Proteomics Mapping of Cord Blood Identifies Haptoglobin “Switch-On” Pattern as Biomarker of Early-Onset Neonatal Sepsis in Preterm Newborns

Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns.We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n = 3) versus GA-matched controls (n = 3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1(st)-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (P<0.001). Western blot concurred in determining that EONS babies had conspicuous Hp&HpRP bands in cord blood ("switch-on pattern") as opposed to non-EONS newborns who had near-absent "switch-off pattern" (P<0.001). Fetal Hp phenotype independently impacted Hp&HpRP. A bayesian latent-class analysis (LCA) was further used for unbiased classification of all 180 cases based on probability of "antenatal IAI exposure" as latent variable. This was then subjected to 2(nd)-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (≤20%) versus high (≥70%) probability of IAI exposure. This approach reclassified ∼30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage.Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the selection of newborns for prompt and targeted treatment at birth

A global reference for human genetic variation

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.We thank the many people who were generous with contributing their samples to the project: the African Caribbean in Barbados; Bengali in Bangladesh; British in England and Scotland; Chinese Dai in Xishuangbanna, China; Colombians in Medellin, Colombia; Esan in Nigeria; Finnish in Finland; Gambian in Western Division – Mandinka; Gujarati Indians in Houston, Texas, USA; Han Chinese in Beijing, China; Iberian populations in Spain; Indian Telugu in the UK; Japanese in Tokyo, Japan; Kinh in Ho Chi Minh City, Vietnam; Luhya in Webuye, Kenya; Mende in Sierra Leone; people with African ancestry in the southwest USA; people with Mexican ancestry in Los Angeles, California, USA; Peruvians in Lima, Peru; Puerto Ricans in Puerto Rico; Punjabi in Lahore, Pakistan; southern Han Chinese; Sri Lankan Tamil in the UK; Toscani in Italia; Utah residents (CEPH) with northern and western European ancestry; and Yoruba in Ibadan, Nigeria. Many thanks to the people who contributed to this project: P. Maul, T. Maul, and C. Foster; Z. Chong, X. Fan, W. Zhou, and T. Chen; N. Sengamalay, S. Ott, L. Sadzewicz, J. Liu, and L. Tallon; L. Merson; O. Folarin, D. Asogun, O. Ikpwonmosa, E. Philomena, G. Akpede, S. Okhobgenin, and O. Omoniwa; the staff of the Institute of Lassa Fever Research and Control (ILFRC), Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria; A. Schlattl and T. Zichner; S. Lewis, E. Appelbaum, and L. Fulton; A. Yurovsky and I. Padioleau; N. Kaelin and F. Laplace; E. Drury and H. Arbery; A. Naranjo, M. Victoria Parra, and C. Duque; S. Däkel, B. Lenz, and S. Schrinner; S. Bumpstead; and C. Fletcher-Hoppe. Funding for this work was from the Wellcome Trust Core Award 090532/Z/09/Z and Senior Investigator Award 095552/Z/11/Z (P.D.), and grants WT098051 (R.D.), WT095908 and WT109497 (P.F.), WT086084/Z/08/Z and WT100956/Z/13/Z (G.M.), WT097307 (W.K.), WT0855322/Z/08/Z (R.L.), WT090770/Z/09/Z (D.K.), the Wellcome Trust Major Overseas program in Vietnam grant 