bluuebunny/crossref_metadata_2025 huggingface dataset:
Grape moth density in Bordeaux vineyards depends on local habitat management despite effects of landscape heterogeneity on their biological control
Authors: Rusch Adrien , Delbac Lionel , Thiéry Denis
Published: December 2016

Biological control of crop pests is a major ecosystem service affected by several variables acting at multiple spatial scales. Among these variables, heterogeneity at the habitat and landscape scales are known key drivers of trophic interactions and pest density in agroecosystems. However, studies that try to disentangle their relative effects in perennial cropping systems are scarce and nothing is known about their impacts on insect pest density and pesticide applications.

We examined the effect of heterogeneity at these two scales on grape moths, one of the most damaging insect pests in European vineyards, and their biological control in 20 vineyards during three consecutive years. We used local vegetation management and the proportion of semi‐natural habitats in the surrounding landscape as proxies of heterogeneity at the habitat and landscape scales. Grape moth density was measured over time, as well as biological control services provided by different groups: birds, invertebrate predators, parasitoids and entomopathogenic fungi.

Over the 3 years, grape moth density was mainly determined by local heterogeneity, with significantly fewer larvae of the first generation established in vineyards with full compared to partial grass cover.

Despite these effects, biological control of grape moths was not primarily affected by local vegetation management but by landscape heterogeneity, and the direction of this effect varied over time. Notably, predation by birds increased with landscape heterogeneity in spring, depending on local vegetation management, while attacks by pathogenic fungi decreased with landscape heterogeneity during winter.

Synthesis and applications. Our results suggest that bottom‐up processes related to habitat heterogeneity drive grape moth occurrence much more than top‐down processes. These results have important implications for the ecological intensification of vineyard landscapes. We found that maintaining full grass cover within vineyards reduced grape moth density to a level below common intervention thresholds. Landscape heterogeneity in the close vicinity of vineyards contributed to improved biological pest control by birds, but depended on local vegetation management. Moreover, opposing effects of landscape management on biological pest control services over time revealed that strategies based only on manipulating landscape heterogeneity might not be the optimal option to limit grape moth density in vineyards.
Impact of cane toads on a community of Australian native frogs, determined by 10 years of automated identification and logging of calling behaviour
Authors: Taylor Andrew , McCallum Hamish I. , Watson Graeme , Grigg Gordon C.
Published: December 2016

Invasive species may have devastating impacts on native biota. Cane toads Rhinella marina continue to invade northern Australia and the consequences for the endemic frogs are unclear. Monitoring frogs in such remote areas is difficult because their activity depends heavily on unpredictable rainfall events.

We developed an autonomous acoustic monitoring system which used machine learning techniques to identify up to 22 calling species in real time. Ten of these systems, capable of operating for at least a year without attention, were deployed over a 10‐year period along the Roper River valley in the Northern Territory, logging more than 4 million records pre‐ and post‐toad invasion.

Within 5 years of their arrival, cane toads became one of the most prominent members of the anuran community. We detected an overall impact, with six frog species declining in calling activity and one apparently increasing. However, almost all species detected initially were detected at the end of the monitoring period, and again on a follow‐up survey after a further 10 years.

Synthesis and applications. The overall impact of cane toads on endemic frogs has been largely one of rarefaction rather than elimination. Rather than having a devastating impact on the endemic frogs, cane toads have become a component of the amphibian community. Autonomous recording and identification systems such as ours have great potential for long term monitoring of vocalising species in remote and variable environments.
Intraspecific variability in growth response to environmental fluctuations modulates the stabilizing effect of species diversity on forest growth
Authors: Aussenac Raphaël , Bergeron Yves , Ghotsa Mekontchou Claudele , Gravel Dominique , Pilch Kamil , Drobyshev Igor
Published: December 2016

Differences between species in their response to environmental fluctuations cause asynchronized growth series, suggesting that species diversity may help communities buffer the effects of environmental fluctuations. However, within‐species variability of responses may impact the stabilizing effect of growth asynchrony.

We used tree ring data to investigate the diversity–stability relationship and its underlying mechanisms within the temperate and boreal mixed woods of Eastern Canada. We worked at the individual tree level to take into account the intraspecific variability of responses to environmental fluctuations.

We found that species diversity stabilized growth in forest ecosystems. The asynchrony of species’ response to climatic fluctuations and to insect outbreaks explained this effect. We also found that the intraspecific variability of responses to environmental fluctuations was high, making the stabilizing effect of diversity highly variable.

Synthesis. Our results are consistent with previous studies suggesting that the asynchrony of species’ response to environmental fluctuations drives the stabilizing effect of diversity. The intraspecific variability of these responses modulates the stabilizing effect of species diversity. Interactions between individuals, variation in tree size and spatial heterogeneity of environmental conditions could play a critical role in the stabilizing effect of diversity.
Ion channels, long QT syndrome and arrhythmogenesis in ageing
Authors: Jeevaratnam Kamalan , Chadda Karan R , Salvage Samantha C , Valli Haseeb , Ahmad Shiraz , Grace Andrew A , Huang Christopher L‐H
Published: December 2016

