Hospitalizations during the last months of life of nursing home residents: a retrospective cohort study from Germany

BACKGROUND: To describe hospitalisations of nursing home (NH) residents in Germany during their last months of life. METHODS: Retrospective cohort study on 792 NH residents in the Rhine-Neckar region in South-West Germany, newly institutionalized in the year 2000, who died until the study end (December 2001). Baseline variables were derived from a standardized medical examination routinely conducted by the medical service of the health care insurance plans in Germany. Information on hospitalisations and deaths was extracted form records of the pertinent health insurance plans. RESULTS: NH residents who died after NH stay of more than 1 year spent 5.8% of their last year of life in hospitals. Relative time spent in hospitals increased from 5.2% twelve months before death (N = 139 persons) to 24.1% in their last week of life (N = 769 persons). No major differences could be observed concerning age, gender or duration of stay in NH. Overall, 229 persons (28.9%) died in hospital. Among these, the last hospital stay lasted less than 3 days for 76 persons (31.9%). Another 25 persons (3.2%) died within three days after hospital discharge. CONCLUSION: Our study indicates that proximity of death is the most important driver of health care utilization among NH residents. The relation of age or gender to health care expenditures seem to be weak once time to death is controlled for. Duration of NH stay does not markedly change rates of hospitalisation during the last months of life

Charged Particle Production in Proton-, Deuteron-, Oxygen- and Sulphur-Nucleus Collisions at 200 GeV per Nucleon

The transverse momentum and rapidity distributions of net protons and negatively charged hadrons have been measured for minimum bias proton-nucleus and deuteron-gold interactions, as well as central oxygen-gold and sulphur-nucleus collisions at 200 GeV per nucleon. The rapidity density of net protons at midrapidity in central nucleus-nucleus collisions increases both with target mass for sulphur projectiles and with the projectile mass for a gold target. The shape of the rapidity distributions of net protons forward of midrapidity for d+Au and central S+Au collisions is similar. The average rapidity loss is larger than 2 units of rapidity for reactions with the gold target. The transverse momentum spectra of net protons for all reactions can be described by a thermal distribution with `temperatures' between 145 +- 11 MeV (p+S interactions) and 244 +- 43 MeV (central S+Au collisions). The multiplicity of negatively charged hadrons increases with the mass of the colliding system. The shape of the transverse momentum spectra of negatively charged hadrons changes from minimum bias p+p and p+S interactions to p+Au and central nucleus-nucleus collisions. The mean transverse momentum is almost constant in the vicinity of midrapidity and shows little variation with the target and projectile masses. The average number of produced negatively charged hadrons per participant baryon increases slightly from p+p, p+A to central S+S,Ag collisions.Comment: 47 pages, submitted to Z. Phys.

Bryostatin-1 Attenuates Ischemia-Elicited Neutrophil Transmigration and Ameliorates Graft Injury after Kidney Transplantation

Data Availability Statement: Not applicable.Copyright: © 2022 by the authors. Ischemia reperfusion injury (IRI) is a form of sterile inflammation whose severity determines short- and long-term graft fates in kidney transplantation. Neutrophils are now recognized as a key cell type mediating early graft injury, which activates further innate immune responses and intensifies acquired immunity and alloimmunity. Since the macrolide Bryostatin-1 has been shown to block neutrophil transmigration, we aimed to determine whether these findings could be translated to the field of kidney transplantation. To study the effects of Bryostatin-1 on ischemia-elicited neutrophil transmigration, an in vitro model of hypoxia and normoxia was equipped with human endothelial cells and neutrophils. To translate these findings, a porcine renal autotransplantation model with eight hours of reperfusion was used to study neutrophil infiltration in vivo. Graft-specific treatment using Bryostatin-1 (100 nM) was applied during static cold storage. Bryostatin-1 dose-dependently blocked neutrophil activation and transmigration over ischemically challenged endothelial cell monolayers. When applied to porcine renal autografts, Bryostatin-1 reduced neutrophil graft infiltration, attenuated histological and ultrastructural damage, and improved renal function. Our novel findings demonstrate that Bryostatin-1 is a promising pharmacological candidate for graft-specific treatment in kidney transplantation, as it provides protection by blocking neutrophil infiltration and attenuating functional graft injury.Royal Society Wolfson Foundation (RSWF\R3\18300 to F.N.E.G); Eastern Star New Idea Award, LSUHSC-S (to F.N.E.G. and J.S.A.)

