bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between Corneal Thickness and Radius to Body Height
Authors: Jonuscheit Sven , Doughty Michael J. , Martín Raúl , Rio-Cristobal Ana
Published: December 2016

Purpose

To investigate the possible association between body stature (height) and corneal thickness and radius in younger-adult Caucasians, especially within the context of previously published literature.

Methods

Body height and weight were measured in 109 healthy subjects, with an average age of 24 ± 6 years (mean ± SD). Subjects underwent an ophthalmic assessment including anterior segment imaging by Scheimpflug topography and specular microscopy. Central and peripheral corneal thickness and corneal radius were analyzed. The relationship between body stature and corneal parameters was assessed using simple and multiple regression analysis. Effect size was determined by generating regression and correlation coefficients.

Results

Body height ranged from 1.54 to 1.86 m (mean ± SD 1.67 ± 0.08 m), central corneal thickness from 465 to 629 μm (554 ± 33 μm), whereas corneal radius measured between 7.16 and 8.49 mm (7.75 ± 0.24 mm). Body height was weakly associated with central corneal thickness and peripheral corneal thickness (r ≥ −0.180), and moderately with corneal radius (r = 0.351). Based on the regression equations, central corneal thickness decreases by 8 μm, whereas corneal radius increases by 0.11 mm for each 0.1-m difference in body height. No significant correlations were found for similar assessments using body weight or body mass index.

Conclusions

Differences in corneal radius and corneal thickness can be linked to body stature. However, effect sizes were consistently small and no more than 13% of the variability in corneal curvature could be explained by variations in body stature.
The Effects of a Park Awareness Campaign on Rural Park Use and Physical Activity
Authors: Banda Jorge A. , Hooker Steven P. , Wilcox Sara , Colabianchi Natalie , Kaczynski Andrew T. , Hussey James
Published: December 2016

To examine the effects of a park awareness campaign on park use in 6 community parks. One-group pretest-posttest design. Six community parks located in a South Carolina county. Children, adolescents, and adults observed in community parks. A 1-month awareness campaign that culminated in single 1.5-hour events at 6 parks in April 2011 and May 2011. The System for Observing Play and Recreation in Communities was used to objectively measure park use in May 2010 (baseline) and May 2011 (postcampaign). Zero-inflated Poisson models tested whether the number of total park users and the number of park users engaged in sedentary, walking, and vigorous activities differed by observation date. Park use was significantly greater at baseline than postcampaign (97 vs 84 users, respectively; χ2 = 4.69, P = .03). There were no significant differences in the number of park users engaged in sedentary (χ2 = 2.45, P = .12), walking (χ2 = 0.29, P = .59), and vigorous (χ2 = 0.20, P = .65) activities between baseline and postcampaign. Although only 97 and 84 people were observed across all parks at baseline and postcampaign, a total of 629 people were observed during the 6 separate 1.5-hour campaign park events. This suggests that there is potential for greater park utilization in these communities, and important questions remain on how to conduct effective awareness campaigns and how to harness interest in park events for the purpose of contributing to future community-wide physical activity and health promotion efforts.
Screening for the ancient polar bear mitochondrial genome reveals low integration of mitochondrial pseudogenes (numts) in bears
Authors: Lammers Fritjof , Janke Axel , Rüecklé Cornelia , Zizka Vera , Nilsson Maria
Published: December 2016

Phylogenetic analyses of nuclear and mitochondrial genomes have shown that polar bears captured the mitochondrial genome of brown bears some 160,00 years ago. This hybridization event likely led to an extinction of the original polar bear mitochondrial genome. However, parts of the mitochondrial DNA occasionally integrates into the nuclear genome, forming pseudogenes callednumts(nuclear mitochondrial integrations). Screening the polar bear genome fornumts,we identified only 13 such integrations. Analyses of whole-genome sequences from additional polar bears, brown and American black bears as well as the giant panda indicates that the discoverednumtsentered the bear lineage before the initial ursid radiation some 14 million years ago. Our findings suggests a low integration rate ofnumtsin the bear lineage and a complete loss of the original polar bear mitochondrial genome.
Subgenome dominance in an interspecific hybrid, synthetic allopolyploid, and a 140 year old naturally established neo-allopolyploid monkeyflower
Authors: Edgar Patrick P. , Smith Ronald , McKain Michael R. , Cooley Arielle M. , Vallejo-Marin Mario , Yuan Yaowu , Bewick Adam J. , Ji Lexiang , Platts Adrian E. , Bowman Megan J. , Childs Kevin L. , Schmitz Robert J , Smith Gregory D. , Pires J. Chris , Puzey Joshua R.
Published: December 2016

The importance and applications of polyploidy have long been recognized, from shaping the evolutionary success of flowering plants to improving agricultural productivity. Recent studies have shown that one of the parental subgenomes in ancient polyploids is generally more dominant - having both retained more genes and being more highly expressed - a phenomenon termed subgenome dominance. How quickly one subgenome dominates within a newly formed polyploid, if immediate or after millions of years, and the genomic features that determine which genome dominates remain poorly understood. To investigate the rate of subgenome dominance emergence, we examined gene expression, gene methylation, and transposable element (TE) methylation in a natural less than 140 year old allopolyploid (Mimulus peregrinus), a resynthesized interspecies triploid hybrid (M. robertsii), a resynthesized allopolyploid (M. peregrinus), and diploid progenitors (M. guttatusandM. luteus). We show that subgenome expression dominance occurs instantly following the hybridization of two divergent genomes and that subgenome expression dominance significantly increases over generations. Additionally, CHH methylation levels are significantly reduced in regions near genes and within transposons in the first generation hybrid, intermediate in the resynthesized allopolyploid, and are repatterned differently between the dominant and submissive subgenomes in the natural allopolyploid. Our analyses reveal that the subgenome differences in levels of TE methylation mirror the increase in expression bias observed over the generations following the hybridization. These findings not only provide important insights into genomic and epigenomic shock that occurs following hybridization and polyploid events, but may also contribute to uncovering the mechanistic basis of heterosis and subgenomic dominance.
A tutorial on Gaussian process regression: Modelling, exploring, and exploiting functions
Authors: Schulz Eric , Speekenbrink Maarten , Krause Andreas
Published: December 2016