Ageing is associated with increased prevalences of both atrial and ventricular arrhythmias, reflecting disruption of the normal sequence of ion channel activation and inactivation generating the propagated cardiac action potential. Experimental models with specific ion channel genetic modifications have helped clarify the interacting functional roles of ion channels and how their dysregulation contributes to arrhythmogenic processes at the cellular and systems level. They have also investigated interactions between these ion channel abnormalities and age‐related processes in producing arrhythmic tendency. Previous reviews have explored the relationships between age and loss‐of‐function Nav1.5 mutations in producing arrhythmogenicity. The present review now explores complementary relationships arising from gain‐of‐function Nav1.5 mutations associated with long QT3 (LQTS3). LQTS3 patients show increased risks of life‐threatening ventricular arrhythmias, particularly after 40 years of age, consistent with such interactions between the ion channel abnormailities and ageing. In turn clinical evidence suggests that ageing is accompanied by structural, particularly fibrotic, as well as electrophysiological change. These abnormalities may result from biochemical changes producing low‐grade inflammation resulting from increased production of reactive oxygen species and superoxide. Experimental studies offer further insights into the underlying mechanisms underlying these phenotypes. Thus, studies in genetically modified murine models for LQTS implicated action potential recovery processes in arrhythmogenesis resulting from functional ion channel abnormalities. In addition, ageing wild type (WT) murine models demonstrated both ion channel alterations and fibrotic changes with ageing. Murine models then suggested evidence for interactions between ageing and ion channel mutations and provided insights into potential arrhythmic mechanisms inviting future exploration.
Obesity, bodily change and health identities: a qualitative study of Canadian women
Authors: Bombak Andrea E. , Monaghan Lee F.
Published: December 2016

Medicalised concerns about an obesity crisis persist yet more needs to be learnt about everyday orientations to weight (loss). This article reports and analyses data generated using qualitative methods, including repeated interviews and fieldwork conducted over one year in Canada with women (n = 13) identifying as (formerly) obese. Three ideal types are explored using empirical data: (1) hopeful narratives; (2) disordered eating distress; and (3) weight‐cycling or stagnation. Core themes include women's desire to embody a thin(ner) future and the good life, the harms of intentional weight‐loss, and resignation to living as a fat woman whilst nonetheless challenging stigma. The article contributes to critical studies of weight/fatness, the sociology of bodily change and the embodiment of health identities. In concluding, we call for reflexive change in bodies of health knowledge, policy and practice.
Local anaesthesia during endometrial ablation: a systematic review
Authors: Reinders IMA , Geomini PMAJ , Timmermans A , de Lange ME , Bongers MY
Published: December 2016

Background

Endometrial ablation has been widely implemented in the outpatient setting. Many different protocols of local anaesthesia during endometrial ablation are used and described. However, prospective studies to assess and evaluate these protocols appear to be scarce.

Objectives

To evaluate systematically the different local anaesthesia techniques in relation to pain perception during endometrial ablation.

Search strategy

Medline and Embase were systematically searched and reference lists of selected articles were checked for missed publications.

Selection criteria

All types of studies reporting the performance of endometrial ablation under local anaesthesia in ten or more women were included.

Data collection and analysis

Data about the procedure, the protocol of local anaesthesia, the acceptability and side‐effects were extracted.

Main results

Twenty‐five studies, involving 2013 women, were included. Applied anaesthesia techniques included intracervical, paracervical and intrauterine anaesthesia or a combination of these techniques. Women who received a combination of either intra‐ or paracervical anaesthesia and intrauterine injections reported significantly lower pain scores than those who received no local anaesthesia or intra‐ or paracervical anaesthesia alone (P = 0.000), but the quality of evidence is low. The acceptability of endometrial ablation under local anaesthesia was high (77–94%).

Conclusion

Endometrial ablation under local anaesthesia is a safe, feasible and acceptable procedure. The combination of either intra‐ or paracervical anaesthesia with intrauterine injections seems to be promising, but has to be investigated more thoroughly.

Tweetable abstract

Systematic review of local anaesthesia techniques during endometrial ablation.
Noninvasive experimental bladder pain assessment in painful bladder syndrome
Authors: Tu FF , Kane JN , Hellman KM
Published: December 2016

Objective

To compare bladder sensitivity between patients with pelvic pain and patients who were pain free, undergoing noninvasive, controlled bladder distension via diuresis. We also sought to measure potential mechanisms underlying bladder sensitivity.

Design

Prospective observational study.

Setting

Community teaching hospital.

Population

Reproductive‐age women with non‐bladder chronic pelvic pain (CPP, n = 23), painful bladder syndrome (PBS, n = 23), and pelvic pain‐free controls (n = 42)

Methods

Participants were compared on cystometric capacity, pelvic floor pressure‐pain thresholds (PPTs), pelvic muscle function, O'Leary‐Sant bladder questionnaire, and psychosocial instruments using Wilcoxon rank‐sum tests. Multivariate regression was used to identify factors underlying bladder pain phenotypes.

Main outcome measures

Pelvic floor pain thresholds; self‐reported bladder distension pain.

Results

Participants with PBS exhibited higher bladder distension pain than those with CPP, with both groups reporting higher pain levels than controls (P < 0.05). No significant associations were found between bladder distension pain and pelvic muscle structure or pain sensitivity measures; however, bladder distension pain positively correlates with both vaginal PPTs adjacent to the bladder (r = 0.46) and pain with transvaginal bladder palpation (r = 0.56). Pain at maximal distension was less influenced by somatic sensitivity than bladder symptoms (r = 0.35 versus r = 0.59; P < 0.05). Multivariate regression identified three independent components of bladder symptoms in PBS: bladder distension pain, bladder sensation, and somatic symptoms.

