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151.
152.
Thomas Grischott Stefan Zechmann Yael Rachamin Stefan Markun Corinne Chmiel Oliver Senn Thomas Rosemann Nicolas Rodondi Stefan Neuner-Jehle 《Implementation science : IS》2018,13(1):155
Background
Inappropriate medication and polypharmacy increase morbidity, hospitalisation rate, costs and mortality in multimorbid patients. At hospital discharge of elderly patients, polypharmacy is often even more pronounced than at admission. However, the optimal discharge strategy in view of sustained medication appropriateness remains unclear. In particular, unreflectingly switching back to the pre-hospitalisation medication must be avoided. Therefore, both the patients and the follow-up physicians should be involved in the discharge process. In this study, we aim to test whether a brief medication review which takes the patients’ priorities into account, combined with a standardised communication strategy at hospital discharge, leads to sustained medication appropriateness and extends readmission times among elderly multimorbid patients.Methods
The study is designed as a two-armed, double-blinded, cluster-randomised trial, involving 42 senior hospital physicians (HPs) with their junior HPs and 2100 multimorbid patients aged 60 years or older.Using a randomised minimisation strategy, senior HPs will be assigned to either intervention or control group. Following instructions of the study team, the senior HPs in the intervention group will teach their junior HPs how to integrate a simple medication review tool combined with a defined communication strategy into their ward’s discharge procedure. The untrained HPs in the control group will provide data on usual care, and their patients will be discharged following usual local routines.Primary outcome is the time until readmission within 6 months after discharge, and secondary outcomes cover readmission rates, number of emergency and GP visits, classes and numbers of drugs prescribed, proportions of potentially inappropriate medications, and the patients’ quality of life after discharge. Additionally, the characteristics of both the HPs as well as the patients will be collected before the intervention. Process evaluation outcomes will be assessed parallel to the ongoing core study using qualitative research methods.Discussion
So far, interventions to reduce polypharmacy are still scarce at the crucial interface between HPs and GPs. To our knowledge, this trial is the first to analyse the combination of a brief deprescribing intervention with a standardised communication strategy at hospital discharge and in the early post-discharge period.Trial registration
ISRCTN, ISRCTN18427377. Registered 11 January 2018153.
Signatures of competition and strain structure within the major blood‐stage antigen of Plasmodium falciparum in a local community in Ghana 下载免费PDF全文
Mary M. Rorick Yael Artzy‐Randrup Shazia Ruybal‐Pesántez Kathryn E. Tiedje Thomas S. Rask Abraham Oduro Anita Ghansah Kwadwo Koram Karen P. Day Mercedes Pascual 《Ecology and evolution》2018,8(7):3574-3588
The concept of niche partitioning has received considerable theoretical attention at the interface of ecology and evolution of infectious diseases. Strain theory postulates that pathogen populations can be structured into distinct nonoverlapping strains by frequency‐dependent selection in response to intraspecific competition for host immune space. The malaria parasite Plasmodium falciparum presents an opportunity to investigate this phenomenon in nature, under conditions of high recombination rate and extensive antigenic diversity. The parasite's major blood‐stage antigen, PfEMP1, is encoded by the hyperdiverse var genes. With a dataset that includes thousands of var DBLα sequence types sampled from asymptomatic cases within an area of high endemicity in Ghana, we address how var diversity is distributed within isolates and compare this to the distribution of microsatellite allelic diversity within isolates to test whether antigenic and neutral regions of the genome are structured differently. With respect to var DBLα sequence types, we find that on average isolates exhibit significantly lower overlap than expected randomly, but that there also exists frequent pairs of isolates that are highly related. Furthermore, the linkage network of var DBLα sequence types reveals a pattern of nonrandom modularity unique to these antigenic genes, and we find that modules of highly linked DBLα types are not explainable by neutral forces related to var recombination constraints, microsatellite diversity, sampling location, host age, or multiplicity of infection. These findings of reduced overlap and modularity among the var antigenic genes are consistent with a role for immune selection as proposed by strain theory. Identifying the evolutionary and ecological dynamics that are responsible for the nonrandom structure in P. falciparum antigenic diversity is important for designing effective intervention in endemic areas. 相似文献
154.
