bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental Knowledge Production in Cambodia: A Case Study of Development Research and Attempted Discursive Domination
Authors: Fforde Adam
Published: January 2018

The effects of foreign trade on the environment in the cases of rice, cassava, and fish in Cambodia are examined in this article, but as a case study analyzing markers of developmental discursive practice. The study identifies and analyzes five rhetorical techniques in discursive practice—assertion, provincialism, dismissal of positive outcomes, reference to external causes, and policy fetishism—then argues that these have in common the denial of local voice. It argues that their deployment tends to increase where a discursive order is more contested. In general, the case study shows how much of development policy literature is rather disreputable.
Exposure–response characterization of tofacitinib efficacy in moderate to severe ulcerative colitis: Results from a dose‐ranging phase 2 trial
Authors: Mukherjee Arnab , Hazra Anasuya , Smith Mike K. , Martin Steven W. , Mould Diane R. , Su Chinyu , Niezychowski Wojciech
Published: January 2018

Aims

Tofacitinib is an oral, small molecule JAK inhibitor being investigated for ulcerative colitis (UC). In a phase 2 dose‐ranging study, tofacitinib demonstrated efficacy vs. placebo as UC induction therapy. In this posthoc analysis, we aimed to compare tofacitinib dose and plasma concentration as predictors of efficacy and identify covariates that determined efficacy in patients with UC.

Methods

One‐ and two‐compartment pharmacokinetic models, with first‐order absorption and elimination, were evaluated to describe plasma tofacitinib concentration‐time data at baseline and week 8. Relationships between tofacitinib exposure (dose, average plasma drug concentration during a dosing interval at steady state [Cav,ss] and trough plasma concentration at steady state [Ctrough,ss]) and week 8 efficacy endpoints were characterized using logistic regression analysis. Baseline disease, demographics, prior and concurrent UC treatment were evaluated as covariates.

Results

Plasma tofacitinib concentrations increased proportionately with dose and estimated oral clearance, and Cav,ss values were not significantly different between baseline and week 8. Dose, Cav,ss and Ctrough,ss performed similarly as predictors of efficacy based on statistical criteria for model fit and comparison of model predictions for each endpoint. Individual Cav,ss values were similar between clinical remitters and nonremitters at predicted efficacious doses (10 and 15 mg twice daily). Baseline Mayo score was a significant determinant of efficacy. Predicted differences from placebo in clinical remission at 10 mg twice daily for patients with baseline Mayo score >8 and ≤8 were 39% (95% CI: 7–70) and 21% (–2–50), respectively.

Conclusions

Exposure–response characterization demonstrated the potential of tofacitinib 10 and 15 mg twice daily as induction therapy for UC without monitoring of plasma drug concentrations for dose optimization.
Potassium channel dysfunction in neurons and astrocytes in Huntington's disease
Authors: Zhang Xiao , Wan Jie‐Qing , Tong Xiao‐Ping
Published: January 2018

Huntington's disease (HD) is a late‐onset fatal neurodegenerative disease, characterized by progressive movement disorders, psychiatric symptoms, and cognitive impairment. The cytosine‐adenine‐guanine (CAG) triplet expansion encoding glutamine present in the protein huntingtin (Htt), produces widespread neuronal and glial pathology. Mutant huntingtin (mHtt) nuclear aggregates are the primary cause of cortical and striatal neuron degeneration, neuronal inflammation, apoptosis and eventual cell loss. The precise mechanisms underlying the pathogenesis of neurodegeneration in HD remain poorly understood and HD patients have no current cure. Potassium channels are widely expressed in most cell types. In neurons, they play a crucial role in setting the resting membrane potential, mediating the rapid repolarization phase of the action potential and controlling sub‐threshold oscillations of membrane potentials. In glial cells, their major contributions are maintaining the resting membrane potential and buffering extracellular K+. Thus, potassium channels have an essential function in both physiological and pathological brain conditions. This review summarizes recent progress on potassium channels involved in the pathology of HD by using different HD mouse models. Exploring the dysfunction of potassium channels in the brain illustrates new approaches for targeting this channel for the treatment of HD.
Conserving biodiversity and Indigenous bush tucker: Practical application of the strategic foresight framework to invasive alien species management planning
Authors: Adams Vanessa M. , Douglas Michael M. , Jackson Sue E. , Scheepers Kelly , Kool Johnathan T. , Setterfield Samantha A.
Published: January 2018

Invasive alien species are a major driver of global biodiversity loss. Constrained conservation budgets demand that threat abatement strategies take into account the heterogeneity of areas in need of protection, such as significant ecological and cultural sites, as well as the competing values, preferences, and objectives of stakeholders. We used strategic foresight to assess the threat that invasive alien grasses pose to environmental and Indigenous cultural values on the floodplains of a comanaged, World Heritage‐inscribed national park. We found strategic foresight to be a useful framework to set management priorities that simultaneously conserve biological and cultural diversity. However, it required the development and application of novel ecological and participatory tools and significant time, financial, and human resources. This was the first study to apply strategic foresight to weed management planning in a realistic, culturally complex setting and our work provides an exemplar for the application of the strategic foresight framework and our tools to other contexts.
Increasing kidney donor profile index sequence does not adversely affect medium‐term health‐related quality of life after kidney transplantation
Authors: Forbes Rachel C. , Feurer Irene D. , LaNeve David , Concepcion Beatrice P. , Gamble Christianna , Rega Scott A. , Pinson C. Wright , Shaffer David
Published: January 2018

Background

The United Network for Organ Sharing system allocates deceased donor kidneys based on the kidney donor profile index (KDPI), stratified as sequences (A ≤ 20%, B > 20‐<35%, C ≥ 35‐≤85%, and D > 85%), with increasing KDPI associated with decreased graft survival. While health‐related quality of life (HRQOL) may improve after transplantation, the effect of donor kidney quality, reflected by KDPI sequence, on post‐transplant HRQOL has not been reported.