089276/Z.09/Z (S.D.), the Medical Research Council UK grant G0801823 (J.L.M.), the UK Biotechnology and Biological Sciences Research Council grants BB/I02593X/1 (G.M.) and BB/I021213/1 (A.R.L.), the British Heart Foundation (C.A.A.), the Monument Trust (J.H.), the European Molecular Biology Laboratory (P.F.), the European Research Council grant 617306 (J.L.M.), the Chinese 863 Program 2012AA02A201, the National Basic Research program of China 973 program no. 2011CB809201, 2011CB809202 and 2011CB809203, Natural Science Foundation of China 31161130357, the Shenzhen Municipal Government of China grant ZYC201105170397A (J.W.), the Canadian Institutes of Health Research Operating grant 136855 and Canada Research Chair (S.G.), Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research (M.K.D.), a Le Fonds de Recherche duQuébec-Santé (FRQS) research fellowship (A.H.), Genome Quebec (P.A.), the Ontario Ministry of Research and Innovation – Ontario Institute for Cancer Research Investigator Award (P.A., J.S.), the Quebec Ministry of Economic Development, Innovation, and Exports grant PSR-SIIRI-195 (P.A.), the German Federal Ministry of Education and Research (BMBF) grants 0315428A and 01GS08201 (R.H.), the Max Planck Society (H.L., G.M., R.S.), BMBF-EPITREAT grant 0316190A (R.H., M.L.), the German Research Foundation (Deutsche Forschungsgemeinschaft) Emmy Noether Grant KO4037/1-1 (J.O.K.), the Beatriu de Pinos Program grants 2006 BP-A 10144 and 2009 BP-B 00274 (M.V.), the Spanish National Institute for Health Research grant PRB2 IPT13/0001-ISCIII-SGEFI/FEDER (A.O.), Ewha Womans University (C.L.), the Japan Society for the Promotion of Science Fellowship number PE13075 (N.P.), the Louis Jeantet Foundation (E.T.D.), the Marie Curie Actions Career Integration grant 303772 (C.A.), the Swiss National Science Foundation 31003A_130342 and NCCR “Frontiers in Genetics” (E.T.D.), the University of Geneva (E.T.D., T.L., G.M.), the US National Institutes of Health National Center for Biotechnology Information (S.S.) and grants U54HG3067 (E.S.L.), U54HG3273 and U01HG5211 (R.A.G.), U54HG3079 (R.K.W., E.R.M.), R01HG2898 (S.E.D.), R01HG2385 (E.E.E.), RC2HG5552 and U01HG6513 (G.T.M., G.R.A.), U01HG5214 (A.C.), U01HG5715 (C.D.B.), U01HG5718 (M.G.), U01HG5728 (Y.X.F.), U41HG7635 (R.K.W., E.E.E., P.H.S.), U41HG7497 (C.L., M.A.B., K.C., L.D., E.E.E., M.G., J.O.K., G.T.M., S.A.M., R.E.M., J.L.S., K.Y.), R01HG4960 and R01HG5701 (B.L.B.), R01HG5214 (G.A.), R01HG6855 (S.M.), R01HG7068 (R.E.M.), R01HG7644 (R.D.H.), DP2OD6514 (P.S.), DP5OD9154 (J.K.), R01CA166661 (S.E.D.), R01CA172652 (K.C.), P01GM99568 (S.R.B.), R01GM59290 (L.B.J., M.A.B.), R01GM104390 (L.B.J., M.Y.Y.), T32GM7790 (C.D.B., A.R.M.), P01GM99568 (S.R.B.), R01HL87699 and R01HL104608 (K.C.B.), T32HL94284 (J.L.R.F.), and contracts HHSN268201100040C (A.M.R.) and HHSN272201000025C (P.S.), Harvard Medical School Eleanor and Miles Shore Fellowship (K.L.), Lundbeck Foundation Grant R170-2014-1039 (K.L.), NIJ Grant 2014-DN-BX-K089 (Y.E.), the Mary Beryl Patch Turnbull Scholar Program (K.C.B.), NSF Graduate Research Fellowship DGE-1147470 (G.D.P.), the Simons Foundation SFARI award SF51 (M.W.), and a Sloan Foundation Fellowship (R.D.H.). E.E.E. is an investigator of the Howard Hughes Medical Institute

