bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient‐reported outcomes in a large North American cohort living with chronic hepatitis B virus: a cross‐sectional analysis
Authors: Evon Donna M. , Lin Hsing‐Hua S. , Khalili Mandana , Fontana Robert J. , Yim Colina , Wahed Abdus S. , Fried Michael W. , Hoofnagle Jay H. ,   for the Hepatitis B Research Network (HBRN)
Published: January 2020

Background

Patient‐reported outcomes (PROs) such as health‐related quality of life (HRQoL) and symptoms associated with chronic hepatitis B viral (HBV) infection have not been well‐described in North American cohorts.

Aims

To evaluate several PROs and associations with HBV disease activity markers.

Methods

Cross‐sectional analysis including 876 adults who completed PRO measures during the Hepatitis B Research Network Adult Cohort Study. Participants on HBV treatment were excluded. Outcomes included: HRQoL using the SF‐36 mental component summary and physical component summary scores; symptom burden using a 10‐item Total Symptom Checklist and fatigue using an instrument from the Patient‐Reported Outcomes Measurement Information System®. Covariates included laboratory markers of disease severity, virological status, comorbidities and medications.

Results

Median age was 42 (range: 19‐79), 51% were female, 73% Asian, 19% HBeAg (+), 2% had AST‐platelet ratio index (APRI) ≥1.5 and 74% without comorbidities. Mean mental component summary T‐score = 52, physical component summary T‐score = 54 and PROMIS Fatigue T‐score = 47. On a scale from 0 (none) to 40 (extreme), the mean Symptom Checklist score = 3 and 25% reported no symptoms. The most frequent symptoms were fatigue (60%), irritability (32%) and itching (32%). Most symptoms were ‘a little bit’ bothersome. In multivariable regressions, APRI ≥1.50 and more comorbidities were associated with worse patient‐reported outcomes; virological markers were not. Adding the Total Symptom Checklist score to original regression models increased explanation of variation in the mental component summary score from 4% to 44% and the Physical Component Summary Score from 17% to 34%.

Conclusions

Untreated North American HBV patients with mild liver disease report favourable health‐related quality of life and minimal symptoms. HBV does not impact health‐related quality of life unless advanced liver disease or comorbidities are present. High symptom burden explains substantial variation in health‐related quality of life. (CT.gov identifier: NCT01263587).
A missense variant in complement factor B (CFB) is a potential predictor of 24‐week off‐treatment response to PegIFNα therapy in Chinese HBeAg‐positive chronic hepatitis B patients
Authors: Chen Haitao , Sun Jian , Zhou Bin , Peng Jinxin , Xie Qing , Liang Xieer , Fan Rong , Conran Carly , Xu Jianfeng , Ji Yuan , Zhang Xinxin , Sun Li , Jia Jidong , Wang Guiqiang , Hou Jinlin , Jiang De‐Ke
Published: January 2020

Background

To date, 14 single‐nucleotide polymorphisms (SNPs) have been identified as susceptibility loci for chronic hepatitis B (CHB).

Aim

To investigate if these SNPs are associated with treatment response of hepatitis B e antigen (HBeAg)‐positive CHB patients.

Methods

We performed a retrospective analysis of 1623 Han Chinese HBeAg‐positive CHB patients (782 patients treated with pegylated interferon alpha [PegIFNα] for 48 weeks plus 24 weeks follow‐up, and 841 patients treated with nucleos(t)ide analogues [NUCs] for 104 weeks) included in four phase‐IV multicentre randomised controlled trials. All 14 SNPs were genotyped for each CHB patient. A polygenic score (PGS) was used to evaluate the cumulative effect of multiple SNPs. The associations of SNPs or PGS with combined response (CR) and hepatitis B s antigen (HBsAg) loss were assessed.

Results

We found that rs12614, a missense variant of complement factor B (CFB), was significantly associated with CR in PegIFNα‐treated patients, and the CR rate in patients with the rs12614 TT/CT genotype was less than one‐third of that in patients with the CC genotype (7.4% vs 22.6%, P = 0.009). Moreover, a PGS integrating CFB rs12614 and STAT4 rs7574865 (previously reported to be associated with response to PegIFNα) was significantly associated with both CR (P‐trend = 4.000 × 10−4) and HBsAg loss (P‐trend = 0.010) in PegIFNα‐treated patients. However, none of the SNPs were associated with treatment response in NUCs‐treated patients.

Conclusions

CFB rs12614 is an independent predictor of response to PegIFNα therapy in Chinese HBeAg‐positive CHB patients. A PGS integrating CFB rs12614 with STAT4 rs7574865 can effectively discriminate responders to PegIFNα from nonresponders.
The natural flavonoid galangin ameliorates dextran sulphate sodium–induced ulcerative colitis in mice: Effect on Toll‐like receptor 4, inflammation and oxidative stress
Authors: Gerges Samar H. , Tolba Mai F. , Elsherbiny Doaa A. , El‐Demerdash Ebtehal
Published: January 2020

