Likelihood of death among hospital inpatients in New Zealand: prevalent cohort study

Objectives: (1) To establish the likelihood of dying within 12 months for a cohort of hospital inpatients in New Zealand (NZ) on a fixed census date; (2) to identify associations between likelihood of death and key sociodemographic, diagnostic and service-related factors and (3) to compare results with, and extend findings of, a Scottish study undertaken for the same time period and census date. National databases of hospitalisations and death registrations were used, linked by unique health identifier. Participants: 6074 patients stayed overnight in NZ hospitals on the census date (10 April 2013), 40.8% of whom were aged ≥65 years; 54.4% were women; 69.1% of patients were NZ European; 15.3% were Maori; 7.6% were Pacific; 6.1% were Asian and 1.9% were ‘other’. Setting: All NZ hospitals. Results: 14.5% patients (n=878) had died within 12 months: 1.6% by 7 days; 4.5% by 30 days; 8.0% by 3 months and 10.9% by 6 months. In logistic regression models, the strongest predictors of death within 12 months were: age ≥80 years (OR=5.52(95% CI 4.31 to 7.07)); a history of cancer (OR=4.20(3.53 to 4.98)); being Māori (OR=1.62(1.25 to 2.10)) and being admitted to a medical specialty, compared with a surgical specialty (OR=3.16(2.66 to 3.76)). Conclusion: While hospitals are an important site of end of life care in NZ, their role is less significant than in Scotland, where 30% of an inpatient cohort recruited using similar methods and undertaken on the same census date had died within 12 months. One reason for this finding may be the extended role of residential long-term care facilities in end of life care provision in NZ

In Vivo Chemical Screening for Modulators of Hematopoiesis and Hematological Diseases

In vivo chemical screening is a broadly applicable approach not only for dissecting genetic pathways governing hematopoiesis and hematological diseases, but also for finding critical components in those pathways that may be pharmacologically modulated. Both high-throughput chemical screening and facile detection of blood-cell-related phenotypes are feasible in embryonic/larval zebrafish. Two recent studies utilizing phenotypic chemical screens in zebrafish have identified several compounds that promote hematopoietic stem cell formation and reverse the hematopoietic phenotypes of a leukemia oncogene, respectively. These studies illustrate efficient drug discovery processes in zebrafish and reveal novel biological roles of prostaglandin E2 in hematopoietic and leukemia stem cells. Furthermore, the compounds discovered in zebrafish screens have become promising therapeutic candidates against leukemia and included in a clinical trial for enhancing hematopoietic stem cells during hematopoietic cell transplantation

Splice variants of DOMINO control Drosophila circadian behavior and pacemaker neuron maintenance.

Circadian clocks control daily rhythms in behavior and physiology. In Drosophila, the small ventral lateral neurons (sLNvs) expressing PIGMENT DISPERSING FACTOR (PDF) are the master pacemaker neurons generating locomotor rhythms. Despite the importance of sLNvs and PDF in circadian behavior, little is known about factors that control sLNvs maintenance and PDF accumulation. Here, we identify the Drosophila SWI2/SNF2 protein DOMINO (DOM) as a key regulator of circadian behavior. Depletion of DOM in circadian neurons eliminates morning anticipatory activity under light dark cycle and impairs behavioral rhythmicity in constant darkness. Interestingly, the two major splice variants of DOM, DOM-A and DOM-B have distinct circadian functions. DOM-A depletion mainly leads to arrhythmic behavior, while DOM-B knockdown lengthens circadian period without affecting the circadian rhythmicity. Both DOM-A and DOM-B bind to the promoter regions of key pacemaker genes period and timeless, and regulate their protein expression. However, we identify that only DOM-A is required for the maintenance of sLNvs and transcription of pdf. Lastly, constitutive activation of PDF-receptor signaling rescued the arrhythmia and period lengthening of DOM downregulation. Taken together, our findings reveal that two splice variants of DOM play distinct roles in circadian rhythms through regulating abundance of pacemaker proteins and sLNvs maintenance

An integrated machine learning approach for predicting DosR-regulated genes in Mycobacterium tuberculosis.

BACKGROUND: DosR is an important regulator of the response to stress such as limited oxygen availability in Mycobacterium tuberculosis. Time course gene expression data enable us to dissect this response on the gene regulatory level. The mRNA expression profile of a regulator, however, is not necessarily a direct reflection of its activity. Knowing the transcription factor activity (TFA) can be exploited to predict novel target genes regulated by the same transcription factor. Various approaches have been proposed to reconstruct TFAs from gene expression data. Most of them capture only a first-order approximation to the complex transcriptional processes by assuming linear gene responses and linear dynamics in TFA, or ignore the temporal information in data from such systems. RESULTS: In this paper, we approach the problem of inferring dynamic hidden TFAs using Gaussian processes (GP). We are able to model dynamic TFAs and to account for both linear and nonlinear gene responses. To test the validity of the proposed approach, we reconstruct the hidden TFA of p53, a tumour suppressor activated by DNA damage, using published time course gene expression data. Our reconstructed TFA is closer to the experimentally determined profile of p53 concentration than that from the original study. We then apply the model to time course gene expression data obtained from chemostat cultures of M. tuberculosis under reduced oxygen availability. After estimation of the TFA of DosR based on a number of known target genes using the GP model, we predict novel DosR-regulated genes: the parameters of the model are interpreted as relevance parameters indicating an existing functional relationship between TFA and gene expression. We further improve the prediction by integrating promoter sequence information in a logistic regression model. Apart from the documented DosR-regulated genes, our prediction yields ten novel genes under direct control of DosR. CONCLUSIONS: Chemostat cultures are an ideal experimental system for controlling noise and variability when monitoring the response of bacterial organisms such as M. tuberculosis to finely controlled changes in culture conditions and available metabolites. Nonlinear hidden TFA dynamics of regulators can be reconstructed remarkably well with Gaussian processes from such data. Moreover, estimated parameters of the GP can be used to assess whether a gene is controlled by the reconstructed TFA or not. It is straightforward to combine these parameters with further information, such as the presence of binding motifs, to increase prediction accuracy.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A Bayesian Change point model for differential gene expression patterns of the DosR regulon of Mycobacterium tuberculosis.

