bluuebunny/crossref_metadata_2025 huggingface dataset:
Campaigns to reduce mental illness stigma in Europe: a scoping review
Authors: Borschmann R. , Greenberg N. , Jones N. , Henderson R. C.
Published: September 2018

Background: Evidence has emerged in recent decades about effective and ineffective methods to reduce mental illness related stigma and discrimination. As more European countries start national anti-stigma campaigns, there is potentially more to learn from their experiences, but also a risk that, with such rapid developments, lessons may be missed.

Aim: This scoping review aims to identify and discuss European stigma reduction campaigns conducted to date.

Methods: We searched electronic databases, hand-searched reference lists of identified articles and contacted stigma experts to enquire about ongoing initiatives.

Results: We identified anti-stigma campaigns in 21 European countries and regions. We found considerable variation in their content, delivery formats, duration and target groups.

Conclusions: Although anti-stigma campaigns have been implemented in many European countries, the level of attention paid to sharing lessons learned is variable. It is vital that campaigns are evaluated, to maximise their potential impact both on the target population, and that the findings are disseminated widely to allow international learning.
Psychiatry in Russia
Authors: Krasnov V. N.
Published: September 2018

Russian psychiatry has dramatic history, and till now is at a transitional stage of development. It is facing the problems not only common in world psychiatry, but also specific for the Eastern Europe, in particular for Russia. Starting from the beginning of 1990s considerable changes have occurred in psychiatry, especially after 1992 when “The law on psychiatric care and guarantees of citizens rights in its provision was adopted”. It became the ideological and legislative basis for reforms. However there are the definite obstacles for structural reforms in psychiatry. They are as follows: unfavourable technical conditions in many psychiatric clinics, hypercentralization of psychiatric services, shortage of clinical psychologists and social workers in psychiatry, some difficulties in cooperation between psychiatric and general medical institutions. Economic difficulties of the transition period of Russia’s social development prevent overcoming these problem. They are being actively discussed and part of them is being gradually solved, e.g. organization of team work in mental health services, increasing number of specialists on social work, involvement of NGO’s in psychosocial rehabilitation.
Psychotherapie der Borderline-Persönlichkeitsstörung
Authors: Stiglmayr C.
Published: September 2018

Bei der Borderline-Persönlichkeitsstörung handelt es sich um eine schwere psychische Erkrankung, gekennzeichnet durch Störungen der Affektregulation, der Identität sowie der sozialen Interaktion. Die durch die BPS entstehenden Krankheitskosten sind mit 27 000 € pro Patient/Jahr als sehr hoch einzuschätzen. Aktuell gibt es vier therapeutische Verfahren zur Behandlung der BPS, die im Rahmen von kontrolliert-randomisierten Studien (RCT) untersucht worden sind. Von diesen Verfahren wird in diesem Beitrag die Dialektisch-Behaviorale-Therapie (DBT) näher dargestellt. Primäres Ziel der DBT-Behandlung ist eine emotionale Stabilisierung und damit die Reduktion schwerer Probleme auf der Verhaltensebene, wie z. B. suizidales oder schweres selbstschädigendes Verhalten. Die Wirksamkeit der DBT konnte in zahlreichen Studien belegt werden.
Chronische Depression und Persönlichkeitsstörung – zwei Seiten derselben Medaille?
Authors: Klein J. P. , Fassbinder E. , Schweiger U.
Published: September 2018

Häufig wird angenommen, bei einer chronischen Depression (CD) müsse auch immer eine Persönlichkeitsstörung (PS) vorliegen. Beides seien nur unterschiedliche Begriffe für dasselbe Phänomen. In diesem Beitrag beschreiben wir, dass vor allem Patienten, deren CD vor dem 21. Lebensjahr begann, häufiger an einer PS leiden. Dieser Komorbidität könnten gemeinsame Faktoren zugrunde liegen, welche die Entstehung und Aufrechterhaltung der Störungen erklären. Dazu zählen eine frühe Traumatisierung und das Bestehen von selbst herbeigeführten interpersonellen Problemen. Am Beispiel des für die CD entwickelten Cognitive Behavioral Analysis System of Psychotherapy beschreiben wir, wie diese zugrundeliegenden Probleme psychotherapeutisch bearbeitet werden können.
Die Behandlung von ADHS im Erwachsenenalter mit retardiertem Methylphenidat
Authors: Ahlers E. , Neuhaus A.
Published: September 2018

Die Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) im Erwachsenenalter ist mit verhaltensbezogenen und psychopharmakologischen Maßnahmen symptomatisch behandelbar. Die Ätiologie der Störung ist noch nicht zur Gänze geklärt, wobei genetische Faktoren einen großen Stellenwert einnehmen. Neurobiologisch wird ein Defizit dopaminerger und noradrenerger Funktionen modellhaft angenommen. Zur pharmakologischen Behand-lung stehen mehrere Substanzen zur Verfügung. Zugelassen sind aktuell in Deutschland zur Neueinstellung im Erwachsenenalter Medikinet® adult (Methylphenidat retard) und Strattera® (Atomoxetin). Eine Behandlung mit Methylphenidat gilt als erste Wahl. Methylphenidat wird dabei die Wirkung im Sinne eines starken Dopamin- und Noradrenalin-Wiederaufnahmehemmers als ursächlich für den therapeutischen Effekt zugeschrieben. Unerwünschte Wirkungen in der Behandlung mit Methylphenidat ergeben sich vordringlich aus den sympathomimetischen peripheren Effekten. An ein Missbrauchspotenzial und mögliche depressiogene Effekte sollte gedacht werden. Erste Daten aus Langzeitstudien lassen bei guter Verträglichkeit auf eine zuverlässige positive Wirkung auf die Kernsymptomatik, den Komorbiditätsstatus sowie auf assoziierte Probleme bei ADHS schließen. Es besteht weiterhin großer Forschungsbedarf was die Ursachen der Störung sowie die genaue Wirkungsweise der Substanzen angeht.
Neurobiologische Modelle bei somatoformen Beschwerden
Authors: Gündel H. , Noll-Hussong M.
Published: September 2018

