bluuebunny/crossref_metadata_2025 huggingface dataset:
Does type 2 diabetes confer higher relative rates of cardiovascular events in women compared with men?
Authors: Malmborg Morten , Schmiegelow Michelle D S , Nørgaard Caroline H , Munch Anders , Gerds Thomas , Schou Morten , Kistorp Caroline , Torp-Pedersen Christian , Hlatky Mark A , Gislason Gunnar
Published: December 2019

Aims

To investigate whether diabetes confers higher relative rates of cardiovascular events in women compared with men using contemporary data, and whether these sex-differences depend on age.

Methods and results

All Danish residents aged 40–89 years without a history major adverse cardiovascular events, including heart failure, as of 1 January 2012 until 31 December 2016 were categorized by diabetes-status and characterized by individual-level linkage of Danish nationwide administrative registers. We used Poisson regression to calculate overall and age-dependent incidence rates, incidence rate ratios, and women-to-men ratios for myocardial infarction, heart failure, ischaemic stroke, or cardiovascular death (MACE-HF). Among 218 549 (46% women) individuals with diabetes, the absolute rate of MACE-HF was higher in men than in women (24.9 vs. 19.9 per 1000 person-years). Corresponding absolute rates in men and women without diabetes were 10.1 vs. 7.0 per 1000 person-years. Comparing individuals with and without diabetes, women had higher relative rates of MACE-HF than men [2.8 (confidence interval, CI 2.9–2.9) in women vs. 2.5 (CI 2.4–2.5) in men] with a women-to-men ratio of 1.15 (CI 1.11–1.19, P < 0.001). The relative rates of MACE-HF were highest in the youngest and decreased with advancing age for both men and women, but the relative rates were higher in women across all ages, with the highest women-to-men ratio between age 50 and 60 years.

Conclusion

Although men have higher absolute rates of cardiovascular complications, the relative rates of cardiovascular complications associated with diabetes are higher in women than in men across all ages in the modern era.
Microsporidia with Vertical Transmission Were Likely Shaped by Nonadaptive Processes
Authors: Haag Karen L , Pombert Jean-François , Sun Yukun , de Albuquerque Nathalia Rammé M , Batliner Brendan , Fields Peter , Lopes Tiago Falcon , Ebert Dieter
Published: December 2019

Microsporidia have the leanest genomes among eukaryotes, and their physiological and genomic simplicity has been attributed to their intracellular, obligate parasitic life-style. However, not all microsporidia genomes are small or lean, with the largest dwarfing the smallest ones by at least an order of magnitude. To better understand the evolutionary mechanisms behind this genomic diversification, we explore here two clades of microsporidia with distinct life histories, Ordospora and Hamiltosporidium, parasitizing the same host species, Daphnia magna. Based on seven newly assembled genomes, we show that mixed-mode transmission (the combination of horizontal and vertical transmission), which occurs in Hamiltosporidium, is found to be associated with larger and AT-biased genomes, more genes, and longer intergenic regions, as compared with the exclusively horizontally transmitted Ordospora. Furthermore, the Hamiltosporidium genome assemblies contain a variety of repetitive elements and long segmental duplications. We show that there is an excess of nonsynonymous substitutions in the microsporidia with mixed-mode transmission, which cannot be solely attributed to the lack of recombination, suggesting that bursts of genome size in these microsporidia result primarily from genetic drift. Overall, these findings suggest that the switch from a horizontal-only to a mixed mode of transmission likely produces population bottlenecks in Hamiltosporidium species, therefore reducing the effectiveness of natural selection, and allowing their genomic features to be largely shaped by nonadaptive processes.
Budgetary Consequences of High Medical Spending Across Age and Social Status: Evidence from the Consumer Expenditure Surveys
Authors: Mueller Collin W , Charron-Chénier Raphaël , Bartlett Bryce J , Brown Tyson H
Published: December 2019

Background and Objectives

This study examines high medical spending among younger, midlife, and older households.

Research Design and Methods

We investigate high medical spending using data from the 2010 through March 2018 Consumer Expenditures Surveys (n = 92,951). We classify and describe high medical spenders relative to others within three age groups (household heads age 25–44, 45–64, and 65+) using finite mixture models and multinomial logistic regression, respectively. We then use hierarchical linear models to estimate the effects of high medical spending on nonmedical spending.

Results

Among younger households, high medical spending is positively associated with higher education and increased spending on housing and food. Among older households, high medical spending is associated with lower education and decreased nonmedical spending.

Discussion and Implications

Earlier in the life course, high medical spending is more likely to indicate an investment in future household well-being, while at older ages, high medical spending is likely to indicate medical consumption.
Arrival-angle effects on two-receiver measurements of phase velocity
Authors: Magrini Fabrizio , Diaferia Giovanni , Boschi Lapo , Cammarano Fabio
Published: December 2019

We compile a data set of Rayleigh-wave phase velocities between pairs of stations, based on teleseismic events located on the same great circle as the two stations. We validate our observations against dispersion estimates based on ambient-noise cross correlations at the same station pairs. Discrepancies between the results of the two methods can in principle be explained by deviations in the wave propagation path between earthquake and receivers, due to lateral heterogeneity in the Earth’s structure, but the latter effect has, so far, not been precisely quantified nor corrected for. We implement an algorithm to measure the arrival angle of earthquake-generated surface waves and correct the dispersion measurements accordingly. Application to a data set from the Central-Western Mediterranean shows that the arrival-angle correction almost entirely accounts for the discrepancy in question, decreasing significantly the velocity bias for a wide range of periods.
On the Structure of Graded Commutative Exponential functors
Authors: Touzé Antoine
Published: December 2019

