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Sampling of the North Sea trawl fishery for lesser sandeel (Ammodytes marinus) showed that 96% of the catch weight consisted of the target species, and experimental sea trials demonstrated that the observed small bycatch percentages of haddock (Melanogrammus aeglefinus), mackerel (Scomber scombrus) and grey gurnard (Eutrigla gurnardus) could be significantly lowered by inserting a netting-based sorting device, an Excluder, in front of the codend. The sandeel fishery is conducted with small meshes in the codend, due to the small size and elongated body shape of this species. It is not mandatory for sandeel trawls to have any other selection devices than the small-meshed codend, and this can potentially cause problems with bycatch of unwanted species, if these are abundant on the fishing grounds. Therefore, we sampled the catch composition in this fishery and further, we compared the capture efficiency and species composition of a standard trawl, and one fitted with an additional sorting device called the Excluder. Overall, results showed small percentages of bycatch in the trips sampled and during the trials, the excluder significantly reduced the bycatches of mackerel, grey gurnard, and haddock above certain sizes. For other bycatch species results were inconclusive due to wide confidence limits affected by low bycatch numbers during the trials. The overall capture efficiency for the target species was not affected by adding the excluder in the trawl except for a significant reduction for a few semi-centimetre groups of the largest sizes of the species. These results highlight the potential of the Excluder as a bycatch reduction tool in the sandeel fishery for situations where bycatch can constitute a problem.

Purpose – This study aims to present a vision-guided robotic system design for application in vat photopolymerization additive manufacturing (AM), enabling vat photopolymerization AM hybrid with injection molding process. Design/methodology/approach – In the system, a robot equipped with a camera and a custom-made gripper as well as driven by a visual servoing (VS) controller is expected to perceive objective, handle variation, connect multi-process steps in soft tooling process and realize automation of vat photopolymerization AM. Meanwhile, the vat photopolymerization AM printer is customized in both hardware and software to interact with the robotic system. Findings – By ArUco marker-based vision-guided robotic system, the printing platform can be manipulated in arbitrary initial position quickly and robustly, which constitutes the first step in exploring automation of vat photopolymerization AM hybrid with soft tooling process. Originality/value – The vision-guided robotic system monitors and controls vat photopolymerization AM process, which has potential for vat photopolymerization AM hybrid with other mass production methods, for instance, injection molding.

Direct engagement of the fishing industry in the provision and co-creation of knowledge and data for research and management is increasingly prevalent. In both the North Atlantic and North Pacific, enhanced and targeted engagement is evident. More is needed. Science-Industry collaborative approaches to developing questions, collecting data, interpreting data, and sharing knowledge create opportunities for information transfer and improved understanding of ecosystem interactions, stock dynamics, economic incentives, and response to management. These collaborations require clear communication and awareness of objectives and outcomes. These initiatives also require careful attention to conditions and interactions that foster respect, trust, and communication. Respect is critical and entails acknowledging the respective skills and expertise of both scientists and fishers. Trust is needed to build confidence in the information developed and its use. Communication is essential to maintain relationships and leverage shared insights. To assess current trends and future opportunities related to this type of engagement, we convened a networking session of research scientists, industry scientists, industry leaders, and fishers at the Annual Science Meeting of the International Council for the Exploration of the Sea (ICES) to address the following questions: (1) What are scientific needs that could be addressed with industry-collected data or knowledge? And (2) How can science-industry collaboration be made sustainable? Here we identify opportunities and acknowledge challenges, outline necessary conditions for respectful and sustainable collaborative research, and highlight ways to promote stakeholder involvement in developing science. We address industry concerns and solicit industry advice. We also address challenges to scientists in ensuring standards for scientific data, conflict of interest, and applying information to advise management. The discussions in this session and subsequent correspondence have led to a set of guidelines and best practices that provide a framework to advance further collaboration between industry and research science. We identify opportunities for directed engagement. We also detail potential approaches to clarify expectations and develop avenues for iterative communication and engagement to sustain collaborative efforts over time. The intent is to improve and expand data streams and contextual understanding of ecosystem processes, stock assessment, and socio-economic dynamics to the benefits of science and industry alike.