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Psychiatry and the Hirsch h-index : the relationship between journal impact factors and accrued citations

There is considerable debate on the use and abuse of journal impact factors and on selecting the most appropriate indicator to assess research outcome for an individual or group of scientists. Internet searches using Web of Science and Scopus were conducted to retrieve citation data for an individual in order to calculate nine variants of Hirsch’s h-index. Citations to articles published in a wide range of psychiatric journals in the periods 1995–99 and 2000–05 were analyzed using Web of Science. Comparisons were made between journal impact factor, h-index of citations from publication to 2008, and the proportion of articles cited at least 30 or 50 times. For up to 14 years post-publication, there was a strong positive relationship between journal impact factor and h-index for citations received. Journal impact factor was also compared to the percentage of articles cited at least 30 or 50 times - a comparison that showed wide variations between journals with similar impact factors. This study found that 40%–50% of the articles published in the top ten psychiatry journals ranked by impact factor acquire 30 to 50 citations within ten to fifteen years. Despite certain flaws and weaknesses, the h-index provides a better way to assess long-term performance of articles or authors than using a journal’s impact factor, and it provides an alternative way to assess a journal’s long-term ranking

A comparison of patient and staff satisfaction with services after relocating to a new purpose-built mental health facility

Objective: This study measured patient satisfaction levels and staff views regarding their expectations and workplace and other opinions after relocation to a new purpose-built mental health facility within the grounds of a general repatriation hospital. Method: Patients were interviewed face-to-face using a standardized satisfaction survey at least 2 months after the move to the new facility. In addition, surveys were sent by mail to all clinical staff rostered to work the same period that the patient interviews were conducted. Results: One hundred patients were interviewed and 123 staff returned the survey (56% response rate). Patients and staff rated the new ward environment and food services most highly and were least satisfied with patient information and medical services. Less satisfaction was expressed about resource issues such as information technology and dedicated staff facilities. Most staff (70-80%) rated services provided to patients to be the same or better than their original expectations. Conclusions: The results indicate that the hospital move did not have any measurable negative impact on overall service provision or patient satisfaction. In fact, expectations were met or improved for several clinically relevant areas after relocating the mental health facility. Another survey is planned in 12 months to assess if patient and staff ratings change

The experience and views of mental health nurses regarding nursing care delivery in an integrated, inpatient setting

Positive and effective consumer outcomes hinge on having in place optimal models of nursing care delivery. The aim of this study was to ascertain the experience and views of mental health nurses, working in hospitals in an area mental health service, regarding nursing care delivery in those settings. Surveys (n = 250) were sent to all mental health nurses working in inpatient settings and 118 (47%) were returned. Results showed that the quality of nursing care achieved high ratings (by 87%), and that two-thirds of respondents were proud to be a mental health nurse and would choose to be a mental health nurse again. Similarly, the majority (71%) would recommend mental health nursing to others. Concern was, however, expressed about the continuity and consistency of nursing work and information technology resources. Nurses with community experiences rated the importance of the following items, or their confidence, higher than those without previous community placements: the importance of interdisciplinary teamwork; the importance of participating in case review; the importance of collaborating with community staff; confidence in performing mental state examinations; and confidence in collaborating with community staff, suggesting that this placement had positive effects on acute care nursing

Seclusion and its context in acute inpatient psychiatric care

In acute inpatient mental health services, patients commonly demonstrate extreme behaviours. A number of coercive practices, such as locked doors, enforced medication and seclusion, are used in these settings to control such behaviours. The aim of this report is to explore briefly some of the contemporary debates pertaining to seclusion. A perusal of the literature reveals a clarion call to end the practice of seclusion, without consideration of feasible alternatives. It is hoped that this brief report will encourage further evidence-based discussion and research initiatives on this important ethical topic

The quest to fund research : playing research lotto

Objective: To provide some direction for those interested in obtaining funding with the purpose of highlighting opportunities for beginner researchers in the health-care field. Method: Features of a good grant application are described and an audit of seven mental health professional journals was undertaken, the latter to determine, inter alia, whether the paper reported research findings and whether the authors received formal research funding. Result: The audit revealed that many types of papers that are published do not receive formal research funding and describe, for example, services, training issues, clinical practice and education programmes. Conclusion: Innovative and enterprising efforts are required to secure clinical research funding. Submissions must be detailed, comprehensive and relevant, but the onus is also on the researcher to ensure a feasible study, where funding obligations can be fulfilled and findings readily disseminated. Many research studies are conducted without achieving competitive funding, and getting published – and getting started in writing – does not hinge on conducting formal research or receiving research funding

Dealing with bullying in the workplace : toward zero tolerance

Recent reports indicate an absence of respect in workplace culture. Every person has the right to a workplace that is fair and equitable and in which he or she is treated with respect and dignity. Working in a collegial manner is challenging when environments have staff who engage in unprofessional or disruptive behaviors. A number of steps can be taken to support a healthy workplace and prevent bullying. Healthy workplaces are ones in which leaders and managers lead by example, champion respect, and set the tone and expectation for behaviors essential for fostering a harmonious and collaborative environment. The role of the leader/manager is crucial in developing a positive workplace culture that supports a high level of professionalism and a culture of zero tolerance toward bullying