Conclusions

Diuresis‐induced bladder pain differentiates CPP from PBS. Experimental bladder pain is not predicted by pelvic floor sensitivity. Compared with patient‐reported outcomes it appears less influenced by psychological factors. Further study is needed to determine whether screening for experimental bladder pain sensitivity could predict future risk of PBS.

Tweetable abstract

Controlled, water ingestion‐provoked bladder pain can objectively identify visceral pain sensitivity.
The Relative Effectiveness of Simultaneous versus Sequential Negotiation Strategies in Auditor‐Client Negotiations
Authors: Perreault Stephen , Kida Thomas , David Piercey M.
Published: December 2016

Since most audit engagements identify multiple proposed audit adjustments, auditors must decide how best to present and negotiate these adjustments with their clients. Prior research indicates that auditors can negotiate adjustments individually (a sequential strategy) or can negotiate multiple adjustments within the same negotiation setting (a simultaneous strategy). This paper examines the relative effectiveness of a simultaneous versus sequential negotiation strategy in eliciting concessions from clients and engendering greater client satisfaction. Participants negotiated audit adjustments with a simulated auditor who employed one of the two negotiation strategies. We find evidence that a simultaneous strategy elicits significantly greater total concessions from client managers and also generates more positive attitudes toward the auditor. We also manipulate the magnitude of the issues negotiated and find that significantly greater concessions are offered when larger issues are presented first. These findings have important implications for auditors, as they suggest that negotiating issues simultaneously and presenting larger issues first can result in significantly improved negotiation outcomes.
Drinking, Alcohol Use Disorder, and Treatment Access and Utilization Among U.S. Racial/Ethnic Groups
Authors: Vaeth Patrice A. C. , Wang‐Schweig Meme , Caetano Raul
Published: December 2016

Data from approximately 140 articles and reports published since 2000 on drinking, alcohol use disorder (AUD), correlates of drinking and AUD, and treatment needs, access, and utilization were critically examined and summarized. Epidemiological evidence demonstrates alcohol‐related disparities across U.S. racial/ethnic groups. American Indians/Alaska Natives generally drink more and are disproportionately affected by alcohol problems, having some of the highest rates for AUD. In contrast, Asian Americans are less affected. Differences across Whites, Blacks, and Hispanics are more nuanced. The diversity in drinking and problem rates that is observed across groups also exists within groups, particularly among Hispanics, Asian Americans, and American Indians/Alaska Natives. Research findings also suggest that acculturation to the United States and nativity affect drinking. Recent studies on ethnic drinking cultures uncover the possible influence that native countries’ cultural norms around consumption still have on immigrants’ alcohol use. The reasons for racial/ethnic disparities in drinking and AUD are complex and are associated with historically rooted patterns of racial discrimination and persistent socioeconomic disadvantage. This disadvantage is present at both individual and environmental levels. Finally, these data indicate that admission to alcohol treatment is also complex and is dependent on the presence and severity of alcohol problems but also on a variety of other factors. These include individuals’ sociodemographic characteristics, the availability of appropriate services, factors that may trigger coercion into treatment by family, friends, employers, and the legal system, and the overall organization of the treatment system. More research is needed to understand facilitators and barriers to treatment to improve access to services and support. Additional directions for future research are discussed.
The effect of Ureaplasma urealyticum on the level of P34H expression, the activity of hyaluronidase, and DNA fragmentation in human spermatozoa
Authors: Ma Xiao‐ping , Gao Xiao‐qin
Published: December 2016

Background

To study the effect of Ureaplasma urealyticum on the level of P34H expression, the activity of hyaluronidase, and the DNA fragmentation in human spermatozoa.

Method

Western blot was used to detect the level of P34H expression on spermatozoa.The localization of this protein on human spermatozoa was determined by indirect immunofluorescent and observed by laser scanning confocal microscope. The activity of hyaluronidase was examined by improved fixed‐substrate film method. The DNA fragmentation was assayed with the use of TUNEL.

Results

There were significant differences in the level of P34H protein expression, the percentage of the P34H‐positive rate, the activity of HYD, and the percentage of DNA fragmentation between each infertile group and the control (P<.05). The relation among the P34H protein expression, the percentage of P34H‐positive rate and HYD‐positive rate, HYD‐activity intensity had a significant positive correlation; Both the P34H protein expression and the percentage of P34H‐positive rate were inversely correlated with the percentages of sperm DNA fragmentation.

Conclusion

Ureaplasma urealyticum infection may affect the level of P34H protein expression, the percentage of the P34H‐positive rate, the activity of HYD, and DNA fragmentation that influence fertility.
Interatrial block and interatrial septal thickness in patients with paroxysmal atrial fibrillation undergoing catheter ablation: Long‐term follow‐up study
Authors: Gul Enes E. , Pal Raveen , Caldwell Jane , Boles Usama , Hopman Wilma , Glover Benedict , Michael Kevin A. , Redfearn Damian , Simpson Chris , Abdollah Hoshiar , Baranchuk Adrian
Published: December 2016

Background

Interatrial block (IAB) is a strong predictor of recurrence of atrial fibrillation (AF). IAB is a conduction delay through the Bachman region, which is located in the upper region of the interatrial space. During IAB, the impulse travels from the right atrium to the interatrial septum (IAS) and coronary sinus to finally reach the left atrium in a caudocranial direction. No relation between the presence of IAB and IAS thickness has been established yet.

