Oncoplastic breast surgery: A guide to good practice.

Oncoplastic Breast Surgery has become standard of care in the management of Breast Cancer patients. These guidelines written by an Expert Advisory Group; convened by the Association of Breast Surgery (ABS) and the British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS), are designed to provide all members of the breast cancer multidisciplinary team (MDT) with guidance on the best breast surgical oncoplastic and reconstructive practice at each stage of a patient's journey, based on current evidence. It is hoped they will also be of benefit to the wide range of professionals and service commissioners who are involved in this area of clinical practice.

Breed effects and heterosis for weight traits and tick count in a cross between an indigenous fat-tailed and a commercial sheep breed.

Ticks can compromise productivity and welfare in free-ranging sheep. Chemical tick control may not be sustainable in the long term. Alternative control measures must be sought for an integrated control programme. Birth and weaning weights as well as log transformed overall tick count of indigenous fat-tailed Namaqua Afrikaner (NA), commercial Dorper and NA x Dorper cross lambs were studied under extensive conditions. Relative to NA lambs, Dorper lambs were 22.2% heavier at weaning (P < 0.05). Geometric means for total tick count on Dorper lambs exceeded those of their Namaqua Afrikaner contemporaries by more than twofold (P < 0.05). Relative to the pure-breed midparent value, the mean performance of NA x Dorper lambs was 7.9% more for birth weight, 11.2% more for weaning weight and 26.2% less for the back transformed means for total tick count (P < 0.05). Heterosis for total tick count was slightly greater at -29.3% when data were adjusted for the larger size of NA x Dorper lambs. Crossing commercial Dorper sheep with a hardy, indigenous breed therefore resulted in lower levels of tick infestation without compromising live weight in progeny so derived. Hardy, indigenous genetic resources like the NA should be conserved and used in further studies of ovine genetics of resistance to ticks in South Africa.

The importance of dominance and genotype-by-environment interactions on grain yield variation in a large-scale public cooperative maize experiment.

High-dimensional and high-throughput genomic, field performance, and environmental data are becoming increasingly available to crop breeding programs, and their integration can facilitate genomic prediction within and across environments and provide insights into the genetic architecture of complex traits and the nature of genotype-by-environment interactions. To partition trait variation into additive and dominance (main effect) genetic and corresponding genetic-by-environment variances, and to identify specific environmental factors that influence genotype-by-environment interactions, we curated and analyzed genotypic and phenotypic data on 1918 maize (Zea mays L.) hybrids and environmental data from 65 testing environments. For grain yield, dominance variance was similar in magnitude to additive variance, and genetic-by-environment variances were more important than genetic main effect variances. Models involving both additive and dominance relationships best fit the data and modeling unique genetic covariances among all environments provided the best characterization of the genotype-by-environment interaction patterns. Similarity of relative hybrid performance among environments was modeled as a function of underlying weather variables, permitting identification of weather covariates driving correlations of genetic effects across environments. The resulting models can be used for genomic prediction of mean hybrid performance across populations of environments tested or for environment-specific predictions. These results can also guide efforts to incorporate high-throughput environmental data into genomic prediction models and predict values in new environments characterized with the same environmental characteristics.

Genetic parameters for test-day milk yield, lactation persistency, and fertility in low-, medium-, and high-production systems in Kenya.

Genetic parameters for test-day milk yield, lactation persistency, and age at first calving (as a fertility trait) were estimated for the first 4 lactations in multiple-breed dairy cows in low-, medium-, and high-production systems in Kenya. Data included 223,285 test-day milk yield records from 11,450 cows calving from 1990 to 2015 in 148 herds. A multivariate random regression model was used to estimate variance and covariance components. The fixed effects in the model included herd, year, and test month, and age as a covariate. The lactation profile over days in milk (DIM) was fitted as a cubic smoothing spline. Random effects included herd, year, and test month interaction effects, genetic group effects, and additive genetic and permanent environmental effects modeled with a cubic Legendre polynomial function. The residual variance was heterogeneous with 11 classes. Consequently, the variance components were varied over the lactation and with the production system. The estimated heritability for milk yield was lower in the low-production system (0.04-0.48) than in the medium- (0.22-0.59) and high-production (0.21-0 60) systems. The genetic correlations estimated between different DIM within lactations decreased as the time interval increased, becoming negative between the ends of the lactations in the low- and medium-production systems. Low (0.05) to medium (0.60) genetic correlations were estimated among first lactation test-day milk yields across the 3 production systems. Genetic correlations between the first lactation test-day milk yield and age at first calving ranged from 0.27 to 0.49, 0 to 0.81, and -0.08 to 0.27 in the low-, medium-, and high-production systems, respectively. Medium to high heritabilities (0.17-0.44) were estimated for persistency, with moderate to high (0.30-0.87) genetic correlations between 305-d milk yield and persistency. This indicates that genetic improvement in persistency would lead to increased milk yield. The low to medium genetic correlations between test-day milk yield between production systems indicate that sires may be re-ranked between production systems. Therefore, we conclude that sires should be selected based on a genetic evaluation within the target production system.

