Chondrodysplasia, enchondromas and a chest deformity causing severe pulmonary morbidity in a boy with a PTHLH duplication:A case report

Parathyroid hormone-like hormone (PTHLH) plays an important role in bone formation. Several skeletal dysplasias have been described that are associated with disruption of PTHLH functioning. Here we report on a new patient with a 898 Kb duplication on chromosome 12p11.22 including the PTHLH gene. The boy has multiple skeletal abnormalities including chondrodysplasia, lesions radiographically resembling enchondromas and posterior rib deformities leading to a severe chest deformity. Severe pulmonary symptoms were thought to be caused by limited mobility and secondary sputum evacuation problems due to the chest deformity. Imaging studies during follow-up revealed progression of the number of skeletal lesions over time. This case extends the phenotypic spectrum associated with copy number variation of PTHLH

Corporate image: a service recovery perspective

This article explores direct and indirect antecedents that contribute to corporate image formation in a service recovery context. Two studies were carried out in Egypt. Study 1 comprises 29 semistructured interviews with complainants of mobile phone network service providers in Egypt. Study 2 encompasses a mail survey of another 437 complainants. Findings reveal the importance of perceived justice, namely, interactional justice, in corporate image formation, as well as the mediating role of satisfaction with service recovery in the perceived justice-corporate image relationship. Results also reveal two empirical relationships: problem solving as a determinant of distributive justice and follow-up as a driver of procedural justice. Accordingly, this study contributes to the service field by providing the first empirical evaluation of new direct and indirect antecedents of corporate image formation in a service recovery context. Managerial recommendations are provided that encourage service practitioners to emphasize perceived justice and satisfaction with a service recovery process to enhance the company’s image. Additionally, companies should invest in implementing problem solving and follow-up as service recovery strategies since both significantly enhance perceived justice

Habitat preference of geese is affected by livestock grazing:Seasonal variation in an experimental field evaluation

The number of staging geese in northwestern Europe has increased dramatically. Growing goose numbers put strong grazing pressure on agricultural pastures. Damage to agricultural land may be mitigated by managing nature reserves in order to optimally accommodate large numbers of grazing geese. Livestock grazing has been shown to facilitate foraging geese; we take the novel approach of determining the effects of four different livestock grazing treatments in a replicated experiment on the distribution of geese. We present experimental field evidence that livestock grazing of a salt marsh in summer affects the habitat preference of foraging geese during autumn and spring staging. In an experimental field set-up with four different livestock grazing treatments we assessed goose visitation through dropping counts, in both autumn and spring. Grazing treatments included 0.5 or 1 horse ha(-1) and 0.5 or 1 cattle ha(-1) during the summer season. The livestock grazing regime affected goose distribution in autumn, just after livestock had been removed from the salt marsh. In autumn, goose visitation was highest in the 1 head ha(-1) grazing treatments, where grazing intensity by livestock was also highest. In line with this result, goose visitation was lowest in the 0.5 head ha(-1) livestock grazing treatments, where the grazing intensity by livestock was lowest. The differences in goose visitation among the experimental treatments in autumn could not be explained by the canopy height. In spring we did not find any effect of livestock grazing treatment on goose visitation. Differences in the distribution of geese over the experiment between autumn and spring may be explained by changes in the availability of nutrient-rich vegetation. Livestock summer grazing with a high stocking density, especially with horses, can be used to attract geese to salt marshes in autumn and potentially reduces damage caused by geese to inland farmland. From a nature conservation interest point of view, however, variation in structure of the vegetation is a prerequisite for other groups of organisms. Hence, we recommend grazing of salt marshes with densities of 0.5 head ha(-1) of livestock when goose conservation is not the only management issue

Virology Experts in the Boundary Zone Between Science, Policy and the Public: A Biographical Analysis

This article aims to open up the biographical black box of three experts working in the boundary zone between science, policy and public debate. A biographical-narrative approach is used to analyse the roles played by the virologists Albert Osterhaus, Roel Coutinho and Jaap Goudsmit in policy and public debate. These figures were among the few leading virologists visibly active in the Netherlands during the revival of infectious diseases in the 1980s. Osterhaus and Coutinho in particular are still the key figures today, as demonstrated during the outbreak of novel influenza A (H1N1). This article studies the various political and communicative challenges and dilemmas encountered by these three virologists, and discusses the way in which, strategically or not, they handled those challenges and dilemmas during the various stages of the field’s recent history. Important in this respect is their pursuit of a public role that is both effective and credible. We will conclude with a reflection on the H1N1 pandemic, and the historical and biographical ties between emerging governance arrangements and the experts involved in the development of such arrangements

Quantum bits with Josephson junctions

Already in the first edition of this book (Barone and Paterno, "Fundamentals and Physics and Applications of the Josephson Effect", Wiley 1982), a great number of interesting and important applications for Josephson junctions were discussed. In the decades that have passed since then, several new applications have emerged. This chapter treats one such new class of applications: quantum optics and quantum information processing (QIP) based on superconducting circuits with Josephson junctions. In this chapter, we aim to explain the basics of superconducting quantum circuits with Josephson junctions and demonstrate how these systems open up new prospects, both for QIP and for the study of quantum optics and atomic physics.Comment: 30 pages, 10 figures. Book chapter for a new edition of Barone and Paterno's "Fundamentals and Physics and Applications of the Josephson Effect". Final versio

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Funder: CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. iCOGS: the European Community's Seventh Framework Programme under grant agreement No. 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer (CRN-87521), and the Ministry of Economic Development, Innovation and Export Trade (PSR-SIIRI-701), Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Italian Association for Cancer Research (AIRC; grant no.16933) to L. Ottini. Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo. Jacopo Azzollini is supported by funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5x1000’). DEMOKRITOS: European Union (European Social Fund – ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. FPGMX: FISPI05/2275 and Mutua Madrileña Foundation (FMMA). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association “Le cancer du sein, parlons-en!” Award, the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and the French National Institute of Cancer (INCa grants 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015). GEORGETOWN: the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008), the Fisher Center for Hereditary Cancer and Clinical Genomics Research, and Swing Fore the Cure. G-FAST: Bruce Poppe is a senior clinical investigator of FWO. Mattias Van Heetvelde obtained funding from IWT. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HRBCP: Hong Kong Sanatorium and Hospital, Dr Ellen Li Charitable Foundation, The Kerry Group Kuok Foundation, National Institute of Health1R 03CA130065, and North California Cancer Center. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and OTKA K-112228. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563 and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and “5x1000” Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201),and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MODSQUAD: MH CZ - DRO (MMCI, 00209805), MEYS - NPS I - LO1413 to LF and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) to LF, and by Charles University in Prague project UNCE204024 (MZ). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NAROD: 1R01 CA149429-01. NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NICCC: Clalit Health Services in Israel, the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-12007). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SEABASS: Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032, P20CA233307, American Cancer Society (MRSG-13-063-01-TBG, CRP-10-119-01-CCE), Breast Cancer Research Foundation, Susan G. Komen Foundation (SAC110026), and Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance. Mr. Qian was supported by the Alpha Omega Alpha Carolyn L. Cuckein Student Research Fellowship. UCLA: Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Research UK. UPENN: Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124.Abstract: Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. Results: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94–1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85–1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06–1.48) and HR = 1.59 (95% CI: 1.08–2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). Conclusion: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results The ER-negative PRS showed the strongest association with BC risk forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes.Peer reviewe