Objective

To determine whether a correlation exists between the degree of IAB and the thickness of the IAS and to determine whether IAS thickness predicts AF recurrence.

Methods

Sixty‐two patients with diagnosis of paroxysmal AF undergoing catheter ablation were enrolled. IAB was defined as P‐wave duration ≥120 ms. IAS thickness was measured by cardiac computed tomography.

Results

Among 62 patients with paroxysmal AF, 45 patients (72%) were diagnosed with IAB. Advanced IAB was diagnosed in 24 patients (39%). Forty‐seven patients were male. During a mean follow‐up period of 49.8 ± 22 months (range 12–60 months), 32 patients (51%) developed AF recurrence. IAS thickness was similar in patients with and without IAB (4.5 ± 2.0 mm vs. 4.0 ± 1.4 mm; p = .45) and did not predict AF. Left atrial size was significantly enlarged in patients with IAB (40.9 ± 5.7 mm vs. 37.2 ± 4.0 mm; p = .03). Advanced IAB predicted AF recurrence after the ablation (OR: 3.34, CI: 1.12–9.93; p = .03).

Conclusions

IAS thickness was not significantly correlated to IAB and did not predict AF recurrence. IAB as previously demonstrated was an independent predictor of AF recurrence.
Helicobacter pylori serology testing is a useful diagnostic screening tool for symptomatic inner city children
Authors: Raj Priya , Thompson John F. , Pan Debra H.
Published: December 2016

Aim

This study assessed the Helicobacter pylori (H. pylori) serum antibody test as a diagnostic screening tool in symptomatic inner city children.

Methods

This was a retrospective study of patients aged one to 18 years who were referred to our paediatric gastroenterology department from 2009 to 2013. We included all patients who had H. pylori serum antibodies and/or faecal antigens who underwent esophagogastroduodenoscopy (EGD) for histology, with or without a gastric tissue rapid urease test.

Results

A total of 395 patients had EGDs carried out to evaluate epigastric pain, heartburn and nausea or vomiting, and their overall socio‐economic Z‐score was −2.62. The histology was positive for H. pylori infection in 52 of 395 patients (13%), and epigastric pain was documented in 45 of these 52 patients (87%). Compared to histology, the serum H. pylori antibody test had a sensitivity of 88.4% and a specificity of 93.4%. The tissue rapid urease test and faecal antigen test had sensitivities of 89.3% and 55.6% and specificities of 89.9% and 98.9%, respectively.

Conclusion

The serum H. pylori antibody test had high sensitivity and specificity, and it was a good diagnostic screening tool in our study. Epigastric pain was strongly associated with a current H. pylori infection in our population.
A cultural take on the links between religiosity, identity, and meaning in life in religious emerging adults
Authors: Negru‐Subtirica Oana , Tiganasu Alexandra , Dezutter Jessie , Luyckx Koen
Published: December 2016

Identity and meaning in life are core developmental assets in emerging adulthood. We analysed how religiosity is related to these intentional strivings in emerging adults enrolled in theological education, by depicting (1) identity strivings and meaning in life accounts in faith narratives (Study 1) and (2) links between personal identity and meaning in life profiles and religious beliefs, behaviours, and subjective experiences (Study 2). Both studies highlighted that a Foreclosed status, with high personal commitment and reduced exploration, was dominant in faith narratives and personal identity profiles. Also, in narratives meaning in life was reflected by a strong focus on presence of meaning through religious insights. Nonetheless, global meaning in life profiles indicated that many emerging adults were searching for a meaning in their lives, while reporting lower levels of presence of meaning. Identity Achievement and High Presence–High Search profiles were linked to the highest levels of subjective, behavioural, and cognitive religiosity. We highlighted the multidimensionality of identity and meaning in life strivings in emerging adults attending theological schools. We pointed out that even in a somewhat foreclosed cultural context (e.g., Romanian Christian Orthodox theological schools), religion represents a dynamic social and ideological context for self‐development.

Statement of contribution

What is already known on this subject?

Religious beliefs increase in emerging adults, doubled by decreases in religious behaviours, linked to an adherence to a more personal approach to religion.

Religious youth are more committed to their faith and also explore identity and life meaning in relation to their religious strivings.

Youth religious exemplars report close links between their religious faith and strivings for meaningful life goals.

What does this study add?

We investigated Christian Orthodox theology students, for whom religion is a normative dimension of personal and vocational development.

A Foreclosed status, with high personal commitment and reduced exploration was dominant in faith narratives and in personal identity profiles.

Many emerging adults were searching for a meaning in their lives, while at the same time reporting lower levels of presence of meaning.

