Sleep assessment by patients and nurses in the intensive care: An exploratory descriptive study

© 2016. Background: Sleep disruption is common in intensive care unit (ICU) patients, with reports indicating reduced quality and quantity of sleep in many patients. There is growing evidence that sleep in this setting may be improved. Aim: To describe ICU patients' self-report assessment of sleep, examine the relationship between patients' self-reported sleep and their reported sleep by the bedside nurse, and describe the strategies suggested by patients to promote sleep. Methods: An exploratory descriptive study was undertaken with communicative adult patients consecutively recruited in 2014-2015. Patients reported sleep using the Richards-Campbell Sleep Questionnaire (score range 0-100. mm; higher score indicates better sleep quality), with nursing assessment of sleep documented across a five level ordinal variable. Patients were asked daily to describe strategies that helped or hindered their sleep. Ethical approval for the study was gained. Descriptive statistical analysis was performed [median (interquartile range)]; relationships were tested using Spearman's rank correlation and differences assessed using the Kruskal-Wallis test; . p . <. 0.05 was considered significant. Results: Participants (n = 151) were recruited [age: 60 (46-71) years; ICU length of stay 4 (2-9) days] with 356 self-reports of sleep. Median perceived sleep quality was 46 (26-65) mm. A moderate relationship existed between patients' self-assessment and nurses' assessment of sleep (Spearman's rank correlation coefficient 0.39-0.50; . p . <. 0.001). Strategies identified by patients to improve sleep included adequate pain relief and sedative medication, a peaceful and comfortable environment and physical interventions, e.g. clustering care, ear plugs. Conclusion: Patients reported on their sleep a median of 2 (1-3) days during their ICU stay, suggesting that routine use of self-report was feasible. These reports revealed low sleep quality. Patients reported multiple facilitators and barriers for sleep, with environmental and patient comfort factors being most common. Interventions that target these factors to improve patient sleep should be implemented

Deficient resident memory T-cell and Cd8 T-cell response to commensals in inflammatory bowel disease

Background Aims: The intestinal microbiota is closely associated with resident memory lymphocytes in mucosal tissue. We sought to understand how acquired cellular and humoral immunity to the microbiota differ in health versus inflammatory bowel disease (IBD). Methods Resident memory T-cells (Trm) in colonic biopsies and local antibody responses to intraepithelial microbes were analyzed. Systemic antigen-specific immune T- and B-cell memory to a panel of commensal microbes was assessed. Results Systemically, healthy blood showed CD4 and occasional CD8 memory T-cell responses to selected intestinal bacteria but few memory B-cell responses. In IBD, CD8 memory T-cell responses decreased although B-cell responses and circulating plasmablasts increased. Possibly secondary to loss of systemic CD8 T-cell responses in IBD, dramatically reduced numbers of mucosal CD8+ Trm and γδ T-cells were observed. IgA responses to intraepithelial bacteria were increased. Colonic Trm expressed CD39 and CD73 ectonucleotidases, characteristic of regulatory T-cells. Cytokines/factors required for Trm differentiation were identified, and in vitro-generated Trm expressed regulatory T-cell function via CD39. Cognate interaction between T-cells and dendritic cells induced T-bet expression in dendritic cells, a key mechanism in regulating cell-mediated mucosal responses. Conclusions A previously unrecognized imbalance exists between cellular and humoral immunity to the microbiota in IBD, with loss of mucosal T-cell-mediated barrier immunity and uncontrolled antibody responses. Regulatory function of Trm may explain their association with intestinal health. Promoting Trm and their interaction with dendritic cells rather than immunosuppression may reinforce tissue immunity, improve barrier function and prevent B-cell dysfunction in microbiota-associated disease and IBD etiology

Genome3D: integrating a collaborative data pipeline to expand the depth and breadth of consensus protein structure annotation.

