bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmakotherapie im Alter
Authors: Hefner G. , Hiemke C. 
Published: September 2018

ZusammenfassungBei Alterspatienten bestimmen nicht nur altersbedingte normale pharmakokinetische und pharmakodynamische Veränderungen, sondern auch Faktoren wie Lebensgewohnheiten oder chronische Erkrankungen die unterschiedliche Wirksamkeit und Verträglichkeit von Arzneimitteln im Vergleich zu jüngeren Patienten. Darüber hinaus sind Alterspatienten, insbesondere bei Komorbidität, von den meisten klinischen Studien ausgeschlossen. Daher gibt es nur beschränkte Evidenz für die Wirksamkeit vieler Medikamente. Die mangelhafte Evidenz und die große Variabilität der Pharmakokinetik und Pharmakodynamik erfordern im Alter eine individualisierte Pharmakotherapie. Zur Risikominimierung gilt es, inadäquate Medikamente, übermäßige Polypharmazie, unerwünschte Arzneimittelwechselwirkungen, aber auch eine medikamentöse Unterversorgung zu vermeiden. Das Dictum für Alterspatienten „Start low, go slow“ bezüglich Arzneimitteldosis sollte nicht bei jedem Patienten angewandt werden. Aufgrund der hohen interindividuellen Variabilität der Pharmakokinetik und Pharmakodynamik sollte bei Alterspatienten während der medikamentösen Behandlung ein enges Monitoring bzgl. Wirksamkeit und Verträglichkeit erfolgen. Blutspiegelmessungen von Psychopharmaka sollten genutzt werden, um pharmakokinetische Besonderheiten und die bei Alterspatienten häufigen Complianceprobleme zu erkennen.
Gewalt- und Tötungsdelikte junger Menschen
Authors: Remschmidt H. , Martin M. , Niebergall G. , Heinzel-Gutenbrunner M. 
Published: September 2018

Zusammenfassung
Fragestellung: Berichtet wird über eine Verlaufsuntersuchung an jugendlichen und heranwachsenden Gewalt- und Tötungsdelinquenten (n=114), deren legale Entwicklung über einen Zeitraum von 12,8 Jahren verfolgt werden konnte. Ergebnisse: Unter den psychiatrischen Diagnosen nach ICD-10 (nur in 18 Fällen war keine solche zu stellen) standen in der Delinquentenstichprobe an erster Stelle Persönlichkeits- und Verhaltensstörungen (41,2%), gefolgt von Störungen des Sozialverhaltens (27,2%), Schizophrenien und wahnhaften Störungen (7%) und Störungen durch psychotrope Substanzen (5,3%). 2 Probanden (1,8%) litten an einem hyperkinetischen Syndrom und je einer an einer affektiven bzw. neurotischen Störung. Im Vergleich mit einer parallelisierten Patientenstichprobe wiesen die Straftäter im Marburger Symptom Rating (MSR) signifikant höhere Werte auf in den Symptomen Dissoziales Verhalten, Aggressivität, Drogen- und Alkoholmissbrauch, jedoch signifikant niedrigere Angstwerte. 44 der Probanden (38,5%) entwickelten sich zu chronischen Straftätern, die auch nach der Indextat weitere Delikte verübten. Als Untergruppe der chronischen Straftäter konnten 13 (11,4% der Gesamtstichprobe) als Mehrfachintensivtäter identifiziert werden, die in jeder Hinsicht am auffälligsten waren.
Zerebrale und psychische Folgen sportassoziierter Schädelhirntraumata
Authors: Henkel K. , Schneider F. 
Published: September 2018