Identity Achievement and High Presence–High Search profiles were linked to higher levels of subjective, behavioural, and cognitive religiosity.
Inflammasome activation and innate immunity in Alzheimer's disease
Authors: Heneka Michael T.
Published: December 2016

Activation of innate immunity and the assembly of microglial cells at sites of Alzheimer disease pathology has long been regarded as bystander phenomenon, which does not actively contribute to disease pathogenesis and progression. Recent data emerging from genetics, clinical imaging and animal experimentation point to an intimate and mutual interaction of innate immune mechanisms and neurodegenerative processes. NOD‐like receptor (NLR) family, pyrin domain containing 3 and 1 inflammasomes, present in myeloid cells and neurons, respectively, represent key components of the innate immune reaction observed in Alzheimer patient brains. Inhibition of inflammasome activation just begins to prove beneficial and protective from cognitive deficits and neuronal death in cell culture and animal models of Alzheimer's disease, thereby opening a new avenue for therapeutic intervention.
Serelaxin in clinical development: past, present and future
Authors: Unemori Elaine
Published: December 2016

The availability of highly purified recombinant human relaxin, serelaxin, has allowed clinical trials to be conducted in several indications and the elucidation of its pharmacology in human subjects. These studies have demonstrated that serelaxin has unique haemodynamic properties that are likely to contribute to organ protection and long‐term outcome benefits in acute heart failure. Clinical observations support its consideration for therapeutic use in other patient populations, including those with chronic heart failure, coronary artery disease, portal hypertension and acute renal failure.

Linked Articles

This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc
Selection and early clinical evaluation of the brain‐penetrant 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) inhibitor UE2343 (Xanamem™)
Authors: Webster Scott P , McBride Andrew , Binnie Margaret , Sooy Karen , Seckl Jonathan R , Andrew Ruth , Pallin T David , Hunt Hazel J , Perrior Trevor R , Ruffles Vincent S , Ketelbey J William , Boyd Alan , Walker Brian R
Published: December 2016

Background and Purpose

Reducing glucocorticoid exposure in the brain via intracellular inhibition of the cortisol‐regenerating enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) has emerged as a therapeutic strategy to treat cognitive impairment in early Alzheimer's disease (AD). We sought to discover novel, brain‐penetrant 11β‐HSD1 inhibitors as potential medicines for the treatment of AD.

Experimental Approach

Medicinal chemistry optimization of a series of amido‐thiophene analogues was performed to identify potent and selective 11β‐HSD1 inhibitors with optimized oral pharmacokinetics able to access the brain. Single and multiple ascending dose studies were conducted in healthy human subjects to determine the safety, pharmacokinetic and pharmacodynamic characteristics of the candidate compound.

Results

UE2343 was identified as a potent, orally bioavailable, brain‐penetrant 11β‐HSD1 inhibitor and selected for clinical studies. No major safety issues occurred in human subjects. Plasma adrenocorticotropic hormone was elevated (a marker of systemic enzyme inhibition) at doses of 10 mg and above, but plasma cortisol levels were unchanged. Following multiple doses of UE2343, plasma levels were approximately dose proportional and the terminal t1/2 ranged from 10 to 14 h. The urinary tetrahydrocortisols/tetrahydrocortisone ratio was reduced at doses of 10 mg and above, indicating maximal 11β‐HSD1 inhibition in the liver. Concentrations of UE2343 in the CSF were 33% of free plasma levels, and the peak concentration in CSF was ninefold greater than the UE2343 IC50.

Conclusions and Implications

UE2343 is safe, well tolerated and reaches the brain at concentrations predicted to inhibit 11β‐HSD1. UE2343 is therefore a suitable candidate to test the hypothesis that 11β‐HSD1 inhibition in brain improves memory in patients with AD.
Is there a quality bias in the Canadian CPI? Evidence from microdata
Authors: Kryvtsov Oleksiy
Published: December 2016

Rising consumer prices may reflect shifts by consumers to new higher‐priced products, mostly for durable and semi‐durable goods. I apply Bils’ (2009) methodology to newly available Canadian consumer price data for non‐shelter goods and services to estimate how price increases can be divided between quality growth and price inflation. I find that less than one third of observed price increases during model changeovers should be attributed to quality growth. This implies overall price inflation close to inflation measured by the official index. I conclude that, according to Bils’ methodology, the quality bias is not an important source of potential mismeasurement of CPI inflation in Canada.
Trade in variety and domestic production: Evidence from US manufacturing
Authors: Lewrick Ulf , Mohler Lukas , Weder Rolf
Published: December 2016

Welfare gains from increasing product variety are an important source of the gains from international trade. Previous empirical studies, however, typically focus on measuring gains from imported varieties. This paper introduces a measure to analyze changes in domestically produced varieties to estimate the total variety gains. Our analysis suggests that, for US manufacturing, losses in domestic varieties from 1992 to 2006 seem substantial given the large decline in the number of US establishments. Yet, once we account for the reallocation of resources towards large multi‐variety firms, we find considerable domestic variety gains, adding to those from imported varieties.
Long‐term outcomes of proton beam therapy in patients with previously untreated hepatocellular carcinoma
Authors: Fukuda Kuniaki , Okumura Toshiyuki , Abei Masato , Fukumitsu Nobuyoshi , Ishige Kazunori , Mizumoto Masashi , Hasegawa Naoyuki , Numajiri Haruko , Ohnishi Kayoko , Ishikawa Hitoshi , Tsuboi Koji , Sakurai Hideyuki , Hyodo Ichinosuke
Published: December 2016