This study was carried out to investigate the potential therapeutic effect of galangin, a promising active principle of honeybee propolis, in dextran sulphate sodium (DSS)–induced colitis in mice. We explored the possible underlying mechanisms for galangin action and the therapeutic benefit of adding galangin to the standard therapy sulphasalazine. A galangin dose of 40 mg/kg was selected based on a preliminary dose‐selection study for investigation in a 4‐week cyclical model of DSS‐induced colitis. Mice received 3% DSS in their drinking water during the first and third weeks and were administered the treatments (40 mg/kg galangin, 100 mg/kg sulphasalazine and a combination of 20 mg/kg galangin and 50 mg/kg sulphasalazine) daily starting from the second week. Galangin significantly ameliorated DSS‐induced histopathological alterations and tissue injury, down‐regulated Toll‐like receptor 4 expression, suppressed NF‐κB p65 activation, lowered inflammatory cytokine levels and demonstrated antioxidant effects. The combination of galangin and sulphasalazine at half doses yielded comparable results to either drug alone at full dose. This study highlights galangin as a promising therapy for colitis management.
Safety and efficacy of eltrombopag plus pulsed dexamethasone as first‐line therapy for immune thrombocytopenia
Authors: Zhang Lunqing , Zhang Mingjie , Du Xin , Cheng Yunfeng , Cheng Gregory
Published: January 2020

Current first‐line treatments for immune thrombocytopenia (ITP) usually have transient effects and sustained platelet response off therapy remains low. We evaluated whether eltrombopag plus pulsed dexamethasone as first‐line therapy can increase the proportion of patients maintaining platelet counts >50 × 109/l for a prolonged period without further ITP therapy. Treatment consisted of eltrombopag 25–75 mg daily according to platelet response for 12 weeks plus dexamethasone, 40 mg daily for four consecutive days every four weeks for 1–3 courses. Primary endpoint was durable response off therapy defined as maintaining platelet counts >50 × 109/l for more than six months without further ITP therapy. Fifty ITP subjects were enrolled between November 2014 and March 2019. Out of 46 evaluable subjects, 26 (56·5%) had achieved the primary endpoint. The median platelet counts at six months off‐treatment follow‐up were 158 × 109/l. Only two out of 26 responders had relapsed at eight‐ and nine‐month follow‐up. The remaining 24 are still maintaining platelet counts >50 × 109/l, the longest over three years. All subjects tolerated treatment well and no Grade 3 or above adverse effects were reported. Eltrombopag plus pulsed dexamethasone as a first‐line therapy could result in durable response off therapy in a significant number of ITP subjects.
The role of the Polochic Fault as part of the North American and Caribbean Plate boundary: Insights from the infill of the Lake Izabal Basin
Authors: Obrist‐Farner Jonathan , Eckert Andreas , Locmelis Marek , Crowley James L. , Mota‐Vidaure Byron , Lodolo Emanuele , Rosenfeld Joshua , Duarte Edward
Published: January 2020

The Lake Izabal Basin in Guatemala is a major pull‐apart basin along the sinistral Polochic Fault, which is part of the North American and Caribbean plate boundary. The basin infill contains information about the tectonic and sedimentological processes that have imparted a significant control on its sedimentary section. The inception of the basin has been linked to the relative importance of the Polochic Fault in the tectonic history of the plate boundary; yet, its sedimentological record and its inception age have been poorly documented. This study integrates diverse datasets, including industry reports, well logs and reports, well cuttings, vintage seismic data, outcrop observations and geochronological data to constrain the initial infill and age of inception of the basin. The integrated data show that during the Oligocene–Miocene, a marine carbonate platform was established in the region which was later uplifted and eroded in the early Miocene. The fluvial–lacustrine deposits above this carbonate platform are part of the initial infill of the basin and are constrained with zircon weighted‐mean 206Pb/238U ages of 12.060 ± 0.008 from a volcanic tuff ~30 m above the unconformity. Sandstone, mudstone and coal dominate the interval from 12 to 4 Ma, with an increase in conglomerate correlating to the uplift of the Mico Mountains and San Gil Hill at 4 Ma. Fault switch activity between the Polochic and Motagua faults has been hypothesized to explain total offset along the Polochic Fault and the geologic and geodetic slip rates along the two faults. The 12 Ma age determined for the initial infill of the basin confirms this hypothesis. Consequently, our study confirms that at ~12 Ma the Polochic Fault served as the main fault of the plate boundary with inferred slip rates ranging from 13 to 21 mm/yr with a strong possibility that the Polochic Fault was, at some point between 15 Ma and 7 Ma, the only active fault of the plate boundary. The results of this study show that tectonic records preserved in sediments of strike‐slip basins improve the understanding of the relative significance of individual faults and the implications with respect to strain partitioning throughout its tectonic history.
Insect herbivory and herbivores ofFicusspecies along a rain forest elevational gradient in Papua New Guinea
Authors: Sam Katerina , Koane Bonny , Sam Legi , Mrazova Anna , Segar Simon , Volf Martin , Moos Martin , Simek Petr , Sisol Mentap , Novotny Vojtech
Published: January 2020

