Hochschule für Technik und Wirtschaft Dresden – University of Applied Sciences

BACKGROUND: Clinical pathways are structured multidisciplinary care plans used by health services to detail essential steps in the care of patients with a specific clinical problem. They aim to link evidence to practice and optimise clinical outcomes whilst maximising clinical efficiency. OBJECTIVES: To assess the effect of clinical pathways on professional practice, patient outcomes, length of stay and hospital costs. SEARCH STRATEGY: We searched the Database of Abstracts of Reviews of Effectiveness (DARE), the Effective Practice and Organisation of Care (EPOC) Register, the Cochrane Central Register of Controlled Trials (CENTRAL) and bibliographic databases including MEDLINE, EMBASE, CINAHL, NHS EED and Global Health. We also searched the reference lists of relevant articles and contacted relevant professional organisations. SELECTION CRITERIA: Randomised controlled trials, controlled clinical trials, controlled before and after studies and interrupted time series studies comparing stand alone clinical pathways with usual care as well as clinical pathways as part of a multifaceted intervention with usual care. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all titles to assess eligibility and methodological quality. Studies were grouped into those comparing clinical pathways with usual care and those comparing clinical pathways as part of a multifaceted intervention with usual care. MAIN RESULTS: Twenty-seven studies involving 11,398 participants met the eligibility and study quality criteria for inclusion. Twenty studies compared stand alone clinical pathways with usual care. These studies indicated a reduction in in-hospital complications (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.36 to 0.94) and improved documentation (OR 13.65: 95%CI 5.38 to 34.64). There was no evidence of differences in readmission to hospital or in-hospital mortality. Length of stay was the most commonly employed outcome measure with most studies reporting significant reductions. A decrease in hospital costs/ charges was also observed, ranging from WMD +261 US$ favouring usual care to WMD -4919 US$ favouring clinical pathways (in US$ dollar standardized to the year 2000). Considerable heterogeneity prevented meta-analysis of length of stay and hospital cost results. An assessment of whether lower hospital costs contributed to cost shifting to another health sector was not undertaken.Seven studies compared clinical pathways as part of a multifaceted intervention with usual care. No evidence of differences were found between intervention and control groups. AUTHORS' CONCLUSIONS: Clinical pathways are associated with reduced in-hospital complications and improved documentation without negatively impacting on length of stay and hospital costs.

Based on the nomenclature of the early papers in the field privacy by data minimization, we develop a terminology which is both expressive and precise. More particularly, we define anonymity, unlinkability, linkability, undetectability, unobservability, pseudonymity (pseudonyms and digital pseudonyms, and their attributes), identifiability, identity, partial identity, digital identity and identity management. In addition, we describe the relationships between these terms, give a rationale why we define them as we do, and sketch the main mechanisms to provide for the properties defined.

The last 60 years has seen unprecedented groundwater extraction and overdraft as well as development of new technologies for water treatment that together drive the advance in intentional groundwater replenishment known as managed aquifer recharge (MAR). This paper is the first known attempt to quantify the volume of MAR at global scale, and to illustrate the advancement of all the major types of MAR and relate these to research and regulatory advancements. Faced with changing climate and rising intensity of climate extremes, MAR is an increasingly important water management strategy, alongside demand management, to maintain, enhance and secure stressed groundwater systems and to protect and improve water quality. During this time, scientific research—on hydraulic design of facilities, tracer studies, managing clogging, recovery efficiency and water quality changes in aquifers—has underpinned practical improvements in MAR and has had broader benefits in hydrogeology. Recharge wells have greatly accelerated recharge, particularly in urban areas and for mine water management. In recent years, research into governance, operating practices, reliability, economics, risk assessment and public acceptance of MAR has been undertaken. Since the 1960s, implementation of MAR has accelerated at a rate of 5%/year, but is not keeping pace with increasing groundwater extraction. Currently, MAR has reached an estimated 10 km3/year, ~2.4% of groundwater extraction in countries reporting MAR (or ~1.0% of global groundwater extraction). MAR is likely to exceed 10% of global extraction, based on experience where MAR is more advanced, to sustain quantity, reliability and quality of water supplies.

