Explore the vast range of titles available.

Study Design Retrospective cohort study. Objective Professional hockey players have a high incidence of lumbar disc herniations (LDH). The purpose of this study was to determine the impact of LDH on the performance and financial earnings of National Hockey League (NHL) players. Methods NHL players who sustained a LDH were retrospectively reviewed utilizing an online database and a 2:1 matched control cohort. Player performance and game usage was compared at one- and three-season(s) pre- and post-injury season within the cohorts. Injured and matched players were divided into 3 groups based on the player’s adjusted index season salary. Results A total of 181 players were included, with 62 LDH players matched to 119 healthy controls. Return to play after LDH was 79%. The LDH cohort had fewer seasons played throughout their career compared to the matched group (12.5 ± 4.3 vs 14.2 ± 3.8; P = .031). At 1 season post-index, the LDH cohort had significantly fewer goals per 60 and points per 60 when compared to pre-index. At 3 seasons post-index, the LDH cohort exhibited a significant decline in time-on-ice per game played, goals per 60, and points per 60 compared to pre-index. Conclusion The majority of NHL players who sustained a LDH returned to play (79%) but had shorter careers overall and decreased performance outcomes when compared to matched cohorts at both 1 and 3 seasons post-injury.

Exposure to ambient particulate matter (PM) air pollution is a leading risk factor for morbidity and mortality, associated with up to 8.9 million deaths/year worldwide. Measurement of personal exposure to PM is hindered by poor spatial resolution of monitoring networks. Low-cost PM sensors may improve monitoring resolution in a cost-effective manner but there are doubts regarding data reliability. PM sensor boxes were constructed using four low-cost PM micro-sensor models. Three boxes were deployed at each of two schools in Southampton, UK, for around one year and sensor performance was analysed. Comparison of sensor readings with a nearby background station showed moderate to good correlation (0.61 < r < 0.88, p < 0.0001), but indicated that low-cost sensor performance varies with different PM sources and background concentrations, and to a lesser extent relative humidity and temperature. This may have implications for their potential use in different locations. Data also indicates that these sensors can track short-lived events of pollution, especially in conjunction with wind data. We conclude that, with appropriate consideration of potential confounding factors, low-cost PM sensors may be suitable for PM monitoring where reference-standard equipment is not available or feasible, and that they may be useful in studying spatially localised airborne PM concentrations.

Air Quality (AQ) is a very topical issue for many cities and has a direct impact on citizen health. The AQ of a large UK city is being investigated using low-cost Particulate Matter (PM) sensors, and the results obtained by these sensors have been compared with government operated AQ stations. In the first pilot deployment, six AQ Internet of Things (IoT) devices have been designed and built, each with four different low-cost PM sensors, and they have been deployed at two locations within the city. These devices are equipped with LoRaWAN wireless network transceivers to test city scale Low-Power Wide Area Network (LPWAN) coverage. The study concludes that (i) the physical device developed can operate at a city scale; (ii) some low-cost PM sensors are viable for monitoring AQ and for detecting PM trends; (iii) LoRaWAN is suitable for city scale sensor coverage where connectivity is an issue. Based on the findings from this first pilot project, a larger LoRaWAN enabled AQ sensor network is being deployed across the city of Southampton in the UK.

Numerous acoustic Doppler current profiler (ADCP) surveys were performed in the Inner Sound of the Pentland Firth, a channel between the Orkney Islands and the northern coast of Scotland connecting the Atlantic Ocean to the west and the North Sea to the east. The Pentland Firth has the highest tidal streams of the British Isles, and one of the highest that can be found around the globe. Here, the tidal energy industry is in its demonstration phase, but not many real current measurements are in the public domain. The authors present real current data, measured during different phases of the tidal cycle, using a vessel-mounted ADCP. The tidal changes can be rapid, and because the underway measurements take time, the apparent spatial patterns are affected by temporal variation. A method is described that estimated and corrected this temporal distortion using a hydrodynamic model. It appeared that ebb and flood streams did not fully overlap, and that the tidal streams were more complicated, turbulent, and variable than existing models suggest. The data were analyzed for characteristics pertinent to practical tidal stream energy exploitation, and two favorable sites in the Inner Sound are identified. All original current data are available from the British Oceanographic Data Centre (BODC).