Classic research on elevational gradients in plant–herbivore interactions holds that insect herbivore pressure is stronger under warmer climates of low elevations. However, recent work has questioned this paradigm, arguing that it oversimplifies the ecological complexity in which plant–insect herbivore interactions are embedded. Knowledge of antagonistic networks of plants and herbivores is however crucial for understanding the mechanisms that govern ecosystem functioning. We examined herbivore damage and insect herbivores of eight species of genusFicus(105 saplings) and plant constitutive defensive traits of two of these species, along a rain forest elevational gradient of Mt. Wilhelm (200–2,700 m a.s.l.), in tropical Papua New Guinea. We report overall herbivore damage 2.4% of leaf area, ranging from 0.03% inFicus endochaeteat 1,700 m a.s.l. to 6.1% inF. hombronianaat 700 m a.s.l. Herbivore damage and herbivore abundances varied significantly with elevation, as well as among the tree species, and between the wet and dry season. Community‐wide herbivore damage followed a hump‐shaped pattern with the peak between 700 and 1,200 m a.s.l. and this pattern corresponded with abundance of herbivores. For two tree species surveyed in detail, we observed decreasing and hump‐shaped patterns in herbivory, in general matching the trends found in the set of plant defenses measured here. Our results imply that vegetation growing at mid‐elevations of the elevational gradient, that is at the climatically most favorable elevations where water is abundant, and temperatures still relatively warm, suffers the maximum amount of herbivorous damage which changes seasonally, reflecting the water availability.
Hospital volume and postoperative 5‐year survival for five different cancer sites: A population‐based study in Japan
Authors: Okawa Sumiyo , Tabuchi Takahiro , Morishima Toshitaka , Koyama Shihoko , Taniyama Yukari , Miyashiro Isao
Published: January 2020

The relationship between hospital volume and patient outcome is globally known; thus, hospital volume is widely used as a quality indicator. In Japan, however, recent studies on this topic are scarce. The present study examined whether hospital surgery volume is associated with postoperative 5‐year survival among cancer patients. Using the Osaka Cancer Registry, we identified a sample of 86 145 patients who were diagnosed with cancer at any of five different sites (stomach, colorectum, lung, breast and uterus) and underwent surgeries between 2007 and 2011 in Osaka. We ranked hospitals by annual surgical volume, sorted patients in descending order by hospital volume, and assigned them into quartiles (high, medium, low and very low volume). We analyzed the association between hospital volume and 5‐year survival among 80 959 patients aged between 15 and 84 years using Cox proportional hazard models. Adjustments were made for characteristics of patients, type of surgery and adjuvant treatment received. The mortality hazard of patients treated at very low‐volume hospitals was 1.36‐1.82‐fold higher than that of patients treated at high‐volume hospitals. Absolute differences in adjusted survival rates between high‐volume and very low‐volume hospitals varied with the cancer site: 14.9 in stomach, 11.5 in colorectal, 10.8 in lung, 2.4 in breast and 3.3 in uterine cancers. Hospitals with lower surgery volumes showed higher mortality risks after cancer surgery than those with higher volumes. Monitoring site‐specific surgery volumes and referring patients from low‐volume to high‐volume hospitals may be beneficial for improving the long‐term survival of cancer patients.
Icariin prevents oestrogen deficiency–induced alveolar bone loss through promoting osteogenesis via STAT3
Authors: Xu Hongyuan , Zhou Siru , Qu Ranyi , Yang Yiling , Gong Xinyi , Hong Yueyang , Jin Anting , Huang Xiangru , Dai Qinggang , Jiang Lingyong
Published: January 2020

Objectives

Alveolar bone osteoporosis has attracted more and more attention because of its profound impact on stomatognathic function and treatment, but current treatments have not been targeted to alveolar bone and might even cause severe side effects. Thus, identifying the effects of anti‐osteoporosis agents on alveolar bone is essential. Icariin ameliorates metabolic dysfunction of long bones, but its effects on alveolar bone remain unclarified.

Materials and methods

BMSCs were isolated from rat mandibles (mBMSCs). The osteogenic potential of mBMSCs and the signalling pathway involved under icariin treatment were measured by ALP and alizarin red staining, reverse transcription‐polymerase chain reaction (RT‐PCR), Western blotting and immunofluorescence. Dual‐luciferase assay, chromatin immunoprecipitation (ChIP) and co‐immunoprecipitation were used to investigate the molecular mechanism. Ovariectomized and sham‐operated rats treated with or without icariin were analysed by micro‐CT, TRAP staining and calcein double labelling.

Results

We found that icariin promoted osteoblast differentiation of mBMSCs. Furthermore, STAT3 was critical for icariin‐promoted osteoblast differentiation, as indicated by increased phosphorylation levels in icariin‐treated mBMSCs, while preventing STAT3 activation blocked icariin‐induced osteoblast differentiation. Mechanistically, icariin‐promoted transcription of the downstream osteogenic gene osteocalcin (Ocn) through STAT3 and STAT3 bound to the promoter of Ocn. Notably, icariin prevented the alveolar bone osteoporosis induced by oestrogen deficiency through promoting bone formation.

