bluuebunny/crossref_metadata_2025 huggingface dataset:
Substitutions between dairy products and risk of stroke: results from the European Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort
Authors: Laursen Anne Sofie D. , Sluijs Ivonne , Boer Jolanda M. A. , Verschuren W. M. Monique , van der Schouw Yvonne T. , Jakobsen Marianne U.
Published: March 2019

The association between intake of different dairy products and the risk of stroke remains unclear. We therefore investigated substitutions between dairy product subgroups and risk of stroke. We included 36 886 Dutch men and women. Information about dairy product intake was collected through a FFQ. Dairy products were grouped as low-fat milk, whole-fat milk, buttermilk, low-fat yogurt, whole-fat yogurt, cheese and butter. Incident stroke cases were identified in national registers. We used Cox proportional hazards regression to calculate associations for substitutions between dairy products with the rate of stroke. During a median follow-up of 15·2 years we identified 884 stroke cases (503 ischaemic and 244 haemorrhagic). Median intake of total dairy products was four servings/d. Low-fat yogurt substituted for whole-fat yogurt was associated with a higher rate of ischaemic stroke (hazard ratio (HR) = 2·58 (95 % CI 1·11, 5·97)/serving per d). Whole-fat yogurt as a substitution for any other subgroup was associated with a lower rate of ischaemic stroke (HR between 0·33 and 0·36/serving per d). We did not observe any associations for haemorrhagic stroke. In conclusion, whole-fat yogurt as a substitution for low-fat yogurt, cheese, butter, buttermilk or milk, regardless of fat content, was associated with a lower rate of ischaemic stroke.
Reichweite von Suchtprävention aus der Perspektive jugendlicher Endadressaten
Authors: Rehbein Florian , Weber Jan , Christine Bergmann Marie , Rumpf Hans-Jürgen , Baier Dirk
Published: March 2019

Zusammenfassung. Ziele: In dieser Studie wird ermittelt, welcher Anteil von Neuntklässler_innen in ihrem bisherigen Leben durch Suchtpräventionsmaßnahmen zu spezifischen Konsumrisiken (Alkohol, Rauchen, Cannabis, Ecstasy/LSD, Glücksspiel, Computerspiel) erreicht wurde (Reichweite von Suchtprävention). Methodik: Datengrundlage bildet eine niedersachenweite repräsentative Befragung von Schüler_innen der neunten Jahrgangsstufe (n = 10.638). Ergebnisse: 82,7 Prozent der befragten Jugendlichen nimmt bis zur neunten Klasse an Suchtprävention zu mindestens einem Konsumrisiko teil. Die Reichweite von Suchtprävention variiert zwischen den zu adressierenden Konsumrisiken: Rauchen: 66,5 %; Alkohol: 73,3 %; Cannabis: 53,6 %; Ecstasy/LSD: 37,4 %; Glücksspiel: 22,1 %; Computerspiele: 35,7 %. Ebenso variieren die eingesetzten Vermittlungsmethoden: Unterricht durch Lehrkraft: 55,5 %; Workshop: 26,6 %; Projektwoche: 24,4 %; Wettbewerb: 8,5 %; Mitmach-Station: 11,5 %; Infomaterialien: 26,8 %; Online-Informationen: 28,1 %. Während dem Urbanisierungsgrad der Wohnregion kaum eine Bedeutung für die Reichweite von Suchtprävention zukommt, haben Hauptschüler_innen gegenüber Gymnasiast_innen in geringerem Maße an extern vermittelten suchtpräventiven Angeboten teilgenommen. Schlussfolgerungen: Die Ergebnisse zeigen, dass Suchtprävention zum Themenfeld illegale Substanzen und insbesondere exzessiv-belohnenden Verhaltensangeboten einen zu geringen Anteil von Jugendlichen erreicht und ausgebaut werden sollte.
Interannual Variability of the Atlantic North Equatorial Undercurrent and Its Impact on Oxygen
Authors: Burmeister K. , Lübbecke J. F. , Brandt P. , Duteil O.
Published: March 2019

The North Equatorial Undercurrent (NEUC) has been suggested to act as an important oxygen supply route toward the oxygen minimum zone in the eastern tropical North Atlantic. Observational estimates of the mean NEUC strength are uncertain due to the presence of elevated mesoscale activities, and models have difficulties in simulating a realistic NEUC. Here we investigate the interannual variability of the NEUC and its impact onto oxygen based on the output of a high‐resolution Ocean General Circulation Model (OGCM) and contrast the results with an unique data set of 21 ship sections along 23° W and a conceptual model. We find that the interannual variability of the NEUC in the OGCM is related to the Atlantic meridional mode with a stronger and more northward NEUC during negative Atlantic meridional mode phases. Discrepancies between the OGCM and observations suggest a different role of the NEUC in setting the regional oxygen distribution. In the model a stronger NEUC is associated with a weaker oxygen supply toward the east. We attribute this to a too strong recirculation between the NEUC and the northern branch of the South Equatorial Current in the OGCM. Idealized experiments with the conceptual model support the idea that the impact of NEUC variability on oxygen depends on the source water pathway. A strengthening of the NEUC supplied out of the western boundary acts to increase oxygen levels within the NEUC. A strengthening of the recirculations between NEUC and the northern branch of the South Equatorial Current results in a reduction of oxygen levels within the NEUC.
Do Uncertainties in the Reconstruction of Land Cover Affect the Simulation of Air Temperature and Rainfall in the CORDEX Region of East Asia?
Authors: Ge Jun , Pitman Andrew J. , Guo Weidong , Wang Shuyu , Fu Congbin
Published: March 2019