AIMS: To assess if treatment with the alpha-glucosidase inhibitor acarbose can reduce cardiovascular events in type 2 diabetic patients. METHODS AND RESULTS: This meta-analysis included seven randomized, double-blind, placebo-controlled acarbose studies with a minimum treatment duration of 52 weeks. Type 2 diabetic patients valid for safety were randomized to either acarbose (n=1248) or placebo (n=932). The primary outcome measure was the time to develop a cardiovascular event. Primary analysis was conducted using Cox regression analysis. The effect of acarbose on metabolic parameters was also investigated. Acarbose therapy showed favourable trends towards risk reduction for all selected cardiovascular event categories. The treatment significantly reduced the risk for "myocardial infarction" (hazards ratio=0.36 [95% Cl 0.16-0.80], P=0.0120) and "any cardiovascular event" (0.65 [95% Cl 0.48-0.88], P=0.0061). Glycaemic control, triglyceride levels, body weight and systolic blood pressure also improved significantly during acarbose treatment. CONCLUSION: Intervention with acarbose can prevent myocardial infarction and cardiovascular disease in type 2 diabetic patients while most of them are already on intensive concomitant cardiovascular medication.

PURPOSE: Biomarkers for outcome after immune-checkpoint blockade are strongly needed as these may influence individual treatment selection or sequence. We aimed to identify baseline factors associated with overall survival (OS) after pembrolizumab treatment in melanoma patients. EXPERIMENTAL DESIGN: Serum lactate dehydrogenase (LDH), routine blood count parameters, and clinical characteristics were investigated in 616 patients. Endpoints were OS and best overall response following pembrolizumab treatment. Kaplan-Meier analysis and Cox regression were applied for survival analysis. RESULTS: Relative eosinophil count (REC) ≥1.5%, relative lymphocyte count (RLC) ≥17.5%, ≤2.5-fold elevation of LDH, and the absence of metastasis other than soft-tissue/lung were associated with favorable OS in the discovery (n = 177) and the confirmation (n = 182) cohort and had independent positive impact (all P < 0.001). Their independent role was subsequently confirmed in the validation cohort (n = 257; all P < 0.01). The number of favorable factors was strongly associated with prognosis. One-year OS probabilities of 83.9% versus 14.7% and response rates of 58.3% versus 3.3% were observed in patients with four of four compared to those with none of four favorable baseline factors present, respectively. CONCLUSIONS: High REC and RLC, low LDH, and absence of metastasis other than soft-tissue/lung are independent baseline characteristics associated with favorable OS of patients with melanoma treated with pembrolizumab. Presence of four favorable factors in combination identifies a subgroup with excellent prognosis. In contrast, patients with no favorable factors present have a poor prognosis, despite pembrolizumab, and additional treatment advances are still needed. A potential predictive impact needs to be further investigated. Clin Cancer Res; 22(22); 5487-96. ©2016 AACR.

The identity and unique capacity of cancer stem cells (CSC) to drive tumor growth and resistance have been challenged in brain tumors. Here we report that cells expressing CSC-associated cell membrane markers in Glioblastoma (GBM) do not represent a clonal entity defined by distinct functional properties and transcriptomic profiles, but rather a plastic state that most cancer cells can adopt. We show that phenotypic heterogeneity arises from non-hierarchical, reversible state transitions, instructed by the microenvironment and is predictable by mathematical modeling. Although functional stem cell properties were similar in vitro, accelerated reconstitution of heterogeneity provides a growth advantage in vivo, suggesting that tumorigenic potential is linked to intrinsic plasticity rather than CSC multipotency. The capacity of any given cancer cell to reconstitute tumor heterogeneity cautions against therapies targeting CSC-associated membrane epitopes. Instead inherent cancer cell plasticity emerges as a novel relevant target for treatment.