Genetic-based interactions among tree neighbors: identification of the most influential neighbors, and estimation of correlations among direct and indirect genetic effects for leaf disease and growth in Eucalyptus globulus.

An individual's genes may influence the phenotype of neighboring conspecifics. Such indirect genetic effects (IGEs) are important as they can affect the apparent total heritable variance in a population, and thus the response to selection. We studied these effects in a large, pedigreed population of Eucalyptus globulus using variance component analyses of Mycosphearella leaf disease, diameter growth at age 2 years, and post-infection diameter growth at ages 4 and 8 years. In a novel approach, we initially modeled IGEs using a factor analytic (FA) structure to identify the most influential neighbor positions, with the FA loadings being position-specific regressions on the IGEs. This involved sequentially comparing FA models for the variance-covariance matrices of the direct and indirect effects of each neighbor. We then modeled IGEs as a distance-based, combined effect of the most influential neighbors. This often increased the magnitude and significance of indirect genetic variance estimates relative to using all neighbors. The extension of a univariate IGEs model to bivariate analyses also provided insights into the genetic architecture of this population, revealing that: (1) IGEs arising from increased probability of neighbor infection were not associated with reduced growth of neighbors, despite adverse fitness effects being evident at the direct genetic level; and (2) the strong, genetic-based competitive interactions for growth, established early in stand development, were highly positively correlated over time. Our results highlight the complexities of genetic-based interactions at the multi-trait level due to (co)variances associated with IGEs, and the marked discrepancy occurring between direct and total heritable variances.

Decreased hippocampal translocator protein (18 kDa) expression in alcohol dependence: a [11C]PBR28 PET study.

Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [11C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [11C]PBR28. Regional volumes of distribution (VT) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [11C]PBR28 VT, in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in VT in other ROIs. Hippocampal [11C]PBR28 VT was positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [11C]PBR28 VT, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.

The undergraduate preparation of dentists: Confidence levels of final year dental students at the School of Dentistry in Cardiff.

Objective To investigate the self-reported confidence and preparedness of final year undergraduate students in undertaking a range of clinical procedures.Methods A questionnaire was distributed to final year dental students at Cardiff University, six months prior to graduation. Respondents rated their confidence in undertaking 39 clinical procedures using a 5-point scale (1 = can undertake on own with confidence, 5 = unable to undertake). Students also responded yes/no to experiencing four difficulties and to three statements about general preparedness.Results 71% (N = 51) responded of which 55% (N = 28) were female. Over half reported being 'anxious that the supervisor was not helping enough' (57%) and 'relying heavily on supervisor for help' (53%). Eighty percent 'felt unprepared for the clinical work presented' and gender differences were most notable here (male: 65% N = 33; females: 93% N = 47). Mean confidence scores were calculated for each clinical procedure (1 = lowest; 5 = highest). Confidence was highest in performing 'simple scale' and 'fissure sealant' (mean-score = 5). Lowest scores were reported for 'surgical extractions involving a flap (mean-score = 2.28)', 'simple surgical procedures' (mean-score = 2.58) and the 'design/fit/adjustment of orthodontic appliances' (mean-score = 2.88).Conclusions As expected complex procedures that were least practised scored the lowest in overall mean confidence. Gender differences were noted in self-reported confidence for carrying out treatment unsupervised and feeling unprepared for clinical work.

A critical review of cell culture strategies for modelling intracortical brain implant material reactions.

The capacity to predict in vivo responses to medical devices in humans currently relies greatly on implantation in animal models. Researchers have been striving to develop in vitro techniques that can overcome the limitations associated with in vivo approaches. This review focuses on a critical analysis of the major in vitro strategies being utilized in laboratories around the world to improve understanding of the biological performance of intracortical, brain-implanted microdevices. Of particular interest to the current review are in vitro models for studying cell responses to penetrating intracortical devices and their materials, such as electrode arrays used for brain computer interface (BCI) and deep brain stimulation electrode probes implanted through the cortex. A background on the neural interface challenge is presented, followed by discussion of relevant in vitro culture strategies and their advantages and disadvantages. Future development of 2D culture models that exhibit developmental changes capable of mimicking normal, postnatal development will form the basis for more complex accurate predictive models in the future. Although not within the scope of this review, innovations in 3D scaffold technologies and microfluidic constructs will further improve the utility of in vitro approaches.

Genetic selection for increased mean and reduced variance of twinning rate in Belclare ewes.