B-cell acute lymphoblastic leukaemia (B-ALL) is a common childhood cancer. Here, the authors conducted a meta-analysis with four genome-wide association studies, totalling 5,321 cases and 16,666 controls of European descent, identifying B-ALL risk loci, whose integration with epigenomic profiling indicates cell-cycle and B-cell development deregulation as central mechanisms in B-ALL susceptibility, often in a subtype-specific fashion.

Mesopelagic fish species represent a large potentially unexploited resource for the fishing industry and the fish meal, oil, nutraceutical, and pharmaceutical production. However, thorough investigation on ecological sustainability and socio-economic viability are fundamental prerequisites for potential exploitation. The current study explores the economic viability of a potential mesopelagic fishery investigating minimum catch rates, under the assumption of previous assessments of biological sustainability of such exploitation. We analyzed fishery data from the North-East Atlantic fisheries of the Danish large pelagic fleet from 2015 to 2019, by comparing the combined data on fishing dynamics and cost-structures with data from interviews of key pelagic producer organization representatives to develop scenarios of profitability. The results show full year-round fleet occupation with the ongoing fisheries, exposing the need of switching from existing activities, or investing into new vessels for conducting potential mesopelagic fishery. Economic analyses revealed that the minimum revenue to break even (zero profit) by trip varies among métiers between 60,000 and 200,000 euro showing strong positive correlation with vessel sizes. High profitability was discovered for herring, Atlantic mackerel and blue whiting fisheries while low profitability was observed for the Norway pout fishery. Due to the lack of mesopelagic fishery data, different scenarios of profitability were investigated as informed by the pelagic catch sector stakeholder perceptions of prices and costs and compared to current economic dynamics. A high break-even revenue per trip was forecasted given the increased perceived costs for fuel, modifications of gears and on-board processing methods and potential new vessel investments. High profitability may be reached if the catches exceed 220–1,060 tons per trip depending on costs and vessel storage capacity. If the conservation methods are improved from current refrigerated sea water, fishing trips could last longer than 5 days, being the major limiting economic factor for potential mesopelagic fishery. Future investigations on realistic mesopelagic catches, trip durations and spatio-temporal distribution of fisheries in relation to location, resource abundance, fishing rights, storage and conservation methods will be essential to test the robustness of the scenarios proposed in this study, and will in turn benefit of the economic requirements evaluated herein.

A new bycatch reduction device, termed "Excluder", is presented as an alternative to a traditional rigid sorting grid, mandatory in the small-meshed Norway Pout (Trisopterus esmarkii) trawl fishery in the North Sea. The fishery is a high-volume fishery with large vessels, large demersal trawls and catches up to 100 tons per haul of this small forage fish. The Excluder is a 30 m long netting-based sorting system, developed to reduce bycatch (70 mm square meshes) and improving on board gear-handling and safety. The Excluder was tested against a 5.8 m2 standard sorting grid (35 mm bar spacing) in a twin-trawl experiment from the commercial 70 m trawler "S364 Rockall". Catch data were analysed by species and length using the catch comparison method. For all bycatch species analysed, the Excluder had significantly lower catches relative to the grid: herring (21%), whiting (6%), mackerel (5%), American plaice (70%), witch flounder (15%), and lesser silver smelt (71%). For Norway Pout there was a significant increase in the overall catch efficiency of 32%. These results are explained by a 10 cm smaller L50 (the length of fish with 50% probability of being rejected by the sorting system) of the Excluder and a 15 times larger sorting area, which reduces the risk of clogging and loss of function. With these documented effects of improved sorting and target species catch efficiency, implementation of the Excluder would improve sustainability and address two main barriers of the current Norway pout fishery that limit quota capitalization; a tendency for Norway pout to mix with herring and whiting and lowered catch rates from grid-clogging. Additionally, gear-handling and safety on board would be improved.

While GWAS have uncovered susceptibility loci for B-cell precursor acute lymphoblastic leukemia (BCP-ALL), much of the heritable risk remains undiscovered. Here, the authors perform a meta-analysis of two existing BCP-ALL GWAS together with an unpublished GWAS to identify risk loci at 8q24.21 and 2q22.3.

