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This study examines how the mechanisms that entrepreneurs use to successfully mobilize financial resources influence the long-term viability of their ventures. Through an inductive analysis of crowdfunded consumer drone ventures, we empirically illustrate and theoretically conceptualize the link between the claims entrepreneurs use to mobilize resources and the actions entrepreneurs must then take to develop successful ventures. We induct a theoretical framework to suggest that unbounded claims drive up the financial resources that ventures mobilize but reduce the likelihood of their long-term viability because of unmanageable technological complexity and uncontrolled organizational scaling, whereas bounded claims limit the financial resources that ventures mobilize but increase the likelihood of their long-term viability because of manageable technological complexity and controlled organizational scaling. We contribute to the resource mobilization literature by expounding on how the mechanisms that entrepreneurs use to mobilize financial resources are critical for ventures’ long-term viability over and above the amount of resources they mobilize. We contribute to the cultural entrepreneurship literature by linking research on claim making to the actions entrepreneurs must then take to deliver on their claims. Finally, we contribute to the literature on crowdfunding by connecting entrepreneurs’ campaign actions to the postcampaign outcome of on-time and on-scope product delivery.

This article explores the contexts of nonconformism and social purity that underpin Michael Field’s (Katharine Bradley and Edith Cooper) verse drama Brutus Ultor (1886). Based on new archival research, the article explores Bradley’s role in the Ladies National Association for the Repeal of the Contagious Diseases Act and argues that the play is a complex commentary on the social purity movement and, in particular, on W.T. Stead’s campaigning journalism. More broadly, the article argues for the importance of Michael Field’s nonconformist background in the development of their oeuvre.

OBJECTIVE To determine the frequency of germline and somatic pathogenic BRCA1 and BRCA2 variants in patients with high-grade serous ovarian cancer tested by next-generation sequencing (NGS), with the aim of defining the best strategy to be implemented in future routine testing. DESIGN National retrospective audit. SETTING The All Wales Medical Genomics Service (AWMGS). POPULATION Patients with high-grade serous ovarian/fallopian tube/peritoneal cancer referred by oncologists to the AWMGS between February 2015 and February 2021 for germline and/or tumour testing of the BRCA1 and BRCA2 genes by NGS. METHODS Analysis of NGS data from germline and/or tumour testing. MAIN OUTCOME MEASURES Frequency of BRCA1 and BRCA2 pathogenic variants. RESULTS The overall observed germline/somatic pathogenic variant detection rate was 11.6% in the 844 patients included in this study, with a 9.2% (73/791) germline pathogenic variant detection rate. Parallel tumour and germline testing was carried out for 169 patients and the overall pathogenic variant detection rate for this cohort was 14.8%, with 6.5% (11/169) shown to have a somatic pathogenic variant. Two BRCA1 dosage variants were found during germline screens, representing 2.0% (2/98) of patients with a pathogenic variant that would have been missed through tumour testing alone. CONCLUSIONS Parallel germline and tumour BRCA1 and BRCA2 testing maximises the detection of pathogenic variants in patients with high-grade serous ovarian cancer. TWEETABLE ABSTRACT Parallel germline and tumour testing maximises BRCA pathogenic variant detection in ovarian cancer.

This paper explores blockchain technology’s potential to alter contracting both in the market and within organizations. We identify and discuss how blockchain reduces certain types of transaction c...

Organizations are increasingly deploying technologies that have the ability to parse through large amounts of data, acquire skills and knowledge, and operate autonomously. These technologies diverg...

Germline pathogenic variants (GPVs) in the cancer predisposition genes

The preservative effects of low temperature on biological materials have been long recognised, and cryopreservation is now widely used in biomedicine, including in organ transplantation, regenerative medicine and drug discovery. The lack of organs for transplantation constitutes a major medical challenge, stemming largely from the inability to preserve donated organs until a suitable recipient is found. Here, we review the latest cryopreservation methods and applications. We describe the main challenges—scaling up to large volumes and complex tissues, preventing ice formation and mitigating cryoprotectant toxicity—discuss advantages and disadvantages of current methods and outline prospects for the future of the field.