We investigate the structure of graded commutative exponential functors. We give applications of these structure results, including computations of the homology of the symmetric groups and of extensions in the category of strict polynomial functors.
Evaluation of the clinical practice of aminoglycoside use in paediatric patients in Kenya: findings and implications for lower-middle income countries
Authors: Onyango Elias Joseph , Okalebo Faith , Oluka Margaret , Kinuthia Rosaline , Achieng Loice , Godman Brian , Kurdi Amanj
Published: December 2019

Objectives

To evaluate the practice of aminoglycoside use/monitoring in Kenya and explore healthcare worker (HCW) perceptions of aminoglycoside monitoring to identify gaps and opportunities for future improvements, given the low therapeutic index of aminoglycosides.

Methods

This was a two-phase study whereby we reviewed patients’ medical records at Kenyatta National Hospital (October–December 2016) in Phase 1 and interviewed HCWs face to face in Phase 2. Outcome measures included describing and evaluating the practice of aminoglycoside use and monitoring and compliance to guidelines. Data were analysed using descriptive and inferential analysis.

Results

Overall, out of the 2318 patients admitted, 192 patients (8.3%) were prescribed an aminoglycoside, of which 102 (53.1%) had aminoglycoside doses that did not conform to national guidelines. Aminoglycoside-related adverse effects were suspected in 65 (33.9%) patients. Monitoring of aminoglycoside therapy was performed in only 17 (8.9%) patients, with no therapeutic drug monitoring (TDM), attributed mainly to knowledge and skill gaps and lack of resources. Out of the 28 recruited HCWs, 18 (64.3%) needed training in how to perform and interpret TDM results.

Conclusions

The practice of using and monitoring aminoglycosides was suboptimal, raising concerns around potential avoidable harm to patients. The identified gaps could form the basis for developing strategies to improve the future use of aminoglycosides, not only in Kenya but also in other countries with similar settings and resources.
The ‘mitochondrial contact site and cristae organising system’ (MICOS) in health and human disease
Authors: Eramo Matthew J , Lisnyak Valerie , Formosa Luke E , Ryan Michael T
Published: December 2019

The ‘mitochondrial contact site and cristae organising system’ (MICOS) is an essential protein complex that promotes the formation, maintenance and stability of mitochondrial cristae. As such, loss of core MICOS components disrupts cristae structure and impairs mitochondrial function. Aberrant mitochondrial cristae morphology and diminished mitochondrial function is a pathological hallmark observed across many human diseases such as neurodegenerative conditions, obesity and diabetes mellitus, cardiomyopathy, and in muscular dystrophies and myopathies. While mitochondrial abnormalities are often an associated secondary effect to the pathological disease process, a direct role for the MICOS in health and human disease is emerging. This review describes the role of MICOS in the maintenance of mitochondrial architecture and summarizes both the direct and associated roles of the MICOS in human disease.
The Impact of Immigration on Wage Dynamics: Evidence from the Algerian Independence War
Authors: Edo Anthony
Published: December 2019

This paper investigates the dynamics of wage adjustment to an exogenous increase in labor supply exploiting the sudden and unexpected inflow of repatriates to France resulting from Algerian independence in 1962. I measure the impact of this particular supply shift on the average wage of pre-existing native workers across French regions between 1962 and 1976. I find that regional wages decreased between 1962 and 1968, before returning to their pre-shock level 15 years after. I also investigate the dynamics of skill-specific wages in response to the regional penetration of repatriates and find that the wages of high and low educated native workers declined initially but fully recovered by 1976.
Music Therapists’ Perceptions of the Therapeutic Potentials Using Music When Working With Verbal Children on the Autism Spectrum: A Qualitative Analysis
Authors: Epstein Shulamit , Elefant Cochavit , Thompson Grace
Published: December 2019

While there are numerous descriptions of the use of music and its therapeutic potential by music therapists working with nonverbal children on the autism spectrum, only limited literature focuses on exploring how music therapists use music and perceive its therapeutic potential when working with children on the spectrum who have verbal skills. This qualitative study aimed to explore music therapists’ descriptions of the use of music and its therapeutic potential in their work with children on the autism spectrum who have verbal skills. Semi-structured interviews were conducted with six qualified music therapists from Israel and then analyzed according to the principles of interpretative phenomenological analysis (IPA). Three main themes were identified: (a) musical infrastructure, which describes how the music therapists facilitated musical experiences to support the children’s ability to regulate their arousal, attention and emotions; (b) the meeting point between musical and verbal playfulness, which reflects the music therapists’ beliefs about how musical experiences add vitality and support the development of both verbal and nonverbal imaginative play; and (c) musical responses, which describes the different ways music therapists use their voice and songs to interact musically with verbal children. The experiences described by the participants emphasize the importance of the therapist musically attuning to the child’s emotional, physiological, creative, and playful qualities, even when the child has verbal skills. These musical interactions help to create a shared experience between the child and therapist that are perceived to help the child’s different forms of regulation, continuity, and vitality within the play.
White Blood Cell Count and Risk of Incident Lung Cancer in the UK Biobank
Authors: Wong Jason Y Y , Bassig Bryan A , Loftfield Erikka , Hu Wei , Freedman Neal D , Ji Bu-tian , Elliott Paul , Silverman Debra T , Chanock Stephen J , Rothman Nathaniel , Lan Qing
Published: December 2019

Background

The contribution of measurable immunological and inflammatory parameters to lung cancer development remains unclear, particularly among never smokers. We investigated the relationship between total and differential white blood cell (WBC) counts and incident lung cancer risk overall and among subgroups defined by smoking status and sex in the United Kingdom (UK).

