Homozygosity mapping reveals novel and known mutations in Pakistani families with inherited retinal dystrophies.

Inherited retinal dystrophies are phenotypically and genetically heterogeneous. This extensive heterogeneity poses a challenge when performing molecular diagnosis of patients, especially in developing countries. In this study, we applied homozygosity mapping as a tool to reduce the complexity given by genetic heterogeneity and identify disease-causing variants in consanguineous Pakistani pedigrees. DNA samples from eight families with autosomal recessive retinal dystrophies were subjected to genome wide homozygosity mapping (seven by SNP arrays and one by STR markers) and genes comprised within the detected homozygous regions were analyzed by Sanger sequencing. All families displayed consistent autozygous genomic regions. Sequence analysis of candidate genes identified four previously-reported mutations in CNGB3, CNGA3, RHO, and PDE6A, as well as three novel mutations: c.2656C > T (p.L886F) in RPGRIP1, c.991G > C (p.G331R) in CNGA3, and c.413-1G > A (IVS6-1G > A) in CNGB1. This latter mutation impacted pre-mRNA splicing of CNGB1 by creating a -1 frameshift leading to a premature termination codon. In addition to better delineating the genetic landscape of inherited retinal dystrophies in Pakistan, our data confirm that combining homozygosity mapping and candidate gene sequencing is a powerful approach for mutation identification in populations where consanguineous unions are common

Challenges and satisfaction in Cardiothoracic Surgery Residency Programmes: insights from a Europe-wide survey.

OBJECTIVES: The increasing complexity of surgical patients and working time constraints represent challenges for training. In this study, the European Association for Cardio-Thoracic Surgery Residents' Committee aimed to evaluate satisfaction with current training programmes across Europe. METHODS: We conducted an online survey between October 2018 and April 2019, completed by a total of 219 participants from 24 countries. RESULTS: The average respondent was in the fourth or fifth year of training, mostly on a cardiac surgery pathway. Most trainees follow a 5-6-year programme, with a compulsory final certification exam, but no regular skills evaluation. Only a minority are expected to take the examination by the European Board of Cardiothoracic Surgery. Participants work on average 61.0 ± 13.1 h per week, including 27.1 ± 20.2 on-call. In total, only 19.7% confirmed the implementation of the European Working Time Directive, with 42.0% being unaware that European regulations existed. Having designated time for research was reported by 13.0%, despite 47.0% having a postgraduate degree. On average, respondents rated their satisfaction 7.9 out of 10, although 56.2% of participants were not satisfied with their training opportunities. We found an association between trainee satisfaction and regular skills evaluation, first operator experience and protected research time. CONCLUSIONS: On average, residents are satisfied with their training, despite significant disparities in the quality and structure of cardiothoracic surgery training across Europe. Areas for potential improvement include increasing structured feedback, research time integration and better working hours compliance. The development of European guidelines on training standards may support this

ENVIRONMENTAL FACTORS AFFECTING PERFORMANCE TRAITS OF CROSSBRED AND LOCAL DAIRY COWS AT MIRPUR AZAD JAMMU AND KASHMIR

Data on about 3999 records from 1990 to 2003 collected at artificial insemination center Mirpur city were utilized for this study and analyzed using Harvey's Mixed Model Least Squares and Maximum Likelihood Computer Program to study the environmental sources of variation on some performance traits of Desi /Iocal, F1 (Holstein Friesian and Jersey X Desi), Holstein Friesian, Jersey and Sahiwal dairy cows of different genotype. The least squares means for number of services per conception, age at first service and gestation period were 1.07±0.18, 990.37±239.24 days and 280.84±0.35 days, respectively. The coefficient of variation for these traits was 24.31, 21.97 and 1.71 percent respectively. The least squares means for daily milk yield was 8.72±0.18 liters with 32.42 % coefficient of variation. The analysis of variance for age at first service revealed that year and genotype showed significant differences (P< 0.05), however, the season of birth had non-significant effect on age at first service. Moreover, data revealed that the year of service and genotype have significant (P<0.01) influence on number of services per conception during the study period, however, the season of service and parity showed nonsignificant difference. There was no significant difference due to age at service of the cows. The difference was non-significant in the number of services per conception due to increase in the age of cow. It was further observed that the gestation period in the present data set was significantly (P<0.05) different due to year / season of birth, genotype, parity and sex of the calf born. The variability in daily milk yield was significant (P<0.05) due to year of calving and genotype of animal, whereas, there was non significant difference in daily milk yield due to increase in the age of animal. INTRODUCTION Azad Jammu and Kashmir is covering an area of 13,297 squares kilometers. It is located in foothills of Himalayas; mainly hilly and mountainous characterized by deep ravines, rugged and undulating terrain. The livestock is primarily raised in small herds and it does not exceed more than four animals. The animals are pre-dominantly reared on mixed system of feeding (grazing and stall feeding) and they are contributing about 62% in the GDP of Azad Jammu and Kashmir (AJK) when compared with agriculture. There are 0.53 and 0.48 million dairy cows and buffaloes, respectively. The population of dairy cattle at Mirpur district was 93457 heads comprising 40.25 % cows and 59.75 % Buffaloes. The population was dominated by (47.83 %) nondescript and 23.83% Dhani, 17.41 % crossbred and followed by 2.41 percent Sahiwal cattle. The overall strength of dairy animals was 1.97 heads. The house holds preference for rearing milch animals was 54. 48 % Buffaloes, 18.57 % cows and 26.96 % both cow and Buffaloes (Anon.1996). In order to improve the diet and nutrition of farm families, and poverty alleviation by enhancing the income from increased sales of livestock products Le. milk and meat, Artificial insemination activities were started during 1985 in AJK. The long term objective was to establish dairy cattle breed and enhance production potential of existing animals by crossing with improved exotic germ plasm, suitable to the variable climatic conditions in AJK. The study was aimed to evaluate the achievements and changes attained through cross breeding in the production potential of dairy cattle from Desi to improved exotic type. It is also envisaged to evaluate the environmental sources of variation for some performance traits of dairy cattle at Mirpur, AJK

