bluuebunny/crossref_metadata_2025 huggingface dataset:
Is trazodone more effective than clomipramine in major depressed outpatients? A single-blind study with intravenous and oral administration
Authors: Buoli Massimiliano , Rovera Chiara , Pozzoli Sara Maria , Fiorentini Alessio , Cremaschi Laura , Caldiroli Alice , Altamura A. Carlo
Published: October 2017

Objective

Some antidepressants, such as trazodone or clomipramine, can be administered intravenously in patients with major depressive disorder (MDD), with potential benefits compared to the standard oral treatment, but available data about their efficacy are limited. The present study was aimed to compare the effectiveness of trazodone and clomipramine (intravenous [i.v.] followed by oral administration).

Methods

Some 42 patients with a diagnosis of MDD according to the DSM–5 were selected and treated with i.v. trazodone or clomipramine according to clinical judgment. The Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Montgomery-Åsberg Depression Rating Scale were administered at baseline, after 2 weeks, and after 6 weeks, as well as after 1 week of intravenous antidepressant administration. Raters were blinded to type of treatment.

Results

No significant differences were found between treatment groups in terms of effectiveness at endpoint. Borderline statistical significance was found in terms of number of responders in favor of trazodone. In addition, patients treated with trazodone reported fewer total side effects than those treated with clomipramine.

Conclusion

Both i.v. trazodone and clomipramine are rapid and effective options for improving depressive symptoms, although trazodone appears to be tolerated better. Further studies with larger samples and double-blind conditions are warranted to confirm our results.
Experiences of Improving Access to Psychological Therapy Services for Perinatal Mental Health Difficulties: a Qualitative Study of Women's and Therapists’ Views
Authors: Millett Lottie , Taylor Billie Lever , Howard Louise M. , Bick Debra , Stanley Nicky , Johnson Sonia
Published: October 2017

Background:Perinatal mental health difficulties are highly prevalent. In England, the Improving Access to Psychological Therapy (IAPT) programme provides evidence-based psychological treatment, predominantly in the form of brief manualized cognitive behavioural therapy (CBT), to people with mild to moderate depression or anxiety. Yet little is known about the experiences of women referred to IAPT with perinatal mental health difficulties.Aims:The aim of this qualitative study was to investigate how women view IAPT support for perinatal mental health. We also gained the perspective of IAPT therapists.Method:Semi-structured interviews were conducted with twelve women who had been referred to and/or received therapy from IAPT during the perinatal period. Additionally, fourteen IAPT therapists participated in two focus groups. Thematic analysis was used.Results:Key themes centred on barriers to access and the need to tailor support to (expectant) mothers. Women and therapists suggested that experiences could be improved by supporting healthcare professionals to provide women with more help with referrals, better tailoring support to the perinatal context, improving perinatal-specific training, supervision and resources, and offering a more individualized treatment environment.Conclusions:Overall, women reported positive experiences of support offered by IAPT for perinatal mental health difficulties. However, services should seek to facilitate access to support and to enable therapists to better tailor treatment.
Immediate and Delayed Neuropsychological Effects of Carbon Monoxide Poisoning: A Meta-analysis
Authors: Watt Stephanie , Prado Catherine E. , Crowe Simon F.
Published: October 2017

Background: Carbon monoxide (CO) poisoning is the leading cause of accidental poisoning worldwide. This study undertook a meta-analysis to examine differences in neuropsychological functioning in patients with CO poisoning as compared to healthy controls, and examined the longer-term neuropsychological effects of CO poisoning. Methods: Studies performed between the years 1995 and 2016 were identified through a search of the electronic databases Medline and PsycInfo. Data from the papers identified were pooled to determine standard mean differences using a random-effects model. Results: Ten studies were included in the analysis, with healthy controls performing significantly better than CO poisoned participants on the domains of divided attention, immediate memory, and processing speed. No statistically significant differences were found for sustained attention, recent memory, working memory, visuospatial/constructional ability, and expressive language. Performance by participants with CO poisoning for the domains of sustained attention, recent memory, visuospatial/constructional abilities, and working memory significantly improved over time after initial exposure, demonstrating recovery of these functions over time. No statistically significant differences were evident for divided attention or expressive language. Conclusions: This evidence indicates that healthy controls perform better than do individuals with CO poisoning on a range of neuropsychological domains; however, it also indicates that performance in some domains does improve over time. (JINS, 2018, 24, 405–415)
ARE RISK PREMIA RELATED TO REAL EXCHANGE RATE SWINGS? EVIDENCE FROMI(2) CVARs WITH SURVEY EXPECTATIONS
Authors: Stillwagon Josh R.
Published: October 2017

This paper finds strong evidence of a positive relationship between currency risk premia and real exchange rate swings, significant at the 1% if not 0.1% level, for three US$ exchange rate samples. The risk premia are measured using survey data on traders' exchange rate forecasts. This circumvents the need for an auxiliary hypothesis of rationality and enables more direct focus on risk behavior. The analysis is conducted using theI(2) cointegrated VAR, which allows for time-varying trends in the variables. Evidence of persistent changes is found for interest rates, prices, and nominal and real exchange rates. Interest rate shocks appear to drive the system, whereas expectations are correcting only in the longer run.
PATTERNS OF UNEMPLOYMENT DYNAMICS IN GERMANY
Authors: Rahn Daniela , Weber Enzo
Published: October 2017