ZusammenfassungAuch leichte sportbedingte Schädelhirntraumata (SHT), inklusive Gehirnerschütterungen, können zu kurzfristigen, prolongierten und dauerhaften strukturellen und funktionellen Hirnschädigungen führen. Es besteht eine Evidenz für kumulative Schädigungsrisiken bei repetitiven Traumata. Die resultierenden Störungen betreffen kognitive, psychische und motorische Funktionen. Die strukturellen Alterationen reichen von Konnektivitätsänderungen über Fasertraktläsionen bis hin zu schwerwiegenden neurodegenerativen Prozessen. Mittels moderner Diagnoseverfahren lassen sich auch subklinische Funktionsstörungen nachweisen. Zudem mehren sich die Erkenntnisse, dass auch wiederholte subklinische SHT zu relevanten zerebralen Veränderungen führen können. Ein adäquates initiales Trauma-management kann dazu beitragen, schwerwiegende Folgeerscheinungen zu minimieren.
Utilizing TAPBPR to promote exogenous peptide loading onto cell surface MHC I molecules
Authors: Ilca F. Tudor , Neerincx Andreas , Wills Mark R. , de la Roche Maike , Boyle Louise H. 
Published: September 2018

SignificanceMHC class I molecules present small fragments of proteins from within the cell to alert the immune system to infection and cellular damage. Two protein accessory proteins, tapasin and TAPBPR, assist in the loading and selection of these peptides inside the cell. Here we show that one of these proteins, TAPBPR, surprisingly still works when delivered to the outside of cells and can be used to load peptides from viruses and tumours directly on surface MHC molecules. Therefore, we have found an efficient way to override the peptides naturally presented by cells and can use this to target immune responses against cells. This may prove beneficial to mount immune responses against cancer in the future.
Ecological Interdependence via Constraints
Authors: Eliot Christopher H. 
Published: September 2018

AbstractAlthough ecological theory has historically focused on negative interactions among populations, like competition and predation, ecologists and conservation biologists highlight the significance of interdependence. It is not clear, however, what is asserted in the causal hypothesis that one population is interdependent on others. This essay argues that the most informative causal regularities for representing dependencies are those connecting populations through environmental constraint variables. Interdependence among populations can thus be understood as constraint-mediated dependency relations connected in a circuit.
Fibroblast growth factor 23 is associated with fractional excretion of sodium in patients with chronic kidney disease
Authors: Xu Hong , Hashem Ali , Witasp Anna , Mencke Rik , Goldsmith David , Barany Peter , Bruchfeld Annette , Wernerson Annika , Carrero Juan-Jesus , Olauson Hannes 
Published: September 2018

Abstract

Background
Recent studies suggest that the phosphaturic hormone fibroblast growth factor 23 (FGF23) is involved in regulation of renal sodium excretion and blood pressure. There is evidence of both direct effects via regulation of the sodium-chloride symporter (NCC) in the distal tubule, and indirect effects through interactions with the renin–angiotensin–aldosterone system. However, clinical data on the association between FGF23 and renal sodium regulation is lacking. Herein, we investigated the associations of FGF23 with renal sodium handling and blood pressure in non-dialysis CKD patients.

Methods
This was a cross-sectional study encompassing 180 CKD patients Stage 1–5, undergoing renal biopsy. Plasma intact FGF23, 24-h urinary sodium excretion, fractional excretion of sodium (FENa) and blood pressure were measured at baseline. The association between FGF23 and renal sodium handling was explored by multivariate regression analysis.

Results
The median age was 52.8 years, 60.6% were men and the median estimated glomerular filtration rate (eGFR) was 50.6 mL/min/1.73 m2. In univariate analysis, FGF23 was positively associated with FENa (Spearman’s rho = 0.47; P < 0.001) and systolic blood pressure (rho = 0.17, P < 0.05), but not with plasma sodium, 24-h urinary sodium excretion or mean arterial blood pressure. The association between FGF23 and FENa remained significant after adjustment for potential confounders (multivariable adjusted β coefficient 0.60, P < 0.001). This association was stronger among the 107 individuals with eGFR <60 mL/min/1.73 m2 (β = 0.47, P = 0.04) and in the 73 individuals on any diuretics (β = 0.88, P < 0.001). Adjustment for measured GFR instead of eGFR did not alter the relationship.

