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Funding Information: Catalina M. Valencia reports no conflicts of interest. Ben W. Mol reports an investigator grant from NHMRC; consultancy for ObsEva; and research funding from Guerbet, Ferring, and Merck KGaA. Bo Jacobbson reports research grants from Swedish Research Council, Norwegian Research Council, March of Dimes, Burroughs Wellcome Fund and the US National Institute of Health; clinical diagnostic trials on NIPT with Ariosa (completed), Natera (ongoing), Vanadis (completed) and Hologic (ongoing) with expendidures reimbused per patient; clinical probiotic studies with product provided by FukoPharma (ongoing, no funding) and BioGaia (ongoing; also provided a research grant for the specific study); collaboration in IMPACT study where Roche, Perkin Elmer and Thermo Fisher provided reagents to PLGF analyses; coordination of scientific conferences and meetings with commercial partners as such as NNFM 2015, ESPBC 2016 and a Nordic educational meeting about NIPT and preeclampsia screening. Bo Jacobbson is also Chair of the FIGO Working Group for Preterm Birth and the European Association of Perinatal Medicine's special interest group of preterm delivery; steering group member of Genomic Medicine Sweden; chairs the Genomic Medicine Sweden complex diseases group; and is Swedish representative in the Nordic Society of Precision Medicine.

In 1971, the British pharmaceuticals corporation Burroughs Wellcome held an elaborate celebration on both sides of the Atlantic to mark the upcoming opening of its new headquarters in Research Triangle Park near Durham,North Carolina (the building opened officially in April 1972).Designed by architect Paul Rudolph, the new headquarters aimed to invoke southern cultural and architectural traditions while also conveying the energy and excitement ofmodern science. As Vyta Pivo demonstrates in “PhDs Among the Possums”: Paul Rudolph’s Burroughs Wellcome Headquarters and the Transformation of Laboratory Architecture, while Rudolph’s use of the structural A-frame as an organizing matrix created spaces that inspired awe and mystery, his design also generated practical challenges in terms of both use and maintenance. Although Rudolph’s adoption of industrial construction techniques and unproven experimental materials was intended to expedite the building process and lower costs, it nearly jeopardized the entire project. By reconstructing the historical context of the BurroughsWellcome Headquarters, Pivo advances our understanding of the fundamental goals and challenges involved in the development of new suburban corporate headquarters and laboratory building typologies.

The cervix acts as a dynamic barrier between the uterus and vagina, retaining the fetus during pregnancy and allowing birth at term. Critical to this function, the physical properties of the cervix change, or remodel, but dysfunctional remodeling can lead to preterm birth (PTB). Although cervical remodeling has been studied, the complex 3D cervical microstructure has not been well-characterized. In this complex, dynamic, and heterogeneous tissue microenvironment, the microstructural changes are likely also heterogeneous. Using quantitative, 3D, second-harmonic generation microscopy, we demonstrate that cervical remodeling is not uniform across the cervix; during pregnancy, the collagen fibers orient progressively more perpendicular to the cervical canals in the inner cervical zone, but do not reorient in other regions. Furthermore, regions that are microstructurally distinct early in pregnancy become more similar as pregnancy progresses. We use a finite element simulation to show that heterogeneous regional changes influence cervical funneling, an important marker of increased risk for PTB; the proximal portion of the cervix shows ~6.5x larger radial displacement when fibers in the inner cervical zone are parallel to the cervical canals compared to when fibers are perpendicular to the canals. Our results provide new insights into the microstructural and tissue-level cervical changes that have been correlated with PTB and provide a new explanation for a possible origin of cervical funneling. Funding Information: Kimani C. Toussaint, Ph.D., holds a 2017 Preterm Birth Research Grant from the Burroughs Wellcome Fund (#1017300). Research reported in this publication was partly supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number T32EB019944. Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics Approval Statement: All procedures were approved by the Institutional Animal Care and Use Committee at the University of Illinois at Urbana-Champaign.

Physicians engaged in biomedical research are well positioned to directly focus the discovery process on human biology. However, the relative proportion of investigators engaged in both caring for patients and conducting research is decreasing. To address the dwindling numbers of physician-scientists nationally, the Burroughs Wellcome Fund created the Physician-Scientist Institutional Awards Program by dedicating 25 million dollars to new initiatives at 10 degree granting, accredited medical schools in North America, awarded on the basis of institutions' proposals. The perceived barriers to physician-scientist training, program initiatives, and commitment to training a diverse group of future researchers were articulated in each application. In all, the Burroughs Wellcome Fund review committee considered 136 distinct proposals from 83 medical schools, representing 54% of all accredited medical schools in North America. Barriers identified by more than one-third of the applicant institutions included the absence of both mentors and role models, student indebtedness, institutional cultures that valued clinical care delivery above the discovery process, limited prior relevant research experience, and structural barriers that limited scheduling flexibility during training. Awards were granted to institutions with programs designed to be sustainable and overcome critical, prospectively identified barriers to training and retention of physician-scientists. Potential solutions from the 10 funded programs were focused on different stages of the training experience. Though a determination about the relative success of each of the initiatives will take many years, careful consideration of the barriers identified and more general application of specific program component may be beneficial in increasing the numbers of physicians actively involved in biomedical research.