PURPOSE: Stiffness is a sequelae of elbow trauma. Arthrolysis may be considered to increase range of movement (ROM). Little is published on the outcomes/complications of elbow arthrolysis. We present our series of primary open arthrolysis in posttraumatic elbow stiffness. METHODS: A consecutive series of patients that underwent primary open arthrolysis for posttraumatic elbow stiffness in our unit (2011–2018) were analysed. All procedures were performed by an elbow surgeon. Postoperative rehabilitation followed protocol with early motion; continuous passive motion (CPM) was utilised if requested. Data collected included patient demographics, traumatic injury type, arthrolysis technique, preoperative, intraoperative and postoperative elbow ROM, complications and postoperative Oxford Elbow Score (OES). RESULTS: 41 patients were included. 59% were male. Mean age at time of arthrolysis was 43 years (range 12–79 years). Mean duration of follow-up was 53 months (range 8–100 months). Median duration from time of injury to arthrolysis was 11 months (range 2–553 months). Mean preoperative flexion-extension arc (FEA) was 70°, improving to 104° postoperatively (p

The objective of this study was to compare the pick-up rate of pathogenic BRCA variants in those with a high-grade serous ovarian carcinoma (HGSOC) undergoing oncology-led testing with the traditio...

We examine how entrepreneurs acquire financial resources for their early-stage ventures from distributed non-professionals via crowdfunding. Through an inductive analysis of entrepreneurs’ successful and unsuccessful non-equity crowdfunding campaigns, we derive a holistic framework of community-based resource mobilization. Our framework consists of three distinct processes entrepreneurs use to attain financial capital from non-professional resource providers over time: community building to establish psychological bonds with individuals possessing domain-relevant knowledge, community engaging to foster social identification with existing resource providers, and community spanning to leverage proofpoints with intermediaries who can help orchestrate resource mobilization with broader audiences. Entrepreneurs’ enactment and temporal sequencing of these three processes distinguish successful versus unsuccessful resource mobilization efforts in a crowdfunding setting. Community building is used by successful entrepreneurs primarily prior to a campaign’s launch, community engaging is used throughout a campaign, and community spanning is most effectively used after achieving a campaign’s initially-stated funding goal. This study empirically illustrates and theoretically conceptualizes the dynamics of resource mobilization in a crowdfunding setting.

Literature has long highlighted that entrepreneurs benefit from having the right network connections. We observe, however, that although the large and growing literature on entrepreneur network evo...