Einleitung: Somatoforme Störungen sind eine in sich heterogene Gruppe. Schmerzen stellen dabei eine sehr häufige Symptomatik dar. Das Wissen über neurobiologische Korrelate somatoformer Schmerzen ist enorm gewachsen. Methodik: Mittels einer selektiven Literaturanalyse werden aktuelle Erkenntnisse zum Zusammenhang von somatoformen Schmerzen und zwischenmenschlichen Beziehungsstörungen dargestellt. Ergebnisse: Sowohl (frühkindliche) Beziehungstraumata als auch biografisch spätere und aktuelle Störungen der zwischenmenschlichen Beziehungen können sich in Form von chronischen Schmerzen äußern. Schmerz kann in einer Untergruppe von Betroffenen den Charakter eines Gefühls wie Wut, Angst oder Traurigkeit annehmen. Die diesbezüglichen neurobiologischen Grundlagen sind hochkomplex und betreffen u.a. sowohl genetische, molekulare und neurale Mechanismen. Schlussfolgerung: Die Ätiologie von somatoformen Störungen ist multifaktoriell, die Grenzen zwischen einer mehr primär psychoreaktiven bzw. psychosozialen und einer mehr primär biologischen Genese fließend. Psychosoziale Einflüsse spielen gerade in Anbetracht der modernen neurobiologischen Erkenntnisse bei vielen chronischen Schmerzpatienten eine wichtige Rolle. Primär seelischer Schmerz kann sich primär somatisch ausdrücken, aber auch in anderer Richtung gibt es eine entsprechende Beeinflussbarkeit. Daher sollte die Möglichkeit psychotherapeutischer (Mit-)Behandlung bei vorliegender chronischer Schmerzstörung immer sorgfältig geprüft werden. Hierbei müssen zusätzlich kulturelle wie historische Einflüsse berücksichtigt werden.
Komplexe affektive Erkrankungen – eine klinische Herausforderung
Authors: Jobst A. , Sabaß L. , Falkai P. , Padberg F.
Published: September 2018

Fragestellung: Patienten mit komplexer, anhaltender affektiver Symptomatik einschließlich verschiedener Verlaufsformen chronischer Depressionen sind schwer zu behandeln und stellen eine besondere Herausforderung dar. Auch die Diagnosefindung ist aufgrund von Komorbiditäten und fehlender spezifischer Diagnosekriterien oft erschwert. Die vorliegende Fallvignette zeigt Herangehensweisen in der Behandlung dieser komplexen Störungsbilder auf. Methode: Eine 33-jährige Patientin wurde mit einem depressiv-suizidalen Syndrom vor dem Hintergrund traumatischer Kindheitserfahrungen auf die psychiatrische Akutstation aufgenommen. Nach prolongierter Behandlung und Diagnosefindung wurde die Patientin mit der Arbeitsdiagnose einer „chronischen Depression“ zur stationären Psychotherapie auf die Spezialstation für komplexe affektive Erkrankungen verlegt. Dort lag der Schwerpunkt auf der psychotherapeutischen Behandlung nach dem Konzept des Cognitive Behavioral Analysis System of Psychotherapy (CBASP). Zusammenfassung: Mit diesem Fall beschreiben wir eine wirksame Therapiemethode für Patienten mit komplexen affektiven Erkrankungen. Auch für Patienten mit Komorbiditäten könnte das CBASP eine vielversprechende Behandlungsmethode sein.
Prävention – Herausforderungen an eine Entwicklungspsychiatrie
Authors: Schury K. , Fegert J. M.
Published: September 2018

Beeinträchtigte individuelle Lebensqualität und die zunehmende ökonomische Bedeutung psychischer Erkrankungen machen eine genuin entwicklungspsychiatrische Diskussion über Prävention und Frühintervention bei psychischen Erkrankungen unabdingbar. Allerdings scheint sich die medizinisch psychiatrische Kompetenz hierbei primär auf die kurative Seite zu beschränken oder beschränken zu lassen. In Europa existieren zahlreiche Präventionsprogramme. Die einzelnen Akteure sind jedoch oft unkoordiniert, Maßnahmen nicht abgestimmt und häufig nicht empirisch evaluiert. Wachsende Erkenntnisse über molekulare Entstehungsprozesse psychischer Erkrankungen lassen Therapieoptionen, die bereits in der Krankheitsentstehung ansetzen, zukünftig möglich erscheinen. Die Rolle von Surrogat-Markern und die Rahmenbedingungen für die Erforschung indizierter Präventions- und Frühinterventionsansätze müssen jedoch definiert werden. Die psychiatrischen Fächer könnten mit ihrer Expertise in der Evaluation von Interventionen und ihrem Wissen um protektive Faktoren und Entwicklungsverläufe wichtige Beiträge für eine empirischfundierte wirksame Prävention psychischer Störungen in der Lebensspanne leisten.
Experimentelle Behandlungsverfahren bei Angsterkrankungen - Einblick in die Therapieforschung
Authors: Vennewald N. , Diemer J. , Fallgatter A. , Mühlberger A. , Ströhle A. , Zwanzger P.
Published: September 2018