This tutorial introduces the reader to Gaussian process regression as an expressive tool to model, actively explore and exploit unknown functions. Gaussian process regression is a powerful, non-parametric Bayesian approach towards regression problems that can be utilized in exploration and exploitation scenarios. This tutorial aims to provide an accessible introduction to these techniques. We will introduce Gaussian processes which generate distributions over functions used for Bayesian non-parametric regression, and demonstrate their use in applications and didactic examples including simple regression problems, a demonstration of kernel-encoded prior assumptions and compositions, a pure exploration scenario within an optimal design framework, and a bandit-like exploration-exploitation scenario where the goal is to recommend movies. Beyond that, we describe a situation modelling risk-averse exploration in which an additional constraint (not to sample below a certain threshold) needs to be accounted for. Lastly, we summarize recent psychological experiments utilizing Gaussian processes. Software and literature pointers are also provided.
Design of a multilayer-based collimated plane-grating monochromator for tender X-ray range
Authors: Yang Xiaowei , Wang Hongchang , Hand Matthew , Sawhney Kawal , Kaulich Burkhard , Kozhevnikov Igor V. , Huang Qiushi , Wang Zhanshan
Published: December 2016

Collimated plane-grating monochromators (cPGMs), consisting of a plane mirror and plane diffraction grating, are essential optics in synchrotron radiation sources for their remarkable flexibility and good optical characteristics in the soft X-ray region. However, the poor energy transport efficiency of a conventional cPGM (single-layer-coated) degrades the source intensity and leaves reduced flux at the sample, especially for the tender X-ray range (1–4 keV) that covers a large number of K- and L-edges of medium-Z elements, and M-edges of high-Z elements. To overcome this limitation, the use of a multilayer-based cPGM is proposed, combining a multilayer-coated plane mirror with blazed multilayer gratings. With this combination, the effective efficiency of cPGMs can be increased by an order of magnitude compared with the conventional single-layer cPGMs. In addition, higher resolving power can be achieved with improved efficiency by increasing the blaze angle and working at higher diffraction order.
Research Note: The sensitivity of surface seismic P‐wave data in transversely isotropic media to reflector depth
Authors: Alkhalifah Tariq
Published: December 2016

The leading component of the high‐frequency asymptotic description of the wavefield, given by the travel time, is governed by the eikonal equation. In anisotropic media, traveltime measurements from seismic experiments conducted along one surface cannot constrain the long‐wavelength attribute of the medium along the orthogonal‐to‐the‐surface direction, as anisotropy introduces an independent parameter controlling wave propagation in the orthogonal direction. Since travel times measured on the Earth's surface in transversely isotropic media with a vertical symmetry axis are mainly insensitive to the absolute value of the anisotropic parameter responsible for relating these observations to depth δ, the travel time was perturbed laterally to investigate the traveltime sensitivity to lateral variations in δ. This formulation can be used to develop inversion strategies for lateral variations in δ in acoustic transversely isotropic media, as the surface‐recorded data are sensitive to it even if the model is described by the normal moveout velocity and horizontal velocity, or the anellipticity parameter η. Numerical tests demonstrate the enhanced sensitivity of our data when the model is parameterised with a lateral change in δ.
The Populist Surge in Post‐Democratic Times: Theoretical and Political Challenges
Authors: Katsambekis Giorgos
Published: December 2016

Populism has often been described as a great challenge and threat to Western democracies. Not surprisingly, at a time in which we are witnessing a significant rise in populist actors in Europe and the US, scientific analyses and commentary regarding populism have become particularly popular and, indeed, necessary. My aim in this article is to offer a brief yet comprehensive overview of the ongoing debates in a bid to problematise the supposed ‘imminent threat’ of populism in light of recent developments within the political systems and societies of established democracies, especially under conditions of crisis. I understand populism as a specific type of discourse, and thus as a way—among others—of doing politics and appealing to groups of people. Thus, I highlight the varying orientations that populist movements might take, depending on the ideological traditions with which they are closely articulated and the sociopolitical environment in which they manifest. Last, I relate the ‘populist surge’ to discussions regarding post‐democracy.
Hyperemesis gravidarum and long‐term mortality: a population‐based cohort study
Authors: Fossum S , Vikanes ÅV , Næss Ø , Vos L , Grotmol T , Halvorsen S
Published: December 2016

Objective

To investigate whether exposure to hyperemesis gravidarum (HG) is associated with increased maternal long‐term mortality.

Design

Population‐based cohort study.

Setting

Medical Birth Registry of Norway (1967–2002) linked to the Cause of Death Registry.

Population

Women in Norway with singleton births in the period 1967–2002, with and without HG. Women were followed until 2009 or death.

Methods

Cox proportional hazard regression model was applied to estimate hazard ratios (HRs) with 95% confidence interval (CI).