Methods

Health‐related quality of life was measured using the eight scales and physical and mental component summaries (PCS, MCS) of the SF‐36® Health Survey. Multivariable mixed effects models that adjusted for age, gender, rejection, and previous transplant and analysis of variance methods tested the effects of time and KDPI sequence on post‐transplant HRQOL.

Results

A total of 141 waitlisted adults and 505 recipients (>1700 observations) were included. Pretransplant PCS and MCS averaged, respectively, slightly below and within general population norms (GPN; 40‐60). At 31 ± 26 months post‐transplant, average PCS (41 ± 11) and MCS (51 ± 11), overall and within each KDPI sequence, were within GPN. KDPI sequence was not related to post‐transplant HRQOL (P > .134) or its trajectory (interaction P > .163).

Conclusion

Increasing KDPI does not adversely affect the medium‐term values and trajectories of HRQOL after kidney transplantation. This may reassure patients and centers when considering using high KDPI kidneys.
Ivory as Cultural Document: The Crushing Burden of Conservation
Authors: Curnow Kathy
Published: January 2018

Efforts to stop the international ivory trade and save the affected elephants have increasingly emphasized public ivory crushes of confiscated tusks and carved works. While this and other efforts to involve the public in conservation are commendable, they have a burdensome side. First, African cultural ivories, the artists who made them, and the people who used them may be scapegoated in a misplaced desire to identify perpetrators and hold them responsible for elephant loss. Second, simpler but authentic cultural ivories may remain unidentified and accidentally destroyed. Last, even seemingly negligible tourist art and fakes hold cultural information and deserve individual photographic records for future research. This paper examines the cultural value encoded in select African ivory objects made for small‐scale societies, major kingdoms, and foreign markets to demonstrate the value African societies have for the elephant and its products in the hope that institutions and federal agencies can work together to preserve these cultural documents.
Assessing the economic value of maintained improvements in Type 1 diabetes management, in terms of HbA1c, weight and hypoglycaemic event incidence
Authors: McEwan P. , Bennett H. , Bolin K. , Evans M. , Bergenheim K.
Published: January 2018

Aims

Insulin therapy is indicated for people with Type 1 diabetes mellitus; however, treatment‐related weight gain and hypoglycaemia represent barriers to optimal glycaemic management. This study assessed the health economic value of maintained reductions in HbA1c, BMI and hypoglycaemia incidence among the UK Type 1 diabetes population.

Methods

The Cardiff Type 1 Diabetes Model was used to estimate lifetime costs, life‐years and quality‐adjusted life‐years (QALYs) for individuals with Type 1 diabetes at different baseline HbA1c, BMI and hypoglycaemic event rates. Results were discounted at 3.5%, and the net monetary benefit associated with improving Type 1 diabetes management was derived at £20 000/QALY gained. Per‐person outputs were inflated to national levels using UK Type 1 diabetes prevalence estimates.

Results

Modelled subjects with an HbA1c of 86 mmol/mol (10.0%) were associated with discounted lifetime per‐person costs of £23 795; £12 649 of which may be avoided by maintaining an HbA1c of 42 mmol/mol (6.0%). Combined with estimated QALY gains of 2.80, an HbA1c of 42 mmol/mol (6.0%) vs. 86 mmol/mol (10.0%) was associated with a £68 621 per‐person net monetary benefit. Over 1 year, unit reductions in BMI produced £120 per‐person net monetary benefit, and up to £197 for the avoidance of one non‐severe hypoglyceamic event.

Conclusions

Maintained reductions in HbA1c significantly alleviate the burden associated with Type 1 diabetes in the UK. Given the influence of weight and hypoglycaemia on health economic outcomes, they must also be key considerations when assessing the value of Type 1 diabetes technologies in clinical practice.
Chantey Castings: A Hands‐On Simulation to Teach Constraint Management and Demand‐Driven Supply Chain Approaches
Authors: Grandzol Christian J. , Grandzol John R.
Published: January 2018

Supply chain design and constraint management are widely‐adopted techniques in industry, necessitating that operations and supply chain educators teach these topics in ways that enhance student learning and retention, optimize resource utilization (especially time), and maximize student interest. The Chantey Castings Simulation provides a platform to accomplish all three criteria. In a fun, collaborative environment, students learn important concepts related to these techniques by identifying obstacles to matching customer demand with sourcing, production, and logistics for a variety of products made from Play‐Doh. Assessment data indicate the simulation is a highly‐effective experiential learning activity.
A System's View of E‐Learning Success Model
Authors: Eom Sean B. , Ashill Nicholas J.
Published: January 2018

