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Ecosystem-based approaches are increasingly used in fisheries management to account for the direct trophic impacts of fish population harvesting. However, fisheries can also indirectly alter ecosystem structure and functioning, for instance via the provision of new feeding opportunities to marine predators. For instance, marine depredation, where predators feed on fishery catches on fishing gear, is a behaviour developed by many marine species globally. This behaviour can modify both the ecological role of predators and fisheries performance. Yet, these ecosystem-wide effects of depredation are rarely considered holistically. In this study, we explored different ways of incorporating depredation into an Ecopath trophic model. We assessed, through a subantarctic case study, how three alternative model structures can account for depredation effects on fishery catches, predator and non-commercial prey populations, as well as target fish stocks. While none adequately addresses all facets of depredation, the alternative models can to some extent capture how depredation can lead to increased fishing pressure on stocks. As structural specificities of Ecopath prevented us from representing other depredation effects such as provisioning effects for predator populations, we conclude this study with a set of guidance to effectively capture the complex effects of depredation in marine ecosystems and fisheries models.

Summary In a rapidly changing world, scientists and research institutions need to plan for the infrastructure, skills, and policy engagement that will help society navigate social-ecological challenges. Foresighting draws on approaches used in strategic and long-range (>10 years) planning and participatory futures studies. Here, we describe a new quantitative approach to develop and rank 14 foresight scenarios across a range of general and marine-relevant science domains. Indicators for each foresight were used to assess the time-specific probability of each scenario being realized. Assessments by scientists in 2 consecutive years showed foresight scoring consistency and revealed surprises. Despite high variation among scientists in scoring the year that each indicator would occur, there was overall consistency across the foresights between years. We show that foresighting can be quantitative and that individual performance and changes in likelihood can be evaluated. This approach can motivate and guide strategic planning and investment decisions by scientific institutions in response to different anticipated futures and build skills in futures thinking.

Poly(ADP-ribose) polymerase (PARP) inhibitors improve survival in BRCA-mutant high-grade serous ovarian carcinoma. As a result, germline and somatic BRCA1/2 testing has become standard practice in women diagnosed with ovarian cancer. We outline changes in testing and detection rates of germline BRCA1/2 pathogenic variants (PVs) in cases of non-mucinous epithelial ovarian cancer diagnosed during three eras, spanning 12 years, within the North West of England, and compare the uptake of cascade testing in families identified by oncology-led mainstreaming versus regional genetics clinics. Eras included: Period 1 (20% risk threshold for testing): between January 2007 and May 2013; Period 2 (10% risk threshold for testing): between June 2013 and October 2017 and; Period 3 (mainstream testing): between November 2017 and November 2019. A total of 1081 women underwent germline BRCA1/2 testing between January 2007 and November 2019 and 222 (20.5%) were found to have a PV. The monthly testing rate increased by 3.3-fold and 2.5-fold between Periods 1–2 and Periods 2–3, respectively. A similar incidence of germline BRCA1/2 PVs were detected in Period 2 (17.2%) and Period 3 (18.5%). Uptake of cascade testing from first-degree relatives was significantly lower in those women undergoing mainstream testing compared with those tested in regional genetics clinics (31.6% versus 47.3%, P = 0.038). Mainstream testing allows timely detection of germline BRCA1/2 status to select patients for PARP inhibitors, but shortfalls in the uptake of cascade testing in first-degree relatives requires optimisation to broaden benefits within families.

16 pages, 6 figures, 3 tables, supplementary data https://doi.org/10.1016/j.pocean.2021.102659.-- Code and data availability: The experimental protocol in this paper has no code associated with it. Forcing data from CMIP5 used for the protocol, and the FishMIP model outputs presented in this paper are available on the ISIMIP servers (https://www.isimip.org/), Climate change is warming the ocean and impacting lower trophic level (LTL) organisms. Marine ecosystem models can provide estimates of how these changes will propagate to larger animals and impact societal services such as fisheries, but at present these estimates vary widely. A better understanding of what drives this inter-model variation will improve our ability to project fisheries and other ecosystem services into the future, while also helping to identify uncertainties in process understanding. Here, we explore the mechanisms that underlie the diversity of responses to changes in temperature and LTLs in eight global marine ecosystem models from the Fisheries and Marine Ecosystem Model Intercomparison Project (FishMIP). Temperature and LTL impacts on total consumer biomass and ecosystem structure (defined as the relative change of small and large organism biomass) were isolated using a comparative experimental protocol. Total model biomass varied between −35% to +3% in response to warming, and -17% to +15% in response to LTL changes. There was little consensus about the spatial redistribution of biomass or changes in the balance between small and large organisms (ecosystem structure) in response to warming, an LTL impacts on total consumer biomass varied depending on the choice of LTL forcing terms. Overall, climate change impacts on consumer biomass and ecosystem structure are well approximated by the sum of temperature and LTL impacts, indicating an absence of nonlinear interaction between the models’ drivers. Our results highlight a lack of theoretical clarity about how to represent fundamental ecological mechanisms, most importantly how temperature impacts scale from individual to ecosystem level, and the need to better understand the two-way coupling between LTL organisms and consumers. We finish by identifying future research needs to strengthen global marine ecosystem modelling and improve projections of climate change impacts, JDE was funded by Australian Research Council Discovery Projects DP150102656 and DP190102293. MC, JS, NB and OM received financial support by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 817578 (Triatlas project). CH received funding from the Open Philanthropy Project. NB and OM also acknowledge the support of the French ANR project CIGOEF (grant ANR-17-CE32-0008-01). DPT acknowledges funding from the ISI-MIP project to support a workshop on this topic, and the Jarislowsky Foundation. EDG received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 682602, BIGSEA). RFH was funded by the Spanish Ministry of Science, Innovation and Universities through the Acciones de Programación Conjunta Internacional (PCIN-2017-115). MC acknowledges the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S) to the Institute of Marine Science (ICM-CSIC). TDE acknowledges funding from the ISIMIP project to support a workshop on this topic and the Fisheries and Oceans Canada Atlantic Fisheries Fund. All authors declare no conflict of interest with respect to this study. JAFS received funding from the European Union’s Horizon 2020 FutureMARES project (#869300).

Chlamydia trachomatis is the leading cause of infectious blindness and a sexually transmitted infection. All chlamydiae are obligate intracellular bacteria that replicate within a membrane-bound vacuole termed the inclusion. From the confines of the inclusion, the bacteria must interact with many host organelles to acquire key nutrients necessary for replication, all while promoting host cell viability and subverting host defense mechanisms. To achieve these feats, C. trachomatis delivers an arsenal of virulence factors into the eukaryotic cell via a type 3 secretion system (T3SS) that facilitates invasion, manipulation of host vesicular trafficking, subversion of host defense mechanisms and promotes bacteria egress at the conclusion of the developmental cycle. A subset of these proteins intercalate into the inclusion and are thus referred to as inclusion membrane proteins. Whereas others, referred to as conventional T3SS effectors, are released into the host cell where they localize to various eukaryotic organelles or remain in the cytosol. Here, we discuss the functions of T3SS effector proteins with a focus on how advances in chlamydial genetics have facilitated the identification and molecular characterization of these important factors., In this article, the authors review the function of Chlamydia trachomatis secreted effector proteins and Incs, with special emphasis on how the advancement of chlamydial genetics has enabled functional characterization of these important proteins.