Main outcome measures

The primary outcome was all‐cause mortality during follow up. Secondary outcomes were cause‐specific mortality (cardiovascular mortality, deaths due to cancer, external causes or mental and behavioural disorders).

Results

Of 999 161 women with singleton births, 13 397 (1.3%) experienced HG. During a median follow up of 26 years (25 902 036 person‐years), 43 470 women died (4.4%). Women exposed to HG had a lower risk of long‐term all‐cause mortality compared with women without HG (crude HR 0.82; 95% CI 0.75–0.90). When adjusting for confounders, this reduction was no longer significant (adjusted HR 0.92; 95% CI 0.84–1.01). Women exposed to HG had a similar risk of cardiovascular death as women not exposed (adjusted HR 1.04; 95% CI 0.83–1.29), but a lower long‐term risk of death from cancer (adjusted HR 0.86; 95% CI 0.75–0.98).

Conclusion

In this large population‐based cohort study, HG was not associated with an increased risk of long‐term all‐cause mortality. Women exposed to HG had no increase in mortality due to cardiovascular disease, but had a reduced risk of death from cancer.

Tweetable abstract

Population‐based cohort study: Hyperemesis was not associated with an increased risk of long‐term mortality.
Assisted reproductive technology and severe postpartum haemorrhage: a case–control study
Authors: Nyfløt LT , Sandven I , Oldereid NB , Stray‐Pedersen B , Vangen S
Published: December 2016

Objective

To investigate the association between assisted reproductive technology and severe postpartum haemorrhage.

Design

Case–control study.

Setting

The study was conducted in Norway; Division of Gynaecology and Obstetrics at Oslo University Hospital and Department of Obstetrics and Gynaecology at Drammen Hospital.

Population

A source population including all women admitted for delivery at Oslo University Hospital and Drammen Hospital during the time period 1 January 2008 to 31 December 2011. The study population consisted of all cases of severe postpartum haemorrhage (n = 1064) and a random sample of controls (n = 2059).

Methods

We used an explanatory strategy in the analysis, with multivariable logistic regression.

Main outcome measures

Severe postpartum haemorrhage; defined as blood loss ≥1500 ml or need for blood transfusion.

Results

Assisted reproductive technology was associated with an increased risk of severe postpartum haemorrhage (crude OR = 2.92; 95% CI 2.18–3.92, P < 0.001). Mode of delivery and anticoagulant medication had significant confounding effects. Strong interaction was found for multiple pregnancies. After adjusting for confounding and interaction, an increased risk was observed both in the strata of multiple pregnancies (adjusted OR = 7.00, 95% CI 2.70–18.12, P < 0.001), and in the strata of single gestation (adjusted OR = 1.58, 95% CI 1.12–2.24, P = 0.010).

Conclusions

Our findings warrant an increased awareness of the risk of severe postpartum haemorrhage in women conceiving with assisted reproductive technology. Furthermore, the high risk of severe postpartum haemorrhage in the presence of a twin or triplet pregnancy is an additional argument for single embryo transfer.

Tweetable abstract

Assisted reproductive technology is associated with an increased risk of severe postpartum haemorrhage.
Validation of Toolmark Comparisons Made At Different Vertical and Horizontal Angles
Authors: Macziewski Chad , Spotts Ryan , Chumbley Scott
Published: December 2016

Numerous studies have focused on determining whether objective statistical methods can be used to discriminate between known matches and nonmatches when comparing laboratory prepared toolmarks. This study involved an analysis of striated toolmarks made as a function of varying vertical and horizontal angles of attack. Comparisons based on experimental data show that replicate toolmarks from the same tool show high correlation values at identical vertical and horizontal angles, with the correlation decreasing as the angular difference increases, especially for horizontal angular changes. Comparisons between nonmatching samples produce low correlation values that remain unchanged as horizontal angular differences increase. While complete statistical separation was not achieved between matching and nonmatching samples, there is evidence demonstrating that toolmarks can be identified if the variation in horizontal angle is within 10°. The experiment shows that computer‐aided comparison techniques could be viable for identification with the proper statistical algorithm.
The Etiology of Basal Vacuolizations in Renal Tubular Epithelial Cells Evaluated in an Isolated Perfused Kidney Model
Authors: Zhou Chong , Yool Andrea J. , Byard Roger W.
Published: December 2016

To determine whether basal lipid vacuolization characteristic of ketoacidosis could be induced with short‐term hypertriglyceridemia, adult Sprague Dawley rat kidneys were perfused in an isolated perfused kidney model with, and without, 11.3 mM (10 g/L) of triglycerides in Krebs‐Henseleit buffer, for 1 and 2 h (n = 5/group). Additional treatments included perfusion with triglycerides with 20 mM of β‐hydroxybutyrate and 2 mM of acetoacetate (n = 5) and perfusion with triglycerides with 70 mM of glucose (n = 1). Basal vacuolization was produced in all groups, but differed in morphology to that reported in postmortem studies. There was no further increase in vacuolization after 2 h of perfusion compared to 1 h (p = 0.24), and the addition of ketones did not alter the morphology or extent of vacuolization. This study using an ex vivo model has confirmed that isolated hypertriglyceridemia is sufficient to cause basal lipid vacuolization in renal tubular epithelial cells, but with different morphology to vacuoles observed in lethal ketoacidosis at autopsy.
Armanni–Ebstein Lesions in Terminal Hyperglycemia
Authors: Zhou Chong , Yool Andrea J. , Byard Roger W.
Published: December 2016

