Materials Imaging and Dynamics (MID) instrument at the European X-ray Free-Electron Laser Facility.

The Materials Imaging and Dynamics (MID) instrument at the European X-ray Free-Electron Laser (EuXFEL) facility is described. EuXFEL is the first hard X-ray free-electron laser operating in the MHz repetition range which provides novel science opportunities. The aim of MID is to enable studies of nano-structured materials, liquids, and soft- and hard-condensed matter using the bright X-ray beams generated by EuXFEL. Particular emphasis is on studies of structure and dynamics in materials by coherent scattering and imaging using hard X-rays. Commission of MID started at the end of 2018 and first experiments were performed in 2019.

Efficacy of piperacillin in combination with novel ß-lactamase inhibitor IID572 against ß-lactamase-producing strains of Enterobacteriaceae and Staphylococcus aureus in murine neutropenic thigh infection models.

OBJECTIVES: The neutropenic murine thigh infection model was used to assess the effectiveness of IID572, a novel ß-lactamase inhibitor, in rescuing piperacillin activity against bacterial strains expressing various ß-lactamase enzymes. METHODS: Mice (n = 4/group) were inoculated with Enterobacteriaceae or Staphylococcus aureus bacterial strains expressing a range of ß-lactamases via intramuscular injection. Two hours after bacterial inoculation, subcutaneous treatment with piperacillin/IID572 or piperacillin/tazobactam every 3 h was initiated. Animals were euthanized via CO2 24 h after the start of therapy and bacterial cfu (log10 cfu) per thigh was determined, and the static dose was calculated. RESULTS: In a dose-dependent manner, piperacillin/IID572 reduced the thigh bacterial burden in models established with Enterobacteriaceae producing class A, C and D ß-lactamases (e.g. ESBLs, KPC, CMY-2 and OXA-48). Piperacillin/IID572 was also efficacious against MSSA strains, including one producing ß-lactamase. Static doses of piperacillin/IID572 were calculable from animals infected with all strains tested and the calculated static doses ranged from 195 to 4612 mg/kg/day piperacillin, the active component in the combination. Of the 13 strains investigated, a 1 log10 bacterial reduction was achieved for 9 isolates and a 2 log10 reduction was achieved for 3 isolates; piperacillin/tazobactam was not efficacious against 6 of the 13 isolates tested. CONCLUSIONS: In contrast to tazobactam, IID572 was able to rescue piperacillin efficacy in murine thigh infection models established with ß-lactamase-producing strains of Enterobacteriaceae and S. aureus, including those expressing ESBLs or serine carbapenemases.

Anti-Müllerian hormone in managed African and Asian rhino species.

Serum collected across the lifespan of four managed rhino species: black (Diceros bicornis, n = 16), white (Ceratotherium simum simum, n = 19), greater one-horned (GOH, Rhinoceros unicornis, n = 11) and Sumatran (Dicerorhinus sumatrensis, n = 6) were validated and analyzed in an anti-Müllerian hormone (AMH) enzyme- linked immunoassay. Concentrations of AMH were examined over time, between sexes and throughout different reproductive states which included n = 3 female white rhinos immunocontracepted with porcine zona pellucida (pZP). Across species, males produced higher AMH concentrations compared to females. Among males, AMH concentrations varied by species aside from comparable values secreted between black and white rhinos. The GOH and Sumatran rhino secreted the highest and lowest male AMH concentrations, respectively. However, within each species, AMH concentrations were similar across male age categories. Preliminary insight into male AMH changes from birth to sexual maturity suggest its potential as a marker for onset of testicular maturation. Female black, GOH and Sumatran rhinos secreted comparable AMH concentrations which were higher than those in white rhino. Within each species, inter-individual variation in AMH secretion occurred among females of similar age. While AMH secretion did not differ across the ages sampled for female white (4->26 yr) and GOH (4-26 yr) rhinos, black and Sumatran rhinos >26 and <4 yr, respectively secreted lower AMH compared to conspecific females 7-26 yr of age. Two idiopathic infertility cases corresponded to low (outside species range) AMH values. The establishment of normative AMH concentrations in managed African and Asian rhinos provides an additional metric beyond traditional sex steroids to assess gonadal function. Further work is needed to determine if AMH can predict fertility potential in rhinos.

Pharmacokinetics and pharmacodynamics of the novel monobactam LYS228 in a neutropenic murine thigh model of infection.