Angsterkrankungen gehören zu den häufigsten psychischen Störungen und stellen wegen ihrer erheblichen Tendenz zur Chronifizierung auch in sozioökonomischer Hinsicht eine Belastung dar. Therapeutisch zählen sowohl die Kognitive Verhaltenstherapie (KVT) als auch die Pharmakotherapie zu den Verfahren der ersten Wahl. Allerdings spricht ein Teil der Patienten nicht oder nur unzureichend auf die Behandlung an. Die Verbesserung bestehender sowie die Entwicklung neuer Therapieverfahren sind daher weiterhin zentrales Forschungsziel. Ein Forschungsansatz beschäftigt sich mit experimentellen Behandlungsverfahren, darunter die repetitive Transkranielle Magnetstimulation (rTMS), die Expositionstherapie in Virtueller Realität (VR) sowie die Augmentation einer Expositionstherapie mit D-Cycloserin (DCS).
Inhalatives Loxapin – Neue Option in der Therapie akuter Agitation bei Patienten mit Schizophrenie oder bipolaren
Störungen
Authors: Juckel G.
Published: September 2018

Inhalatives Loxapin ist eine neue nicht-invasive Therapieoption zur Behandlung akuter Agitation bei Patienten mit Schizophrenie oder bipolaren Störungen. Zu dem Wirkstoff selbst liegen umfangreiche Wirksamkeits- und Verträglichkeitsdaten vor, da er international bereits seit vielen Jahren in der Behandlung psychotischer Störungen eingesetzt wird. Klinische Studiendaten zu der neuen inhalativen Darreichungsform von Loxapin zeigen in der Behandlung leichter bis mittelschwerer Agitation eine rasche Wirkung auf die akute Symptomatik. Der in klinischen Studien dokumentierte Wirkeintritt ist mit zehn Minuten sehr schnell. Das nachfolgende Review fasst die pharmakologischen und klinischen Studiendaten zu inhalativem Loxapin zusammen.
Correction: Knowledge management for policy impact: the case of the European Commission’s Joint Research Centre
Authors: Topp Lene , Mair David , Smillie Laura , Cairney Paul
Published: September 2018

The affiliation for authors Lene Topp, David Mair and Laura Smillie was incorrectly stated as “Joint Research Centre, European Commission, Retieseweg 111, 2440, Geel, Belgium”. This has been corrected to “Joint Research Centre, European Commission, Brussels, Belgium”.

In Table 2, the row labeled “Advising policymakers”, in the column labeled “The cautionary tale” the cell reads “Researchers become marginalised and rarely trusted in day to day politics. Policymakers receive evidence but remain sure about its relevance and risk of inaction”. This has been corrected to “The cautionary tale” the cell reads “Researchers become marginalised and rarely trusted in day to day politics. Policymakers receive evidence but remain unsure about its relevance and risk of inaction”.

This has been corrected in both the HTML and PDF versions of this paper.
Building maps in collective variable space
Authors: Gimondi Ilaria , Tribello Gareth A. , Salvalaglio Matteo
Published: September 2018

Enhanced sampling techniques such as umbrella sampling and metadynamics are now routinely used to provide information on how the thermodynamic potential, or free energy, depends on a small number of collective variables (CVs). The free energy surfaces that one extracts by using these techniques provide a simplified or coarse-grained representation of the configurational ensemble. In this work, we discuss how auxiliary variables can be mapped in CV space. We show that maps of auxiliary variables allow one to analyze both the physics of the molecular system under investigation and the quality of the reduced representation of the system that is encoded in a set of CVs. We apply this approach to analyze the degeneracy of CVs and to compute entropy and enthalpy surfaces in CV space both for conformational transitions in alanine dipeptide and for phase transitions in carbon dioxide molecular crystals under pressure.
Experimental study on the transition between patterned and homogeneous glow in a pulse-modulated radio frequency atmospheric pressure dielectric barrier discharge in helium
Authors: Huo W. G. , Zhu Y. T. , Liu C. S. , Ding Z. F.
Published: September 2018

In a pulse-modulated radio frequency atmospheric pressure dielectric barrier discharge in helium, the influence of the pulse width on the transition from a patterned glow discharge to a homogeneous glow discharge is experimentally investigated. The experimental results show that the discharge mode can transit from a patterned glow to a homogeneous glow at a moderate pulse width (7 μs) but only has a patterned glow at a short pulse width (4 μs) or a homogeneous glow at a long pulse width (18 μs). The characteristic regions of patterned and homogeneous glow discharges are also acquired. The results can be explained using the breakdown characteristics of the pulse-modulated radio frequency atmospheric pressure discharge.
An automated instrument for polarization-enhanced broadband nuclear quadrupole resonance (NQR) spectroscopy
Authors: Glickstein Jarred , Mandal Soumyajit
Published: September 2018

An automated instrument for improving the sensitivity of nuclear quadrupole resonance (NQR) spectroscopy is presented. The device is capable of pre-polarizing samples within a custom Halbach-type permanent magnet and then moving them into an external probe for zero-field NQR detection. Polarization transfer between protons and nitrogen (14N) nuclei in the sample occurs during demagnetization, thus increasing the amplitude of the detected NQR signals. The sample motion profile is completely programmable, thus providing a high level of control over the sample position and velocity for optimizing the polarization transfer process for various samples. Moreover, the magnet and motion controller are combined with a shielded sample probe and ultra-broadband front-end electronics (both designed in-house) to realize a complete scientific instrument for 14N NQR experiments. Compared with previous work in the field, the system is designed to be programmable, robust, and easy to use. Experimental results from several samples are also presented.
Calculation of vibrational spectroscopic and geometrical characteristics of the [F(HF)2]− and [F(DF)2]− complexes using the second-order vibrational perturbation theory and a 6D variational method
Authors: Bulychev V. P. , Buturlimova M. V. , Tokhadze K. G.
Published: September 2018