Armanni–Ebstein lesions (AEL) occur in deaths related to uncontrolled diabetes mellitus. To investigate the relationship between AEL and terminal hyperglycemia, we retrospectively reviewed 71 cases with vitreous glucose levels ≥11.1 mmol/L; 27 (38%) cases had AEL (vitreous glucose 14.0–77.3 mmol/L); and 44 cases (62%) did not (vitreous glucose 11.1–91.9 mmol/L). There was no significant difference (p = 0.271) in vitreous glucose levels between the cases with AEL (mean 39.2, SD 16.7 mmol/L) and those without (mean 34.2, SD 19.8 mmol/L). Similarly, there was no difference in the degree of dehydration, renal failure, or osmolality. However, there was a significantly higher level of β‐hydroxybutyrate among the cases with AEL compared to those without (p = 0.007), suggesting that ketoacidosis may facilitate the development of AEL. Given the possible synergistic role of β‐hydroxybutyrate, the correlation between AEL and terminal hyperglycemia in animal studies may not be applicable to humans. AEL may also possibly occur with sublethal elevations in glucose.
Survival and Growth of Probiotic Lactic Acid Bacteria in Refrigerated Pickle Products
Authors: Fan Sicun , Breidt Fred , Price Robert , Pérez‐Díaz Ilenys
Published: December 2016

We examined 10 lactic acid bacteria that have been previously characterized for commercial use as probiotic cultures, mostly for dairy products, including 1 Pediococcus and 9 Lactobacilli. Our objectives were to develop a rapid procedure for determining the long‐term survivability of these cultures in acidified vegetable products and to identify suitable cultures for probiotic brined vegetable products. We therefore developed assays to measure acid resistance of these cultures to lactic and acetic acids, which are present in pickled vegetable products. We used relatively high acid concentrations (compared to commercial products) of 360 mM lactic acid and 420 mM acetic acid to determine acid resistance with a 1 h treatment. Growth rates were measured in a cucumber juice medium at pH 5.3, 4.2, and 3.8, at 30 °C and 0% to 2% NaCl. Significant differences in acid resistance and growth rates were found among the 10 cultures. In general, the acid resistant strains had slower growth rates than the acid sensitive strains. Based on the acid resistance data, selected cultures were tested for long‐term survival in a simulated acidified refrigerated cucumber product. We found that one of the most acid resistant strains (Lactobacillus casei) could survive for up to 63 d at 4 °C without significant loss of viability at 108 CFU/mL. These data may aid in the development of commercial probiotic refrigerated pickle products.
Safety and efficacy of transcatheter arterial chemoembolization with embospheres in treatment of hepatocellular carcinoma
Authors: Hao Ming Zhi , Lin Hai Lan , Chen Qi Zhong , Hu Yu Bin , Chen Jian Bin , Zheng Jian Xiong , Zhou Dong , Zhang Hui
Published: December 2016

Objective

To investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE) with embospheres for the treatment of unresectable hepatocellular carcinoma (HCC).

Methods

Patients with unresectable HCC who were treated with TACE followed by embosphere treatment (Embo‐TACE) or conventional TACE (cTACE) between May 2010 and March 2014 were retrospectively included in this study. The Embo‐TACE group received lipiodol and chemotherapeutic agent emulsion, followed by embospheres. The cTACE group received lipiodol and chemotherapeutic agent emulsion, followed by gelatin sponge pellets. Time to progression (TTP), overall survival (OS), overall response rate (ORR), and safety were compared between the two groups. Univariate and multivariate regression analyses of the factors affecting survival were conducted.

Results

The median TTP and OS in the Embo‐TACE group were significantly longer than those in the cTACE group (TPP: 7.0 months vs 5.4 months, P = 0.035; OS: 15 months vs 12 months, P = 0.032). Seven days after the first TACE treatment, alanine aminotransferase level was higher in the cTACE group than in the Embo‐TACE group (P = 0.015). The ORR did not significantly differ between the two groups (P = 0.827). Additional therapy and local responses one month after the first TACE treatment were associated with OS.

Conclusions

Embo‐TACE resulted in a significant improvement in TTP and OS for patients with unresectable HCC, compared with cTACE. Furthermore, Embo‐TACE was better tolerated. Additional therapy and local responses one month after the first TACE were independent prognostic factors for OS.
Insulin treatment restores islet microvascular vasomotion function in diabetic mice
Authors: Liu Mingming , Zhang Xiaoyan , Li Ailing , Zhang Xu , Wang Bing , Li Bingwei , Liu Shuying , Li Hongwei , Xiu Ruijuan
Published: December 2016

Background

The microcirculation plays an important role in the pathogenesis of diabetes and its complications. We hypothesized that pancreatic islet microvascular (PIM) vasomotion, as a parameter of pancreatic islet microcirculation function, is abnormal in diabetic mice and that insulin treatment may reverse this dysfunction.

Methods

Mice were randomly assigned to non‐diabetic control, untreated diabetic, and insulin‐treated diabetic groups (n = 6 in each group). Separate groups of streptozotocin (STZ)‐induced diabetic and high‐fat diet‐fed mice were used as a model of hyperglycemia. Insulin‐treated diabetic mice were treated with 1–1.5 IU/day insulin for 1 week. Laser Doppler monitors were used to evaluate PIM vasomotion. Morphological and ultrastructural changes in islet endothelial cells were determined by immunohistochemistry and transmission electron microscopy. Glucagon, insulin, vascular endothelial growth factor (VEGF)‐A, and platelet endothelial cell adhesion molecule (PECAM‐1) expression was determined by immunohistochemistry and Western blotting.