Using a structural vector autoregressive (SVAR) model, this paper provides deeper insight into unemployment dynamics in Germany. We identify a technology shock and two policy shocks that play a central role in business cycle research. Accordingly, we enrich the discussion on the sources of unemployment dynamics by considering demand-side impulses. The worker reallocation process varies substantially with the identified shocks. The job-finding rate plays a larger role after a technology shock and a monetary policy shock, whereas the separation rate appears to be the dominant margin after a fiscal policy shock. Technology shocks turn out to be relatively important for variations in the transition rates. Regarding policy shocks, our results point toward fiscal interventions as a promising instrument but with several limitations.
Different settings, different approaches: a qualitative comparison of Portuguese dietitians’ beliefs, attitudes and practices about obesity in public and private settings
Authors: Teixeira Filipa V , Pais-Ribeiro José Luis , Maia Ângela
Published: October 2017

Objective

With obesity being a major public health epidemic, dietitians are charged with the difficult task to assist clients in modifying their behaviours. Since there are inconsistent data about dietitians’ beliefs, attitudes and practices concerning obesity and little is known concerning differences in public and private practice, we conducted the present study to address those gaps.

Design

Semi-structured interviews analysed according to thematic analysis procedures.

Setting

Public primary-care and private settings.

Subjects

Seventeen Portuguese registered dietitians working in public primary-care (n10) and private settings (n7).

Results

Regardless of work context, ‘persistence of efforts’ emerged as the main characteristic of dietitians’ action. Besides holding negative attitudes towards obese patients, their practices are not negatively influenced. They perceive themselves as active agents in promoting lifestyle changes, offering as many management strategies as possible to empower patients, feeling positive about the accomplishment of a successful weight loss, believing in their own efficacy and competency in helping patients. However, differences in reimbursement, work environment, perceived barriers, patient characteristics and availability of resources seem to contribute to differences in persistence according to the setting in which dietitians are working, evidenced by an increase of efforts and engagement in private practice and a decrease in public primary-care practice.

Conclusions

Portuguese dietitians present a positive mindset and actions about obesity treatment outcomes; however, education in behaviour change strategies should be improved. The public health system requires reorganization to enhance effective obesity management delivery. Motivation driving dietitians’ work in private settings should be addressed.
Systematic review of the design, implementation and effectiveness of mass media and nutrition education interventions for infant and young child feeding
Authors: Graziose Matthew M , Downs Shauna M , O’Brien Quentin , Fanzo Jessica
Published: October 2017

Objective

To systematically review the design, implementation and effectiveness of mass media and nutrition education interventions for improving infant and young child feeding (IYCF) practices and related psychosocial factors.

Design

A search of PubMed, Embase and PsycINFO databases, a Google search, and a consultation with experts in the field of IYCF performed in July 2016.

Setting

Low- and middle-income countries, as defined by the World Bank Group.

Subjects

Eligible studies: included a mass media component (with or without nutrition education); conducted a pre–post evaluation (with or without a control group); assessed IYCF knowledge, attitudes, beliefs and/or practices; and were published in English between 2000 and present.

Results

Eighteen unique studies were identified that examined the effect of mass media (types included: television; print; voice and/or SMS (text) messages; radio; megaphones/loudspeakers; videos; social media; songs/dramas) and nutrition education interventions on IYCF practices within thirteen countries. Of these, fifteen studies reported improvements in breast- and/or complementary feeding practices, using indicators recommended by the WHO, and six studies reported improvements in related psychosocial factors. However, little detail was provided on the use of formative research, a formal behaviour change theory and behaviour change techniques. Few studies reported both dose delivered and participants’ exposure to the intervention.

Conclusions

Despite evidence of effectiveness, few common elements in the design of interventions were identified. Future research should consistently report these details to open the ‘black box’ of IYCF interventions, identify effective design components and ensure replicability.
The Eating Motivation Survey: results from the USA, India and Germany
Authors: Sproesser Gudrun , Ruby Matthew B , Arbit Naomi , Rozin Paul , Schupp Harald T , Renner Britta
Published: October 2017

Objective

Research has shown that there is a large variety of different motives underlying why people eat what they eat, which can be assessed with The Eating Motivation Survey (TEMS). The present study investigates the consistency and measurement invariance of the fifteen basic motives included in TEMS in countries with greatly differing eating environments.

Design

The fifteen-factor structure of TEMS (brief version: forty-six items) was tested in confirmatory factor analyses.

Setting

An online survey was conducted.

Subjects

US-American, Indian and German adults (total N 749) took part.

Results

Despite the complexity of the model, fit indices indicated a reasonable model fit (for the total sample: χ
2/df=4·03; standardized root-mean-squared residual (SRMR)=0·063; root-mean-square error of approximation (RMSEA)=0·064 (95 % CI 0·062, 0·066)). Only the comparative fit index (CFI) was below the recommended threshold (for the total sample: CFI=0·84). Altogether, 181 out of 184 item loadings were above the recommended threshold of 0·30. Furthermore, the factorial structure of TEMS was invariant across countries with respect to factor configuration and factor loadings (configural v. metric invariance model: ΔCFI=0·009; ΔRMSEA=0·001; ΔSRMR=0·001). Moreover, forty-three out of forty-six items showed invariant intercepts across countries.