Methods

We evaluated 424 407 adults aged 37–73 years from the UK Biobank. Questionnaires, physical measurements, and blood were administered and collected at baseline in 2006–2010. Complete blood cell counts were measured using standard methods. Lung cancer diagnoses and histological classifications were obtained from cancer registries. Multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals of incident lung cancer in relation to quartiles (Q) of total WBC and subtype-specific counts, with Q1 as the reference.

Results

There were 1493 incident cases diagnosed over an average 7-year follow-up. Overall, the highest quartile of total WBC count was statistically significantly associated with elevated lung cancer risk (HRQ4 = 1.67, 95% CI = 1.41 to 1.98). Among women, increased risks were found in current smokers (ncases / n = 244 / 19 464, HRQ4 = 2.15, 95% CI = 1.46 to 3.16), former smokers (ncases / n = 280 / 69 198, HRQ4 = 1.75, 95% CI = 1.24 to 2.47), and never smokers without environmental tobacco smoke exposure (ncases / n = 108 / 111 294, HRQ4 = 1.93, 95% CI = 1.11 to 3.35). Among men, stronger associations were identified in current smokers (ncase s / n = 329 / 22 934, HRQ4 = 2.95, 95% CI = 2.04 to 4.26) and former smokers (ncases / n = 358/71 616, HRQ4 = 2.38, 95% CI = 1.74 to 3.27) but not in never smokers. Findings were similar for lung adenocarcinoma and squamous cell carcinoma and were driven primarily by elevated neutrophil fractions.

Conclusions

Elevated WBCs could potentially be one of many important markers for increased lung cancer risk, especially among never-smoking women and ever-smoking men.
Friendships in Pediatric Brain Tumor Survivors and Non-Central Nervous System Tumor Survivors
Authors: Hocking Matthew C , Noll Robert B , Kazak Anne E , Brodsky Cole , Phillips Peter , Barakat Lamia P
Published: December 2019

Objective

Brain tumors during childhood may disrupt the development and maintenance of friendships due to the impact of disease- and treatment-related factors on functioning. The goal of this study was to determine if children treated for either a brain tumor or a non-central nervous system (CNS) solid tumor could name a friend and to evaluate the social information processes associated with the ability to name a friend.

Method

Youth (ages 7–14) treated for either a brain tumor (n = 47; mean age = 10.51 years) or a non-CNS solid tumor (n = 34; mean age = 11.29) completed an assessment within 6 months of the conclusion of treatment that included asking participants to name a friend and completing measures of social information processing (SIP). Rates of self-reported friendship were compared between groups and correlates of being able to name a friend were evaluated.

Results

Youth treated for a brain tumor (61.7%) were significantly less likely to name a friend compared with youth treated for a non-CNS solid tumor (85.3%). Diagnosis type (brain vs. non-CNS), relapse status, attribution style, and facial affect recognition were significant predictors of being able to name a friend or not in a logistic regression model.

Conclusions

Youth treated for a brain tumor and those who experienced a disease relapse are at risk for impairments in friendships; difficulties with SIP may increase this risk. Targeted screening and intervention efforts for children diagnosed with brain tumors and those who have relapsed could address difficulties with peers.
Perception of karrikins by plants: a continuing enigma
Authors: Yao Jiaren , Waters Mark T
Published: December 2019

Karrikins are small butenolide molecules with the capacity to promote germination and enhance seedling establishment. Generated abiotically from partial combustion of vegetation, karrikins are comparatively rare in the environment, but studying their mode of action has been most informative in revealing a new regulatory pathway for plant development that uses the karrikin perception machinery. Recent studies suggest that the karrikin receptor protein KAI2 and downstream transcriptional co-repressors in the SMXL family influence seed germination, seedling photomorphogenesis, root morphology, and responses to abiotic stress such as drought. Based on taxonomic distribution, this pathway is ubiquitous and likely to be evolutionarily ancient, originating prior to land plants. However, we still do not have a good grasp on how karrikins actually activate the receptor protein, and we have yet to discover the assumed endogenous ligand for KAI2 that karrikins are thought to mimic. This review covers recent progress in this field, as well as current gaps in our knowledge.
Implications of the search for optical counterparts during the first six months of the Advanced LIGO’s and Advanced Virgo’s third observing run: possible limits on the ejecta mass and binary properties
Authors: Coughlin Michael W , Dietrich Tim , Antier Sarah , Bulla Mattia , Foucart Francois , Hotokezaka Kenta , Raaijmakers Geert , Hinderer Tanja , Nissanke Samaya
Published: December 2019