Conclusions

For the first time, our work provides evidence supporting the potential application of icariin in promoting osteogenesis and treating alveolar bone osteoporosis.
CD10 and p63 expression in a sarcomatoid undifferentiated melanoma: A cautionary (and molecularly annotated) tale
Authors: Lefferts Joel A , Loehrer Andrew P. , Yan Shaofeng , Green Donald C. , Deharvengt Sophie J. , LeBlanc Robert E.
Published: January 2020

Undifferentiated melanoma should be considered in the differential diagnosis of sarcomatoid cutaneous malignancies to ensure that patients receive the correct treatment. Dermatopathologists should recognize the pitfalls of relying too heavily on immunohistochemistry to establish this diagnosis and consider ancillary tests, including single‐nucleotide polymorphism (SNP) copy number arrays and targeted next‐generation sequencing (NGS), when a definitive diagnosis cannot be rendered on a primary or metastatic tumor. This technology can also help to exclude a collision of melanoma and sarcoma when both differentiated and undifferentiated components are juxtaposed. We describe an exceedingly rare, illustrative example of undifferentiated sarcomatoid melanoma presenting as a pedunculated nodule. The clinical context and presence of a small differentiated component helped to establish the diagnosis; however, the transition from differentiated to undifferentiated melanoma was accompanied by an abrupt loss of S100, Sox10, MITF, MelanA, and HMB45 with gain of CD10 and p63 staining. SNP copy number array and NGS revealed shared chromosomal copy number changes and overlapping mutations with additional aberrances detected exclusively in the sarcomatoid component, thereby excluding a collision tumor and confirming our putative impression of melanoma with progression to an undifferentiated sarcomatoid phenotype.
Akhirin regulates the proliferation and differentiation of neural stem cells/progenitor cells at neurogenic niches in mouse brain
Authors: Anam Mohammad Badrul , Ahmad Shah Adil Ishtiyaq , Kudo Mikiko , Istiaq Arif , Felemban Athary Abdulhaleem M. , Ito Naofumi , Ohta Kunimasa
Published: January 2020

Specialized microenvironment, or neurogenic niche, in embryonic and postnatal mouse brain plays critical roles during neurogenesis throughout adulthood. The subventricular zone (SVZ) and the dentate gyrus (DG) of hippocampus in the mouse brain are two major neurogenic niches where neurogenesis is directed by numerous regulatory factors. Now, we report Akhirin (AKH), a stem cell maintenance factor in mouse spinal cord, plays a pivotal regulatory role in the SVZ and in the DG. AKH showed specific distribution during development in embryonic and postnatal neurogenic niches. Loss of AKH led to abnormal development of the ventricular zone and the DG along with reduction of cellular proliferation in both regions. In AKH knockout mice (AKH−/−), quiescent neural stem cells (NSCs) increased, while proliferative NSCs or neural progenitor cells decreased at both neurogenic niches. In vitro NSC culture assay showed increased number of neurospheres and reduced neurogenesis in AKH−/−. These results indicate that AKH, at the neurogenic niche, exerts dynamic regulatory role on NSC self‐renewal, proliferation and differentiation during SVZ and hippocampal neurogenesis.
A qualitative study of clinician attitudes towards closed‐loop systems in mainstream diabetes care in England
Authors: Farrington C. , Murphy H. R. , Hovorka R.
Published: January 2020

Aim

Clinicians mediate access to new technologies. Consequently, their views on specific devices may influence user access to diabetes technology in mainstream care. As yet, little is known about clinicians’ views about closed‐loop systems. This qualitative study explored clinicians’ views on the likely impacts of future closed‐loop systems in mainstream diabetes care in England.

Methods

We conducted interviews with 36 clinicians from a range of professional backgrounds in five hospital outpatient clinics (two adult, two pregnancy, one paediatric) in England to explore possible consequences of closed‐loop systems for users and clinicians. Data analysis utilized a framework approach.

Results

Clinicians reported a range of expected benefits for future users, including improved glucose control and quality of life. Expected burdens included continued need for manual input and the risk of losing basic self‐care skills. In terms of future clinical workloads, three clinicians emphasized only positive impacts, seven emphasized both positive and negative impacts, and 17 mentioned only negative impacts. Our most prominent finding, expressed by 24 clinicians, was that closed‐loop systems would generate initial challenges due to the need for staff training, user education and support, and new analytical capacities, alongside existing intra‐clinic variations in technological experience.

Conclusions

Clinicians recognize the value of closed‐loop systems in terms of health benefits, but also identify a range of concerns for both users and healthcare staff, which could impact negatively on user access. Future implementation efforts should address these concerns by providing training and support for healthcare teams, taking varied technological expertise into account.
The changing face of agriculture in Tanzania: Indicators of transformation
Authors: Wineman Ayala , Jayne Thomas S. , Isinika Modamba Emma , Kray Holger
Published: January 2020

Motivation

The extent to which African farming systems are undergoing transformation continues to be strongly debated.

Purpose

With a focus on Tanzania, this study assesses whether recent trends in farm behaviour, the structure of farming, and agricultural commercialization and productivity conform to stylized facts about agricultural transformation. In the process, we propose an updated typology of farms that reflects recent changes in the relative importance of different farm categories and sheds light on the heterogeneity found even among smallholder farms.

Approach and methods

To this end, we refer to farm‐household survey data over the period 2008–2014.

Findings

We find that medium‐scale farms and small, farm‐focused, commercialized farms are claiming an increasingly prominent role in Tanzanian agriculture. Farmers are more likely to participate in markets for land and labour, to engage in some forms of agricultural intensification and to exhibit a commercial orientation. Over the study period, the real value of agricultural output grew substantially, mostly reflecting a remarkable expansion of cropland rather than increased land productivity. Labour productivity also grew, driven by a reduction in labour intensity. At the same time, Tanzania is experiencing a dramatic movement of labour out of agriculture.