Vibrational spectroscopic and average geometrical parameters of the strong H-bonded complexes [F(HF)2]− and [F(DF)2]− are determined for the first time from nine-dimensional (9D) perturbative and 6D variational calculations. The frequencies and intensities for all fundamental and some combination and overtone transitions obtained by the method of second-order vibrational perturbation theory (VPT2) are reported. A two-fold decrease in the H–F (D–F) stretching band frequency and a more than ten-fold increase in the intensity of this band upon complexation are predicted. The theoretical frequencies for both isolated isotopologues are in satisfactory agreement (to better than 70 cm−1) with the scarce experimental data obtained in condensed phases. The main purpose of variational calculations is to analyze the intermode anharmonic coupling and the changes in the geometrical parameters upon vibrational excitation and H/D isotopic substitution. The equilibrium nuclear configuration and the 2D potential energy surface (PES) of [F(HF)2]− for H–F stretches are calculated in the MP2/6-311++G(3df,3pd), CCSD(T)/6-311++G(3df,3pd), CCSD(T)/aug-cc-pVTZ, and CCSD(T)/d-aug-cc-pVTZ approximations with the basis set superposition error taken into account. Anharmonic vibrational problems are solved by the variational method for 2D, 4D, and 6D systems of H-bond and H–F (D–F) stretches and in-plane bends. The VPT2 calculations and calculations of the PESs for 4D and 6D systems are performed in the MP2/6-311++G(3df,3pd) approximation. Comparison of variational anharmonic solutions for different vibrational subsystems demonstrates the influence of intermode anharmonic coupling on the mixing of wave functions and spectroscopic and geometrical characteristics. The inverse Ubbelohde effect is predicted and substantiated.
A pressure-tuned Fabry Pérot interferometer for laser frequency stabilization and tuning
Authors: Orr Keegan , George Ian , Reinhard Aaron
Published: September 2018

We present a simple, inexpensive pressure-tuned Fabry Pérot interferometer which can be used to frequency stabilize and tune a laser when no suitable atomic reference is available. Our design, made largely from off-the-shelf parts, yields a tuning range of about 4 GHz and offers an absolute tuning accuracy of better than 1 MHz. The interferometer, which uses air as its working medium, is characterized by a low thermal drift rate of order 1 MHz per hour.
Note: A Laue crystal imager for high energy quasi-monochromatic x-ray
Authors: Zhang Zhe , Nishimura Hiroaki , Yao Akira , Suzuki Yosuke , Shobu Takahisa , Yasuda Ryo , Yogo Akifumi , Li Yutong
Published: September 2018

A newly designed transmission type x-ray Laue imager for tens of keV hard x-rays is reported. Compared with the traditional reflection type x-ray crystal imager, the transmission geometry produces a much better image quality for high energy hard x-rays. This system was assessed via a calibration experiment performed at the SPring8 synchrotron radiation facility. With a Ta x-ray fluorescer, the mono-energetic x-ray at 70 keV from the synchrotron radiation was converted to an isotropically emitted Ta K-shell source at 57.5 keV and 65 keV. A tungsten pinhole array was employed as the test object, and clear images of the pinholes with a magnification of ∼5 were acquired. These images exhibited superior quality in the dispersion plane. As an extension of this work, a slit-free full-spectral Laue imager is proposed for high resolution hard x-ray imaging.
Forced coupling vibration analysis of FBAR based on two-dimensional equations associated with state-vector approach
Authors: Li Nian , Qian Zhenghua , Wang Bin
Published: September 2018

In our previous work, a system of two-dimensional equations for piezoelectric thin-film acoustic wave resonators (FBAR) has been derived and then successfully applied on the free vibration analysis of a finite FBAR plate. In this paper, we analyzed the forced vibrations of FBAR with alternating voltage applied on its electrodes. The derived two dimensional equations were simplified based on straight-crested wave approximations and were rewritten into matrix formalism by state-vector approach. With the knowledge of matrix function, the state-vector equation was successfully solved. Results of admittance were obtained with the dependence on the driving frequency and the aspect ratio. The obtained figure was compared with the frequency spectra obtained in free vibration analysis. Different aspect ratios and quality factors were taken to study the effects of them on the admittance. It is shown that admittance is highly influenced by mode couplings. Thus the work in this paper will be important for the thorough understanding of the coupling vibration of FBAR and its optimization design.
A novel lightweight TE01-TE20 mode converter with broad bandwidth and aligned ports
Authors: Zhao Peng , Wang Qingyuan , Deng Jie
Published: September 2018

A novel TE01-TE20 mode converter is designed and fabricated by 3-D printing in this paper. It can realize high-efficiency (>97.5%) mode conversion in broadband from 27 to 40 GHz. Its weight is 0.011 kg only, and its coupling cavity normalized length is 0.39λ. An out-of-phase power divider is designed to verify the mode converter by observing the difference of output phase and flat frequency characteristics when connected to the mode converter. A sample converter with a power divider was then tested. Flat frequency characteristics for power dividing and anti-phase outputs are obtained in the working bandwidth to verify the mode converter with a good performance of mode conversion.
Free energy of hydration and heat capacity of calcium dipicolinate in Bacillus spore cores
Authors: Mishra Ankit , Krishnamoorthy Aravind , Rajak Pankaj , Tiwari Subodh , Sheng Chunyang , Kalia Rajiv K. , Nakano Aiichiro , Vashishta Priya
Published: September 2018

