bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of proton pump inhibitors and risk of iron deficiency: a population‐based case–control study
Authors: Tran‐Duy A. , Connell N. J. , Vanmolkot F. H. , Souverein P. C. , de Wit N. J. , Stehouwer C. D. A. , Hoes A. W. , de Vries F. , de Boer A.
Published: August 2018

Background

Hypochlorhydric states are an important cause of iron deficiency (ID). Nevertheless, the association between therapy with proton pump inhibitors (PPIs) and ID has long been a subject of debate. This case–control study aimed to investigate the risk of ID associated with the use of PPIs using the UK Clinical Practice Research Datalink (CPRD) database.

Methods

Cases were patients aged 19 years or older with first‐time diagnosis of ID between 2005 and 2016 (n = 26 806). The dates of first diagnosis of ID in cases defined the index dates. For each case, one control was matched by age, gender and general practice. A PPI “full” user (PFU) was defined as a subject who had received PPIs for a continuous duration of at least 1 year prior to the index date. A PPI “limited” users (PLU) was a subject who intermittently received PPI therapy. A PPI non‐user (PNU) was a subject who received no PPI prescriptions prior to the index date. The odds ratio of ID in PFU and PLU compared to PNU was estimated using conditional logistic regression.

Results

Among cases, 2960 were PFU, 6607 PLU and 17 239 PNU. Among controls, 1091 were PFU, 5058 PLU and 20 657 PNU. Adjusted odds ratio of ID in PFU and PLU compared to PNU was 3.60 (95%CI, [3.32–3.91]) and 1.51 (95% CI, [1.44–1.58]). Positive dose–response and time–response relationships were observed.

Conclusions

Chronic PPI use increases the risk of ID. Physicians should consider this when balancing the risks and benefits of chronic PPI prescription.
The weight of nutrients: kynurenine metabolites in obesity and exercise
Authors: Dadvar S. , Ferreira D. M. S. , Cervenka I. , Ruas J. L.
Published: August 2018

Obesity ultimately results from an imbalance between energy intake and expenditure. However, in addition to their bioenergetic value, nutrients and their metabolites can function as important signalling molecules in energy homeostasis. Indeed, macronutrients and their metabolites can be direct regulators of metabolism through their actions on different organs. In turn, target organs can decide to use, store or transform the incoming nutrients depending on their physiological context and in coordination with other cell types. Tryptophan‐kynurenine metabolites are an example of a family of compounds that can serve as systemic integrators of energy metabolism by signalling to different cell types. These include adipocytes, immune cells and muscle fibres, in addition to the well‐known effects of kynurenine metabolites on the central nervous system. In the context of energy metabolism, several of the effects elicited by kynurenic acid are mediated by the G‐protein‐coupled receptor, GPR35. As GPR35 is expressed in tissues such as the adipose tissue, immune cells and the gastrointestinal tract, this receptor could be a potential therapeutic target for the treatment of obesity, diabetes and other metabolic diseases. In addition, metabolic disorders often coincide with states of chronic inflammation, which further highlights GPR35 as an integration node in conditions where inflammation skews metabolism. Defining the molecular interplay between different tissues in the regulation of energy homeostasis can help us understand interindividual variability in the response to nutrient intake and develop safe and efficient therapies to fight obesity and metabolic disease.
Anticancer properties of lipid and poly(ε-caprolactone) nanocapsules loaded with ferrocenyl-tamoxifen derivatives
Authors: Najlaoui Feten , Pigeon Pascal , Aroui Sonia , Pezet Mylène , Sancey Lucie , Marrakchi Naziha , Rhouma Ali , Jaouen Gérard , De Waard Michel , Busser Benoit , Gibaud Stéphane
Published: August 2018

Objective

We synthesized new tamoxifen derivatives as anticancer drug candidates and elaborated on convection-enhanced delivery (CED) as a strategy for delivery.

Methods

To overcome the issue of their poor solubility, these ferrocenyl-tamoxifen derivatives were esterified and encapsulated into different nanocarriers, that is lipid (LNC) and polymeric nanocapsules (PNL-NC). We describe the chemistry, the encapsulation and the physicochemical characterization of these formulations.

Key findings

Starting compounds [phthalimido-ferrocidiphenol and succinimido-ferrocidiphenol], esterified prodrugs and their nanocapsules formulations were characterized.

These drug candidates displayed a strong in vitro activity against breast and glioblastoma cancer cells. The ester prodrugs were toxic for glioblastoma cells (IC50 = 9.2 × 10−2 μm and 6.7 × 10−2 μm, respectively). The IC50 values for breast cancer cells were higher for these compounds. The encapsulation of the esterified compounds in LNCs (≈50 nm) or PCL-NCs (≈300 nm) did not prevent their efficacy on glioblastoma cells. These anticancer effects were due to both blockade in the S-phase of the cell cycle and apoptosis. Moreover, the tamoxifen derivatives-loaded nanocapsules induced no toxicity for healthy astrocytes and showed no haemolytic properties. Loaded Lipid Nanocapsules (LNCs) presented interesting profiles for the optimal delivery of active compounds.