Conclusions

The fifteen-factor structure of TEMS was, in general, confirmed across countries despite marked differences in eating environments. Moreover, latent means of fourteen out of fifteen motive factors can be compared across countries in future studies. This is a first step towards determining generalizability of the fifteen basic eating motives of TEMS across eating environments.
Layering, Kludgeocracy and Disability Rights: The Limited Influence of the Social Model in American Disability Policy
Authors: Burke Thomas F. , Barnes Jeb
Published: October 2017

The United States has been a leader in the creation of disability rights law, providing a policy template for other nations. Yet the social model, the animating philosophy behind the disability rights movement, has had little effect on the wide range of welfare programs that serve people with disabilities. These programs, whose creation preceded the modern disability rights movement, reflect a medical model of disability that is at odds with the social model. Analysing the Americans with Disabilities Act (which embodies the social model) and Social Security Disability Insurance (the largest welfare program for people with disabilities), we explore how and why this layering of contradictory disability rights and welfare programs developed and how it has been maintained. We argue that the tension between these policies engendered a series of patches, or ‘kludges’, that allow the policies to coexist without meaningful synthesis. We contend that the United States is particularly prone to this layering of ‘tense policies’, but that it is likely characteristic of disability policy in many nations. Finally we argue that accurate benchmarking of disability rights regimes across nations requires analysts to dig through all the layers of disability policy.
Archetypical barriers to adapting water governance in river basins to climate change
Authors: OBERLACK CHRISTOPH , EISENACK KLAUS
Published: October 2017

Can we explain barriers to adaptation of collective action to changes in the natural environment? One reason for adaptation is the impacts of climate change. Ample case study evidence shows that such adaptation is rarely a smooth process. However, generalisable patterns of how and why barriers arise remain scarce. The study adopts a collective action perspective and the archetypes approach in a meta-analysis of 26 selected publications to explain how barriers arise in specific conditions. Focusing on adaptation of water governance in river basins, the study finds 21 reappearing patterns. Less well-established patterns relate to water property rights, hydrological standards, adaptation externalities, non-climatological uncertainty and vertical coordination. Results further show how barriers impede collective action in specific ways. The paper precisely introduces the archetypes approach, and shows that reported problems in adapting collective action under climate change arise from attributes of actors and pre-existing institutions rather than biophysical characteristics.
Das komplexe regionale Schmerzsyndrom. Epidemiologie, Pathophysiologie und Behandlung. Ein Update.
Authors: Freiermuth David , Aeschbach Armin , Ruppen Wilhelm
Published: October 2017

Zusammenfassung. Die Behandlung eines komplexen regionalen Schmerzsyndroms stellt nach wie vor eine grosse Herausforderung dar, sowohl für den Patienten als auch für die in die Behandlung involvierten Ärzte und Therapeuten. Die Diagnose wird rein klinisch gemäss der Vorgabe der International Association for the Study of Pain (IASP) anhand der validierten und zuletzt im 2007 modifizierten „Budapester Kriterien“ gestellt. Diagnosekriterien älteren Datums sollten nicht mehr verwendet werden, da sie einerseits zu einer falsch hohen Anzahl Diagnosen führen und andererseits auch versicherungstechnisch und bei Kostengutsprachen zu Problemen führen könnten. Das Hauptmerkmal des „komplexen regionalen Schmerzsyndroms“ sind wie in der Bezeichnung enthalten starke Schmerzen, welche überproportional zum auslösenden Momentum (z. B. Bagatelltrauma, operativer Eingriff) erscheinen. Das Syndrom betrifft dabei praktisch ausschliesslich die Extremitäten. Die pathophysiologische Endstrecke scheint eine übermässig aktivierte Entzündungsreaktion zu sein, welche sich selber unterhält. Dabei spielen je nach Patientenkasuistik verschiedene Mechanismen mit. Zu diesen gehört unter anderem eine pathologische Aktivierung / Dysregulierung des Sympathikus, eine lokale Erhöhung von Entzündungsmediatoren wie Cytokinen, Interleukinen, eine aktivierte Osteoklastenaktivität mit erhöhtem Knochenabbau sowie humorale Faktoren mit Autoantikörpern u. a. gegen alpha1-Rezeptoren. Das klinische Bild eines CRPS scheint eher die gemeinsame Endstrecke von noch nicht im ganzen Umfang verstandenen Pathologien zu sein als das Resultat eines einzelnen spezifischen Pathomechanismus. Entsprechend wird bei Inexistenz einer kausalen „Standardtherapie“ die Behandlung dem Patienten angepasst. Neben Medikamenten sind auch physikalische Massnahmen und je nach Schweregrad und Leidensdruck parallel psychologische / psychoedukative Therapien indiziert. Die Prognose eines schweren CRPS ist nach wie vor ungünstig und bis zu 30 % der Patienten erleben einen permanenten Arbeitsplatzverlust im Verlauf der Erkrankung.
Cannabinoide in der Schmerztherapie
Authors: Briner Adrian , Schneider Tobias
Published: October 2017