Background: Disease progression (PD) after frontline IC therapy for DLBCL is a clinically significant event and only 20-40% of patients achieve durable remissions with salvage chemotherapy. Patients who experience early PD or have disease refractory to IC have especially poor outcomes. Chimeric antigen receptor T-cell therapy has emerged as a novel effective therapy for selected cases of relapsed or refractory (r/r) DLBCL, although its availability is limited by cost and logistic challenges. Simple, clinically applicable prognostic tools would be useful for selecting patients for consideration for novel therapies vs those who are more likely to be successfully managed by conventional therapies, but few have been developed for r/r DLBCL. Methods: Model building was performed in patients with PD after IC from 13 frontline, multicenter, randomized DLBCL clinical trials from the SEAL Consortium. All patients received rituximab and an anthracycline-based combination IC and were followed systematically; however therapy received, clinical, and laboratory data at progression were not available. OS was defined as time from first progression until death from any cause. Associations between variables and OS were evaluated using Cox models; splines were used to model functional forms. Validation was performed in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) and Danish LYFO cohorts. Model performance was assessed using time-dependent concordance indices (c-stat), Brier scores, and calibration with metrics evaluated at two years from progression. Results: Model Development (SEAL): 1125 of 5112 patients had PD after IC. Median time to PD (TTP) was 11.8 months (IQR 6.6-23.5); median age at PD was 68 years (IQR 60-73). At a median follow-up of 21 months from PD (IQR 7-43), 732 patients (65%) had died and 24 month overall survival after PD (OS24) was 35% (95% CI: 32-38). TTP was strongly associated with post PD OS (spline p-value 36 months (Figure A). Additionally, age at PD (spline p-value External Validation (MER): The model was validated in 290 patients with DLBCL who initiated 2nd line therapy after PD to IC. Median age at PD was younger than the SEAL cohort at 62 years (IQR 57-70). Patients with biopsy proven indolent histology at relapse were excluded. Median TTP was 8.2 months (IQR 5.1-17.0). At a median follow-up of 87 months from PD, 201 patients (69%) had died. OS24 was 47% (95% CI: 41-53). The model showed similar concordance (c-stat=0.65), but underestimated OS24 (predicted =33% vs. 47% actual, Figure C). External Validation (LYFO): The model was validated in 599 patients with DLBCL and PD after frontline IC. Median age at PD was 67 years (IQR 60-73). Median TTP was 10.1 months (IQR 6.0-19.4). At a median follow-up of 82 months from PD, 435 patients (73%) had died. OS24 was 38% (95% CI: 34-42). The model showed similar concordance (c-stat=0.67) when applied to the LYFO cohort, but again underestimated OS24 (predicted =32% vs. 38% actual, Figure D). Case vignettes: A 74 year old patient who progressed 9 months after diagnosis would have a predicted OS24 of 20%. A 58 year old patient who progressed 32 months after diagnosis would have a predicted OS24 of 65% Conclusions: TTP to following IC is strongly associated with post-progression survival in DLBCL. We developed a model from the largest frontline clinical trial dataset in DLBCL and validated a simple to apply clinical prognostic tool in the r/r setting. The model allows better understanding of expected outcomes in r/r DLBCL and can aid design and interpretation of trial results in this setting. The model underestimated the actual survival probability when applied to non-trial validation cohorts. Recalibration of the model for transplant eligible patients and development of smartphone based point-of-care application of the model is ongoing. Figure Disclosures Maurer: Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees. Schmitz:Riemser: Consultancy, Honoraria; Celgene: Equity Ownership; Gilead: Honoraria; Novartis: Honoraria. Farooq:Kite Pharma: Research Funding; Celgene: Honoraria. Flowers:Optimum Rx: Consultancy; Burroughs Wellcome Fund: Research Funding; BeiGene: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Bayer: Consultancy; TG Therapeutics: Research Funding; Acerta: Research Funding; Celgene: Consultancy, Research Funding; National Cancer Institute: Research Funding; Denovo Biopharma: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy; Millenium/Takeda: Research Funding; AbbVie: Consultancy, Research Funding; V Foundation: Research Funding. Frederiksen:Alexion: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding; Novartis: Research Funding. Cunningham:Eli Lilly: Research Funding; 4SC: Research Funding; Bayer: Research Funding; MedImmune: Research Funding; Celgene: Research Funding; AstraZeneca: Research Funding; Merrimack: Research Funding; Sanofi: Research Funding; Amgen: Research Funding; Janssen: Research Funding; Merck: Research Funding; Clovis: Research Funding. Jørgensen:Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Poeschel:Amgen: Other: Travel, accommodations, expenses; Abbvie: Other: Travel, accomodations, expenses; Hexal: Speakers Bureau; Roche: Other: Travel, accomodations, expenses. Nowakowski:F. Hoffmann-La Roche Ltd: Research Funding; Curis: Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees; NanoString: Research Funding; MorphoSys: Consultancy, Research Funding; Genentech, Inc.: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Seymour:Takeda: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Acerta: Consultancy; Janssen: Consultancy, Research Funding; Roche: Consultancy, Research Funding, Speakers Bureau. Merli:Takeda: Honoraria, Other: Travel Expenses; Gilead: Honoraria; Mundipharma: Honoraria; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses; Janssen: Honoraria. Haioun:novartis: Honoraria; celgene: Honoraria; roche: Consultancy; celgene: Consultancy; gilead: Consultancy; takeda: Consultancy; janssen cilag: Consultancy; amgen: Honoraria; servier: Honoraria. Tilly:roche: Membership on an entity's Board of Directors or advisory committees; servier: Honoraria; merck: Honoraria; Gilead: Honoraria; Janssen: Honoraria; BMS: Honoraria; Karyopharm: Consultancy; Astra-Zeneca: Consultancy; Celgene: Consultancy, Research Funding; Roche: Consultancy. Salles:Amgen: Honoraria, Other: Educational events; BMS: Honoraria; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Epizyme: Consultancy, Honoraria; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events. El-Galaly:Roche: Employment, Other: Travel support; Takeda: Other: Travel support.

Recent revolutionary advances at the intersection of medicine, omics, data sciences, computing, epidemiology, and related technologies inspire us to ponder their impact on health. Their potential impact is particularly germane to the biology of pregnancy and perinatal medicine, where limited improvement in health outcomes for women and children has remained a global challenge. We assembled a group of experts to establish a Pregnancy Think Tank to discuss a broad spectrum of major gestational disorders and adverse pregnancy outcomes that affect maternal-infant lifelong health and should serve as targets for leveraging the many recent advances. This report reflects avenues for future effects that hold great potential in 3 major areas: developmental genomics, including the application of methodologies designed to bridge genotypes, physiology, and diseases, addressing vexing questions in early human development; gestational physiology, from immune tolerance to growth and the timing of parturition; and personalized and population medicine, focusing on amalgamating health record data and deep phenotypes to create broad knowledge that can be integrated into healthcare systems and drive discovery to address pregnancy-related disease and promote general health. We propose a series of questions reflecting development, systems biology, diseases, clinical approaches and tools, and population health, and a call for scientific action. Clearly, transdisciplinary science must advance and accelerate to address adverse pregnancy outcomes. Disciplines not traditionally involved in the reproductive sciences, such as computer science, engineering, mathematics, and pharmacology, should be engaged at the study design phase to optimize the information gathered and to identify and further evaluate potentially actionable therapeutic targets. Information sources should include noninvasive personalized sensors and monitors, alongside instructive "liquid biopsies" for noninvasive pregnancy assessment. Future research should also address the diversity of human cohorts in terms of geography, racial and ethnic distributions, and social and health disparities. Modern technologies, for both data-gathering and data-analyzing, make this possible at a scale that was previously unachievable. Finally, the psychosocial and economic environment in which pregnancy takes place must be considered to promote the health and wellness of communities worldwide.