Land cover type reconstructions, required in climate models, commonly utilize remote sensing products. There are inevitable misclassifications in land cover reconstructions due to the retrieval process. We use the Weather Research and Forecasting model to determine whether these misclassifications can affect the simulations of air temperature and rainfall over the Coordinated Regional Climate Downscaling Experiment (CORDEX) East Asia region, where the accuracy of the land cover classification is low. The Moderate Resolution Imaging Spectroradiometer land cover map is used for the control simulations and is then replaced by the most likely alternative land cover type at pixels where the classification confidence is below various threshold values. Results show that misclassification‐induced land cover change can affect key biogeophysical characteristics (albedo, leaf area index, and roughness length) and these can affect the sensible and latent heat fluxes at regional scales. However, the impact on air temperature is very limited and is restricted to the Tibetan Plateau where warming of up to 2 °C occurs associated with the replacement of barren or sparsely vegetated land to grassland. The impact on rainfall is negligible, and most changes are likely caused by model internal variability rather than land cover change. Overall, uncertainties in the reconstruction of land cover have negligible impacts, and the Moderate Resolution Imaging Spectroradiometer land cover product can be used in regional simulations over East Asia. However, we note that land cover change experiments incorporating uncertainties must utilize large numbers of simulations if air temperature and rainfall changes are to be examined robustly.
Some Waterfalls May Be Self-Made
Authors: Cartier Kimberly
Published: March 2019

Waterfalls sometimes imply a past dramatic event, like tectonic uplift or a landslide. Self-formed waterfalls could challenge that interpretation.
Soil microbial responses to drought and exotic plants shift carbon metabolism
Authors: Pérez Castro Sherlynette , Cleland Elsa E , Wagner Robert , Sawad Risha Al , Lipson David A
Published: March 2019

Significant gaps in our understanding of how global change drivers interact to affect the resistance and functioning of microbial communities hinders our ability to model ecosystem responses and feedbacks to co-occurring global stressors. Here, we investigated the effects of extreme drought and exotic plants, two of the most significant threats to Mediterranean-type ecosystems, on soil microbial community composition and carbon metabolic genes within a four-year field rainfall manipulation experiment. We combined measurements of bulk microbial and soil properties with high-throughput microbial community analyses to elucidate microbial responses and microbial-mediated alterations to carbon cycling. While microbial responses to experimental droughts were weak, scant rainfall periods resulted in decreased microbial biomass and activity, and relative abundances of bacterial groups such as Proteobacteria, Verrucomicrobia, and Acidobacteria decreased concomitantly with increases in Actinobacteria, Chloroflexi, and Firmicutes abundance. Soils under exotic plants had increased temperatures, enhanced infiltration during rainfall events, and decreased water retention and labile carbon in comparison to soils under native plants. Higher peaks and more seasonally variable microbial activity were found under exotic plants and, like drought periods, the microbial community shifted towards osmotic stress life-strategies. Relationships found between microbial taxonomic groups and carbon metabolic genes support the interpretation that exotic plants change microbial carbon cycling by altering the soil microclimate and supplying easily decomposed high-quality litter. Soil microbial community responses to drought and exotic plants could potentially impact ecosystem C storage by producing a smaller, more vulnerable C pool of microbial biomass that is prone to increased pulses of heterotrophic respiration.
Physiological adaptations to serpentinization in the Samail Ophiolite, Oman
Authors: Fones Elizabeth M , Colman Daniel R , Kraus Emily A , Nothaft Daniel B , Poudel Saroj , Rempfert Kaitlin R , Spear John R , Templeton Alexis S , Boyd Eric S
Published: March 2019

Hydration of ultramafic rock during the geologic process of serpentinization can generate reduced substrates that microorganisms may use to fuel their carbon and energy metabolisms. However, serpentinizing environments also place multiple constraints on microbial life by generating highly reduced hyperalkaline waters that are limited in dissolved inorganic carbon. To better understand how microbial life persists under these conditions, we performed geochemical measurements on waters from a serpentinizing environment and subjected planktonic microbial cells to metagenomic and physiological analyses. Metabolic potential inferred from metagenomes correlated with fluid type, and genes involved in anaerobic metabolisms were enriched in hyperalkaline waters. The abundance of planktonic cells and their rates of utilization of select single-carbon compounds were lower in hyperalkaline waters than alkaline waters. However, the ratios of substrate assimilation to dissimilation were higher in hyperalkaline waters than alkaline waters, which may represent adaptation to minimize energetic and physiologic stress imposed by highly reducing, carbon-limited conditions. Consistent with this hypothesis, estimated genome sizes and average oxidation states of carbon in inferred proteomes were lower in hyperalkaline waters than in alkaline waters. These data suggest that microorganisms inhabiting serpentinized waters exhibit a unique suite of physiological adaptations that allow for their persistence under these polyextremophilic conditions.
Two Chloroflexi classes independently evolved the ability to persist on atmospheric hydrogen and carbon monoxide
Authors: Islam Zahra F , Cordero Paul R F , Feng Joanna , Chen Ya-Jou , Bay Sean K , Jirapanjawat Thanavit , Gleadow Roslyn M , Carere Carlo R , Stott Matthew B , Chiri Eleonora , Greening Chris
Published: March 2019