Conclusions

Phthalimido- and Succinimido-esters represent an innovative approach to treat cancers with cerebral localizations such as glioblastoma or brain metastases from breast cancers.
Understanding facilitators and barriers of direct‐acting antiviral therapy for hepatitis C virus infection in prison
Authors: Lafferty Lise , Rance Jake , Grebely Jason , Lloyd Andrew R. , Dore Gregory J. , Treloar Carla ,   the SToP‐C Study Group
Published: August 2018

Hepatitis C virus (HCV) infection is a major public health concern. Globally, 15% of those incarcerated are HCV‐antibody positive (anti‐HCV). Even where HCV treatment is available within prisons, treatment uptake has remained low. This qualitative study was conducted to understand the barriers and facilitators for the delivery of HCV treatment in prisons from the perspectives of prisoners. This is important to inform health messaging for HCV treatment within correctional institutions. Thirty‐two prisoners (including eight women) with a history of injecting drug use participated in this qualitative study. Participants were equally recruited across four correctional centres (n = 8 per site). Overall, 16 participants (50%) had chronic HCV at their most recent test, and two participants were awaiting test results at time of interview. Structural (eg proximity of health clinic) and patient‐level (routine and motivation) factors were viewed as facilitators of HCV treatment within the prison setting. Structural (eg risk of reinfection) and social (eg lack of confidentiality and lack of social support) factors were perceived as barriers to prison‐based HCV care and treatment. In conclusion, to increase HCV treatment uptake, prison‐based programmes should implement (or advocate for) patient‐centred treatment approaches that protect privacy, provide social support, and promote access to clean needles and substitution therapy to protect prisoners from reinfection.
Findings from a large Asian chronic hepatitis C real‐life study
Authors: Lim Seng Gee , Phyo Wah Wah , Shah Samir R. , Win Khin Maung , Hamid Saeed , Piratvisuth Teerha , Tan Soek Siam , Dan Yock Young , Lee Yin Mei , Ahmed Taufique , Yang Wei Lyn , Chen Kok Pun , Kamat Mrunal , Wadhawan Manav , Madan Kaushal , Mehta Rajiv , Shukla Akash , Dhore Prashant , Eapen Chundamannil E. , Abraham Priya , Tyagi Satyendra , Koshy Abraham , Bwa Aung Hlaing , Jafri Wasim , Abid Shahab , Arisar Fakhar Ali Qazi , Tanwandee Tewesak , Yin Thing Phee , Tee Hoi Poh , Hj Md Said Rosaida Binti , Goh Khean Lee , Ho Shiaw Hooi , Mohamed Rosmawati , Abu Bakar Norasiah
Published: August 2018

There is a paucity of information on chronic hepatitis C (CHC) patients treated with direct antiviral agents (DAAs) in Asia. We invited Asia‐Pacific physicians to collate databases of patients enrolled for CHC treatment, recording baseline clinical, virologic and biochemical characteristics, sustained virologic response at week 12 (SVR12) and virologic failure. SVR12 outcome was based on intention to treat (ITT). Multivariate analysis was used to assess independent risk factors for SVR12 using SPSS version 20. A total of 2171 patients from India (n = 977), Myanmar (n = 552), Pakistan (n = 406), Thailand (n = 139), Singapore (n = 72) and Malaysia (n = 25) were collected. At baseline, mean age was 49 years, 50.2% were males, and 41.8% had cirrhosis. Overall, SVR12 was 89.5% and by genotype (GT) based on ITT and treatment completion, respectively, was 91% and 92% for GT1, 100% and 100% for GT2, 91% and 97% for GT3, 64% and 95% for GT4, 87% and 87% for GT6 and 79% and 91% for GT untested. Patients with cirrhosis had SVR12 of 85% vs 93% for noncirrhosis (P < 0.001) (RR 2.1, 95% CI 1.4‐3.1, P = 0.0002). Patients with GT1 and GT3 treated with sofosbuvir/ribavirin (SR) had 88% and 89% SVR12, respectively, but those GT6 treated with sofosbuvir/ledipasvir (SL) had only 77.6% SVR12. Multivariate analysis showed absence of cirrhosis was associated with higher SVR12 (OR 2.0, 95% CI 1.3‐3.1, P = 0.002).

In conclusion, patients with GT1 and GT3 with/without cirrhosis had surprisingly high efficacy using SR, suggesting that Asians may respond better to some DAAs. However, poor GT6 response to SL suggests this regimen is suboptimal for this genotype.
Similar recovery of liver function after response to all‐oral HCV therapy in patients with cirrhosis with and without HIV coinfection
Authors: Macías Juan , Granados Rafael , Téllez Francisco , Merino Dolores , Pérez Montserrat , Morano Luis E. , Palacios Rosario , Paniagua María , Frías Mario , Merchante Nicolás , Pineda Juan A. ,   On behalf of the HEPAVIR GEHEP, RIS‐HEP07 study groups
Published: August 2018