We show that SARS-CoV-2 spike protein interacts with cell surface heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain. Docking studies suggest a putative heparin/heparan sulfate-binding site adjacent to the domain that binds to ACE2. In vitro, binding of ACE2 and heparin to spike protein ectodomains occurs independently and a ternary complex can be generated using heparin as a template. Contrary to studies with purified components, spike protein binding to heparan sulfate and ACE2 on cells occurs codependently. Unfractionated heparin, non-anticoagulant heparin, treatment with heparin lyases, and purified lung heparan sulfate potently block spike protein binding and infection by spike protein-pseudotyped virus and SARS-CoV-2 virus. These findings support a model for SARS-CoV-2 infection in which viral attachment and infection involves formation of a complex between heparan sulfate and ACE2. Manipulation of heparan sulfate or inhibition of viral adhesion by exogenous heparin may represent new therapeutic opportunities. Funding: This work was supported by RAPID grant 2031989 from the National Science Foundation and Project 3 of NIH P01 HL131474 to J.D.E.; The Alfred Benzon Foundation to T.M.C; NIH R01 AI146779 and a Massachusetts Consortium on Pathogenesis Readiness MassCPR grant to A.G.S.; DOD grant W81XWH-20-1-0270 and Fluomics/NOSI U19 AI135972 to S.K.C; a Career Award for Medical Scientists from the Burroughs Wellcome Fund to A.F.C.; Bill and Melinda Gates Foundation grant OPP1170236 to A.B.W.; COVID19 seed funding from the Huck Institutes of the Life Sciences and Penn State start-up funds to J.J.; and T32 training grants GM007753 for B.M.H. and T.C and AI007245 for J.F.; J.P. received funding from the Innovation Fund Denmark and VAR2 Pharmaceuticals. Conflict of Interest: J.D.E. is a co-founder of TEGA Therapeutics. J.D.E. and The Regents of the University of California have licensed a University invention to and have an equity interest in TEGA Therapeutics. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. C.A.G and B.E.T are employees of TEGA Therapeutics. Ethical Approval: The collection of human tissue in this study abided by the Helsinki Principles. This work included postmortem human tissue, collected at the University Hospital, at the University of Copenhagen in Denmark. The patient provided informed consent for the tissue to be used for research purposes. All samples were completely deidentified before transfer to the researchers and this did not need specific IRB approval.

This essay examines early twentieth-century international disputes over alleged Chinese copying of the trademarks and brand recipes of Burroughs Wellcome and Company’s Hazeline Snow vanishi...

Chapter four suggests that although the practical application of anti-diphtheria immunization in Cork achieved good results, its success was qualified somewhat by the limitations of Burroughs Wellcome’s anti-diphtheria serum TAM. To reduce the occurrence of post-treatment diphtheria cases – occurrences which undermined public confidence in active immunization – field epidemiologist Jack Saunders introduced an experimental ‘one-shot’ Burroughs Wellcome anti-diphtheria antigen in Cork. This chapter explores the development of Burroughs Wellcome’s Alum-Toxoid anti-diphtheria antigen and the relationships that developed between the British pharmaceutical company and Irish medical officers: the former eager to field trial experimental anti-diphtheria serums unrestrained by restrictive British legislation and the latter eager to embrace any solution, however radical, to leverage a modicum of control over diphtheria and its often-fatal consequences, even if this meant side-lining the rights of vulnerable children residing in state-run institutions.

PURPOSE Documenting the career characteristics of a highly selective group of researchers provides some insight into how a successful career begins. This knowledge is of value to early-career faculty and those who evaluate them, as well as trainees who aspire to the professoriate and those who educate them. METHOD In 2010, the authors extracted information by hand from the curricula vitae of 196 basic scientists who have been supported by the Burroughs Wellcome Fund's early faculty career development programs from 1982 to 2010. Data were collected on awardees' education, awards and honors, funding, promotion, publication, service, and training activities. The end point for data was December 2010. Analyses quantified participants' time to terminal degree, faculty appointment, and first R01; determined their publication productivity; and calculated their rates of training graduate students and postdoctoral fellows. RESULTS This group moved into jobs and gained first R01s faster than average. Surprisingly, those who train the most students and fellows do not publish the most. Women and men trained different numbers of undergraduates, PhDs, and postdocs. Women awardees had fewer publications on average than men. CONCLUSIONS Researchers who are highly competitive at the early faculty career stage have generally been both timely in their arrival at important benchmarks and productive in terms of their scientific output. Newly trained researchers and the people and institutions that train them share responsibility for attaining expeditious progress, developing a substantial track record, and staking out fertile intellectual ground from which to grow an independent faculty career.

This article examines the overlooked synergy between American economic expansion and British imperialism in the late nineteenth century. The established scholarship on American empire in this period focuses on the domestic origins of US expansion into the markets of the Western Hemisphere. This article contends, however, that informal American expansion was shaped by external collaborations with the British World. Between 1865 and 1914, an American "colony" of expatriate businessmen emerged in London that is central to this study. The American "colony" integrated itself within the social and economic networks upon which British imperialism depended and mediated new inter-imperial collaborations. Migrants, knowledge, and investment flowed through these intersections, shaping the geography of American expansion around the global footprint of the British World. A snapshot of the pharmaceutical firm Burroughs Wellcome and Co. spotlights these processes, highlighting the mutual imbrications of the British and American empires and the inter-imperial reciprocities sustaining late-nineteenth century globalisation. © Edinburgh University Press.

