Bone Density and Cross-sectional Geometry of the Proximal Femur Are Bilaterally Elevated in Elite Cricket Fast Bowlers

The skeleton of a cricket fast bowler is exposed to a unique combination of gravitational and torsional loading in the form of substantial ground reaction forces delivered through the front landing foot, and anterior-posterior shear forces mediated by regional muscle contractions across the lumbo-pelvic region. The objectives of this study were to compare the hip structural characteristics of elite fast bowlers with recreationally active age-matched controls, and to examine unilateral bone properties in fast bowlers. Dual-energy X-ray absorptiometry of the proximal femur was performed in 26 elite male fast bowlers and 26 normally active controls. Hip structural analysis (GE Lunar; enCORE version 15.0) determined areal bone mineral density (BMD) of the proximal femur, and cross-sectional area, section modulus (Z), cross-sectional moment of inertia, and femoral strength index at the narrow region of the femoral neck. Mean femoral neck and trochanter BMD were greater in fast bowlers than in controls (p  0.05). Elite fast bowlers have superior bone characteristics of the proximal femur, with results inferring enhanced resistance to axial compression (cross-sectional area), and bending (Z) forces, and enhanced strength to withstand a fall impact as indicated by their higher femoral strength index. No asymmetries in hip bone properties were identified, suggesting that both torsional and gravitational loading offer significant osteogenic potential

Mixture and non-mixture cure models for health technology assessment: what you need to know

There is increasing interest in the use of cure modelling to inform health technology assessment (HTA) due to the development of new treatments that appear to offer the potential for cure in some patients. However, cure models are often not included in evidence dossiers submitted to HTA agencies, and they are relatively rarely relied upon to inform decision-making. This is likely due to a lack of understanding of how cure models work, what they assume, and how reliable they are. In this tutorial we explain why and when cure models may be useful for HTA, describe the key characteristics of mixture and non-mixture cure models, and demonstrate their use in a range of scenarios, providing Stata code. We highlight key issues that must be taken into account by analysts when fitting these models and by reviewers and decision-makers when interpreting their predictions. In particular, we note that flexible parametric non-mixture cure models have not been used in HTA, but they offer advantages that make them well suited to an HTA context when a cure assumption is valid but follow-up is limited

The failure of microglia to digest developmental apoptotic cells contributes to the pathology of RNASET2-deficient leukoencephalopathy

The contribution of microglia in neurological disorders is emerging as a leading disease driver rather than a consequence of pathology. RNAseT2‐deficient leukoencephalopathy is a severe childhood white matter disorder affecting patients in their first year of life and mimicking a cytomegalovirus brain infection. The early onset and resemblance of the symptoms to a viral infection suggest an inflammatory and embryonic origin of the pathology. There are no treatments available for this disease as our understanding of the cellular drivers of the pathology are still unknown. In this study, using a zebrafish mutant for the orthologous rnaset2 gene, we have identified an inflammatory signature in early development and an antiviral immune response in mature adult brains. Using the optical transparency and the ex utero development of the zebrafish larvae we studied immune cell behavior during brain development and identified abnormal microglia as an early marker of pathology. Live imaging and electron microscopy identified that mutant microglia displayed an engorged morphology and were filled with undigested apoptotic cells and undigested substrate. Using microglia‐specific depletion and rescue experiments, we identified microglia as drivers of this embryonic phenotype and potential key cellular player in the pathology of RNAseT2‐deficient leukoencephalopathy. Our zebrafish model also presented with reduced survival and locomotor defects, therefore recapitulating many aspects of the human disease. Our study therefore placed our rnaset2 mutant at the forefront of leukodystrophy preclinical models and highlighted tissue‐specific approaches as future therapeutic avenues

Survival extrapolation incorporating general population mortality using excess hazard and cure models: a tutorial

Background Different parametric survival models can lead to widely discordant extrapolations and decision uncertainty in cost-effectiveness analyses. The use of excess hazard (EH) methods, which incorporate general population mortality data, has the potential to reduce model uncertainty. This review highlights key practical considerations of EH methods for estimating long-term survival. Methods Demonstration of methods used a case study of 686 patients from the German Breast Cancer Study Group, followed for a maximum of 7.3 y and divided into low (1/2) and high (3) grade cancers. Seven standard parametric survival models were fit to each group separately. The same 7 distributions were then used in an EH framework, which incorporated general population mortality rates, and fitted both with and without a cure parameter. Survival extrapolations, restricted mean survival time (RMST), and difference in RMST between high and low grades were compared up to 30 years along with Akaike information criterion goodness-of-fit and cure fraction estimates. The sensitivity of the EH models to lifetable misspecification was investigated. Results In our case study, variability in survival extrapolations was extensive across the standard models, with 30-y RMST ranging from 7.5 to 14.3 y. Incorporation of general population mortality rates using EH cure methods substantially reduced model uncertainty, whereas EH models without cure had less of an effect. Long-term treatment effects approached the null for most models but at varying rates. Lifetable misspecification had minimal effect on RMST differences. Conclusions EH methods may be useful for survival extrapolation, and in cancer, EHs may decrease over time and be easier to extrapolate than all-cause hazards. EH cure models may be helpful when cure is plausible and likely to result in less extrapolation variability