Zusammenfassung. In den letzten Jahren wurden zahlreiche wissenschaftliche Arbeiten zum Gebrauch von Cannabisextrakten und synthetischen Cannabinoiden in der Schmerztherapie publiziert. Gleichzeitig haben Berichte in Populärmedien dazu geführt, dass diese Medikamente durch Patienten vermehrt nachgefragt werden. In der Schweiz wurde die Möglichkeit, diese Substanzen zu verschreiben durch Gesetzesänderungen zwar erleichtert, für die meisten Indikationen braucht es aber nach wie vor eine Ausnahmegenehmigung des Bundes. Δ9-trans-Tetrahydrocannabinol (THC) und Cannabidiol (CBD) sind die Hauptwirkstoffe dieser Medikamente. Diese sind zurzeit nicht kassenpflichtig und im Vergleich zu Standardtherapien deutlich teurer. Randomisierte kontrollierte Studien zeigen zum Teil eine gute Wirksamkeit gegen Spastik bei Multipler Sklerose und nach Rückenmarksverletzungen sowie bei Schmerzen von neuropathischem Charakter und Tumorschmerzen. Kürzlich durchgeführte grosse Metaanalysen erbrachten weniger klare Resultate. Werden die Kontraindikationen berücksichtigt, sind schwere psychiatrische Nebenwirkungen im Vergleich zu Placebo nicht häufiger. Als typische Nebenwirkung der psychotropen Wirkung von THC treten Müdigkeit und Schwindel auf. Da Standardtherapien oftmals ein deutlich besseres Wirkungs-/Nebenwirkungsverhältnis haben, sollten Cannabinoide nicht als erste Medikation eingesetzt werden. Bei ausgewählten Patienten können Cannabismedikamente bei nicht ausreichendem Effekt von Erst- und Zweitlinientherapien in Betracht gezogen werden. Neue Erkenntnisse in der Grundlagenforschung zum Endocannabinoid-System lassen in der Zukunft auf spezifischere Cannabinoid-Medikamente mit besserer Wirkung hoffen. Allfällige Folgen einer langjährigen Cannabismedikation lassen sich aktuell mangels Studien nicht abschätzen.
Hippocampal GABA enables inhibitory control over unwanted thoughts
Authors: Schmitz Taylor W. , Correia Marta M. , Ferreira Catarina S. , Prescot Andrew P. , Anderson Michael C.
Published: October 2017

Intrusive memories, images, and hallucinations are hallmark symptoms of psychiatric disorders. Although often attributed to deficient inhibitory control by the prefrontal cortex, difficulty in controlling intrusive thoughts is also associated with hippocampal hyperactivity, arising from dysfunctional GABAergic interneurons. How hippocampal GABA contributes to stopping unwanted thoughts is unknown. Here we show that GABAergic inhibition of hippocampal retrieval activity forms a key link in a fronto-hippocampal inhibitory control pathway underlying thought suppression. Subjects viewed reminders of unwanted thoughts and tried to suppress retrieval while being scanned with functional magnetic resonance imaging. Suppression reduced hippocampal activity and memory for suppressed content. 1H magnetic resonance spectroscopy revealed that greater resting concentrations of hippocampal GABA predicted better mnemonic control. Higher hippocampal, but not prefrontal GABA, predicted stronger fronto-hippocampal coupling during suppression, suggesting that interneurons local to the hippocampus implement control over intrusive thoughts. Stopping actions did not engage this pathway. These findings specify a multi-level mechanistic model of how the content of awareness is voluntarily controlled.
Evolutionary genetics of immunological supertypes reveals two faces of the Red Queen
Authors: Lighten Jackie , Papadopulos Alexander S. T. , Mohammed Ryan S. , Ward Ben J. , G. Paterson Ian , Baillie Lyndsey , Bradbury Ian R. , Hendry Andrew P. , Bentzen Paul , van Oosterhout Cock
Published: October 2017

Red Queen host–parasite co-evolution can drive adaptations of immune genes by positive selection that erodes genetic variation (Red Queen arms race) or results in a balanced polymorphism (Red Queen dynamics) and long-term preservation of genetic variation (trans-species polymorphism). These two Red Queen processes are opposite extremes of the co-evolutionary spectrum. Here we show that both Red Queen processes can operate simultaneously by analysing the major histocompatibility complex (MHC) in guppies (Poecilia reticulata and P. obscura) and swamp guppies (Micropoecilia picta). Sub-functionalisation of MHC alleles into ‘supertypes’ explains how polymorphisms persist during rapid host–parasite co-evolution. Simulations show the maintenance of supertypes as balanced polymorphisms, consistent with Red Queen dynamics, whereas alleles within supertypes are subject to positive selection in a Red Queen arms race. Building on the divergent allele advantage hypothesis, we show that functional aspects of allelic diversity help to elucidate the evolution of polymorphic genes involved in Red Queen co-evolution.
Neuronal baseline shifts underlying boundary setting during free recall
Authors: Norman Yitzhak , Yeagle Erin M. , Harel Michal , Mehta Ashesh D. , Malach Rafael
Published: October 2017

Asked to freely recall items from a predefined set (e.g., animals), we rarely recall a wrong exemplar (e.g., a vegetable). This capability is so powerful and effortless that it is essentially taken for granted, yet, surprisingly, the underlying neuronal mechanisms are unknown. Here we investigate this boundary setting mechanism using intracranial recordings (ECoG), in 12 patients undergoing epilepsy monitoring engaged in episodic free recall. After viewing vivid photographs from two categories (famous faces and places), patients were asked to freely recall these items, targeting each category in separate blocks. Our results reveal a rapid and sustained rise in neuronal activity (“baseline shift”) in high-order visual areas that persists throughout the free recall period and reflects the targeted category. We further show a more transient reactivation linked to individual recall events. The results point to baseline shift as a flexible top−down mechanism that biases spontaneous recall to remain within the required categorical boundaries.
Blue light and CO2 signals converge to regulate light-induced stomatal opening
Authors: Hiyama Asami , Takemiya Atsushi , Munemasa Shintaro , Okuma Eiji , Sugiyama Naoyuki , Tada Yasuomi , Murata Yoshiyuki , Shimazaki Ken-ichiro
Published: October 2017