This paper examines the narrative of British history and culture on display at the Wellcome Historical Medical Museum in London from 1913-1932. The Museum was founded by Henry Wellcome (1853-1936), an American pharmaceuticals magnate and naturalized British citizen. This paper focuses on the British scientific relics and healing amulets displayed at the Museum. By way of comparison, it explores the vision of British Empire that was portrayed in the advertising literature produced by Wellcome's firm, Burroughs Wellcome and Company. It also investigates Wellcome's relationship with the British folklorist, Edward Lovett (1852-1933). My collection of curiosities, Indian [Native American] relics etc. tally admirably with the house, and so everybody seems rather fascinated with the effect, and in fact I rather like it myself. Some call it ‘Aesthetic’, some say ‘Heathenish’, some ‘Bohemian’, ‘Ideal’, ‘Artistic’, etc. … All in it is very cheerful … [Wellcome's] gray eyes glow under his bush...

Introduction: Umbralisib (UMB) is a next generation, once daily, PI3Kδ/CK1ε inhibitor, active in patients with relapsed or refractory (rel/ref) hematologic malignancies that, in long-term follow-up, has demonstrated a uniquely differentiated safety profile from prior PI3Kδ inhibitors (Davids, 2018). Ublituximab (UTX) is a novel glycoengineered mAb targeting a unique epitope on the CD20 antigen. Bendamustine (Benda) is an active chemotherapy agent in pts with lymphoma. The combination of UMB + UTX (U2) is tolerable and active in patients with rel/ref hematologic malignancies and registration directed trials for patients with CLL & NHL are ongoing. This Phase 1 trial evaluates the safety and efficacy of U2 + Benda in patients with advanced diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Methods: Eligible patients had rel/ref DLBCL or FL with an ECOG PS ≤ 2 w/o limit to number of prior therapies. ANC of ≥ 750 and Platelets ≥ 50,000 were required; no growth factor support was permitted in Cycle 1 (cohort escalation group only). Patients refractory to prior PI3Kδ, Benda, or anti-CD20's were eligible. UTX was dosed on Days 1, 8, 15 of Cycle 1, Day 1 of Cycle 2-6, followed by Cycle 9 & 12. UMB was started at 800 mg QD with a -1 dose reduction cohort at 600 mg if not tolerated in ≥ 2/6 patients. Benda was dosed at 90 mg/m2 on Days 1 & 2 of Cycles 1-6 only. Primary endpoints included safety and efficacy (Cheson 2007). Results: Thirty-nine patients were evaluable for safety: 26 DLBCL and 13 FL. Med age 67 yo (range 31-81); 23 M/16 F; median prior treatment regimens = 2 (range 1-6); 22 pts (56%) were refractory to prior treatment and 6 patients had progressed post-transplant; ECOG PS 0/1/2 (12/25/2). Initially 2/4 patients at 800 mg UMB experienced AE's in Cycle 1 that led to treatment interruption (rash, neutropenia) thus the 600 mg dose of TGR-1202 was explored. No additional Cycle 1 treatment delays were reported at the 600 mg dose level, which was later expanded and the 800 mg UMB dose was evaluated with the use of growth factor support in cycle 1 permitted. The most common AE's regardless of causality included diarrhea (54%; G3/4 15%), nausea (49%; G3/4 5%), vomiting (38%; G3/4 0%), neutropenia (33%; G3/4 33%) and pyrexia (31%; G3/4 0%). Thirty-eight patients (25 DLBCL/13 FL) were evaluable for efficacy (1 DLBCL patient came off study for G4 neutropenia prior to first assessment). ORR in the respective groups is shown in Table 1. The median time to response was 8 weeks. The median DOR was 9.6 months (95% CI: 2.5-NR) for patients with DLBCL, and was not reached (95% CI: 8.0-NR) for patients with FL, at a median duration of follow-up for responders of 11.5 months (range 2.9 - 30+ mos). Conclusions: The combination of U2 + bendamustine has exhibited manageable toxicity with significant activity in advanced DLBCL and FL patients, including an encouraging CR rate in advanced patients. Based upon the early activity of the triplet, a registration directed study is underway for patients with rel/ref DLBCL (UNITY-NHL). Disclosures Lunning: Gilead: Consultancy; Astra-Zeneca: Consultancy; Genentech: Consultancy; Spectrum: Consultancy; TG Therapeutics: Consultancy; Bayer: Consultancy; Celgene: Consultancy; AbbVie: Consultancy; Genzyme: Consultancy; Kite: Consultancy; Juno: Consultancy; Genentech: Consultancy; Portola: Consultancy; Janssen: Consultancy; Seattle Genetics: Consultancy; Verastem: Consultancy. Siddiqi:Juno Therapeutics: Other: Steering committee. Flowers:Abbvie: Research Funding; TG Therapeutics: Research Funding; Gilead: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; Genentech/Roche: Research Funding; Genentech/Roche: Consultancy; Pharmacyclics: Research Funding; V Foundation: Research Funding; Abbvie: Consultancy, Research Funding; Bayer: Consultancy; Karyopharm: Consultancy; Burroughs Wellcome Fund: Research Funding; Celgene: Research Funding; BeiGene: Research Funding; Gilead: Consultancy; Millennium/Takeda: Research Funding; OptumRx: Consultancy; Pharmacyclics/ Janssen: Consultancy; Spectrum: Consultancy; Janssen Pharmaceutical: Research Funding; Denovo Biopharma: Consultancy; Acerta: Research Funding. Cohen:Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Janssen: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BioInvent: Consultancy; Takeda: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy. Blumel:TG Therapeutics, Inc.: Consultancy. Cutter:TG Therapeutics, Inc.: Consultancy. Pauli:TG Therapeutics, Inc.: Consultancy. Sportelli:TG Therapeutics: Employment, Equity Ownership. Miskin:TG Therapeutics: Employment, Equity Ownership. Weiss:TG Therapeutics: Employment, Equity Ownership. Vose:Kite Pharma: Research Funding; Legend Pharmaceuticals: Honoraria; Roche: Honoraria; Incyte Corp.: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Honoraria, Research Funding; Abbvie: Honoraria; Seattle Genetics, Inc.: Research Funding; Merck Sharp & Dohme Corp.: Research Funding; Acerta Pharma: Research Funding; Epizyme: Honoraria; Celgene: Research Funding.