Conclusions
FGF23 is independently associated with increased FENa in non-dialysis CKD patients. These data do not support the notion that FGF23 causes clinically significant sodium retention. Further studies are warranted to explore the mechanism underlying this association.
Social capital as an instrument for common pool resource management: a case study of irrigation management in Sri Lanka
Authors: Aida Takeshi 
Published: September 2018

Abstract
Although social capital is considered to be a key instrument for common pool resource (CPR) management, its effect among heterogenous players such as upstream and downstream farmers along an irrigation canal is not clear. Using a combination of lab-in-the-field experiments to measure social capital and household survey data in a unique natural experimental setting, this study shows that upstream farmers with higher trust toward the downstream farmers are more likely to be satisfied with their water usage. This finding is consistent with the hypothesis that upstream farmers with higher trust demand less water and leave more water in a canal because they expect reciprocal behaviour from downstream farmers. Since the incentive structures of irrigation management closely resemble those of the standard experiments to measure social capital, this finding also provides a unique case study of the real-world relevance of these experiments.
Minority Party Government and Independent MPs: A Comparative Analysis of Australia and Ireland
Authors: Kefford Glenn , Weeks Liam 
Published: September 2018

Abstract
Minority government is becoming more common. With support declining for traditional parties and increasing for anti-establishment movements, government formation is becoming increasingly difficult in many jurisdictions. While minority government has been the subject of much normative debate, one type of minority arrangement that has not attracted much attention is that involving independent parliamentarians. Government in most countries tends to be party government, but in this article, we examine the experience in Australia and Ireland of independents supporting minority government. We assess the performance of these administrations in terms of their stability, their productivity and their electoral performance. We find that, contrary to expectation, minority government involving independents is not a recipe for instability nor necessarily results in an efficient parliament.
Cue-related phase reset accounts for age differences in phasic alerting
Authors: Wiegand Iris , Sander Myriam C. 
Published: September 2018

AbstractAlertness is fundamental for the efficiency of information processing. A person’s level of alertness refers to the system’s state of general responsiveness, and can be temporarily increased by presenting a neutral warning cue shortly before an event occurs (Posner & Petersen, 1990). However, effects of alerts on subsequent stimulus processing are less consistent in older than in younger individuals. In this study, we investigated the neural underpinnings of age differences in processing of auditory alerting cues. We measured electroencephalographic power and phase locking in response to alerting cues in a visual letter report task, in which younger but not older adults showed a cue-related behavioral advantage.Alerting cues evoked a significant increase in power as well as in inter-trial phase locking, with a maximum effect in the alpha frequency (8–12 Hz) in both age groups. Importantly, these cue-related increases in phase locking and power were stronger in older than in younger adults and were negatively correlated with the behavioral alerting effect in the older sample.Our results are in accordance with the assumption that older adults’ neural responses may be more strongly driven by external input and less variable than younger adults’. A stronger resetting of the system in response to the auditory cue may have hindered older adults’ effective use of the warning signal to foster processing of the following visual stimulus.
Control of synaptic specificity by limiting promiscuous synapse formation
Authors: Xu Chundi , Theisen Emma , Rumbaut Elijah , Shum Bryan , Peng Jing , Tarnogorska Dorota , Borycz Jolanta A. , Tan Liming , Courgeon Maximilien , Meinertzhagen Ian A. , Pecot Matthew Y. 
Published: September 2018

SUMMARYThe ability of neurons to distinguish appropriate from inappropriate synaptic partners in their local environment is fundamental to the proper assembly and function of neural circuits. How synaptic partner selection is regulated is a longstanding question in Neurobiology. A prevailing hypothesis is that appropriate partners express complementary molecules that match them together and promote synaptogenesis. Dpr and DIP IgSF proteins bind heterophilically and are expressed in a complementary manner between synaptic partners in the Drosophila visual system. Here, we show that in the lamina, DIP mis-expression is sufficient to promote synapse formation with Dpr-expressing neurons, and that DIP proteins are not necessary for synaptogenesis but rather function to prevent ectopic synapse formation. These findings indicate that Dpr-DIP interactions regulate synaptic specificity by biasing synapse formation towards specific cell-types. We propose that synaptogenesis occurs independent of synaptic partner choice, and that precise synaptic connectivity is established by limiting promiscuous synapse formation.
Genetic insights into the social organisation of the Avar period elite in the 7thcentury AD Carpathian Basin
Authors: Csáky Veronika , Gerber Dániel , Koncz István , Csiky Gergely , Mende Balázs G. , Szeifert Bea , Egyed Balázs , Pamjav Horolma , Marcsik Antónia , Molnár Erika , Pálfi György , Gulyás András , Kovacsóczy Bernadett , Lezsák Gabriella M. , Lőrinczy Gábor , Szécsényi-Nagy Anna , Vida Tivadar 
Published: September 2018