Breast and prostate cancer risks; Pathogenic variant Riscos de càncer de mama i pròstata; Variants patogèniques Riesgos de cáncer de mama y próstata; Variantes patogénicas Background Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management. The CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A20861 and PPRPGM-Nov20\100002. The research leading to these results has received funding from the Italian Association for Cancer Research (AIRC) under IG 2018 - ID. 21389 and the Italian League for the Fight Against Cancer (LILT) under IG 2019 projects, P.I. Ottini Laura and Italian Ministry of Education, Universities and Research-Dipartimenti di Eccellenza-L. 232/2016. CIMBA: GCT is a National Health and Medical Research Council (NHMRC) Research Fellow. iCOGS and OncoArray data: 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 (NIH) (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 Personalized Risk Stratification for Prevention and Early Detection of Breast Cancer (PERSPECTIVE) and PERSPECTIVE I&I projects were supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation and the Ontario Research Fund. Breast Cancer Family Registry (BCFR): UM1 CA164920 from the National Cancer Institute (NCI). Baltic Familial Breast Ovarian Cancer Consortium (BFBOCC): Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015. Beth Israel Deaconess Medical Center (BIDMC): Breast Cancer Research Foundation. BRCA-gene mutations and breast cancer in South African women (BMBSA): Cancer Association of South Africa (PI Elizabeth J. van Rensburg). Spanish National Cancer Centre (CNIO): Spanish Ministry of Health PI16/00440 supported by Fondo Europeo de Desarrollo Regional (FEDER) funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). City of Hope - Clinical Cancer Genomics Community Research Network (COH-CCGCRN): Research reported in this publication was supported by the NCI of the NIH under grant No. R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the NCI and the Office of the Director, NIH. CONsorzio Studi ITaliani sui Tumori Ereditari Alla Mammella (CONSIT TEAM): Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 No.15547) to P. Radice. 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’) to S. Manoukian. Associazione CAOS Varese to M.G. Tibiletti. AIRC (IG2015 No.16732) to P. Peterlongo. National Centre for Scientific Research Demokritos (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. German Cancer Research Center (DFKZ): German Cancer Research Center. Epidemiological Study of Familial Breast Cancer (EMBRACE): Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an National Institute for Health Research (NIHR) grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden National Health Service (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. Fox Chase Cancer Center (FCCC): The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. AKG was in part funded by the NCI (R01 CA214545 and R01 CA140323), The Kansas Institute for Precision Medicine (P20 GM130423), and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. is the Chancellors Distinguished Chair in Biomedical Sciences Professor. Fundación Pública Galega de Medicina Xenómica (FPGMX): FISPI05/2275 and Mutua Madrileña Foundation (FMMA). German Familial Breast Group (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 No. 713-241202, No. 713-241202, No. 14505/2470, and No. 14575/2470). Genetic Modifiers of cancer risk in BRCA1/2 mutation carriers (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 University (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. Ghent University Hospital (G-FAST): Bruce Poppe is a senior clinical investigator of FWO. Mattias Van Heetvelde obtained funding from IWT. Hospital Clinico San Carlos (HCSC): Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. Helsinki Breast Cancer Study (HEBCS): Helsinki University Hospital Research Fund, the Finnish Cancer Society and the Sigrid Juselius Foundation. Hereditary Breast and Ovarian cancer study the Netherlands (HEBON): the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HEBON thanks the registration teams of Dutch Cancer Registry (IKNL; S. Siesling, J. Verloop) and the Dutch Pathology database (PALGA; L. Overbeek) for part of the data collection. Study of Genetic Mutations in Breast and Ovarian Cancer patients in Hong Kong and Asia (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. Molecular Genetic Studies of Breast- and Ovarian Cancer in Hungary (HUNBOCS): Hungarian Research Grants KTIA-OTKA CK-80745 and NKFI_OTKA K-112228. Institut Català d’Oncologia (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 “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). International Hereditary Cancer Centre (IHCC): PBZ_KBN_122/P05/2004. Iceland Landspitali – University Hospital (ILUH): Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INterdisciplinary HEalth Research Internal Team BReast CAncer susceptibility (INHERIT): Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program—grant No. CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade—grant No. PSR-SIIRI-701. Istituto Oncologico Veneto (IOVHBOCS): Ministero della Salute and “5x1000” Istituto Oncologico Veneto grant. Portuguese Oncology Institute-Porto Breast Cancer Study (IPOBCS): Liga Portuguesa Contra o Cancro. Kathleen Cuningham Consortium for Research into Familial Breast Cancer (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. Korean Hereditary Breast Cancer Study (KOHBRA): the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 1020350; 1420190). Mayo Clinic (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 University (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). Modifier Study of Quantitative Effects on Disease (MODSQUAD): MH CZ—DRO (MMCI, 00209805), MEYS—NPS I—LO1413 to LF, and by Charles University in Prague project UNCE204024 (MZ). Memorial Sloane Kettering Cancer Center (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). Women’s College Research Institute Hereditary Breast and Ovarian Cancer Study (NAROD): 1R01 CA149429-01. National Cancer Institute (NCI): the Intramural Research Program of the US NCI, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. National Israeli Cancer Control Center (NICCC): Clalit Health Services in Israel, the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. N.N. Petrov Institute of Oncology (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. The Ohio State University Comprehensive Cancer Center (OSUCCG): Ohio State University Comprehensive Cancer Center. Università di Pisa (PBCS): AIRC [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. South East Asian Breast Cancer Association Study (SEABASS): Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. Sheba Medical Centre (SMC): the Israeli Cancer Association. Swedish Breast Cancer Study (SWE-BRCA): the Swedish Cancer Society. University of Chicago (UCHICAGO): NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women’s Cancer Research Alliance and the Breast Cancer research Foundation. OIO is an American Cancer Society (ACS) Clinical Research Professor. University of California Los Angeles (UCLA): Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. University of California San Francisco (UCSF): UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UK Familial Ovarian Cancer Registry (UKFOCR): Cancer Research UK. University of Pennsylvania (UPENN): NIH (R01-CA102776 and R01-CA083855); Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. Cancer Family Registry University of Pittsburg (UPITT/MWH): Hackers for Hope Pittsburgh. Victorian Familial Cancer Trials Group (VFCTG): Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. Women’s Cancer Program at Cedars-Sinai Medical Center (WCP): Dr Karlan is funded by the ACS Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. TN-D is a recipient of a Career Development Fellow from the National Breast Cancer Foundation (Australia, ECF-17-001).