At a time when pharmaceuticals were becoming one of the most successful science-based sectors in Britain and the British pharmaceutical industry was beginning to rank among the world's most innovative, c. 1945–1975, physical methods and electronic instrumentation revolutionised structural organic chemistry. Their introduction is described in three companies (Burroughs Wellcome Co., Glaxo, and Imperial Chemical Industries); when, how and why British pharmaceutical laboratories adopted these methods is examined. The impact they had on pharmaceutical innovation at that time is explored, and what this tells us about and, in turn, what can we learn from the material culture of British pharmaceutical laboratories in the Golden Age of Drug Discovery is discussed.

The literature relating to networks and organizational culture has acknowledged trust to be a valuable intangible asset. This article reviews the theoretical literature and the limited empirical research on trust in relation to business organizations and activity. Within this framework, the early history of Burroughs Wellcome & Co. reveals the importance of trust in building a cohesive organization and in establishing a reputation with the medical profession and with the trade. The study shows the construction of trust to have been an essential dimension in the company's growth to become the leading pharmaceutical manufacturer in Britain by 1914.

Drawing on methodologies and theories used to understand forms of material culture, this paper traces the spatio-temporal lives of a group of medicine chests manufactured by Burroughs Wellcome and Co., the business co-founded by Henry Wellcome which is now known as GlaxoSmithKline. The paper examines the biographical, historical and commercial histories connected with these objects. In particular, it considers how the chests became embroiled within narratives of progress and modernity associated with the production and promotion of ‘modern’ pharmaceuticals and the establishment of a collection of objects through which Wellcome attempted to trace the ‘history of medicine and mankind’ from evolutionary perspectives. Using empirical research from a variety of contexts, the paper therefore reflects on how the chests’ circulation, use and display shed light on historical geographies of science, collecting, commerce and empire in the late nineteenth and early twentieth centuries. Le parcours des pharmacies port...

Professor Garth L. Nicolson is President, Chief Scientific Officer and Research Professor at the Institute for Molecular Medicine in Huntington Beach, California. He formerly held the David Bruton Jr. Chair in Cancer Research and was Chairman at the University of Texas M.D. Anderson Cancer Center in Houston. He was also Professor of Internal Medicine and of Pathology and Laboratory Medicine at the University of Texas Medical School at Houston and Professor of Comparative Pathology at Texas A & M University. Among the most cited scientists in the world, having published over 550 medical and scientific papers (including 3 Current Contents Citation Classics), Prof. Nicolson has edited 14 books and served on the Editorial Boards of 20 medical and scientific journals and is currently serving as Editor of two (Clinical & Experimental Metastasis and the Journal of Cellular Biochemistry). Professor Nicolson has received peer-reviewed research grants from the U.S. Army, National Cancer Institute, National Institutes of Health, American Cancer Society and the National Foundation for Cancer Research. Dr. Garth Nicolson has won many awards, such as the Burroughs Wellcome Medal of the Royal Society of Medicine, the Stephen Paget Award of the Metastasis Research Society and the National Cancer Institute Outstanding Investigator Award. He is also a Colonel (Honorary) of the U.S. Army Special Forces and a U.S. Navy SEAL (Honorary) [ed. "SEAL" represents SEa Air Land; it is a special forces unit of the U.S. Navy] for his work on Armed Forces and veterans' illnesses.

The Wellcome Foundation Archive (WFA) comprises the surviving records of The Wellcome Foundation Ltd, the pharmaceutical company from which the fortunes of Henry Solomon Wellcome (1853–1936), and the Wellcome Trust, were derived.1 The Wellcome Foundation Ltd was formed in 1924, as an amalgamation of Wellcome's business and other interests (including the Wellcome Bureau of Scientific Research—incorporating the Wellcome Physiological Research Laboratories and the Wellcome Chemical Research Laboratories, and also including the Wellcome Tropical Research Laboratories, and the Wellcome Historical Medical Museum) under one umbrella.2 Before 1924 the business was known as Burroughs Wellcome & Company (BW&Co.), and it had its origins in the 1880 partnership between Wellcome and Silas Mainville Burroughs (1846–1895).3 The Burroughs Wellcome name continued to be used in some parts of the world—and indeed is still used as the name for the US equivalent of the Wellcome Trust today.4 The WFA was acquired by, or rather returned to, the Wellcome Trust in 2001, from the now-defunct GlaxoSmithKline (GSK) Heritage Archives at Greenford, Middlesex, and it is now part of the Wellcome Library's Archives and Manuscripts holdings.

Britain in the final decades of the nineteenth century was a vibrant market place for purveyors of medicines, including, inter alia, drug peddlars and travelling quacks, dispensing doctors and chemists, and established compounding companies such as Allen & Hanburys (est. 1715). Regulation and control of the manufacture, quality and efficacy of medicines were practically non-existent, and Weights and Measures and Poisons Acts were the principal relevant pieces of legislation. During the same period, nationwide press and poster advertising, and the easier country-wide distribution of goods opened up by the railroads, contributed to the rise of the ‘branded’ commodity. Medicines, pills potions and nostrums were not exempt, and products such as Friar's Balsam, Wards Drop and Beechams Powders all achieved prominence and success in the second half of the nineteenth century. One such manufacturer, Thomas Holloway, was said to be spending £50 000 a year on advertising in 1883, the year of his death. In Europe however, especially in Germany and Switzerland and to a lesser extent in France, several research-based scientific manufacturing companies were emerging. The rise of the dye industry in Germany, itself a byproduct of a coal-tar industry, provided a cadre of well qualified chemists whose scientific investigations of dye products led to the recognition of medicinal effects, and consequently to the creation of several pharmaceutical companies including Hoechst, Bayer, Sandoz and Ciba1. In Britain, the only company to engage seriously in such research activities was Burroughs, Wellcome & Co, founded in London in 1880 by two young American pharmacists.

Language is the most important evolutionary invention of the last few mil-lion years. How human language evolved from animal communication is a challengingquestion for evolutionary biology. In this paper we use mathematical models to analyzethe major transitions in language evolution. We begin by discussing the evolution ofcoordinated associations between signals and objects in a population. We then analyzeword-formation and its relationship to Shannon’s noisy coding theorem. Finally, wemodel the population dynamics of words and the adaptive emergence of syntax.Keywords: Language evolution; evolutionary game theory; Shannon’s noisy codingtheorem; phoneme. ∗ The authors gratefully acknowledge support from the Alfred P. Sloan Foundation, The Ambrose MonellFoundation, The Florence Gould Foundation, and the J. Seward Johnson Trust. J.B.P also acknowledgessupport from the National Science Foundation and the Burroughs Wellcome Fund c 2001 by the authors. Reproduction for noncommercial purposes permitted.