As atmospheric CO2 levels continue to rise so too does the risk of severe impacts. Scientists clearly have an important role to play in preparing for and responding to climate change impacts; however, calls by scientists for global action have not led to the required changes. It is timely, therefore, for scientists to critically consider their own approach toward climate change research, particularly if we are to ameliorate or adapt to unwanted outcomes. Here we present three different pathways that allow scientists and scientific institutions to conceptualize the implications of their responses to climate change scenarios. These pathways are illustrated via three plausible futures for the marine environment under climate change. This approach allows future responsibilities, outcomes, and implication to be explored within and across pathways and can be applied to different scenarios for scientists and scientific institutions to anticipate and better prepare to contribute effectively to the future.

IntroductionPoly(ADP-ribose) polymerase inhibitors significantly improve progression-free survival in platinum-sensitive high-grade serous and endometrioid ovarian carcinoma, with greatest benefits observed in women with a pathogenic BRCA1/2 variant. Consequently, the demand for germline BRCA1/2 testing in ovarian cancer has increased substantially, leading to the screening of unselected populations of patients. We aimed to determine the prevalence of pathogenic germline BRCA1/2 variants in women diagnosed with epithelial ovarian cancer, categorised according to the established risk factors for hereditary breast and ovarian cancer syndrome and the Manchester BRCA Score, to inform risk stratification.MethodsA cohort of sequential epithelial ovarian cancer cases recruited between June 2013 and September 2018 underwent germline BRCA1/2 testing by next-generation sequencing and multiplex ligation-dependent probe amplification.ResultsFive hundred and fifty-seven patients were screened. Of these, 18% had inherited a pathogenic BRCA1/2 variant. The prevalence of pathogenic BRCA1/2 variants was >10% in women diagnosed with ovarian cancer earlier than 60 years of age (21%) and those diagnosed later than 60 years of age with a family history of breast and/or ovarian cancer (17%) or a medical history of breast cancer (34%). The prevalence of pathogenic BRCA1/2 variants was also >10% in women with a Manchester BRCA Score of ≥15 points (14%).DiscussionOur study suggests that age at diagnosis, family history of breast and/or ovarian cancer, medical history of breast cancer or a Manchester BRCA Score of ≥15 points are associated with a >10% prevalence of germline pathogenic BRCA1/2 variants in epithelial ovarian cancer.

In a rapidly changing world, scientists and their research institutions need to plan for the infrastructure, skills, and policy engagement that will be demanded to help society navigate current and emergent social-ecological challenges. Foresighting draws on approaches used in strategic and long-range (>10 year) planning, and participatory futures studies. It is outcome-oriented and typically involves development of scenario narratives that can inform planning in a qualitative sense. Here we describe a new quantitative approach to develop and rank 14 foresight scenarios of potential futures across a range of general and marine-relevant science domains. Indicators for each foresight were used to assess the time-specific probability of each scenario being realised and assessments by scientists were undertaken in two consecutive years to test for foresight scoring consistency and outliers (surprises). Despite high variation among scientists in scoring the year that each indicator would occur, there was overall consistency across the foresights between years. Our approach shows that foresighting can be quantitative, by using time specific evaluation of indicators which is an improvement over traditional descriptive approaches, as individual performance and changes in likelihood can be evaluated. This approach can motivate and guide strategic planning and investment decisions by scientific institutions in response to different anticipated futures and build the skills of staff in futures thinking.

6 pages, 5 figures, supporting information https://doi.org/10.1073/pnas.1900194116.-- All data reported in this paper are archived and publicly available at http://dataservices.gfz-potsdam.de/pik/showshort.php?id=escidoc:2956913., While the physical dimensions of climate change are now routinely assessed through multimodel intercomparisons, projected impacts on the global ocean ecosystem generally rely on individual models with a specific set of assumptions. To address these single-model limitations, we present standardized ensemble projections from six global marine ecosystem models forced with two Earth system models and four emission scenarios with and without fishing. We derive average biomass trends and associated uncertainties across the marine food web. Without fishing, mean global animal biomass decreased by 5% (±4% SD) under low emissions and 17% (±11% SD) under high emissions by 2100, with an average 5% decline for every 1 °C of warming. Projected biomass declines were primarily driven by increasing temperature and decreasing primary production, and were more pronounced at higher trophic levels, a process known as trophic amplification. Fishing did not substantially alter the effects of climate change. Considerable regional variation featured strong biomass increases at high latitudes and decreases at middle to low latitudes, with good model agreement on the direction of change but variable magnitude. Uncertainties due to variations in marine ecosystem and Earth system models were similar. Ensemble projections performed well compared with empirical data, emphasizing the benefits of multimodel inference to project future outcomes. Our results indicate that global ocean animal biomass consistently declines with climate change, and that these impacts are amplified at higher trophic levels. Next steps for model development include dynamic scenarios of fishing, cumulative human impacts, and the effects of management measures on future ocean biomass trends, Financial support was provided by the German Federal Ministry of Education and Research through ISI-MIP (Grant01LS1201A1), the European Union’s Horizon 2020 Research and Innovation Program (Grant 678193), and the Ocean Frontier Institute (Module G). We acknowledge additional financial support as follows: to H.K.L., W.W.L.C., and B.W. from the Natural Sciences and Engineering Research Council (NSERC) of Canada; to D.P.T. from the Kanne Rasmussen Foundation Denmark; to A.B.-B. from the NSERC Transatlantic Ocean Science and Technology Program; to W.W.L.C. and T.D.E. from the Nippon Foundation-Nereus Program; to E.D.G., M.C. and J. Steenbeek from the European Union’s Horizon 2020 Re-search and Innovation Program (Grants 682602 and 689518); to E.A.F., J.L.B., andT.R. from Commonwealth Scientific and Industrial Research Organization and the Australian Research Council; to N.B., L.B., and O.M. from the French Agence Nationale de la Recherche and Pôle de Calcul et de Données pour la Mer; and to S.J. from the UK Department of Environment, Food and Rural Affairs

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed &gt, 1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p &lt, 0.001). The median age was 54 (IQR = 51–62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51–71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes.

Climate change is shifting the abundance and distribution of marine species with consequences for ecosystem functioning, seafood supply, management and conservation. Several approaches for future projection exist but these have never been compared systematically to assess their variability. We conducted standardized ensemble projections including 6 global fisheries and marine ecosystem models, forced with 2 Earth-system models and 4 emission scenarios in a fished and unfished ocean, to derive average trends and associated uncertainties. Without fishing, mean global animal biomass decreased by 5% (±4%) under low and 17% (±11%) under high emissions by 2100, primarily driven by increasing temperature and decreasing primary production. These climate-change effects were slightly weaker for larger animals and in a fished ocean. Considerable regional variation ranged from strong biomass increases in high latitudes to strong decreases in mid-low latitudes, with good model agreement on the direction of change but variable magnitude. Uncertainties due to differences among ecosystem or Earth-system models were similar, suggesting equal need for model improvement. Our ensemble projections provide the most comprehensive outlook on potential climate-driven ecological changes in the ocean to date. Realized future trends will largely depend on how fisheries and management adapt to these changes in a changing climate.