Most aerobic bacteria exist in dormant states within natural environments. In these states, they endure adverse environmental conditions such as nutrient starvation by decreasing metabolic expenditure and using alternative energy sources. In this study, we investigated the energy sources that support persistence of two aerobic thermophilic strains of the environmentally widespread but understudied phylum Chloroflexi. A transcriptome study revealed that Thermomicrobium roseum (class Chloroflexia) extensively remodels its respiratory chain upon entry into stationary phase due to nutrient limitation. Whereas primary dehydrogenases associated with heterotrophic respiration were downregulated, putative operons encoding enzymes involved in molecular hydrogen (H2), carbon monoxide (CO), and sulfur compound oxidation were significantly upregulated. Gas chromatography and microsensor experiments showed that T. roseum aerobically respires H2 and CO at a range of environmentally relevant concentrations to sub-atmospheric levels. Phylogenetic analysis suggests that the hydrogenases and carbon monoxide dehydrogenases mediating these processes are widely distributed in Chloroflexi genomes and have probably been horizontally acquired on more than one occasion. Consistently, we confirmed that the sporulating isolate Thermogemmatispora sp. T81 (class Ktedonobacteria) also oxidises atmospheric H2 and CO during persistence, though further studies are required to determine if these findings extend to mesophilic strains. This study provides axenic culture evidence that atmospheric CO supports bacterial persistence and reports the third phylum, following Actinobacteria and Acidobacteria, to be experimentally shown to mediate the biogeochemically and ecologically important process of atmospheric H2 oxidation. This adds to the growing body of evidence that atmospheric trace gases are dependable energy sources for bacterial persistence.
Correction: Brain region-specific alterations of RNA editing in PDE8A mRNA in suicide decedents
Authors: Chimienti Fabrice , Cavarec Laurent , Vincent Laurent , Salvetat Nicolas , Arango Victoria , Underwood Mark D. , Mann J. John , Pujol Jean-François , Weissmann Dinah
Published: March 2019

Author forgot to attach a supplementary doc file which includes the supplementary methods and supplementary figure legends.
Chiral benzazaboroles as catalysts for enantioselective sulfonylation of cis-1,2-diols
Authors: Kuwano Satoru , Hosaka Yusei , Arai Takayoshi
Published: March 2019

Chiral benzazaboroles that function as catalysts for enantioselective reactions were developed.
Synthesis, characterization and structure of (NH4)4[Zn5VIV4VV16O56H2(H2O)4] with a novel V5O14 layer
Authors: Yuan Youyou , Wang Xiaoge , Chen Pohua , Sun Junliang
Published: March 2019

A new three-dimensional framework structure (NH4)4[Zn5VIV4VV16O56H2(H2O)4] was synthesized with a novel V5O14 layer in an all-inorganic synthesis system.
Preparation and characterization of Nephila clavipes tubuliform silk gut
Authors: Ruiz Víctor , Jiang Ping , Müller Claudia , Jorge Inmaculada , Vázquez Jesús , Ridruejo Álvaro , Aznar-Cervantes Salvador D. , Cenis José Luis , Messeguer-Olmo Luis , Elices Manuel , Guinea Gustavo Víctor , Pérez-Rigueiro José
Published: March 2019

Tubuliform silk gut shows intrinsic properties comparable to those of natural spider tubuliform silk fibers, but is obtained with an alternative spinning procedure that yields fibers with a cross-sectional area four orders of magnitude larger than that of the natural material.
Estimation of 3D human hand poses with structured pose prior
Authors: Guo Fangtai , He Zaixing , Zhang Shuyou , Zhao Xinyue
Published: March 2019

Here, the authors present multistage estimation model embedding with structured pose prior (SPP), a novel coarse‐to‐fine framework for real‐time 3D hand estimation from single depth image. Authors’ main contributions can be summarised as follows: (i) The authors proposed SPP to enforce constraints of canonical hand pose instead of original hand pose. (ii) The authors are the first to adopt under‐complete stacked denoising auto‐encoder (SDA) to construct pose prior by mapping canonical hand pose to latent representation. In the case of enforcing constraints of canonical hand pose, the authors empirically validate that under‐complete SDA outperforms over‐complete SDA in improving the hand estimation accuracy. (iii) The authors propose candidate keypoints patches (CKP) as intermediate data to conduct further hand pose refinement. Experimental evaluation on two publically available datasets shows that authors’ model is competitive both in accuracy and computation time. Especially, authors’ method placed first in the location of palm key‐point on both two datasets, and the high accuracy of hand palm key‐point plays an important role in many applications, such as that manipulator can grasp objects to specific coordinates with the guiding of human hand palm.
Agieren statt resignieren: Wie ein professioneller Einkauf mit Monopollieferanten umgeht
Authors: Schlüchtermann Jörg , Krampf Peter
Published: March 2019

Viele Einkäufer haben schon leidvolle eigene Erfahrungen gemacht: das komplette Handwerkszeug des Einkaufs scheint zu versagen, wenn auf der Lieferantenseite ein Monopolist sitzt, der auch noch arrogant auftritt und kontinuierlich neue Forderungen stellt. Doch es ist Zeit, den Mythos auszuräumen, dass der Einkäufer den Monopolisten chancenlos ausgeliefert ist. Ganz im Gegenteil – professionelle Einkäufer stecken den Kopf nicht in den Sand, sondern ergreifen aktiv Gegenmaßnahmen, um sich aus der einseitigen Machtposition der Zulieferer zu befreien.
Wirksame Sachkostensteuerung im Klinikeinkauf: Im Meer der Kennzahlen
Authors: Kleinhans Jennifer , Wimmer Verena
Published: March 2019