At the core of literary decadence is a conflicted relationship with modernity. For some decadent writers, the onset of rapid social and technological change could usher in possibilities for living and loving in hitherto unimagined ways, yet for others of a more conservative hue, modernization was to be rejected, tradition embraced. This essay argues that experience can be used as a framework for articulating these very different forms of decadence. The essay begins with an exploration of aesthetic modernity as an attempt to articulate the shock of the new, whereby the experience (present) or sensation becomes the ground for the erosion of collective tradition (experience past). Decadent and aestheticist writers such as Walter Pater, Arthur Symons, and Oscar Wilde embraced these new experiences, rejecting the “fruits of experience” as a ground for knowledge. In contradistinction to this valorization of sensation, I examine the “conservative” decadent aesthetic of Lionel Johnson and Michael Field. These writers’ embrace of nostalgia and jingoistic nationalism, I argue, demands we expand our current critical frameworks to more fully encompass the politics of decadence.Edith Cooper (1862–1913), the younger half of the aunt and niece who published as Michael Field, wrote in Works and Days on New Year's Eve, 1893: “I do not yet realise where modernity is taking me.”Footnote1 Among decadent writers, she was far from alone in expressing anxiety at the dramatic social and technological flux of the fin de siècle. Along with her aunt, Katharine Bradley (1846–1914), she would use a wide range of literary forms to capture, but also to critique, the experience of modernity. Yet there was little consistency either to that experience or to the literary forms that decadent writers deployed to capture it. Defining the nature of that experience and how decadent literature might respond to it is the task of this essay. Our understanding of decadence has largely glossed over the ways in which it emerges out of the “destruction of experience” that, for Giorgio Agamben, is the constituent feature of modernity. Decadent writers, I argue, responded in two very different ways (often simultaneously): either by reveling in the immediacy of sensation or by valorizing the transmission of knowledge from the past. Of these two, the former has dominated our understanding of decadence, but the latter is just as significant. This latter strain, which I will articulate as a conservative one, will be my primary focus here as I offer two examples of writers whose work emphasized the power of tradition for confronting the experience of modernity: Lionel Johnson and Michael Field.

From trauma wards to chemotherapy, red blood cells are essential in modern medicine. Current methods to bank red blood cells typically use glycerol (40 wt %) as a cryoprotective agent. Although highly effective, the deglycerolization process, post-thaw, is time-consuming and results in some loss of red blood cells during the washing procedures. Here, we demonstrate that a polyampholyte, a macromolecular cryoprotectant, synergistically enhances ovine red blood cell cryopreservation in a mixed cryoprotectant system. Screening of DMSO and trehalose mixtures identified optimized conditions, where cytotoxicity was minimized but cryoprotective benefit maximized. Supplementation with polyampholyte allowed 97% post-thaw recovery (3% hemolysis), even under extremely challenging slow-freezing and -thawing conditions. Post-thaw washing of the cryoprotectants was tolerated by the cells, which is crucial for any application, and the optimized mixture could be applied directly to cells, causing no hemolysis after 1 h of exposure. The procedure was also scaled to use blood bags, showing utility on a scale relevant for application. Flow cytometry and adenosine triphosphate assays confirmed the integrity of the blood cells post-thaw. Microscopy confirmed intact red blood cells were recovered but with some shrinkage, suggesting that optimization of post-thaw washing could further improve this method. These results show that macromolecular cryoprotectants can provide synergistic benefit, alongside small molecule cryoprotectants, for the storage of essential cell types, as well as potential practical benefits in terms of processing/handling.\ud \ud

Vernon Lee is regularly upheld as a model of late-Victorian cosmopolitanism, with her travel writing, in particular that dealing with Italy, displaying an openness to other places and cultures. Yet, as this essay argues, there is in Lee’s model of topographical writing a neglect of the people who live and dwell within landscapes. Examining in detail her critically neglected travel writing of the British Isles, published between 1899 and 1916, the essay surveys her hostility towards English landscapes and towards the forces of industrial modernity that shape them. From her antipathy to London to her celebration of the empty landscapes of Northern England, Lee’s travel writing suggests her cosmopolitanism raises ethical questions about her relationship to those people and places that do not accord with her aesthetic taste.

The presence of civilian witnesses and victims in court is central to the effective operation of the criminal justice system. However, there is evidence of significant non-attendance which can result in ineffective and cracked trials. To address this, West Midlands Police Witness Care Unit and the Behavioural Insights Team designed an intervention using behavioural insight principles consisting of (1) a new conversation guide for Witness Care Officers (WCOs); (2) a redesigned ‘Warning Letter’ confirming details of the proceedings; and (3) a new reminder call and SMS. The impact of the new approach was evaluated through a randomised controlled trial in which 36 WCOs were randomly assigned to either “business as usual” (control) or treatment. The evaluation used an intention-to-treat design with implementation guided and encouraged at several points. Subgroup analysis was undertaken to explore whether differential effects were seen for domestic violence cases or between those that were victims and witnesses. Results indicated that the treatment approach was directionally positive in all cases, but that the increase in attendance was not statistically significant. This is in line with findings of other similar research in this area.