Abstract Background There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline BRCA1 and BRCA2 (gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group. Methods The study comprised 802 women (median age 40 years, range 19–76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation. Results A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (BRCA1: n = 118, 14.7%; BRCA2: n = 9, 1.1%). The mutation prevalence was 32.9% in the age group 20–29 years compared to 6.9% in the age group 60–69 years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10 year decrease, 95%CI 1.50–2.32, p 10% for women diagnosed below approximately 50 years. Conclusions Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50 years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation.

The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.

Background: Acute pancreatitis (AP) is a serious, mechanistically not entirely resolved side effect of L-asparaginase-containing treatment for acute lymphoblastic leukemia (ALL). To find new candidate variations for AP, we conducted a genome-wide association study (GWAS). Methods: In all, 1,004,623 single-nucleotide variants (SNVs) were analyzed in 51 pediatric ALL patients with AP (cases) and 1388 patients without AP (controls). Replication used independent patients. Results: The top-ranked SNV (rs4148513) was located within the ABCC4 gene (odds ratio (OR) 84.1; p = 1.04 × 10−14). Independent replication of our 20 top SNVs was not supportive of initial results, partly because rare variants were neither present in cases nor present in controls. However, results of combined analysis (GWAS and replication cohorts) remained significant (e.g., rs4148513; OR = 47.2; p = 7.31 × 10−9). Subsequently, we sequenced the entire ABCC4 gene and its close relative, the cystic fibrosis associated CFTR gene, a strong AP candidate gene, in 48 cases and 47 controls. Six AP-associated variants in ABCC4 and one variant in CFTR were detected. Replication confirmed the six ABCC4 variants but not the CFTR variant. Conclusions: Genetic variation within the ABCC4 gene was associated with AP during the treatment of ALL. No association of AP with CFTR was observed. Larger international studies are necessary to more conclusively assess the risk of rare clinical phenotypes.

Joubert syndrome (JS) is a congenital autosomal-recessive or—in rare cases–X-linked inherited disease. The diagnostic hallmark of the so-called molar tooth sign describes the morphological manifestation of the mid- and hind-brain in axial brain scans. Affected individuals show delayed development, intellectual disability, ataxia, hyperpnea, sleep apnea, abnormal eye, and tongue movements as well as hypotonia. At the cellular level, JS is associated with the compromised biogenesis of sensory cilia, which identifies JS as a member of the large group of ciliopathies. Here we report on the identification of novel compound heterozygous variants (p.Y503C and p.Q485*) in the centrosomal gene PIBF1 in a patient with JS via trio whole exome sequencing. We have studied the underlying disease mechanism in the frog Xenopus, which offers fast assessment of cilia functions in a number of embryological contexts. Morpholino oligomer (MO) mediated knockdown of the orthologous Xenopus pibf1 gene resulted in defective mucociliary clearance in the larval epidermis, due to reduced cilia numbers and motility on multiciliated cells. To functionally assess patient alleles, mutations were analyzed in the larval skin: the p.Q485* nonsense mutation resulted in a disturbed localization of PIBF1 to the ciliary base. This mutant failed to rescue the ciliation phenotype following knockdown of endogenous pibf1. In contrast, the missense variant p.Y503C resulted in attenuated rescue capacity compared to the wild type allele. Based on these results, we conclude that in the case of this patient, JS is the result of a pathogenic combination of an amorphic and a hypomorphic PIBF1 allele. Our study underscores the versatility of the Xenopus model to study ciliopathies such as JS in a rapid and cost-effective manner, which should render this animal model attractive for future studies of human ciliopathies.

In 2009, the Danish nation state implemented a history canon, Historie 09 , as an obligatory part of the history national curriculum in primary and lower secondary schools. The history canon was part of a high-profile 'cultural battle' that the Danish liberal–conservative political and intellectual elite initiated during the first decade of the twenty-first century – a conflict that also included several other curricular canons. The Danish history curriculum was meant to satisfy three aims: (1) to bolster students with historical cultural ballast as they are prepared to be a part of the globalized economy and community; (2) to revitalize a chronologically structured master narrative about the historical and cultural origins of the Danish nation; and (3) to incorporate history teaching into an ongoing political struggle against some of the possible consequences of increasing cultural and religious diversity in Denmark – and, accordingly, to further a re-traditionalized vision of Denmark as a culturally homogeneous society, presumably existing as distinct from the membership of a heterogeneous European Union. This paper analyses the background of the history canon project in terms of educational policy, how it was realized in the revised history curriculum of 2009, which is still in force, and finally how representatives of the political elite who framed the history canon interpret the history curriculum. I will conclude by briefly discussing how history teachers have responded to the history canon project.