The past several decades of e‐learning empirical research have advanced our understanding of the effective management of critical success factors (CSFs) of e‐learning. Meanwhile, the proliferation of measures of dependent and independent variables has been overelaborated. We argue that a significant reduction in dependent and independent variables and their measures is necessary for building an e‐learning success model, and such a model should incorporate the interdependent (not independent) process nature of e‐learning success. We applied structural equation modeling to empirically validate a comprehensive model of e‐learning success at the university level. Our research advances existing literature on CSFs of e‐learning and provides a basis for comparing existing research results as well as guiding future empirical research to build robust e‐learning theories. A total of 372 valid unduplicated responses from students who have completed at least one online course at a university in the Midwestern United States were used to examine the structural model. Findings indicated that the e‐learning success model satisfactorily explains and predicts the interdependency of six CSFs of e‐learning systems (course design quality, instructor, motivation, student‐student dialog, student‐instructor dialog, and self‐regulated learning) and perceived learning outcomes.
Can there be a moral obligation to participate in biomedical research?
Authors: Seiler Christian
Published: January 2018

In clinical medicine, the moral obligation to care for the individual patient is absolute. Patient care means at least and by negative terms to minimize any risk of treatment. In this context, the question arises about the compatibility of clinical ethics and human biomedical research ethics. Or conversely, is there a common ground between the two? At the opposite end of the field between clinical ethics and biomedical research ethics is the proposal of an obligation to participate in biomedical research, which is argued for on the basis of biomedical knowledge being a public good available to the community as a whole. While patient accrual during a clinical investigation would certainly be facilitated by obligatory research participation, and the data obtained would be—at first sight—more representative for the population studied, the still feasible refusal to participate would be stigmatizing and as such detrimental for the patient‐physician relation. This essay seeks to provide a reply to the titled question by focusing on aspects such as individual vs common medical claims, shared grounds between the two and an important document of medical research ethics, that is the Nuremberg code.
Delayed myelination and neurodevelopment in male seizure‐prone versus seizure‐resistant rats
Authors: Sharma Pragati , Powell Kim L. , Wlodek Mary E. , O'Brien Terence J. , Gilby Krista L.
Published: January 2018

Objective

Aberrant myelination and developmental delay have been reported in epilepsy. However, it is unclear whether these are linked to intrinsic mechanisms that support a predisposition toward seizures and the development of epilepsy. Thus, we compared rates of myelination and neurodevelopment in male rats selectively bred for enhanced susceptibility to kindling epileptogenesis (FAST) with male rats bred for resistance (SLOW).

Methods

Myelin‐specific gene expression was compared in the brainstem, cerebellum, and cerebral hemisphere of FAST and SLOW rats on postnatal days (PNDs) 5, 11, 17, 23, and 90 to determine strain‐specific myelination rates. Myelin protein levels were also compared at PNDs 5 and 23 in the brainstem. Relative rates of neurodevelopment were evaluated between PNDs 5 and 21 using physical growth landmarks and neuromotor tests including righting reflex, cliff avoidance, negative geotaxis, and locomotor activity.

Results

Myelin‐specific mRNA expression was significantly down‐regulated in FAST rats on PNDs 5 and 11 in all 3 brain structures, indicating relatively delayed myelination. Likewise, corresponding protein levels were significantly lower in FAST brainstem on PND 5. Developmental delay was evident in the FAST strain such that only 9% of FAST pups, compared to 81% of SLOW, had open eyes by PND 13, locomotor activity was significantly reduced between PNDs 12 and 16, and neuromotor task acquisition was delayed between PNDs 5 and 10.

Significance

Relative delays in myelination and neurodevelopment co‐occurred in the seizure‐prone FAST strain in the absence of seizures. These findings suggest these symptoms are not seizure‐induced and may be mechanistically linked to an underlying pathophysiology supporting a predisposition toward developing epilepsy.
Native or not? Ancient DNA rejects persistence of New Zealand's endemic black swan: A reply to Montano et al.
Authors: Rawlence Nicolas J. , Kardamaki Afroditi , Easton Luke J. , Tennyson Alan J. D. , Scofield Richard P. , Waters Jonathan M.
Published: January 2018

Montano et al.'s (Evolutionary Applications, 2017) recent coalescent analysis of modern black swan (Cygnus atratus) genotypes concluded that New Zealand's native black swan survived prehistoric hunting, to later hybridize with introduced black swans from Australia. However, this persistence scenario conflicts with new ancient DNA, morphometric and archaeological analyses of prehistoric New Zealand swan (C. sumnerensis) remains, which instead support a wholesale extinction‐replacement scenario. Multiple lines of evidence indicate that C. sumnerensis did not survive beyond the earliest phase of Polynesian settlement in New Zealand and thus question the reliability of coalescent inferences derived from small numbers of microsatellite loci.
Occupational risks of working with horses: A questionnaire survey of equine veterinary surgeons
Authors: Parkin T. D. H. , Brown J. , Macdonald E. B.
Published: January 2018