Policy implications

Together, the evidence suggests that Tanzania is on the cusp of larger transformational processes in the decades to come. With this knowledge, policies can be thoughtfully shaped to support agricultural growth (particularly in land productivity) and meet farmers' diverse needs.
Climate limitation at the cold edge: contrasting perspectives from species distribution modelling and a transplant experiment
Authors: Greiser Caroline , Hylander Kristoffer , Meineri Eric , Luoto Miska , Ehrlén Johan
Published: January 2020

The role of climate in determining range margins is often studied using species distribution models (SDMs), which are easily applied but have well‐known limitations, e.g. due to their correlative nature and colonization and extinction time lags. Transplant experiments can give more direct information on environmental effects, but often cover small spatial and temporal scales. We simultaneously applied a SDM using high‐resolution spatial predictors and an integral projection (demographic) model based on a transplant experiment at 58 sites to examine the effects of microclimate, light and soil conditions on the distribution and performance of a forest herb,Lathyrus vernus, at its cold range margin in central Sweden. In the SDM, occurrences were strongly associated with warmer climates. In contrast, only weak effects of climate were detected in the transplant experiment, whereas effects of soil conditions and light dominated. The higher contribution of climate in the SDM is likely a result from its correlation with soil quality, forest type and potentially historic land use, which were unaccounted for in the model. Predicted habitat suitability and population growth rate, yielded by the two approaches, were not correlated across the transplant sites. We argue that the ranking of site habitat suitability is probably more reliable in the transplant experiment than in the SDM because predictors in the former better describe understory conditions, but that ranking might vary among years, e.g. due to differences in climate. Our results suggest thatL. vernusis limited by soil and light rather than directly by climate at its northern range edge, where conifers dominate forests and create suboptimal conditions of soil and canopy‐penetrating light. A general implication of our study is that to better understand how climate change influences range dynamics, we should not only strive to improve existing approaches but also to use multiple approaches in concert.
samc: an R package for connectivity modeling with spatial absorbing Markov chains
Authors: Marx Andrew J. , Wang Chao , Sefair Jorge A. , Acevedo Miguel A. , Fletcher Robert J.
Published: January 2020

Quantifying landscape connectivity is fundamental to better understand and predict how populations respond to environmental change. Currently, popular methods to quantify landscape connectivity emphasize how landscape features provide resistance to movement. While many tools are available to quantify landscape resistance, these do not discern between two fundamentally different sources of resistance: movement behavior and mortality. To address this issue, we developed the samc R package that quantifies landscape connectivity using absorbing Markov chain theory. Within this mathematical framework, movements are represented as transient states in the Markov chain, while mortality is represented by transitions to absorbing states. Not only does this framework explicitly account for these different issues, it provides a probabilistic approach that can incorporate both short‐term and long‐term dynamics, as well as species distribution and abundance. The package includes functions to quantify life expectancy, long‐term visitation rates, and various spatially and temporally explicit measures of mortality and movement at the local and landscape scales. These functions in samc have been optimized to find computationally practical solutions in landscapes comprised of > 2 × 106cells. Here, we illustrate the workflow of the samc package with publicly available movement and mortality data on the endangered Florida pantherPuma concolor coryi. This analysis showed that movement and mortality are generally correlated except for locations near roads (areas of high mortality risk) that are within the dispersal range of source locations. This pattern would have been undetectable with current methods that quantify movement resistance. Overall, the samc package provides a means for implementing spatial absorbing Markov chains that can distinguish between movement behavior and mortality resulting in more reliable landscape connectivity measures.
Habitats of Pleistocene megaherbivores reconstructed from the frozen fauna remains
Authors: Axmanová Irena , Robovský Jan , Tichý Lubomír , Danihelka Jiří , Troeva Elena , Protopopov Albert , Chytrý Milan
Published: January 2020

The Late Pleistocene landscape in northern Eurasia and North America was inhabited by a specific megafaunal complex, which largely disappeared during the Pleistocene/Holocene transition. Vegetation changes are considered as one of the factors responsible for these extinctions, but the structure and composition of the Pleistocene vegetation are still poorly known. Here we complement previous studies by comparing the taxonomic composition of the plant remains found in the gastrointestinal tracts of the frozen carcasses of Pleistocene megaherbivores with the species composition of the current Siberian vegetation. We compiled a dataset of palaeobotanical records from frozen individuals of Pleistocene megaherbivores found in northern Siberia and Beringia and dated to the period from more than 50 kyr BP to 9 kyr BP. We also compiled a dataset of vegetation plots from several regions in Siberia. We analysed the similarity in taxonomic composition of plants between these two datasets using a novel method that accounts for variable taxonomic resolution in palaeobotanical data. For most megaherbivore individuals, plant remains in their gastrointestinal tracts corresponded to tundra, forest and mire vegetation, while they showed low similarity to steppe. This pattern was relatively constant over time, showing no remarkable differences between the Last Glacial Maximum and the periods before and afterwards. This suggests that during the Upper Pleistocene, a mosaic of mesic and wet vegetation types such as tundra with patches of forests and mires was common in northern Siberia and Beringia. In contrast, the steppe was rare to absent in the landscape or underused by the megaherbivores as a pasture since they found enough food in the widespread mesic and wet habitats with more productive vegetation.
Does alpha phase modulate visual target detection? Three experiments with tACS‐phase‐based stimulus presentation
Authors: de Graaf Tom A. , Thomson Alix , Janssens Shanice E.W. , van Bree Sander , ten Oever Sanne , Sack Alexander T.
Published: January 2020

