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Significant inter-centre variability in the intensity of endomyocardial biopsy surveillance for rejection following paediatric cardiac transplantation has been reported. Our aim was to determine if low-intensity biopsy surveillance with two scheduled biopsies in the first year would produce outcomes similar to published registry outcomes.
A retrospective study of paediatric recipients transplanted between 2008 and 2014 using a low-intensity biopsy protocol consisting of two surveillance biopsies at 3 and 12–13 months in the first post-transplant year, then annually thereafter. Additional biopsies were performed based on echocardiographic and clinical surveillance. Excluded were recipients that were re-transplanted or multi-organ transplanted or were followed at another institution.
A total of 81 recipients in the first 13 months after transplant underwent an average of 2 (SD ± 1.3) biopsies, 24 ± 6.8 echocardiograms, and 17 ± 4.4 clinic visits per recipient. During the 13-month period, 19 recipients had 24 treated rejection episodes, with the first at an average of 2.8 months post-transplant. The 3-, 12-, 36-, and 60-month conditional on discharge graft survival were 100%, 98.8%, 98.8%, and 90.4%, respectively, comparable to reported figures in major paediatric registries. At a mean follow-up of 4.7 ± 2.1 years, four patients (4.9%) developed cardiac allograft vasculopathy, three (3.7%) developed a malignancy, and seven (8.6%) suffered graft loss.
Rejection surveillance with a low-intensity biopsy protocol demonstrated similar intermediate-term outcomes and safety measures as international registries up to 5 years post-transplant.
Although food from grazed animals is increasingly sought by consumers because of perceived animal welfare advantages, grazing systems provide the farmer and the animal with unique challenges. The system is dependent almost daily on the climate for feed supply, with the importation of large amounts of feed from off farm, and associated labour and mechanisation costs, sometimes reducing economic viability. Furthermore, the cow may have to walk long distances and be able to harvest feed efficiently in a highly competitive environment because of the need for high levels of pasture utilisation. She must, also, be: (1) highly fertile, with a requirement for pregnancy within ~80 days post-calving; (2) ‘easy care’, because of the need for the management of large herds with limited labour; (3) able to walk long distances; and (4) robust to changes in feed supply and quality, so that short-term nutritional insults do not unduly influence her production and reproduction cycles. These are very different and are in addition to demands placed on cows in housed systems offered pre-made mixed rations. Furthermore, additional demands in environmental sustainability and animal welfare, in conjunction with the need for greater system-level biological efficiency (i.e. ‘sustainable intensification’), will add to the ‘robustness’ requirements of cows in the future. Increasingly, there is evidence that certain genotypes of cows perform better or worse in grazing systems, indicating a genotype×environment interaction. This has led to the development of tailored breeding objectives within countries for important heritable traits to maximise the profitability and sustainability of their production system. To date, these breeding objectives have focussed on the more easily measured traits and those of highest relative economic importance. In the future, there will be greater emphasis on more difficult to measure traits that are important to the quality of life of the animal in each production system and to reduce the system’s environmental footprint.
Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
Our ALMA observations of HCO+ and HCN show such redshifted absorption toward an isolated core, BHR 71. Both lines show a similar redshifted absorption profile. We also found emissions of complex organic molecules (COMs) around 345 GHz from a compact region centered on the continuum source, which is barely resolved with a beam of 0″27, corresponding to ∼50 AU.