Limited scientific evidence from other countries and plenty of anecdotal evidence suggest that the risk of personal injury in equine veterinary practice is high. However, a comprehensive description of the types of risks to which equine veterinary surgeons expose themselves has not previously been available. The aim of this study was to quantify the number, types and causes of personal injury sustained by equine veterinary practitioners in the UK. An interview (and online) questionnaire‐based survey was conducted with a large number of equine veterinary practitioners. Questions were designed to identify the number of injuries sustained during the respondent's career to date and to acquire details of the worst injury sustained including cause, treatment and short‐ and long‐term outcomes. A total of 2292 injuries were reported by 620 respondents, equating to one injury every 3 years 7 months in those respondents. Most ‘worst’ injuries occurred while the veterinary surgeon was conducting most common reasons for equine examination. The most frequent sites of this ‘worst’ injury were the leg and the head with the main cause of injury being a kick with hindlimb. Of all reports, 33% of injuries resulted in a hospital admission of which 43% required hospital admission for longer than 24 h and 7% of reports resulted in a loss of consciousness. The main limitation of this work is the descriptive nature of the survey. It would be unwise to assume that the procedures identified as being most commonly associated with injury in the study are more risky than other less commonly conducted procedures. In conclusion, equine veterinary practice is a risky profession. Greater emphasis on and awareness of methods to avoid or mitigate risk should be a priority for anyone working with horses and their employers.
Atypical myopathy in the South‐East of England: Clinicopathological data and outcome in hospitalised horses
Authors: Dunkel B. , Ryan A. , Haggett E. , Knowles E. J.
Published: January 2018

This retrospective case series describes clinicopathological data and outcome of hospitalised atypical myopathy (AM) cases in the South‐East of England. The study aimed to describe the frequency of metabolic abnormalities (hyperglycaemia, hyperlactataemia, hypertriglyceridaemia) and outcome in AM cases in the South‐East of England and test the hypothesis that serum creatine kinase (CK) activity and blood glucose, lactate and triglyceride concentrations are associated with outcome. Medical records (2011–2017) from three referral hospitals were reviewed for cases with a clinical diagnosis of AM. A previously described algorithm was applied and cases were included if a diagnosis of AM was considered highly likely. In cases admitted after 2013 known or possible exposure to sycamore trees was also required for inclusion. Sixty‐four animals were included, 44% (28/64) survived. Hyperglycaemia, hyperlactataemia and hypertriglyceridaemia were present in 76%, 89% and 92% of horses on admission, respectively. Survivors had lower blood lactate concentrations (survivors: median 3.5 mmol/L; range 0.5–10.4 mmol/L vs. nonsurvivors: median 7.3 mmol/L; range 2.5–16.5 mmol/L; P = 0.011) and serum CK activities (survivors: median 38,369 U/L; range 7024–570,498 U/L vs. nonsurvivors: median 172,687 U/L; range 2036–570,953 U/L; P = 0.027) on admission when compared to nonsurvivors. Increasing CK activity (P = 0.008) and triglyceride concentrations (P = 0.038) during hospitalisation were associated with nonsurvival. More nonsurvivors required sedation (18/29; 62.1% vs. 4/22; 18.2%; P = 0.002). The prognosis for hospitalised horses with AM is guarded and outcome in this population was associated with admission CK activity and lactate concentrations, and increasing CK activity and triglyceride concentrations and need for sedation during hospitalisation.
Investigation of Thulium and Other Rare Earth Element Mass Fractions in NIST SRM 1632a Bituminous Coal Reference Material by Quadrupole ICP‐MS
Authors: Roth Elliot , Bank Tracy L. , Granite Evan
Published: January 2018

Inductively coupled plasma‐mass spectrometry after lithium metaborate fusion and digestion was used to measure the rare earth element (REE) mass fractions of several reference materials including NIST SRM 1632a, a historical bituminous Pennsylvania seam coal. While most of the REE mass fractions measured in this study were consistent with the published consensus data, the measured mass fraction of thulium for NIST SRM 1632a was consistently lower compared with the published data. Chondrite normalisation of the published consensus data for NIST SRM 1632a produced a positive thulium anomaly (Tm = 1.78), which is inconsistent with a terrestrial source of sediment. Normalisation of REE mass fractions collected in this study produced no significant Tm anomaly (Tm = 0.93), which agrees with the sedimentary depositional environment of coal. Therefore, a revised mass fraction of 0.16 mg kg−1 Tm in NIST SRM 1632a is recommended.
Multicenter, randomized, controlled trial of S‐1 monotherapy versus S‐1 and interferon‐α combination therapy for hepatocellular carcinoma with extrahepatic metastases
Authors: Nagano Hiroaki , Obi Shuntaro , Hatano Etsuro , Kaneko Shuichi , Kanai Fumihiko , Omata Masao , Tsuji Akihito , Itamoto Toshiyuki , Yamamoto Kazuhide , Tanaka Masatoshi , Kubo Shoji , Hirata Koichi , Nakamura Hideji , Tomimaru Yoshito , Yamanaka Takeharu , Kojima Shinsuke , Monden Morito
Published: January 2018

Aim

No effective therapies for extrahepatic metastases from hepatocellular carcinoma (HCC) have yet been identified. Previous studies suggested a potentially promising antitumor effect of combination therapy of S‐1, a novel oral dihydropyrimidine dehydrogenase inhibitor, and interferon (IFN)‐α. The present study aimed to investigate the clinical efficacy of single agent S‐1 and S‐1/IFN‐α for HCC patients with extrahepatic metastases in a randomized, open‐label, multicenter trial.

Methods

A total of 103 patients with HCC with extrahepatic metastases were randomly assigned to the S‐1/IFN‐α group, receiving the combination of S‐1 and IFN‐α, or the S‐1 group, receiving the single agent of S‐1. Clinical efficacy and adverse events were compared between the two groups.