BRCA1 and BRCA2 mutation carriers have an increased risk of contralateral breast cancer after primary breast cancer. Risk reduction strategies are discussed after assessment of risk factors for developing contralateral breast cancer. We assessed potential risk factors that could be of use in clinical practice, including the novel use of single nucleotide polymorphisms (SNP) testing. 506 BRCA1 and 505 BRCA2 mutation carriers with a diagnosis of breast cancer were observed for up to 30 years. The risk of a contralateral breast cancer is approximately 2-3% per year, remaining constant for at least 20 years. This was similar in both BRCA1 and BRCA2 carriers. Initial breast cancer before age 40-years was a significant risk factor, which was more pronounced in BRCA1 patients. The effect of risk-reducing oophorectomy on contralateral breast cancer risk may be overestimated because of bias. No significant association was found between overall breast cancer risk SNP score and contralateral breast cancer development. Young mutation carriers, particularly those with BRCA1 mutations, who develop breast cancer have a significantly higher risk of developing contralateral breast cancer, remaining constant for over 20 years. Contralateral risk-reducing mastectomy should be considered in this group, in particular as there is a survival benefit. Caution is advised when counselling women considering risk-reducing oophorectomy as, after accounting for statistical bias, the associated risk reduction was found to be non-significant, and potentially smaller than has been previously reported. SNP testing did not add any further discriminatory information when assessing contralateral breast cancer risk.

Neurofibromatosis type 2 (NF2) is associated with the development of several types of benign nervous system tumours, while malignancies are rare. We report a 22-year-old man who presented with retroperitoneal and spinal high-grade sarcomas with epithelial features. Samples showed a mixed epithelioid and spindled cell content with little associated matrix and inconclusive immunochemistry. Genetic analysis of a schwannoma and matched blood samples demonstrated a constitutional de novo substitution at the splice donor site of intron 8 of the NF2 gene and aa acquired large deletion of the entire NF2 gene as a second hit, with some loss of SMARCB1. The sarcoma also showed evidence of loss of SMARCB1 and NF2 with loss of INI1 staining. Unfortunately the mass was unresectable and the patient died 6 months after diagnosis. This malignancy was most consistent with SMARCB1-deficient epithelioid malignant peripheral nerve sheath tumour, although a significant differential was proximal-type epithelial sarcoma. Each differential has previously been reported only once with NF2. This demonstrates an extremely rare potential complication of the condition.

Background Randomised phase 3 trials have demonstrated that poly (ADP-ribose) polymerase (PARP) inhibitors significantly improve progression-free survival in BRCA-mutant high-grade serous and endometrioid ovarian carcinoma. Consequently, the demand for germline and tumour BRCA1/2testing has increased significantly throughout the UK. We report results from a tumour BRCA1/2testing service available to cancer centres across England, Wales and Northern Ireland from July 2017 to February 2019. Methods DNA extracted from formalin fixed, paraffin-embedded tumour samples underwent next generation sequencing for BRCA1/2 variants. Eligibility criteria included relapsed, platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer with germline BRCA1/2wild-type or unknown germline. Patients also had to have received ≥2 prior lines of platinum-based chemotherapy. A confirmatory histopathology report was requested as part of the tumour BRCA1/2testing service. Results Two hundred and ninety-three histologically-confirmed high-grade serous and/or endometrioid ovarian cancer tumour samples underwent tumour BRCA1/2testing. The prevalence of pathogenic (class 5) or likely pathogenic (class 4) variants was 17.7% (52/293). The germline BRCA1/2was wild-type for 185/293 (63.1%) of patients, with the remaining 36.9% (108/293) with germline BRCA1/2unknown. There were at least 36 (12.3%) pathogenic/likely pathogenic somatic BRCA1/2variants detected. The allele fraction for somatic BRCA1/2pathogenic variants ranged from 0.06 to 0.98, with 50% (18/36) reported with an allele fraction of ≥ 0.5 (50%), in keeping with putative biallelic loss-of-function. Conclusions Prospective evaluation of paired germline and tumour BRCA1/2testing in all women who are diagnosed with platinum-sensitive high-grade serous and/or endometrioid ovarian cancer in the UK is now required to validate these findings. Legal entity responsible for the study AstraZeneca. Funding AstraZeneca. Disclosure All authors have declared no conflicts of interest.

Eddy, T.D. ... et al.-- 14 pages, 6 figures, supporting Information, Since the 1950s, invertebrate fisheries catches have rapidly expanded globally to more than 10 million tonnes annually, with twice as many target species, and are now significant contributors to global seafood provision, export, trade and local livelihoods. Invertebrates play important and diverse functional roles in marine ecosystems, yet the ecosystem effects of their exploitation are poorly understood. Using 12 ecosystem models distributed worldwide, we analysed the trade-offs of various invertebrate fisheries and their ecosystem effects as well as ecological indicators. Although less recognized for their contributions to marine food webs, our results show that the magnitude of trophic impacts of invertebrates on other species of commercial and conservation interest is comparable with those of forage fish. Generally, cephalopods showed the strongest ecosystem effects and were characterized by a strong top-down predatory role. Lobster, and to a lesser extent, crabs, shrimp and prawns, also showed strong ecosystem effects, but at lower trophic levels. Benthic invertebrates, including epifauna and infauna, also showed considerable ecosystem effects, but with strong bottom-up characteristics. In contrast, urchins, bivalves, and gastropods showed generally lower ecosystem effects in our simulations. Invertebrates also strongly contributed to benthic–pelagic coupling, with exploitation of benthic invertebrates impacting pelagic fishes and vice versa. Finally, on average, invertebrates produced maximum sustainable yield at lower levels of depletion (~45%) than forage fish (~65%), highlighting the need for management targets that avoid negative consequences for target species and marine ecosystems as a whole, Key financial support for this project was provided by the Lenfest Ocean Program with a grant to HKL. MC was partially funded by the European Commission through the Marie Curie Career Integration Grant Fellowships – PCIG10-GA-2011-303534 – to the BIOWEB project and by the Spanish National Program Ramon y Cajal. VC acknowledges support from NSERC, Canada. SM gratefully acknowledges the support provided by Defra project M1228 ‘Fizzyfish’

