from Royal Society.This is the accepted manuscript. The final version is available from ACS at http://pubs.acs.org/doi/abs/10.1021/jp303597m

Mining and analysis of audiology data to find significant factors associated with tinnitus masker

Objectives: The objective of this research is to find the factors associated with tinnitus masker from the literature, and by using the large amount of audiology data available from a large NHS (National Health Services, UK) hearing aid clinic. The factors evaluated were hearing impairment, age, gender, hearing aid type, mould and clinical comments. Design: The research includes literature survey for factors associated with tinnitus masker, and performs the analysis of audiology data using statistical and data mining techniques. Setting: This research uses a large audiology data but it also faced the problem of limited data for tinnitus. Participants: It uses 1,316 records for tinnitus and other diagnoses, and 10,437 records of clinical comments from a hearing aid clinic. Primary and secondary outcome measures: The research is looking for variables associated with tinnitus masker, and in future, these variables can be combined into a single model to develop a decision support system to predict about tinnitus masker for a patient. Results: The results demonstrated that tinnitus maskers are more likely to be fit to individuals with milder forms of hearing loss, and the factors age, gender, type of hearing aid and mould were all found significantly associated with tinnitus masker. In particular, those patients having Age<=55 years were more likely to wear a tinnitus masker, as well as those with milder forms of hearing loss. ITE (in the ear) hearing aids were also found associated with tinnitus masker. A feedback on the results of association of mould with tinnitus masker from a professional audiologist of a large NHS (National Health Services, UK) was also taken to better understand them. The results were obtained with different accuracy for different techniques. For example, the chi-squared test results were obtained with 95% accuracy, for Support and Confidence only those results were retained which had more than 1% Support and 80% Confidence. Conclusions: The variables audiograms, age, gender, hearing aid type and mould were found associated with the choice of tinnitus masker in the literature and by using statistical and data mining techniques. The further work in this research would lead to the development of a decision support system for tinnitus masker with an explanation that how that decision was obtained

Tinnitus referral pathways within the National Health Service in England: a survey of their perceived effectiveness among audiology staff

<p>Abstract</p> <p>Background</p> <p>In the UK, audiology services deliver the majority of tinnitus patient care, but not all patients experience the same level of service. In 2009, the Department of Health released a Good Practice Guide to inform commissioners about key aspects of a quality tinnitus service in order to promote equity of tinnitus patient care in UK primary care, audiology, and in specialist multi-disciplinary centres. The purpose of the present research was to evaluate utilisation and opinions on pathways for the referral of tinnitus patients to and from English Audiology Departments.</p> <p>Methods</p> <p>We surveyed all audiology staff engaged in providing tinnitus services across England. A 36-item questionnaire was mailed to 351 clinicians in all 163 National Health Service (NHS) Trusts identified as having a tinnitus service. 138 clinicians responded. The results presented here describe experiences and opinions of the current patient pathways to and from the audiology tinnitus service.</p> <p>Results</p> <p>The most common referral pathway was from general practice to a hospital-based Ear, Nose & Throat department and from there to a hospital-based audiology department (64%). Respondents considered the NHS tinnitus referral process to be generally effective (67%), but expressed needs for improving GP referral and patients' access to services. 'Open access' to the audiology clinic was rarely an option for patients (9%), nor was the opportunity to access specialist counselling provided by clinical psychology (35%). To decrease the number of inappropriate referrals, 40% of respondents called for greater awareness by referrers about the audiology tinnitus service.</p> <p>Conclusions</p> <p>Respondents in the present survey were generally satisfied with the tinnitus referral system. However, they highlighted some potential targets for service improvement including 1] faster and more appropriate referral from GPs, to be achieved through education on tinnitus referral criteria, 2] improved access to psychological services through audiologist training, and 3] ongoing support from tinnitus support groups, national charities, or open access to the tinnitus clinic for existing patients.</p

Measuring our universe from galaxy redshift surveys

Galaxy redshift surveys have achieved significant progress over the last couple of decades. Those surveys tell us in the most straightforward way what our local universe looks like. While the galaxy distribution traces the bright side of the universe, detailed quantitative analyses of the data have even revealed the dark side of the universe dominated by non-baryonic dark matter as well as more mysterious dark energy (or Einstein's cosmological constant). We describe several methodologies of using galaxy redshift surveys as cosmological probes, and then summarize the recent results from the existing surveys. Finally we present our views on the future of redshift surveys in the era of Precision Cosmology.Comment: 82 pages, 31 figures, invited review article published in Living Reviews in Relativity, http://www.livingreviews.org/lrr-2004-

Internally coupled ears in living mammals.