Volcanically Induced Transient Atmospheres on the Moon:Assessment of Duration, Significance, and Contributions to Polar Volatile Traps

A transient lunar atmosphere formed during a peak period of volcanic outgassing and lasting up to about ~70 Ma was recently proposed. We utilize forward-modeling of individual lunar basaltic eruptions and the observed geologic record to predict eruption frequency, magma volumes, and rates of volcanic volatile release. Typical lunar mare basalt eruptions have volumes of ~102–103 km3, last less than a year, and have a rapidly decreasing volatile release rate. The total volume of lunar mare basalts erupted is small, and the repose period between individual eruptions is predicted to range from 20,000 to 60,000 years. Only under very exceptional circumstances could sufficient volatiles be released in a single eruption to create a transient atmosphere with a pressure as large as ~0.5 Pa. The frequency of eruptions was likely too low to sustain any such atmosphere for more than a few thousand years. Transient, volcanically induced atmospheres were probably inefficient sources for volatile delivery to permanently shadowed lunar polar regions. ©2020. American Geophysical Union. All Rights Reserved

Lack of association between KIR and HLA-C type and susceptibility to idiopathic bronchiectasis

SummaryIntroductionIdiopathic bronchiectasis is a poorly defined disease characterised by persistent inflammation, infection and progressive lung damage. Natural killer (NK) cells provide a major defense against infection, through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin-like receptors (KIR), and human leukocyte antigens (HLA) class I molecules. Homozygosity for HLA-C has been shown in a single study to confer increased genetic susceptibility to idiopathic bronchiectasis. We aimed to assess whether the KIR and HLA repertoire, alone or in combination, may influence the risk of developing idiopathic bronchiectasis, in an independent replication study.MethodsIn this prospective, observational, case-control association study, 79 idiopathic bronchiectasis patients diagnosed following extensive aetiological investigation were compared with 98 anonymous, healthy, age, sex and ethnically-matched controls attending blood donor sessions in the same geographical location. DNA extraction was performed according to standardised techniques. Determination of presence or absence of KIR genes was performed by a sequence specific oligonucleotide probe method. Allele frequencies for the proposed KIR, HLA-B and HLA-C risk alleles both individually and in combinations were compared.ResultsWe found no significant differences in allele frequency between the idiopathic bronchiectasis and control samples, whether considering HLA-C group homozygosity alone or in combination with the KIR type.DiscussionOur results do not show an association between HLA-C and KIR and therefore do not confirm previous positive findings. This may be explained by the lower frequency of HLA-C1 group homozygosity in the control population of the previous study (27.2%), compared to 42.3% in our study, which is consistent with the genetic profiling of control groups across the UK. The previous positive association study may therefore have been driven by an anomalous control group. Further larger prospective multicentre replication studies are needed to determine if an association exists

Area of hock hair loss in dairy cows : risk factors and correlation to a categorical scale

Data from 3691 dairy cows from 76 farms were used to investigate the risk factors associated with area of hair loss over the lateral aspect of the hock, and the correlation between the area of hair loss as calculated using a hock map and hock lesion scores determined using a pre-existing categorical scale. Six factors were associated with a greater area of hair loss, including cows with locomotion score 3, a cleanliness score (10-18/28), high daily milk yield (25.1 - 58.1 kg), poor body condition score (1-1.5), duration of winter housing (≥41 days) and some combinations of cubicle base and bedding materials. Compared with cows housed in cubicles with a concrete base and whole straw or rape straw bedding, cows housed in cubicles with concrete bases with sand or chopped straw bedding had smaller areas of hair loss and cows housed on a mattress base with whole straw or rape straw bedding had a larger area of hair loss. Area of hair loss, as measured on hock maps, was not significantly different between cows with score 1 (median=23.6 cm2) and score 2 (median=20.3 cm2) on the categorical scale for hock lesions. This suggests that the categorical scale was not reflecting the extent of hair loss and that hock maps are a good alternative for studying the dynamics of hock lesions over time. Further work is required to explore the aetiology of hock lesions and find better ways to control this common condition. Keywords: Hock lesions; Hair loss; Dairy cow; Welfare; Hock map