Results

A total of 49 patients in the S‐1/IFN‐α group and 51 patients in the S‐1 group were included in the efficacy analysis. The response rate was 22.4% (11/49) in the S‐1/IFN‐α group and 13.7% (7/51) in the S‐1 group; there was no significant difference. Overall and progression‐free survival in the two groups were also not significantly different (1‐year overall survival 50.8% vs. 72.4%, median progression‐free survival 127 days vs. 157 days). The incidence of grade ≥3 adverse events in the S‐1/IFN‐α group was 62.7% (32/51), which tended to be higher than in the S‐1 group (43.1% [22/51]).

Conclusions

Oncological outcomes in both treatment groups were favorable compared with previous reports, though there was no significant beneficial effect of adding IFN‐α to S‐1 for the treatment of HCC patients with extrahepatic metastases.
Epigeal spider assemblage responses to vegetation structure under contrasting grazing management in upland calcareous grasslands
Authors: Lyons Ashley , Ashton Paul A. , Powell Ian , Oxbrough Anne
Published: January 2018

Calcareous grassland is one of the most species rich and diverse habitats within Europe, but has faced decline due to agricultural intensification and abandonment. In recent years, conservation organisations have altered grazing practices in an attempt to maintain floristic components. However, there has been little consideration of the effects of changes in grazing practices on invertebrates. This study determines the impacts of commonly used grazing practices in upland calcareous grasslands on spiders in relation to vegetation structural complexity.

Typical grazing management regimes were examined in three regions of upland calcareous grassland in Britain. Spiders were sampled from April to August 2014 and vegetation structural complexity was recorded in 2 × 2 m quadrats paired with pitfall traps sequentially throughout the sample period.

There were three distinct spider assemblages among the grazing regimes; ungrazed, heavy sheep grazed and one shared between cattle and light sheep (which had a comparable grazing intensity). The distinct spider assemblages among grazing regimes can be attributed to the interaction of grazing and habitat structure.

Increased vegetation structural complexity in ungrazed regimes resulted in an assemblage dominated by ‘sheet web weavers’ (dominated by Linyphiidae). In contrast, reduced vegetation structural complexity and homogeneity in heavy sheep grazing resulted in an assemblage dominated by ‘other hunters’ (includingOedothoraxandErigonegenera).

Grazing regime alters vegetation structural complexity and is important in supporting distinct spider assemblages. This research indicates that low intensity conservation grazing regimes, in addition to no grazing, should be promoted across upland calcareous grassland landscapes to maintain heterogeneity.
Simultaneous surface and bulk crystallization of Bi1.5ZnNb1.5O7‐type pyrochlores and related crystals in glasses
Authors: Shimamura Keisuke , Honma Tsuyoshi , Shinozaki Kenji , Komatsu Takayuki
Published: January 2018

New glasses based on the systems of Bi2O3‐ZnO‐Nb2O5‐B2O3 and ‐GeO2 were synthesized using a conventional melt‐quenching method, and the formation behavior of pyrochlore‐type Bi1.5ZnNb1.5O7 crystals was examined to develop new dielectric glass‐ceramics. It was demonstrated that pyrochlore‐type Bi1.5ZnNb1.5O7 crystals are formed in 15Bi2O3‐20ZnO‐15Nb2O5‐50B2O3 glass, ie, pseudo‐binary Bi1.5ZnNb1.5O7‐B2O3 glass. The formation of a new crystalline phase consisting of mainly Bi2O3 and Nb2O5 was detected in 15Bi2O3‐20ZnO‐15Nb2O5‐50GeO2 glass, in which a simultaneous crystallization of new crystals with different morphologies was found at the surface and in the inside of the glass. The crystallized sample of 21Bi2O3‐28ZnO‐21Nb2O5‐30GeO2 glass exhibited the dielectric constant of εr=91 at f = 100 kHz, suggesting a potential for optoelectronic device applications.
Incorporation of gluten and hydrolysed gluten proteins has different effects on dough rheology and cookie characteristics
Authors: Bravo‐Nuñez Ángela , Sahagún Marta , Martínez Paula , Gómez Manuel
Published: January 2018

This study aims to establish how the substitution of wheat flour by high levels (15%, 30% and 45%) of gluten or hydrolysed gluten proteins affects sugar‐snap cookies properties. An increase in water‐binding capacity was observed when proteins were present. An increase in the dough elastic modulus was observed for gluten protein, but it decreased when hydrolysed gluten protein was used. Regarding the physical characteristics of the cookies, for the same protein percentage, the presence of gluten protein decreased spread ratio and increased hardness, while hydrolysed gluten protein increased spread ratio and yielded darker cookies without modifying the hardness. As for sensory characteristics, taste was negatively influenced by hydrolysed protein and visual acceptability was enhanced when gluten protein was present. Overall acceptability was decreased for the highest levels of hydrolysed gluten protein. Nevertheless, the highest levels of gluten protein did not modify the acceptability.
Analysis and mathematical modelling of the behaviour of Escherichia coli in the mascarpone cheese during cold storage
Authors: Kowalik Jaroslaw , Lobacz Adriana , Zulewska Justyna , Dec Bogdan
Published: January 2018