Objectives: The neutropenic murine thigh infection model and a dose-fractionation approach were used to determine the pharmacokinetic/pharmacodynamic (PK/PD) relationship of LYS228, a novel monobactam antibiotic with activity against Enterobacteriaceae including carbapenem-resistant strains. Methods: Mice (n = 4 per group) were inoculated with Enterobacteriaceae strains via intramuscular injection. Two hours post-bacterial inoculation, treatment with LYS228 was initiated. Animals were euthanized with CO2 24 h after the start of therapy and bacterial counts (log10 cfu) per thigh were determined. PK parameters were calculated using free (f) plasma drug levels. Results: Following a dose-fractionation study, non-linear regression analysis determined that the predominant PK/PD parameter associated with antibacterial efficacy of LYS228 was the percentage of the dosing interval that free drug concentrations remained above the MIC (%fT>MIC). In a dose-dependent manner, LYS228 reduced the thigh bacterial burden in models established with Enterobacteriaceae producing ß-lactamase enzymes of all classes (e.g. ESBLs, NDM-1, KPC, CMY-2 and OXA-48). The range of the calculated static dose was 86-649 mg/kg/day for the isolates tested, and the magnitude of the driver of efficacy was 37-83 %fT>MIC. %fT>MIC was confirmed as the parameter predominantly driving efficacy as evidenced by a strong coefficient of determination (r2 = 0.68). Neutrophils had minimal impact on the effect of LYS228 in the murine thigh infection model. Conclusions: LYS228 is efficacious in murine thigh infection models using ß-lactamase-producing strains of Enterobacteriaceae, including those expressing metallo-ß-lactamases, ESBLs and serine carbapenemases, with the PK/PD driver of efficacy identified as %T>MIC.

[Interdisciplinary management in geriatric trauma surgery : Results of a survey in Austria]. / Interdisziplinäres Management in der Alterstraumatologie : Ergebnisse einer österreichweiten Umfrage.

BACKGROUND: The treatment of geriatric patients in the field of trauma surgery is increasingly gaining importance. To provide optimized treatment to these mostly multimorbid patients, interdisciplinary treatment concepts between trauma surgeons and geriatricians have been designed and implemented successfully. OBJECTIVES: The aim of this survey was to evaluate the current state of interdisciplinary management in the treatment of geriatric patients on trauma surgery wards throughout Austria. MATERIAL AND METHODS: The directors of 64 Austrian trauma surgery wards were surveyed using an online-questionnaire regarding the current interdisciplinary treatment of geriatric patients. RESULTS: A total of 39 (61 %) questionnaires were analyzed. Of the participating wards, 20 % distinguished between geriatric and non-geriatric patients. There were various criteria to classify the patients. The average percentage of patients older than 70 years was 43 %. Of the participating wards, 26 % had established a periodical cooperation between trauma surgeons and geriatricians and 8 % of the participants stated that there is no interdisciplinary cooperation. The establishment of an interdisciplinary treatment concept in the near future was planned in 28 %. The most commonly mentioned obstacle that prevented trauma surgery wards from establishing an interdisciplinary management model was the lack of personnel resources (59 %) - especially the lack of geriatricians (62 %). CONCLUSION: The survey's results underline the geriatric trauma surgery's great importance especially regarding the high percentage of geriatric patients, as well as the fact that the significance of the interdisciplinary cooperation between trauma surgeons and geriatricians is not yet perceived by the majority of Austrian trauma surgery wards.

Age-related changes in Egr1 transcription and DNA methylation within the hippocampus.

Aged animals show functional alterations in hippocampal neurons that lead to deficits in synaptic plasticity and changes in cognitive function. Transcription of immediate-early genes (IEGs), including Egr1, is necessary for processes such as long-term potentiation and memory consolidation. Here, we show an age-related reduction in the transcription of Egr1 in the dentate gyrus following spatial behavior, whereas in the area CA1, Egr1 is reduced at rest, but its transcription can be effectively driven by spatial behavior to levels equivalent to those observed in adult animals. One mechanism possibly contributing to these aging-related changes is an age-associated, CpG site-specific change in methylation in DNA associated with the promoter region of the Egr1 gene. Our results add to a growing body of work demonstrating that complex transcriptional and epigenetic changes in the hippocampus significantly contribute to brain and cognitive aging. © 2016 Wiley Periodicals, Inc.

Orthogeriatric co-management improves the outcome of long-term care residents with fragility fractures.