GW170817 showed that neutron star mergers not only emit gravitational waves but also can release electromagnetic signatures in multiple wavelengths. Within the first half of the third observing run of the Advanced LIGO and Virgo detectors, there have been a number of gravitational wave candidates of compact binary systems for which at least one component is potentially a neutron star. In this article, we look at the candidates S190425z, S190426c, S190510g, S190901ap, and S190910h, predicted to have potentially a non-zero remnant mass, in more detail. All these triggers have been followed up with extensive campaigns by the astronomical community doing electromagnetic searches for their optical counterparts; however, according to the released classification, there is a high probability that some of these events might not be of extraterrestrial origin. Assuming that the triggers are caused by a compact binary coalescence and that the individual source locations have been covered during the EM follow-up campaigns, we employ three different kilonova models and apply them to derive possible constraints on the matter ejection consistent with the publicly available gravitational-wave trigger information and the lack of a kilonova detection. These upper bounds on the ejecta mass can be related to limits on the maximum mass of the binary neutron star candidate S190425z and to constraints on the mass-ratio, spin, and NS compactness for the potential black hole–neutron star candidate S190426c. Our results show that deeper electromagnetic observations for future gravitational wave events near the horizon limit of the advanced detectors are essential.
A parallel-GPU code for asteroid aggregation problems with angular particles
Authors: Ferrari Fabio , Lavagna Michèle , Blazquez Emmanuel
Published: December 2019

The paper presents a numerical implementation of the gravitational N-body problem with contact interactions between non-spherically shaped bodies. The work builds up on a previous implementation of the code and extends its capabilities. The number of bodies handled is significantly increased through the use of a CUDA/GPU-parallel octree structure. The implementation of the code is discussed and its performance is compared against direct N2 integration. The code features both smooth (force-based) and non-smooth (impulse-based) methods, as well as a visco-elastic non-smooth method, to handle contact interaction between bodies. The numerical problem of simulating ‘rubble-pile’ asteroid gravitational aggregation processes is addressed. We discuss the features of the problem and derive criteria to set up the numerical simulation from the dynamical constraints of the combined gravitational–collisional problem. Examples of asteroid aggregation scenarios that could benefit from such implementation are finally presented.
The ACCELERATION programme: I. Cosmology with the redshift drift
Authors: Cooke Ryan
Published: December 2019

Detecting the change of a cosmological object’s redshift due to the time evolution of the Universal expansion rate is an ambitious experiment that will be attempted with future telescope facilities. In this paper, we describe the ACCELERATION programme, which aims to study the properties of the most underdense regions of the Universe. One of the highlight goals of this programme is to prepare for the redshift drift measurement. Using the EAGLE cosmological hydrodynamic simulations, we estimate the peculiar acceleration of gas in galaxies and the Lyα forest. We find that star-forming ‘cold neutral gas’ exhibits large peculiar acceleration due to the high local density of baryons near star-forming regions. We conclude that absorption by cold neutral gas is unlikely to yield a detection of the cosmological redshift drift. On the other hand, we find that the peculiar accelerations of Lyα forest absorbers are more than an order of magnitude below the expected cosmological signal. We also highlight that the numerous low H i column density systems display lower peculiar acceleration. Finally, we propose a new ‘Lyα cell’ technique that applies a small correction to the wavelength calibration to secure a relative measurement of the cosmic drift between two unrelated cosmological sources at different redshifts. For suitable combinations of absorption lines, the cosmological signal can be more than doubled, while the affect of the observer peculiar acceleration is mitigated. Using current data of four suitable Lyα cells, we infer a limit on the cosmological redshift drift to be $\dot{v}_{\rm obs}\lt 65~{\rm m~s}^{-1}~{\rm yr}^{-1}$ (2σ).
Post-transplantation plasma malondialdehyde is associated with cardiovascular mortality in renal transplant recipients: a prospective cohort study
Authors: Yepes-Calderón Manuela , Sotomayor Camilo G , Gans Rijk O B , Berger Stefan P , Leuvenink Henri G D , Tsikas Dimitrios , Rodrigo Ramón , Navis Gerjan J , Bakker Stephan J L
Published: December 2019

Background

In renal transplant recipients (RTRs), cardiovascular mortality is the most common cause of long-term renal graft loss. Oxidative stress (OS) has been associated with cardiovascular disease and is known to be enhanced in RTRs. We aimed to prospectively investigate whether the concentration of the OS biomarker malondialdehyde (MDA) is associated with long-term risk of cardiovascular mortality in a large cohort of RTRs.

Methods

The plasma MDA concentration was measured using the thiobarbituric acid reaction assay in 604 extensively phenotyped RTRs with a functioning allograft for ≥1 year. The association between MDA and cardiovascular mortality was assessed using Cox proportional hazard regression analyses in the overall cohort and within subgroups according to significant effect modifiers.

Results

Median circulating MDA concentration at baseline was 5.38 [interquartile range (IQR) 4.31–6.45] μmol/L. During a follow-up period of 6.4 (IQR 5.6–6.8) years, 110 (18%) RTRs died, with 40% of deaths due to cardiovascular causes. MDA concentration was significantly associated with the risk for cardiovascular mortality {hazard ratio [HR] 1.31 [95% confidence interval (CI) 1.03–1.67] per 1-SD increment}, independent of adjustment for potential confounders, including renal function, immunosuppressive therapy, smoking status and blood pressure. The association between MDA concentration and the risk for cardiovascular mortality was stronger in RTRs with relatively lower plasma ascorbic acid concentrations [≤42.5 µmol/L; HR 1.79 (95% CI 1.30–2.48) per 1-SD increment] or relatively lower estimated glomerular filtration rates [≤45 mL/min/1.73 m2; HR 2.09 (95% CI 1.45–3.00) per 1-SD increment].