The purpose of this study was to determine cognitive correlates of olfactory performance across three different tasks. A total of 170 men and women (30-87 years of age) were assessed in olfactory sensitivity, discrimination, and identification. Also, participants were tested in a range of cognitive tests covering executive functioning, semantic memory, and episodic memory. Hierarchical regression analyses showed that proficiency in executive functioning and semantic memory contributed significantly to odor discrimination and identification performance, whereas all of the cognitive factors proved unrelated to performance in the odor threshold test. This pattern of outcome suggests that an individual's cognitive profile exerts a reliable influence on performance in higher order olfactory tasks.

OBJECTIVE: We tested the hypothesis that expression of transcripts adjacent to the chromosome 9p21 (Chr9p21) locus of coronary artery disease was affected by the genotype at this locus and associated with atherosclerosis risk. METHODS AND RESULTS: We replicated the locus for coronary artery disease (P=0.007; OR=1.28) and other manifestations of atherosclerosis such as carotid plaque (P=0.003; OR=1.31) in the Leipzig Heart Study, a cohort of 1134 patients with varying degree of angiographically assessed coronary artery disease. Expression analysis in peripheral blood mononuclear cells (n=1098) revealed that transcripts EU741058 and NR_003529 of antisense noncoding RNA in the INK4 locus (ANRIL) were significantly increased in carriers of the risk haplotype (P=2.1x10(-12) and P=1.6x10(-5), respectively). In contrast, transcript DQ485454 remained unaffected, suggesting differential expression of ANRIL transcripts at Chr9p21. Results were replicated in whole blood (n=769) and atherosclerotic plaque tissue (n=41). Moreover, expression of ANRIL transcripts was directly correlated with severity of atherosclerosis (EU741058 and NR_003529; P=0.02 and P=0.001, respectively). No consistent association of Chr9p21 or atherosclerosis was found with expression of other genes such as CDKN2A, CDKN2B, C9orf53, and MTAP. CONCLUSIONS: Our data provide robust evidence for an association of ANRIL but not CDKN2A, CDKN2B, C9orf53, and MTAP, with atherosclerosis and Chr9p21 genotype in a large cohort.

In AKI, dying renal cells release intracellular molecules that stimulate immune cells to secrete proinflammatory cytokines, which trigger leukocyte recruitment and renal inflammation. Whether the release of histones, specifically, from dying cells contributes to the inflammation of AKI is unknown. In this study, we found that dying tubular epithelial cells released histones into the extracellular space, which directly interacted with Toll-like receptor (TLR)-2 (TLR2) and TLR4 to induce MyD88, NF-κB, and mitogen activated protein kinase signaling. Extracellular histones also had directly toxic effects on renal endothelial cells and tubular epithelial cells in vitro. In addition, direct injection of histones into the renal arteries of mice demonstrated that histones induce leukocyte recruitment, microvascular vascular leakage, renal inflammation, and structural features of AKI in a TLR2/TLR4-dependent manner. Antihistone IgG, which neutralizes the immunostimulatory effects of histones, suppressed intrarenal inflammation, neutrophil infiltration, and tubular cell necrosis and improved excretory renal function. In summary, the release of histones from dying cells aggravates AKI via both its direct toxicity to renal cells and its proinflammatory effects. Because the induction of proinflammatory cytokines in dendritic cells requires TLR2 and TLR4, these results support the concept that renal damage triggers an innate immune response, which contributes to the pathogenesis of AKI.

1 Shadow economies all over the world: new estimates for 162 countries from 1999 to 20071 Friedrich Schneider, Andreas Buehn and Claudio E. Montenegro 1.1 INTRODUCTION Activities associated with shadow economies are facts of life around the world....