Genome3D (https://www.genome3d.eu) is a freely available resource that provides consensus structural annotations for representative protein sequences taken from a selection of model organisms. Since the last NAR update in 2015, the method of data submission has been overhauled, with annotations now being 'pushed' to the database via an API. As a result, contributing groups are now able to manage their own structural annotations, making the resource more flexible and maintainable. The new submission protocol brings a number of additional benefits including: providing instant validation of data and avoiding the requirement to synchronise releases between resources. It also makes it possible to implement the submission of these structural annotations as an automated part of existing internal workflows. In turn, these improvements facilitate Genome3D being opened up to new prediction algorithms and groups. For the latest release of Genome3D (v2.1), the underlying dataset of sequences used as prediction targets has been updated using the latest reference proteomes available in UniProtKB. A number of new reference proteomes have also been added of particular interest to the wider scientific community: cow, pig, wheat and mycobacterium tuberculosis. These additions, along with improvements to the underlying predictions from contributing resources, has ensured that the number of annotations in Genome3D has nearly doubled since the last NAR update article. The new API has also been used to facilitate the dissemination of Genome3D data into InterPro, thereby widening the visibility of both the annotation data and annotation algorithms

Stellar structure and compact objects before 1940: Towards relativistic astrophysics

Since the mid-1920s, different strands of research used stars as "physics laboratories" for investigating the nature of matter under extreme densities and pressures, impossible to realize on Earth. To trace this process this paper is following the evolution of the concept of a dense core in stars, which was important both for an understanding of stellar evolution and as a testing ground for the fast-evolving field of nuclear physics. In spite of the divide between physicists and astrophysicists, some key actors working in the cross-fertilized soil of overlapping but different scientific cultures formulated models and tentative theories that gradually evolved into more realistic and structured astrophysical objects. These investigations culminated in the first contact with general relativity in 1939, when J. Robert Oppenheimer and his students George Volkoff and Hartland Snyder systematically applied the theory to the dense core of a collapsing neutron star. This pioneering application of Einstein's theory to an astrophysical compact object can be regarded as a milestone in the path eventually leading to the emergence of relativistic astrophysics in the early 1960s.Comment: 83 pages, 4 figures, submitted to the European Physical Journal

Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth

Targeted cancer therapies, which act on specific cancer-associated molecular targets, are predominantly inhibitors of oncogenic kinases. While these drugs have achieved some clinical success, the inactivation of kinase signaling via stimulation of endogenous phosphatases has received minimal attention as an alternative targeted approach. Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. Our group previously developed a series of orally bioavailable small molecule activators of PP2A, termed SMAPs. We now report that SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse xenografts and transgenic models. Mechanistically, we found that SMAPs act by binding to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. These results show that PP2A can be activated in cancer cells to inhibit proliferation. Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins

Gravitational-wave research as an emerging field in the Max Planck Society. The long roots of GEO600 and of the Albert Einstein Institute

On the occasion of the 50th anniversary since the beginning of the search for gravitational waves at the Max Planck Society, and in coincidence with the 25th anniversary of the foundation of the Albert Einstein Institute, we explore the interplay between the renaissance of general relativity and the advent of relativistic astrophysics following the German early involvement in gravitational-wave research, to the point when gravitational-wave detection became established by the appearance of full-scale detectors and international collaborations. On the background of the spectacular astrophysical discoveries of the 1960s and the growing role of relativistic astrophysics, Ludwig Biermann and his collaborators at the Max Planck Institute for Astrophysics in Munich became deeply involved in research related to such new horizons. At the end of the 1960s, Joseph Weber's announcements claiming detection of gravitational waves sparked the decisive entry of this group into the field, in parallel with the appointment of the renowned relativist Juergen Ehlers. The Munich area group of Max Planck institutes provided the fertile ground for acquiring a leading position in the 1970s, facilitating the experimental transition from resonant bars towards laser interferometry and its innovation at increasingly large scales, eventually moving to a dedicated site in Hannover in the early 1990s. The Hannover group emphasized perfecting experimental systems at pilot scales, and never developed a full-sized detector, rather joining the LIGO Scientific Collaboration at the end of the century. In parallel, the Max Planck Institute for Gravitational Physics (Albert Einstein Institute) had been founded in Potsdam, and both sites, in Hannover and Potsdam, became a unified entity in the early 2000s and were central contributors to the first detection of gravitational waves in 2015.Comment: 94 pages. Enlarged version including new results from further archival research. A previous version appears as a chapter in the volume The Renaissance of General Relativity in Context, edited by A. Blum, R. Lalli and J. Renn (Boston: Birkhauser, 2020

