The effects of three days of sub-maximal-intensity mountain biking on sleep

Objectives. We determined the effect of three consecutive days of sub-maximal-intensity mountain biking (4.5 hours per day, ~64 km per day), on the sleep of ten healthy, trained male and female mountain bikers. Methods. The sleep of the mountain bikers was assessed both subjectively (visual analogue scales and sleep questionnaires) and objectively (activity data logger) on each night of mountain biking and for seven nights when they were not cycling (pre-exercise, mean of seven nights). The cyclists’ mood and muscular pain were assessed each night using visual analogue scales. The cyclists slept at home in their normal environment. Results. There was no significant difference between the mountain bikers’ muscular pain and mood (calm/anxious visual analogue scale) measured during the pre-exercise stage and their pain and mood measured on each of the mountain biking nights (p>0.05). However, compared with the pre-exercise stage, the mountain bikers reported that they were significantly more tired (tired/energetic visual analogue scale) on each night of cycling (p<0.01). The sleep of the mountain bikers was disrupted on the night of the third day of mountain biking only. On this night, compared with the pre-exercise stage, the mountain bikers reported that they woke up more during the night (double the number of times) (p<0.001), and an activity data logger recorded that they were awake for about half an hour longer during the night (p<0.05). Conclusion. We have shown that three days of repeated, endurance sub-maximal mountain biking disrupted the sleep of the mountain bikers on the third night of cycling

The AGATA Spectrometer

Abstract The Advanced GAmma Tracking Array (AGATA) is a European project to develop and operate a high-resolution gamma-ray spectrometer. AGATA is based on the technique of gamma-ray energy tracking in electrically segmented high-purity germanium crystals. The tracking technique requires the accurate determination of the energy, time and position of every interaction as a gamma ray deposits its energy within the detector volume. AGATA can measure gamma rays from 10’s of keV to 10 MeV with excellent efficiency and position resolution and has a very high count rate capability. The realisation of AGATA and gamma-ray tracking is a result of many technical advances. AGATA has operated in a series of successful scientific campaigns at Legnaro National Laboratory in Italy, GSI in Germany and GANIL in France. AGATA is now in its next phase of development as it evolves to the full 4π instrument. It is presently starting its next campaign at Legnaro.</jats:p

International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact

Background: Pneumococcal conjugate vaccines have reduced the incidence of invasive pneumococcal disease, caused by vaccine serotypes, but non-vaccine-serotypes remain a concern. We used whole genome sequencing to study pneumococcal serotype, antibiotic resistance and invasiveness, in the context of genetic background. / Methods: Our dataset of 13,454 genomes, combined with four published genomic datasets, represented Africa (40%), Asia (25%), Europe (19%), North America (12%), and South America (5%). These 20,027 pneumococcal genomes were clustered into lineages using PopPUNK, and named Global Pneumococcal Sequence Clusters (GPSCs). From our dataset, we additionally derived serotype and sequence type, and predicted antibiotic sensitivity. We then measured invasiveness using odds ratios that relating prevalence in invasive pneumococcal disease to carriage. / Findings: The combined collections (n = 20,027) were clustered into 621 GPSCs. Thirty-five GPSCs observed in our dataset were represented by >100 isolates, and subsequently classed as dominant-GPSCs. In 22/35 (63%) of dominant-GPSCs both non-vaccine serotypes and vaccine serotypes were observed in the years up until, and including, the first year of pneumococcal conjugate vaccine introduction. Penicillin and multidrug resistance were higher (p < .05) in a subset dominant-GPSCs (14/35, 9/35 respectively), and resistance to an increasing number of antibiotic classes was associated with increased recombination (R2 = 0.27 p < .0001). In 28/35 dominant-GPSCs, the country of isolation was a significant predictor (p < .05) of its antibiogram (mean misclassification error 0.28, SD ± 0.13). We detected increased invasiveness of six genetic backgrounds, when compared to other genetic backgrounds expressing the same serotype. Up to 1.6-fold changes in invasiveness odds ratio were observed. / Interpretation: We define GPSCs that can be assigned to any pneumococcal genomic dataset, to aid international comparisons. Existing non-vaccine-serotypes in most GPSCs preclude the removal of these lineages by pneumococcal conjugate vaccines; leaving potential for serotype replacement. A subset of GPSCs have increased resistance, and/or serotype-independent invasiveness

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Visualizing variation within Global Pneumococcal Sequence Clusters (GPSCs) and country population snapshots to contextualize pneumococcal isolates

Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact. Gene presence and absence defined using Roary, and recombination profiles derived from Gubbins are presented in Phandango for each GPSC. Temporal phylogenetic signal was assessed for each GPSC using BactDating. We provide examples of how such resources can be used. In our example use of a country-specific phylogenetic snapshot we determined that serotype 14 was observed in nine unrelated genetic backgrounds in South Africa. The international phylogenetic snapshot of GPSC9, in which most serotype 14 isolates from South Africa were observed, highlights that there were three independent sub-clusters represented by South African serotype 14 isolates. We estimated from the GPSC9-dated tree that the sub-clusters were each established in South Africa during the 1980s. We show how recombination plots allowed the identification of a 20kb recombination spanning the capsular polysaccharide locus within GPSC97. This was consistent with a switch from serotype 6A to 19A estimated to have occured in the 1990s from the GPSC97-dated tree. Plots of gene presence/absence of resistance genes (tet, erm, cat) across the GPSC23 phylogeny were consistent with acquisition of a composite transposon. We estimated from the GPSC23-dated tree that the acquisition occurred between 1953 and 1975. Finally, we demonstrate the assignment of GPSC31 to 17 externally generated pneumococcal serotype 1 assemblies from Utah via Pathogenwatch. Most of the Utah isolates clustered within GPSC31 in a USA-specific clade with the most recent common ancestor estimated between 1958 and 1981. The resources we have provided can be used to explore to data, test hypothesis and generate new hypotheses. The accessible assignment of GPSCs allows others to contextualize their own collections beyond the data presented here