Excessive abdominal fat might be associated with more severe metabolic disorders in Holstein cows. Our hypothesis was that there are genetic differences between cows with low and high abdominal fat deposition and a normal cover of subcutaneous adipose tissue. The objective of this study was to assess the genetic basis for variation in visceral adiposity in US Holstein cows. The study included adult Holstein cows sampled from a slaughterhouse (Green Bay, WI, USA) during September 2016. Only animals with a body condition score between 2.75 and 3.25 were considered. The extent of omental fat at the level of the insertion of the lesser omentum over the pylorus area was assessed. A group of 100 Holstein cows with an omental fold <5 mm in thickness and minimum fat deposition throughout the entire omentum, and the second group of 100 cows with an omental fold ⩾20 mm in thickness and with a marked fat deposition observed throughout the entire omentum were sampled. A small piece of muscle from the neck was collected from each cow into a sterile container for DNA extraction. Samples were submitted to a commercial laboratory for interrogation of genome-wide genomic variation using the Illumina BovineHD Beadchip. Genome-Wide association analysis was performed to test potential associations between fat deposition and genomic variation. A univariate mixed linear model analysis was performed using genome-wide efficient mixed model association to identify single nucleotide polymorphisms (SNPs) significantly associated with variation in a visceral fat deposition. The chip heritability was 0.686 and the estimated additive genetic and residual variance components were 0.427 and 0.074, respectively. In total, 11 SNPs defining four quantitative trait locus (QTL) regions were found to be significantly associated with visceral fat deposition (P<0.00001). Among them, two of the QTL were detected with four and five significantly associated SNPs, respectively; whereas, the QTLs detected on BTA12 and BTA19 were each detected with only one significantly associated SNP. No enriched gene ontology terms were found within the gene networks harboring these genes when supplied to DAVID using either the Bos taurus or human gene ontology databases. We conclude that excessive omental fat in Holstein cows with similar body condition scores is not caused by a single Mendelian locus and that the trait appears to be at least moderately heritable; consequently, selection to reduce excessive omental fat is potentially possible, but would require the generation of predicted transmitting abilities from larger and random samples of Holstein cattle.
People with pancreatic cancer have poor survival, and management is challenging. Pancreatic cancer patients' perceptions of their care coordination and its association with their outcomes have not been well-studied. Our objective was to determine if perception of care coordination is associated with patient-reported outcomes or survival.
People with pancreatic cancer who were 1–8 months postdiagnosis (52 with completed resection and 58 with no resection) completed a patient-reported questionnaire that assessed their perceptions of care coordination, quality of life, anxiety, and depression using validated instruments. Mean scores for 15 care-coordination items were calculated and then ranked from highest (best experience) to lowest (worst experience). Associations between care-coordination scores (including communication and navigation domains) and patient-reported outcomes and survival were investigated using general linear regression and Cox regression, respectively. All analyses were stratified by whether or not the tumor had been resected.
In both groups, the highest-ranked care-coordination items were: knowing who was responsible for coordinating care, health professionals being informed about their history, and waiting times. The worst-ranked items related to: how often patients were asked about visits with other health professionals and how well they and their family were coping, knowing the symptoms they should monitor, having sufficient emotional help from staff, and access to additional specialist services. For people who had a resection, better communication and navigation scores were significantly associated with higher quality of life and less anxiety and depression. However, these associations were not statistically significant for those with no resection. Perception of cancer care coordination was not associated with survival in either group.
Significance of results:
Our results suggest that, while many core clinical aspects of care are perceived to be done well for pancreatic cancer patients, improvements in emotional support, referral to specialist services, and self-management education may improve patient-reported outcomes.
C band backscatter parameters contain information about the upper snowpack/firn in the dry snow zone. The wide incidence angle diversity of the Advanced Scatterometer (ASCAT) gives unprecedented characterisation of backscatter anisotropy, revealing the backscatter response to climatic forcing. The A (isotropic component) and M2 (bi-sinusoidal azimuth anisotropy) parameters are investigated here, in conjunction with data from atmospheric and snowpack models, to identify the backscatter response to surface forcing parameters (wind speed and persistence, precipitation, surface temperature, density and grain size). The long-term mean A parameter is successfully recreated with a regression using these drivers, indicating strong links between the A parameter and precipitation on long timescales. While the ASCAT time series is too short to determine which factors drive observed trends, factors influencing the seasonal and short timescale variability are revealed. On these timescales, A strongly responds to the propagation of surface temperature cycles/anomalies downward through the firn, via direct modulation of the dielectric constant. The influence of precipitation on A is small at shorter timescales. The M2 parameter is controlled by wind speed and persistence, through modification of monodirectionally-aligned surface roughness. This variability indicates that throughout much of coastal Antarctica, a microwave ‘snapshot’ is generally not representative of longer-term conditions.
This paper aims to provide a detailed analysis of the diagnostic process of lung cancer from a primary-care perspective.
Diagnosing lung cancer at a stage where curative treatment is possible remains a challenge. Beginning to understand the complexity and difficulty in the diagnostic journey should enable the development of interventions in order to facilitate timelier diagnosis.
A national study of significant events was conducted whereby general practitioners (GPs) in Wales were asked to report data relating to the diagnostic process of recent lung cancer diagnoses using a standard template. Both qualitative and quantitative data were analysed.