Conclusions

Circulating MDA concentration is independently associated with long-term risk for cardiovascular mortality, particularly in RTRs with relatively lower ascorbic acid concentrations or renal function. Further studies are warranted to elucidate whether OS-targeted interventions could decrease cardiovascular mortality in RTRs.
EGFR mutations are associated with response to depatux-m in combination with temozolomide and result in a receptor that is hypersensitive to ligand
Authors: Hoogstrate Youri , Vallentgoed Wies , Kros Johan M , de Heer Iris , de Wit Maurice , Eoli Marica , Sepulveda Juan Manuel , Walenkamp Annemiek M E , Frenel Jean-Sebastien , Franceschi Enrico , Clement Paul M , Weller Micheal , van Royen Martin E , Ansell Peter , Looman Jim , Bain Earle , Morfouace Marie , Gorlia Thierry , Golfinopoulos Vassilis , van den Bent Martin , French Pim J
Published: December 2019

Background

The randomized phase II INTELLANCE-2/EORTC_1410 trial on EGFR-amplified recurrent glioblastomas showed a trend towards improved overall survival when patients were treated with depatux-m plus temozolomide compared with the control arm of alkylating chemotherapy only. We here performed translational research on material derived from this clinical trial to identify patients that benefit from this treatment.

Methods

Targeted DNA-sequencing and whole transcriptome analysis was performed on clinical trial samples. High-throughput, high-content imaging analysis was done to understand the molecular mechanism underlying the survival benefit.

Results

We first define the tumor genomic landscape in this well-annotated patient population. We find that tumors harboring EGFR single-nucleotide variations (SNVs) have improved outcome in the depatux-m + TMZ combination arm. Such SNVs are common to the extracellular domain of the receptor and functionally result in a receptor that is hypersensitive to low-affinity EGFR ligands. These hypersensitizing SNVs and the ligand-independent EGFRvIII variant are inversely correlated, indicating two distinct modes of evolution to increase EGFR signaling in glioblastomas. Ligand hypersensitivity can explain the therapeutic efficacy of depatux-m as increased ligand-induced activation will result in increased exposure of the epitope to the antibody–drug conjugate. We also identified tumors harboring mutations sensitive to “classical” EGFR tyrosine-kinase inhibitors, providing a potential alternative treatment strategy.

Conclusions

These data can help guide treatment for recurrent glioblastoma patients and increase our understanding into the molecular mechanisms underlying EGFR signaling in these tumors.
The effect and safety of exercise therapy in patients with systemic sclerosis: a systematic review
Authors: Liem Sophie I E , Vliet Vlieland Theodora P M , Schoones Jan W , de Vries-Bouwstra Jeska K
Published: December 2019

Given the shortcomings of previous literature reviews evaluating the effect and safety of exercise therapy in SSc, we aimed to carry out a systematic review of the literature specifically on this topic. A structured search strategy was performed in Medline (via PubMed) and other electronic databases from 1990 to 3 September 2019. Randomized controlled trials, observational designs, conference abstracts and trial registrations were included if they concerned SSc patients ≥18 years of age, exercise therapy and reported outcomes related to physical functioning. Nine articles were included. Four randomized controlled trials compared (a) hand exercises, (b) orofacial exercises, (c) aerobic exercises or (d) aerobic exercises plus resistance training with no exercise, demonstrating effects on hand function (a), maximum mouth opening (b), peak oxygen uptake (c + d) and quality of life. All five observational studies concerning hand, orofacial, aerobic and/or strengthening exercises reported improvements of hand function, mouth opening, aerobic capacity and/or muscle strength. In conclusion, the evidence on the effect and safety of exercise therapy in SSc is scanty.
A singular analysis—attribution of illegality following Singularis v Daiwa
Authors: de Lacey Joseph
Published: December 2019

This article considers the Supreme Court’s judgment in Singularis Holdings Ltd (In Official Liquidation) v Daiwa Capital Markets Europe Ltd [2019] UKSC 50. In particular, it examines the court’s ruling in relation to attribution of illegality. This clarifies that, when determining if the knowledge and actions of a director are to be attributed to a company, the answer is to be found in a consideration of the context and purpose for which the attribution is relevant, and not in the identification of the “directing mind and will” of the company.
Getting a head start: identifying pretreatment correlates associated with early weight loss for individuals participating in weight loss treatment
Authors: Wiedemann Ashley A , Baumgardt Sydney S , Ivezaj Valentina , Kerrigan Stephanie G , Lydecker Janet A , Grilo Carlos M , Barnes Rachel D
Published: December 2019

