From white elephant to Nobel Prize: Dennis Gabor’s wavefront reconstruction

Dennis Gabor devised a new concept for optical imaging in 1947 that went by a variety of names over the following decade: holoscopy, wavefront reconstruction, interference microscopy, diffraction microscopy and Gaboroscopy. A well-connected and creative research engineer, Gabor worked actively to publicize and exploit his concept, but the scheme failed to capture the interest of many researchers. Gabor’s theory was repeatedly deemed unintuitive and baffling; the technique was appraised by his contemporaries to be of dubious practicality and, at best, constrained to a narrow branch of science. By the late 1950s, Gabor’s subject had been assessed by its handful of practitioners to be a white elephant. Nevertheless, the concept was later rehabilitated by the research of Emmett Leith and Juris Upatnieks at the University of Michigan, and Yury Denisyuk at the Vavilov Institute in Leningrad. What had been judged a failure was recast as a success: evaluations of Gabor’s work were transformed during the 1960s, when it was represented as the foundation on which to construct the new and distinctly different subject of holography, a re-evaluation that gained the Nobel Prize for Physics for Gabor alone in 1971. This paper focuses on the difficulties experienced in constructing a meaningful subject, a practical application and a viable technical community from Gabor’s ideas during the decade 1947-1957

Information (and library) science at City University London; 50 years of educational development

The development of education for information and library science at City University London over a 50-year period is described in this article. The development of the Masters course in Information Science, and the later equivalent courses in Library Science and in Information Management in the Cultural Sector are described in detail, together with shorter-lived Masters courses in pharmaceutical and health information. The rationale for changes to the courses, and the influence of the professional and educational contexts, are analysed. Issues emerging from this analysis are discussed in seven themes: the nature of the discipline; the library/information spectrum; the student group; the academic/professional balance; curriculum design; local and global issues; and teaching methods. The discussions of the courses are set in the wider context of changes in library/information education over the period in the UK and worldwide

Single Nucleotide Polymorphisms (SNPs) Distinguish Indian-Origin and Chinese-Origin Rhesus Macaques (Macaca Mulatta)

BACKGROUND: Rhesus macaques serve a critical role in the study of human biomedical research. While both Indian and Chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus (SIV) infection. Single nucleotide polymorphisms (SNPs) can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. We sequenced the 3\u27 end of rhesus macaque genes in an effort to identify gene-based SNPs that could distinguish between Indian and Chinese rhesus macaques and aid in association analysis. RESULTS: We surveyed the 3\u27 end of 94 genes in 20 rhesus macaque animals. The study included 10 animals each of Indian and Chinese ancestry. We identified a total of 661 SNPs, 457 of which appeared exclusively in one or the other population. Seventy-nine additional animals were genotyped at 44 of the population-exclusive SNPs. Of those, 38 SNPs were confirmed as being population-specific. CONCLUSION: This study demonstrates that the 3\u27 end of genes is rich in sequence polymorphisms and is suitable for the efficient discovery of gene-linked SNPs. In addition, the results show that the genomic sequences of Indian and Chinese rhesus macaque are remarkably divergent, and include numerous population-specific SNPs. These ancestral SNPs could be used for the rapid scanning of rhesus macaques, both to establish animal ancestry and to identify gene alleles that may contribute to the phenotypic differences observed in these populations

Single nucleotide polymorphisms (SNPs) distinguish Indian-origin and Chinese-origin rhesus macaques (Macaca mulatta)

BACKGROUND: Rhesus macaques serve a critical role in the study of human biomedical research. While both Indian and Chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus (SIV) infection. Single nucleotide polymorphisms (SNPs) can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. We sequenced the 3' end of rhesus macaque genes in an effort to identify gene-based SNPs that could distinguish between Indian and Chinese rhesus macaques and aid in association analysis. RESULTS: We surveyed the 3' end of 94 genes in 20 rhesus macaque animals. The study included 10 animals each of Indian and Chinese ancestry. We identified a total of 661 SNPs, 457 of which appeared exclusively in one or the other population. Seventy-nine additional animals were genotyped at 44 of the population-exclusive SNPs. Of those, 38 SNPs were confirmed as being population-specific. CONCLUSION: This study demonstrates that the 3' end of genes is rich in sequence polymorphisms and is suitable for the efficient discovery of gene-linked SNPs. In addition, the results show that the genomic sequences of Indian and Chinese rhesus macaque are remarkably divergent, and include numerous population-specific SNPs. These ancestral SNPs could be used for the rapid scanning of rhesus macaques, both to establish animal ancestry and to identify gene alleles that may contribute to the phenotypic differences observed in these populations