Stomata regulate gas exchange between plants and atmosphere by integrating opening and closing signals. Stomata open in response to low CO2 concentrations to maximize photosynthesis in the light; however, the mechanisms that coordinate photosynthesis and stomatal conductance have yet to be identified. Here we identify and characterize CBC1/2 (CONVERGENCE OF BLUE LIGHT (BL) AND CO2 1/2), two kinases that link BL, a major component of photosynthetically active radiation (PAR), and the signals from low concentrations of CO2 in guard cells. CBC1/CBC2 redundantly stimulate stomatal opening by inhibition of S-type anion channels in response to both BL and low concentrations of CO2. CBC1/CBC2 function in the signaling pathways of phototropins and HT1 (HIGH LEAF TEMPERATURE 1). CBC1/CBC2 interact with and are phosphorylated by HT1. We propose that CBCs regulate stomatal aperture by integrating signals from BL and CO2 and act as the convergence site for signals from BL and low CO2.
Folding of a bacterial integral outer membrane protein is initiated in the periplasm
Authors: Sikdar Rakesh , Peterson Janine H. , Anderson D. Eric , Bernstein Harris D.
Published: October 2017

The Bam complex promotes the insertion of β-barrel proteins into the bacterial outer membrane, but it is unclear whether it threads β-strands into the lipid bilayer in a stepwise fashion or catalyzes the insertion of pre-folded substrates. Here, to distinguish between these two possibilities, we analyze the biogenesis of UpaG, a trimeric autotransporter adhesin (TAA). TAAs consist of three identical subunits that together form a single β-barrel domain and an extracellular coiled-coil (“passenger”) domain. Using site-specific photocrosslinking to obtain spatial and temporal insights into UpaG assembly, we show that UpaG β-barrel segments fold into a trimeric structure in the periplasm that persists until the termination of passenger-domain translocation. In addition to obtaining evidence that at least some β-barrel proteins begin to fold before they interact with the Bam complex, we identify several discrete steps in the assembly of a poorly characterized class of virulence factors.
Hot carrier cooling mechanisms in halide perovskites
Authors: Fu Jianhui , Xu Qiang , Han Guifang , Wu Bo , Huan Cheng Hon Alfred , Leek Meng Lee , Sum Tze Chien
Published: October 2017

Halide perovskites exhibit unique slow hot-carrier cooling properties capable of unlocking disruptive perovskite photon–electron conversion technologies (e.g., high-efficiency hot-carrier photovoltaics, photo-catalysis, and photodetectors). Presently, the origins and mechanisms of this retardation remain highly contentious (e.g., large polarons, hot-phonon bottleneck, acoustical–optical phonon upconversion etc.). Here, we investigate the fluence-dependent hot-carrier dynamics in methylammonium lead triiodide using transient absorption spectroscopy, and correlate with theoretical modeling and first-principles calculations. At moderate carrier concentrations (around 1018 cm−3), carrier cooling is mediated by polar Fröhlich electron–phonon interactions through zone-center delayed longitudinal optical phonon emissions (i.e., with phonon lifetime τLO around 0.6 ± 0.1 ps) induced by the hot-phonon bottleneck. The hot-phonon effect arises from the suppression of the Klemens relaxation pathway essential for longitudinal optical phonon decay. At high carrier concentrations (around 1019 cm−3), Auger heating further reduces the cooling rates. Our study unravels the intricate interplay between the hot-phonon bottleneck and Auger heating effects on carrier cooling, which will resolve the existing controversy.
Quantum mechanics as classical statistical mechanics with an ontic extension and an epistemic restriction
Authors: Budiyono Agung , Rohrlich Daniel
Published: October 2017

Where does quantum mechanics part ways with classical mechanics? How does quantum randomness differ fundamentally from classical randomness? We cannot fully explain how the theories differ until we can derive them within a single axiomatic framework, allowing an unambiguous account of how one theory is the limit of the other. Here we derive non-relativistic quantum mechanics and classical statistical mechanics within a common framework. The common axioms include conservation of average energy and conservation of probability current. But two axioms distinguish quantum mechanics from classical statistical mechanics: an “ontic extension” defines a nonseparable (global) random variable that generates physical correlations, and an “epistemic restriction” constrains allowed phase space distributions. The ontic extension and epistemic restriction, with strength on the order of Planck’s constant, imply quantum entanglement and uncertainty relations. This framework suggests that the wave function is epistemic, yet it does not provide an ontic dynamics for individual systems.
Dense and accurate whole-chromosome haplotyping of individual genomes
Authors: Porubsky David , Garg Shilpa , Sanders Ashley D. , Korbel Jan O. , Guryev Victor , Lansdorp Peter M. , Marschall Tobias
Published: October 2017