Wet heat treatments are widely used sterilization techniques for inactivating dangerous and resistant sporulating bacteria. The effectiveness of such treatments depends upon the thermodynamics of water uptake by the spore as well as the kinetics of phase transformations in the hydrated spore core. The mechanism behind these chemical and physical processes remains unknown because the thermodynamic properties of the spore core constituents are not well understood. Here, we use reactive molecular dynamics simulations to calculate the vibrational density of states and specific heat of hydrated calcium dipicolinate as well as the free energy of hydration based on Jarzynski's inequality. These two quantities are used to construct a phase diagram of hydrated calcium dipicolinate, indicating the extent of hydration at different pressures and temperatures, which can be used to identify potential regimes for wet-heat sterilization of bacterial spores.
Plasma scientists summarize the potential and challenges of plasma mass separation
Authors: Patrick Chris
Published: September 2018

In a plasma mass separation primer, authors outline applications, approaches and issues of this prospective tool.
Genetic parameters for faecal worm egg count at different ages in Australian sheep under natural challenge
Authors: Li L. , Brown D. J. , Swan A. A. , van der Werf J. H. J.
Published: September 2018

The data used in the present study consisted of 24535 worm egg count records on sheep observed from 63 to 560 days of age under conditions of the natural challenge of trichostrongylid species. Records were extracted from the Information Nucleus Flock database of the Australia Sheep Cooperative Research Centre program from 2007 to 2011. Records were observed at various ages and subdivided into weaning (W, ~3 months), post-weaning (P, ~4 months), yearling (Y, ~12 months) and hogget (H, ~18 months) age stages and were used to investigate genetic variation at different age stages in univariate analyses and estimate genetic correlations between age stages in multi-trait analyses. The full data were also analysed by random regression models to study how heritability and genetic correlations varied with age. Heritability estimates from univariate analyses were 0.20 ± 0.05, 0.15 ± 0.02, 0.36 ± 0.09, 0.22 ± 0.06 for W, P, Y and H age stages respectively. A similar trend of heritability over ages was found from random regression analyses, which decreased from 0.16 at 90 days to 0.09 at 120 days, following a steady increase to 0.32 at ~410 days, and then decreased afterwards to 0.24 at 520 days. Strong genetic correlations (>0.8) were found between W and P age stages, along with Y and H age stages. Sire by flock interaction effects were significant, and accounted for the reduced estimates of heritability and increased genetic correlations between age stages. The results indicated that a multiple-trait approach is required for genetic evaluation of worm egg count when measurements are at different ages, and the accuracy of evaluations would benefit from recording at least two separate age stages.
Cortical circuit activity underlying sleep slow oscillations and spindles
Authors: Niethard Niels , Ngo Hong-Viet V. , Ehrlich Ingrid , Born Jan
Published: September 2018

Significance

Slow oscillations and spindles are hallmarks of the EEG during slow-wave sleep. They are thought to support memory consolidation, particularly in instances where the faster spindle nests into the “upstate” of a slow oscillation. Using two-photon and wide-field imaging, we recorded calcium transients from distinct populations of cortical excitatory and inhibitory neurons during sleep in mice. Compared with spindles or slow oscillations occurring in isolation, events where spindles nested in a slow oscillation upstate were indeed accompanied by a unique pattern of calcium activity where high pyramidal cell activity appears to concur with high perisomatic inhibition through parvalbumin-positive interneurons and with low dendritic inhibition through somatostatin-positive interneurons. These conditions might foster dendritic plasticity.
LRRK2 and its substrate Rab GTPases are sequentially targeted onto stressed lysosomes and maintain their homeostasis
Authors: Eguchi Tomoya , Kuwahara Tomoki , Sakurai Maria , Komori Tadayuki , Fujimoto Tetta , Ito Genta , Yoshimura Shin-ichiro , Harada Akihiro , Fukuda Mitsunori , Koike Masato , Iwatsubo Takeshi
Published: September 2018

Significance

LRRK2, a protein kinase related to Parkinson’s disease, is implicated in the maintenance of lysosomes, and a subset of Rab GTPases has been identified as bona fide substrates of LRRK2. Here, we reveal a key stress-responsive pathway composed of Rab7L1, LRRK2, and phosphorylated Rab8/10 involved in lysosomal homeostasis. Lysosomal overload stress induces translocation of Rab7L1 and LRRK2 to lysosomes, where LRRK2 is activated, and stabilizes Rab8 and Rab10 through phosphorylation. The activation of this machinery protects against lysosomal enlargement and upregulates lysosomal secretion through Rab effectors, EHBP1 and EHBP1L1. These findings elucidate a novel regulatory mechanism of Rab GTPases by phosphorylation by LRRK2 in stressed lysosomes, which may also be involved in the pathomechanism of LRRK2-related disorders.
Xrp1 genetically interacts with the ALS-associated FUS orthologue caz and mediates its toxicity
Authors: Mallik Moushami , Catinozzi Marica , Hug Clemens B. , Zhang Li , Wagner Marina , Bussmann Julia , Bittern Jonas , Mersmann Sina , Klämbt Christian , Drexler Hannes C.A. , Huynen Martijn A. , Vaquerizas Juan M. , Storkebaum Erik
Published: September 2018

Cabeza (caz) is the single Drosophila melanogaster orthologue of the human FET proteins FUS, TAF15, and EWSR1, which have been implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In this study, we identified Xrp1, a nuclear chromatin-binding protein, as a key modifier of caz mutant phenotypes. Xrp1 expression was strongly up-regulated in caz mutants, and Xrp1 heterozygosity rescued their motor defects and life span. Interestingly, selective neuronal Xrp1 knockdown was sufficient to rescue, and neuronal Xrp1 overexpression phenocopied caz mutant phenotypes. The caz/Xrp1 genetic interaction depended on the functionality of the AT-hook DNA-binding domain in Xrp1, and the majority of Xrp1-interacting proteins are involved in gene expression regulation. Consistently, caz mutants displayed gene expression dysregulation, which was mitigated by Xrp1 heterozygosity. Finally, Xrp1 knockdown substantially rescued the motor deficits and life span of flies expressing ALS mutant FUS in motor neurons, implicating gene expression dysregulation in ALS-FUS pathogenesis.
Zebrafish blastomere screen identifies retinoic acid suppression of MYB in adenoid cystic carcinoma
Authors: Mandelbaum Joseph , Shestopalov Ilya A. , Henderson Rachel E. , Chau Nicole G. , Knoechel Birgit , Wick Michael J. , Zon Leonard I.
Published: September 2018

