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An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
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.
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.
Simulation models have been used to investigate the impact of hand hygiene on methicillin-resistant Staphylococcus aureus (MRSA) transmission within the healthcare setting, but they have been limited by their ability to accurately model complex patient–provider interactions.
Using a network-based modeling approach, we created a simulated neonatal intensive care unit (NICU) representing the potential for per-hour infant–infant MRSA transmission via the healthcare worker resulting in subsequent colonization. The starting prevalence of MRSA colonized infants varied from 2% to 8%. Hand hygiene ranged from 0% (none) to 100% (theoretical maximum), with an expected effectiveness of 88% inferred from literature.
Based on empiric care provided within a 1-hour period, the mean number of infant–infant MRSA transmissible opportunities per hour was 1.3. Compared to no hand hygiene and averaged across all initial colonization states, colonization was reduced by approximately 29%, 51%, 67%, 80%, and 86% for the respective levels of hygiene: 24%, 48%, 68%, 88%, and 100%. Preterm infants had a 61% increase in MRSA colonization, and mechanically ventilated infants had a 27% increase.
Even under optimal hygiene conditions, horizontal transmission of MRSA is possible. Additional prevention paradigms should focus on the most acute patients because they are at greatest risk.