BACKGROUND: Fragility fractures are a major health care problem worldwide. Both hip and non-hip fractures are associated with excess mortality in the years following the fracture. Residents of long-term nursing homes represent a special high-risk group for poor outcomes. Orthogeriatric co-management models of care have shown in multiple studies to have medical as well as economic advantages, but their impact on this high-risk group has not been well studied. OBJECTIVE: We studied the outcome of long-term care residents with hip and non-hip fractures admitted to a geriatric fracture center. METHODS: The study design is a single center, prospective cohort study at a level-I trauma center in Austria running a geriatric fracture center. The cohort included all fragility fracture patients aged over 70 admitted from a long-term care residence from May 2009 to November 2011. The data set consisted of 265 patients; the mean age was 86.8 ± 6.7 years, and 80 % were female. The mean follow-up after the index fracture was 789 days, with a range from 1 to 1842 days. Basic clinical and demographic data were collected at hospital admission. Functional status and mobility were assessed during follow-up at 3, 6, and 12 months. Additional outcome data regarding readmissions for new fractures were obtained from the hospital information database; mortality was crosschecked with the death registry from the governmental institute of epidemiology. RESULTS: 187 (70.6 %) patients died during the follow-up period, with 78 patients (29.4 %) dying in the first year. The mean life expectancy after the index fracture was 527 (±431) days. Differences in mortality rates between hip and non-hip fracture patients were not statistically significant. Compared to reported mortality rates in the literature, hip fracture patients in this orthogeriatric-comanaged cohort had a significantly reduced one-year mortality [OR of 0.57 (95 % CI 0.31-0.85)]. After adjustment for confounders, only older age (OR 1.091; p = 0.013; CI 1.019-1.169) and a lower Parker Mobility Scale (PMS) (OR 0.737; p = 0.022; CI 0.568-0.957) remained as independent predictors. During follow-up, 62 patients (23.4 %) sustained at least one subsequent fracture, and 10 patients (3.4 %) experienced multiple fractures; 29 patients (10.9 %) experienced an additional fracture within the first year. Nearly, half (47.1 %) regained their pre-fracture mobility based on the PMS. CONCLUSION: Despite the generally poor outcomes for fragility fracture patients residing in long-term care facilities, orthogeriatric co-management appears to improve the outcome of high-risk fragility fracture patients. One-year mortality was 29.4 % in this cohort, significantly lower than in comparable trials. Orthogeriatric co-management may also have positive impacts on both functional outcome and the risk of subsequent fractures.

The effects of an overnight holding of whole blood at room temperature on haemoglobin modification and in vitro markers of red blood cell aging.

BACKGROUND: Some effects of the red blood cell (RBC) storage lesion are well documented whereas others are not. Whether a period of room temperature hold (RTH) during RBC production enhances the RBC storage lesion has remained controversial. In this study, we compared whole blood (WB)-derived RBCs produced after 24-h RTH with rapidly cooled (RC) RBCs and tested them for classical metabolic markers and signs of oxidative damage. STUDY DESIGN AND METHODS: SAGM-RBCs were prepared from mixed and split pairs (n = 12) of WB units. RBCs prepared after a 24-h period of RTH on day+1 after collection (RTH-RBCs) were compared with RC-RBCs. All RBCs were stored at 4°C for 42 days with assay of in vitro variables on days+1, +15, +22, +29 and +42. The study examined standard quality parameters, glutathione, catalase and superoxide dismutase (SOD) activities, and indicative markers of oxidative cell damage including post-translational haemoglobin modification, malondialdehyde (MDA), and phosphatidylserine expression. RESULTS: RTH-RBCs exhibited decreased levels of potassium (1·98 ± 0·26 vs. 5·23 ± 0·65 mmol/l) and of 2,3-diphosphoglycerate (2,3-DPG) on day+1 compared with RC-RBCs. Haemolysis rate on day+42 was higher in RTH-RBCs than in RC-RBCs (0·52 ± 0·13 vs. 0·37 ± 0·12%). The phosphatidylserine expression amounted to 0·25 ± 0·20% in RTH-RBCs and 0·07 ± 0·12% in RC-RBCs. Haemoglobin modification was not different between both RBC groups. RTH-RBCs showed slightly higher MDA concentration on days +29 and +42. CONCLUSIONS: RC-RBCs and RTH-RBCs show only small differences of classical in vitro parameters and no relevant differences in antioxidative metabolism and oxidative haemoglobin modification. These findings do not explain the loss observed in in vivo survival studies with RBCs.

Efficacy and tolerability studies evaluating a sleep aid and analgesic combination of naproxen sodium and diphenhydramine in the dental impaction pain model in subjects with induced transient insomnia.