BACKGROUND: Low oxygen availability has been shown previously to stimulate M. tuberculosis to establish non-replicative persistence in vitro. The two component sensor/regulator dosRS is a major mediator in the transcriptional response of M. tuberculosis to hypoxia and controls a regulon of approximately 50 genes that are induced under this condition. The aim of this study was to determine whether the induction of the entire DosR regulon is triggered as a synchronous event or if induction can unfold as a cascade of events as the differential expression of subsets of genes is stimulated by different oxygen availabilities. RESULTS: A novel aspect of our work is the use of chemostat cultures of M. tuberculosis which allowed us to control environmental conditions very tightly. We exposed M. tuberculosis to a sudden drop in oxygen availability in chemostat culture and studied the transcriptional response of the organism during the transition from a high oxygen level (10% dissolved oxygen tension or DOT) to a low oxygen level (0.2% DOT) using DNA microarrays. We developed a Bayesian change point analysis method that enabled us to detect subtle shifts in the timing of gene induction. It results in probabilities of a change in gene expression at certain time points. A computational analysis of potential binding sites upstream of the DosR-controlled genes shows how the transcriptional responses of these genes are influenced by the affinity of these binding sites to DosR. Our study also indicates that a subgroup of DosR-controlled genes is regulated indirectly. CONCLUSION: The majority of the dosR-dependent genes were up-regulated at 0.2% DOT, which confirms previous findings that these genes are triggered by hypoxic environments. However, our change point analysis also highlights genes which were up-regulated earlier at levels of about 8% DOT indicating that they respond to small fluctuations in oxygen availability. Our analysis shows that there are pairs of divergent genes where one gene in the pair is up-regulated before the other, presumably for a flexible response to a constantly changing environment in the host.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

User guide for Inferior Frontal Sulcal Hyperintensity (IFSH) Scale and related template

This report describes the data related to the article entitiled: “Relationship between inferior frontal sulcal hyperintensities on brain MRI, ageing and cerebral small vessel disease”. 1. User guide for Inferior Frontal Sulcal Hyperintensity (IFSH) Scale This user guide with detailed definition, description and clear examples aims to rate objectively and reproducibly the amount of hyperintensity demonstrated in the CSF in the inferior frontal sulci of the brain. 2. Inferior Frontal Sulcal Hyperintensity (IFSH) Scale templat

PPAR gamma/mTOR signalling: striking the right balance in cartilage homeostasis

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0http://dx.doi.org/10.1136/annrheumdis-2014-20574

Wooded streets, but not streetlight dimming, favour bat activity in a temperate urban setting

Urbanization damages biodiversity, reducing people’s connection to nature and negatively impacting the survivability of local species. However, with small adjustments, the damage could be mitigated. In temperate regions, several bat species inhabit urban areas, and with urbanization set to increase, adapting urban areas to improve their suitability for bats is imperative. Therefore, we investigated if wooded streets and streetlight dimming in an urban setting influenced bat activity. Static bat detectors were used to compare wooded versus non-wooded, and bright versus dim streets in Leicester, UK, on predominantly residential streets. The collected calls were quantified into bat activity (passes per night). Six species were identified, but the common pipistrelle (Pipistrellus pipistrellus) was dominant, making up 94.1% of all calls, so it was the sole species included in the statistical model. Wooded streets had significantly higher bat activity than non-wooded streets, but bright and dim streets were not significantly different. The results suggest that wooded streets were being used as green corridors, with common pipistrelles possibly following them to conceal themselves from predators, such as the tawny owl, and the proliferation of wooded streets in urban areas could allow the formation of better-connected populations. Streetlight dimming did not affect bat activity, but no light-averse bats were detected, likely because even the most dimmed streets deterred them despite street lighting increasing food availability by attracting insects. Therefore, an alternate solution, such as part-night lighting, may be required to increase the suitability of urban areas to light-averse species

The first symbiotic stars from the LAMOST survey

Symbiotic stars are interacting binary systems with the longest orbital periods. They are typically formed by a white dwarf, a red giant and a nebula. These objects are natural astrophysical laboratories for studying the evolution of binaries. Current estimates of the population of Milky Way symbiotic stars vary from 3000 up to 400000. However, the current census is less than 300. The Large sky Area Multi-Object fiber Spectroscopic Telescope (LAMOST) survey can obtain hundreds of thousands of stellar spectra per year, providing a good opportunity to search for new symbiotic stars. In this work we detect 4 of such binaries among 4,147,802 spectra released by the LAMOST, of which two are new identifications. The first is LAMOST J12280490-014825.7, considered to be an S-type halo symbiotic star. The second is LAMOST J202629.80+423652.0, a D-type symbiotic star