Pluripotent cells have been used to probe developmental pathways that are involved in genetic diseases and oncogenic events. To find new therapies that would target MYB-driven tumors, we developed a pluripotent zebrafish blastomere culture system. We performed a chemical genetic screen and identified retinoic acid agonists as suppressors of c-myb expression. Retinoic acid treatment also decreased c-myb gene expression in human leukemia cells. Translocations that drive overexpression of the oncogenic transcription factor MYB are molecular hallmarks of adenoid cystic carcinoma (ACC), a malignant salivary gland tumor with no effective therapy. Retinoic acid agonists inhibited tumor growth in vivo in ACC patient–derived xenograft models and decreased MYB binding at translocated enhancers, thereby potentially diminishing the MYB positive feedback loop driving ACC. Our findings establish the zebrafish pluripotent cell culture system as a method to identify modulators of tumor formation, particularly establishing retinoic acid as a potential new effective therapy for ACC.
Force localization modes in dynamic epithelial colonies
Authors: Schaumann Erik N. , Staddon Michael F. , Gardel Margaret L. , Banerjee Shiladitya
Published: September 2018

Collective cell behaviors, including tissue remodeling, morphogenesis, and cancer metastasis, rely on dynamics among cells, their neighbors, and the extracellular matrix. The lack of quantitative models precludes understanding of how cell–cell and cell–matrix interactions regulate tissue-scale force transmission to guide morphogenic processes. We integrate biophysical measurements on model epithelial tissues and computational modeling to explore how cell-level dynamics alter mechanical stress organization at multicellular scales. We show that traction stress distribution in epithelial colonies can vary widely for identical geometries. For colonies with peripheral localization of traction stresses, we recapitulate previously described mechanical behavior of cohesive tissues with a continuum model. By contrast, highly motile cells within colonies produce traction stresses that fluctuate in space and time. To predict the traction force dynamics, we introduce an active adherent vertex model (AAVM) for epithelial monolayers. AAVM predicts that increased cellular motility and reduced intercellular mechanical coupling localize traction stresses in the colony interior, in agreement with our experimental data. Furthermore, the model captures a wide spectrum of localized stress production modes that arise from individual cell activities including cell division, rotation, and polarized migration. This approach provides a robust quantitative framework to study how cell-scale dynamics influence force transmission in epithelial tissues.
Hierarchical Brain Network for Face and Voice Integration of Emotion Expression
Authors: Davies-Thompson Jodie , Elli Giulia V , Rezk Mohamed , Benetti Stefania , van Ackeren Markus , Collignon Olivier
Published: September 2018

The brain has separate specialized computational units to process faces and voices located in occipital and temporal cortices. However, humans seamlessly integrate signals from the faces and voices of others for optimal social interaction. How are emotional expressions, when delivered by different sensory modalities (faces and voices), integrated in the brain? In this study, we characterized the brains’ response to faces, voices, and combined face–voice information (congruent, incongruent), which varied in expression (neutral, fearful). Using a whole-brain approach, we found that only the right posterior superior temporal sulcus (rpSTS) responded more to bimodal stimuli than to face or voice alone but only when the stimuli contained emotional expression. Face- and voice-selective regions of interest, extracted from independent functional localizers, similarly revealed multisensory integration in the face-selective rpSTS only; further, this was the only face-selective region that also responded significantly to voices. Dynamic causal modeling revealed that the rpSTS receives unidirectional information from the face-selective fusiform face area, and voice-selective temporal voice area, with emotional expression affecting the connection strength. Our study promotes a hierarchical model of face and voice integration, with convergence in the rpSTS, and that such integration depends on the (emotional) salience of the stimuli.
Meta-analysis of genome-wide association studies
for body fat distribution in 694 649 individuals of European ancestry
Authors: Pulit Sara L , Stoneman Charli , Morris Andrew P , Wood Andrew R , Glastonbury Craig A , Tyrrell Jessica , Yengo Loïc , Ferreira Teresa , Marouli Eirini , Ji Yingjie , Yang Jian , Jones Samuel , Beaumont Robin , Croteau-Chonka Damien C , Winkler Thomas W ,   GIANT Consortium, Hattersley Andrew T , Loos Ruth J F , Hirschhorn Joel N , Visscher Peter M , Frayling Timothy M , Yaghootkar Hanieh , Lindgren Cecilia M
Published: September 2018

More than one in three adults worldwide is either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, are more informative for predicting risk of obesity sequelae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR above the thresholds used for metabolic syndrome. These data, made publicly available, will inform the biology of body fat distribution and its relationship with disease.
Tobacco Use Classification by Inexpensive Urinary Cotinine Immunoassay Test Strips
Authors: Achilihu Honest , Feng June , Wang Lanqing , Bernert John T
Published: September 2018