Localization of an Ataxia-Telangiectasia Gene to an −500-kb Interval on Chromosome 11q23.1: Linkage Analysis of 176 Families by an International Consortium 下载免费PDF全文
Ethan Lange Anna-Lise Borresen Xiaoguang Chen Luciana Chessa Sujata Chiplunkar Patrick Concannon Sugandha Dandekar Steven Gerken Kenneth Lange Teresa Liang Carmel McConville Jeff Polakow Oscar Porras Galit Rotman Ozden Sanal Sepideh Sheikhavandi Yosef Shiloh Eric Sobel Malcolm Taylor Milhan Telatar Sharon Teraoka Aslihan Tolun Nitin Udar Nancy Uhrhammer Lina Vanagaite Zhijun Wang Beth Wapelhorst Jocyndra Wright Huan-Ming Yang Lan Yang Yael Ziv Richard A. Gatti 《American journal of human genetics》1995,57(1):112-119
We describe a 20-point linkage analysis map of chromosome 11q22-23 that is based on genotyping 249 families (59 CEPH and 190 A-T). Monte Carlo linkage analyses of 176 ataxia-telangiectasia (A-T) families localizes the major A-T locus to the region between S1819(A4) and S1818(A2). When seven nonlinking families were excluded from subsequent analyses, a 2-lod support interval of ~500 kb was identified between S1819(A4) and S1294. No recombinants were observed between A-T and markers S384, B7, S535, or S1294. Only 17 of the international consortium families have been assigned to complementation groups. The available evidence favors either a cluster of A-T genes on chromosome 11 or intragenic defects in a single gene. 相似文献
155.
156.
157.
John D Dickinson Yael Alevy Nicole P Malvin Khushbu K Patel Sean P Gunsten Michael J Holtzman 《Autophagy》2016,12(2):397-409
Cytokine modulation of autophagy is increasingly recognized in disease pathogenesis, and current concepts suggest that type 1 cytokines activate autophagy, whereas type 2 cytokines are inhibitory. However, this paradigm derives primarily from studies of immune cells and is poorly characterized in tissue cells, including sentinel epithelial cells that regulate the immune response. In particular, the type 2 cytokine IL13 (interleukin 13) drives the formation of airway goblet cells that secrete excess mucus as a characteristic feature of airway disease, but whether this process is influenced by autophagy was undefined. Here we use a mouse model of airway disease in which IL33 (interleukin 33) stimulation leads to IL13-dependent formation of airway goblet cells as tracked by levels of mucin MUC5AC (mucin 5AC, oligomeric mucus/gel forming), and we show that these cells manifest a block in mucus secretion in autophagy gene Atg16l1-deficient mice compared to wild-type control mice. Similarly, primary-culture human tracheal epithelial cells treated with IL13 to stimulate mucus formation also exhibit a block in MUC5AC secretion in cells depleted of autophagy gene ATG5 (autophagy-related 5) or ATG14 (autophagy-related 14) compared to nondepleted control cells. Our findings indicate that autophagy is essential for airway mucus secretion in a type 2, IL13-dependent immune disease process and thereby provide a novel therapeutic strategy for attenuating airway obstruction in hypersecretory inflammatory diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis lung disease. Taken together, these observations suggest that the regulation of autophagy by Th2 cytokines is cell-context dependent. 相似文献
158.