We have generated a high-density, high-throughput genotyping array for characterizing genome-wide variation in Arctic charr (Salvelinus alpinus). Novel single nucleotide polymorphisms (SNPs) were identified in charr from the Fraser, Nauyuk and Tree River aquaculture strains, which originated from northern Canada and fish from Iceland using high coverage sequencing, reduced representation sequencing and RNA-seq datasets. The array was designed to capture genome-wide variation from a diverse suite of Arctic charr populations. Cross validation of SNPs from various sources and comparison with previously published Arctic charr SNP data provided a set of candidate SNPs that generalize across populations. Further candidate SNPs were identified based on minor allele frequency, association with RNA transcripts, even spacing across intergenic regions and association with the sex determining (sdY) gene. The performance of the 86,503 SNP array was assessed by genotyping Fraser, Nauyuk and Tree River strain individuals, as well as wild Icelandic Arctic charr. Overall, 63,060 of the SNPs were polymorphic within at least one group and 36.8% were unique to one of the four groups, suggesting that the array design allows for characterization of both within and across population genetic diversity. The concordance between sdY markers and known phenotypic sex indicated that the array can accurately determine the sex of individuals based on genotype alone. The Salp87k genotyping array provides researchers and breeders the opportunity to analyze genetic variation in Arctic charr at a more detailed level than previously possible.

A new laser-driven proton therapy facility is being designed by Peking University. The protons will be produced by laser–plasma interaction, using a 2-PW laser to reach proton energies up to 100 MeV. We hope that the construction of this facility will promote the real-world applications of laser accelerators. Based on the experimental results and design experience of existing devices in Peking University, we propose a beam transmission system which is suitable for the beam produced by laser acceleration, and demonstrate its feasibility through theoretical simulation. It is designed with two transport lines to provide both horizontal and vertical irradiation modes. We have used a locally-achromatic design method with new canted-cosine-theta (CCT) magnets. These two measures allow us to mitigate the negative effects of large energy spread produced by laser-acceleration, and to reduce the overall weight of the vertical beamline. The beamline contains a complete energy selection system, which can reduce the energy spread of the laser-accelerated beam enough to meet the application requirements. The users can select the proton beam energy within the range 40–100 MeV, which is then transmitted through the rest of the beamline. A beam spot with diameter of less than 15 mm and energy spread of less than 5% can be provided at the horizontal and vertical irradiation targets.

Anna Andersson, Tanja Gruber, James Downing and colleagues report a genomic analysis of infant acute lymphoblastic leukemias with MLL rearrangements. They identify recurrent activating mutations in tyrosine kinase, phosphatidylinositol 3-kinase and RAS pathway genes but find that these mutations were often present in minor subclones and lost at the time of relapse. Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements ( MLL -R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL -R and 18 non– MLL -R cases) and 20 older children ( MLL -R cases) with leukemia. Our data show that infant MLL -R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL -R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10 −5 ) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL , was rarely mutated in infant MLL -R ALL.