AbstractAfter 568 AD the Avars settled in the Carpathian Basin and founded the Avar Qaganate that was an important power in Central Europe until the 9thcentury. Part of the Avar society was probably of Asian origin, however the localisation of their homeland is hampered by the scarcity of historical and archaeological data.Here, we study mitogenome and Y chromosomal STR variability of twenty-six individuals, a number of them representing a well-characterised elite group buried at the centre of the Carpathian Basin more than a century after the Avar conquest.The studied group has maternal and paternal genetic affinities to several ancient and modern East-Central Asian populations. The majority of the mitochondrial DNA variability represents Asian haplogroups (C, D, F, M, R, Y and Z). The Y-STR variability of the analysed elite males belongs only to five lineages, three N-Tat with mostly Asian parallels and two Q haplotypes. The homogeneity of the Y chromosomes reveals paternal kinship as a cohesive force in the organisation of the Avar elite strata on both social and territorial level. Our results indicate that the Avar elite arrived in the Carpathian Basin as a group of families, and remained mostly endogamous for several generations after the conquest.
Modulation of actin polymerization affects nucleocytoplasmic transport in multiple forms of Amyotrophic Lateral Sclerosis
Authors: Giampetruzzi Anthony , Danielson Eric W. , Jeon Maryangel , Gumina Valentia , Boopathy Sivakumar , Brown Robert H. , Landers John E. , Fallini Claudia 
Published: September 2018

ABSTRACTAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown etiology. Although defects in nucleocytoplasmic transport (NCT) may be central to the pathogenesis of ALS and other neurodegenerative diseases, the molecular mechanisms modulating the nuclear pore function are still largely unknown. Here we show that genetic and pharmacological modulation of actin polymerization disrupts nuclear pore integrity, nuclear import, and downstream pathways such as mRNA post-transcriptional regulation. Importantly, we demonstrate that modulation of actin homeostasis can rescue nuclear pore instability and dysfunction caused by mutant PFN1 as well as by C9ORF72 repeat expansions, the most common mutations in ALS patients. Collectively, our data link NCT defects to ALS-associated pathology and propose the regulation of actin homeostasis as a novel therapeutic strategy for ALS and other neurodegenerative diseases.
An interaction between Gβγ and RNA polymerase II regulates transcription in cardiac fibroblasts
Authors: Khan Shahriar M. , Martin Ryan D. , Gora Sarah , Bouazza Celia , Jones-Tabah Jace , Zhang Andy , MacKinnon Sarah , Trieu Phan , Clarke Paul B.S. , Tanny Jason C. , Hébert Terence E. 
Published: September 2018

SUMMARYGβγ subunits are involved in many different signalling processes in various compartments of the cell, including the nucleus. To gain insight into the functions of nuclear Gβγ, we investigated the functional role of Gβγ signalling in regulation of GPCR-mediated gene expression in primary rat neonatal cardiac fibroblasts. Following activation of the angiotensin II type I receptor in these cells, Gβγ dimers interact with RNA polymerase II (RNAPII). Our findings suggest that Gβ1recruitment to RNAPII negatively regulates the fibrotic transcriptional response, which can be overcome by strong fibrotic stimuli. The interaction between Gβγ subunits and RNAPII expands the role for Gβγ signalling in cardiac fibrosis. The Gβγ-RNAPII interaction was regulated by signaling pathways in HEK 293 cells that diverged from those operating in cardiac fibroblasts. Thus, the interaction may be a conserved feature of transcriptional regulation although such regulation may be cell-specific.
Multiple-kernel learning for genomic data mining and prediction
Authors: Wilson Christopher M. , Li Kaiqiao , Kuan Pei-Fen , Wang Xuefeng 
Published: September 2018