The aim of this work was to study the behaviour of E. coli in mascarpone cheese during storage at the temperatures ranging from 3 to 15 °C, as well as application of predictive microbiology to describe the experimental data. The Baranyi, Gompertz and logistic models were fitted at the stage of primary modelling. Although all applied primary models described the growth of micro‐organisms accurately, the most accurate goodness of fit was obtained for the Gompertz model and the growth rates generated by this model were used for secondary modelling. The polynomial model predicted accurately the influence of temperature on the growth rate of E. coli, reaching the adjusted coefficient of linear regression 0.99. Generated predictive model that describes the growth of E. coli in mascarpone cheese constitutes a valuable tool in assessing the microbiological stability of the food product with similar physicochemical properties.
Low maternal vitamin D status in pregnancy increases the risk of childhood obesity
Authors: Daraki V. , Roumeliotaki T. , Chalkiadaki G. , Katrinaki M. , Karachaliou M. , Leventakou V. , Vafeiadi M. , Sarri K. , Vassilaki M. , Papavasiliou S. , Kogevinas M. , Chatzi L.
Published: January 2018

Background

Vitamin D may modulate adipogenesis. However, limited studies have investigated the effect of maternal vitamin D during pregnancy on offspring adiposity or cardiometabolic parameters with inconclusive results.

Objectives

The objective of this study is to examine the association of maternal 25(OH)‐vitamin D [25(OH)D] status with offspring obesity and cardiometabolic characteristics in 532 mother–child pairs from the prospective pregnancy cohort Rhea in Crete, Greece.

Methods

Maternal 25(OH)D concentrations were measured at the first prenatal visit (mean: 14 weeks, SD: 4). Child outcomes included body mass index standard deviation score, waist circumference, skin‐fold thickness, blood pressure and serum lipids at ages 4 and 6 years. Body fat percentage was also measured at 6 years. Body mass index growth trajectories from birth to 6 years were estimated by mixed effects models with fractional polynomials of age. Adjusted associations were obtained via multivariable linear regression analyses.

Results

About two‐thirds of participating mothers had 25(OH)D concentrations <50 nmol L−1. Offspring of women in the low 25(OH)D tertile (<37.7 nmol L−1) had higher body mass index standard deviation score (β 0.20, 95% CI: 0.03, 0.37), and waist circumference (β 0.87 95% CI: 0.12, 1.63) at preschool age, compared with the offspring of women with higher 25(OH)D measurements (≥37.7 nmol L−1), on covariate‐adjusted analyses. The observed relationships persisted at age 6 years. We found no association between maternal 25(OH)D concentrations and offspring blood pressure or serum lipids at both time points.

Conclusions

Exposure to very low 25(OH)D concentrations in utero may increase childhood adiposity indices. Given that vitamin D is a modifiable risk factor, our findings may have important public health implications.
Variable neighborhood search algorithms for the vehicle routing problem with two‐dimensional loading constraints and mixed linehauls and backhauls
Authors: Pinto Telmo , Alves Cláudio , Valério de Carvalho José
Published: January 2018

In this paper, we explore a vehicle routing problem with two‐dimensional loading constraints and mixed linehauls and backhauls. The addressed problem belongs to a subclass of general pickup and delivery problems. Two‐dimensional loading constraints are also considered. These constraints arise in many real‐world situations and can improve efficiency since backhaul customers do not need to be delayed in a route when it is possible to load their items earlier and without rearrangements of the items. To tackle this problem, we report extensive computational experiments to assess the performance of different variants of the variable neighborhood search approaches. The initial solution relies on an insertion heuristic. Both shaking and local search phases resort to 10 neighborhood structures. Some of those structures were specially developed for this problem. The feasibility of routes is heuristically obtained with a classical bottom‐left based method to tackle the explicit consideration of loading constraints. All the strategies were implemented and exhaustively tested on instances adapted from the literature. The results of this computational study are discussed at the end of this paper.
Eu3+‐doped glass as a color rendering index enhancer in phosphor‐in‐glass
Authors: Orozco Hinostroza Ignacio E. , Desirena Haggeo , Hernandez Jose , Molina Jorge , Moreno Ivan , De la Rosa Elder
Published: January 2018

A new method for improving color rendering index (CRI) and low correlated color temperature (CCT) in high‐power white‐light‐emitting diodes (WLEDs) is proposed. We used a configuration of phosphor‐in‐glass (PIG) and studied light output changes with the increment in concentration of yellow‐emitting Y3Al5O12:Ce3+ (YAG:Ce3+) phosphor. The PIG was coupled on the top of blue‐light‐emitting diodes (LED) chip (465 nm). To compensate the lack of red emission in the phosphor, Eu3+‐doped tellurium glass with different europium content was employed as a red emitter. The suitable contents of YAG:Ce3+ and Eu3+ were 7.5 weight percent (wt%) and 3 mol percent (mol%), respectively. The CRI value went from 72 to 82, whereas the CCT was reduced from 24 933 to 6434 K. The proposed structure can improve CCT as well as CRI of WLEDs just by placing a glass on top.
New insights into nanoindentation crack initiation in ion‐exchanged sodium aluminosilicate glass
Authors: Li Xiaoyu , Jiang Liangbao , Mohagheghian Iman , Dear John P. , Li Lei , Yan Yue
Published: January 2018