Sachkosten sind als Spitze des Eisbergs ein Indikator für den Erfolg von Prozessen des Klinikeinkaufs und seiner Zusammenarbeit mit Anwendern, Lieferanten und Verwaltung. Gerade die Beziehung zum Controlling unterliegt derzeit einem Veränderungsprozess.
Fehlende Fachkompetenz in Kliniken: Der perfekte Einkäufer – nur eine Illusion?
Authors: Mehner Manuela
Published: March 2019

Wie gewinnen wir Nachwuchs für den Klinikeinkauf? Wir diskutieren seit Jahren darüber und finden doch nur halbherzige Lösungen. Dabei ist dieser Beruf Herausforderung und Spannung zugleich. Eine Aufgabe zwischen strategischer Planung, oftmals emotionalen Konflikten, wirtschaftlichem und unternehmerischem Denken sowie Moderationsgeschick. Was genau muss der strategische Einkäufer einer Klinik also können?
Detachable glass micro/nanofluidic device
Authors: Ohta Ryoichi , Mawatari Kazuma , Takeuchi Tomoaki , Morikawa Kyojiro , Kitamori Takehiko
Published: March 2019

Glass is one of the most ideal materials for micro/nanofluidic devices due to its excellent optical transparency, resistance to a wide range of solvents and reagents, and easy to modify surfaces by silane-coupling reagents. From a practical point of view, glass is a hard material and is suitable for real applications. One of the advantages of glass is its reusability; however, this reusability is difficult to realize in certain conditions. Washing or re-modification of micro/nanofluidic channels is sometimes difficult due to the ultrasmall space in these channels. If the glass devices are detachable, it is easy to access the channel surface, and the channels can be cleaned and re-modified. When the substrates are bonded again, the devices are fabricated easily without repeating laborious and expensive micro/nano-fabrication processes. This technology gives researchers and users a choice of glass substrates in fundamental research studies and real-time applications. In this study, we propose a detachable glass micro/nanofluidic device by our low temperature bonding method. The surface bonding energy is controlled to realize both high pressure capacity for micro/nanofluidics and easy separation of glass substrates without fracturing. As a result, at least four times detaching and bonding is confirmed.
Paradoxical Desires
Authors: Jerzak Ethan
Published: March 2019

I present a paradoxical combination of desires. I show why it's paradoxical, and consider ways of responding. The paradox saddles us with an unappealing trilemma: either we reject the possibility of the case by placing surprising restrictions on what we can desire, or we deny plausibly constitutive principles linking desires to the conditions under which they are satisfied, or we revise some bit of classical logic. I argue that denying the possibility of the case is unmotivated on any reasonable way of thinking about mental content, and rejecting those desire-satisfaction principles leads to revenge paradoxes. So the best response is a non-classical one, according to which certain desires are neither determinately satisfied nor determinately not satisfied. Thus, theorizing about paradoxical propositional attitudes helps constrain the space of possibilities for adequate solutions to semantic paradoxes more generally.
Evolution of the Gekkotan Adhesive System: Does Digit Anatomy Point to One or More Origins?
Authors: Russell Anthony P , Gamble Tony
Published: March 2019

Recently-developed, molecularly-based phylogenies of geckos have provided the basis for reassessing the number of times adhesive toe-pads have arisen within the Gekkota. At present both a single origin and multiple origin hypotheses prevail, each of which has consequences that relate to explanations about digit form and evolutionary transitions underlying the enormous variation in adhesive toe pad structure among extant, limbed geckos (pygopods lack pertinent features). These competing hypotheses result from mapping the distribution of toe pads onto a phylogenetic framework employing the simple binary expedient of whether such toe pads are present or absent. It is evident, however, that adhesive toe pads are functional complexes that consist of a suite of integrated structural components that interact to bring about adhesive contact with the substratum and release from it. We evaluated the competing hypotheses about toe pad origins using 34 features associated with digit structure (drawn from the overall form of the digits; the presence and form of adhesive scansors; the proportions and structure of the phalanges; aspects of digital muscular and tendon morphology; presence and form of paraphalangeal elements; and the presence and form of substrate compliance-enhancing structures). We mapped these onto a well-supported phylogeny to reconstruct their evolution. Nineteen of these characters proved to be informative for all extant, limbed geckos, allowing us to assess which of them exhibit co-occurrence and/or clade-specificity. We found the absence of adhesive toe pads to be the ancestral state for the extant Gekkota as a whole, and our data to be consistent with independent origins of adhesive toe pads in the Diplodactylidae, Sphaerodactylidae, Phyllodactylidae, and Gekkonidae, with a strong likelihood of multiple origins in the latter three families. These findings are consistent with recently-published evidence of the presence of adhesively-competent digits in geckos generally regarded as lacking toe pads. Based upon morphology we identify other taxa at various locations within the gekkotan tree that are promising candidates for the expression of the early phases of adhesively-assisted locomotion. Investigation of functionally transitional forms will be valuable for enhancing our understanding of what is necessary and sufficient for the transition to adhesively-assisted locomotion, and for those whose objectives are to develop simulacra of the gekkotan adhesive system for biotechnological applications.
Apurinic/apyrimidinic endonuclease 1 (APE1) is dispensable for activation-induced cytidine deaminase (AID)-dependent somatic hypermutation in the immunoglobulin gene
Authors: Islam Helena , Kobayashi Maki , Honjo Tasuku
Published: March 2019