Darya Y. Orlova Noah Zimmerman Stephen Meehan Connor Meehan Jeffrey Waters Eliver E. B. Ghosn Alexander Filatenkov Gleb A. Kolyagin Yael Gernez Shanel Tsuda Wayne Moore Richard B. Moss Leonore A. Herzenberg Guenther Walther 《PloS one》2016,11(3)
Changes in the frequencies of cell subsets that (co)express characteristic biomarkers, or levels of the biomarkers on the subsets, are widely used as indices of drug response, disease prognosis, stem cell reconstitution, etc. However, although the currently available computational “gating” tools accurately reveal subset frequencies and marker expression levels, they fail to enable statistically reliable judgements as to whether these frequencies and expression levels differ significantly between/among subject groups. Here we introduce flow cytometry data analysis pipeline which includes the Earth Mover’s Distance (EMD) metric as solution to this problem. Well known as an informative quantitative measure of differences between distributions, we present three exemplary studies showing that EMD 1) reveals clinically-relevant shifts in two markers on blood basophils responding to an offending allergen; 2) shows that ablative tumor radiation induces significant changes in the murine colon cancer tumor microenvironment; and, 3) ranks immunological differences in mouse peritoneal cavity cells harvested from three genetically distinct mouse strains. 相似文献
159.
Deborah R. Smith Yong‐Chao Su Reut Berger‐Tal Yael Lubin 《Ecology and evolution》2016,6(15):5479-5490
Dispersal in most group‐living species ensures gene flow among groups, but in cooperative social spiders, juvenile dispersal is suppressed and colonies are highly inbred. It has been suggested that such inbred sociality is advantageous in the short term, but likely to lead to extinction or reduced speciation rates in the long run. In this situation, very low levels of dispersal and gene flow among colonies may have unusually important impacts on fitness and persistence of social spiders. We investigated sex‐specific differences in dispersal and gene flow among colonies, as reflected in the genetic structure within colonies and populations of the African social spider Stegodyphus dumicola Pocock, 1898 (Eresidae). We used DNA fingerprinting and mtDNA sequence data along with spatial mapping of colonies to compare male and female patterns of relatedness within and among colonies at three study sites. Samples were collected during and shortly after the mating season to detect sex‐specific dispersal. Distribution of mtDNA haplotypes was consistent with proliferation of social nests by budding and medium‐ to long‐distance dispersal by ballooning females. Analysis of molecular variance and spatial autocorrelation analyses of AFLPs showed high levels of genetic similarity within colonies, and STRUCTURE analyses revealed that the number of source populations contributing to colonies ranged from one to three. We also showed significant evidence of male dispersal among colonies at one site. These results support the hypothesis that in social spiders, genetic cohesion among populations is maintained by long‐distance dispersal of female colony founders. Genetic diversity within colonies is maintained by colony initiation by multiple dispersing females, and adult male dispersal over short distances. Male dispersal may be particularly important in maintaining gene flow among colonies in local populations. 相似文献
160.
Yosef Shiloh Ram Parshad Moshe Frydman Katherine K. Sanford Sima Portnoi Yael Ziv Gary M. Jones 《Human genetics》1989,84(1):15-18
Summary Ataxia-telangiectasia (A-T) is an autosomal recessive disease involving chromosomal instability, susceptibility to cancer and X-ray hypersensitivity. The latter two features are expressed to a limited extent in the heterozygous carriers of A-T mutations. Although fibroblast lines from A-T heterozygotes clearly show increased susceptibility to the lethal effect of X-irradiation, the difference in post-irradiation survival between cell lines and normal controls is not always large enough to allow the use of X-ray sensitivity as a laboratory assay for carrier detection in A-T. Recently, we have shown in a blind study, that the extent of chromatid damage induced in the G2 phase of the cell cycle by moderate doses of X-rays is markedly higher in A-T heterozygous cells than in normal controls. We have now applied this test to 6 additional obligatory heterozygotes and 24 individuals with different risks of being A-T carriers, from three Israeli A-T families. All 6 cell lines from the obligatory heterozygotes showed the typical hypersensitivity to the clastogenic action of X-rays in G2; of the 24 cell lines with unknown A-T genotype, 16 showed the same hypersensitivity, and 8 responded in a normal way. The proportion of cell lines showing the A-T-heterozygous phenotype was in accord with the expected value, based on Mendelian chance calculations. Since these observations were made, a daughter of two hypersensitive parents in one of these families has been diagnosed as having A-T. This confirmed the presumed A-T heterozygosity of the parents, as indicated by the laboratory assay. 相似文献