The diploid nature of the human genome is neglected in many analyses done today, where a genome is perceived as a set of unphased variants with respect to a reference genome. This lack of haplotype-level analyses can be explained by a lack of methods that can produce dense and accurate chromosome-length haplotypes at reasonable costs. Here we introduce an integrative phasing strategy that combines global, but sparse haplotypes obtained from strand-specific single-cell sequencing (Strand-seq) with dense, yet local, haplotype information available through long-read or linked-read sequencing. We provide comprehensive guidance on the required sequencing depths and reliably assign more than 95% of alleles (NA12878) to their parental haplotypes using as few as 10 Strand-seq libraries in combination with 10-fold coverage PacBio data or, alternatively, 10X Genomics linked-read sequencing data. We conclude that the combination of Strand-seq with different technologies represents an attractive solution to chart the genetic variation of diploid genomes.
Strong-coupling of WSe2 in ultra-compact plasmonic nanocavities at room temperature
Authors: Kleemann Marie-Elena , Chikkaraddy Rohit , Alexeev Evgeny M. , Kos Dean , Carnegie Cloudy , Deacon Will , de Pury Alex Casalis , Große Christoph , de Nijs Bart , Mertens Jan , Tartakovskii Alexander I. , Baumberg Jeremy J.
Published: October 2017

Strong coupling of monolayer metal dichalcogenide semiconductors with light offers encouraging prospects for realistic exciton devices at room temperature. However, the nature of this coupling depends extremely sensitively on the optical confinement and the orientation of electronic dipoles and fields. Here, we show how plasmon strong coupling can be achieved in compact, robust, and easily assembled gold nano-gap resonators at room temperature. We prove that strong-coupling is impossible with monolayers due to the large exciton coherence size, but resolve clear anti-crossings for greater than 7 layer devices with Rabi splittings exceeding 135 meV. We show that such structures improve on prospects for nonlinear exciton functionalities by at least 104, while retaining quantum efficiencies above 50%, and demonstrate evidence for superlinear light emission.
Genomic structural variation-mediated allelic suppression causes hybrid male sterility in rice
Authors: Shen Rongxin , Wang Lan , Liu Xupeng , Wu Jiang , Jin Weiwei , Zhao Xiucai , Xie Xianrong , Zhu Qinlong , Tang Huiwu , Li Qing , Chen Letian , Liu Yao-Guang
Published: October 2017

Hybrids between divergent populations commonly show hybrid sterility; this reproductive barrier hinders hybrid breeding of the japonica and indica rice (Oryza sativa L.) subspecies. Here we show that structural changes and copy number variation at the Sc locus confer japonica–indica hybrid male sterility. The japonica allele, Sc-j, contains a pollen-essential gene encoding a DUF1618-domain protein; the indica allele, Sc-i, contains two or three tandem-duplicated ~ 28-kb segments, each carrying an Sc-j-homolog with a distinct promoter. In Sc-j/Sc-i hybrids, the high-expression of Sc-i in sporophytic cells causes suppression of Sc-j expression in pollen and selective abortion of Sc-j-pollen, leading to transmission ratio distortion. Knocking out one or two of the three Sc-i copies by CRISPR/Cas9 rescues Sc-j expression and male fertility. Our results reveal the gene dosage-dependent allelic suppression as a mechanism of hybrid incompatibility, and provide an effective approach to overcome the reproductive barrier for hybrid breeding.
Structural basis for mutually exclusive co-transcriptional nuclear cap-binding complexes with either NELF-E or ARS2
Authors: Schulze Wiebke Manuela , Cusack Stephen
Published: October 2017

Pol II transcribes diverse classes of RNAs that need to be directed into the appropriate nuclear maturation pathway. All nascent Pol II transcripts are 5′-capped and the cap is immediately sequestered by the nuclear cap-binding complex (CBC). Mutually exclusive interactions of CBC with different partner proteins have been implicated in transcript fate determination. Here, we characterise the direct interactions between CBC and NELF-E, a subunit of the negative elongation factor complex, ARS2 and PHAX. Our biochemical and crystal structure results show that the homologous C-terminal peptides of NELF-E and ARS2 bind identically to CBC and in each case the affinity is enhanced when CBC is bound to a cap analogue. Furthermore, whereas PHAX forms a complex with CBC and ARS2, NELF-E binding to CBC is incompatible with PHAX binding. We thus define two mutually exclusive complexes CBC–NELF–E and CBC–ARS2–PHAX, which likely act in respectively earlier and later phases of transcription.
Strategies for feeding the world more sustainably with organic agriculture
Authors: Muller Adrian , Schader Christian , El-Hage Scialabba Nadia , Brüggemann Judith , Isensee Anne , Erb Karl-Heinz , Smith Pete , Klocke Peter , Leiber Florian , Stolze Matthias , Niggli Urs
Published: October 2017

Organic agriculture is proposed as a promising approach to achieving sustainable food systems, but its feasibility is also contested. We use a food systems model that addresses agronomic characteristics of organic agriculture to analyze the role that organic agriculture could play in sustainable food systems. Here we show that a 100% conversion to organic agriculture needs more land than conventional agriculture but reduces N-surplus and pesticide use. However, in combination with reductions of food wastage and food-competing feed from arable land, with correspondingly reduced production and consumption of animal products, land use under organic agriculture remains below the reference scenario. Other indicators such as greenhouse gas emissions also improve, but adequate nitrogen supply is challenging. Besides focusing on production, sustainable food systems need to address waste, crop–grass–livestock interdependencies and human consumption. None of the corresponding strategies needs full implementation and their combined partial implementation delivers a more sustainable food future.
Pink-beam serial crystallography
Authors: Meents A. , Wiedorn M. O. , Srajer V. , Henning R. , Sarrou I. , Bergtholdt J. , Barthelmess M. , Reinke P. Y. A. , Dierksmeyer D. , Tolstikova A. , Schaible S. , Messerschmidt M. , Ogata C. M. , Kissick D. J. , Taft M. H. , Manstein D. J. , Lieske J. , Oberthuer D. , Fischetti R. F. , Chapman H. N.
Published: October 2017