The influence of age and gender composition on group performance and self-reported health disorders was examined with data from 4,538 federal tax employees working in 222 natural work unit groups. As hypothesized, age diversity correlated positively with performance only in groups solving complex decision-making tasks, and this finding was replicated when analyzing performance data collected 1 year later. Age diversity was also positively correlated with health disorders--but only in groups working on routine decision-making tasks. Gender composition also had a significant effect on group performance, such that groups with a high proportion of female employees performed worse and reported more health disorders than did gender-diverse teams. As expected, effects of gender composition were most pronounced in large groups. Effects of age diversity were found when controlling for gender diversity and vice versa. Thus, age and gender diversity seem to play a unique role in performance and well-being. The moderating role of task complexity for both effects of age diversity and the moderating role of group size for both effects of gender diversity further suggest that the impact of these 2 variables depends on different group processes (e.g., knowledge exchange, variation in gender salience).

Psychological research on gender differences in self-presentation has already revealed that women place higher priority on creating a positive self-presentation, while men are less concerned about the image they present in face-to-face (ftf) communication. Nowadays, with the extensive use of new media, self-presentation is no longer so closely tied to ftf situations, but can also take place in the online world. Specifically, social networking sites (SNS), such as Facebook or MySpace, offer various features such as profile pictures, groups, and virtual bulletin boards with which users can create elaborated online representations of themselves. What remains open is whether this virtual self-presentation on SNS is subject to gender differences. Based on studies emphasizing gender-related differences in Internet communication and behavior in general, it can be assumed that men and women have different motives regarding their SNS usage as well. A multimethodological study, combining results of an online survey and a content analysis of 106 user profiles, assessed users' diverse motives for participating in SNS in general, and their use of specific profile elements or self-presentation in particular. In this sample of StudiVZ users, women tend to be more likely to use SNS for comparing themselves with others and for searching for information. Men, on the other hand, are more likely to look at other people's profiles to find friends. Moreover, women tend to use group names for their self-presentation and prefer adding portrait photos to their profiles, while men choose full-body shots.

Current global environmental issues raise unavoidable challenges for our use of natural resources. Supplying the human population with clean water is becoming a global problem. Numerous organic and inorganic impurities in municipal, industrial, and agricultural waters, ranging from microplastics to high nutrient loads and heavy metals, endanger our nutrition and health. The development of efficient wastewater treatment technologies and circular economic approaches is thus becoming increasingly important. The biomass production of microalgae using industrial wastewater offers the possibility of recycling industrial residues to create new sources of raw materials for energy and material use. This review discusses algae-based wastewater treatment technologies with a special focus on industrial wastewater sources, the potential of non-conventional extremophilic (thermophilic, acidophilic, and psychrophilic) microalgae, and industrial algae-wastewater treatment concepts that have already been put into practice.

BACKGROUND: Ca2+ leak from the sarcoplasmic reticulum (SR) may play an important role in triggering and/or maintaining atrial arrhythmias, including atrial fibrillation (AF). Protein kinase A (PKA) hyperphosphorylation of the cardiac ryanodine receptor (RyR2) resulting in dissociation of the channel-stabilizing subunit calstabin2 (FK506-binding protein or FKBP12.6) causes SR Ca2+ leak in failing hearts and can trigger fatal ventricular arrhythmias. Little is known about the role of RyR2 dysfunction in AF, however. METHODS AND RESULTS: Left and right atrial tissue was obtained from dogs with AF induced by rapid right atrial pacing (n=6 for left atrial, n=4 for right atrial) and sham instrumented controls (n=6 for left atrial, n=4 for right atrial). Right atrial tissue was also collected from humans with AF (n=10) and sinus rhythm (n=10) and normal cardiac function. PKA phosphorylation of immunoprecipitated RyR2 was determined by back-phosphorylation and by immunoblotting with a phosphospecific antibody. The amount of calstabin2 bound to RyR2 was determined by coimmunoprecipitation. RyR2 channel currents were measured in planar lipid bilayers. Atrial tissue from both the AF dogs and humans with chronic AF showed a significant increase in PKA phosphorylation of RyR2, with a corresponding decrease in calstabin2 binding to the channel. Channels isolated from dogs with AF exhibited increased open probability under conditions simulating diastole compared with channels from control hearts, suggesting that these AF channels could predispose to a diastolic SR Ca2+ leak. CONCLUSIONS: SR Ca2+ leak due to RyR2 PKA hyperphosphorylation may play a role in initiation and/or maintenance of AF.