Results of a multicentre UK-wide retrospective study evaluating the efficacy of brentuximab vedotin in relapsed, refractory classical Hodgkin lymphoma in the transplant naive setting

Relapsed or refractory classical Hodgkin lymphoma (cHL) is associated with a poor outcome when standard chemotherapy fails. Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate licensed for use at relapse after autologous stem cell transplant (ASCT) or following two prior therapies in those unsuitable for ASCT. There are limited data assessing the ability of BV to enable curative SCT. We performed a UK-wide retrospective study of 99 SCT-naïve relapsed/refractory cHL. All had received 2 prior lines and were deemed fit for transplant but had an insufficient remission to proceed. The median age was 32 years. Most had nodular sclerosis subtype, Eastern Cooperative Oncology Group performance status 0-1 and advanced stage disease. The median progression-free survival (PFS) was 5·6 months and median overall survival (OS) was 37·2 months. The overall response rate was 56% (29% complete response; 27% partial response). 61% reached SCT: 34% immediately post-BV and 27% following an inadequate BV response but were salvaged and underwent deferred SCT. Patients consolidated with SCT had a superior PFS and OS to those not receiving SCT (P < 0·001). BV is an effective, non-toxic bridge to immediate SCT in 34% and deferred SCT in 27%. 39% never reached SCT with a PFS of 3·0 months, demonstrating the unmet need to improve outcomes in those unsuitable for SCT post-BV

Patient-reported outcomes of brentuximab vedotin in Hodgkin lymphoma and anaplastic large-cell lymphoma

BACKGROUND: Patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) or R/R systemic anaplastic large-cell lymphoma (sALCL) treated with brentuximab vedotin (BV) experienced high remission rates in two Phase II trials. With increased response rates and survival times, patient-reported outcomes (PROs) and health-related quality of life (HRQoL) are becoming increasingly important and can help inform treatment decisions to enhance care of cancer patients. OBJECTIVE: The objective was to qualitatively assess HRQoL in long-term survivors treated with BV. METHODS: An eight-question survey assessing PRO-related aspects was developed and fielded to a subset of patients with HL or sALCL who remained in long-term follow-up after completing BV treatment in the two pivotal studies. RESULTS: The survey was completed by 25 of 38 patients (12 with HL, 13 with sALCL). The majority of patients reported that their energy level, outlook on life, difficulties with daily activities, ability to participate in physical activities, and overall HRQoL improved compared to those before BV treatment. LIMITATIONS: Small sample size and lack of a baseline questionnaire or validated assessment instrument limit broad applicability of these findings to large populations of patients with HL or sALCL. CONCLUSION: This is the first report of BV PRO data in R/R HL and sALCL. Given the patients’ poor prognostic outcomes before stem cell transplant, these encouraging results warrant formal evaluation of PRO end points in BV trials

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Inefficient high-temperature metamorphism in orthogneiss

A novel method utilizing crystallographic orientation and mineral chemistry data, based on large-scale electron backscatter diffraction (EBSD) and microbeam analysis, quantifies the proportion of relict igneous and neoblastic minerals forming variably deformed high-grade orthogneiss. The Cretaceous orthogneiss from Fiordland, New Zealand, comprises intermediate omphacite granulite interlayered with basic eclogite, which was metamorphosed and deformed at T ≈ 850 °C and P ≈ 1.8 GPa after protolith cooling. Detailed mapping of microstructural and physiochemical relations in two strain profiles through subtly distinct intermediate protoliths indicates that up to 32% of the orthogneiss mineralogy is igneous, with the remainder being metamorphic. Domains dominated by igneous minerals occur preferentially in strain shadows to eclogite pods. Distinct metamorphic stages can be identified by texture and chemistry and were at least partially controlled by strain magnitude. At the grain-scale, the coupling of metamorphism and crystal plastic deformation appears to have permitted efficient transformation of an originally igneous assemblage. The effective distinction between igneous and metamorphic paragenesis and their links to deformation history enables greater clarity in interpretations of the makeup of the crust and their causal influence on lithospheric scale processes