Among patients with cirrhosis, recovery of liver function after SVR to all‐oral direct‐acting antivirals (DAA) in HIV/HCV coinfection could be different to that in HCV monoinfection. Because of this, we compared the changes in several markers of liver function between HCV‐monoinfected and HIV/HCV‐coinfected patients with cirrhosis who achieved SVR12 to DAA combinations. In this retrospective cohort study, cirrhotics included in the HEPAVIR‐DAA and GEHEP‐MONO cohorts were selected if they had SVR12 to all‐oral DAAs. Patients treated with atazanavir were excluded. Liver function improvement was defined as Child‐Pugh‐Turcotte (CPT) decrease ≥1 and/or MELD decrease ≥2 between baseline and SVR12. Liver function worsening was defined as a CPT increase ≥1 and/or MELD increase ≥2 and/or decompensations between baseline and SVR12. We included 490 patients, 270 (55%) of them with HIV coinfection. Liver function improved in 50 (56%) HCV‐infected individuals and in 82 (57%) HIV/HCV‐coinfected patients (P = 0.835). Liver function worsened in 33 (15%) HCV‐monoinfected patients and in 33 (13%) HIV/HCV‐coinfected patients (P = 0.370). Factors independently related with liver function improvement were male gender [adjusted OR (AOR) 2.1 (95% confidence interval, 95% CI: 1.03‐4.2), P = 0.040], bilirubin < 1.2 mg/dL (AOR 1.8 [95% CI: 1.004‐3.3], P = 0.49), and INR < 1.3 (AOR 2.4 [95% CI: 1.2‐5.0], P = 0.019) at baseline. After multivariate analysis, albumin < 3.5 g/dL was associated with liver function worsening (AOR 6.1 [95% CI: 3‐12.5], P < 0.001). Liver function worsening and improvement rates after responding to DAA are similar among HCV‐monoinfected and HIV/HCV‐coinfected cirrhotics. Gender, INR, bilirubin, and albumin levels were associated with liver function changes after response to DAAs.
High prevalence and diversity of hepatitis B and hepatitis delta virus in Gabon
Authors: Groc Soraya , Abbate Jessica Lee , Le Gal Frédéric , Gerber Athenaïs , Tuaillon Edouard , Albert Jean‐Louis , Nkoghé Dieudonné , Leroy Eric M. , Roche Benjamin , Becquart Pierre
Published: August 2018

Although central Africa is classified as having a high endemicity of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection, there is paucity of prevalence studies. For the first time on a country‐wide level in Central Africa, we show in Gabon an overall 7.4% prevalence of Hepatitis B surface antigen (HBsAg) and that more than 25% of the HBsAg‐positive population are infected by HDV. Although HBV prevalence did not differ significantly between provinces, there is a north‐south split in the distribution of HDV seroprevalence, with the highest rates (>66.0%) correlating with the presence of specific ethnic groups in the northeastern provinces. Genotyping revealed high genetic diversity of the HBV and HDV strains circulating in Gabon, including many restricted to this region of the globe. This work confirmed that high exposure to HBV and HDV infection reported in selected regions of Gabon holds true across the whole country.
Romantic ecocriticism: History and prospects
Authors: Davies Jeremy
Published: August 2018

This essay examines the origins, development, and future of Romantic ecocriticism. British Romanticism has always been central to discussions of literature and the environment. Here, I offer the most extensive assessment to date of relevant scholarship. I concentrate on book‐length studies of British literature circa 1780–1830, generally excluding books about individual authors. I close by outlining a new agenda for the field. Instead of claiming to reveal the origins of contemporary environmental sensibilities, I argue, Romantic ecocritics should work towards a critical history of regimes of environmental exploitation. Part one of the essay analyses the paths taken and not taken in ecocritical studies of the Romantic period between 1970 and 2000. Part two parses the diversity of Romantic ecocriticism in the early twenty‐first century. Part three argues that Romantic ecocriticism's central concern should be the environmental changes associated with the industrial revolution.
Assisted reproductive technologies in captive rhinoceroses
Authors: Pennington Parker M. , Durrant Barbara S.
Published: August 2018

Survival of the five remaining rhinoceros species is threatened. Four of the five species are in managed collections, but captive populations are not self‐sustaining and low reproductive rates make population growth slow.

Slow population growth, coupled with behavioural incompatibilities, acyclicity, low genetic diversity, and disease susceptibility, creates the need for assisted reproductive technologies (ARTs) to maintain genetic diversity while bolstering population numbers.

Both published and unpublished data are included in this review of ARTs, to facilitate understanding consistencies and variations between and within each rhinoceros species.

Progress has been made to address species‐specific characteristics of reproductive physiology in rhinoceroses. This review outlines the ARTs that have been performed and identifies areas in need of research. In vivo technologies have resulted in live calves by artificial insemination, created genetic reservoirs through semen collection, and provided new avenues of gamete retrieval via ovum pickup. In vitro technologies have enabled genetic rescue post mortem and support early stage embryo production through oocyte maturation and fertilisation.

As conservation efforts focus on rhinoceroses, improvement of existing techniques and development of new technologies will allow for a broader application of successful rhinoceros ARTs.
Mitonuclear genomics challenges the theory of clonality in Trypanosoma congolense: Reply to Tibayrenc and Ayala
Authors: Van den Broeck Frederik , Tavernier Lisse J.M. , Vermeiren Lieve , Dujardin Jean‐Claude , Van Den Abbeele Jan
Published: August 2018