Activation-induced cytidine deaminase (AID) initiates DNA breakage in the variable (V) and switch (S) regions of the immunoglobulin gene, which results in somatic hypermutation (SHM) and class switch recombination (CSR), respectively. Apurinic/apyrimidinic endonuclease 1 (APE1) has been shown to be important for CSR, and is supposed to cleave at abasic sites when AID-dependently deaminated cytidine is removed by uracil DNA glycosylase. However, APE1 is unexpectedly dispensable for SHM in the S region and translocation between immunoglobulin heavy chain (IgH) and c-myc genes in the mouse B lymphoma cell line, CH12F3-2A. This suggested that APE1 is not involved in AID-dependent DNA breakage, but rather, in DNA repair. In order to investigate detailed molecular mechanisms underlying APE1’s involvement in CSR and SHM, we measured apurinic/apyrimidinic (AP) sites via aldehyde reactive probe labeling. Results indicated that the frequencies of AP sites in the S regions were not different between APE1−/−/−CH12F3-2A and wild-type CH12F3-2A cells. To carry out similar experiments in SHM of the V region, we generated an APE1 knockout (APE1−/−) human Burkitt’s lymphoma cell line, and compared SHM between APE1-proficient and -deficient BL2 lymphoma cells. SHM frequencies in the V regions of APE1−/−BL2 and APE1-proficient cells were also similar. Taken together, we showed that AID does not induce AP sites in the S region of the IgH gene, and that APE1 is not necessary for SHM in the V and S regions; however, it is required for DNA repair following DNA breakage in CSR.
Utility of Routine Axillary Ultrasound Surveillance in Breast Cancer Survivors with Previously Diagnosed Metastatic Axillary Adenopathy
Authors: Daugherty Michael W , Niell Bethany L
Published: March 2019

Objective

The purpose of this study is to evaluate the utility of routine axillary ultrasound surveillance in asymptomatic T1 or T2 breast cancer patients with 1 to 2 positive axillary nodes that did not undergo axillary lymph node dissection.

Methods

A retrospective review of our institutional database identified axillary and breast ultrasound examinations performed between February 1, 2011, and August 31, 2017, in asymptomatic T1 or T2 breast cancer patients with 1 to 2 positive axillary nodes that did not undergo axillary lymph node dissection. From the electronic medical record, patient demographics, imaging data, pathology results, and surgical reports were extracted. Positive predictive values (PPVs) 2 and 3 and cancer detection rate (CDR) were calculated with exact 95% confidence intervals (CIs).

Results

An average of 2.1 surveillance examinations was performed in 77 unique patients, yielding 160 total examinations. For 7 patients, 7 biopsies were recommended, and 5 biopsies were performed. No malignancy was diagnosed, yielding a PPV2 of 0% (0/7) (95% CI = 0% to 35%); PPV3 of 0% (0/5) (95% CI = 0% to 45%), and CDR of zero per 1000 (0/160) examinations (95% CI = 0 to 19).

Conclusion

Given the low frequency of axillary recurrence, routine axillary surveillance ultrasound in women with T1 or T2 breast cancers and 1 to 2 positive lymph nodes would be expected to have a low incremental CDR compared to clinical evaluation alone. Axillary surveillance ultrasound should not be routinely recommended or performed.
Transcending Boundaries
Authors: Whatley Sarah
Published: March 2019

This chapter explores the relationship between disability and improvisation within dance, drawing from a number of dancers’ own views about the place of improvisation in their making and performance practice, and referencing work that deliberately incorporates improvisation as a device to blur the boundaries between the fixed and the fluid. The chapter focuses on the role of contact improvisation in the work of disabled dancers. By prioritizing the interaction with different bodies, contact improvisation can support an aesthetic based on sensory adjustment and accommodation. Conversely, contact improvisation might be seen to ‘smooth over’ disorder and involuntary motion that disabled dancing bodies offer as a reconceptualization of the acceptable aesthetic in dance. The discussion also includes reference to Notturnino (2014), a work of choreography by Thomas Hauert, which was commissioned for the Candoco Dance Company and offers a way to examine how dance improvisation has adopted disability in its shifting physical aesthetic.
Hepatitis B virus activity in untreated hepatitis B e antigen–negative human immunodeficiency virus–hepatitis B virus co-infected patients from sub-Saharan Africa
Authors: Boyd Anders , Kouamé Menan Gerard , Houghtaling Laura , Moh Raoul , Gabillard Delphine , Maylin Sarah , Abdou Chekaraou Mariama , Delaugerre Constance , Anglaret Xavier , Eholié Serge Paul , Danel Christine , Zoulim Fabien , Lacombe Karine ,   on behalf of the ANRS 12136 Temprano and ANRS 12240 VarBVA studies
Published: March 2019

Background

In human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infected patients from sub-Saharan Africa with hepatitis B e antigen (HBeAg)-negative status, data are limited on the evolution of HBV activity when antiretroviral treatment (ART) is absent.

Methods

A total of 43 HBeAg-negative co-infected patients not indicated for ART (per concomitant World Health Organization recommendations) were followed during participation in a randomized controlled trial in Côte d’Ivoire. Chronic HBeAg-negative phases were classified at yearly visits and defined as ‘infection’ (HBV DNA ≤10 000 copies/mL and normal alanine aminotransferase [ALT]) or ‘hepatitis’ (HBV DNA >10 000 copies/mL and/or above normal ALT). Dispersion in HBV DNA and ALT levels during follow-up was assessed using interquartile range (IQR) regression.

