Population-based incidence rates of 15 neuromuscular disorders:a nationwide capture-recapture study in the Netherlands

Most neuromuscular disorders are rare, but as a group they are not. Nevertheless, epidemiological data of specific neuromuscular disorders are scarce, especially on the incidence. We applied a capture-recapture approach to a nationwide hospital-based dataset and a patients association-based dataset to estimate the annual incidence rates for fifteen neuromuscular disorders in the Netherlands. The annual incidence rates per 100,000 population varied from 0.03/100,000 (95% CI 0.00 ‒ 0.06) for glycogenosis type 5 to 0.9/100,000 (95% confidence interval 0.7 ‒ 1.0) for myotonic dystrophy type 1. The summed annual incidence rate of these disorders was 4.1 per 100,000 per population. Nine of the provided incidence rates were previously unavailable, three rates were similar to the rates in the literature, and three rates were generally higher compared to previous findings but with overlapping confidence intervals. This study provides nationwide incidence rates for fifteen neuromuscular disorders predominantly diagnosed in adult life, nine which were previously unavailable. The capture-recapture approach provided estimates of the total number of individuals with neuromuscular disorders. To complete the gaps in the knowledge of disease frequencies, there is a need for estimates from an automated, obligatory data collection system of diagnosed and newly diagnosed patients with neuromuscular disorders.</p

Population-based incidence rates of 15 neuromuscular disorders: a nationwide capture-recapture study in the Netherlands

Most neuromuscular disorders are rare, but as a group they are not. Nevertheless, epidemiological data of specific neuromuscular disorders are scarce, especially on the incidence. We applied a capture-recapture approach to a nationwide hospital-based dataset and a patients association-based dataset to estimate the annual incidence rates for fifteen neuromuscular disorders in the Netherlands. The annual incidence rates per 100,000 population varied from 0.03/100,000 (95% CI 0.00 ‒ 0.06) for glycogenosis type 5 to 0.9/100,000 (95% confidence interval 0.7 ‒ 1.0) for myotonic dystrophy type 1. The summed annual incidence rate of these disorders was 4.1 per 100,000 per population. Nine of the provided incidence rates were previously unavailable, three rates were similar to the rates in the literature, and three rates were generally higher compared to previous findings but with overlapping confidence intervals. This study provides nationwide incidence rates for fifteen neuromuscular disorders predominantly diagnosed in adult life, nine which were previously unavailable. The capture-recapture approach provided estimates of the total number of individuals with neuromuscular disorders. To complete the gaps in the knowledge of disease frequencies, there is a need for estimates from an automated, obligatory data collection system of diagnosed and newly diagnosed patients with neuromuscular disorders

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Sialic acid changes in Dalton's lymphoma-bearing mice after cyclophosphamide and cisplatin treatment

Sialic acid changes in Dalton's lymphoma cells and other tissues of 10-12-week-old Swiss albino mice were investigated in relation to tumour growth in vivo and following cyclophosphamide (ip, 200 mg/kg body weight) or cisplatin (ip, 8 mg/kg body weight) treatment. Three to four animals of both sexes were used in each experimental group. The sialic acid level of tumour cells (0.88 µmol/g) increased with tumour progression (1.44-1.59 µmol/g; P<=0.05) in mice. Sialic acid concentration in other tissues (liver, kidney, testes and brain) also increased (~40, 10, 30 and 58%, respectively) in the tumour-bearing hosts as compared with that in the respective tissues of normal mice. In vivo cyclophosphamide or cisplatin treatment resulted in an overall decrease of sialic acid contents in the tissues. Cyclophosphamide was more efficient in lowering tissue sialic acid than cisplatin (P<=0.01, ANOVA). It is suggested that sialic acid residues could be an important factor contributing to the manifestation of malignant properties in cancer cells in general and Dalton's lymphoma cells in particular. A significant decrease in the sialic acid content of Dalton's lymphoma cells after cisplatin or cyclophosphamide treatment may bring about specific changes in tumour cells which could be associated with tumour regression

Behaviour of influenza A viruses differentially expressing segment 2 gene products in vitro and in vivo

The influenza A virus genome comprises eight segments of negative-sense RNA that encode up to 12 proteins. RNA segment 2 encodes three proteins, PB1, PB1-F2 and N40, that are translated from the same mRNA by ribosomal leaky scanning and reinitiation. PB1 is a subunit of the trimeric viral RNA polymerase. PB1-F2 has been reported to be a potential virulence factor, and has been shown to be involved in a number of activities including induction of apoptosis, regulation of virus replication and modulation of the immune response. No function has yet been ascribed to N40, which represents an N-terminally deleted form of PB1. Previous studies on PB1-F2 function mainly used viruses genetically engineered to prevent PB1-F2 expression by mutation of the PB1-F2 start codon. However, ablation of the start codon was shown to increase the expression level of the downstream protein N40. In the present study, we generated recombinant A/WSN/33 viruses carrying different combinations of PB1-F2- and N40-knockout mutations. Overexpression of N40 in a PB1-F2-deficient background had a detrimental effect on virus growth &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. However, ablation of PB1-F2 or N40 expression individually was not disadvantageous for the virus. Primer-extension analyses revealed an increase in vRNA production by viruses that overexpressed N40. Our data suggest that the observed attenuation of mutant viruses &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; results from these changes in transcription and replication