Validation of markerless strain-field optical tracking approach for soft tissue mechanical assessment.

Strain measurement during tissue deformation is crucial to elucidate relationships between mechanical loading and functional changes in biological tissues. When combined with specified loading conditions, assessment of strain fields can be used to craft models that accurately represent the mechanical behavior of soft tissue. Inhomogeneities in strain fields may be indicative of normal or pathological inhomogeneities in mechanical properties. In this study, we present the validation of a modified Demons registration algorithm for non-contact, marker-less strain measurement of tissue undergoing uniaxial loading. We validate the algorithm on a synthetic dataset composed of artificial deformation fields applied to a speckle image, as well as images of aortic sections of varying perceptual quality. Initial results indicate that Demons outperforms recent Optical Flow and Digital Image Correlation methods in terms of accuracy and robustness to low image quality, with similar runtimes. Demons achieves at least 8% lower maximal deviation from ground truth on 50% biaxial and shear strain applied to aortic images. To illustrate utility, we quantified strain fields of multiple human aortic specimens undergoing uniaxial tensile testing, noting the formation of strain concentrations in areas of rupture. The modified Demons algorithm captured a large range of strains (up to 50%) and provided spatially resolved strain fields that could be useful in the assessment of soft tissue pathologies

National survey of UK consultant surgeons’ opinions on surgeon-specific mortality data in cardiothoracic surgery

© 2016 American Heart Association, Inc.Background - In the United Kingdom, cardiothoracic surgeons have led the outcome reporting revolution seen over the last 20 years. The objective of this survey was to assess cardiothoracic surgeons opinions on the topic, with the aim of guiding future debate and policy making for all subspecialties. Methods and Results - A questionnaire was developed using interviews with experts in the field. In January 2015, the survey was sent out to all consultant cardiothoracic surgeons in the United Kingdom (n=361). Logistic regression, bivariate correlation, and the χ 2 test were used to assess whether there was a relationship between answers and demographic variables. Free-text responses were analyzed using the grounded theory approach. The response rate was 73% (n=264). The majority of respondents (58.1% oppose, 34.1% favor, and 7.8% neither) oppose the public release of surgeon-specific mortality data and associate it with several adverse consequences. These include risk-averse behavior, gaming of data, and misinterpretation of data by the public. Despite this, the majority overwhelmingly supports publication of team-based measures of outcome. The free-text responses suggest that this is because most believe that quality of care is multifactorial and not represented by an individuals mortality rate. Conclusions - There is evident opposition to surgeon-specific mortality data among UK cardiothoracic surgeons who associate this with several unintended consequences. Policy makers should refine their strategy behind publication of surgeon-specific mortality data and possibly consider shift toward team-based results for which there will be the required support. Stakeholder feedback and inclusive strategy should be completed before introducing major initiatives to avoid unforeseen consequences and disagreements

Management of chronic type B aortic dissection

The standard of care first-line therapy for uncomplicated acute type B aortic dissection is medical therapy. As a result, many of these dissections progress to become chronic type B aortic dissections (CTBAD). In the following manuscript, we will outline the natural history of these lesions and review what constitutes a CTBAD by anatomy and chronology. We will also describe the long-term medical management and surveillance of these lesions, what constitutes high-risk features, and when intervention should be considered. Endovascular, open and hybrid management strategies, potential complications, and subsequently required surveillance will also be discussed. With proper medical management, surveillance, and intervention, CTBAD can be managed effectively and downstream morbidity minimized