Cytokeratin 18 in plasma of patients with gastrointestinal adenocarcinoma as a biomarker of tumour response

BACKGROUND: Plasma biomarkers may be particularly useful as a predictor or early marker of clinical response to treatment in addition to radiological imaging. Cytokeratin 18 (CK18) is an epithelial-specific cytokeratin that undergoes cleavage by caspases during apoptosis. Measurement of caspase-cleaved (CK18-Asp396) or total cytokeratin 18 (CK18) from epithelial-derived tumours could be a simple, non-invasive way to monitor or predict responses to treatment. METHODS: Soluble plasma CK18-Asp396 and CK18 were measured by ELISA from 73 patients with advanced gastrointestinal adenocarcinomas before treatment and during chemotherapy, as well as 100 healthy volunteers. RESULTS: Both CK18-Asp396 and total CK18 plasma levels were significantly higher in patients compared with the healthy volunteers (P = 0.015, P < 0.001). The total CK18 baseline plasma levels before treatment were significantly higher (P = 0.009) in patients who develop progressive disease than those who achieve partial response or stable disease and this correlation was confirmed in an independent validation set. The peak plasma levels of CK18 occurring in any cycle following treatment were also found to be associated with tumour response, but peak levels of CK18-Asp396 did not reach significance (P = 0.01, and P = 0.07, respectively). CONCLUSION: Plasma levels CK18 are a potential marker of tumour response in patients with advanced gastrointestinal malignancy

Three-Dimensional In Vivo Imaging of the Murine Liver: A Micro-Computed Tomography-Based Anatomical Study

Various murine models are currently used to study acute and chronic pathological processes of the liver, and the efficacy of novel therapeutic regimens. The increasing availability of high-resolution small animal imaging modalities presents researchers with the opportunity to precisely identify and describe pathological processes of the liver. To meet the demands, the objective of this study was to provide a three-dimensional illustration of the macroscopic anatomical location of the murine liver lobes and hepatic vessels using small animal imaging modalities. We analysed micro-CT images of the murine liver by integrating additional information from the published literature to develop comprehensive illustrations of the macroscopic anatomical features of the murine liver and hepatic vasculature. As a result, we provide updated three-dimensional illustrations of the macroscopic anatomy of the murine liver and hepatic vessels using micro-CT. The information presented here provides researchers working in the field of experimental liver disease with a comprehensive, easily accessable overview of the macroscopic anatomy of the murine liver

Queen mandibular pheromone: questions that remain to be resolved

The discovery of ‘queen substance’, and the subsequent identification and synthesis of keycomponents of queen mandibular pheromone, has been of significant importance to beekeepers and to thebeekeeping industry. Fifty years on, there is greater appreciation of the importance and complexity of queenpheromones, but many mysteries remain about the mechanisms through which pheromones operate. Thediscovery of sex pheromone communication in moths occurred within the same time period, but in this case,intense pressure to find better means of pest management resulted in a remarkable focusing of research activityon understanding pheromone detection mechanisms and the central processing of pheromone signals in themoth. We can benefit from this work and here, studies on moths are used to highlight some of the gaps in ourknowledge of pheromone communication in bees. A better understanding of pheromone communication inhoney bees promises improved strategies for the successful management of these extraordinary animals

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Order in Spontaneous Behavior

Brains are usually described as input/output systems: they transform sensory input into motor output. However, the motor output of brains (behavior) is notoriously variable, even under identical sensory conditions. The question of whether this behavioral variability merely reflects residual deviations due to extrinsic random noise in such otherwise deterministic systems or an intrinsic, adaptive indeterminacy trait is central for the basic understanding of brain function. Instead of random noise, we find a fractal order (resembling Lévy flights) in the temporal structure of spontaneous flight maneuvers in tethered Drosophila fruit flies. Lévy-like probabilistic behavior patterns are evolutionarily conserved, suggesting a general neural mechanism underlying spontaneous behavior. Drosophila can produce these patterns endogenously, without any external cues. The fly's behavior is controlled by brain circuits which operate as a nonlinear system with unstable dynamics far from equilibrium. These findings suggest that both general models of brain function and autonomous agents ought to include biologically relevant nonlinear, endogenous behavior-initiating mechanisms if they strive to realistically simulate biological brains or out-compete other agents

Extracting key information from historical data to quantify the transmission dynamics of smallpox

<p>Abstract</p> <p>Background</p> <p>Quantification of the transmission dynamics of smallpox is crucial for optimizing intervention strategies in the event of a bioterrorist attack. This article reviews basic methods and findings in mathematical and statistical studies of smallpox which estimate key transmission parameters from historical data.</p> <p>Main findings</p> <p>First, critically important aspects in extracting key information from historical data are briefly summarized. We mention different sources of heterogeneity and potential pitfalls in utilizing historical records. Second, we discuss how smallpox spreads in the absence of interventions and how the optimal timing of quarantine and isolation measures can be determined. Case studies demonstrate the following. (1) The upper confidence limit of the 99th percentile of the incubation period is 22.2 days, suggesting that quarantine should last 23 days. (2) The highest frequency (61.8%) of secondary transmissions occurs 3–5 days after onset of fever so that infected individuals should be isolated before the appearance of rash. (3) The U-shaped age-specific case fatality implies a vulnerability of infants and elderly among non-immune individuals. Estimates of the transmission potential are subsequently reviewed, followed by an assessment of vaccination effects and of the expected effectiveness of interventions.</p> <p>Conclusion</p> <p>Current debates on bio-terrorism preparedness indicate that public health decision making must account for the complex interplay and balance between vaccination strategies and other public health measures (e.g. case isolation and contact tracing) taking into account the frequency of adverse events to vaccination. In this review, we summarize what has already been clarified and point out needs to analyze previous smallpox outbreaks systematically.</p