Dairy vs beef production – expert views on welfare of cattle in common food production systems

Consumers’ views and concerns about the welfare of farm animals may play an important role in their decision to consume dairy, meat and/or plants as their primary protein source. As animals are killed prematurely in both dairy and beef industries, it is important to quantify and compare welfare compromises in these two sectors before the point of death. Seventy world-leading bovine welfare experts based in 23 countries were asked to evaluate the likelihood of a bovine to experience 12 states of potential welfare concern, inspired by the Welfare Quality® protocol. The evaluation focused on the most common beef and dairy production systems in the experts’ country and was carried out separately for dairy/beef calves raised for red meat, dairy/beef calves raised for veal, dairy/beef calves raised as a replacement, and for dairy/beef cows. The results show experts rated the overall likelihood of a negative welfare state (i.e. welfare risk) to be higher in animals from dairy herds than from beef herds, for all animal categories, regardless of whether they were used to produce milk, red meat or veal. These findings suggest that consuming food products derived from common dairy production systems (dairy or meat) may be more harmful to the welfare of animals than consuming products derived from common beef production systems (i.e. from animals solely raised for their meat). Raising awareness about the linkage between dairy and meat production, and the toll of milk production on the welfare state of animals in the dairy industry, may encourage a more sustainable and responsible food consumption

On the operation of an HDR geothermal reservoir

SIGLEAvailable from British Library Lending Division - LD:3106.129(TPRD/M--1422/N84) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Variations in life history characteristics of the deep-water giant ruby snapper (Etelis sp.) between the Indian and Pacific Oceans and application of a data-poor assessment

The giant ruby snapper, Etelis sp., attains the largest size of any lutjanid in the Indo-Pacific and is one of the most valuable species harvested from deep-water fisheries along the continental and insular shelf margins throughout its broad geographic distribution. Despite this species supporting important commercial, artisanal and subsistence fisheries, quantitative assessments of the status of stocks have been limited by an absence of biological information, unreliable catch and effort statistics, and until recently, misidentification with a cryptic congener. This study aimed, firstly, to describe and compare the age, growth and reproductive characteristics of Etelis sp. between the eastern Indian and western central Pacific Oceans; and secondly, to provide an age-based assessment of the stock in north-western Australia, the only stock for which available data were sufficient to quantify stock status. Although the growth of Etelis sp. differed significantly between sexes and oceans, longevity was similar with a maximum age of 56 years recorded in the Pacific Ocean. Spawning of this species occurred over five months during the austral summer to mid-autumn (i.e. December to April) in the Indian Ocean, but was not well defined in the Pacific Ocean. The estimated ages at 50 % maturity for females and males in the Indian Ocean were similar (i.e. 4–5 years), whereas lengths at 50 % maturity differed ( = 527 and 456 mm fork length, FL, respectively), but were consistent with corresponding differences in growth between sexes. Estimates of the relative female spawning potential ratio for Etelis sp. in north-western Australia suggest the status of this stock remained relatively unchanged from 1997 to 2011, at around 60 % of the unfished level. This assessment provides an example of the relative sustainable exploitation levels for this stock, and potentially other Eteline snappers that exhibit similar life history characteristics, particularly in locations where monitoring and assessments may be data and/or resource limited

Understanding and Measuring Sub-23 nm Particle Emissions from Direct Injection Engines

large fraction of the total number of particles emitted by direct injection engines are below the adopted 23 nm diameter threshold and although the EU aims to regulate these emissions, this is not yet possible due to the absence of accurate and reliable quantification methods, especially under real driving conditions. Four research organisations, three particle measurement instrumentation companies and one automotive OEM have joined forces in the framework of the EU-funded project SUREAL-23 to overcome such barriers by introducing novel technology for the measurement of sub-23 nm exhaust particle concentration, size and composition. The main objectives of SUREAL-23 are to (a) simplify and make more robust the exhaust aerosol sample treatment, (b) elucidate the effect of different diesel and gasoline engine operating conditions on sub-23 nm particle emissions and (c) advance particle measurement technology with the introduction of novel techniques. Herein, we present our latest efforts on instrumentation development and aerosol sampling