The use of multiple antennas at base stations is a key component in the design of cellular communication systems that can meet high-capacity demands in the downlink. Under ideal conditions, the gain of employing multiple antennas is well-recognized: the data throughput increases linearly with the number of transmit antennas if the spatial dimension is utilized to serve many users in parallel. The practical performance of multi-cell systems is, however, limited by a variety of nonidealities, such as insufficient channel knowledge, high computational complexity, heterogeneous user conditions, limited backhaul capacity, transceiver impairments, and the constrained level of coordination between base stations. This tutorial presents a general framework for modeling different multi-cell scenarios, including clustered joint transmission, coordinated beamforming, interference channels, cognitive radio, and spectrum sharing between operators. The framework enables joint analysis and insights that are both scenario independent and dependent. The performance of multi-cell systems depends on the resource allocation; that is, how the time, power, frequency, and spatial resources are divided among users. A comprehensive characterization of resource allocation problem categories is provided, along with the signal processing algorithms that solve them. The inherent difficulties are revealed: (a) the overwhelming spatial degrees-of-freedom created by the multitude of transmit antennas; and (b) the fundamental tradeoff between maximizing aggregate system throughput and maintaining user fairness. The tutorial provides a pragmatic foundation for resource allocation where the system utility metric can be selected to achieve practical feasibility. The structure of optimal resource allocation is also derived, in terms of beamforming parameterizations and optimal operating points. This tutorial provides a solid ground and understanding for optimization of practical multi-cell systems, including the impact of the nonidealities mentioned above. The Matlab code is available online for some of the examples and algorithms in this tutorial.

Leiomyosarcoma (LMS) is an aggressive mesenchymal malignancy with few therapeutic options. The mechanisms underlying LMS development, including clinically actionable genetic vulnerabilities, are largely unknown. Here we show, using whole-exome and transcriptome sequencing, that LMS tumors are characterized by substantial mutational heterogeneity, near-universal inactivation of TP53 and RB1, widespread DNA copy number alterations including chromothripsis, and frequent whole-genome duplication. Furthermore, we detect alternative telomere lengthening in 78% of cases and identify recurrent alterations in telomere maintenance genes such as ATRX, RBL2, and SP100, providing insight into the genetic basis of this mechanism. Finally, most tumors display hallmarks of "BRCAness", including alterations in homologous recombination DNA repair genes, multiple structural rearrangements, and enrichment of specific mutational signatures, and cultured LMS cells are sensitive towards olaparib and cisplatin. This comprehensive study of LMS genomics has uncovered key biological features that may inform future experimental research and enable the design of novel therapies.

This investigation attempts to answer the question why more and more parents have chosen the Gymnasium for their children's secondary school education in post‐war West Germany. Based on the theory of subjective expected utility, the crucial mechanisms of parental educational decisions have been emphasized. From this perspective it is assumed that increasing educational motivation coupled with changes in the subjective evaluation of the cost–benefit of education were important conditions for an increasing participation in upper secondary schools. These were, however, in turn, the result of educational expansion. The empirical analyses for three time‐periods in the 1960s, 1970s, and 1980s confirm these assumptions to a large degree. Additionally, empirical evidence was found to suggest that in addition to the intentions of parents and the educational career of their children, structural moments of educational expansion and their own inertia played an important role in the pupils' transition from one educational level to the next. Finally, evidence was found that persistent class‐specific educational inequality stems from a constant balance in the relative cost–benefit advantages between social classes as well as from an increasing difference of primary origin effect between social classes in the realization of their educational choice.