STUDY OBJECTIVES: The aim of this study was to evaluate the efficacy and tolerability of novel combination naproxen sodium (NS) and diphenhydramine (DPH) in subjects with postoperative dental pain along with transient insomnia induced by 5 h sleep phase advance. The present studies aimed to demonstrate the added benefit and optimal dosages of the combination product over individual ingredients alone in improving sleep and pain. METHODS: Each of the two studies was a two-centre, randomised, double-blind and double-dummy trial. In the first study, subjects were randomised into one of the following treatment arms: NS 440 mg/DPH 50 mg, NS 220 mg/DPH 50 mg, NS 440 mg or DPH 50 mg. In the second study, subjects received either NS 440 mg/DPH 25 mg, NS 440 mg or DPH 50 mg. The co-primary end-points in both studies were wake time after sleep onset (WASO) and sleep latency (SL) measured by actigraphy. Other secondary sleep and pain end-points were also assessed. RESULTS: The intent-to-treat population included 712 and 267 subjects from studies one and two, respectively. In the first study, only the NS 440 mg/DPH 50 mg combination showed significant improvements in both WASO vs. NS alone (-70.3 min p = 0.0002) and SL vs. DPH alone (25.50 and 41.50 min respectively, p < 0.0001). In the second study, the NS 440 mg/DPH 25 mg combination failed to show any significant improvements vs. either component alone. CONCLUSIONS: Only the NS 440 mg/DPH 50 mg combination demonstrated improvement in both sleep latency vs. DPH 50 mg and sleep maintenance (WASO) vs. NS 440 mg. There were no serious or unexpected adverse events reported in either study. CLINICAL TRIAL REGISTRATION: NCT01280591 (study 1); NCT01495858 (study 2).

Multilocular sinonasal malignant melanoma: a poor prognostic subgroup?

Clinical observations show that two subtypes of sinonasal malignant melanoma exist: uni- and multilocular melanoma. The aim of this retrospective study was to determine the prevalence and outcome of multilocular sinonasal malignant melanoma. All patients with sinonasal malignant melanoma treated at our institution between 1992 and 2011 were included. Survival and recurrence data were analyzed related to the distribution pattern of the tumors and other factors. Twenty-five patients were identified and included in the analysis. Seven patients (28 %) suffered from multilocular, the remaining 18 patients (72 %) from unilocular sinonasal malignant melanoma. The first group showed a significantly worse disease-free survival, whereas disease-specific and overall survival did not differ between the two subtypes. Multilocular sinonasal malignant melanoma is associated with an unfavorable disease-free survival compared to its unilocular counterpart.

Fragility non-hip fracture patients are at risk.

INTRODUCTION: Fragility fractures are a growing worldwide health care problem. Hip fractures have been clearly associated with poor outcomes. Fragility fractures of other bones are common reasons for hospital admission and short-term disability, but specific long-term outcome studies of non-hip fragility fractures are rare. The aim of our trial was to evaluate the 1-year outcomes of non-hip fragility fracture patients. METHODS: This study is a retrospective cohort review of 307 consecutive older inpatient non-hip fracture patients. Patient data for analysis included fracture location, comorbidity prevalence, pre-fracture functional status, osteoporosis treatments and sociodemographic characteristics. The main outcomes evaluated were 1-year mortality and post-fracture functional status. RESULTS: As compared to the expected mortality, the observed 1-year mortality was increased in the study group (17.6 vs. 12.2 %, P = 0.005). After logistic regression, three variables remained as independent risk factors for 1-year mortality among non-hip fracture patients: malnutrition (OR 3.3, CI 1.5-7.1), Charlson comorbidity index (CCI) (OR 1.3, CI 1.1-1.5) and the Parker Mobility Score (PMS) (OR 0.85, CI 0.74-0.98). CCI and PMS were independent risk factors for a high grade of dependency after 1 year. Management of osteoporosis did not significantly improve after hospitalization due to a non-hip fragility fracture. CONCLUSION: The outcomes of older non-hip fracture patients are comparable to the poor outcomes of older hip fracture patients, and appear to be primarily related to comorbidities, pre-fracture function and nutritional status. The low rate of patients on osteoporosis medications likely reflects the insufficient recognition of the importance of osteoporosis assessment and treatment in non-hip fracture patients. Increased clinical and academic attention to non-hip fracture patients is needed.

Selection of multiple umbrella species for functional and taxonomic diversity to represent urban biodiversity.