IKZF1 gene deletions have been associated with a poor outcome in pediatric precursor B-cell acute lymphoblastic leukemia. To assess the prognostic relevance of IKZF1 deletions for patients treated on Berlin-Frankfurt-Münster Study Group trial ALL-BFM 2000, we screened 694 diagnostic acute lymphoblastic leukemia samples by Multiplex Ligation-dependent Probe Amplification. Patients whose leukemic cells bore IKZF1 deletions had a lower 5-year event-free survival (0.69±0.05 vs. 0.85±0.01; P

Background Numerous reports have been published on the association between kinetics of leukemic cells during early treatment of childhood acute lymphoblastic leukemia and therapeutic outcome. In contrast, little is known about the prognostic relevance of normal blood counts in this setting.Design and Methods Normal hematopoiesis during and after induction treatment (days 8, 15 and 33) was correlated with therapeutic outcome in a cohort of 256 children with acute lymphoblastic leukemia treated in one of three consecutive ALL-BFM trials at a single institute. Replication analysis of positive findings was performed in an independent cohort of 475 patients from the ALL-BFM 2000 multicenter trial.Results A platelet count in the first quartile on treatment day 33 and a neutrophil count above the median on day 8 were significantly associated with treatment outcome, conferring multivariate risk ratios for an event of 3.27 (95% confidence interval 1.60–6.69) and 2.26 (95% confidence interval 1.23–4.29), respectively. Replication analysis confirmed the prognostic effect of platelet count on treatment day 33 and demonstrated a strong association with minimal residual disease-based risk group distribution (P

The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6 × 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 × 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 × 10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 × 10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8 × 10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3 × 10(-7), p(heterogeneity) = 5.1 × 10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.

Acute lymphoblastic leukemia is the major pediatric cancer in developed countries. To date most association studies of acute lymphoblastic leukemia have been based on the candidate gene approach and have evaluated a restricted number of polymorphisms. Such studies have served to highlight difficulties in conducting statistically and methodologically rigorous investigations into acute lymphoblastic leukemia risk. Recent genome-wide association studies of childhood acute lymphoblastic leukemia have provided robust evidence that common variation at four genetic loci confers a modest increase in risk. The accumulated experience to date and relative lack of success of initial efforts to identify novel acute lymphoblastic leukemia predisposition loci emphasize the need for alternative study designs and methods. The International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium includes 12 research groups in Europe, Asia, the Middle East and the Americas engaged in studying the genetics of acute lymphoblastic leukemia. The initial goal of this consortium is to identify and characterize low-penetrance susceptibility variants for acute lymphoblastic leukemia through association-based analyses. Efforts to develop genome-wide association studies of acute lymphoblastic leukemia, in terms of both sample size and single nucleotide polymorphism coverage, and to increase the number of single nucleotide polymorphisms taken forward to large-scale replication should lead to the identification of additional novel risk variants for acute lymphoblastic leukemia. Ethnic differences in the risk of acute lymphoblastic leukemia are well recognized and thus in assessing the interplay between inherited and non-genetic risk factors, analyses using different population cohorts with different incidence rates are likely to be highly informative. Given that the frequency of many acute lymphoblastic leukemia subgroups is small, identifying differential effects will realistically only be possible through multi-center pooled analyses. Here, we review the rationale for identifying genetic risk variants for acute lymphoblastic leukemia and our proposed strategy for establishing the International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium.