Urinary cotinine is one of the most commonly measured biomarkers reflecting recent exposure to nicotine. In some cases a simple qualitative dichotomization of smokers and non-smokers is all that is required. NicAlert® test strips have been evaluated for this purpose, but other recently introduced, inexpensive single-line test strips have not. In this study we evaluated two such strips with nominal cutoffs of 200 and 10 ng/mL. A total of 800 urine samples with known cotinine concentrations determined by an LC–MS-MS method were examined, including 400 urine samples ranging from 0.23 to more than 24,000 ng/mL by the 200 ng/mL strip, and 400 samples with concentrations <200 ng/mL by the 10 ng/mL cutoff strip. Both test strips performed well in these evaluations. Classification relative to LC–MS-MS by the 200 ng/mL strips had a sensitivity of 99.5% and specificity of 92%, with 95.8% accuracy. The 10 ng/mL strips had a sensitivity of 98.7% and specificity of 90.1%, with 93.3% accuracy. The positive predictive value for the 200 ng/mL strips was 92.6% and the negative predictive value was 99.5%. For the 10 ng/mL strips, the corresponding values were 85.4 and 99.2%, respectively. The prevalence of positive samples was 50% in the 200 ng/mL group, and 37% in the 10 ng/mL set. Each strip was read by two readers with an overall agreement of >98%. Our results suggest that these simple and inexpensive lateral flow immunoassay test strips can provide useful qualitative estimates of nicotine exposures for appropriate applications within the inherent limitations of sensitivity and precision of the immunoassay test strip format.
Final Analysis of the Prevention of Early Menopause Study (POEMS)/SWOG Intergroup S0230
Authors: Moore Halle C F , Unger Joseph M , Phillips Kelly-Anne , Boyle Frances , Hitre Erika , Moseley Anna , Porter David J , Francis Prudence A , Goldstein Lori J , Gomez Henry L , Vallejos Carlos S , Partridge Ann H , Dakhil Shaker R , Garcia Agustin A , Gralow Julie R , Lombard Janine M , Forbes John F , Martino Silvana , Barlow William E , Fabian Carol J , Minasian Lori M , Meyskens Frank L , Gelber Richard D , Hortobagyi Gabriel N , Albain Kathy S
Published: September 2018

Premature menopause is a serious long-term side effect of chemotherapy. We evaluated long-term pregnancy and disease-related outcomes for patients in S0230/POEMS, a study in premenopausal women with stage I–IIIA estrogen receptor–negative, progesterone receptor–negative breast cancer to be treated with cyclophosphamide-containing chemotherapy. Women were randomly assigned to standard chemotherapy with or without goserelin, a gonadotropin-releasing hormone agonist, and were stratified by age and chemotherapy regimen. All statistical tests were two-sided. Of 257 patients, 218 were eligible and evaluable (105 in the chemotherapy + goserelin arm and 113 in the chemotherapy arm). More patients in the chemotherapy + goserelin arm reported at least one pregnancy vs the chemotherapy arm (5-year cumulative incidence = 23.1%, 95% confidence interval [CI] = 15.3% to 31.9%; and 12.2%, 95% CI = 6.8% to 19.2%, respectively; odds ratio = 2.34; 95% CI = 1.07 to 5.11; P = .03). Randomization to goserelin + chemotherapy was associated with a nonstatistically significant improvement in disease-free survival (hazard ratio [HR] = 0.55; 95% CI = 0.27 to 1.10; P = .09) and overall survival (HR = 0.45; 95% CI = 0.19 to 1.04; P = .06). In this long-term analysis of POEMS/S0230, we found continued evidence that patients randomly assigned to receive goserelin + chemotherapy were not only more likely to avoid premature menopause, but were also more likely to become pregnant without adverse effect on disease-related outcomes.
Twenty-Five Years of Intracranial Pressure Monitoring After Severe Traumatic Brain Injury: A Retrospective, Single-Center Analysis
Authors: Donnelly Joseph , Czosnyka Marek , Adams Hadie , Cardim Danilo , Kolias Angelos G , Zeiler Frederick A , Lavinio Andrea , Aries Marcel , Robba Chiara , Smielewski Peter , Hutchinson Peter J A , Menon David K , Pickard John D , Budohoski Karol P
Published: September 2018

BACKGROUND

Intracranial pressure (ICP) is a clinically important variable after severe traumatic brain injury (TBI) and has been monitored, along with clinical outcome, for over 25 yr in Addenbrooke's hospital, Cambridge, United Kingdom. This time period has also seen changes in management strategies with the implementation of protocolled specialist neurocritical care, expansion of neuromonitoring techniques, and adjustments of clinical treatment targets.

OBJECTIVE

To describe the changes in intracranial monitoring variables over the past 25 yr.

METHODS

Data from 1146 TBI patients requiring ICP monitoring were analyzed. Monitored variables included ICP, cerebral perfusion pressure (CPP), and the cerebral pressure reactivity index (PRx). Data were stratified into 5-yr epochs spanning the 25 yr from 1992 to 2017.

RESULTS

CPP increased sharply with specialist neurocritical care management (P < 0.0001) (introduction of a specific TBI management algorithm) before stabilizing from 2000 onwards. ICP decreased significantly over the 25 yr of monitoring from an average of 19 to 12 mmHg (P < 0.0001) but PRx remained unchanged. The mean number of ICP plateau waves and the number of patients developing refractory intracranial hypertension both decreased significantly. Mortality did not significantly change in the cohort (22%).

CONCLUSION

We demonstrate the evolving trends in neurophysiological monitoring over the past 25 yr from a single, academic neurocritical care unit. ICP and CPP were responsive to the introduction of an ICP/CPP protocol while PRx has remained unchanged.
Is Preoperative Duration of Symptoms a Significant Predictor of Functional Outcomes in Patients Undergoing Surgery for the Treatment of Degenerative Cervical Myelopathy?
Authors: Tetreault Lindsay , Wilson Jefferson R , Kotter Mark R N , Côté Pierre , Nouri Aria , Kopjar Branko , Arnold Paul M , Fehlings Michael G
Published: September 2018

BACKGROUND

Preoperative duration of symptoms may significantly impact outcomes in patients treated surgically for degenerative cervical myelopathy (DCM).