Results

During a median 25 months (IQR 19–31), 17 (40%) patients consistently had ‘infection’, 5 (12%) consistently had ‘hepatitis’ and 21 (48%) fluctuated between phases. Wider dispersion in HBV DNA over time was associated with higher baseline HIV RNA (p=0.02) and higher baseline HBV DNA levels (p=0.008), while wider dispersion in ALT was associated with higher baseline HIV RNA (p<0.001), higher baseline ALT levels (p=0.02) and baseline hepatitis surface antigen >4.0 log10 IU/mL (p=0.02).

Conclusions

HBV activity is common with HBeAg-negative status, whose variation is partly linked to HIV replication. Fluctuations in disease phase make it difficult to assess the risk of morbidity and mortality after ART initiation.
How Do We Know That Our Patients Have Benefitted From Our ENT/Audiological Interventions? Presented at the Annual Meeting of ADANO 2016 in Berlin
Authors: Hall Deborah A. , Kitterick Pádraig , Heffernan Eithne , Fackrell Kathryn , Lucas Laura , Ferguson Melanie
Published: March 2019

This short review article gives an introduction to some of the fundamental concepts and challenges facing measurement in hearing healthcare practice and research. The impact of hearing loss almost always extends beyond the sensory impairment itself, even when the measured degree of audiometric loss is mild. Yet, going beyond audibility, into the realm of measuring impact, takes us into a much more complex and less well-defined space. How does one therefore best measure the therapeutic benefit for evaluating efficacy or for clinical practice audit? Three case studies illustrate approaches to overcome such challenges. Each example highlights the importance of thinking critically about what it is one is seeking trying to measure, rather than selecting a questionnaire instrument based simply on its popularity or accessibility. We conclude by highlighting the important role that clinicians can play in collecting clinical data about their preferred instruments so that we have some evidence to inform decisions about good practice (content validity etc.). We would also strongly support open data sharing as we think that this is one of the best ways to make the most rapid progress the field.
Melancholia as Predictor of Electroconvulsive Therapy Outcome in Later Life
Authors: Veltman Eveline M. , de Boer Alef , Dols Annemiek , van Exel Eric , Stek Max L. , Sienaert Pascal , Bouckaert Filip , van der Mast Roos , Rhebergen Didi
Published: March 2019

Objectives

In clinical practice, particularly melancholic depression benefits from electroconvulsive therapy (ECT), albeit research melancholia criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM) is not conclusive. We compared clinical characteristics and ECT outcome of melancholic and nonmelancholic depression, here defined by psychomotor symptoms.

Methods

One hundred ten depressed older in-patients treated with ECT were included in the Mood Disorders in Elderly treated with ECT study. The CORE was used for the assessment of psychomotor symptoms, with a score of 8 or higher defining melancholic depression. Depression severity was measured before, during, and after ECT. Characteristics were compared across melancholic and nonmelancholic patients. Regression analysis was used to assess the relation between psychomotor symptoms and remission/response, and survival analysis was used to examine the difference in time.

Results

Patients with melancholic depression had higher severity, lower cognitive and overall functioning, and lower prevalence of cardiovascular disease. However, no significant relations were found between CORE scores and remission/response. Because psychotic symptoms are a positive predictor of ECT response and remission, we examined whether CORE score was a predictor of response in the nonpsychotic group (n = 49). In nonpsychotic patients, remission was 62%, and the association between CORE scores and remission almost reached significance (P = 0.057).

Discussion

Although melancholically and nonmelancholically depressed patients differed significantly on several clinical characteristics, ECT outcome did not differ. Analyses may be hampered by a high prevalence of psychotic features. In nonpsychotic patients, CORE scores neared significance as predictor of remission, suggesting that CORE scores might be a distinguishing characteristic of melancholia in nonpsychotic patients and a clinical useful predictor of ECT response.
Supramodal Sentence Processing in the Human Brain: Fmri Evidence for the Influence of Syntactic Complexity in More Than 200 Participants
Authors: Uddén Julia , Hultén Annika , Schoffelen Jan-Mathijs , Lam Nietzsche , Harbusch Karin , van den Bosch Antal , Kempen Gerard , Petersson Karl Magnus , Hagoort Peter
Published: March 2019

This study investigated two questions. One is to which degree sentence processing beyond single words is independent of the input modality (speech vs. reading). The second question is which parts of the network recruited by both modalities is sensitive to syntactic complexity. These questions were investigated by having more than 200 participants read or listen to well-formed sentences or series of unconnected words. A largely left-hemisphere fronto-temporoparietal network was found to be supramodal in nature, i.e. independent of input modality. In addition, the left inferior frontal gyrus (LIFG) and the left posterior middle temporal gyrus (LpMTG) were most clearly associated with left-branching complexity. The left anterior middle temporal gyrus (LaMTG) showed the greatest sensitivity to sentences that differed in right-branching complexity. Moreover, activity in LIFG and LpMTG increased from sentence onset to end, in parallel with an increase of the left-branching complexity. While LIFG, bilateral anterior and posterior MTG and left inferior parietal lobe (LIPL) all contribute to the supramodal unification processes, the results suggest that these regions differ in their respective contributions to syntactic complexity related processing. The consequences of these findings for neurobiological models of language processing are discussed.
Dynamic network properties of the interictal brain determine whether seizures appear focal or generalised
Authors: Woldman Wessel , Schmidt Helmut , Abela Eugenio , Chowdhury Fahmida A. , Pawley Adam D. , Jewell Sharon , Richardson Mark P. , Terry John R.
Published: March 2019

Objective

Current explanatory concepts suggest seizures emerge from ongoing dynamics of brain networks. It is unclear how brain network properties determine focal or generalised seizure onset, or how network properties can be described in a clinically-useful manner. Understanding network properties would cast light on seizure-generating mechanisms and allow to quantify in the clinic the extent to which a seizure is focal or generalised.