We recently published the first genomic diversity study of Trypanosoma congolense, a major aetiological agent of Animal African Trypanosomiasis. We demonstrated striking levels of SNP and indel diversity in the Eastern province of Zambia as a consequence of hybridization between divergent trypanosome lineages. We concluded that these and earlier findings in T. congolense challenge the predominant clonal evolution (PCE) model. In a recent comment, Tibayrenc and Ayala claim that there are many features in T. congolense supporting their theory of clonality. While we can follow the reasoning of the authors, we also identify major limitations in their theory and interpretations that resulted in incorrect conclusions. First, we argue that each T. congolense subgroup should be analysed independently as they may represent different (sub)species rather than “near‐clades”. Second, the authors neglect major findings of two robust population genetic studies on Savannah T. congolense that provide clear evidence of frequent recombination. Third, we reveal additional events of introgressive hybridization in T. congolense by analysing the maxicircle coding region using next‐generation sequencing analyses. At last, we pinpoint two important misinterpretations by the authors and show that there are no spatially and temporally widespread clones in T. congolense. We stand by our earlier conclusions that the clonal framework is unlikely to accurately model the population structure of T. congolense. Other theoretical frameworks such as Maynard Smith's epidemic model may better represent the complex ancestry seen in T. congolense, where clones delimited in space and time arise against a background of recombination.
Cost share‐induced technological change and Kaldor’s stylized facts
Authors: Kemp‐Benedict Eric
Published: August 2018

This paper presents a theory of induced technological change in which firms pursue a random, local, and bounded search for productivity‐enhancing innovations. Firms implement profitable innovations at fixed prices, which then spread through the economy. After diffusion, all firms adjust prices and wages. The model is consistent with a variety of price‐setting behaviors, which determine equilibrium positions characterized by constant cost shares and productivity growth rates. A fixed mark‐up can yield Marx‐biased technological change. Target‐return pricing yields Harrod‐neutral technological change with a fixed wage share as a stable equilibrium, consistent with Kaldor's stylized facts, while allowing for deviations from equilibrium, as observed in the longer historical record.
Experiences of using very low energy diets for weight loss by people with overweight or obesity: a review of qualitative research
Authors: Harper C. , Maher J. , Grunseit A. , Seimon R. V. , Sainsbury A.
Published: August 2018

Although very low energy diets (VLEDs) are the most successful non‐surgical, non‐pharmacological treatment for obesity, they are underutilized, and little is known about experiences of people using VLEDs for weight loss. This systematic review synthesizes qualitative studies investigating participants' experiences of undertaking a VLED composed of total meal replacement products to lose weight. Of the 4,911 articles screened, three studies met criteria for inclusion. Thematic synthesis was used to analyse the study findings. Health and appearance were the main motivators to use a VLED for weight loss. Adherence was facilitated by group support meetings, rapid weight loss and ease of use of the diet. Being part of a clinical trial gave a sense of accountability and further reason to adhere to a VLED, and the VLED itself was well accepted by users. Barriers to adherence, such as temptations and social occasions, were overcome by avoidance and distraction strategies. In conclusion, this qualitative synthesis of users' experiences of VLEDs shows that VLEDs are well accepted and positively viewed by users. More in‐depth research could facilitate understanding of how this weight loss strategy influences the weight maintenance period, in order to facilitate better long‐term results.
Role of gut microbiota in chronic low‐grade inflammation as potential driver for atherosclerotic cardiovascular disease: a systematic review of human studies
Authors: van den Munckhof I. C. L. , Kurilshikov A. , ter Horst R. , Riksen N. P. , Joosten L. A. B. , Zhernakova A. , Fu J. , Keating S. T. , Netea M. G. , de Graaf J. , Rutten J. H. W.
Published: August 2018

A hallmark of obesity is chronic low‐grade inflammation, which plays a major role in the process of atherosclerotic cardiovascular disease (ACVD). Gut microbiota is one of the factors influencing systemic immune responses, and profound changes have been found in its composition and metabolic function in individuals with obesity. This systematic review assesses the association between the gut microbiota and markers of low‐grade inflammation in humans. We identified 14 studies which were mostly observational and relatively small (n = 10 to 471). The way in which the microbiome is analysed differed extensively between these studies. Lower gut microbial diversity was associated with higher white blood cell counts and high sensitivity C‐reactive protein (hsCRP) levels. The abundance of Bifidobacterium, Faecalibacterium, Ruminococcus and Prevotella were inversely related to different markers of low‐grade inflammation such as hsCRP and interleukin (IL)‐6. In addition, this review speculates on possible mechanisms through which the gut microbiota can affect low‐grade inflammation and thereby ACVD. We discuss the associations between the microbiome and the inflammasome, the innate immune system, bile acids, gut permeability, the endocannabinoid system and TMAO. These data reinforce the importance of human research into the gut microbiota as potential diagnostic and therapeutic strategy to prevent ACVD.
The oral microbiome in oral lichen planus during a 1‐year randomized clinical trial
Authors: Kragelund Camilla , Keller Mette Kirstine
Published: August 2018

Background

Several recent studies have investigated the oral bacteriome in oral lichen planus (OLP), but longitudinal changes in microbiome have not been investigated.

Objective

To study the bacteriome and mycobiome in OLP over a 1‐year period and the impact of topical treatment.

Material and methods

Samples from 22 symptomatic OLP patients from a double‐blinded, randomized intervention study were collected over a 1‐year course at five visits. Bacterial and fungal abundances were investigated through lesional cytobrush (CB) and full mouthwash (MW). Initially, all patients received conventional (antimycotic or steroid) and probiotic or placebo treatment.