It is sometimes possible to breed for more uniform individuals by selecting animals with a greater tendency to be less variable, that is, those with a smaller environmental variance. This approach has been applied to reproduction traits in various animal species. We have evaluated fecundity in the Irish Belclare sheep breed by analyses of flocks with differing average litter size (number of lambs per ewe per year, NLB) and have estimated the genetic variance in environmental variance of lambing traits using double hierarchical generalized linear models (DHGLM). The data set comprised of 9470 litter size records from 4407 ewes collected in 56 flocks. The percentage of pedigreed lambing ewes with singles, twins and triplets was 30, 54 and 14%, respectively, in 2013 and has been relatively constant for the last 15 years. The variance of NLB increases with the mean in this data; the correlation of mean and standard deviation across sires is 0.50. The breeding goal is to increase the mean NLB without unduly increasing the incidence of triplets and higher litter sizes. The heritability estimates for lambing traits were NLB, 0.09; triplet occurrence (TRI) 0.07; and twin occurrence (TWN), 0.02. The highest and lowest twinning flocks differed by 23% (75% versus 52%) in the proportion of ewes lambing twins. Fitting bivariate sire models to NLB and the residual from the NLB model using a double hierarchical generalized linear model (DHGLM) model found a strong genetic correlation (0.88 ± 0.07) between the sire effect for the magnitude of the residual (VE ) and sire effects for NLB, confirming the general observation that increased average litter size is associated with increased variability in litter size. We propose a threshold model that may help breeders with low litter size increase the percentage of twin bearers without unduly increasing the percentage of ewes bearing triplets in Belclare sheep.

The Exeter technique can lead to a lower incidence of leg-length discrepancy after total hip arthroplasty.

We evaluated an operative technique, described by the Exeter Hip Unit, to assist accurate introduction of the femoral component. We assessed whether it led to a reduction in the rate of leg-length discrepancy after total hip arthroplasty (THA). A total of 100 patients undergoing THA were studied retrospectively; 50 were undertaken using the test method and 50 using conventional methods as a control group. The groups were matched with respect to patient demographics and the grade of surgeon. Three observers measured the depth of placement of the femoral component on post-operative radiographs and measured the length of the legs. There was a strong correlation between the depth of insertion of the femoral component and the templated depth in the test group (R = 0.92), suggesting accuracy of the technique. The mean leg-length discrepancy was 5.1 mm (0.6 to 21.4) pre-operatively and 1.3 mm (0.2 to 9.3) post-operatively. There was no difference between Consultants and Registrars as primary surgeons. Agreement between the templated and post-operative depth of insertion was associated with reduced post-operative leg-length discrepancy. The intra-class coefficient was R ≥ 0.88 for all measurements, indicating high observer agreement. The post-operative leg-length discrepancy was significantly lower in the test group (1.3 mm) compared with the control group (6.3 mm, p < 0.001). The Exeter technique is reproducible and leads to a lower incidence of leg-length discrepancy after THA.

Small bioactive molecules as dual functional co-dopants for conducting polymers.

Biological responses to neural interfacing electrodes can be modulated via biofunctionalisation of conducting polymer (CP) coatings. This study investigated the use of small bioactive molecules with anti-inflammatory properties. Specifically, anionic dexamethasone phosphate (DP) and valproic acid (VA) were used to dope the CP poly(ethylenedioxythiophene) (PEDOT). The impact of DP and VA on material properties was explored both individually and together as a codoped system, compared to the conventional dopant p-toluenesulfonate (pTS). Electrical properties of DP and VA doped PEDOT were reduced in comparison to PEDOT/pTS, however co-doping with both DP and VA was shown to significantly improve the electroactivity of PEDOT in comparison the individually doped coatings. Similarly, while the individually doped PEDOT coatings were mechanically friable, the inclusion of both dopants during electropolymerisation was shown to attenuate this response. In a whole-blood model of inflammation all DP and VA doped CPs retained their bioactivity, causing a significant reduction in levels of the pro-inflammatory cytokine TNF-α. These studies demonstrated that small charged bioactive molecules are able act as dopants for CPs and that co-doping with ions of varied size and doping affinity may provide a means of addressing the limitations of large bulky bimolecular dopants.

The use of real-time digital video in the assessment of post-operative outcomes of breast reconstruction.