Universal Plant DNA Barcode Loci May Not Work in Complex Groups: A Case Study with Indian Berberis Species

BACKGROUND: The concept of DNA barcoding for species identification has gained considerable momentum in animals because of fairly successful species identification using cytochrome oxidase I (COI). In plants, matK and rbcL have been proposed as standard barcodes. However, barcoding in complex genera is a challenging task. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the species discriminatory power of four reportedly most promising plant DNA barcoding loci (one from nuclear genome--ITS, and three from plastid genome--trnH-psbA, rbcL and matK) in species of Indian Berberis L. (Berberidaceae) and two other genera, Ficus L. (Moraceae) and Gossypium L. (Malvaceae). Berberis species were delineated using morphological characters. These characters resulted in a well resolved species tree. Applying both nucleotide distance and nucleotide character-based approaches, we found that none of the loci, either singly or in combinations, could discriminate the species of Berberis. ITS resolved all the tested species of Ficus and Gossypium and trnH-psbA resolved 82% of the tested species in Ficus. The highly regarded matK and rbcL could not resolve all the species. Finally, we employed amplified fragment length polymorphism test in species of Berberis to determine their relationships. Using ten primer pair combinations in AFLP, the data demonstrated incomplete species resolution. Further, AFLP analysis showed that there was a tendency of the Berberis accessions to cluster according to their geographic origin rather than species affiliation. CONCLUSIONS/SIGNIFICANCE: We reconfirm the earlier reports that the concept of universal barcode in plants may not work in a number of genera. Our results also suggest that the matK and rbcL, recommended as universal barcode loci for plants, may not work in all the genera of land plants. Morphological, geographical and molecular data analyses of Indian species of Berberis suggest probable reticulate evolution and thus barcode markers may not work in this case

Incisional hernia following colorectal cancer surgery according to suture technique: Hughes Abdominal Repair Randomized Trial (HART).

BACKGROUND: Incisional hernias cause morbidity and may require further surgery. HART (Hughes Abdominal Repair Trial) assessed the effect of an alternative suture method on the incidence of incisional hernia following colorectal cancer surgery. METHODS: A pragmatic multicentre single-blind RCT allocated patients undergoing midline incision for colorectal cancer to either Hughes closure (double far-near-near-far sutures of 1 nylon suture at 2-cm intervals along the fascia combined with conventional mass closure) or the surgeon's standard closure. The primary outcome was the incidence of incisional hernia at 1 year assessed by clinical examination. An intention-to-treat analysis was performed. RESULTS: Between August 2014 and February 2018, 802 patients were randomized to either Hughes closure (401) or the standard mass closure group (401). At 1 year after surgery, 672 patients (83.7 per cent) were included in the primary outcome analysis; 50 of 339 patients (14.8 per cent) in the Hughes group and 57 of 333 (17.1 per cent) in the standard closure group had incisional hernia (OR 0.84, 95 per cent c.i. 0.55 to 1.27; P = 0.402). At 2 years, 78 patients (28.7 per cent) in the Hughes repair group and 84 (31.8 per cent) in the standard closure group had incisional hernia (OR 0.86, 0.59 to 1.25; P = 0.429). Adverse events were similar in the two groups, apart from the rate of surgical-site infection, which was higher in the Hughes group (13.2 versus 7.7 per cent; OR 1.82, 1.14 to 2.91; P = 0.011). CONCLUSION: The incidence of incisional hernia after colorectal cancer surgery is high. There was no statistical difference in incidence between Hughes closure and mass closure at 1 or 2 years. REGISTRATION NUMBER: ISRCTN25616490 (http://www.controlled-trials.com)