Results

The microbial composition differed between the MW and CB samples. During the study period, the microbial composition was individual, with pronounced variability between visits. Patients grouped according to initial conventional treatment. During the study period, unidirectional change in the bacteriome was seen in the antimycotic group, whereas the mycobiome was stable. Malassezia restricta was the most abundant fungus.

Conclusions

The microbial composition of MW and CB differs in OLP. CB composition is less influenced by conventional and probiotic intervention. Initial antimycotic treatment influenced the bacteriome during the 1‐year period. How the oral microbiome in health and disease is influenced by individual variability of fungi and bacteria, and Malassezia needs further investigation.
Ultrastructural analysis of collagen fibril diameter distribution in cleft lip
Authors: Khan Mohammad Faisal J. , Little Julian , Nag Tapas Chandra , Mossey Peter Anthony , Autelitano Luca , Meazzini Maria Costanza , Merajuddin Ahmed , Singh Anuraag , Rubini Michele
Published: August 2018

Objective

A preliminary study to determine collagen fibril diameter (CF‐ED) distribution on medial and lateral sides of cleft lip (CL).

Material and Methods

Tissue samples from medial and lateral sides of CL were fixed in 2.5% glutaraldehyde and 1% osmium tetroxide and embedded in Araldite CY212 resin for transmission electron microscopy. The analysis of CF‐ED was performed using the ImageJ program. To characterize the packaging of collagen fibrils (CFs) in the two tissues, we estimated the collagen number density (CF‐ND) and fibril‐area‐fraction (FAF). Differences in measurements across the two sides were calculated using Wilcoxon signed‐rank test.

Results

The CF‐ED was statistically significantly (p < 0.001) smaller on the medial side (45.69 ± 7.89 nm) than on the lateral side (54.18 ± 7.62 nm). The medial side had a higher CF‐ND and a higher percentage of FAF than the lateral side.

Conclusion

Our finding of a smaller CF‐ED and higher CF‐ND and FAF for the medial side suggests possible differences in size and distribution of CFs between medial and lateral sides of CL. This finding provides knowledge toward underlying tissue biomechanics that may help reconstruction of perioral tissue scaffolds, ultimately resulting in better treatment of patients with oral clefts.
Relationship between body mass index and outcomes for patients with oral squamous cell carcinoma
Authors: Wang Chong , Pan Yuesong , Xu Qiaoshi , Li Bo , Kim Kyojin , Mao Minghui , Li Jinzhong , Qin Lizheng , Li Hua , Han Zhengxue , Feng Zhien
Published: August 2018

Objective

The purpose of our study was to investigate body mass index (BMI) as a prognostic factor and to examine the relationship between pretreatment BMI and oral squamous cell carcinoma (OSCC) outcomes in northern Chinese patients.

Methods

This retrospective study enrolled 633 patients with OSCC who underwent surgery between 2004 and 2014.

Results

Most baseline characteristics (gender, sites, smoking history, comorbidity, hypertension, T stage, clinical features, perineural invasion, flap reconstruction) were differentiated by BMI groups. Overall, the Kaplan–Meier curves indicated no significant relationship between BMI and disease‐free survival (DFS) or disease‐specific survival (DSS). Interestingly, obese patients exhibited higher risks of recurrence and death than normal‐weight patients (DFS: HR: 1.86, 95% CI: 1.16–2.96; DSS: HR: 2.04, 95% CI: 1.08–3.86). However, postoperative complications occurred more frequently in underweight patients than in normal‐weight patients.

Conclusions

Obesity may contribute to a higher recurrence rate and a worse prognosis in OSCC patients than in normal‐weight patients in northern China. However, underweight patients have a higher risk of postoperative complications.
Demographic and genetic collapses in spatially structured populations: insights from a long‐term survey in wild fish metapopulations
Authors: Mathieu‐Bégné Eglantine , Loot Géraldine , Chevalier Mathieu , Paz‐Vinas Ivan , Blanchet Simon
Published: August 2018

Unraveling the relationship between demographic declines and genetic changes over time is of critical importance to predict the persistence of at‐risk populations and to propose efficient conservation plans. This is particularly relevant in spatially structured populations (i.e. metapopulations) in which the spatial arrangement of local populations can modulate both demographic and genetic changes. We used ten‐year demo‐genetic monitoring to test 1) whether demographic declines were associated with genetic diversity declines and 2) whether the spatial structure of a metapopulation can weaken or reinforce these demographic and genetic temporal trends. We continuously surveyed, over time and across their entire range, two metapopulations of an endemic freshwater fish species Leuciscus burdigalensis: one metapopulation that had experienced a recent demographic decline and a second metapopulation that was stable over time. In the declining metapopulation, the number of alleles rapidly decreased, the inbreeding coefficient increased, and a genetic bottleneck emerged over time. In contrast, genetic indices were constant over time in the stable metapopulation. We further show that, in the declining metapopulation, demographic and genetic declines were not homogeneously distributed across the metapopulation. We notably identify one local population situated downstream as a ‘reservoir’ of individuals and genetic variability that dampens both the demographic and genetic declines measured at the metapopulation level. We demonstrate the usefulness of long‐term monitoring that combines both genetic and demographic parameters to understand and predict temporal population fluctuations of at‐risk species living in a metapopulation context.
Using root traits to understand temporal changes in biodiversity effects in grassland mixtures
Authors: Bakker Lisette M. , Mommer Liesje , van Ruijven Jasper
Published: August 2018