Methods

68 people with epilepsy and 38 healthy controls underwent 19 channel scalp EEG recording. Functional brain networks were estimated in each subject using phase-locking between EEG channels in the 6-9Hz band from segments of 20s without interictal discharges. Simplified brain dynamics were simulated using a computer model. We introduce three concepts: Critical Coupling (Cc), the ability of a network to generate seizures; Onset Index (OI), the tendency of a region to generate seizures; and Participation Index (PI), the tendency of a region to become involved in seizures.

Results

Cc was lower in both patient groups compared with controls. OI and PI were more variable in focal-onset than generalised-onset cases. No regions showed higher OI and PI in generalised-onset cases than in healthy controls; in focal cases, the regions with highest OI and PI corresponded to the side of seizure onset.

Conclusions

Properties of interictal functional networks from scalp EEG can be estimated using a computer model and used to predict seizure likelihood and onset patterns. Our framework, consisting of three clinically-meaningful measures, could be implemented in the clinic to quantify the diagnosis and seizure onset pattern.
Abrogating ALIX interactions results in stuttering of the ESCRT machinery
Authors: Gupta Shilpa , Bendjennat Mourad , Saffarian Saveez
Published: March 2019

ESCRTs are cellular proteins that catalyze the fission of membranes and play an important role in biology of disease including cancer and infectious virus release1. ESCRT associated protein ALIX plays an essential role in HIV budding2-4, exosome release5,6, down regulation of G-protein coupled receptors7, cytokinesis8,9and multi vesicular budding1. The consensus view is that ALIX plays a role by binding to the viral late domains2-4/Syntenin late domain5/Cepp558,9and helps recruit downstream protein CHMP42,8,10,11which along with VPS4 catalyzes the fission of the membrane12,13. Using live imaging we have visualized the recruitment of ALIX, CHMP4 and VPS4 during budding of HIV with abrogated Gag-ALIX interactions. Based on the canonical view, we were expecting to find reduced recruitment of ALIX under these conditions. Instead we report observing multiple rounds of transient recruitment of ALIX, CHMP4 and VPS4 prior to virion release. We further show that during each, transient recruitment, stoichiometry of all ESCRT components remained the same regardless of mutations abrogating ALIX and Gag interaction. In addition, mutations abrogating interactions between Gag and TSG101 result in recruitment of ESCRTs with a substantial delay while maintaining similar stoichiometry. Our results demonstrate that recruitment of ESCRTs is driven by a robust network of interactions resulting in an “On/Off” switch behavior and ALIX’s interactions with late domains of HIV Gag play a crucial role during final catalysis of membrane fission after assembly of the full ESCRT machinery.
A HaloTag-TEV genetic cassette for mechanical phenotyping of proteins from tissues
Authors: Rivas-Pardo Jaime Andrés , Li Yong , Mártonfalvi Zsolt , Tapia-Rojo Rafael , Unger Andreas , Fernández-Trasancos Ángel , Herrero-Galán Elías , Velázquez-Carreras Diana , Fernández Julio M. , Linke Wolfgang A. , Alegre-Cebollada Jorge
Published: March 2019

Single-molecule methods using recombinant proteins have generated transformative hypotheses on how mechanical forces are generated and sensed in biological tissues. However, testing these mechanical hypotheses on native molecules in their natural environment remains inaccessible to conventional genetics, biophysics and molecular biology tools. To address these limitations, here we demonstrate a genetically engineered knock-in mouse model carrying a HaloTag-TEV insertion in the protein titin, the main determinant of myocyte stiffness. Using our system, we have specifically severed the titin filament by digestion with TEV protease, and found that the response of muscle fibers to length changes requires mechanical transduction through titin’s intact polypeptide chain. HaloTag-based covalent tethering has enabled directed examination of the dynamics of titin under 1-100 pN forces using recently developed magnetic tweezers. At pulling forces lower than 10 pN, titin domains are readily recruited to the unfolded state, and produce 41.5 zJ mechanical work during refolding. Our results support an active role of titin in muscle contraction in coordination with actomyosin motors. Insertion of the HaloTag-TEV cassette in proteins with mechanical roles opens new grounds to explore the molecular basis of cellular force generation, mechanosensing and mechanotransduction.
Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc
Authors: Lee Yongchan , Wiriyasermkul Pattama , Jin Chunhuan , Quan Lili , Ohgaki Ryuichi , Okuda Suguru , Kusakizako Tsukasa , Nishizawa Tomohiro , Oda Kazumasa , Ishitani Ryuichiro , Yokoyama Takeshi , Nakane Takanori , Shirouzu Mikako , Endou Hitoshi , Nagamori Shushi , Kanai Yoshikatsu , Nureki Osamu
Published: March 2019