In recent years, the influence of alpha (7–13 Hz) phase on visual processing has received a lot of attention. Magneto‐/encephalography (M/EEG) studies showed that alpha phase indexes visual excitability and task performance. Studies with transcranial alternating current stimulation (tACS) aim to modulate oscillations and causally impact task performance. Here, we applied right occipital tACS (O2 location) to assess the functional role of alpha phase in a series of experiments. We presented visual stimuli at different pre‐determined, experimentally controlled, phases of the entraining tACS signal, hypothesizing that this should result in an oscillatory pattern of visual performance in specifically left hemifield detection tasks. In experiment 1, we applied 10 Hz tACS and used separate psychophysical staircases for six equidistant tACS‐phase conditions, obtaining contrast thresholds for detection of visual gratings in left or right hemifield. In experiments 2 and 3, tACS was at EEG‐based individual peak alpha frequency. In experiment 2, we measured detection rates for gratings with (pseudo‐)fixed contrast. In experiment 3, participants detected brief luminance changes in a custom‐built LED device, at eight equidistant alpha phases. In none of the experiments did the primary outcome measure over phase conditions consistently reflect a one‐cycle sinusoid. However, post hoc analyses of reaction times (RT) suggested that tACS alpha phase did modulate RT for specifically left hemifield targets in both experiments 1 and 2 (not measured in experiment 3). This observation requires future confirmation, but is in line with the idea that alpha phase causally gates visual inputs through cortical excitability modulation.
Exploring the Impact of Firm‐level Legality on Tax Avoidance
Authors: Ginesti Gianluca , Ballestra Luca Vincenzo , Macchioni Riccardo
Published: January 2020

Although the topic of legality is receiving increasing interest in academic and policy debates, examining its economic effects at the firm level remains a relatively underexplored line of research. This study offers further advances to the existing literature by performing an examination of the relationship between corporate legality and tax avoidance. Based on a unique dataset of 1,168 private Italian companies and by exploiting a novel measure of corporate legality developed by the Italian Competition Authority, we provide evidence that firm‐level legality is positively associated with effective tax rates ..(i.e., lower tax avoidance practices). These findings are robust to a battery of additional tests and are informative for local policymakers and international investors since they suggest that legality is an important factor to which attention should be paid in scrutinizing corporate tax strategies.
Association of leaf silicon content with chronic wind exposure across and within herbaceous plant species
Authors: Song Yao‐Bin , Hu Yu‐Kun , Pan Xu , Liu Guo‐Fang , Xiong Wei , Dong Ming , Cornelissen Johannes H. C.
Published: January 2020

Aim

High foliar silicon (henceforth Si) concentration protects plant tissues against herbivory, but protection against several abiotic stressors has also been proposed, although the adaptive significance of these functions is still being debated. We aimed to explore the potential relationships between foliar Si content and chronic wind exposure across a large scale and multiple species and to analyse an overlooked alternative or complementary function of silicon in leaves: mechanical protection against wind.

Location

Mainland China.

Time period

From July to September during 2012–2014.

Major taxa studied

Two hundred and eighty‐two vascular plant species in predominantly herbaceous communities.

Methods

We compiled a dataset for leaf silicon concentration ([Si]) across 27 sites and 153 herbaceous plots within the major climate zones of China. We hypothesized that evolutionary lineages that generally have high [Si] should show positive relationships between leaf [Si] and mean annual wind speed.

Results

Within major families with generally high [Si] (especially grasses, sedges and composites), leaf [Si] exhibits a consistently positive correlation with mean wind speed among species across China. For the seven widespread monocot species with high leaf [Si], including the globally distributed common reed (Phragmites australis), intraspecific variation in leaf [Si] exhibits the same consistent positive correlation with mean wind speed.

Main conclusions

Our findings suggest that high leaf [Si] is likely to have widespread adaptive value for wind exposure of leaves, at least in several very widespread families and species of herbaceous plants. Damage from wind is a danger for plants in many ecosystems, hence these findings are of global significance and indicate that further research into large‐scale variation of leaf Si and mechanical traits in relationship to wind exposure is likely to be illuminating.
SWINGING OF THE BREATH: UNDECIDABILITY AND ZONES OF INDISTINCTION IN HERTA MÜLLER'S ATEMSCHAUKEL
Authors: Hoeeg Mette Leonard
Published: January 2020

In this essay I use Giorgio Agamben's concept of ‘zones of indistinction’ in an investigation of how undecidability functions in the generation of meaning in Herta Müller's Atemschaukel. I argue that, by evoking a number of oppositional pairs, Atemschaukel demarcates an area as a zone of indistinction. Within this zone the thinking and experience of the first‐person narrator, and, by extension, of the reader, oscillate between different modes, and tension is produced and sustained. Through this zone some of the most significant meanings of the narrative regarding the nature of representation, historic truth, and the truth of a specific witness are conveyed. While undecidability on the level of genre and the representation of reality is arguably the most obvious form in Atemschaukel, it is not the main focus of my analysis. Rather, my purpose is to shed light on the interrelation of oppositional pairs and their effect of meaning‐production without subsuming the various forms of undecidability under the obvious one of genre, as a categorisation of the work as ‘autofiction’ would probably do. Thus I challenge the generic categorisation of complex works of undecidability such as Atemschaukel and argue that in order to recognise certain meanings of the work, the reader must accept the unresolved nature of its undecidabilities.
HUMANITY IN DARK TIMES: HANNAH ARENDT AND HERTA MÜLLER
Authors: Haines Brigid
Published: January 2020