Results

In both untreated diabetic groups, the pancreatic islet microcirculation was unable to regulate PIM vasomotion. The rhythm of vasomotion was irregular, and the average blood perfusion, amplitude, frequency, and relative velocity of vasomotion were significantly lower than in non‐diabetic controls. Insulin treatment restored the functional status of PIM vasomotion. In islet endothelial cells from both untreated diabetic groups, the mitochondria were swollen with disarrangement of the cristae, and the distribution of PECAM‐1 was discontinuous. Insulin treatment significantly increased the reduced expression of PECAM‐1 in both untreated diabetic groups and VEGF‐A expression in untreated STZ‐diabetic mice.

Conclusion

The results suggest that the functional status of PIM vasomotion is impaired in diabetic mice but can be restored by insulin.
The role of imaging in the surveillance and diagnosis of hepatocellular cancer
Authors: Dulku Gurjeet , Dhillon Ravinder , Goodwin Mark , Cheng Wendy , Kontorinis Nick , Mendelson Richard
Published: December 2016

A decision support tool has been developed as part of a suite of on‐line evidence‐based and consensus‐based guidelines Diagnostic imaging Pathways (DIP): www.imagingpathways.health.wa.gov.au) in the form of an algorithmic flow chart with supporting evidence and consensus to inform referrers to diagnostic imaging and radiologists as to the optimum strategy for surveillance and diagnosis of primary hepatocellular cancer (HCC) in those patients with risk factors of this disease. A literature review, including reference to several international consensus‐based expert guidelines, has been employed to develop this tool.
Radiation Oncology research grants awarded by the Royal Australian and New Zealand College of Radiologists: Value for money?
Authors: Roos Daniel E , Kartika Joshua K , Hu Marcus Q
Published: December 2016

Introduction

The Royal Australian and New Zealand College of Radiologists (RANZCR) and other medical colleges have provided research grants from their budgets for many years. This survey‐based project aimed to determine whether the RANZCR Faculty of Radiation Oncology (FRO) is realizing value for money from its seed funding, and to compare this with grant activities of the other colleges.

Methods

Eligible FRO grant recipients between 1999 and 2014 were surveyed regarding bibliometric data, subjective outcomes and factors considered important in completing their research projects. The other colleges were also approached via email and phone interviews.

Results

A records search identified 26 eligible individuals who received 42 grants for 41 projects. The survey response rate was 100%, identifying 33 secondary grants, 65 conference presentations, 10 prizes and 69 publications associated with the FRO grants and consequential research. At least seven higher degrees also resulted. The funding process was very positively perceived by grant recipients, and the two factors identified as most important in project completion were local infrastructure and RANZCR funding. In 2015, FRO allocated AUD$150K for grants compared with $10K–$2.6M from 10 of the other 15 Australasian Medical Colleges. In general, appraisal of funding outcomes relative to expenditure has been only low level until recently.

Conclusions

This project has identified significant research output and subjective benefit from relatively modest FRO seed grants, implying a favourable cost‐benefit ratio. Such outcomes monitoring needs to be more widely pursued within Australasian medical colleges.
Partial Protection by Dietary Antioxidants Against Ethanol‐Induced Osteopenia and Changes in Bone Morphology in Female Mice
Authors: Alund Alexander W. , Mercer Kelly E. , Pulliam Casey F. , Suva Larry J. , Chen Jin‐Ran , Badger Thomas M. , Ronis Martin J. J.
Published: December 2016

Background

Chronic alcohol consumption leads to increased fracture risk and an elevated risk of osteoporosis by decreasing bone accrual through increasing osteoclast activity and decreasing osteoblast activity. We have shown that this mechanism involves the generation of reactive oxygen species (ROS) produced by NADPH oxidases. It was hypothesized that different dietary antioxidants, N‐acetyl cysteine (NAC; 1.2 mg/kg/d), and α‐tocopherol (Vit.E; 60 mg/kg/d) would be able to attenuate the NADPH oxidase‐mediated ROS effects on bone due to chronic alcohol intake.

Methods

To study the effects of these antioxidants, female mice received a Lieber–DeCarli liquid diet containing ethanol (EtOH) with or without additional antioxidant for 8 weeks.

Results

Tibias displayed decreased cortical bone mineral density in both the EtOH and EtOH + antioxidant groups compared to pair‐fed (PF) and PF + antioxidant groups (p < 0.05). However, there was significant protection from trabecular bone loss in mice fed either antioxidant (p < 0.05). Microcomputed tomography analysis demonstrated a significant decrease in bone volume (bone volume/tissue volume) and trabecular number (p < 0.05), along with a significant increase in trabecular separation in the EtOH compared to PF (p < 0.05). In contrast, the EtOH + NAC and EtOH + Vit.E did not statistically differ from their respective PF controls. Ex vivo histologic sections of tibias were stained for nitrotyrosine, an indicator of intracellular damage by ROS, and tibias from mice fed EtOH exhibited significantly more staining than PF controls. EtOH treatment significantly increased the number of marrow adipocytes per mm as well as mRNA expression of aP2, an adipocyte marker in bone. Only NAC was able to reduce the number of marrow adipocytes to PF levels. EtOH‐fed mice exhibited reduced bone length (p < 0.05) and had a reduced number of proliferating chondrocytes within the growth plate. NAC and Vit.E prevented this (p < 0.05).