Biodiversity–ecosystem functioning (BEF) studies typically show that species richness enhances community biomass, but the underlying mechanisms remain debated. Here, we combine metrics from BEF research that distinguish the contribution of dominant species (selection effects, SE) from those due to positive interactions such as resource partitioning (complementarity effects, CE) with a functional trait approach in an attempt to reveal the functional characteristics of species that drive community biomass in species mixtures. In a biodiversity experiment with 16 plant species in monocultures, 4‐species and 16‐species mixtures, we used aboveground biomass to determine the relative contributions of CE and SE to biomass production in mixtures in the second, dry year of the experiment. We also measured root traits (specific root length, root length density, root tissue density and the deep root fraction) of each species in monocultures and linked the calculated community weighted mean (CWM) trait values and trait diversity of mixtures to CE and SE. In the second year of the experiment, community biomass, CE and SE increased compared to the first year. The contribution of SE to this positive effect was greater than that of CE. The increased contribution of SE was associated with root traits: SE increased most in communities with high abundance of species with deep, thick and dense roots. In contrast, changes in CE were not related to trait diversity or CWM trait values. Together, these results suggest that increased positive effects of species richness on community biomass in a dry year were mainly driven by increased dominance of deep‐rooting species, supporting the insurance hypothesis of biodiversity. Positive CE indicates that other positive interactions did occur, but we could not find evidence that belowground resource partitioning or facilitation via root trait diversity was important for community productivity in our biodiversity experiment.
Predictive values of alpha‐gal IgE levels and alpha‐gal IgE: Total IgE ratio and oral food challenge‐proven meat allergy in a population with a high prevalence of reported red meat allergy
Authors: Mabelane Tshegofatso , Basera Wisdom , Botha Maresa , Thomas Heidi Facey , Ramjith Jordache , Levin Michael E.
Published: August 2018

Background

Severe meat allergy with anaphylaxis may be caused by sensitization to alpha‐gal. Levels of alpha‐gal sensitization that correlate with high risk of meat allergy are currently unknown. We have identified an area with a high prevalence of reported red meat allergy which offered the opportunity to evaluate the diagnostic value of IgE antibody tests.

Methods

To determine levels of alpha‐gal IgE and alpha‐gal:total IgE ratio in a large cohort of subjects with challenge‐proven meat allergy compared with control subjects from the same environment, we conducted fieldwork assessing 131 participants who reported adverse reactions to meat, and 26 control subjects, by questionnaires, IgE sensitization to alpha‐gal and oral food challenge to beef sausage.

Results

Eighty‐four participants were diagnosed with alpha‐gal allergy. Alpha‐gal IgE ranged between 0.7 and 344.5 kU/L. Alpha‐gal:total IgE ratio ranged from 0.1% to 67.6%. Logistic regression analysis showed both alpha‐gal IgE and alpha‐gal:total IgE ratio strongly correlated with meat allergy, with AUC of 0.95. The values giving the best correct classification were IgE of 2.00 kU/L and ratio of 0.75%. The value above which there is a 95% probability of meat allergy is IgE>5.5 kU/L and ratio of 2.12%.

Conclusion

Alpha‐gal allergy in a population with a high prevalence of reported red meat allergy showed a more rapid onset of symptoms than previously described and a high prevalence of isolated subjective gastrointestinal manifestations. Cutoff values are described for levels of sensitization to alpha‐gal IgE and alpha‐gal:total IgE ratio that are highly likely to result in clinically significant meat allergy.
Devoutness to Islam and the Attitudinal Acceptance of Political Violence Among Young Muslims in Germany
Authors: Hadjar Andreas , Schiefer David , Boehnke Klaus , Frindte Wolfgang , Geschke Daniel
Published: August 2018

This article investigates the links between religious beliefs and capitalist mentalities—namely devoutness to Islam and hierarchic self‐interest (HSI)—and violence‐accepting attitudes among the young Muslim migrant population in Germany. Following a situational perspective, these links are analyzed under different individual conditions structured by (socioeconomic) precariousness and education. Based on framing approaches and concepts from socialization theory, we derive the following hypothesis: The links between religious beliefs and capitalist mentalities and the attitudinal acceptance of violence are stronger among individuals with low levels of education and a precarious economic status (compared to high education/nonprecarious status). The strongest link is expected for a negative status inconsistency (high education/precarious economic status). Structural equation models for data from a random probability sample of 350 Muslims (aged 14–32 years) in Germany indicate that attitudinal acceptance of violence among young Muslims is not predicted by devoutness to Islam but by economic precariousness and by acceptance of capitalist values of the HSI belief system.
Coloring biology in grape skin: a prospective strategy for molecular farming
Authors: Fang Jinggui , Jogaiah Sudisha , Guan Le , Sun Xin , Abdelrahman Mostafa
Published: August 2018