OBJECTIVE

To (i) analyze whether duration of symptoms is associated with preoperative functional impairment, disability, and quality of life and (ii) determine the optimal timing for decompressive surgery.

METHODS

Patients with DCM were prospectively enrolled in either the AOSpine North American or International study at 26 global sites (n = 757). Postoperative functional impairment was evaluated at 1-yr using the modified Japanese Orthopaedic Association (mJOA) score. Change scores between baseline and 1-yr were computed for the mJOA. Duration of symptoms was dichotomized into a “short” and “long” group at several cut-offs. Analysis of covariance was used to evaluate differences in change scores on the mJOA between duration of symptoms groups in 4-mo increments.

RESULTS

Our cohort consisted of 424 men and 255 women, with a mean duration of symptoms of 26.1 ± 36.4 mo (0.25-252 mo). Duration of symptoms was not correlated with preoperative mJOA, Nurick, Neck Disability Index, or Short-Form (SF)-36 Physical and Mental Component Scores. Patients with a duration of symptoms shorter than 4 mo had significantly better functional outcomes on the mJOA than patients with a longer duration of symptoms (>4 mo). Thirty-two months was also a significant cut-off.

CONCLUSION

Patients who are operated on within 4 mo of symptom presentation have better mJOA outcomes than those treated after 4 mo. It is recommended that patients with DCM are diagnosed in a timely fashion and managed appropriately.
RADON IN GROUNDWATER OF MAGADI TALUK, RAMANAGARA DISTRICT IN KARNATAKA
Authors: Vipin Kumar P , Gudennavar S B , Chandrashekara M S , Bubbly S G , Hamsa K S
Published: September 2018

Radon is a water-soluble radioactive noble gas produced from the alpha decay of 226Ra in uranium series. Its presence in drinking water and open air increases the risk of lung and intestinal cancers in human beings. In view of this, radon concentration in groundwater and its dose due to inhalation and ingestion to the population of Magadi taluk of Ramanagara district in Karnataka state, India was studied. The groundwater samples were analyzed for radon concentration using emanometry technique. The study showed that the radon concentration in this area varied from 27.4 ± 1.0 to 167.5 ± 3.9 Bq/L and the effective dose ranged from 104.2 ± 2.7 to 636.2 ± 11.0 μSv/a. The study also revealed that 95% of the 37 samples studied showed higher radon concentration compared to the UNSCEAR recommendation (40 Bq/L) and all the samples showed higher than the USEPA recommendation (11.1 Bq/L). Ten samples have concentration above the maximum permissible level prescribed by WHO (100 Bq/L). The groundwater samples are found to be slightly alkaline within the permissible limit of Indian Standards.
EXPOSURE ASSESSMENT OF PORTABLE WIRELESS DEVICES ABOVE 6 GHz
Authors: Carrasco Eduardo , Colombi Davide , Foster Kenneth R , Ziskin Marvin , Balzano Quirino
Published: September 2018

The emerging 5 G wireless devices working at frequencies above 6 GHz are expected to have antenna arrays formed by dipoles, slots, patches or their combination. At lower frequencies, the accepted criteria for exposure compliance is stated in terms of specific absorption rate. IEEE and ICNIRP are adopting epithelial or transmitted power density (PD through body surface) as the dosimetric reference for frequencies above 6 GHz, which entails the measurement of free space PD. Theoretical and numerical results presented in this article show that it is possible to perform meaningful free space PD assessments at half wave (λ/2) distance from arrays and, with the proper instrumentation, as close as λ/(2π). However, if a dissipative body is placed very close (<λ/2π) to the arrays, its reflection and absorption of RF energy can change the electric currents and charges over the antenna. The relevance of such an effect should be further investigated, for instance by means of experimental analysis including measurements of tissue heating when in the presence of a strong reactive near field.
Energetic increases lead to niche packing in deep-sea wood falls
Authors: McClain Craig R. , Nunnally Clifton , Chapman Abbie S. A. , Barry James P.
Published: September 2018

Mechanisms leading to variation in diversity over energetic gradients continue to challenge ecologists. Changes in diversity may reflect the environmental capacity to support species' coexistence through increased niche packing or niche space expansion. Current ecological theory predicts that increases in energy may lead to both scenarios but not their relative strengths. We use experimental deep-sea, wood-fall communities, where energy supply can be controlled, to test for the importance of niche expansion and packing in functional space over an energetic gradient. Invertebrate communities were identified and counted from 16
Acacia
sp. logs ranging in size from 0.6 to 20.6 kg in mass (corresponding to energy availability) deployed at 3203 m in the Pacific Ocean for 5 years. We use four fundamental energetic species-level functional traits—food source, trophic category, motility and tiering—to characterize species niches. Increases in energy on wood falls lead to increases in species richness. This higher species richness resulted from a substantial increase in mean niche overlap, suggesting that increases in energy may afford reduced competition.
Tales from the crypt: intestinal niche signals in tissue renewal, plasticity and cancer
Authors: Spit Maureen , Koo Bon-Kyoung , Maurice Madelon M.
Published: September 2018

Rapidly renewing tissues such as the intestinal epithelium critically depend on the activity of small-sized stem cell populations that continuously generate new progeny to replace lost and damaged cells. The complex and tightly regulated process of intestinal homeostasis is governed by a variety of signalling pathways that balance cell proliferation and differentiation. Accumulating evidence suggests that stem cell control and daughter cell fate determination is largely dictated by the microenvironment. Here, we review recent developments in the understanding of intestinal stem cell dynamics, focusing on the roles, mechanisms and interconnectivity of prime signalling pathways that regulate stem cell behaviour in intestinal homeostasis. Furthermore, we discuss how mutational activation of these signalling pathways endows colorectal cancer cells with niche-independent growth advantages during carcinogenesis.