Conclusions

These data show that alcohol's pathological effects on bone extend beyond decreasing bone mass and suggest a partial protective effect of the dietary antioxidants NAC and Vit.E at these doses with regard to alcohol effects on bone turnover and bone morphology.
A novel bispecific DARPin targeting FcγRIIB and FcεRI‐bound IgE inhibits allergic responses
Authors: Zellweger F. , Gasser P. , Brigger D. , Buschor P. , Vogel M. , Eggel A.
Published: December 2016

Background

Binding of allergen‐specific IgE to its high‐affinity receptor FcεRI on basophils and mast cells is a central event in the development of allergies. Exposure of these cells to allergens induces the release of soluble mediators causing allergic symptoms. The inhibitory low‐affinity IgG Fc‐receptor FcγRIIB is co‐expressed on allergic effector cells and has been implicated in negative regulation of immediate hypersensitivity responses. In order to harvest the inhibitory function of this receptor, we aimed to select specific binders against FcγRIIB and to generate a bispecific molecule simultaneously targeting FcγRIIB and FcεRI‐bound IgE on the surface of allergic effector cells.

Methods

We selected FcγRIIB‐specific binding molecules from a library of designed ankyrin repeat proteins using ribosome display technology. The bispecific binding modality was generated by molecular cloning and recombinant protein expression. We determined binding characteristics on molecular and cellular levels using SPR, ELISA, and flow cytometry. The inhibitory potential of the newly described molecules was assessed in different cellular degranulation assays ex vivo and in a mouse model of passive systemic anaphylaxis.

Results

We demonstrate that the selected DARPin® proteins recognize FcγRIIB with high affinity. Furthermore, the bispecific binding protein successfully interferes with allergen‐induced cell degranulation and efficiently inhibits systemic anaphylaxis in vivo. Mechanistically, we report that FcγRIIB‐mediated inhibition of effector cell activation requires direct ligation to an activating FcεRI receptor.

Conclusion

The described bispecific DARPin protein has the ability to co‐ligate FcγRIIB with FcεRI‐bound IgE on allergic effector cells and represents an efficient dual‐modality to interfere with allergic hypersensitivity reactions.
The effect of physical fatigue on oscillatory dynamics of the sensorimotor cortex
Authors: Fry A. , Mullinger K. J. , O'Neill G. C. , Brookes M. J. , Folland J. P.
Published: December 2016

Aim

While physical fatigue is known to arise in part from supraspinal mechanisms within the brain, exactly how brain activity is modulated during fatigue is not well understood. Therefore, this study examined how typical neural oscillatory responses to voluntary muscle contractions were affected by fatigue.

Methods

Eleven healthy adults (age 27 ± 4 years) completed two experimental sessions in a randomized crossover design. Both sessions first assessed baseline maximal voluntary isometric wrist‐flexion force (MVFb). Participants then performed an identical series of fourteen test contractions (2 × 100%MVFb, 10 × 40%MVFb, 2 × 100%MVFb) both before and after one of two interventions: forty 12‐s contractions at 55%MVFb (fatigue intervention) or 5%MVFb (control intervention). Magnetoencephalography (MEG) was used to characterize both the movement‐related mu and beta decrease (MRMD and MRBD) and the post‐movement beta rebound (PMBR) within the contralateral sensorimotor cortex during the 40%MVFb test contractions, while the 100%MVFb test contractions were used to monitor physical fatigue.

Results

The fatigue intervention induced a substantial physical fatigue that endured throughout the post‐intervention measurements (28.9–29.5% decrease in MVF, P < 0.001). Fatigue had a significant effect on both PMBR (anova, session × time‐point interaction: P = 0.018) and MRBD (P = 0.021): the magnitude of PMBR increased following the fatigue but not the control interventions, whereas MRBD was decreased post‐control but not post‐fatigue. Mu oscillations were unchanged throughout both sessions.

Conclusion

Physical fatigue resulted in an increased PMBR, and offset attenuations in MRBD associated with task habituation.
Can Investors Identify Managerial Discretion in Corporate Social Responsibility Practices? The Moderate Role of Investor Protection
Authors: Martínez‐Ferrero Jennifer , Villarón‐Peramato Óscar , García‐Sánchez Isabel María
Published: December 2016

This paper analyses investors’ ability to identify if managers use corporate social responsibility as an entrenchment practice to conceal the risk of dismissal associated with managerial discretion and if this detection is determined by the level of investor protection orientation. Results based on an international database of 1949 companies show that investors and markets do not identify managerial entrenchment based on the promotion of sustainable practices, except when such entrenchment is developed by companies located in countries with strong investor protection. In these countries, investors identify and penalise such companies with lower financial performance.
Sulphoraphane Improves Neuronal Mitochondrial Function in Brain Tissue in Acute Carbon Monoxide Poisoning Rats
Authors: Bi Mingjun , Li Qin , Guo Dadong , Ding Xiaoyu , Bi Weikang , Zhang Yueheng , Zou Yong
Published: December 2016