There is increasing evidence for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children. To identify new risk variants for B-cell ALL (B-ALL) we conducted a meta-analysis with four GWAS (genome-wide association studies), totalling 5321 cases and 16,666 controls of European descent. We herein describe novel risk loci for B-ALL at 9q21.31 (rs76925697, P = 2.11 × 10-8), for high-hyperdiploid ALL at 5q31.1 (rs886285, P = 1.56 × 10-8) and 6p21.31 (rs210143 in BAK1, P = 2.21 × 10-8), and ETV6-RUNX1 ALL at 17q21.32 (rs10853104 in IGF2BP1, P = 1.82 × 10-8). Particularly notable are the pleiotropic effects of the BAK1 variant on multiple haematological malignancies and specific effects of IGF2BP1 on ETV6-RUNX1 ALL evidenced by both germline and somatic genomic analyses. Integration of GWAS signals with transcriptomic/epigenomic profiling and 3D chromatin interaction data for these leukaemia risk loci suggests deregulation of B-cell development and the cell cycle as central mechanisms governing genetic susceptibility to ALL.

Sampling of the North Sea trawl fishery for lesser sandeel (Ammodytes marinus) showed that 96% of the catch weight consisted of the target species, and experimental sea trials demonstrated that the observed small bycatch percentages of haddock (Melanogrammus aeglefinus), mackerel (Scomber scombrus) and grey gurnard (Eutrigla gurnardus) could be significantly lowered by inserting a netting-based sorting device, an Excluder, in front of the codend. The sandeel fishery is conducted with small meshes in the codend, due to the small size and elongated body shape of this species. It is not mandatory for sandeel trawls to have any other selection devices than the small-meshed codend, and this can potentially cause problems with bycatch of unwanted species, if these are abundant on the fishing grounds. Therefore, we sampled the catch composition in this fishery and further, we compared the capture efficiency and species composition of a standard trawl, and one fitted with an additional sorting device called the Excluder. Overall, results showed small percentages of bycatch in the trips sampled and during the trials, the excluder significantly reduced the bycatches of mackerel, grey gurnard, and haddock above certain sizes. For other bycatch species results were inconclusive due to wide confidence limits affected by low bycatch numbers during the trials. The overall capture efficiency for the target species was not affected by adding the excluder in the trawl except for a significant reduction for a few semi-centimetre groups of the largest sizes of the species. These results highlight the potential of the Excluder as a bycatch reduction tool in the sandeel fishery for situations where bycatch can constitute a problem. [ABSTRACT FROM AUTHOR]

BackgroundMedulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines.MethodsIn this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma.FindingsWe included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes.InterpretationGenetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics.FundingGerman Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.

We have measured the gamma-ray emission spectrum of the Moon using the data collected by the Large Area Telescope onboard the Fermi satellite during its first seven years of operation, in the energy range from 30 MeV up to a few GeV. We have also studied the time evolution of the flux, finding a correlation with the solar activity. We have developed a full Monte Carlo simulation describing the interactions of cosmic rays with the lunar surface. The results of the present analysis can be explained in the framework of this model, where the production of gamma rays is due to the interactions of cosmic-ray proton and helium nuclei with the surface of the Moon. Finally, we have used our simulation to derive the cosmic-ray proton and helium spectra near Earth from the Moon gamma-ray data.

The ATLAS muon Cathode Strip Chamber (CSC) backend readout system has been upgraded during the LHC 2013-2015 shutdown to be able to handle the higher Level-1 trigger rate of 100 kHz and the higher occupancy at Run-2 luminosity. The readout design is based on the Reconfigurable Cluster Element (RCE) concept for high bandwidth generic DAQ implemented on the Advanced Telecommunication Computing Architecture (ATCA) platform. The RCE design is based on the new System on Chip XILINX ZYNQ series with a processor-centric architecture with ARM processor embedded in FPGA fabric and high speed I/O resources. Together with auxiliary memories, all these components form a versatile DAQ building block that can host applications tapping into both software and firmware resources. The Cluster on Board (COB) ATCA carrier hosts RCE mezzanines and an embedded Fulcrum network switch to form an online DAQ processing cluster. More compact firmware solutions on the ZYNQ for high speed input and output fiberoptic links and TTC allowed the full system of 320 input links from the 32 chambers to be processed by 6 COBs in one ATCA shelf. The full system was installed in September 2014. We will present the RCE/COB design concept, the firmware and software processing architecture, and the experience from the intense commissioning for LHC Run 2.