Serial X-ray crystallography allows macromolecular structure determination at both X-ray free electron lasers (XFELs) and, more recently, synchrotron sources. The time resolution for serial synchrotron crystallography experiments has been limited to millisecond timescales with monochromatic beams. The polychromatic, “pink”, beam provides a more than two orders of magnitude increased photon flux and hence allows accessing much shorter timescales in diffraction experiments at synchrotron sources. Here we report the structure determination of two different protein samples by merging pink-beam diffraction patterns from many crystals, each collected with a single 100 ps X-ray pulse exposure per crystal using a setup optimized for very low scattering background. In contrast to experiments with monochromatic radiation, data from only 50 crystals were required to obtain complete datasets. The high quality of the diffraction data highlights the potential of this method for studying irreversible reactions at sub-microsecond timescales using high-brightness X-ray facilities.
Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis
Authors: Tommiska Johanna , Känsäkoski Johanna , Skibsbye Lasse , Vaaralahti Kirsi , Liu Xiaonan , Lodge Emily J. , Tang Chuyi , Yuan Lei , Fagerholm Rainer , Kanters Jørgen K. , Lahermo Päivi , Kaunisto Mari , Keski-Filppula Riikka , Vuoristo Sanna , Pulli Kristiina , Ebeling Tapani , Valanne Leena , Sankila Eeva-Marja , Kivirikko Sirpa , Lääperi Mitja , Casoni Filippo , Giacobini Paolo , Phan-Hug Franziska , Buki Tal , Tena-Sempere Manuel , Pitteloud Nelly , Veijola Riitta , Lipsanen-Nyman Marita , Kaunisto Kari , Mollard Patrice , Andoniadou Cynthia L. , Hirsch Joel A. , Varjosalo Markku , Jespersen Thomas , Raivio Taneli
Published: October 2017

Familial growth hormone deficiency provides an opportunity to identify new genetic causes of short stature. Here we combine linkage analysis with whole-genome resequencing in patients with growth hormone deficiency and maternally inherited gingival fibromatosis. We report that patients from three unrelated families harbor either of two missense mutations, c.347G>T p.(Arg116Leu) or c.1106C>T p.(Pro369Leu), in KCNQ1, a gene previously implicated in the long QT interval syndrome. Kcnq1 is expressed in hypothalamic GHRH neurons and pituitary somatotropes. Co-expressing KCNQ1 with the KCNE2 β-subunit shows that both KCNQ1 mutants increase current levels in patch clamp analyses and are associated with reduced pituitary hormone secretion from AtT-20 cells. In conclusion, our results reveal a role for the KCNQ1 potassium channel in the regulation of human growth, and show that growth hormone deficiency associated with maternally inherited gingival fibromatosis is an allelic disorder with cardiac arrhythmia syndromes caused by KCNQ1 mutations.
Towards visible soliton microcomb generation
Authors: Lee Seung Hoon , Oh Dong Yoon , Yang Qi-Fan , Shen Boqiang , Wang Heming , Yang Ki Youl , Lai Yu-Hung , Yi Xu , Li Xinbai , Vahala Kerry
Published: October 2017

Frequency combs have applications that extend from the ultra-violet into the mid-infrared bands. Microcombs, a miniature and often semiconductor-chip-based device, can potentially access most of these applications, but are currently more limited in spectral reach. Here, we demonstrate mode-locked silica microcombs with emission near the edge of the visible spectrum. By using both geometrical and mode-hybridization dispersion control, devices are engineered for soliton generation while also maintaining optical Q factors as high as 80 million. Electronics-bandwidth-compatible (20 GHz) soliton mode locking is achieved with low pumping powers (parametric oscillation threshold powers as low as 5.4 mW). These are the shortest wavelength soliton microcombs demonstrated to date and could be used in miniature optical clocks. The results should also extend to visible and potentially ultra-violet bands.
Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex
Authors: Boniecki Michal T. , Freibert Sven A. , Mühlenhoff Ulrich , Lill Roland , Cygler Miroslaw
Published: October 2017

Iron–sulfur (Fe/S) clusters are essential protein cofactors crucial for many cellular functions including DNA maintenance, protein translation, and energy conversion. De novo Fe/S cluster synthesis occurs on the mitochondrial scaffold protein ISCU and requires cysteine desulfurase NFS1, ferredoxin, frataxin, and the small factors ISD11 and ACP (acyl carrier protein). Both the mechanism of Fe/S cluster synthesis and function of ISD11-ACP are poorly understood. Here, we present crystal structures of three different NFS1-ISD11-ACP complexes with and without ISCU, and we use SAXS analyses to define the 3D architecture of the complete mitochondrial Fe/S cluster biosynthetic complex. Our structural and biochemical studies provide mechanistic insights into Fe/S cluster synthesis at the catalytic center defined by the active-site Cys of NFS1 and conserved Cys, Asp, and His residues of ISCU. We assign specific regulatory rather than catalytic roles to ISD11-ACP that link Fe/S cluster synthesis with mitochondrial lipid synthesis and cellular energy status.
Cell-permeable organic fluorescent probes for live-cell long-term super-resolution imaging reveal lysosome-mitochondrion interactions
Authors: Han Yubing , Li Meihua , Qiu Fengwu , Zhang Meng , Zhang Yu-Hui
Published: October 2017