Early weight loss is associated with greater weight loss following treatment cessation and years later. The present study aimed to identify pretreatment correlates associated with early weight loss in adults participating in weight-loss treatment in primary care. Participants (N = 89) were in the overweight/obesity range seeking weight-loss treatment in primary-care settings and randomized to one of three treatments: Motivational Interviewing and Internet Condition (MIC), Nutrition Psychoeducation and Internet Condition (NPC), or Usual Care (UC). At baseline, participants were assessed with the Eating Disorder Examination (EDE) interview and completed self-report measures of emotional overeating, exercise, exercise self-efficacy, and depression. Percent weight loss at week six was used as the Early Weight Loss variable. MIC/NPC groups had significantly greater Early Weight Loss than UC. Among MIC/NPC participants only, greater Early Weight Loss was associated with significantly lower pretreatment disordered eating and depressive symptoms. Participants in MIC/NPC who achieved clinically meaningful weight loss (>2.5%) by week six compared with those who did not (<2.5%) reported lower pretreatment disordered eating. Demographic factors and binge-eating disorder diagnosis were unrelated to Early Weight Loss. Our findings suggest that greater early weight loss may be associated with less pretreatment disordered eating and depressive symptoms.

Clinical Trials

NCT01558297
Mechanism of freezing resistance in eco-dormant birch buds under winter subzero temperatures
Authors: Endoh Keita , Fujikawa Seizo
Published: December 2019

Maximum freezing resistance is a component of winter survival and is associated with the eco-dormant state. Differential thermal analysis (DTA) has shown that changes of the freezing response of the dormant buds depend not only on species and bud type, but also on cooling rates. In order to clarify the freezing adaptation at the cellular level of eco-dormant buds in Japanese white birch, birch buds cooled at a rate of 0.2 °C min−1 and 5 °C day−1 were precisely examined by cryo-scanning electron microscopy (cryo-SEM). Freezing responses of floral dormant buds having female inflorescent primordia and leaf primordia with high-cold hardiness were assessed for extracellular freezing patterns by DTA. Cryo-SEM observation showed freezing of viscous solution filling intercellular spaces within buds and formation of extracellular ice in a random distribution within certain tissues, including green scales, leaf primordia and peduncles. The tissues producing extracellular ice had the common property that distinct intercellular spaces were present among cells having comparatively thick primary walls. In contrast, extracellular ice was not formed within flower primordium and parts of leaf primordium. These tissues had also the common property that no detectable intercellular spaces existed around the cells having thin primary walls. Cryo-SEM observation confirmed that all cells in tissues, regardless of whether extracellular ice was formed within tissues, and also regardless of differences in cooling rates, showed distinct cellular shrinkage by freezing. Recrystallization experiments by cryo-SEM confirmed that all freezable water in cells was eliminated by cooling at 0.2 °C min−1 at least to −30 °C. These results confirmed that all cells in birch buds responded to subzero temperatures through rapid equilibrium dehydration. In contrast to deep supercooling associated with extraorgan freezing of other freezing resistant buds of trees in an eco-dormant state, the mechanism of freezing resistance in eco-dormant birch buds is freezing adaptations by extracellular freezing.
Differences in growth and gas exchange between southern and northern provenances of silver birch (Betula pendula Roth) in northern Europe
Authors: Tenkanen Antti , Keski-Saari Sarita , Salojärvi Jarkko , Oksanen Elina , Keinänen Markku , Kontunen-Soppela Sari
Published: December 2019

Due to its ubiquity across northern latitudes, silver birch (Betula pendula Roth) is an attractive model species for studying geographical trait variation and acclimation capacity. Six birch provenances from 60 to 67°N across Finland were grown in a common garden and studied for provenance and genotype variation. We looked for differences in height growth, photosynthetic gas exchange and chlorophyll content index (CCI) and compared the gas exchange of early and late leaves on short and long shoots, respectively. The provenances stratified into southern and northern groups. Northern provenances attained less height growth increment and had higher stomatal conductance (gs) and lower intrinsic water-use efficiency (WUE, Anet/gs) than southern provenances, whereas net photosynthesis (Anet) or CCI did not show clear grouping. Short shoot leaves had lower gs and higher WUE than long shoot leaves in all provenances, but there was no difference in Anet between shoot types. The separation of the provenances into two groups according to their physiological responses might reflect the evolutionary history of B. pendula. Latitudinal differences in gas exchange and water use traits can have plausible consequences for global carbon and water fluxes in a warming climate.
Elevated temperature and ozone modify structural characteristics of silver birch (Betula pendula) leaves
Authors: Hartikainen Kaisa , Kivimäenpää Minna , Nerg Anne-Marja , Mäenpää Maarit , Oksanen Elina , Rousi Matti , Holopainen Toini
Published: December 2019