It is generally held that the right and left middle ears of mammals are acoustically isolated from each other, such that mammals must rely on neural computation to derive sound localisation cues. There are, however, some unusual species in which the middle ear cavities intercommunicate, in which case each ear might be able to act as a pressure-difference receiver. This could improve sound localisation at lower frequencies. The platypus Ornithorhynchus is apparently unique among mammals in that its tympanic cavities are widely open to the pharynx, a morphology resembling that of some non-mammalian tetrapods. The right and left middle ear cavities of certain talpid and golden moles are connected through air passages within the basicranium; one experimental study on Talpa has shown that the middle ears are indeed acoustically coupled by these means. Having a basisphenoid component to the middle ear cavity walls could be an important prerequisite for the development of this form of interaural communication. Little is known about the hearing abilities of platypus, talpid and golden moles, but their audition may well be limited to relatively low frequencies. If so, these mammals could, in principle, benefit from the sound localisation cues available to them through internally coupled ears. Whether or not they actually do remains to be established experimentally.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00422-015-0675-

Safety and efficacy of bexarotene in patients with relapsing-remitting multiple sclerosis (CCMR One): a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study

Background: Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis. Methods: This randomised, double-blind, placebo-controlled, parallel-group, phase 2a trial (CCMR One) recruited patients with relapsing-remitting multiple sclerosis from two centres in the UK. Eligible participants were aged 18–50 years and had been receiving dimethyl fumarate for at least 6 months. Via a web-based system run by an independent statistician, participants were randomly assigned (1:1), by probability-weighted minimisation using four binary factors, to receive 300 mg/m2 of body surface area per day of oral bexarotene or oral placebo for 6 months. Participants, investigators, and outcome assessors were masked to treatment allocation. MRI scans were done at baseline and at 6 months. The primary safety outcome was the number of adverse events and withdrawals attributable to bexarotene. The primary efficacy outcome was the patient-level change in mean lesional magnetisation transfer ratio between baseline and month 6 for lesions that had a baseline magnetisation transfer ratio less than the within-patient median. We analysed the primary safety outcome in the safety population, which comprised participants who received at least one dose of their allocated treatment. We analysed the primary efficacy outcome in the intention-to-treat population, which comprised all patients who completed the study. This study is registered in the ISRCTN Registry, 14265371, and has been completed. Findings: Between Jan 17, 2017, and May 17, 2019, 52 participants were randomly assigned to receive either bexarotene (n=26) or placebo (n=26). Participants who received bexarotene had a higher mean number of adverse events (6·12 [SD 3·09]; 159 events in total) than did participants who received placebo (1·63 [SD 1·50]; 39 events in total). All bexarotene-treated participants had at least one adverse event, which included central hypothyroidism (n=26 vs none on placebo), hypertriglyceridaemia (n=24 vs none on placebo), rash (n=13 vs one on placebo), and neutropenia (n=10 vs none on placebo). Five (19%) participants on bexarotene and two (8%) on placebo discontinued the study drug due to adverse events. One episode of cholecystitis in a placebo-treated participant was the only serious adverse event. The change in mean lesional magnetisation transfer ratio was not different between the bexarotene group (0·25 percentage units [pu; SD 0·98]) and the placebo group (0·09 pu [0·84]; adjusted bexarotene–placebo difference 0·16 pu, 95% CI –0·39 to 0·71; p=0·55). Interpretation: We do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. However, statistically significant effects were seen in some exploratory MRI and electrophysiological analyses, suggesting that other retinoid X receptor agonists might have small biological effects that could be investigated in further studies. Funding: Multiple Sclerosis Society of the United Kingdom