Grapevine is one of the earliest domesticated fruit crops that has been widely prized and cultivated for its fruit and wine. Grapes exhibit a wide range of colors, ranging from the green/yellow to the dark blue tones according to the amount and composition of anthocyanin. During the last decades, many studies regarding the genetic control of the grape color in European, American and Asian cultivars have been well documented. DNA binding genes for several transcription factors, such as MYBA1 and MYBA2 haplotype compositions at the color locus are the key determinant of anthocyanin diversity and grape skin color development. Retrotransposon in the MYBA1 promoter region and mutation in MYBA2 coding sequence resulted in a white‐skinned grape. The MYB haplotypes affect the ratio of tri/di‐hydroxylated anthocyanins and methylated/non‐methylated anthocyanins through the regulation of several structural genes involved in the anthocyanin biosynthesis, resulting in diverse colored tones. The present review provides an overview of the current state of the molecular mechanisms underlying the genetic regulations of the anthocyanin accumulation and diversification in grapes. The hypothesized models described in this review is a step forward to potentially predict the color diversification in different grape cultivars, which translate the advances in fundamental plant biology toward the application of grape molecular breeding.
The certification effect of R&D subsidies from the central and local governments: evidence from China
Authors: Wei Jiang , Zuo Yan
Published: August 2018

This paper explores whether the certification effect of R&D subsidies exists in China, a typical transition economy, and how subsidies from different sources present distinct signals to external investors. Using the sample of Chinese listed companies and a multivariate regression model, our results suggest that R&D subsidies from the central government send a negative signal about the quality of R&D projects and worsen the access of subsidized firms to external capital. In contrast, subsidies from local governments serve as a positive signal and the access is eased. We contribute to the studies of the certification effect by taking the distinct incentives of different government agencies in China into account and by investigating the relevance of such incentives to the diverse types of signal. The implications of our findings and related directions for future research are further discussed.
Effects of transgenic American chestnut leaf litter on growth and survival of wood frog larvae
Authors: Goldspiel Harrison B. , Newhouse Andrew E. , Powell William A. , Gibbs James P.
Published: August 2018

Biotechnology offers a new approach for the restoration of tree species affected by exotic pathogens; however, nontarget impacts of this novel strategy on other organisms have not been comprehensively assessed. We evaluated the effect of transgenic American chestnut (Castanea dentata) leaf litter on the growth and survival of larval wood frogs (Lithobates sylvaticus), a forest‐dwelling amphibian species widely sympatric with American chestnut, that forage almost entirely on periphyton and litter detritus that accumulate in temporary vernal pools in forests. We reared wood frog larvae onCastanealeaf litter (American chestnut genetically engineered for blight tolerance, nontransgenic American chestnut, Chinese chestnut [Castanea mollissima], and an American–Chinese chestnut hybrid) and litter from two non‐Castanea, nontransgenic “control” tree species, coupled with two levels of supplementary food. We observed no differences in growth or survival of wood frog larvae reared on transgenic versus nontransgenic American chestnut leaves. Without supplementary food, wood frog larvae provided leaves from American chestnut (both types) developed faster and grew larger than those exposed to other leaf litter treatments. Results of this study provide preliminary evidence that (1) American chestnut may have formerly been an important source of food for forest‐dwelling amphibians and (2) transgenic American chestnut litter generated as part of chestnut restoration efforts is unlikely to present direct novel risks to developing amphibian larvae in the forest environment.
Spatial Transmission Models: A Taxonomy and Framework
Authors: Robertson Duncan A.
Published: August 2018

Within risk analysis and, more broadly, the decision behind the choice of which modeling technique to use to study the spread of disease, epidemics, fires, technology, rumors, or, more generally, spatial dynamics, is not well documented. While individual models are well defined and the modeling techniques are well understood by practitioners, there is little deliberate choice made as to thetypeof model to be used, with modelers using techniques that are well accepted in the field, sometimes with little thought as to whether alternative modeling techniques could or should be used. In this article, we divide modeling techniques for spatial transmission into four main categories: population‐level models, where a macro‐level estimate of the infected population is required; cellular models, where the transmission takes place between connected domains, but is restricted to a fixed topology of neighboring cells; network models, where host‐to‐host transmission routes are modeled, either as planar spatial graphs or where shortcuts can take place as in social networks; and, finally, agent‐based models that model the local transmission between agents, either as host‐to‐host geographical contacts, or by modeling the movement of the disease vector, with dynamic movement of hosts and vectors possible, on a Euclidian space or a more complex space deformed by the existence of information about the topology of the landscape. We summarize these techniques by introducing a taxonomy classifying these modeling approaches. Finally, we present a framework for choosing the most appropriate spatial modeling method, highlighting the links between seemingly disparate methodologies, bearing in mind that the choice of technique rests with the subject expert.
Changes in practice and perception of hepatitis C and liver transplantation: Results of a national survey
Authors: Shaffer Ashton A. , Thomas Alvin G. , Bowring Mary Grace , Van Pilsum Rasmussen Sarah E. , Cash Ayla , Kucirka Lauren M. , Alqahtani Saleh A. , Gurakar Ahmet , Sulkowski Mark S. , Cameron Andrew M. , Segev Dorry L. , Durand Christine M.
Published: August 2018