British decadence has long been identified with London, the home of theaters and publishing houses. Most decadent writers lived and worked in the city, setting many of the great works of British decadence in its streets and squares. Yet decadence, as a literary style and a cultural concept, reached all parts of the United Kingdom, and in the process changed the nature of this literary tradition. Moving from Cornwall and Wales to the north of Ireland and Scotland, this essay charts a British decadence with close ties to the Celtic Revival, one that embraces nature and that looks to a future beyond the autumn of decline. From writers vacationing in the west of Britain, to the Ulster literary revival, to the embrace of natural cycles as an antidote to metropolitan ennui in Scotland, the writing examined here demonstrates the variety of forms that British decadence could take.

Sylvia Townsend Warner's work is richly allusive, yet the precise purpose of her myriad references to, and echoes of, earlier works of literature often remains opaque. This essay explores one particular intertext in her work from the 1920s: the poetry of William Blake. In her essays, poetry, and in particular Lolly Willowes (1926), Warner, I argue, attempts to liberate Blake from both jingoistic nationalism and from progressive improvement. It is in particular in the intertextual dialogue she opens up with rural preservationist J. W. Robertson Scott that we can see how Warner seeks to free Blake from those who believed that Jerusalem could be literally built, rather than it being the preserve of an unfettered imagination. As I demonstrate, Laura Willowes has a series of Blakean epiphanies that allow her to become a critic of the materialism of modernity.

The larvae of Drosophila melanogaster is a model organism widely used to study the muscular and nervous systems. Drosophila larvae are surrounded by a waxy cuticle that prevents permeation by most substances. Here we develop a method to remove this layer, rendering the larvae permeable to small molecules without causing death, allowing the larvae to develop to adulthood and reproduce. Permeability was assessed using fluorescein diacetate dye uptake, and mortality upon exposure to toxic levels of ethylene glycol (EG) and Dimethyl sulfoxide (DMSO). Potential uses for this method include drug delivery, toxicity assays, cryopreservation, staining, and fixation.

A BRCA2 prostate cancer cluster region (PCCR) was recently proposed (c.7914 to 3′) wherein pathogenic variants (PVs) are associated with higher prostate cancer (PCa) risk than PVs elsewhere in the BRCA2 gene. Using a prospective cohort study of 447 male BRCA2 PV carriers recruited in the UK and Ireland from 1998 to 2016, we estimated standardised incidence ratios (SIRs) compared with population incidences and assessed variation in risk by PV location. Carriers of PVs in the PCCR had a PCa SIR of 8.33 (95% confidence interval [CI] 4.46–15.6) and were at a higher risk of PCa than carriers of other BRCA2 PVs (SIR = 3.31, 95% CI 1.97–5.57; hazard ratio = 2.34, 95% CI 1.09–5.03). PCCR PV carriers had an estimated cumulative PCa risk of 44% (95% CI 23–72%) by the age of 75 yr and 78% (95% CI 54–94%) by the age of 85 yr. Our results corroborate the existence of a PCCR in BRCA2 in a prospective cohort. Patient summary In this report, we investigated whether the risk of prostate cancer for men with a harmful mutation in the BRCA2 gene differs based on where in the gene the mutation is located. We found that men with mutations in one region of BRCA2 had a higher risk of prostate cancer than men with mutations elsewhere in the gene., Take Home Message BRCA2 pathogenic variants located in a recently proposed prostate cancer cluster region confers higher risks of prostate cancer than other BRCA2 variants. This report corroborates the existence of this prostate cancer cluster region in a large prospective cohort study.

The work of John Dos Passos has been recognised for its acute visual qualities, and for the revolutionary use of the Camera Eye sections of his U.S.A. trilogy to capture subjective seeing. Most scholarship emphasises the role that cinema and modernist art played in the develop of Dos Passos's unique approach to vision, yet this essay argues there is a more fundamental source for vision in his novels: the author's treatment for visual impairment. The essay traces the influence that W. H. Bates's method for correcting visual impairment had on Dos Passos's novelistic craft, drawing on hitherto unexamined notes of the novelist on visual training.

Background Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. Results We develop CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes (C9orf40, CDC25A, CDCA4, CKAP2, GTF3C4, HAUS4, IMMT, MCM7, MTHFD2, MYBL2, NEK2, NIPA2, and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. Conclusions Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence.