Early modern human behavioural responses to marginal landscapes : Middle Stone Age geoarchaeology in Highland Lesotho

Figure S6. Effect of geographic representation of study patients on outcomes: mortality. Figure S7. Effect of geographic representation of study patients on outcomes: infections. (DOCX 190 kb

Managerial Preferences and Competition in Internal Capital Markets

It is often argued that managers follow some preference function. The internal capital market literature, for example, most commonly treats managers as empire builders who receive increased private ben-e ts from having more funds under their control. However, recent empirical work (Bertrand and Mullainathan 2003), shows that some managers might prefer to be left to run a limited number of projects. This "enjoying the quiet life " constitutes an alternative type of man-agerial behavior. In this contribution, we demonstrate how empire building and quiet life preferences work under competition. Our analy-sis shows that quiet life managers can generally only be motivated by threatening them with competition, while empire builders also value enhanced investment prospects. As we also demonstrate, this leads to di¤erent optimal wages in regard to managerial preferences. Ad-ditionally we identify two organizational ways to improve managerial incentives. Namely, by letting managers with di¤erent investment prospects compete for funds and by altering the ex ante distribution of funds among the department managers. Again, results vary signif-icantly with di¤erent managerial preferences

In Patients With Severe Alcoholic Hepatitis, Prednisolone Increases Susceptibility to Infection and Infection-Related Mortality, and Is Associated With High Circulating Levels of Bacterial DNA

Background & Aims Infections are common in patients with severe alcoholic hepatitis (SAH), but little information is available on how to predict their development or their effects on patients. Prednisolone is advocated for treatment of SAH, but can increase susceptibility to infection. We compared the effects of infection on clinical outcomes of patients treated with and without prednisolone, and identified risk factors for development of infection in SAH. Methods We analyzed data from 1092 patients enrolled in a double-blind placebo-controlled trial to evaluate the efficacy of treatment with prednisolone (40 mg daily) or pentoxifylline (400 mg 3 times each day) in patients with SAH. The 2 × 2 factorial design led to 547 patients receiving prednisolone; 546 were treated with pentoxifylline. The trial was conducted in the United Kingdom from January 2011 through February 2014. Data on development of infection were collected at evaluations performed at screening, baseline, weekly during admission, on discharge, and after 90 days. Patients were diagnosed with infection based on published clinical and microbiologic criteria. Risk factors for development of infection and effects on 90-day mortality were evaluated separately in patients treated with prednisolone (n = 547) and patients not treated with prednisolone (n = 545) using logistic regression. Pretreatment blood levels of bacterial DNA (bDNA) were measured in 731 patients. Results Of the 1092 patients in the study, 135 had an infection at baseline, 251 developed infections during treatment, and 89 patients developed an infection after treatment. There was no association between pentoxifylline therapy and the risk of serious infection (P = .084), infection during treatment (P = .20), or infection after treatment (P = .27). Infections classified as serious were more frequent in patients treated with prednisolone (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.27−2.92; P = .002). There was no association between prednisolone therapy and infection during treatment (OR, 1.04; 95% CI, 0.78−1.37; P = .80). However, a higher proportion (10%) of patients receiving prednisolone developed an infection after treatment than of patients not given prednisolone (6%) (OR, 1.70; 95% CI, 1.07−2.69; P = .024). Development of infection was associated with increased 90-day mortality in patients with SAH treated with prednisolone, independent of model for end-stage liver disease or Lille score (OR, 2.46; 95% CI, 1.41−4.30; P = .002). High circulating bDNA predicted infection that developed within 7 days of prednisolone therapy, independent of Model for End-Stage Liver Disease and white blood cell count (OR, 4.68; 95% CI, 1.80−12.17; P = .001). In patients who did not receive prednisolone, infection was not independently associated with 90-day mortality (OR, 0.94; 95% CI, 0.54−1.62; P = .82) or levels of bDNA (OR, 0.83; 95% CI, 0.39−1.75; P = .62). Conclusions Patients with SAH given prednisolone are at greater risk for developing serious infections and infections after treatment than patients not given prednisolone, which may offset its therapeutic benefit. Level of circulating bDNA before treatment could identify patients at high risk of infection if given prednisolone; these data could be used to select therapies for patients with SAH. EudraCT no: 2009-013897-42; Current Controlled Trials no: ISRCTN88782125

Clinical Frailty Scale (CFS) reliably stratifies octogenarians in German ICUs: a multicentre prospective cohort study

Background: In intensive care units (ICU) octogenarians become a routine patients group with aggravated therapeutic and diagnostic decision-making. Due to increased mortality and a reduced quality of life in this high-risk population, medical decision-making a fortiori requires an optimum of risk stratification. Recently, the VIP-1 trial prospectively observed that the clinical frailty scale (CFS) performed well in ICU patients in overall-survival and short-term outcome prediction. However, it is known that healthcare systems differ in the 21 countries contributing to the VIP-1 trial. Hence, our main focus was to investigate whether the CFS is usable for risk stratification in octogenarians admitted to diversified and high tech German ICUs. Methods: This multicentre prospective cohort study analyses very old patients admitted to 20 German ICUs as a sub-analysis of the VIP-1 trial. Three hundred and eight patients of 80 years of age or older admitted consecutively to participating ICUs. CFS, cause of admission, APACHE II, SAPS II and SOFA scores, use of ICU resources and ICU- and 30-day mortality were recorded. Multivariate logistic regression analysis was used to identify factors associated with 30-day mortality. Results: Patients had a median age of 84 [IQR 82–87] years and a mean CFS of 4.75 (± 1.6 standard-deviation) points. More than half of the patients (53.6%) were classified as frail (CFS ≥ 5). ICU-mortality was 17.3% and 30-day mortality was 31.2%. The cause of admission (planned vs. unplanned), (OR 5.74) and the CFS (OR 1.44 per point increase) were independent predictors of 30-day survival. Conclusions: The CFS is an easy determinable valuable tool for prediction of 30-day ICU survival in octogenarians, thus, it may facilitate decision-making for intensive care givers in Germany. Trial registration: The VIP-1 study was retrospectively registered on ClinicalTrials.gov (ID: NCT03134807 ) on May 1, 2017

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions

Background: Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). Methods: The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. Results: PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73–0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). Conclusion: PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. Trial registration: NCT01535534. Registered 14.02.201

Community library programs that work: Building youth and family literacy

A collection of versatile best practices for promoting literacy development by utilizing local community connections in school and public libraries. This book provides a fresh approach to learning as well as guidelines for creating dynamic and relevant library programs for children, teens, and families. Organized thematically, each chapter includes relevant topical research and three to eight community-focused approaches. Programs range from small, single-library initiatives in rural communities to multi-site, cross-border initiatives. This resource includes collaborative and locally inspired programs, many of which can be scaled to the budget of any library, school, or community organization

Sepsis und bestehende Komorbiditäten bei internistischen Intensivpatienten: Analyse der Todesursache durch unterschiedliche Kliniker – eine Pilotstudie

Abstract Background There is an ongoing debate as to whether death with sepsis is primarily caused by sepsis or, more often, by the underlying disease. There are no data on the influence of a researcher’s background on such an assessment. Therefore, the aim of this analysis was to assess the cause of death in sepsis and the influence of an investigator’s professional background on such an assessment. Materials and methods We performed a retrospective observational cohort study of sepsis patients treated in the medical intensive care unit (ICU) of a tertiary care center. For deceased patients, comorbidities and severity of illness were documented. The cause of death (sepsis or comorbidities or both combined) was independently assessed by four assessors with different professional backgrounds (medical student, senior physician in the medical ICU, anesthesiological intensivist, and senior physician specialized in the predominant comorbidity). Results In all, 78 of 235 patients died in hospital. Agreement between assessors about cause of death was low (κ 0.37, 95% confidence interval 0.29–0.44). Depending on the assessor, sepsis was the sole cause of death in 6–12% of cases, sepsis and comorbidities in 54–76%, and comorbidities alone in 18–40%. Conclusions In a relevant proportion of patients with sepsis treated in the medical ICU, comorbidities contribute significantly to mortality, and death from sepsis without relevant comorbidities is a rare event. Designation of the cause of death in sepsis patients is highly subjective and may be influenced by the professional background of the assessor.Zusammenfassung Hintergrund Es wird immer wieder diskutiert, ob der Tod bei Sepsis überwiegend durch die Sepsis oder häufiger durch eine Grunderkrankung verursacht wird. Es gibt keine Daten über den Einfluss des Hintergrunds eines Forschers auf eine solche Beurteilung. Ziel dieser Analyse war es daher, die Todesursache bei Sepsis und den Einfluss des beruflichen Hintergrunds des Beurteilers auf seine diesbezügliche Einschätzung zu bewerten. Methodik Wir führten eine retrospektive Kohortenstudie an Sepsispatienten durch, die auf der medizinischen Intensivstation eines tertiären Versorgungszentrums behandelt wurden. Bei verstorbenen Patienten wurden Komorbiditäten und der Schweregrad der Erkrankung dokumentiert. Die Todesursache (Sepsis oder Komorbiditäten oder beides zusammen) wurde unabhängig voneinander von 4 Beurteilern mit unterschiedlichem beruflichem Hintergrund (Medizinstudent, Oberarzt der medizinischen Intensivstation, anästhesiologischer Intensivmediziner und auf die vorherrschende Komorbidität spezialisierter Arzt) evaluiert. Ergebnisse Insgesamt starben 78 von 235 Patienten im Krankenhaus. Die Übereinstimmung zwischen den Beurteilern bezüglich der Todesursache war gering (κ 0,37; 95 %-Konfidenzintervall 0,29–0,44). Je nach Beurteiler wurde in 6–12 % der Fälle die Sepsis als alleinige Todesursache festgestellt, in 54–76 % die Sepsis gemeinsam mit den Komorbiditäten und in 18–40 % nur die Komorbiditäten. Diskussion Bei einem relevanten Anteil der auf der medizinischen Intensivstation behandelten Sepsispatienten tragen Komorbiditäten wesentlich zur Mortalität bei und der Tod durch Sepsis ohne relevante Komorbiditäten ist ein seltenes Ereignis. Die Beantwortung der Frage nach der Todesursache bei Sepsispatienten ist in hohem Maß subjektiv und kann durch den beruflichen Hintergrund des Beurteilers beeinflusst werden