Carbon monoxide (CO) poisoning is one of the leading causes of toxicity‐related mortality and morbidity worldwide, primarily manifested by acute and delayed central nervous system (CNS) injuries and other organ damages. However, its definite pathogenesis is poorly understood. The aim of this study was to explore the pathogenesis of the ultrastructural and functional impairment of mitochondria and the protection of sulphoraphane (SFP) at different dosages on hippocampus neurons in rats after exposure to CO. We found that CO poisoning could induce advanced cognitive dysfunction, while the mitochondrial ultrastructure of neurons in rats of the CO poisoning group was seriously damaged and mitochondrial membrane potential (ΔΨm) was accordingly reduced by transmission electron microscopy (TEM) and JC‐1 fluorescent probe assay. CO poisoning could also increase the expressions of both nuclear factor erythroid 2‐related factor 2 (Nrf‐2) and thioredoxin‐1 (Trx‐1) proteins and their mRNA in brain tissue with immunohistochemistry and quantitative PCR (qPCR) techniques. Early administration of either middle‐dose or high‐dose SFP could efficiently improve mitochondrial structure and function and enhance the antioxidative stress ability, thus exerting a positive effect against brain damage induced by acute CO poisoning.
Ublituximab (TG‐1101), a novel glycoengineered anti‐CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial
Authors: Sharman Jeff P. , Farber Charles M. , Mahadevan Daruka , Schreeder Marshall T. , Brooks Heather D. , Kolibaba Kathryn S. , Fanning Suzanne , Klein Leonard , Greenwald Daniel R. , Sportelli Peter , Miskin Hari P. , Weiss Michael S. , Burke John M.
Published: December 2016

Ibrutinib is effective in patients with chronic lymphocytic leukaemia (CLL); however, treatment resistance remains a problem. Ublituximab is a novel, glycoengineered anti‐CD20 monoclonal antibody with single‐agent activity in relapsed CLL. We report the results of a phase 2 study evaluating combination therapy with ibrutinib and ublituximab in patients with relapsed or refractory CLL. Patients received ibrutinib 420 mg once daily. Ublituximab was administered on days 1, 8 and 15 of cycle 1 followed by day 1 of cycles 2–6. Response assessments were completed at cycles 3 and 6; patients then continued on ibrutinib monotherapy per standard of care. Forty‐one of 45 enrolled patients were evaluable for efficacy. Safety was consistent with prior experience for each drug, with infusion reactions the most prevalent adverse event. Combination therapy resulted in an overall response rate (ORR) of 88% at 6 months. In the 20 patients with high‐risk features (17p or 11q deletions or TP53 mutation) and evaluable for efficacy, the ORR was 95%, with three patients (15%) achieving negative minimal residual disease. Median time to response was 8 weeks. Ublituximab in combination with ibrutinib resulted in rapid and high response rates. The long‐term clinical benefit of ublituximab will be defined by an ongoing phase 3 trial (NCT 02301156).
Outcomes of primary refractory diffuse large B‐cell lymphoma (DLBCL) treated with salvage chemotherapy and intention to transplant in the rituximab era
Authors: Vardhana Santosha A. , Sauter Craig S. , Matasar Matthew J. , Zelenetz Andrew D. , Galasso Natasha , Woo Kaitlin M. , Zhang Zhigang , Moskowitz Craig H.
Published: December 2016

Rituximab‐containing salvage chemotherapy followed by high‐dose therapy and autologous stem cell transplant (ASCT) in chemosensitive patients remains the standard of care for patients with relapsed and refractory diffuse large B‐cell lymphoma (DLBCL). However, its role in those patients achieving less than a complete response to first‐line therapy (primary refractory disease) in the rituximab era is not well defined. We reviewed the outcomes of 82 transplant‐eligible patients with primary refractory DLBCL who underwent salvage therapy with the intent of administering high‐dose therapy and ASCT to patients achieving chemosensitive remission. The estimated 3‐year overall and progression‐free survival for all patients was 38% and 29%, respectively, and 65% and 60% respectively for patients proceeding to stem cell transplant. Long‐term remission was achieved in 45% of patients achieving a partial response (PR) to initial induction therapy and <20% of patients with stable or progression of disease following initial therapy. These results suggest that salvage chemotherapy with the intent of subsequent high‐dose therapy and ASCT remains a feasible strategy in certain patients with primary refractory DLBCL, particularly for those achieving a PR to frontline therapy. The primary barrier to curative therapy in patients with primary refractory disease is resistance to salvage therapy, and future studies should be aimed towards increasing the response rate in this population.
Li‐Fraumeni syndrome: a paradigm for the understanding of hereditary cancer predisposition
Authors: Valdez Jessica M. , Nichols Kim E. , Kesserwan Chimene
Published: December 2016

Li‐Fraumeni syndrome (LFS) is a rare cancer predisposing condition caused by germline mutations in TP53, the gene encoding the TP53 transcription factor. LFS is typified by the development of a wide spectrum of childhood and adult‐onset malignancies, which includes, among others, the lymphoid and myeloid leukaemias, myelodysplastic syndrome and, to a lesser extent, lymphoma. Accordingly, it is important that haematologists/oncologists be familiar with this pleiotropic hereditary cancer syndrome. The high cancer risk and variability in type and age of cancer onset have raised questions about the underlying biology and optimal treatment approaches for individuals with LFS. Since its description almost 50 years ago, many clinical and basic research investigations have provided insights into the pathogenesis, manifestations, genetic testing and management strategies for individuals with LFS. Here we provide an update on the current state of knowledge regarding LFS with an emphasis, where possible, on information relevant to practicing haematologists.
The promise of chimeric antigen receptor T cells (CARTs) in leukaemia
Authors: Orlowski Robert J. , Porter David L. , Frey Noelle V.
Published: December 2016

The success of genetically engineered T cells that express chimeric antigen receptors (CARTs) has been a momentous step forward in harnessing the potent cancer fighting abilities of the immune system. The efficacy seen in relapsed/refractory (r/r) acute lymphoblastic leukaemia (ALL), not only by inducing remission, but also in maintaining long‐term disease control, has been unprecedented. While the foundation for this approach has been firmly set in place, continued development will improve the efficacy, toxicity and applicability to other malignancies of this new class of ‘living drugs’. In this review, we provide a comprehensive overview of the most current clinical trial data in both acute and chronic leukaemias, and discuss some of the potential ways to enhance the activity and safety of CART therapy going forward.
Perturbations environnementales et migrations au Vietnam
Authors: Haemmerli Guillaume , Bélanger Danièle , Fleury Charles , Bich Ngoc Luu
Published: December 2016

Faits saillants

Les perturbations environnementales ne sont pas un facteur significatif de la migration au sein des ménages au Vietnam.