The 2014–2016 JET results are reviewed in the light of their significance for optimising the ITER research plan for the active and non-active operation. More than 60 h of plasma operation with ITER first wall materials successfully took place since its installation in 2011. New multi-machine scaling of the type I-ELM divertor energy flux density to ITER is supported by first principle modelling. ITER relevant disruption experiments and first principle modelling are reported with a set of three disruption mitigation valves mimicking the ITER setup. Insights of the L–H power threshold in Deuterium and Hydrogen are given, stressing the importance of the magnetic configurations and the recent measurements of fine-scale structures in the edge radial electric. Dimensionless scans of the core and pedestal confinement provide new information to elucidate the importance of the first wall material on the fusion performance. H-mode plasmas at ITER triangularity (H = 1 at ßN ~ 1.8 and n/nGW ~ 0.6) have been sustained at 2 MA during 5 s. The ITER neutronics codes have been validated on high performance experiments. Prospects for the coming D–T campaign and 14 MeV neutron calibration strategy are reviewed. This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under grant agreement No 633053. Peer Reviewed Article signat per 1.173 autors/es: X. Litaudon35, S. Abduallev39, M. Abhangi46, P. Abreu53, M. Afzal7, K.M. Aggarwal29, T. Ahlgren101, J.H. Ahn8, L. Aho-Mantila112, N. Aiba69, M. Airila112, R. Albanese105, V. Aldred7, D. Alegre93, E. Alessi45, P. Aleynikov55, A. Alfier12, A. Alkseev72, M. Allinson7, B. Alper7, E. Alves53, G. Ambrosino105, R. Ambrosino106, L. Amicucci90, V. Amosov88, E. Andersson Sundén22, M. Angelone90, M. Anghel85, C. Angioni62, L. Appel7, C. Appelbee7, P. Arena30, M. Ariola106, H. Arnichand8, S. Arshad41, A. Ash7, N. Ashikawa68, V. Aslanyan64, O. Asunta1, F. Auriemma12, Y. Austin7, L. Avotina103, M.D. Axton7, C. Ayres7, M. Bacharis24, A. Baciero57, D. Baião53, S. Bailey7, A. Baker7, I. Balboa7, M. Balden62, N. Balshaw7, R. Bament7, J.W. Banks7, Y.F. Baranov7, M.A. Barnard7, D. Barnes7, M. Barnes27, R. Barnsley55, A. Baron Wiechec7, L. Barrera Orte34, M. Baruzzo12, V. Basiuk8, M. Bassan55, R. Bastow7, A. Batista53, P. Batistoni90, R. Baughan7, B. Bauvir55, L. Baylor73, B. Bazylev56, J. Beal110, P.S. Beaumont7, M. Beckers39, B. Beckett7, A. Becoulet8, N. Bekris35, M. Beldishevski7, K. Bell7, F. Belli90, M. Bellinger7, É. Belonohy62, N. Ben Ayed7, N.A. Benterman7, H. Bergsåker42, J. Bernardo53, M. Bernert62, M. Berry7, L. Bertalot55, C. Besliu7, M. Beurskens63, B. Bieg61, J. Bielecki47, T. Biewer73, M. Bigi12, P. Bílková50, F. Binda22, A. Bisoffi31, J.P.S. Bizarro53, C. Björkas101, J. Blackburn7, K. Blackman7, T.R. Blackman7, P. Blanchard33, P. Blatchford7, V. Bobkov62, A. Boboc7, G. Bodnár113, O. Bogar18, I. Bolshakova60, T. Bolzonella12, N. Bonanomi97, F. Bonelli56, J. Boom62, J. Booth7, D. Borba35,53, D. Borodin39, I. Borodkina39, A. Botrugno90, C. Bottereau8, P. Boulting7, C. Bourdelle8, M. Bowden7, C. Bower7, C. Bowman110, T. Boyce7, C. Boyd7, H.J. Boyer7, J.M.A. Bradshaw7, V. Braic87, R. Bravanec40, B. Breizman107, S. Bremond8, P.D. Brennan7, S. Breton8, A. Brett7, S. Brezinsek39, M.D.J. Bright7, M. Brix7, W. Broeckx78, M. Brombin12, A. Brosławski65, D.P.D. Brown7, M. Brown7, E. Bruno55, J. Bucalossi8, J. Buch46, J. Buchanan7, M.A. Buckley7, R. Budny76, H. Bufferand8, M. Bulman7, N. Bulmer7, P. Bunting7, P. Buratti90, A. Burckhart62, A. Buscarino30, A. Busse7, N.K. Butler7, I. Bykov42, J. Byrne7, P. Cahyna50, G. Calabrò90, I. Calvo57, Y. Camenen4, P. Camp7, D.C. Campling7, J. Cane7, B. Cannas17, A.J. Capel7, P.J. Card7, A. Cardinali90, P. Carman7, M. Carr7, D. Carralero62, L. Carraro12, B.B. Carvalho53, I. 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Trimble7, M. Tripsky58, M. Tsalas38, P. Tsavalas71, D. Tskhakaya jun102, I. Turner7, M.M. Turner32, M. Turnyanskiy34, G. Tvalashvili7, S.G.J. Tyrrell7, A. Uccello45, Z. Ul-Abidin7, J. Uljanovs1, D. Ulyatt7, H. Urano69, I. Uytdenhouwen78, A.P. Vadgama7, D. Valcarcel7, M. Valentinuzzi8, M. Valisa12, P. Vallejos Olivares42, M. Valovic7, M. Van De Mortel7, D. Van Eester58, W. Van Renterghem78, G.J. van Rooij38, J. Varje1, S. Varoutis56, S. Vartanian8, K. Vasava46, T. Vasilopoulou71, J. Vega57, G. Verdoolaege58, R. Verhoeven7, C. Verona95, G. Verona Rinati95, E. Veshchev55, N. Vianello45, J. Vicente53, E. Viezzer62,92, S. Villari90, F. Villone100, P. Vincenzi12, I. Vinyar74, B. Viola90, A. Vitins103, Z. Vizvary7, M. Vlad86, I. Voitsekhovitch34, P. Vondráček50, N. Vora7, T. Vu8, W.W. Pires de Sa52, B. Wakeling7, C.W.F. Waldon7, N. Walkden7, M. Walker7, R. Walker7, M. Walsh55, E. Wang39, N. Wang39, S. Warder7, R.J. Warren7, J. Waterhouse7, N.W. Watkins28, C. Watts55, T. Wauters58, A. Weckmann42, J. Weiland23, H. Weisen33, M. Weiszflog22, C. Wellstood7, A.T. West7, M.R. Wheatley7, S. Whetham7, A.M. Whitehead7, B.D. Whitehead7, A.M. Widdowson7, S. Wiesen39, J. Wilkinson7, J. Williams7, M. Williams7, A.R. Wilson7, D.J. Wilson7, H.R. Wilson110, J. Wilson7, M. Wischmeier62, G. Withenshaw7, A. Withycombe7, D.M. Witts7, D. Wood7, R. Wood7, C. Woodley7, S. Wray7, J. Wright7, J.C. Wright64, J. Wu89, S. Wukitch64, A. Wynn110, T. Xu7, D. Yadikin16, W. Yanling39, L. Yao89, V. Yavorskij102, M.G. Yoo80, C. Young7, D. Young7, I.D. Young7, R. Young7, J. Zacks7, R. Zagorski49, F.S. Zaitsev18, R. Zanino75, A. Zarins103, K.D. Zastrow7, M. Zerbini90, W. Zhang62, Y. Zhou42, E. Zilli12, V. Zoita86, S. Zoletnik113, I. Zychor65 and JET Contributorsa // EUROfusion Consortium JET, Culham Science Centre, Abingdon, OX14 3DB, United Kingdom / 1 Aalto University, PO Box 14100, FIN-00076 Aalto, Finland / 2 Aix Marseille Université, CNRS, Centrale Marseille, M2P2 UMR 7340, 13451, Marseille, France / 3 Aix-Marseille Université, CNRS, IUSTI UMR 7343, 13013 Marseille, France / 4 Aix-Marseille Université, CNRS, PIIM, UMR 7345, 13013 Marseille, France / 5 Arizona State University, Tempe, AZ, United States of America / 6 Barcelona Supercomputing Center, Barcelona, Spain / 7 CCFE, Culham Science Centre, Abingdon, Oxon, OX14 3DB, United Kingdom / 8 CEA, IRFM, F-13108 Saint Paul Lez Durance, France / 9 Center for Energy Research, University of California at San Diego, La Jolla, CA 92093, United States of America / 10 Centro Brasileiro de Pesquisas Fisicas, Rua Xavier Sigaud, 160, Rio de Janeiro CEP 22290-180, Brazil / 11 Consorzio CREATE, Via Claudio 21, 80125 Napoli, Italy / 12 Consorzio RFX, corso Stati Uniti 4, 35127 Padova, Italy / 13 Daegu University, Jillyang, Gyeongsan, Gyeongbuk 712-174, Republic of Korea / 14 Departamento de Física, Universidad Carlos III de Madrid, 28911 Leganés, Madrid, Spain / 15 Department of Applied Physics UG (Ghent University) St-Pietersnieuwstraat 41 B-9000 Ghent, Belgium / 16 Department of Earth and Space Sciences, Chalmers University of Technology, SE-41296 Gothenburg, Sweden / 17 Department of Electrical and Electronic Engineering, University of Cagliari, Piazza d’Armi 09123, Cagliari, Italy / 18 Department of Experimental Physics, Faculty of Mathematics, Physics and Informatics Comenius University Mlynska dolina F2, 84248 Bratislava, Slovakia / 19 Department of Materials Science, Warsaw University of Technology, PL-01-152 Warsaw, Poland / 20 Department of Nuclear and Quantum Engineering, KAIST, Daejeon 34141, Korea / 21 Department of Physics and Applied Physics, University of Strathclyde, Glasgow, G4 ONG, United Kingdom / 22 Department of Physics and Astronomy, Uppsala University, SE-75120 Uppsala, Sweden / 23 Department of Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden / 24 Department of Physics, Imperial College London, London, SW7 2AZ, United Kingdom / 25 Department of Physics, SCI, KTH, SE-10691 Stockholm, Sweden / 26 Department of Physics, University of Basel, Basel, Switzerland / 27 Department of Physics, University of Oxford, Oxford, OX1 2JD, United Kingdom / 28 Department of Physics, University of Warwick, Coventry, CV4 7AL, United Kingdom / 29 Department of Pure and Applied Physics, Queens University, Belfast, BT7 1NN, United Kingdom / 30 Dipartimento di Ingegneria Elettrica Elettronica e Informatica, Università degli Studi di Catania, 95125 Catania, Italy / 31 Dipartimento di Ingegneria Industriale, University of Trento, Trento, Italy / 32 Dublin City University (DCU), Dublin, Ireland / 33 Ecole Polytechnique Fédérale de Lausanne (EPFL), Swiss Plasma Center (SPC), CH-1015 Lausanne, Switzerland / 34 EUROfusion Programme Management Unit, Boltzmannstr. 