Long‐term efficacy of proton beam therapy (PBT) remains unclear for patients with previously untreated hepatocellular carcinoma (HCC). We aimed to study the long‐term outcomes of PBT according to Barcelona Clinic Liver Cancer (BCLC) staging classifications in patients with previously untreated HCC. The major eligibility criteria of this observational study were an Eastern Cooperative Oncology Group performance status (PS) 0–2, Child–Pugh grade A or B, previously untreated HCC covered within an irradiation field, and no massive ascites. A total of 66.0–77.0 GyE was administered in 10–35 fractions. Local tumor control (LTC), defined as no progression in the irradiated field, progression‐free survival (PFS), and overall survival (OS) were assessed according to BCLC staging. From 2002 to 2009 at our institution, 129 patients were eligible. The 5‐year LTC, PFS, and OS rates were 94%, 28%, and 69% for patients with 0/A stage disease (n = 9/21), 87%, 23%, and 66% for patients with B stage disease (n = 34), and 75%, 9%, and 25% for patients with C stage disease (n = 65), respectively. The 5‐year LTC and OS rates of 15 patients with tumor thrombi in major vessels were 90% and 34%, respectively. Multivariate analyses revealed that PS (0 versus 1–2) was a significant prognostic factor for OS. No grade 3 or higher adverse effects were observed. PBT showed favorable long‐term efficacies with mild adverse effects in BCLC stage 0 to C, and can be an alternative treatment for localized HCC especially when accompanied with tumor thrombi. This study was registered with UMIN Clinical Trials Registry (UMIN000025342).
miR‐3941: A novel microRNA that controls IGBP1 expression and is associated with malignant progression of lung adenocarcinoma
Authors: Sato Taiki , Shiba‐Ishii Aya , Kim Yunjung , Dai Tomoko , Husni Ryan Edbert , Hong JeongMin , Kano Junko , Sakashita Shingo , Iijima Tatsuo , Noguchi Masayuki
Published: December 2016

Immunoglobulin (CD79a) binding protein 1 (IGBP1) is universally overexpressed in lung adenocarcinoma and exerts an anti‐apoptotic effect by binding to PP2Ac. However, the molecular mechanism of IGBP1 overexpression is still unclear. In the present study, we used a microRNA (miRNA) array and TargetScan Human software to detect IGBP1‐related miRNAs that regulate IGBP1 expression. The miRNA array analysis revealed more than 100 miRNAs that are dysregulated in early invasive adenocarcinoma. On the other hand, in silico analysis using TargetScan Human revealed 79 miRNAs that are associated with IGBP1 protein expression. Among the miRNAs selected by miRNA array analysis, six (miR‐34b, miR‐138, miR‐374a, miR‐374b, miR‐1909, miR‐3941) were also included among those selected by TargetScan analysis. Real‐time reverse transcription PCR (real‐time RT‐PCR) showed that the six microRNAs were downregulated in invasive adenocarcinoma (IGBP1+) relative to adjacent normal lung tissue (IGBP1−). Among these microRNAs, only miR‐34b and miR‐3941 depressed luciferase activity by targeting 3′UTR‐IGBP1 in the luciferase vector. We transfected miR‐34b and miR‐3941 into lung adenocarcinoma cell lines (A549, PC‐9), and both of them suppressed IGBP1 expression and cell proliferation. Moreover, the transfected miR‐34b and miR‐3941 induced apoptosis of a lung adenocarcinoma cell line, similarly to the effect of siIGBP1 RNA. As well as miR‐34b, we found that miR‐3941 targeted IGBP1 specifically and was able to exclusively downregulate IGBP1 expression. These findings indicate that suppression of miR‐3941 has an important role in the progression of lung adenocarcinoma at an early stage.
Tumour-activated liver stromal cells regulate myeloid-derived suppressor cells accumulation in the liver
Authors: Zhang H , He G , Kong Y , Chen Y , Wang B , Sun X , Jia B , Xie X , Wang X , Chen D , Wei L , Zhang M , Zeng H , Chen H
Published: December 2016

Regulating mechanisms underlying hepatic myeloid-derived suppressor cell (MDSC) accumulation remain to be described. Here, we provide evidence for the involvement of tumour-activated liver stromal cells in the process of hepatic MDSCs migration and accumulation. Our data showed an elevated frequency of MDSCs in the liver of tumour-bearing mice. Moreover, tumour-activated liver stromal cells promote MDSC migration into the liver site. Further investigation indicated higher levels of cytokine and chemokine expression in liver stromal cells after exposure to the tumour-conditioned supernatant. Notably, the expression levels of proinflammatory factors, mainly including macrophage colony stimulating factor (M-CSF), transforming growth factor-β (TGF-β), monocyte chemotactic protein-1 (MCP-1) and stromal-derived factor-1 (SDF-1), increased after treatment with tumour-conditioned supernatant, and blockade of MCP-1 or SDF-1 decreased the proportion of tumour infiltrated MDSCs in mice co-transplanted with liver stromal cells and tumour cells, but not in mice with only tumour cells injection. These findings demonstrate that tumour-activated liver stromal cells produce higher levels of chemokines and cytokines, which may contribute to MDSC accumulation into the liver site in patients with liver cancer.
Diversification shifts in leafroller moths linked to continental colonization and the rise of angiosperms
Authors: Fagua Giovanny , Condamine Fabien L. , Horak Marianne , Zwick Andreas , Sperling Felix A.H.
Published: December 2016