Characterizing the long-term nanometer-scale interactions between lysosomes and mitochondria in live cells is essential for understanding their functions but remains challenging due to limitations of the existing fluorescent probes. Here, we develop cell-permeable organic fluorescent probes for lysosomes with excellent specificity and high photostability. We also use an existing Atto 647N dye with high brightness and excellent photostability to achieve specific labeling of mitochondria in live cells. Using these probes, we obtain dual-color structured illumination microscopy (SIM) images of dynamic physical lysosome-mitochondrion interactions in live cells at an ~90-nm resolution over a long time course of ~13 min. We successfully record the consecutive dynamic processes of lysosomal fusion and fission, as well as four types of physical lysosome-mitochondrion interactions by super-resolution imaging. Our probes provide an avenue for understanding the functions and the dynamic interplay of lysosomes and mitochondria in live cells.
Programmed cell senescence in skeleton during late puberty
Authors: Li Changjun , Chai Yu , Wang Lei , Gao Bo , Chen Hao , Gao Peisong , Zhou Feng-Quan , Luo Xianghang , Crane Janet L. , Yu Bin , Cao Xu , Wan Mei
Published: October 2017

Mesenchymal stem/progenitor cells (MSPCs) undergo rapid self-renewal and differentiation, contributing to fast skeletal growth during childhood and puberty. It remains unclear whether these cells change their properties during late puberty to young adulthood, when bone growth and accrual decelerate. Here we show that MSPCs in primary spongiosa of long bone in mice at late puberty undergo normal programmed senescence, characterized by loss of nestin expression. MSPC senescence is epigenetically controlled by the polycomb histone methyltransferase enhancer of zeste homolog 2 (Ezh2) and its trimethylation of histone H3 on Lysine 27 (H3K27me3) mark. Ezh2 maintains the repression of key cell senescence inducer genes through H3K27me3, and deletion of Ezh2 in early pubertal mice results in premature cellular senescence, depleted MSPCs pool, and impaired osteogenesis as well as osteoporosis in later life. Our data reveals a programmed cell fate change in postnatal skeleton and unravels a regulatory mechanism underlying this phenomenon.
Direct observation of valley-polarized topological edge states in designer surface plasmon crystals
Authors: Wu Xiaoxiao , Meng Yan , Tian Jingxuan , Huang Yingzhou , Xiang Hong , Han Dezhuan , Wen Weijia
Published: October 2017

The extensive research of two-dimensional layered materials has revealed that valleys, as energy extrema in momentum space, could offer a new degree of freedom for carrying information. Based on this concept, researchers have predicted valley-Hall topological insulators that could support valley-polarized edge states at non-trivial domain walls. Recently, several kinds of photonic and sonic crystals have been proposed as classical counterparts of valley-Hall topological insulators. However, direct experimental observation of valley-polarized edge states in photonic crystals has remained difficult until now. Here, we demonstrate a designer surface plasmon crystal comprising metallic patterns deposited on a dielectric substrate, which can become a valley-Hall photonic topological insulator by exploiting the mirror-symmetry-breaking mechanism. Topological edge states with valley-dependent transport are directly visualized in the microwave regime. The observed edge states are confirmed to be fully valley-polarized through spatial Fourier transforms. Topological protection of the edge states at sharp corners is also experimentally demonstrated.
Author correction: Micromotor-enabled active drug delivery for in vivo treatment of stomach infection
Authors: de Ávila Berta Esteban-Fernández , Angsantikul Pavimol , Li Jinxing , Angel Lopez-Ramirez Miguel , Ramírez-Herrera Doris E. , Thamphiwatana Soracha , Chen Chuanrui , Delezuk Jorge , Samakapiruk Richard , Ramez Valentin , Obonyo Marygorret , Zhang Liangfang , Wang Joseph
Published: October 2017

Marygorret Obonyo, who provided the H. pylori SS1 strain for this work and participated in the design of H. pylori infection studies, was inadvertently omitted from the author list. This has now been corrected in both the PDF and HTML versions of the Article.
Age is no barrier: predictors of academic success in older learners
Authors: Imlach Abbie-Rose , Ward David D. , Stuart Kimberley E. , Summers Mathew J. , Valenzuela Michael J. , King Anna E. , Saunders Nichole L. , Summers Jeffrey , Srikanth Velandai K. , Robinson Andrew , Vickers James C.
Published: October 2017

Although predictors of academic success have been identified in young adults, such predictors are unlikely to translate directly to an older student population, where such information is scarce. The current study aimed to examine cognitive, psychosocial, lifetime, and genetic predictors of university-level academic performance in older adults (50–79 years old). Participants were mostly female (71%) and had a greater than high school education level (M = 14.06 years, SD = 2.76), on average. Two multiple linear regression analyses were conducted. The first examined all potential predictors of grade point average (GPA) in the subset of participants who had volunteered samples for genetic analysis (N = 181). Significant predictors of GPA were then re-examined in a second multiple linear regression using the full sample (N = 329). Our data show that the cognitive domains of episodic memory and language processing, in conjunction with midlife engagement in cognitively stimulating activities, have a role in predicting academic performance as measured by GPA in the first year of study. In contrast, it was determined that age, IQ, gender, working memory, psychosocial factors, and common brain gene polymorphisms linked to brain function, plasticity and degeneration (APOE, BDNF, COMT, KIBRA, SERT) did not influence academic performance. These findings demonstrate that ageing does not impede academic achievement, and that discrete cognitive skills as well as lifetime engagement in cognitively stimulating activities can promote academic success in older adults.