2, 85748 Garching, Germany / 35 EUROfusion Programme Management Unit, Culham Science Centre, Culham, OX14 3DB, United Kingdom / 36 European Commission, B-1049 Brussels, Belgium / 37 Fluid and Plasma Dynamics, ULB—Campus Plaine—CP 231 Boulevard du Triomphe, 1050 Bruxelles, Belgium / 38 FOM Institute DIFFER, Eindhoven, Netherlands / 39 Forschungszentrum Jülich GmbH, Institut für Energie- und Klimaforschung—Plasmaphysik, 52425 Jülich, Germany / 40 Fourth State Research, 503 Lockhart Dr, Austin, TX, United States of America / 41 Fusion for Energy Joint Undertaking, Josep Pl. 2, Torres Diagonal Litoral B3, 08019, Barcelona, Spain / 42 Fusion Plasma Physics, EES, KTH, SE-10044 Stockholm, Sweden / 43 General Atomics, PO Box 85608, San Diego, CA 92186-5608, United States of America / 44 HRS Fusion, West Orange, NJ, United States of America / 45 IFP-CNR, via R. Cozzi 53, 20125 Milano, Italy / 46 Institute for Plasma Research, Bhat, Gandhinagar-382 428, Gujarat State, India / 47 Institute of Nuclear Physics, Radzikowskiego 152, 31-342 Kraków, Poland / 48 Institute of Physics, Opole University, Oleska 48, 45-052 Opole, Poland / 49 Institute of Plasma Physics and Laser Microfusion, Hery 23, 01-497 Warsaw, Poland / 50 Institute of Plasma Physics AS CR, Za Slovankou 1782/3, 182 00 Praha 8, Czechia / 51 Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031, People’s Republic of China / 52 Instituto de Física, Universidade de São Paulo, Rua do Matão Travessa R Nr.187 CEP 05508-090 Cidade Universitária, São Paulo, Brasil / 53 Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal / 54 Ioffe Physico-Technical Institute, 26 Politekhnicheskaya, St Petersburg 194021, Russian Federation / 55 ITER Organization, Route de Vinon, CS 90 046, 13067 Saint Paul Lez Durance, France / 56 Karlsruhe Institute of Technology, PO Box 3640, D-76021 Karlsruhe, Germany / 57 Laboratorio Nacional de Fusión, CIEMAT, Madrid, Spain / 58 Laboratory for Plasma Physics Koninklijke Militaire School—Ecole Royale Militaire, Renaissancelaan 30 Avenue de la Renaissance B-1000, Brussels, Belgium / 59 Lithuanian energy institute, Breslaujos g. 3, LT-44403, Kaunas, Lithuania / 60 Magnetic Sensor Laboratory, Lviv Polytechnic National University, Lviv, Ukraine / 61 Maritime University of Szczecin, Waly Chrobrego 1-2, 70-500 Szczecin, Poland / 62 Max-Planck-Institut für Plasmaphysik, D-85748 Garching, Germany / 63 Max-Planck-Institut für Plasmaphysik, Teilinsitut Greifswald, D-17491 Greifswald, Germany / 64 MIT Plasma Science and Fusion Centre, Cambridge, MA 02139, United States of America / 65 National Centre for Nuclear Research (NCBJ), 05-400 Otwock-Świerk, Poland / 66 National Fusion Research Institute (NFRI), 169-148 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea / 67 National Institute for Fusion Science, Oroshi, Toki, Gifu 509-5292, Japan / 68 National Institute for Fusion Science, Toki, 509-5292, Japan / 69 National Institutes for Quantum and Radiological Science and Technology, Naka, Ibaraki 311-0193, Japan / 70 National Technical University of Athens, Iroon Politechniou 9, 157 73 Zografou, Athens, Greece / 71 NCSR ‘Demokritos’, 153 10, Agia Paraskevi Attikis, Greece / 72 NRC Kurchatov Institute, 1 Kurchatov Square, Moscow 123182, Russian Federation / 73 Oak Ridge National Laboratory, Oak Ridge, TN 37831-6169, United States of America / 74 PELIN LLC, 27a, Gzhatskaya Ulitsa, Saint Petersburg, 195220, Russian Federation / 75 Politecnico di Torino, Corso Duca degli Abruzzi 24, I-10129 Torino, Italy / 76 Princeton Plasma Physics Laboratory, James Forrestal Campus, Princeton, NJ 08543, United States of America / 77 Purdue University, 610 Purdue Mall, West Lafayette, IN 47907, United States of America / 78 SCK-CEN, Nuclear Research Centre, 2400 Mol, Belgium / 79 Second University of Napoli, Consorzio CREATE, Via Claudio 21, 80125 Napoli, Italy / 80 Seoul National University, Shilim-Dong, Gwanak-Gu, Republic of Korea / 81 Slovenian Fusion Association (SFA), Jozef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia / 82 Space and Plasma Physics, EES, KTH SE-100 44 Stockholm, Sweden / 83 Technical University of Denmark, Department of Physics, Bldg 309, DK-2800 Kgs Lyngby, Denmark / 84 The ‘Horia Hulubei’ National Institute for Physics and Nuclear Engineering, Magurele-Bucharest, Romania / 85 The National Institute for Cryogenics and Isotopic Technology, Ramnicu Valcea, Romania / 86 The National Institute for Laser, Plasma and Radiation Physics, Magurele-Bucharest, Romania / 87 The National Institute for Optoelectronics, Magurele-Bucharest, Romania / 88 Troitsk Insitute of Innovating and Thermonuclear Research (TRINITI), Troitsk 142190, Moscow Region, Russian Federation / 89 University of Electronic Science and Technology of China, Chengdu, People’s Republic of China / 90 Unità Tecnica Fusione, ENEA C. R. Frascati, via E. Fermi 45, 00044 Frascati (Roma), Italy / 91 Universidad Complutense de Madrid, Madrid, Spain / 92 Universidad de Sevilla, Sevilla, Spain / 93 Universidad Nacional de Educación a Distancia, Madrid, Spain / 94 Universidad Politécnica de Madrid, Grupo I2A2, Madrid, Spain / 95 Università di Roma Tor Vergata, Via del Politecnico 1, Roma, Italy / 96 University College Cork (UCC), Ireland / 97 University Milano-Bicocca, piazza della Scienza 3, 20126 Milano, Italy / 98 University of Basilicata, Consorzio CREATE, Via Claudio 21, 80125 Napoli, Italy / 99 University of California, 1111 Franklin St., Oakland, CA 94607, United States of America / 100 University of Cassino, Consorzio CREATE, Via Claudio 21, 80125 Napoli, Italy / 101 University of Helsinki, PO Box 43, FI-00014 University of Helsinki, Finland / 102 University of Innsbruck, Fusion@Österreichische Akademie der Wissenschaften (ÖAW), Innsbruck, Austria / 103 University of Latvia, 19 Raina Blvd., Riga, LV 1586, Latvia / 104 University of Lorraine, CNRS, UMR7198, YIJL, Nancy, France / 105 University of Napoli ‘Federico II’, Consorzio CREATE, Via Claudio 21, 80125 Napoli, Italy / 106 University of Napoli Parthenope, Consorzio CREATE, Via Claudio 21, 80125 Napoli, Italy / 107 University of Texas at Austin, Institute for Fusion Studies, Austin, TX 78712, United States of America / 108 University of Toyama, Toyama, 930-8555, Japan / 109 University of Tuscia, DEIM, Via del Paradiso 47, 01100 Viterbo, Italy / 110 University of York, Heslington, York YO10 5DD, United Kingdom / 111 Vienna University of Technology, Fusion@Österreichische Akademie der Wissenschaften (ÖAW), Austria / 112 VTT Technical Research Centre of Finland, PO Box 1000, FIN-02044 VTT, Finland / 113 Wigner Research Centre for Physics, PO Box 49, H-1525 Budapest, Hungary