Tectonic dynamics and niche availability play intertwined roles in determining patterns of diversification. Such drivers explain the current distribution of many clades, whereas events such as the rise of angiosperms can have more specific impacts, such as on the diversification rates of herbivores. The Tortricidae, a diverse group of phytophagous moths, are ideal for testing the effects of these determinants on the diversification of herbivorous clades. To estimate ancestral areas and diversification patterns in Tortricidae, a complete tribal‐level dated tree was inferred using molecular markers (one mitochondrial and five nuclear) and calibrated using fossil constraints. We found that Tortricidae diverged from their sister group c. 120 Myr ago (Ma) and diversified c. 97 Ma, a timeframe synchronous with the rise of angiosperms in the Early–mid Cretaceous. Ancestral areas analysis, based on updated Wallace's biogeographical regions, supports the hypothesis of a Gondwanan origin of Tortricidae in the South American plate. We also detected an increase in speciation rate that coincided with the peak of angiosperm diversification in the Cretaceous. This in turn probably was further heightened by continental colonization of the Palaeotropics when angiosperms became dominant by the end of the Late Cretaceous.
Follicular lymphomatoid papulosis with follicular mucinosis: a clinicopathologic study of 3 cases with literature review and conceptual reappraisal
Authors: Dore Emilie , Swick Brian L. , Link Brian K. , Ghahramani Grant K. , Liu Vincent
Published: December 2016

Lymphomatoid papulosis (LyP), characterized by recurring, waxing and waning, cutaneous papulonodules, is increasingly recognized to represent a heterogeneous collection of pathologically dissimilar subtypes. Recently, a follicular LyP variant was proposed, featuring folliculotropism. Folliculotropism by atypical lymphocytes is conventionally associated with follicular mucinosis and mycosis fungoides (MF), and review of the literature suggests co‐occurrence of folliculotropism and follicular mucinosis in LyP to be rare, with only 3 cases identified to date. Herein we describe 3 additional cases, each manifesting a typical LyP clinical picture, with the additional element of folliculotropism and follicular mucinosis on pathology. These cases suggest that LyP should be considered alongside MF in the differential diagnosis of follicular mucinosis with accompanying atypical lymphocytic infiltration. As LyP can occur with other lymphoproliferative disorders such as MF, the finding of follicular mucinosis in LyP may further represent a conceptual intersection between the 2 disease processes.
Management of drooling in neurological disabilities: more evidence is needed
Authors: Reddihough Dinah
Published: December 2016

This commentary is on the original article by van Hulst et al. on pages
531–537 of this issue.
Metabolic effects of Lactobacillus reuteriDSM 17938 in people with type 2 diabetes: A randomized controlled trial
Authors: Mobini Reza , Tremaroli Valentina , Ståhlman Marcus , Karlsson Fredrik , Levin Max , Ljungberg Maria , Sohlin Maja , Bertéus Forslund Heléne , Perkins Rosie , Bäckhed Fredrik , Jansson Per‐Anders
Published: December 2016

Aims

To investigate the metabolic effects of 12‐week oral supplementation with
Lactobacillus reuteri DSM 17938 in patients with type 2 diabetes on insulin therapy.

Materials and methods

In a double‐blind trial, we randomized 46 people with type 2 diabetes to placebo or a low (108 CFU/d) or high dose (1010 CFU/d) of
L. reuteri DSM 17938 for 12 weeks. The primary endpoint was the effect of supplementation on glycated haemoglobin (HbA1c). Secondary endpoints were insulin sensitivity (assessed by glucose clamp), liver fat content, body composition, body fat distribution, faecal microbiota composition and serum bile acids.

Results

Supplementation with
L. reuteri DSM 17938 for 12 weeks did not affect HbA1c, liver steatosis, adiposity or microbiota composition. Participants who received the highest dose of
L. reuteri exhibited increases in insulin sensitivity index (ISI) and serum levels of the secondary bile acid deoxycholic acid (DCA) compared with baseline, but these differences were not significant in the between‐group analyses. Post hoc analysis showed that participants who responded with increased ISI after
L. reuteri supplementation had higher microbial diversity at baseline, and increased serum levels of DCA after supplementation. In addition, increases in DCA levels correlated with improvement in insulin sensitivity in the probiotic recipients.

Conclusions

Intake of
L. reuteri DSM 17938 for 12 weeks did not affect HbA1c in people with type 2 diabetes on insulin therapy; however,
L. reuteri improved insulin sensitivity in a subset of participants and we propose that high diversity of the gut microbiota at baseline may be important.
Efficacy, safety and albuminuria‐reducing effect of gemigliptin in Korean type 2 diabetes patients with moderate to severe renal impairment: A 12‐week, double‐blind randomized study (the GUARD Study)
Authors: Yoon Sun A. , Han Byoung G. , Kim Sung G. , Han Sang Y. , Jo Young I. , Jeong Kyung H. , Oh Kook H. , Park Hyeong C. , Park Sun H. , Kang Shin W. , Na Ki R. , Kang Sun W. , Kim Nam H. , Jang Young H. , Shin Seong H. , Cha Dae R.
Published: December 2016

Aims

This multicentre, randomized, double‐blind study investigated the efficacy and safety of gemigliptin in Korean type 2 diabetes mellitus (T2DM) patients with moderate to severe renal impairment (RI).

Methods

The study comprised a 12‐week main part and a 40‐week extension. We report here the results from the main part. In total, 132 patients were randomized to receive gemigliptin (n = 66) or placebo (n = 66). Changes in glycated haemoglobin (HbA1c; primary endpoint), other glycaemic control parameters (fasting plasma glucose, glycated albumin and fructosamine), lipid profiles, renal function parameters and safety profiles were evaluated.