Support by the National Institutes of Health (R01 GM62968 and P41 RR 12255) and by the La Jolla Interfaces in Science Program/Burroughs Wellcome Fund is gratefully acknowledged.

Burroughs Wellcome & Co. . Knowledge, Trust, Profit and the Transformation of the British Pharmaceutical Industry, 1880-1940. By Roy Church and E. M. Tansey . Crucible Books, Lancaster, UK, 2007. 592 pp. Paper, $39.99, £19.99. ISBN 9781905472079. The authors describe the history of the British pharmaceutical firm from its 1880 origin through the establishment of the Wellcome Trust.

To the Editor: An important concern with respect to protecting human research participants is that institutional review boards (IRBs) have insufficient resources.1 However, there are few reports of the actual costs of IRB review.2–4 To estimate the cost of operating academic IRBs in 2002, we undertook a survey with the support of the Doris Duke Charitable Foundation and the Burroughs Wellcome Fund. We surveyed 121 U.S. medical schools with active IRBs; 63 representative institutions responded. Institutions documented the education, experience, and job titles of IRB staff; the composition of the IRB itself; the estimated amounts of time spent on . . .

Background The debate regarding ‘When to Start’ antiretroviral therapy has raged since the introduction of zidovudine in 1987. Based on the entry criteria for the original Burroughs Wellcome 002 study, the field has been anchored to CD4 cell counts as the prime metric to indicate treatment initiation for asymptomatic individuals infected with Human Immunodeficiency Virus. The pendulum has swung back and forth based mostly on the relative efficacy, toxicity and convenience of available regimens.

Mivacurium is a benzylisoquinolinium diester. The drug is a nondepolarizing relaxant which is hydrolysed by plasma cholinesterase at 70-88% of the rate of suxamethonium. Enzymatic hydrolysis gives the drug its short duration of action. The length of paralysis is about 2-2.5 times that of suxamethonium and one-half to one-third that of the intermediate-acting nondepolarizers. The development of mivacurium represents a collaboration between industrial pharmacologists and chemists at Burroughs Wellcome Co. (USA) and investigators at the Massachusetts General Hospital, Boston, MA, USA.

Premature infants whose mothers received corticosteroid treatment before delivery are less likely to develop respiratory distress syndrome and its associated complications.’ Despite a substantial body of clinical evidence accumulated over more than 20 years that documents these benefits, there is still no consensus among clinicians regarding the safety and efficacy of antenatal corticosteroid treatment. In response, the National Institutes of Health convened a Consensus Development Conference on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. This article is based on an analysis of the VermontOxford Trials Network Database and was prepared at the request of the Consensus Conference Panel.” It describes the effects of antenatal corticosteroids on morbidity and mortality for infants whose birth weights ranged from 501 to 1500 gm born during 1991 and 1992. The plan for analysis and format for presentation were developed jointly with representatives of three other organizations with neonatal databases (Burroughs Wellcome Company, National Institute of Child Health and Development Neonatal Research Network, and Ross Laboratories).3 Each of these organizations has also presented their individual results4-”

FINANCIAL SUPPORT AND DISCLOSURES: No financial support was obtained for this article. All authors declare no conflicts of interest. TK is supported in part by a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund and by a CIHR Training Grant from the Canadian Child Health Clinician Scientist Program, in partnership with Sick Kids Foundation, Child & Family Research Institute (British Columbia), Women & Children’s Health Research Institute (Alberta) and the Manitoba Institute of Child Health. AUTHOR CONTRIBUTIONS: MCMM drafted the manuscript. JC, PT, JH and TK critically revised the manuscript for content. All authors saw and approved the final manuscript.

OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, clinical efficacy, and safety of atovaquone. DATA IDENTIFICATION: An English-language literature search using MEDLINE (1984-1993), programs and abstracts of the 30th, 31st, and 32nd Interscience Conferences on Antimicrobial Agents and Chemotherapy, program and abstracts of the VIII International Conference on AIDS, and unpublished information from Burroughs Wellcome, the manufacturer of atovaquone. STUDY SELECTION: All available pharmacokinetic and clinical trials were reviewed. DATA EXTRACTION: Study quality was assessed by a critical appraisal of study design and methods. Pharmacokinetic studies were evaluated for sampling, methods used to determine pharmacokinetic properties, and the presence of concentration-response and concentration-toxicity relationships. Clinical trials were assessed primarily for comparative efficacy and toxicity. RESULTS: Atovaquone is a novel hydroxynaphthoquinone with potent activity against Pneumocystis carinii and Toxoplasma gondii. Its pharmacokinetic properties are characterized by relatively poor bioavailability, excretion almost exclusively through the feces, lack of hepatic metabolism and urinary excretion, low steady-state plasma concentrations, high protein binding, and a long elimination half-life (50-70 h). Results from comparative clinical trials in AIDS patients with mild-to-moderate P. carinii pneumonia (PCP) reveal similar overall treatment success rates for atovaquone, trimethoprim/sulfamethoxazole (TMP/SMX), and pentamidine. Treatment failure because of lack of therapeutic response was significantly greater in patients who received atovaquone compared with those treated with TMP/SMX (p=0.002). More atovaquone-patients experienced treatment failure compared with their pentamidine-treated counterparts, although statistical significance was not achieved. Treatment failure secondary to drug toxicity was significantly higher in the TMP/SMX- and pentamidine-treated patients (pCONCLUSIONS: Atovaquone appears to be better tolerated but less effective than TMP/SMX and pentamidine in the treatment of mild-to-moderate PCP. There is not enough information available on the use of atovaquone for PCP prophylaxis or the treatment of TE to definitively describe its efficacy. Comparative clinical trials are needed to assess its role in this clinical setting.