Sea-level constraints on the amplitude and source distribution of Meltwater Pulse 1A.

During the last deglaciation, sea levels rose as ice sheets retreated. This climate transition was punctuated by periods of more intense melting; the largest and most rapid of these—Meltwater Pulse 1A—occurred about 14,500 years ago, with rates of sea-level rise reaching approximately 4 m per century1, 2, 3. Such rates of rise suggest ice-sheet instability, but the meltwater sources are poorly constrained, thus limiting our understanding of the causes and impacts of the event4, 5, 6, 7. In particular, geophysical modelling studies constrained by tropical sea-level records1, 8, 9 suggest an Antarctic contribution of more than seven metres, whereas most reconstructions10 from Antarctica indicate no substantial change in ice-sheet volume around the time of Meltwater Pulse 1A. Here we use a glacial isostatic adjustment model to reinterpret tropical sea-level reconstructions from Barbados2, the Sunda Shelf3 and Tahiti1. According to our results, global mean sea-level rise during Meltwater Pulse 1A was between 8.6 and 14.6 m (95% probability). As for the melt partitioning, we find an allowable contribution from Antarctica of either 4.1 to 10.0 m or 0 to 6.9 m (95% probability), using two recent estimates11, 12 of the contribution from the North American ice sheets. We conclude that with current geologic constraints, the method applied here is unable to support or refute the possibility of a significant Antarctic contribution to Meltwater Pulse 1A

Improving Ethical Review of Research Involving Incentives for Health Promotion

Alex London and colleagues propose new ethical frameworks for evaluating the risks associated with research in which financial or other incentives are used to promote healthy behavior

Involvement of a Natural Fusion of a Cytochrome P450 and a Hydrolase in Mycophenolic Acid Biosynthesis

Mycophenolic acid (MPA) is a fungal secondary metabolite and the active component in several immunosuppressive pharmaceuticals. The gene cluster coding for the MPA biosynthetic pathway has recently been discovered in Penicillium brevicompactum, demonstrating that the first step is catalyzed by MpaC, a polyketide synthase producing 5-methylorsellinic acid (5-MOA). However, the biochemical role of the enzymes encoded by the remaining genes in the MPA gene cluster is still unknown. Based on bioinformatic analysis of the MPA gene cluster, we hypothesized that the step following 5-MOA production in the pathway is carried out by a natural fusion enzyme MpaDE, consisting of a cytochrome P450 (MpaD) in the N-terminal region and a hydrolase (MpaE) in the C-terminal region. We verified that the fusion gene is indeed expressed in P. brevicompactum by obtaining full-length sequence of the mpaDE cDNA prepared from the extracted RNA. Heterologous coexpression of mpaC and the fusion gene mpaDE in the MPA-nonproducer Aspergillus nidulans resulted in the production of 5,7-dihydroxy-4-methylphthalide (DHMP), the second intermediate in MPA biosynthesis. Analysis of the strain coexpressing mpaC and the mpaD part of mpaDE shows that the P450 catalyzes hydroxylation of 5-MOA to 4,6-dihydroxy-2-(hydroxymethyl)-3-methylbenzoic acid (DHMB). DHMB is then converted to DHMP, and our results suggest that the hydrolase domain aids this second step by acting as a lactone synthase that catalyzes the ring closure. Overall, the chimeric enzyme MpaDE provides insight into the genetic organization of the MPA biosynthesis pathway

Modelling India’s coal production with a negatively skewed curve-fitting model

India’s coal demand is forecast to increase at a rapid pace in the future due to the country’s economic and population growth. Analyzing the scope for future production of India’s domestic coal resources, therefore, plays a vital role in the country’s development of sound energy policies. This paper presents a quantitative scenario analysis of India’s potential future coal production by using a negatively skewed curve-fitting model and a range of estimates of the country’s ultimately recoverable resources (URR) of coal. The results show that the resource base is sufficient for India’s coal production to keep increasing over the next few decades, to reach between 2400 and 3200 Mt/y at 2050, depending on the assumed value of URR. A further analysis shows that the high end of this range, which corresponds to our ‘GSI’ scenario, can be considered as the probable upper-bound to India’s domestic coal production. Comparison of production based on the ‘GSI’ scenario with India’s predicted demand shows that the domestic production of coal will be insufficient to meet the country’s rising coal demand, with the gap between demand and production increasing from its current value of about 268 Mt/y to reach 300 Mt/y in 2035, and 700 Mt/y by 2050. This increasing gap will be challenging for the energy security of India