Results

Baseline characteristics were comparable between the groups (mean HbA1c, 8.4% [68 mmol/mol]; age, 62.0 years; duration of type 2 diabetes, 16.3 years; estimated glomerular filtration rate, 33.3 mL/min/1.73 m2). At Week 12, the adjusted mean change ± standard error in HbA1c with gemigliptin was −0.82% ± 0.14% (−8.9 ± 1.5 mmol/mol), whereas it was 0.38% ± 0.14% (4.2 ± 1.5 mmol/mol) with placebo (significant between‐group difference,
P
 < .001). Other glycaemic control parameters showed beneficial changes as well. Body weight change (gemigliptin, −0.3 kg; placebo, −0.2 kg) was not significant. In the gemigliptin group, the mean decrease in urinary albumin creatinine ratio (UACR) was significant, both in patients with microalbuminuria (−41.9 mg/g creatinine,
P
 = .03) and macroalbuminuria (−528.9 mg/g creatinine,
P
 < .001). Drug‐related adverse events were similar with gemigliptin and placebo (15% and 12%, respectively).

Conclusions

A 12‐week treatment with gemigliptin improved glycaemic control and provided UACR reduction in T2DM patients with moderate to severe RI. Gemigliptin was well tolerated, with no additional risk of hypoglycaemia and change in body weight.
The effects of atrasentan on urinary metabolites in patients with type 2 diabetes and nephropathy
Authors: Pena Michelle J. , de Zeeuw Dick , Andress Dennis , Brennan John J. , Correa‐Rotter Ricardo , Coll Blai , Kohan Donald E. , Makino Hirofumi , Perkovic Vlado , Remuzzi Giuseppe , Tobe Sheldon W. , Toto Robert , Parving Hans‐Henrik , Sharma Shoba , Corringham Tom , Sharma Kumar , Heerspink Hiddo J. L.
Published: December 2016

We assessed the effect of atrasentan therapy on a pre‐specified panel of 13 urinary metabolites known to reflect mitochondrial function in patients with diabetic kidney disease. This post‐hoc analysis was performed using urine samples collected during the RADAR study which was a randomized, double‐blind, placebo‐controlled trial that tested the effects of atrasentan on albuminuria reduction in patients with type 2 diabetes and nephropathy. At baseline, 4 of the 13 metabolites, quantified by gas‐chromatography mass spectrometry, were below detectable levels, and 6 were reduced in patients with eGFR < 60 mL/min/1.73 m2. After 12 weeks of atrasentan treatment in patients with eGFR < 60 mL/min/1.73 m2, a single‐value index of the metabolites changed by −0.31 (95%CI −0.60 to −0.02;
P
 = .035), −0.08 (−12 to 0.29;
P
 = .43) and 0.01 (−0.21 to 0.19;
P
 = .913) in placebo, atrasentan 0.75 and 1.25 mg/d, respectively. The metabolite index difference compared to placebo was 0.13 (−0.17 to 0.43;
P
 = .40) and 0.35 (0.05‐0.65;
P
 = .02) for atrasentan 0.75 and 1.25 mg/d, respectively. These data corroborate previous findings of mitochondrial dysfunction in patients with type 2 diabetes, nephropathy and eGFR < 60 mL/min/1.73 m2, suggesting that atrasentan may prevent the progression of mitochondrial dysfunction common to this specific patient population. Future studies of longer treatment duration with atrasentan are indicated.
Immunoglobulin A: magic bullet or Trojan horse?
Authors: Heineke Marieke H. , van Egmond Marjolein
Published: December 2016

Background

Neutrophils participate in the first line of defense by executing several killing mechanisms, including phagocytosis, degranulation and the release of neutrophil extracellular traps. Additionally, they can orchestrate the adaptive immune system by secreting cytokines and chemokines. Opsonization with antibodies aids in the recognition of pathogens, via binding to Fc receptors on the neutrophil surface. Immunoglobulin A (IgA) is the most abundant antibody at mucosal sites and has multiple functions in homeostasis and immunity. Neutrophils and IgA can interact via the IgA Fc receptor Fc?RI (CD89), leading to pro‐ or anti‐inflammatory responses.

Aims

The aim of this review is to give a concise overview of the interplay between IgA, Fc?RI and neutrophils and to explore potential therapies for autoimmune diseases and cancer.

Results

Crosslinking of FcαRI by IgA‐immune complexes yields potent neutrophil activation and pro‐inflammatory effector functions, including the recruitment of neutrophils. This can lead to neutrophil accumulation and tissue destruction during IgA‐autoantibody mediated diseases. Conversely, for cancer treatment, the myriad of powerful neutrophil effector functions after targeting FcαRI may contribute to effective immunotherapy.

Conclusion

By interfering with or actively promoting the interaction between IgA and FcαRI, therapies for multiple maladies could be developed
Remittances and incumbency: Theory and evidence
Authors: Ahmed Faisal Z.
Published: December 2016

By raising household income, remittances lower the marginal utility of targeted electoral transfers, thus weakening the efficacy of vote buying. Yet, remittances make individuals wealthier and believe the national economy is performing well, which is positively attributed to the incumbent. Building on these insights, I show that the confluence of these divergent channels generate a surprising result that at increasingly higher levels of dissatisfaction with the incumbent, a remittance recipient is more likely to vote for the incumbent than a non‐remittance recipient. These predictions and their underlying mechanisms are substantiated across 18 Latin American countries.