The effect of ion‐exchange on the fracture behavior and the threshold load is investigated for radial crack initiation resulting from cube‐corner indentation. Both tin and air sides of the sodium aluminosilicate float glass are considered. The threshold load and mechanical properties are experimentally measured by nanoindentation. A qualitative explanation of crack initiation is developed by analyzing the stresses at the indentation site. The ion‐exchanged glasses show a lower threshold load for radial crack initiation with a cube‐corner indenter than the raw glass, and this is due to a higher crack driving stress for ion‐exchanged glasses. However, the compressive stress on the surface of the ion‐exchanged glasses can inhibit the expanding of the radial cracks. The air side always shows higher values for the threshold load than the tin side before and after ion‐exchange, which is in accordance with the calculated crack driving stress results.
The effects of participation, performance, and interest in a game‐based writing environment
Authors: Liao Calvin C. Y. , Chang Wan‐Chen , Chan Tak‐Wai
Published: January 2018

We have observed that many computer‐supported writing environments based on pedagogical strategies have only been designed to incorporate the cognitive aspects, but motivational aspects should also be included. Hence, we theorize that integrating game‐based learning into the writing environment may be a practical approach that can facilitate student participation, not only helping students learn how to write, but also sustaining their willingness to write. In this study, we investigate the effects of the game‐based writing environment on improving students' participation, performance, and interest in writing. An experiment was conducted to compare the effectiveness of 2 approaches to writing in language arts at an elementary school. Two hundred forty‐five third grade students participated in the experiment over a period of 1 year. One hundred thirty‐nine students were assigned to an experimental group and learned with a game‐based writing environment, and 106 students were in the contrast group and learned with an online writing environment. The empirical results show that the game‐based writing environment can effectively promote students' writing participation, writing performance, interest in writing, as well as their perceptions of the use of educational self‐management games. Some implications of the experimental results are also discussed.
Physical exosome:exosome interactions
Authors: Beit‐Yannai Elie , Tabak Saray , Stamer W. Daniel
Published: January 2018

Exosomes are extracellular nanovesicles that mediate a number of cellular processes, including intracellular signalling. There are many published examples of exosome–exosome dimers; however, their relevance has not been explored. Here, we propose that cells release exosomes to physically interact with incoming exosomes, forming dimers that we hypothesize attenuate incoming exosome‐mediated signalling. We discuss experiments to test this hypothesis and potential relevance in health and disease.
Hypothesis: apo‐lactoferrin–Galantamine Proteo‐alkaloid Conjugate for Alzheimer's disease Intervention
Authors: Akilo Olufemi D. , Kumar Pradeep , Choonara Yahya E. , Pradeep Priyamvada , du Toit Lisa C. , Pillay Viness
Published: January 2018

Alzheimer's disease (AD) is known to be caused by the accumulation of deformed beta amyloid and hyperphosphorylated tau proteins resulting into formation and aggregation of senile plaques and neurofibrillary tangles in the brain. Additionally, AD is associated with the accumulation of iron or metal ions in the brain which causes oxidative stress. Galantamine (Gal) is one of the therapeutic agents that has been approved for the treatment of AD, but still saddled with numerous side effects and could not address the issue of iron accumulation in the brain. The use of metal chelators to address the iron accumulation has not been successful due to toxicity and inability to address the aggregation of the plaques. We therefore hypothesize a combinatorial antioxidant–metal–chelator approach by formulating a single dosage form that has the ability to prevent the formation of free radicals, plaques and accumulation of iron in the brain. This can be achieved by conjugating Gal with apo‐lactoferrin (ApoLf), a natural compound that has high binding affinity for iron, to form an apo‐lactoferrin–galantamine proteo‐alkaloid conjugate (ApoLf–Gal) as a single dosage form for AD management. The conjugation is achieved through self‐assembly of ApoLf which results in encapsulation of Gal. ApoLf changes its conformational structure in the presence of iron; therefore, ApoLf–Gal is proposed to deliver Gal and pick up excess iron when in contact with iron. This strategy has the potential to proffer a dual neuroprotection and neurotherapeutic interventions for the management of AD.
The FDA approved PI3K inhibitor GDC‐0941 enhances in vitro the anti‐neoplastic efficacy of Axitinib against c‐myc‐amplified high‐risk medulloblastoma
Authors: Ehrhardt Michael , Craveiro Rogerio B. , Velz Julia , Olschewski Martin , Casati Anna , Schönberger Stefan , Pietsch Torsten , Dilloo Dagmar
Published: January 2018

Aberrant receptor kinase signalling and tumour neovascularization are hallmarks of medulloblastoma development and are both considered valuable therapeutic targets. In addition to VEGFR1/2, expression of PDGFR α/β in particular has been documented as characteristic of metastatic disease correlating with poor prognosis. Therefore, we have been suggested that the clinically approved multi‐kinase angiogenesis inhibitor Axitinib, which specifically targets these kinases, might constitute a promising option for medulloblastoma treatment. Indeed, our results delineate anti‐neoplastic activity of Axitinib in medulloblastoma cell lines modelling the most aggressive c‐myc‐amplified Non‐WNT/Non‐SHH and SHH‐TP53‐mutated tumours. Exposure of medulloblastoma cell lines to Axitinib results in marked inhibition of proliferation and profound induction of cell death. The differential efficacy of Axitinib is in line with target expression of medulloblastoma cells identifying VEGFR 1/2, PDGFR α/β and c‐kit as potential markers for drug application. The high specificity of Axitinib and the consequential low impact on the haematopoietic and immune system render this drug ideal multi‐modal treatment approaches. In this context, we demonstrate that the clinically available PI3K inhibitor GDC‐0941 enhances the anti‐neoplastic efficacy of Axitinib against c‐myc‐amplified medulloblastoma. Our findings provide a rational to further evaluate Axitinib alone and in combination with other therapeutic agents for the treatment of most aggressive medulloblastoma subtypes.
The relationship between myocardial fibrosis and myocardial microRNAs in dilated cardiomyopathy: A link between mir‐133a and cardiovascular events
Authors: Rubiś Paweł , Totoń‐Żurańska Justyna , Wiśniowska‐Śmiałek Sylwia , Dziewięcka Ewa , Kołton‐Wróż Maria , Wołkow Paweł , Pitera Ewelina , Rudnicka‐Sosin Lucyna , Garlitski Ann C. , Gackowski Andrzej , Podolec Piotr
Published: January 2018