With new practice guidelines, it is important to understand how liver transplant (LT) centers have incorporated direct‐acting antivirals (DAAs) into the management of hepatitis C virus‐infected (HCV+) candidates and recipients. To explore how DAAs have affected LT centers’ willingness to treat HCV+ candidates and recipients and to use HCV+ donors, we surveyed high volume US LT centers (11/2014‐12/2015) regarding practices for HCV+ candidates, recipients, and donors, before vs after DAAs. We used the Scientific Registry of Transplant Recipients to compare centers’ number of LTs, HCV+ recipients, and HCV+ donors in the years before (1/1/2012‐12/31/2013) and after (1/1/2016‐12/31/2017) survey administration. Of 80 centers contacted, 57 (71.3%) responded, representing 69.0% of the total volume of LTs in 2013. After DAAs, most centers increased treating candidates with low (≤15) model for end‐stage liver disease (MELD) (85.2%), intermediate/high (>15) MELD (92.6%), and hepatocellular carcinoma (79.6%). There was consensus to treat low MELD candidates (90.8% “most of the time/always”), but less certainty for intermediate/high MELD candidates (48.2% “sometimes”). Universal post‐LT HCV treatment increased (7.4% vs 57.4%). After DAAs, 42.6% were more willing to use HCV+ donors for HCV+ candidates, and 38.9% were willing to consider using HCV+ donors for HCV− candidates. Overall, with DAAs, centers were more willing to treat HCV+ candidates and recipients and to use HCV+ donors; recent recommendations may help to guide treatment decisions for intermediate/high MELD candidates.
Socio‐epidemiological characterisation of blood donors with asymptomatic Leishmania infantum infection from three Brazilian endemic regions and analysis of the transfusional transmission risk of visceral leishmaniasis
Authors: Ferreira‐Silva M. M. , Teixeira L. A. S. , Tibúrcio M. S. , Pereira G. A. , Rodrigues V. , Palis M. , Afonso P. , Alves M. , Feitosa J. M. , Urias E. , Santos E. M. , Carvalho S. F. G. , Moraes‐Souza H.
Published: August 2018

Objectives

This study assessed the prevalence of visceral leishmaniasis in blood donors from three endemic regions in Brazil and evaluated the risk of transmission by transfusion.

Background

Despite strong evidence of the transmission of visceral leishmaniasis through blood transfusion, the real risk, an essential condition for taking effective measures to control this serious disease, has not been determined.

Methods

A multicentre study was performed in highly endemic areas. Candidates eligible for their first blood donation underwent a socio‐epidemiological interview, and blood samples were collected for enzyme‐linked immunosorbent assay (ELISA) analysis, Western blot and polymerase chain reaction (PCR). Patients transfused with red blood cells or random platelet concentrates collected from these donors were also studied. The results were analysed using descriptive statistics and prevalence estimates, with significance defined as p‐values <0·05.

Results

Of the 608 eligible donors, 37 (6·1%) were positive for visceral leishmaniasis as per ELISA. The socio‐epidemiological analysis showed a significantly higher prevalence in non‐Caucasians (p = 0·008). Among 296 patients who received blood components from these donors, the pre‐transfusion seropositivity was 7·7%, and 13 patients received blood positive for Leishmania infantum. Six patients were followed up for 90 days, of which two (33·3%) had serological conversion at 60 days.

Conclusions

The results confirm the high prevalence of L. infantum seropositivity among donors in the three regions; the seroconversion in a short period of time in two of six patients suggests the possibility of transmission of the infection by transfusion.
Evaluation of immunological parameters in pit bull terrier‐type dogs with juvenile onset generalized demodicosis and age‐matched healthy pit bull terrier‐type dogs
Authors: Souza Clarissa P. , Schissler Jennifer R. , Contreras Elena T. , Dow Steven W. , Hopkins Leone S. , Coy Jonathan W. , Rosychuk Rod A.W. , Hawley Jennifer R. , Lappin Michael R.
Published: August 2018

Background

Juvenile onset generalized demodicosis (JOGD) is thought to occur due to immunological abnormalities and is over‐represented in pit bull terrier‐type dogs.

Animals

Twelve pit bull terrier‐type dogs with JOGD and 12 age‐matched healthy pit bull terrier‐type dogs.

Objective

To investigate immunological differences between age‐matched healthy and JOGD pit bull terrier‐type dogs by flow cytometry, multiplex, molecular and serological assays.

Methods and materials

Flow cytometry quantified B cells expressing MHCII or surface‐bound IgG, CD4+ T cells expressing MHCII, CD8 T cells expressing MHCII or CD11a, neutrophil and monocyte markers. Surface expression was quantified by calculating the geometric mean fluorescence index. The Wilcoxon rank sum test was used to compare median results for IL‐2, IL‐4, IL‐6, IL‐7, IL‐8, IL‐10, IL‐13, IL‐18, FOXP3, monocyte chemoattractant protein‐1, GM‐CSF, KC, IgE, IgA, IgG, IgM, C‐reactive protein, lymphocyte, neutrophil and monocyte in the groups. IFN‐gamma, IP‐10, IL‐15, IL‐31 and TNF‐alpha also were measured; however, insufficient dogs (<5) had values that were in range of the assay to allow for statistical evaluation. Significance was defined as P < 0.05.

Results

Serum concentrations of IL‐2, IL‐18 and MCP‐1 were significantly higher (P = 0.01, P = 0.01, P = 0.04) in the JOGD group. Also, IgA median value was significantly higher (P = 0.002) in pit bull terrier‐type dogs with JOGD. Flow cytometry revealed that T‐cell, neutrophil and monocyte markers were not different between groups.

Conclusions

Results suggest an appropriate compensatory immune response by pit bull terrier‐type dogs in the JOGD group and do not support the explanation of global immune deficiency in these dogs.