The L-type amino acid transporter 1 (LAT1) transports large neutral amino acids and drugs across the plasma membrane and is crucial for nutrient uptake, brain drug delivery and tumor growth. LAT1 is a unique solute carrier that forms a disulfide-linked heterodimer with the cell-surface glycoprotein CD98 heavy chain (CD98hc), but the mechanisms of its molecular assembly and amino acid transport are poorly understood. Here we report the cryo-EM structure of the human LAT1-CD98hc heterodimer at 3.4 Å resolution, revealing the hitherto unprecedented architecture of a solute carrier-glycoprotein heterocomplex. LAT1 features a canonical LeuT-fold while exhibiting an unusual loop structure on transmembrane helix 6, creating an extended cavity to accommodate bulky hydrophobic amino acids and drugs. CD98hc engages with LAT1 through multiple interactions, not only in the extracellular and transmembrane domains but also in the interdomain linker. The heterodimer interface features multiple sterol molecules, corroborating previous biochemical data on the role of cholesterols in heterodimer stabilization. We also visualized the binding modes of two anti-CD98 antibodies and show that they recognize distinct, multiple epitopes on CD98hc but not its glycans, explaining their robust reactivities despite the glycan heterogeneity. Furthermore, we mapped disease-causing mutations onto the structure and homology models, which rationalized some of the phenotypes of SLC3- and SLC7-related congenital disorders. Together, these results shed light on the principles of the structural assembly between a glycoprotein and a solute carrier, and provide a template for improving preclinical drugs and therapeutic antibodies targeting LAT1 and CD98.
Generation of anisotropic strain dysregulates wild-type cell division at the interface between host and oncogenic tissue
Authors: Moruzzi Megan , Nestor-Bergmann Alexander , Goddard Georgina K. , Brennan Keith , Woolner Sarah
Published: March 2019

Epithelial tissues are highly sensitive to anisotropies in mechanical force, with cells altering fundamental behaviours such as cell adhesion, migration and cell division [1-5]. It is well known that in the later stages of carcinoma (epithelial cancer), the presence of tumours alters the mechanical properties of a host tissue and that these changes contribute to disease progression [6-9]. However, in the earliest stages of carcinoma, when a clonal cluster of oncogene-expressing cells first establishes in the epithelium, the extent to which mechanical changes alter cell behaviour in the tissue as a whole remains unclear. This is despite knowledge that many common oncogenes, such as oncogenic Ras, alter cell stiffness and contractility [10-13]. Here, we investigate how mechanical changes at the cellular level of an oncogenic cluster can translate into the generation of anisotropic strain across an epithelium, altering cell behaviour in neighbouring host tissue. We generated clusters of oncogene-expressing cells within otherwise normal in vivo epithelium, using Xenopus laevis embryos. We find that cells in kRasV12, but not cMYC, clusters have increased contractility, which introduces radial stress in the tissue and deforms surrounding host cells. The strain imposed by kRasV12 clusters leads to increased cell division and altered division orientation in the neighbouring host tissue, effects that can be rescued by reducing actomyosin contractility specifically in the kRasV12 cells. Our findings indicate that some oncogenes can alter the mechanical and proliferative properties of host tissue from the very earliest stages of cancer development, changes which have the potential to contribute to tumorigenesis.
Facile synthesis of novel antimony selenide nanocrystals with hierarchical architecture by physical vapor deposition technique
Authors: Bibin J. , Kunjomana A. G.
Published: March 2019

Stoichiometric antimony selenide (Sb2Se3) nanocrystals have been successfully engineered by a facile physical vapor deposition method, employing a single precursor of polycrystalline Sb2Se3 charge in a closed quartz ampoule under high vacuum without any foreign seed or extraneous chemical elements. This work underscores the efficacy of the vapor deposition process and provides synthetic strategies to scale down bulk Sb2Se3 into novel nanostructures. The morphological evolution of the tailored architecture was examined on micro and nano size scales by scanning electron microscopy and high-resolution transmission electron microscopy. The intrinsic mechanism governing the nanostructure formation is revealed as layer-by-layer growth, related to the unique layered structure of Sb2Se3. The optical properties of the grown crystals were probed by UV–vis–NIR and photoluminescence tools. The band-gap values of the microfibers, nanorods, nanooctahedra and nanospheres estimated from UV–vis–NIR analysis are found to be 1.25, 1.47, 1.51 and 1.75 eV, respectively. Powder X-ray diffraction, energy-dispersive analysis by X-rays, X-ray photoelectron spectroscopy, Raman spectroscopy and photoluminescence studies confirmed the quality, phase purity and homogeneity of the as-grown nanostructures. The adopted physical vapor deposition method is thus shown to be a simple and elegant route which resulted in the enhancement of the band gap for the Sb2Se3 samples compared with their counterparts grown by chemical methods. This approach has great potential for further applications in optoelectronics.
Virtuality at work and social media use among dispersed workers
Authors: Tijunaitis Karolis , Jeske Debora , Shultz Kenneth S.
Published: March 2019

Purpose

Technology and globalization of services have facilitated the digitalization of many processes at work. However, their impact on social capital is unknown. The purpose of this paper is to examine the relationships between virtuality in the workplace and social capital.

Design/methodology/approach

Using an online survey, the authors recruited 152 female student workers using an opportunity sampling approach.

Findings

Participants who used social media at work (n=112) reported higher social capital overall than participants who did not use any social media to communicate with colleagues at work (n=40). This difference also presented itself in terms of the social capital subscales (network ties, shared vision and trust). Mediation analysis conducted with users of social media at work revealed that social media use was a significant mediator in the relationship between virtuality at work and social capital overall (partial mediation). Subsequent analyses with the subscales for virtuality and social capital suggested full mediation of the relationship in most instances (with the exception of work practices).

Originality/value

This is the first study to examine the relationship between virtuality, social media and social capital at work. The result of this study suggests that social media use at work between colleagues can play a significant role in promoting social capital in workplaces that are heavily reliant on technological application to support interactions at work and feature geographical and temporal dispersion.