This paper reads Herta Müller's life and works in the light of those of Hannah Arendt in order to explore Müller's place within broad currents of European history, literature, and thought. Arendt and Müller are ethical, phenomenological, and instinctively iconoclastic thinkers who insist on the value of experience and are unafraid to think and speak, to use Arendt's term, ‘without a banister’. Both mount a modernist challenge to totalising discourses and seek out the possibilities of humanity in dark times, locating these in ideology's opposites: singularity, newness, and infinite possibility, in short, in the ‘natality’ (Arendt) which characterises the human condition. Müller's protagonists experience the loneliness and atomisation that Arendt identified as central to totalitarian rule, but they are also survivors and witnesses whose stories illuminate across time. Müller's disorienting collage technique, reminiscent of Benjamin's montages of quotations, promotes in the consumer a process of judgement and thought, a ‘vigilant partiality’ (Arendt on G. E. Lessing) which spurs engagement with the issues of their own era.
In the gateway's shadow: Interactions between Singapore's Hinterlands
Authors: Hutchinson Francis E.
Published: January 2020

During the 1990s, Singapore, the Malaysian state of Johor and the Riau Islands in Indonesia marketed themselves as a single investment destination. Due to its capital, technology, and superior logistics, Singapore was the “gateway”; Johor and the Riau Islands were the hinterland—supplying land, labour, and resources. Since then, production networks between the three territories have deepened. Interactions with Singapore have also catalysed connections between Johor and the Riau Islands. To date, research has focussed on the city‐state as the gateway and/or linkages between it and one of the two hinterlands. This emphasis is inherent in the “Gateway City” framework, which focusses on the primary city at the expense of its hinterlands and also overlooks mediating influences such as borders and border regimes. This article proposes complementing the Gateway City with the Cross‐Border Region framework to gain stronger purchase on the unit of analysis and focusing on inter‐hinterland dynamics to gain a more complete picture of how gateway cities affect their surrounding areas. Through applying this expanded theoretical framework to study the interactions of Johor and the Riau Islands, this article seeks to shed light on an under‐theorised and under‐studied aspect of gateway cities.
Institutional context and place‐based policy: The case of Coventry & Warwickshire
Authors: Glückler Johannes
Published: January 2020

A key problem of downscaling or transferring policies across regions is embedding these policies into a place for them to unleash the full potential of regional economies. This paper elaborates on the analytical framework of “institutional context” to bridge the gap between rich theorizations and poor empirical capture of institutions in studies of regional development. The institutional context is constituted by three pillars—regulations, organizations, and institutions—as well as by the interrelations between these pillars. Applied to the British region of Coventry and Warwickshire, a qualitative analysis of expert interviews finds institutional patterns of short‐termism, moderate levels of social capital and an embryonic relational infrastructure to constrain the place‐based strategy for industrial diversification. This regional case illustrates the more general challenge for regional policy in the UK of devising place‐based strategies under conditions of continuous rescaling of regional governance and the implementation of a new National Industrial Strategy. In conclusion, the analysis suggests a shift from “nodal” to “linking” policies that support cross‐network connections and help grow a regional field for collective action to cross‐fertilize knowledge and foster innovation and entrepreneurship in emerging industries.
Association of hepatocellular carcinoma risk with polymorphisms in tumour necrosis factor alpha gene in a Chinese Han population
Authors: Yue Xin , Jiang Xin , Zou Hongjiu , Li Gaokai , Wang Jinan , Liu Ying
Published: January 2020

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. Studies have shown that the tumour necrosis factor alpha (TNF‐α) plays an important role in the development of HCC; however, the association between genetic variations of TNF‐α and HCC is not yet fully understood. To evaluate the correlation of TNF‐α polymorphisms with HCC, we randomly selected 327 HCC patients and 432 healthy controls, all these subjects reported Han nationality. Genotyping of four TNF‐α SNPs (rs1799724, rs1800629, rs1799964 and rs1800610) was performed using the matrix‐assisted laser desorption ionization‐time of flight mass spectrometry (MALDI‐TOF‐MS) method. Distributions of rs1799964 genotypes and rs1800610 alleles were found to be significantly different between cases and controls (p = .011, p = .001). The recessive model of rs1799964 significantly increased HCC risk (p = .0015), while the dominant and over‐dominant models of rs1800610 significantly reduced HCC risk (p = .0096, p = .014). Haplotype analysis of the four TNF‐α SNPs revealed that the TGTA haplotype was associated with a reduced HCC risk (p = .0033, OR = 0.53), while the TGTG haplotype was associated with an increased HCC risk (p = .0032, OR = 9.69). These findings indicated that specific TNF‐α polymorphisms may be associated with the susceptibility to HCC.
Portopulmonary hypertension: prognosis and management in the current treatment era – results from the REHAP registry
Authors: Lazaro Salvador Maria , Quezada Loaiza Carlos A. , Rodríguez Padial Luis , Barberá Joan A. , López‐Meseguer Manuel , López‐Reyes Raquel , Sala‐Llinas Ernest , Alcolea Sergio , Blanco Isabel , Escribano‐Subías Pilar ,   REHAP Investigators
Published: January 2020

Background

Portopulmonary hypertension (PoPH) is a rare condition with poorer survival compared to idiopathic/familial pulmonary arterial hypertension (IPAH/FPAH).