The discovery of the immunosuppressant Cyclosporin A (CsA) has improved the survival of transplanted kidneys and has made other solid organ transplants a practical reality. Transplant centres were initially reluctant to use CsA in pediatric patients because of a perceived poor-risk benefit ratio of the drug. However, improved transplant survival, largely because of CsA use in adult transplants, made all centres recognize that withholding this drug from children was not warranted. Hirsutism, coarsening of skin, and nephrotoxicity were the major problems associated with its use. However overall pediatric renal survival rates worldwide were below adult survival figures. 1 The need to improve kidney transplant survival has resulted in the widespread use of CsA along with changes in donor profiles and surgical and postoperative care. The change to CsA in pediatric transplantation has become the backbone of most posttransplant immunosuppressant regimes. The previously used myelotoxic drugs such as Imuran (Burroughs Wellcome Inc, Canada) remain in use for triple therapy regimes or for patients in whom CsA toxicity is particularly prominent. We have had a relatively long experience with CsA, and its use in children has been accepted. The question that was originally asked still looms: Do children have any unique toxicity to this drug, and will the dire predictions of centres that first refused to use it in children be borne out with time?

Burroughs Wellcome Co. uses a slightly modified version of the Food and Drug Administration (FDA) COSTART terminology for encoding all adverse drug experiences (ADEs) reported to the company, including foreign reports. A hardcopy dictionary is available for translations between ADE verbatim text (raw terms) and preferred COSTART termsA pilot project was initiated in July 1987 to evaluate the feasibility of automated translation of raw terms into COSTART. The pilot translation of 500 new raw terms using a “hashing” search algorithm, a word-to-synonym thesaurus, and historical Synonym-COSTART frequencies resulted in a coding accuracy of 73%, compared with an accuracy of 88% from manual codingAn extension of the pilot implementation retains the hashing search algorithm but uses logical groupings of synonym codes to isolate the preferred COSTART phrase. This extension provides an improvement in accuracy (overall coding accuracy of 98% for the previously described 500 raw terms), as well as a decrease in data ...

The Career Award in Biomedical Sciences (CABS) was launched by the Burroughs Wellcome Fund to assist talented scientists to cross the “bridge” that connects postdoctoral training with independent investigator status. This study examines the causal effects of CABS, using both conventional methods and a newer method (propensity score analysis) in attempting to account for selection biases (e.g., selecting the “best and the brightest”) in estimating the award's impact. The results indicated that grantees outperformed unsuccessful applicants in obtaining a faculty position, competing for an R01 grant, and publishing in prestigious journals. However, it was nearly impossible to remove all the effects of selection bias from estimates of program effects. Because selection bias is a pervasive problem in assessing these programs, recommendations for improving evaluations of similar merit-based programs are offered.

Recent studies have used dense markers to examine the human genome in ancestrally homogeneous populations for hallmarks of selection. No genomewide studies have focused on recently admixed groups--populations that have experienced admixing among continentally divided ancestral populations within the past 200-500 years. New World admixed populations are unique in that they represent the sudden confluence of geographically diverged genomes with novel environmental challenges. Here, we present a novel approach for studying selection by examining the genomewide distribution of ancestry in the genetically admixed Puerto Ricans. We find strong statistical evidence of recent selection in three chromosomal regions, including the human leukocyte antigen region on chromosome 6p, chromosome 8q, and chromosome 11q. Two of these regions harbor genes for olfactory receptors. Interestingly, all three regions exhibit deficiencies in the European-ancestry proportion.

Glucose ingestion after an overnight fast triggers an insulin-dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry-based strategy to simultaneously measure 191 metabolites following glucose ingestion. In two groups of healthy individuals (n=22 and 25), 18 plasma metabolites changed reproducibly, including bile acids, urea cycle intermediates, and purine degradation products, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed insulin's known actions along four key axes--proteolysis, lipolysis, ketogenesis, and glycolysis--reflecting a switch from catabolism to anabolism. In pre-diabetics (n=25), we observed a blunted response in all four axes that correlated with insulin resistance. Multivariate analysis revealed that declines in glycerol and leucine/isoleucine (markers of lipolysis and proteolysis, respectively) jointly provide the strongest predictor of insulin sensitivity. This observation indicates that some humans are selectively resistant to insulin's suppression of proteolysis, whereas others, to insulin's suppression of lipolysis. Our findings lay the groundwork for using metabolic profiling to define an individual's 'insulin response profile', which could have value in predicting diabetes, its complications, and in guiding therapy.

The focus of this chapter is a specific museum, or perhaps one should say, since in a sense it no longer exists, the ghost of a museum. It is, or was, one of the most famous museums in the world: the enormous collection of ‘things’, as he called them, amassed by Henry Solomon Wellcome during the first three and a half decades of the twentieth century. Wellcome was the co-founder of Burroughs Wellcome&Co., an enormously successful pharmaceutical company. His motivation in becoming one of the world’s most extraordinary collectors was, as he famously put it, to demonstrate ‘by means of objects … the actuality of every notable step in the evolution and progress from the first germ of life to the fully developed man of today’.1 Wellcome was, one might suggest, to the world of objects what Hegel had been a century earlier to the world of spirit. His aim was, to put it in the terms used by one of the curators of a fairly recent exhibition of objects from the collection, ‘no less than to trace the history of the human body, in sickness and in health, throughout the whole broad sweep of human history’ (The Phantom Museum, p. 1).