To study the effects of slightly elevated temperature and ozone (O3) on leaf structural characteristics of silver birch (Betula pendula Roth), saplings of four clonal genotypes of this species were exposed to elevated temperature (ambient air temperature +0.8–1.0 °C) and elevated O3 (1.3–1.4× ambient O3), alone and in combination, in an open-air exposure field over two growing seasons (2007 and 2008). So far, the impacts of moderate elevation of temperature or the combination of elevated temperature and O3 on leaf structure of silver birch have not been intensively studied, thus showing the urgent need for this type of studies. Elevated temperature significantly increased leaf size, reduced non-glandular trichome density, decreased epidermis thickness and increased plastoglobuli size in birch leaves during one or both growing seasons. During the second growing season, O3 elevation reduced leaf size, increased palisade layer thickness and decreased the number of plastoglobuli in spongy cells. Certain leaf structural changes observed under a single treatment of elevated temperature or O3, such as increase in the amount of chloroplasts or vacuole, were no longer detected at the combined treatment. Leaf structural responses to O3 and rising temperature may also depend on timing of the exposure during the plant and leaf development as indicated by the distinct changes in leaf structure along the experiment. Genotype-dependent cellular responses to the treatments were detected particularly in the palisade cells. Overall, this study showed that even a slight but realistic elevation in ambient temperature can notably modify leaf structure of silver birch saplings. Leaf structure, in turn, influences leaf function, thus potentially affecting acclimation capacity under changing climate.
Datamining, Genetic Diversity Analyses, and Phylogeographic Reconstructions Redefine the Worldwide Evolutionary History of Grapevine Pinot gris virus and Grapevine berry inner necrosis virus
Authors: Hily Jean-Michel , Poulicard Nils , Candresse Thierry , Vigne Emmanuelle , Beuve Monique , Renault Lauriane , Velt Amandine , Spilmont Anne-Sophie , Lemaire Olivier
Published: December 2019

The recently described member of the genus Trichovirus grapevine Pinot gris virus (GPGV) has now been detected in most grape-growing countries. While it has been associated with severe mottling and deformation symptoms under some circumstances, it has generally been detected in asymptomatic infections. The cause(s) underlying this variable association with symptoms remain(s) subject to speculations. GPGV genetic diversity has been studied using short genomic regions amplified by RT-PCR but not so far at the pan-genomic level. In an attempt to gain insight into GPGV diversity and evolutionary history, a systematic datamining effort was performed on our own high-throughput sequencing (HTS) data as well as on publicly available sequence read archive files. One hundred new complete or near complete GPGV genomic sequences were thus obtained, together with 69 new complete genomes for the other grapevine-infecting Trichovirus, grapevine berry inner necrosis virus (GINV). Phylogenetic and diversity analyses revealed that both viruses likely have their origin in Asia and that China is the most probable country of origin of GPGV. However, despite their common taxonomy, origin, and host, these two trichoviruses display very distinct genetic features and evolutionary traits. GINV shows an important overall genetic diversity, and is likely evolving under a balancing selection in a very restricted region of the world. On the contrary, GPGV shows a worldwide distribution with a modest genetic diversity and presents a strong selective sweep pattern. Taken together, these results show how two closely related trichoviruses differ drastically in their evolutionary history and epidemiological success. Possible causes for these differences are discussed.

[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Tapping Pennisetum violaceum, a Wild Relative of Pearl Millet (Pennisetum glaucum), for Resistance to Blast (caused by Magnaporthe grisea) and Rust (caused by Puccinia substriata var. indica)
Authors: Sharma Rajan , Sharma Shivali , Gate Vishal L.
Published: December 2019

Blast (Magnaporthe grisea) and rust (Puccinia substriata var. indica) are the two important foliar diseases of pearl millet (Pennisetum glaucum (L.) R. Br.) that can be best managed through host plant resistance. For identification of diverse sources of blast and rust resistance, 305 accessions of Pennisetum violaceum, a wild relative of pearl millet, were screened under greenhouse conditions against five pathotype-isolates of M. grisea and a local isolate of P. substriata var. indica collected from ICRISAT farm, Patancheru, India. Based on the mean blast score (1 to 9 scale), 17 accessions (IP 21525, 21531, 21536, 21540, 21594, 21610, 21640, 21706, 21711, 21716, 21719, 21720, 21721, 21724, 21987, 21988, and 22160) were found resistant (score ≤3.0) to all five pathotypes, and 24 accessions were resistant to four pathotypes of M. grisea. As there was variability for rust resistance within some accessions, individual rust-resistant (<5% severity) plants from 17 accessions were selected, grown in pots and advanced to next generation by selfing, and rescreened for three to four generations following pedigree selection to develop rust-resistant genetic stocks. Single plant selections from nine accessions (IP 21629, 21645, 21658, 21660, 21662, 21711, 21974, 21975, and 22038) were found highly resistant to rust (0% rust severity) after four generations of pedigree selection and subsequent screening. Some of the blast-resistant accessions and rust-resistant genetic stocks are being utilized in a prebreeding program at ICRISAT for introgressing resistance genes from the wild into the parental lines of cultivated and potential pearl millet hybrids and varieties.
Anti-diabetic drug metformin inhibits cell proliferation and tumor growth in gallbladder cancer via G0/G1 cell cycle arrest
Authors: Yamashita Takuma , Kato Kiyohito , Fujihara Shintaro , Iwama Hisakazu , Morishita Asahiro , Yamana Hiroki , Kobayashi Kiyoyuki , Kamada Hideki , Chiyo Taiga , Kobara Hideki , Tsutsui Kunihiko , Okano Keiichi , Suzuki Yasuyuki , Masaki Tsutomu
Published: December 2019