Aims

To compare the characteristics, survival, prognostic factors and management of PoPH and IPAH/FPAH patients and to assess the impact of treatment on survival of PoPH patients.

Methods

Analysis of data of prevalent and incident PoPH patients enrolled in the Spanish registry of PAH (REHAP) from January 1998 to December 2017 and comparison with IPAH/FPAH patients. Variables analysed: patient and disease (PAH and liver) characteristics, first‐line PAH‐targeted therapy, causes of death, prognostic factors and survival (according to aetiology and treatment in PoPH patients).

Results

Compared to IPAH/FPAH patients (n = 678), patients with PoPH (n = 237) were predominantly men, older and had better functional class and higher prevalence of ascites. Haemodynamics were better. Biomarkers for heart failure were worse. Age‐ and sex‐adjusted 5‐year survival rate from diagnosis was 49.3% for PoPH patients and 68.7% for IPAH patients (P < 0.001). Treated PoPH had better survival than non‐treated. PAH‐ and liver‐related causes accounted for 30.2% and 24.7% of deaths in PoPH patients. PoPH patients were less likely to receive first‐line PAH‐targeted therapy and this was associated with greater mortality. Increasing age, worse exercise capacity and ascites were independent prognostic factors of poorer survival; first‐line oral monotherapy was associated with improved survival. Eight (3.4%) PoPH patients underwent liver transplantation.

Conclusions

PoPH patients are undertreated and show poorer survival than IPAH/FPAH patients. First‐line treatment with PAH‐targeted therapy was associated with better survival. Presence of ascites was a predictor of mortality.
Investment and financing for cash flow discounted with group diversity
Authors: Luo Pengfei , Yang Zhaojun
Published: January 2020

We consider a firm's investment and financing decisions made by a group of agents on behalf of shareholders, of which each individual utilizes a different discount rate following a given probability distribution for the valuation of equity. We measure group diversity by the variance of the distribution. The price of debt is determined by an equilibrium method in a competitive market. We show that a greater group diversity increases the project value, accelerates investment and postpones default. The value of the investment option increases but the optimal leverage decrease with the group diversity. The inefficiency from asset substitution increases but that from debt overhang decreases with the group diversity. Our predictions are documented by empirical evidences.
Serious outcomes of medically attended, laboratory‐confirmed influenza illness among school‐aged children with and without asthma, 2007‐2018
Authors: McLean Huong Q. , Hanson Kayla E. , Foster Allison D. , Olson Scott C. , Kemble Sarah K. , Belongia Edward A.
Published: January 2020

Background

Asthma was associated with influenza hospitalizations in children during the 2009 pandemic, but it is unclear if asthma is associated with serious illness during seasonal epidemics. Little is known regarding the effect of vaccination on influenza severity in children with asthma.

Methods

Children aged 5‐17 years in a community cohort presenting with acute respiratory illness were prospectively enrolled and tested for influenza from 2007‐08 through 2017‐18 (excluding the 2009‐10 pandemic season). Data from the electronic health record were extracted to determine asthma status and serious outcomes associated with influenza infection. A serious outcome was defined as hospitalization, emergency department visit, and/or pneumonia diagnosis within 30 days of symptom onset. Multivariable logistic regression models were used to assess asthma status and effect of vaccination on odds of a serious outcome.

Results

One thousand seven hundred and sixty four medically‐attended influenza infections among school‐aged children were included. Asthma was confirmed in 287 (16%) children. A serious influenza‐associated outcome occurred in 104 (6%) children. The odds of a serious outcome did not differ between those with confirmed asthma and those without asthma [adjusted odds ratio (aOR): 1.35, 95% confidence interval (CI): (0.77‐2.35), P = .3]. The effect of vaccination on serious outcomes was not modified by asthma status [aOR for children without asthma: 0.55 (95% CI: 0.28‐1.07), children with asthma: 1.39 (95% CI: 0.53‐3.69); interaction P‐value = .12].

Conclusions

Asthma was not a risk factor for serious illness among children with influenza. Additional studies are needed to better understand the role of influenza vaccination in preventing serious outcomes among children with asthma.
Large‐scale ciliary reversal mediates capture of individual algal prey by Müller's larva
Authors: von Dassow George , Ellison Christina I.
Published: January 2020

We documented capture of microalgal prey by several species of wild‐caught Müller's larvae of polyclad flatworms. To our knowledge, this is the first direct observation of feeding mechanism in this classical larval type. High‐speed video recordings showed that virtually all captures were mediated by large‐scale transient ciliary reversal over one or more portions of the main ciliary band corresponding to individual lobes or tentacles. Local ciliary beat reversals altered near‐field flow to suck parcels of food‐containing water mouthward. Many capture episodes entailed sufficient coordinated flow disruption that these compact‐bodied larvae tumbled dramatically. Similar behaviors were recorded in at least four distinct species, one of which corresponds to the ascidian‐eating polyclad Pseudoceros canadensis.