Low-trophic level species account for more than 30% of global fisheries production and contribute substantially to global food security. We used a range of ecosystem models to explore the effects of fishing low-trophic level species on marine ecosystems, including marine mammals and seabirds, and on other commercially important species. In five well-studied ecosystems, we found that fishing these species at conventional maximum sustainable yield (MSY) levels can have large impacts on other parts of the ecosystem, particularly when they constitute a high proportion of the biomass in the ecosystem or are highly connected in the food web. Halving exploitation rates would result in much lower impacts on marine ecosystems while still achieving 80% of MSY.

Background Cystic fibrosis (CF) is produced by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator Gene (CFTR) gene. Methods One hundred twenty eight patients with CF were analysed for mutations in the CFTR gene in order to establish the frequency of CF mutations in the Romanian population. The chief methods of analysis were polymerase chain reaction (PCR) of DNA extracted from blood and electrophoresis of PCR products. Results The frequency of F508del in CF chromosomes from Romania is approximately 56.3%. Other frequent mutations noted are: G542X (3.9%), W1282X (2.3%), and CFTRdele2,3(21 kb)(1.6%); the remaining mutations have frequencies below 1%. Conclusions We consider that the frequency of F508del in CF patients from Romania is higher than in previous reports, reaching 56.3%, probably owing to more rigorous selection of patients for genetic testing, allowing improved calculation of mutation frequencies.

To develop a simple scoring system for the likelihood of identifying a BRCA1 or BRCA2 mutation.DNA samples from affected subjects from 422 non-Jewish families with a history of breast and/or ovarian cancer were screened for BRCA1 mutations and a subset of 318 was screened for BRCA2 by whole gene screening techniques. Using a combination of results from screening and the family history of mutation negative and positive kindreds, a simple scoring system (Manchester scoring system) was devised to predict pathogenic mutations and particularly to discriminate at the 10% likelihood level. A second separate dataset of 192 samples was subsequently used to test the model's predictive value. This was further validated on a third set of 258 samples and compared against existing models.The scoring system includes a cut-off at 10 points for each gene. This equates to10% probability of a pathogenic mutation in BRCA1 and BRCA2 individually. The Manchester scoring system had the best trade-off between sensitivity and specificity at 10% prediction for the presence of mutations as shown by its highest C-statistic and was far superior to BRCAPRO.The scoring system is useful in identifying mutations particularly in BRCA2. The algorithm may need modifying to include pathological data when calculating whether to screen for BRCA1 mutations. It is considerably less time-consuming for clinicians than using computer models and if implemented routinely in clinical practice will aid in selecting families most suitable for DNA sampling for diagnostic testing.

The hematophagous sucking louse Microthoracius mazzai Werneck, 1932, is redescribed and identified as a parasite of alpacas, Lama pacos L. Specimens were collected on animals 10-14 mo old, located on a large community farm at 4,600 m above sea level in the Peruvian Andes. In total, 26 scanning electron microscope (SEM) figures are included that highlight salient and differential characteristics, especially the unique elongated spindle-shaped head, which is almost as long as its abdomen. Alpacas, 1 of the 4 species of South American camelids, are important for their production of high-quality wool in the Andes Mountain range countries, especially Peru and Bolivia; to a lesser degree Chile; and more recently Argentina, where breeding and disease control programs are receiving increased technical support. Information is given on the prevalence of lice infestations in the flock, clinical signs, and economic losses. We report the efficacy of moxidectin (SC, 200 mcg/kg, b.w.) in a repeated treatment program of 7-10 d, which is currently used for mange control in these ruminants.

33 families with a history of male breast cancer aged 60 or less or with a family history of male and female breast cancer were screened for the presence of BRCA2 mutations. 12 pathogenic BRCA2 mutations were identified (36%) in samples from an affected family member. All mutations segregated with disease where it was possible to check. Of the 14 families fulfilling BCLC criteria, 9 (64%) had mutations whilst only 3/16 (19%) of male breast cancer patients with less significant female breast cancer family history having a mutation. All 3 families with ovarian cancer and 3 families with multiple male breast cancer cases had BRCA2 mutations. These data are a further guide to how to prioritise samples for BRCA2 mutation analysis.

Globally, many fish species are overexploited, and many stocks have collapsed. This crisis, along with increasing concerns over flow-on effects on ecosystems, has caused a reevaluation of traditional fisheries management practices, and a new ecosystem-based fisheries management (EBFM) paradigm has emerged. As part of this approach, selective fishing is widely encouraged in the belief that nonselective fishing has many adverse impacts. In particular, incidental bycatch is seen as wasteful and a negative feature of fishing, and methods to reduce bycatch are implemented in many fisheries. However, recent advances in fishery science and ecology suggest that a selective approach may also result in undesirable impacts both to fisheries and marine ecosystems. Selective fishing applies one or more of the “6-S” selections: species, stock, size, sex, season, and space. However, selective fishing alters biodiversity, which in turn changes ecosystem functioning and may affect fisheries production, hindering rather than helping achieve the goals of EBFM. We argue here that a “balanced exploitation” approach might alleviate many of the ecological effects of fishing by avoiding intensive removal of particular components of the ecosystem, while still supporting sustainable fisheries. This concept may require reducing exploitation rates on certain target species or groups to protect vulnerable components of the ecosystem. Benefits to society could be maintained or even increased because a greater proportion of the entire suite of harvested species is used.