Gallbladder cancer is the most common biliary tract cancer with poor prognosis and wide variation in incidence rates worldwide, being very high in some countries in Latin America and Asia. Treatment of type 2 diabetes with metformin causes a reduction in the incidence of cancer. Till date, there are no reports on the anti-tumor effects of metformin in gall bladder cancer. Therefore, this study evaluated the effects of metformin on the proliferation of human gallbladder adenocarcinoma cells in vitro and in vivo, as well as explored the microRNAs associated with the anti-tumor effects of metformin. Metformin inhibited the proliferation in gallbladder adenocarcinoma cell lines NOZ, TGBC14TKB, and TGBC24TKB, and blocked the G0 to G1 transition in the cell cycle. This was accompanied by strong reduction in the expression of G1 cyclins, especially cyclin D1 and its catalytic subunits including cyclin-dependent kinase 4, and in retinoblastoma protein phosphorylation. In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-β, and TIMP-1. Moreover, metformin also markedly altered microRNA expression profile leading to an anti-tumor effect. Treatment of athymic nude mice bearing xenograft tumors with metformin inhibited tumor growth. These results suggest that metformin may be used clinically for the treatment of gallbladder adenocarcinoma.
Changing treatment landscape for early cervical cancer: outcomes reported with minimally invasive surgery compared with an open approach
Authors: Melamed Alexander , Ramirez Pedro T.
Published: December 2019

Purpose of review

The aim of the article is to review recent studies that compare the oncologic efficacy of minimally invasive radical hysterectomy with that of open radical hysterectomy.

Recent findings

The Laparoscopic Approach to Cervical Cancer (LACC) trial, a randomized study design to test the hypothesis that minimally invasive radical hysterectomy is not inferior to open radical hysterectomy, was stopped early by the data and safety monitoring committee after enrolling 631 of a planned 740 patients. The disease-free survival rate at 4.5 years was 86% among women assigned to minimally invasive surgery and 96.5% in those who underwent open surgery (hazard ratio [HR] 3.74; 95% confidence interval [CI] 1.63–8.58). Minimally invasive surgery was also associated with inferior overall survival (HR 6.00; 95% CI 1.44–12.7). Recent well designed, adequately powered observational studies mostly corroborate the findings of the LACC trial.

After a decade of widespread acceptance and increasing popularity, the preponderance of evidence now suggests that minimally invasive radical hysterectomy for cervical cancer confers an excess risk of recurrence and death compared with open abdominal radical hysterectomy.
Secondary Prevention of Intrauterine Adhesions Following Hysteroscopic Surgery in Women With Asherman Syndrome: Is Something Better Than Nothing?
Authors: KELLEY ANGELA S. , GIULIANI EMMA , SCHON SAMANTHA B.
Published: December 2019

Asherman syndrome is a reproductive disorder characterized by intrauterine adhesions and amenorrhea, infertility, abnormal placentation, or pregnancy loss. Treatment of Asherman syndrome involves hysteroscopic lysis of adhesions. Many surgeons utilize postoperative measures such as hormone therapy, solid mechanical devices, or barrier gels to prevent recurrent adhesions in this setting. However, there is limited high-quality evidence to support their use. Additional research is needed on the safety and efficacy of these commonly used methods to guide patient care.
Improving Quality Measurement
Authors: Atkinson J. Graham
Published: December 2019

The use of quality measures to adjust health care payments and to rank providers is growing rapidly, but there are many problems with the quality measures that are currently being used. This article discusses some of these problems and then lays out some principles and procedures that should be used in the development and combination of quality measures. Many of the problems with existing quality measures would have been avoided had these principles been applied as they were developed.
The promise of autism genetics: Still waiting
Authors: Johnson Heather L.
Published: December 2019

The condition presently known as autism spectrum disorder was first described in the literature nearly 80 years ago. Since then, the research community has mounted a quest to discover the etiology of the condition in hopes of discovering prevention, treatment, and cures for this developmental disorder. The field of autism genetics has made progress in understanding what genes are and what are not associated with autism. This article provides a brief overview of the evolution of autism genetics and describes the current state of science in realizing genetically informed prevention and treatments.
A tree with deep roots: 54th anniversary of nurse practitioners
Authors: Earp Jaibun K.
Published: December 2019

More than 270,000 nurse practitioners (NPs) celebrate the profession's 54th anniversary this year. NPs have significantly expanded patient care options and availability. Many states now allow full practice authority for NPs, and all states now allow NPs to prescribe. Doctor of Nursing Practice–prepared NP enrollment is rising. The NP profession as an integral part of the US health care system has significantly strengthened our health care system, making the tree with deep roots even stronger and more substantial than ever.
Update on long-term outcomes for chronic rhinosinusitis in cystic fibrosis
Authors: Chang Michael T. , Patel Zara M.
Published: December 2019

Purpose of review

This article reviews the existing body of literature regarding long-term outcomes of various treatments for chronic rhinosinusitis (CRS) in the cystic fibrosis population.

Recent findings

The management of CRS in cystic fibrosis involves a multitude of medical and surgical therapies. Despite their high usage amongst clinicians, corticosteroids and antibiotics currently have little outcome data supporting their use. There is emerging evidence demonstrating beneficial outcomes for DNAse mucolytics and molecular modulators of cystic fibrosis transmembrane conductor regulator (CFTR). Endoscopic sinus surgery (ESS) improves sinonasal outcomes in cystic fibrosis CRS; however, the benefit on pulmonary outcomes remains unclear.

Successful management of CRS in cystic fibrosis requires multimodal and multidisciplinary care. The long-term outcome data is variable for different treatment modalities. There is recent evidence supporting the role of DNAse mucolytics, CFTR-targeting therapies, and ESS in management of cystic fibrosis CRS.