Case reports were received from 96 general practices on 118 patients. A total of 96 patients (81.4%) presented with respiratory symptoms. A total of 79 patients (66.9%) had a GP-initiated X-ray before diagnosis. A total of 23 patients (19.5%) had a chest X-ray that did not initially show suspicion of lung cancer. A total of 25 patients (21.2%) were diagnosed after a GP-initiated acute admission. Analysis of free-text qualitative data showed that, for many patients, their GP behaved in an exemplary manner. However, for some patients, the GP could have made more of the opportunities presented for timelier diagnosis. There were a number of atypical and complex presentations, where the opportunities for more timely diagnosis were more limited. A variety of causes of diagnostic delays in secondary care were reported. These findings will inform health policy, and will inform the design of interventions to try to facilitate more timely diagnosis for symptomatic patients. We encourage greater compliance with diagnostic guidelines and greater vigilance for patients presenting with atypical symptoms, as well as for patients whose initial chest X-rays are normal.
We sought to explain seasonality and other aspects of Campylobacter jejuni epidemiology by integrating population genetic and epidemiological analysis in a large 3-year longitudinal, two-centre, population-based study. Epidemiological information was collected for 1505 isolates, which were multilocus sequence-typed. Analyses compared pathogen population structure between areas, over time, and between clinical presentations. Pooled analysis was performed with published international datasets. Subtype association with virulence was not observed. UK sites had nearly identical C. jejuni populations. A clade formed by ST45 and ST283 clonal complexes showed a summer peak. This clade was common in a Finnish dataset but not in New Zealand and Australian collections, countries with less marked seasonality. The UK, New Zealand and Australian collections were otherwise similar. These findings map to known in-vitro differences of this clade. This identifies a target for studies to elucidate the drivers of the summer peak in human C. jejuni infection.
Coronary artery disease is a major problem worldwide causing 7.2 million deaths worldwide annually, resulting from vascular occlusion, myocardial infarction and its complications. Stent implantation is a percutaneous interventional procedure that mitigates vessel stenosis, providing mechanical support within the artery. However, stenting causes physical damage to the arterial wall. It is well accepted that a valuable route to reduce in-stent re-stenosis can be based on promoting cell response to nano-structured stainless steel (SS) surfaces such as, for example, by patterning nano-pits in SS. In this regard patterning by Focussed Ion-Beam (FIB) milling offers several advantages for flexible prototyping (i) practically any substrate material that is able to withstand high vacuum conditions of the microscope chamber can be used, (ii) there is high flexibility in the obtainable shapes and geometries by modulating the ion beam current and the patterning conditions, (iii) reduced complexity of the pattering process e.g. it is a single-step process with a possibility of real-time monitoring of the milling progression. On the other hand FIB patterning of polycrystalline metals is greatly influenced by channelling effects and re-deposition. Correlative microscopy methods present an opportunity to study such effects comprehensively and derive structure-property understanding that is important for developing improved pattering. In this report we present a FIB patterning protocol for nano-structuring features (concaves) ordered in rectangular arrays on pre-polished 316L Stainless Steel (SS) surfaces. An investigation based on correlative microscopy approach of the size, shape and depth of the developed arrays in relation to the crystal orientation of the underlying SS domains, is presented. The correlative microscopy protocol is based on cross-correlation of top-view Scanning Electron Microscopy (SEM), Electron Backscattered Diffraction (EBSD), and Atomic Force Microscopy (AFM).Various dose tests were performed, aiming at improved productivity by preserving nano-size accuracy of the patterned process. The optimal FIB patterning conditions for achieving reasonably high throughput (patterned rate of about 0.03 mm2 per hour) and nano-size accuracy in dimensions and shapes of the features, are discussed as well.
Examine the association of oral disease with future dementia/cognitive decline in a cohort of people with type 2 diabetes.
A total of 11,140 men and women aged 55–88 years at study induction with type 2 diabetes participated in a baseline medical examination when they reported the number of natural teeth and days of bleeding gums. Dementia and cognitive decline were ascertained periodically during a 5-year follow-up.
Relative to the group with the greatest number of teeth (more than or equal to 22), having no teeth was associated with the highest risk of both dementia (hazard ratio; 95% confidence interval: 1.48; 1.24, 1.78) and cognitive decline (1.39; 1.21, 1.59). Number of days of bleeding gums was unrelated to these outcomes.
Tooth loss was associated with an increased risk of both dementia and cognitive decline.