Patterns and impact of hypoglycemia, hyperglycemia, and glucose variability on inpatients with insulin-treated cystic fibrosis-related diabetes

Introduction: Mortality in patients with cystic fibrosis-related diabetes (CFRD) is higher than that in patients with cystic fibrosis without diabetes. Hypoglycemia, hyperglycemia, and glucose variability confer excess mortality and morbidity in the general inpatient population with diabetes. Methods: We investigated patterns of hypoglycemia and the association of hypoglycemia, hyperglycemia, and glucose variability with mortality and readmission rate in inpatients with CFRD. All capillary blood glucose (CBG) readings (measured using the Abbott Precision web system) of patients with insulin-treated CFRD measured within our health board between January 2009 and January 2015 were. Frequency and timing of hypoglycemia (<4 mmol/L) and was recorded. The effect of dysglycemia on readmission and mortality was investigated with survival analysis. Results: Sixty-six patients were included. A total of 22,711 CBG results were included in the initial analysis. Hypoglycemia was common with 1433 episodes (6.3%). Hypoglycemia ascertainment was highest between 2400 and 0600 h. Hypoglycemia was associated with a significantly higher rate of readmission or death over the 3.5-year follow-up period (P = 0.03). There was no significant association between hyperglycemia or glucose variability and the rate of readmission and mortality. Conclusion: Among inpatients with CFRD hypoglycemia is common and is associated with an increased composite endpoint of readmission and death. As with previously reported trends in general inpatient population this group shows a peak incidence of hypoglycemic during the night

Increasing the power of genome wide association studies in natural populations using repeated measures - evaluation and implementation

1. Genomewide association studies (GWAS) enable detailed dissections of the genetic basis for organisms' ability to adapt to a changing environment. In long-term studies of natural populations, individuals are often marked at one point in their life and then repeatedly recaptured. It is therefore essential that a method for GWAS includes the process of repeated sampling. In a GWAS, the effects of thousands of single-nucleotide polymorphisms (SNPs) need to be fitted and any model development is constrained by the computational requirements. A method is therefore required that can fit a highly hierarchical model and at the same time is computationally fast enough to be useful. 2. Our method fits fixed SNP effects in a linear mixed model that can include both random polygenic effects and permanent environmental effects. In this way, the model can correct for population structure and model repeated measures. The covariance structure of the linear mixed model is first estimated and subsequently used in a generalized least squares setting to fit the SNP effects. The method was evaluated in a simulation study based on observed genotypes from a long-term study of collared flycatchers in Sweden. 3. The method we present here was successful in estimating permanent environmental effects from simulated repeated measures data. Additionally, we found that especially for variable phenotypes having large variation between years, the repeated measurements model has a substantial increase in power compared to a model using average phenotypes as a response. 4. The method is available in the R package RepeatABEL. It increases the power in GWAS having repeated measures, especially for long-term studies of natural populations, and the R implementation is expected to facilitate modelling of longitudinal data for studies of both animal and human populations.Peer reviewe

Measurement artefacts lead to false positives in the study of birdsong in noise

Numerous studies over the past decade have reported correlations between elevated levels of anthropogenic noise and a rise in the minimum frequency of acoustic signals of animals living in noisy habitats. This pattern appears to be occurring globally, and higher pitched signals have been hypothesized to be adaptive changes that reduce masking by low‐frequency traffic noise. However, the sound analysis methods most often used in these studies are prone to measurement errors that can result in false positives. In addition, the commonly used method of measuring frequencies visually from spectrograms might also lead to observer‐expectancy biases that could exacerbate measurement errors. We conducted an experiment to (i) quantify the size and type of errors that result from ‘eye‐balling’ frequency measurements with cursors placed manually on spectrograms of signals recorded in noise and no‐noise conditions, and (ii) to test whether observer expectations lead to significant errors in frequency measurements. We asked 54 volunteers, blind to the true intention of our study, to visually measure the minimum frequency of a variety of natural and synthesized bird sounds, recorded either in noise, or no‐noise conditions. Test subjects were either informed or uninformed about the hypothesized results of the measurements. Our results demonstrate that inappropriate methodology in acoustic analysis can yield false positives with effect sizes as large, or even larger, than those reported in published studies. In addition to these measurement artefacts, psychological observer biases also led to false positives – when observers expected signals to have higher minimum frequencies in noise, they measured significantly higher minimum frequencies than uninformed observers, who had not been primed with any expectation. The use of improper analysis methods in bioacoustics can lead to the publication of spurious results. We discuss alternative methods that yield unbiased frequency measures and we caution that it is imperative for researchers to familiarize themselves both with the functions and limitations of their sound analysis programmes. In addition, observer‐expectancy biases are a potential source of error not only in the field of bioacoustics, but in any situation where measurements can be influenced by human subjectivity

Heterogeneity of genetic parameters for calving difficulty in Holstein heifers in Ireland

Calving difficulty is a trait that greatly affects animal welfare, herd profitability, and the amount of labor required by cattle farmers. It is influenced by direct and maternal genetic components. Selection and breeding strategies can optimize the accuracy of genetic evaluations and correctly emphasize calving difficulty in multiple-trait indices provided there are accurate estimates of genetic parameters. In Ireland, large differences exist in the age at which heifers first give birth to calves. The objective of this study was to estimate genetic parameters for calving difficulty in first-parity Holsteins and to determine whether these differed with age of the heifer at calving. Transformed calving difficulty records for 18,798 Holstein heifers, which calved between January 2002 and May 2006, were analyzed using univariate, multitrait, and random regression linear sire-maternal grandsire models. The model that 1) fitted a second-order random regression of dam age at first parity for the direct component, 2) treated the maternal component as a single trait regardless of dam age, and 3) fitted a single residual variance component was optimal. Heritabilities for direct (0.13) and maternal (0.04) calving difficulty were significantly different from zero. These 2 components were moderately negatively correlated (¿0.47). Estimates of direct genetic variance and heritability were heterogeneous along the dam age trajectory, decreasing initially with dam age before subsequently increasing. Heritability estimates ranged between 0.11 and 0.37 and were higher for records with younger and older dams at parturition. Genetic correlations between the direct components of calving difficulty decreased from unity to 0.5 with increasing distance between dam ages at parturition. The results of this study indicated that heterogeneity of direct genetic variance existed for calving difficulty, depending on dam age at first parturition