Surrogates, such as umbrella species, are commonly used to reduce the complexity of quantifying biodiversity for conservation purposes. The presence of umbrella species is often indicative of high taxonomic diversity; however, functional diversity is now recognized as an important metric for biodiversity and thus should be considered when choosing umbrella species. We identified umbrella species associated with high taxonomic and functional biodiversity in urban areas in Switzerland. We analyzed 39,752 individuals of 574 animal species from 96 study plots and 1397 presences of 262 plant species from 58 plots. Thirty-one biodiversity measures of 7 taxonomic groups (plants, spiders, bees, ground beetles, lady bugs, weevils and birds) were included in within- and across-taxa analyses. Sixteen measures were taxonomical (species richness and species diversity), whereas 15 were functional (species traits including mobility, resource use, and reproduction). We used indicator value analysis to identify umbrella species associated with single or multiple biodiversity measures. Many umbrella species were indicators of high biodiversity within their own taxonomic group (from 33.3% in weevils to 93.8% in birds), to a lesser extent they were indicators across taxa. Principal component analysis revealed that umbrella species for multiple measures of biodiversity represented different aspects of biodiversity, especially with respect to measures of taxonomic and functional diversity. Thus, even umbrella species for multiple measures of biodiversity were complementary in the biodiversity aspects they represented. Thus, the choice of umbrella species based solely on taxonomic diversity is questionable and may not represent biodiversity comprehensively. Our results suggest that, depending on conservation priorities, managers should choose multiple and complementary umbrella species to assess the state of biodiversity.

Algorithm for anticoagulation management in geriatric hip fracture patients--Surgeons save Blood.

During the past decades, the number of hip fractures has been increasing steadily. Perioperative thromboprophylaxis has become a routine aspect in the care of geriatric hip fracture patients. In addition, a large proportion of these patients are already anticoagulated because of internistic comorbidities before they sustained the hip fracture. Although the management of preexisting anticoagulation in both orthopedic elective and emergency procedures is well reported, proximal femoral fractures are classified as "acute" and therefore represent neither of these two categories. In this study, we review the different options of handling preexisting anticoagulation and antiaggregation as well as perioperative thromboprophylaxis. The Innsbruck Algorithm for the management of anticoagulation in geriatric hip fracture patients suggests how perioperative bleeding risk can be minimized, while still addressing the underlying disease.

Differential hippocampal gene expression is associated with climate-related natural variation in memory and the hippocampus in food-caching chickadees.

There is significant and often heritable variation in cognition and its underlying neural mechanisms, yet specific genetic contributions to such variation are not well characterized. Black-capped chickadees present a good model to investigate the genetic basis of cognition because they exhibit tremendous climate-related variation in memory, hippocampal morphology and neurogenesis rates throughout the North American continent, and these cognitive traits appear to have a heritable basis. We examined the hippocampal transcriptome profiles of laboratory-reared chickadees from the two most divergent populations to test whether differential gene expression in the hippocampus is associated with population differences in spatial memory, hippocampal morphology and adult hippocampal neurogenesis rates. Using high-resolution mRNA sequencing coupled to a de novo transcriptome assembly, we generated 23 295 consensus sequences, which predicted 16 206 protein sequences with 13 982 showing high similarity to known protein sequences or conserved hypothetical proteins in other species. Of these, we identified differential expression in nearly 380 genes, with 47 genes specifically linked to neurogenesis, apoptosis, synaptic function, and learning and memory processes. Many of the other differentially expressed genes, however, may be associated with other functions. Our study presents the first avian hippocampal transcriptome, and it is the first study identifying differential gene expression associated with natural variation in cognition and the hippocampus. Our results provide additional support to the hypothesis that population differences in memory, hippocampal morphology and neurogenesis in chickadees have likely resulted from natural selection that appears to act on memory and its underlying neural mechanisms.

High-precision x-ray polarimetry.

The polarization purity of 6.457- and 12.914-keV x rays has been improved to the level of 2.4×10(-10) and 5.7×10(-10). The polarizers are channel-cut silicon crystals using six 90° reflections. Their performance and possible applications are demonstrated in the measurement of the optical activity of a sucrose solution.

Parental responsiveness moderates the association between early-life stress and reduced telomere length.

Early-life stress, such as maltreatment, institutionalization, and exposure to violence, is associated with accelerated telomere shortening. Telomere shortening may thus represent a biomarker of early adversity. Previous studies have suggested that responsive parenting may protect children from the negative biological and behavioral consequences of early adversity. This study examined the role of parental responsiveness in buffering children from telomere shortening following experiences of early-life stress. We found that high-risk children had significantly shorter telomeres than low-risk children, controlling for household income, birth weight, gender, and minority status. Further, parental responsiveness moderated the association between risk and telomere length, with more responsive parenting associated with longer telomeres only among high-risk children. These findings suggest that responsive parenting may have protective benefits on telomere shortening for young children exposed to early-life stress. Therefore, this study has important implications for early parenting interventions.