This study was designed to determine whether orange roughy reproduce throughout their distribution in Australian waters, and if so, whether commencement of spawning and length at maturity vary within the region. We found that females from four widely separated sampling areas reproduced in 1988, but that the onset of spawning and length at maturity were not the same in all the areas. In New South Wales, ovulation was finished by mid‐June, and 50% of females were mature at 28 cm standard length (S.L.). On the other hand, females from eastern and western Tasmania and South Australia did not spawn until mid‐July, and 50% of females from Tasmania were not mature until 32 cm S.L. Females from all areas had oocytes with yolk granules at least 5 months before ovulation. However, in the few months before spawning, some adult females from all areas had not undergone vitellogenesis or were resorbing all yolky oocytes. The best estimates of the proportion of these non‐reproductive females were made in March and April, when the single batch of eggs to be spawned was clearly distinguishable, and before spawning aggregations had formed. In 1990 in eastern Tasmania, at the site of a major spawning aggregation, the best estimate of the proportion of non‐reproductive fish was 45%. We suggest that scarcity of food, coupled with the cost of joining a spawning aggregation, may result in intermittent spawning in this long‐lived species. Copyright © 1992, Wiley Blackwell. All rights reserved

We wish to reply to the interesting comments concerning our paper on phenocopies in families positive for mutations in BRCA1/2 genes since its electronic publication in October 2006.1 We understand the reservations about changing practice in reassuring individuals who test negative for a family mutation based on one largely retrospective analysis of families, and clearly there is a need to confirm our results in other large series. We were particularly careful to obviate …

Background: The identification of BRCA1 and BRCA2 mutations in familial breast cancer kindreds allows genetic testing of at-risk relatives. Those who test negative are usually reassured and additional breast cancer surveillance is discontinued. However, we postulated that in high-risk families, such as those seen in clinical genetics centres, the risk of breast cancer might be influenced not only by the BRCA1 / BRCA2 mutation but also by modifier genes. One manifestation of this would be the presence of phenocopies in BRCA1/BRCA2 kindreds. Methods: 277 families with pathogenic BRCA1 / BRCA2 mutations were reviewed and 28 breast cancer phenocopies identified. The relative risk of breast cancer in those testing negative was assessed using incidence rates from our cancer registry based on local population. Results: Phenocopies constituted up to 24% of tests on women with breast cancer after the identification of the mutation in the proband. The standardised incidence ratio for women who tested negative for the BRCA1 / BRCA2 family mutation was 5.3 for all relatives, 5.0 for all first-degree relatives (FDRs) and 3.2 (95% confidence interval 2.0 to 4.9) for FDRs in whose family all other cases of breast and ovarian cancer could be explained by the identified mutation. 13 of 107 (12.1%) FDRs with breast cancer and no unexplained family history tested negative. Conclusion: In high-risk families, women who test negative for the familial BRCA1/BRCA2 mutation have an increased risk of breast cancer consistent with genetic modifiers. In light of this, such women should still be considered for continued surveillance.

The prevalence of BRCA1 and BRCA2 mutations in families with breast and ovarian cancers depends on the type of cancer found, the number of cases, and the ethnic background of the family.1 The proportion of breast cancers attributable to BRCA1 or BRCA2 may also depend on the ethnic origin of families. Several mutations have been identified that are found only in specific countries or ethnic groups, suggesting that they are founder mutations. Individuals with the same founder mutation will also share the same alleles at polymorphic markers within the gene or adjacent to the gene. Some common mutations do not segregate with the same alleles and are therefore recurrent mutations. They occur at ‘hot spots’ for mutation; unstable parts of the gene. In countries with a small founder population, very few mutations may account for the vast majority of breast cancer families. The Ashkenazi Jewish population have three founder mutations, which are found in 2% of the Ashkenazi Jewish population.2 Population studies have shown that the 185delAG mutation predates the separation of the Sephardi and Ashkenazi Jewish populations and is probably 2000 years old.3 Full gene screening for mutations in the northwest of England has identified two recurrent mutations.4 BRCA1 4182delAATC (4184del TCAA or 4184del4) is a frameshift mutation that results in a stop at codon 1364, causing a truncated protein product. This mutation has been reported 75 times in the Breast Cancer Information Core (BIC) website (www.nhgri.nih.gov/Intramural\_research/Lab\_transfer/Bic/).5 In one study, it was identified in breast cancer cases in Britain, France, and the United States.6 The mutation was associated with three different haplotypes, indicating that it is a recurrent rather than a founder mutation. BRCA2 2157delG is also a frameshift mutation resulting in a stop at codon 659, causing a truncated protein product. …

33 families with a history of male breast cancer aged 60 or less or with a family history of male and female breast cancer were screened for the presence of BRCA2 mutations. 12 pathogenic BRCA2 mutations were identified (36%) in samples from an affected family member. All mutations segregated with disease where it was possible to check. Of the 14 families fulfilling BCLC criteria, 9 (64%) had mutations whilst only 3/16 (19%) of male breast cancer patients with less significant female breast cancer family history having a mutation. All 3 families with ovarian cancer and 3 families with multiple male breast cancer cases had BRCA2 mutations. These data are a further guide to how to prioritise samples for BRCA2 mutation analysis.

Pre-test and post-test computational fluid dynamics (CFD) data have been generated for an experimental scramjet fuel injector concept. These cold-flow calculations are part of an experimental and computational evaluation of an innovative, flush-mounted fuel injector designed by Aerojet General Corporation to provide maximum penetration with minimal losses. The key to the success of the design is the concept of local pressure matching. Results show fuel penetration far in excess of a priori expectations for the test conditions but reasonable agreement between CFD and experiment. As a result of excessive penetration, shock strength is higher than expected and total pressure losses are also high. Mixing efficiencies are comparable to those produced by an equivalent normal circular injector. Data obtained from CFD have proven beneficial to the experimental program by alerting researchers to potential problems, illuminating flow features inaccessible by current testing methods, and guiding the selection of fuel pressures for the achievement of local pressure matching.

On the basis of positive skin snips for Onchocerca cervicalis microfilariae (MF), 45 horses were chosen from 48 in a total of 257 screened on 12 locations in the northeast Province of Formosa (Argentina), and randomly assigned to two treatment groups of 20 horses each, and a nontreated control group of five horses. On Day 14 post-treatment (PT), skin snip samples in the ivermectin-treated (0.2 mg/kg) group were negative for normal viable microfilariae (MF), while horses in the control group maintained their pretreatment level of infection. On the same Day in the moxidectin-treated (0.4 mg/kg) group, 18 horses were negative for MF, but the remaining two had a total of 1 and 2 MF, respectively (equivalent to 10 and 20 MF/g of skin), but all three parasites showed marked cuticular and structural damage. Both horses were negative in a repeat biopsy on Day 21. From Day 3 PT, one ivermectin-treated horse (5%) evidenced an approximate 15 x 2 x 3 cm-sized, apparently nonpainful, oedematous swelling on the ventral midline, 20 cm in front of the navel, which remained unchanged on Day 14 PT. Adverse reactions were not observed in the moxidectin-treated group. Parasitaemia was found in 18.7% of sampled horses (48 of 257), and the number of MF varied between 10–1820/g of skin snip ( x 172). Similar prevalence and total counts had been described previously in 1985 and 1986 in cattle-farm horses in the same area of Argentina; in surveys in Texas (1974) and Louisiana (1995) in the USA, infection rates were also similar, but total counts much higher. It is concluded that moxidectin 2% equine oral gel and ivermectin 2% equine oral paste, were equally 100% effective in the control of O. cervicalis MF. Contrary to ivermectin, moxidectin did not cause post-treatment dermal reactions.