AbstractAdvances in medical technology have allowed for customized prognosis, diagnosis, and personalized treatment regimens that utilize multiple heterogeneous data sources. Multiple kernel learning (MKL) is well suited for integration of multiple high throughput data sources, however, there are currently no implementations of MKL in R. In this paper, we give some background material for support vector machine (SVM) and introduce an R package, RMKL, which provides R and C++ code to implement several MKL algorithms for classification and regression problems. The provided implementations of MKL are compared using benchmark data and TCGA ovarian cancer. We demonstrate that combining multiple data sources can lead to a better classification scheme than simply using a single data source.
Growth characteristics of pneumococcus vary with the chemical composition of the capsule and with environmental conditions
Authors: Tothpal Adrienn , Desobry Katherine , Joshi Shreyas , Wyllie Anne L. , Weinberger Daniel M. 
Published: September 2018

AbstractBackgroundPneumococcus, a bacterium that typically resides in the nasopharynx, is exposed to a variety of temperature and oxygen levels in the upper respiratory tract and as it invades the lung, tissues, and blood. The response to these variations likely varies by strain and could influence the fitness of a strain and its virulence. We sought to determine the effect of environmental variability on the growth characteristics of pneumococcus and to evaluate correlations between variability in growth characteristics between strains and biological and epidemiological characteristics.MethodsWe evaluated the effect of temperature and oxygen on the growth of 256 pneumococcal isolates representing 53 serotypes, recovered from healthy carriers and from disease patients. Strains were grown at a range of temperatures anaerobically or in ambient air with and without catalase and were monitored by reading the optical density. Regression models were used to evaluate bacterial and environmental factors associated with characteristics of the growth curves.ResultsMost isolates grew to the maximal density at the temperature of the nasopharynx (~33C) and under aerobic conditions (with catalase). Maximum density achieved was positively associated with the presence of N-acetylated sugars in the capsule and negatively associated with the presence of uronic acids. Reaching a greater density at an early time point was positively associated with the prevalence of serotypes among healthy carriers in the pre-vaccine period.DiscussionEnvironmental variability affects the growth of pneumococcus, with notable differences between isolates and by serotype. Such variability could be influenced by characteristics of the capsule and might affect virulence and transmissibility.
Design and Analysis of a Whole Body Non-Contact Electromagnetic Stimulation Device with Field Modulation
Authors: Makarov Sergey N. , Bogdanov Gene , Noetscher Gregory M. , Appleyard William , Ludwig Reinhold , Joutsa Juho , Deng Zhi-De 
Published: September 2018

AbstractThis study describes a whole-body, non-contact electromagnetic stimulation device based on the concept of a conventional MRI Radio Frequency (RF) resonating coil, but at a much lower resonant frequency (100–150 kHz), with a field modulation option (0.5–100 Hz) and with an input power of up to 3 kW. Its unique features include a high electric field level within the biological tissue due to the resonance effect and a low power dissipation level, or a low Specific Absorption Rate (SAR), in the body itself. Because of its large resonator volume together with non-contact coupling, the subject may be located anywhere within the coil over a longer period at moderate and safe electric field levels. The electric field effect does not depend on body position within the resonator. However, field penetration is deep anywhere within the body, including the extremities where muscles, bones, and peripheral tissues are mostly affected. A potential clinical application of this device is treatment of chronic pain. Substantial attention is paid to device safety; this includes both AC power safety and exposure of human subjects to electromagnetic fields. In the former case, we employ inductive coupling which eliminates a direct current path from AC power to the coil. Our design enhances overall device safety at any power level, even when operated under higher-power conditions. Human exposure to electromagnetic fields within the coil is evaluated by performing modeling with two independent numerical methods and with an anatomically realistic multi-tissue human phantom. We show that SAR levels within the body correspond to International Electrotechnical Commission (IEC) safety standards when the input power level of the amplifier driver does not exceed 3 kW. We also show that electric field levels generally comply with International Commission on Non-Ionizing Radiation Protection safety standards if the input power level does not exceed 1.5 kW.