We describe CShapes, a new dataset that provides historical maps of state boundaries and capitals in the post-World War II period. The dataset is coded according to both the Correlates of War and the CitationGleditsch and Ward (1999) state lists, and is therefore compatible with a great number of existing databases in the discipline. Provided in a geographic data format, CShapes can be used directly with standard GIS software, allowing a wide range of spatial computations. In addition, we supply a CShapes package for the R statistical toolkit. This package enables researchers without GIS skills to perform various useful operations on the GIS maps. The paper introduces the CShapes dataset and structure and gives three examples of how to use CShapes in political science research. First, we show how results from quantitative analysis can be depicted intuitively as a map. The second application gives an example of computing indicators on the CShapes maps, which can then be used in statistical tests. Third, we illustrate the use of CShapes for generating different weights matrices in spatial statistical applications. All the examples can be replicated using the freely available R package and do not require specialized GIS skills. The dataset is available for download from the CShapes website (http://nils.weidmann.ws/projects/cshapes).

This paper presents the results of the neuro-fuzzy model using remote-sensing data and geographic information system for landslide susceptibility analysis in a part of the Cameron Highlands areas in Malaysia. Landslide locations in the study area were identified by interpreting aerial photographs and satellite images, supported by extensive field surveys. Landsat TM satellite imagery was used to map the vegetation index. Maps of the topography, lineaments, Normalized Difference Vegetation Index (NDVI), and land cover were constructed from the spatial data sets. Eight landslide conditioning factors such as altitude, slope gradient, curvature, distance from the drainage, distance from the road, lithology, distance from the faults, and NDVI were extracted from the spatial database. These factors were analyzed using a neuro-fuzzy model adaptive neuro-fuzzy inference system to produce the landslide susceptibility maps. During the model development works, a total of five landslide susceptibility models were constructed. For verification, the results of the analyses were then compared with the field-verified landslide locations. Additionally, the receiver operating characteristic curves for all landslide susceptibility models were drawn, and the area under curve values were calculated. Landslide locations were used to validate the results of the landslide susceptibility map, and the verification results showed a 97% accuracy for model 5, employing all parameters produced in the present study as the landslide conditioning factors. The validation results showed a sufficient agreement between the obtained susceptibility map and the existing data on the landslide areas. Qualitatively, the model yields reasonable results, which can be used for preliminary land-use planning purposes.

We have measured the spin-dependent structure function ${g}_{1}^{p}$ in inclusive deep-inelastic scattering of polarized muons off polarized protons, in the kinematic range $0.003&lt;x&lt;0.7$ and $1{\mathrm{GeV}}^{2}&lt;{Q}^{2}&lt;60{\mathrm{GeV}}^{2}.$ A next-to-leading order QCD analysis is used to evolve the measured ${g}_{1}^{p}{(x,Q}^{2})$ to a fixed ${Q}_{0}^{2}.$ The first moment of ${g}_{1}^{p}$ at ${Q}_{0}^{2}=10{\mathrm{GeV}}^{2}$ is ${\ensuremath{\Gamma}}_{1}^{p}=0.136\ifmmode\pm\else\textpm\fi{}0.013$ (stat) $\ifmmode\pm\else\textpm\fi{}0.009$ (syst) $\ifmmode\pm\else\textpm\fi{}0.005$ (evol). This result is below the prediction of the Ellis-Jaffe sum rule by more than two standard deviations. The singlet axial charge ${a}_{0}$ is found to be $0.28\ifmmode\pm\else\textpm\fi{}0.16.$ In the Adler-Bardeen factorization scheme, $\ensuremath{\Delta}g\ensuremath{\simeq}2$ is required to bring \ensuremath{\Delta}\ensuremath{\Sigma} in agreement with the quark-parton model. A combined analysis of all available proton, deuteron, and ${}^{3}\mathrm{He}$ data confirms the Bjorken sum rule.