Affected individuals from 431 families gave blood for mutational analysis in BRCA1 and BRCA2 mainly to develop genetic tests for their family. Individuals were eligible if there was at least a 50% chance of a gene predisposing to breast cancer (not necessarily BRCA1/2 ) in their family. Assessment was made using the Cancer and Steroid Hormone (CASH) dataset and the Claus curves.1,2 A minimal requirement was two close relatives with breast cancer before the age of 50 years, but combinations of male and female breast cancer, and breast and ovarian cancer were particularly identified. An exception to this were two research projects where population based cases of breast cancer before the age of 31 years3 and sporadic breast cancer before the age of 36 years4 were screened for both genes. Male breast cancer (MBC) families presenting to the clinic with at least one MBC before the age of 60 years or at any age if female breast cancer had occurred were screened for BRCA2 .5 Initial screening for mutations involved a whole gene assessment using single strand conformational polymorphism (SSCP) analysis and protein truncation testing (PTT) of exon 11 in each gene. All mutations were confirmed, in both orientations, by direct fluorescent sequencing of the appropriate exon. We excluded one exon 13 duplication and two exonic deletions detected on screening 95 BRCA1 negative breast/ovarian families. A further two exon 13 duplications in five subsequent BRCA1 negative breast/ovary families originating from east of the Pennines were also excluded. Of the non large-scale rearrangement mutations, 26/78 (33%) were detected outside the commonly screened regions of BRCA1 (exons 2, 11, 20) in the UK (table 1). Similarly 15/50 (30%) BRCA2 mutations were detected outside exons 10 and 11. View this table: Table 1 Mutations in BRCA1/2 outside the commonly screened exons in the UK …

The demersal fish community on the mid-slope off southern Tasmania in south-eastern Australia is dominated by orange roughy Hoplostethus atlanticus (Trachichthyidae), several species of oreosomatids, macrourids, squalids, alepocephalids and a synaphobranchid eel. Cluster analysis based on diet dissimilarities of proportional prey weight identified five major trophic guilds: pyrosome-feeders, crustacean feeders, piscivores, benthopelagic omnivores and benthic-invertebrate feeders. Overall, the fish fed predominantly on pelagic or benthopelagic prey, consistent with other trophic studies in the Australasian region and the Northern Hemisphere. H. atlanticus, warty dory Allocyttus verrucosus, and the macrourid Coryphaenoides serrulatus were benthopelagic omnivores that ate mesopelagic fishes, crustaceans and squid. The first two species ate more mesopelagic fishes as their sizes increased. The squalids were predominantly piscivorous but might also scavenge. Macrourids were benthic-invertebrate feeders, pelagic crustacean feeders or benthopelagic omnivores. The alepocephalids and the smooth oreo Pseudocyttus maculatus were pyrosome-feeders. No seasonal variation in diet was found for any species. Ecological indices varied within each guild. Benthopelagic omnivores and piscivores had the largest diet breadth, evenness and diversity. Trophic levels ranged from 3.0 for pyrosome-feeders to 4.9 for piscivores and the overall average for the community was 3.7.

Each of the new approaches to treating SLE offers some hope in the ongoing effort to respond effectively to the challenges of this debilitating and often lethal condition. Research is extremely active and promises to accelerate as more is learned.

Diets of 15 species of demersal and pelagic fishes on the upper continental slope (420 to 550 m) were determined, based on samples taken every two months over 13 mo (April 1984 to April 1985) off eastern Tasmania. The calorific contribution of each prey item to the diets was determined. The fish could be divided into four trophic categories: pelagic piscivores, epibenthic piscivores, epibenthic invertebrate feeders and benthopelagic omnivores. Dietary overlap between the groups was low. The pelagic piscivores Apogonops anomalus, Trachurus declivis, Brama brama, Lepidopus caudatus and Macruronus novaezelandiae primarily consume the shelf-break myctophid Lampanyctodes hectoris; their diet is narrow, with a large overlap between species. The epibenthic piscivores Deania calcea and Genypterus blacodes both take a greater variety of prey, but have little dietary overlap. The fish feeding on epibenthic invertebrates, Coelorinchus sp. 2 and Centriscops humerosus, obtain most of their energy from benthic Crustacea and Ophiuroidea, supplemented with Lampanyctodes hectoris; the diet is broad, with little overlap. Among the benthopelagic omnivores (Cyttus traversi, Coelorinchus sp. 4, Lepidorhynchus denticulatus, Neocyttus rhomboidalis, Helicolenus percoides, Epigonus denticulatus and E. lenimen), most diets are broad and show slight overlap. All but E. denticulatus consume significant quantities of Lampanyctodes hectoris as well as Crustacea, particularly Polychaeta, Euphausiacea and Pyrosoma atlanticum. Seasonal changes in diet occurred in G. blacodes, T. declivis, Lepidopus caudatus, Coelorinchus sp. 4, Lepidorhynchus denticulatus, H. percoides, E. denticulatus and E. lenimen; these were related to changes in abundance of particular prey species, not to alterations in feeding habits. Only three species, Lepidopus caudatus, Coelorinchus sp. 2 and H. percoides, showed significant diel feeding periodicity. Ontogenetic dietary changes were evident in Cyttus traversi, Coelorinchus sp. 2, Lepidorhynchus denticulatus and H. percoides. Cyttus traversi and H. percoides progressively changed from crustaceans to fish as their size increased. The diets of size classes within species showed little overlap, except for Lepidorhynchus denticulatus, which eats chiefly euphausiids and Lampanyctodes hectoris at all sizes. In addition to describing the diets and trophic relationships of 90% of the fish biomass, the results emphasize the importance to the entire fish community of mesopelagic food resources, particularly Lampanyctodes hectoris. Many benthopelagic species undertake extensive vertical migrations in search of prey, thus playing a major role in the transport of energy from midwater regions to the benthos of the continental slope.

An outbreak of tropical theileriosis (T. annulata infection) is reported in artificial insemination Holstein bulls in Kabul (Afghanistan). The diagnostic work at the Central Veterinary Diagnostic Laboratory is described and the treatment given and results obtained by the Kabul Animal Health Clinic are reported. This case report constitutes the first account of the disease in Afghanistan where diagnostic confirmation has been made from material sent to internatinational reference centres.

The age, growth and mortality of the lanternfish Lampanyctodes hectoris (Gunther) were investigated by examining the otoliths, length-frequency data, and seasonal abundance of fish collected from continental slope waters of eastern Tasmania between April 1984 and June 1985. Although L. hectoris can live to 3 yr old, it has a high annual mortality (79%) and few live past their first year. Growth, described here by a variation of the Von Bertalanffy model, takes place mainly in the first six months of life and only during late spring and summer. The hypothesis of daily deposition of primary growth increments in myctophids was supported by comparing the back-calculated birth dates of daily-aged individuals of L. hectoris with the spawning season of this species.