L'analyse multivariée montre que les caractéristiques socioéconomiques sont les facteurs les plus importants pour expliquer la propension à migrer suite à un évènement climatique extrême.

Une contradiction apparait entre la perception subjective de l'impact des évènements climatiques et leurs effets mesurés par des variables objectives.
Protective effects of β‐sheet breaker α/β‐hybrid peptide against amyloid β‐induced neuronal apoptosis in vitro
Authors: Kumar Sourav , Paul Ashim , Kalita Sourav , Ghosh Anup Kumar , Mandal Bhubaneswar , Mondal Amal Chandra
Published: December 2016

Alzheimer's disease is most common neurodegenerative disorder and is characterized by increased production of soluble amyloid‐β oligomers, the main toxic species predominantly formed from aggregation of monomeric amyloid‐β (Aβ). Increased production of Aβ invokes a cascade of oxidative damages to neurons and eventually leads to neuronal death. This study was aimed to investigate the neuroprotective effects of a β‐sheet breaker α/β‐hybrid peptide (BSBHp) and the underlying mechanisms against Aβ40‐induced neurotoxicity in human neuroblastomaSH‐SY5Y cells. Cells were pretreated with the peptide Aβ40to induce neurotoxicity. Assays for cell viability, cell membrane damage, cellular apoptosis, generation of reactive oxygen species (ROS), intracellular free Ca2+, and key apoptotic protein levels were performed in vitro. Our results showed that pretreatment withBSBHp significantly attenuates Aβ40‐induced toxicity by retaining cell viability, suppressing generation ofROS, Ca2+levels, and effectively protects neuronal apoptosis by suppressing pro‐apoptotic protein Bax and up‐regulating antiapoptotic protein Bcl‐2. These results suggest that α/β‐hybrid peptide has neuroprotective effects against Aβ40‐induced oxidative stress, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases.
Environmental tobacco smoke exposure and periodontitis prevalence among nonsmokers in the hispanic community Health Study/Study of Latinos
Authors: Akinkugbe Aderonke A. , Sanders Anne E. , Preisser John S. , Cai Jianwen , Salazar Christian R. , Beck James D.
Published: December 2016

Objective

To describe self‐reported exposure to environmental tobacco smoke (ETS) and its association with periodontitis prevalence in a diverse group of Hispanics/Latinos.

Methods

Data came from 8675 lifetime nonsmokers in the 2008–2011 Hispanic Community Health Study/Study of Latinos. Exposure to ETS was self‐reported, while periodontitis was defined using the Centers for Disease Control and Prevention‐American Academy of Periodontology criteria and the proportion of sites affected by clinical attachment level of ≥3 mm or pocket depth of ≥4 mm. Survey logistic regression estimated prevalence odds ratios (POR) and 95% confidence intervals (CI). In addition, we assessed whether greater hours of exposure to ETS in the past year was associated with greater periodontitis prevalence, and lastly, we conducted a simple sensitivity analysis of ETS misclassification.

Results

Age‐standardized prevalence estimates (95% CI) for ETS exposure and periodontitis were 57.6% (55.9, 59.4) and 39.8% (38.1, 41.4), respectively. After adjusting for confounders and periodontitis risk factors, we estimated an overall adjusted POR (95% CI) for the ETS–periodontitis association as 1.09 (0.95–1.26) with a confidence limit ratio (CLR) of 1.34. This association varied in magnitude by Hispanic/Latino background, ranging from 1.04 (0.75, 1.43 with a CLR = 1.91) among Central Americans to 1.76 (1.16, 2.66 with a CLR = 2.29) in Puerto Ricans.

Conclusions

Previously reported associations between ETS and periodontitis appear weak in this study. However, the magnitude of the association differs according to Hispanic/Latino background.
A total evidence phylogeny for the processionary moths of the genus Thaumetopoea (Lepidoptera: Notodontidae: Thaumetopoeinae)
Authors: Basso Andrea , Negrisolo Enrico , Zilli Alberto , Battisti Andrea , Cerretti Pierfilippo
Published: December 2016

Processionary moths belong to a group of about 100 species well known for their social behaviour and their urticating systems. The genus Thaumetopoea s.l. includes about 15 species and has been divided into three genera (Helianthocampa, Thaumetopoea s.s., and Traumatocampa) in the last revision, based on key morphological features of the adults and on the host plants of the larvae. We performed a total evidence approach to resolve the phylogeny of the genus Thaumetopoea s.l., analysing all valid taxa included in this group, plus a broad array of close relatives. Thaumetopoea was monophyletic and supported by several apomorphies. Further subclades corroborated by synapomorphies were identified. Our phylogeny suggests that Thaumetopoea must be regarded as a single genus. The mapping of key life history traits on the total evidence tree allowed us to sketch a plausible identikit of the Thaumetopoea ancestor and to track the evolution of the genus. The ancestor originated in the eastern Mediterranean area, and used broadleaved host plants. Subsequently, a switch to conifers occurred, just once, in a large subclade. The ancestor pupated in the soil, like several current species, but in a few taxa this trait was lost, together with the related morphological adaptations.