English Abstract: My studies at the Vienna University of Economics and Business Administration and at the University of North Carolina at Chapel Hill allowed me to discuss in more detail the impact of mergers on regional systems. This master thesis focuses on an empirical case study: the 1995 pharmaceutical merger between Glaxo and Burroughs Wellcome in the Metropolitan Statistical Area Raleigh-Durham-Chapel Hill (North Carolina). Comparing this study region to an appropriate comparison region, the analysis present the evolution over time of three different indicators: (A) Innovation Input Indicator, (B) Establishments & Employment Indicator, (C) Research Collaborations Indicator. Results first show that, although the merger had a positive impact on the entrepreneurial activities of the region, the employment level did not increase at the same path, leading to many small-sized life sciences establishments. However, a sub-sector of the life sciences industry that experienced a significant increase in both numbers of establishments and employees was the “R&D in the physical, engineering, & life sciences” class. Additionally, the increase in establishments does not result in a similar monetary increase of National Institutes of Health funding, leading to the situation that many companies/universities receive each less money. Moreover, the network analysis showed that being part of a network after a merger increases the innovation capacity of the actors. This case study, as well as the literature review, lay the emphasis on a regional approach of M&A, which academics could interestingly take into account for further research.German Abstract: Mein Studium an der Wirtschaftsuniversitat Wien und an der University of North Carolina at Chapel Hill ermoglichten mir den Einfluss von Fusionen auf regionale Systeme naher zu beleuchten und zu untersuchen. Diese Diplomarbeit behandelt eine empirische Fallstudie: die pharmazeutische Fusion zwischen Glaxo und Burroughs Wellcome in der Region „Raleigh-Durham-Chapel Hill“ in North Carolina in 1995. Die Analyse vergleicht dieses Untersuchungsgebiet mit einer angemessen Vergleichsregion uber eine bestimmte Zeitspanne und mit drei verschiedenen Indikatoren: (A) Innovation Input Indikator, (B) Establishments & Employment Indikator, (C) Research Collaboration Indikator. Die Ergebnisse zeigen, dass, obwohl die Fusion einen positiven Einfluss auf die Anzahl der Unternehmensgrundungen in der Region hatte, das Beschaftigungsniveau nicht gleich schnell gewachsen ist. Dies hatte die Entstehung vieler kleiner Life Sciences Unternehmen zur Folge. Allerdings konnte eine Untergruppe der Life Sciences Industrie, sowohl in der Anzahl von Unternehmen als auch in der Anzahl von Beschaftigten, einen erheblichen Anstieg verzeichnen: die “R&D in the physical, engineering, & life sciences” Kategorie. Zusatzlich steigen die Subventionen vom National Institutes of Health nicht proportional mit den Unternehmensgrundungen: diese Situation fuhrt dazu, dass viele regionale Firmen/Universitaten einzeln weniger Geld erhalten. Schlussendlich zeigte die Netzwerk Analyse, dass eine Firma/Universitat welche Teil eines lokalen Forschungsnetzwerks ist, nach einer Fusion seine Innovationskapazitat steigern kann. Die Fallstudie sowie die Literatur Zusammenfassung zeigen die Wichtigkeit der Forcierung einer regionalen Sichtweise von M&A auf, welche Forscher fur weitere Studien nutzen konnten.

Human cytomegalovirus (HCMV), a dsDNA, enveloped virus, is a ubiquitous pathogen that establishes lifelong latent infections and caused disease in persons with compromised immune systems, e.g., organ transplant recipients or AIDS patients. HCMV is also a leading cause of congenital viral infections in newborns. Entry of HCMV into cells requires the conserved glycoprotein B (gB), thought to function as a fusogen and reported to bind signaling receptors. gB also elicits a strong immune response in humans and induces the production of neutralizing antibodies although most anti-gB Abs are non-neutralizing. Here, we report the crystal structure of the HCMV gB ectodomain determined to 3.6-Å resolution, which is the first atomic-level structure of any betaherpesvirus glycoprotein. The structure of HCMV gB resembles the postfusion structures of HSV-1 and EBV homologs, establishing it as a new member of the class III viral fusogens. Despite structural similarities, each gB has a unique domain arrangement, demonstrating structural plasticity of gB that may accommodate virus-specific functional requirements. The structure illustrates how extensive glycosylation of the gB ectodomain influences antibody recognition. Antigenic sites that elicit neutralizing antibodies are more heavily glycosylated than those that elicit non-neutralizing antibodies, which suggest that HCMV gB uses glycans to shield neutralizing epitopes while exposing non-neutralizing epitopes. This glycosylation pattern may have evolved to direct the immune response towards generation of non-neutralizing antibodies thus helping HCMV to avoid clearance. HCMV gB structure provides a starting point for elucidation of its antigenic and immunogenic properties and aid in the design of recombinant vaccines and monoclonal antibody therapies.

Investigators, sponsors, and other stakeholders in clinical research should “foster a culture in which data sharing is the expected norm,” a US Institute of Medicine committee has concluded in a report issued on 14 January.1 “The issue is no longer whether to share clinical trial data, but what specific data to share, at what time, and under what conditions,” said Bernard Lo, the committee’s chair and president of the Greenwall Foundation, in the report’s preface. The Institute of Medicine convened the committee to develop guiding principles and a framework for sharing clinical trial data. The report was sponsored by the National Institutes of Health, the Food and Drug Administration, the Doris Duke Charitable Foundation, the Medical Research Council, the Wellcome Trust, and the Burroughs Wellcome Fund, as well as more than a dozen major drug companies. Sharing clinical data—allowing investigators to carry out additional analyses and reproduce published findings—is in the public …

The continued threat of vector-borne diseases calls for both reactive and proactive efforts to mitigate the significant morbidity and mortality they cause. To anticipate future demands for novel vector control strategies, the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) formalized a work plan to evaluate genetic-control strategies for prevention of the transmission of selected vector-borne diseases. The original plan focused only on malaria, but was later expanded to include dengue fever. The plan calls for research to determine if genetics, and specifically genetically modified mosquito vectors, could be used to supplement established control methods that rely on chemicals and environmental management. Buoyed by support provided by TDR, the John D. and Catherine T. MacArthur Foundation, the Wellcome Trust, the Burroughs Wellcome Fund, National Institutes of Health (USA) and other funding agencies, research on genetically modified vectors (GMVs) has resulted in the proof-of-principle demonstration that malaria-resistant and dengue-resistant mosquitoes can be produced. It remains to be demonstrated that laboratory-derived engineered mosquito strains can be deployed effectively and safely in the field. Following the laboratory achievements in genetically modifying mosquitoes, three workshops (London 2001, Atlanta 2001, Wageningen 2002) began a process to discuss issues of benefits and risks in the use of GMVs. A number of recommendations were proposed at the different workshops and are summarized here

Institutions that have been longtime rivals are merging. In Massachusetts, Brigham and Women's Hospital and the Massachusetts General Hospital have merged, and two of the state's largest health maintenance organizations (HMOs) — Harvard Community Health Plan and Pilgrim Health Care — have merged. In Philadelphia, Hahnemann Medical School and the Medical College of Pennsylvania have merged. Glaxo merged with Burroughs Wellcome, and Upjohn merged with Pharmacia. Many health care organizations are also expanding their range of services by acquiring other organizations. Hospitals across the country are acquiring groups of primary care physicians, outpatient clinics, rehabilitation units, nursing homes, and home . . .