Carriers of cancer predisposing variants are at an increased risk of developing subsequent malignant neoplasms among those who have survived childhood cancer. We aimed to investigate whether cancer predisposing variants contribute to the risk of subsequent malignant neoplasm-related late mortality (5 years or more after diagnosis). In this analysis, data were included from two retrospective cohort studies, St Jude Lifetime Cohort (SJLIFE) and the Childhood Cancer Survivor Study (CCSS), with prospective follow-up of patients who were alive for at least 5 years after diagnosis with childhood cancer (ie, long-term childhood cancer survivors) with corresponding germline whole genome or whole exome sequencing data. Cancer predisposing variants affecting 60 genes associated with well-established autosomal-dominant cancer-predisposition syndromes were characterised. Subsequent malignant neoplasms were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 with modifications. Cause-specific late mortality was based on linkage with the US National Death Index and systematic cohort follow up. Fine-Gray subdistribution hazard models were used to estimate subsequent malignant neoplasm-related late mortality starting from the first biospecimen collection, treating non-subsequent malignant neoplasm-related deaths as a competing risk, adjusting for genetic ancestry, sex, age at diagnosis, and cancer treatment exposures. SJLIFE (NCT00760656) and CCSS (NCT01120353) are registered with ClinicalTrials.gov. 12 469 (6172 male and 6297 female) participants were included, 4402 from the SJLIFE cohort (median follow-up time since collection of the first biospecimen 7·4 years [IQR 3·1–9·4]) and 8067 from the CCSS cohort (median follow-up time since collection of the first biospecimen 12·6 years [2·2–16·6]). 641 (5·1%) of 12 469 participants carried cancer predisposing variants (294 [6·7%] in the SJLIFE cohort and 347 [4·3%] in the CCSS cohort), which were significantly associated with an increased severity of subsequent malignant neoplasms (CTCAE grade ≥4 vs grade <4: odds ratio 2·15, 95% CI 1·18–4·19, p=0·0085). 263 (2·1%) subsequent malignant neoplasm-related deaths (44 [1·0%] in the SJLIFE cohort; and 219 [2·7%] in the CCSS cohort) and 426 (3·4%) other-cause deaths (103 [2·3%] in SJLIFE; and 323 [4·0%] in CCSS) occurred. Cumulative subsequent malignant neoplasm-related mortality at 10 years after the first biospecimen collection in carriers of cancer predisposing variants was 3·7% (95% CI 1·2–8·5) in SJLIFE and 6·9% (4·1–10·7) in CCSS versus 1·5% (1·0–2·1) in SJLIFE and 2·1% (1·7–2·5) in CCSS in non-carriers. Carrying a cancer predisposing variant was associated with an increased risk of subsequent malignant neoplasm-related mortality (SJLIFE: subdistribution hazard ratio 3·40 [95% CI 1·37–8·43]; p=0·0082; CCSS: 3·58 [2·27–5·63]; p<0·0001). Identifying participants at increased risk of subsequent malignant neoplasms via genetic counselling and clinical genetic testing for cancer predisposing variants and implementing early personalised cancer surveillance and prevention strategies might reduce the substantial subsequent malignant neoplasm-related mortality burden. American Lebanese Syrian Associated Charities and US National Institutes of Health.

Suzanne Baker, Jinghui Zhang and colleagues report the identification of recurrent somatic mutations in the bone morphogenetic protein (BMP) receptor ACVR1 in 32% of diffuse intrinsic pontine gliomas. Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis 1 . We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX , in both DIPGs and NBS-HGGs 2 , 3 , 4 , 5 . Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase–RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem.

Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the global HIV/AIDS epidemic and the establishment of an integrated HIV-1 reservoir remains the primary obstacle to cure. Upon therapy interruption, reactivation of the persistent HIV-1 reservoir propagates viral rebound and mediates continued immunological decline. While furthering understanding of the HIV-1 reservoir is essential for HIV-1 cure, commonly used sequencing strategies are often limited by the reliance on short-read sequencing across separate assays to determine integration sites and proviral integrity – something that does not always adequately resolve complex human genomic repeats or low complexity regions. Simultaneous identification of proviral integration sites and proviral integrity at the single molecule level would enable HIV-1 reservoir characterization with minimal imputation or bioinformatic reconstruction. Here we present HIV Single Molecule Real Time Capture (HIV SMRTcap), a novel molecular and computational pipeline that directly and simultaneously identifies HIV-1 integration sites, defines proviral integrity, and characterizes clonal expansion of HIV-1 provirus-containing cells with single molecule resolution. In combination with long-read, single-molecule, real-time (SMRT) sequencing and custom analytic pipelines, HIV SMRTcap enables a highly comprehensive characterization of HIV-1 reservoirs. Moreover, we demonstrate here that HIV SMRTcap performs robustly across the major global subtypes (HIV-1 subtype A, B, C, D and A/D recombinant viruses), and can use both cell- and tissue-derived inputs, including samples from antiretroviral therapy (ART) treated individuals with undetectable viral loads. Our results demonstrate that HIV SMRTcap serves as a comprehensive, robust method for unbiased HIV-1 reservoir characterization. Used alone, or in combination with single-cell based methods, HIV SMRTcap will enable novel exploration of viral reservoirs across subtypes and in tissue-specific compartments, providing critical information needed to inform HIV-1 cure.