It is unknown whether fibrosis‐associated microRNAs: miR‐21, miR‐26, miR‐29, miR‐30 and miR‐133a are linked to cardiovascular (CV) outcome. The study evaluated the levels of extracellular matrix (ECM) fibrosis and the prevalence of particular microRNAs in patients with dilated cardiomyopathy (DCM) to investigate any correlation with CV events. Methods: Seventy DCM patients (48 ± 12 years, EF 24.4 ± 7.4%) underwent right ventricular biopsy. The control group was comprised of 7 patients with CAD who underwent CABG and intraoperative biopsy. MicroRNAs were measured in blood and myocardial tissue via qPCR. The end‐point was a combination of CV death and urgent HF hospitalization at the end of 12 months. There were differential levels of circulating and myocardial miR‐26 and miR‐29 as well as myocardial miR‐133a when the DCM and CABG groups were compared. Corresponding circulating and myocardial microRNAs did not correlate with one another. There was no correlation between microRNA and ECM fibrosis. By the end of the 12‐month period of the study, CV death had occurred in 6 patients, and a further 19 patients required urgent HF hospitalization. None of the circulating microRNAs was a predictor of the combined end‐point; however, myocardial miR‐133a was an independent predictor in unadjusted models (HR 1.53; 95% CI 1.14‐2.05; P < .004) and adjusted models (HR 1.57; 95% CI 1.14‐2.17; P < .005). The best cut‐off value for the miR‐133a level for the prediction of the combined end‐point was 0.74 ΔCq, with an AUC of 0.67. The absence of a correlation between the corresponding circulating and myocardial microRNAs calls into question their cellular source. This study sheds new light on the role of microRNAs in ECM fibrosis in DCM, which warrants further exploration.
The influence of exposome on acne
Authors: Dréno B. , Bettoli V. , Araviiskaia E. , Sanchez Viera M. , Bouloc A.
Published: January 2018

Background

Acne vulgaris is one of the main reasons for dermatological consultations. Severity and response to treatment may be impacted by various external factors or exposome.

Aim

To assess the impact of environmental factors on acne and to provide a comprehensive overview of the acne exposome.

Methods

Two consensus meetings of five European dermatologists and a comprehensive literature search on exposome factors triggering acne served as a basis for this review.

Results

Acne exposome was defined as the sum of all environmental factors influencing the occurrence, duration and severity of acne. Exposome factors impact on the response and the frequency of relapse to treatments by interacting with the skin barrier, sebaceous gland, innate immunity and cutaneous microbiota. They may be classified into the following six main categories: nutrition, psychological and lifestyle factors, occupational factors including cosmetics, as well as pollutants, medication and climatic factors. Moreover, practical considerations for the dermatologist's clinical practice are proposed.

Conclusion

Exposome factors including nutrition, medication, occupational factors, pollutants, climatic factors, and psychosocial and lifestyle factors may impact on the course and severity of acne and on treatment efficacy. Identifying and reducing the impact of exposome is important for an adequate acne disease management.
Bacterial Surface Traits Influence Digestion by Tetrahymena pyriformis and Alter Opportunity to Escape from Food Vacuoles
Authors: Siegmund Lisa , Schweikert Michael , Fischer Martin S. , Wöstemeyer Johannes
Published: January 2018

Endosymbiotic interactions are frequently found in nature, especially in the group of protists. Even though many endosymbioses have been studied in detail, little is known about the mechanistic origins and physiological prerequisites of endosymbiont establishment. A logical step towards the development of endocytobiotic associations is evading digestion and escaping from the host's food vacuoles. Surface properties of bacteria are probably involved in these processes. Therefore, we chemically modified the surface of a transformant strain of Escherichia coli prior to feeding to Tetrahymena pyriformis. N‐(3‐dimethylaminopropyl)‐N’‐ethylcarbodiimide allows any substance carrying amino‐ or carboxyl groups to be bound covalently to the bacterial surface by forming a peptide bond, thus, altering its properties biochemically and biophysically in a predictable manner. The effect of different traits on digestion of T. pyriformis was examined by fluorescence and transmission electron microscopy. The efficiency of digestion differs considerably depending on the coupled substances. Alkaline substances inhibit digestion partially, resulting in incomplete digestion and slightly enhanced escape rates. Increasing hydrophobicity leads to much higher escape frequencies. Both results point to possible mechanisms employed by pathogenic bacteria or potential endosymbionts in evading digestion and transmission to the host's cytoplasm.