INTRODUCTION: Outcome measures of breast reconstruction have used panel assessment of photographs. This provides limited information to the assessor as these images are static.. The aim of this study was to assess whether the use of digital video was a valid assessment tool and to compare its use against photography. METHODS: 35 patients post-reconstruction underwent photography, digital video capture and completed Breast Cancer Treatment Outcomes Scale (BCTOS) questionnaires. The photographs/video clips were randomised and shown to a 21 member panel. Opinions on aesthetic aspects of the reconstruction were assessed using the BCTOS and Harris scale. Panel inter-rater agreement and patient-panel correlation was assessed using Kendall's Coefficient of Concordance and Spearman's rank correlation tests respectively. RESULTS: There was a "moderate" degree of inter-rater agreement amongst panel members in all categories. Greater agreement occurred using video footage to assess overall cosmesis (0.548 vs 0.507) and shape (0.505 vs 0.486). Video showed a greater degree of correlation with patient self-assessment scores in comparison to photography (0.311 vs 0.281). CONCLUSION: Video footage coupled with panel assessment is a valid method of assessing post-operative outcomes of breast reconstruction and appears superior to still photographs in terms of inter-rater agreement and correlation with patient self-assessment.

Communication and professionalism skills of a new graduate: the expectations and experiences of dental foundation trainers.

AIM: The aim of this study was to investigate dental foundation year 1 (DF1) trainers' expectations of the dental graduate specifically in relation to non-clinical (professionalism and communication) skills and to explore whether these expectations were being met. METHOD: In the UK, dental graduates undertake 1 year of foundation training prior to being permitted to undertake NHS practice. An online survey was distributed to DF1 trainers via all 11 English deaneries and the Northern Ireland deanery. Demographic information and a general view of trainers' expectations of a new trainee were collected. Specific questions relating to six generic trainee problems were followed by 11 ability statements where trainers indicated their expectation of a trainee's ability to perform the skill on a 5-point scale (on own with confidence-unable to undertake). Statements were repeated and trainers were required to respond using the same scale in relation to experience of their current trainee. RESULTS: Five hundred and ten (53%) trainers completed the questionnaire with no missing data. Expectations were high with almost 50% of trainers expecting a new graduate to manage a full list of patients on their own. Experience of new graduates did not always match these expectations. Of concern was the ability to 'keep accurate patient records' and 'self-reflection and knowing when to seek help', where a small proportion of trainers experienced difficulties. CONCLUSIONS: Trainers' expectation and experience in relation to non-clinical skills of a new graduate were investigated. Although they had high expectations, the majority reported only minor problems overall. There were a few areas where concern was raised.

Genetic parameters for meat quality traits of Australian lamb meat.

Genetic parameters were estimated for a range of meat quality traits recorded on Australian lamb meat. Data were collected from Merino and crossbred progeny of Merino, terminal and maternal meat breed sires of the Information Nucleus programme. Lambs born between 2007 and 2010 (n=8968) were slaughtered, these being the progeny of 372 sires and 5309 dams. Meat quality traits were found generally to be of moderate heritability (estimates between 0.15 and 0.30 for measures of meat tenderness, meat colour, polyunsaturated fat content, mineral content and muscle oxidative capacity), with notable exceptions of intramuscular fat (0.48), ultimate pH (0.08) and fresh meat colour a* (0.08) and b* (0.10) values. Genetic correlations between hot carcass weight and the meat quality traits were low. The genetic correlation between intramuscular fat and shear force was high (-0.62). Several measures of meat quality (fresh meat redness, retail meat redness, retail oxy/met value and iron content) appear to have potential for inclusion in meat sheep breeding objectives.

Cytotoxic activity of extracts from Hypochaeris radicata.

Pasture-associated stringhalt is an acquired equine disease characterized by peripheral neuropathy and hyperflexion of the pelvic limbs. The disease occurs most commonly during periods of drought in horses grazing pastures heavily contaminated by Hypochaeris radicata. We hypothesized that stringhalt is caused by neurotoxins elaborated by H. radicata in response to the stress of drought conditions. Supernates were collected from H. radicata that were stressed (or not) by immersion in copper chloride solution, then extracted with ethyl acetate and dried. Dilutions of extracts from stressed (SE) and control, unstressed (UE) plants were incubated with myelinating spinal cord cultures (MSCC) established from fetal Swiss mice, and with spinal ganglion cultures (SGC) and dermal fibroblast cultures derived from neonatal mouse tissues. Cytotoxicity in culture monolayers was evaluated both morphologically by microscopy and by release of lactate dehydrogenase activity into culture supernates. Three different SGC preparations were exposed to a single H. radicata extract and single preparations of fibroblasts and MSCC were exposed to three different extracts. Repin, a plant-derived sesquiterpene lactone neurotoxin, was included as a positive control. Significant dose-dependent cytotoxicity was seen within 24 h in all three culture types when incubated with SE or repin. Complete morphologic destruction of culture monolayers was induced by the highest concentrations tested of SE (100 µg/mL) and repin (30 µg/mL). Cytotoxic effect of SE was significantly greater than that of UE for all three cell types and was not due to copper contamination of the extract. This study has identified a cytotoxic activity in leaf exudates of H. radicata that was upregulated by the model stressor, copper chloride.