bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct telomere differences within a reproductively bimodal common lizard population
Authors: McLennan Darryl , Recknagel Hans , Elmer Kathryn R. , Monaghan Pat
Published: July 2019

Different strategies of reproductive mode, either oviparity (egg‐laying) or viviparity (live‐bearing), will be associated with a range of other life‐history differences that are expected to affect patterns of ageing and longevity. It is usually difficult to compare the effects of alternative reproductive modes because of evolutionary and ecological divergence. However, the very rare exemplars of reproductive bimodality, in which different modes exist within a single species, offer an opportunity for robust and controlled comparisons.

One trait of interest that could be associated with life history, ageing and longevity is the length of the telomeres, which form protective caps at the chromosome ends and are generally considered a good indicator of cellular health. The shortening of these telomeres has been linked to stressful conditions; therefore, it is possible that differing reproductive costs will influence patterns of telomere loss. This is important because a number of studies have linked a shorter telomere length to reduced survival.

Here, we have studied maternal and offspring telomere dynamics in the common lizard (Zootoca vivipara). Our study has focused on a population where oviparous and viviparous individuals co‐occur in the same habitat and occasionally interbreed to form admixed individuals.

While viviparity confers many advantages for offspring, it might also incur substantial costs for the mother, for example require more energy. Therefore, we predicted that viviparous mothers would have relatively shorter telomeres than oviparous mothers, with admixed mothers having intermediate telomere lengths. There is thought to be a heritable component to telomere length; therefore, we also hypothesized that offspring would follow the same pattern as the mothers.

Contrary to our predictions, the viviparous mothers and offspring had the longest telomeres, and the oviparous mothers and offspring had the shortest telomeres. The differing telomere lengths may have evolved as an effect of the life‐history divergence between the reproductive modes, for example due to the increased growth rate that viviparous individuals may undergo to reach a similar size at reproduction.

A freePlain Language Summarycan be found within the Supporting Information of this article.
Ethyl Glucuronide Concentration in Hair of Detainees: A Preliminary Study
Authors: Pascali Jennifer Paola , Palumbo Diego , Umani Ronchi Federica , Mari Francesco , Fioravanti Alessia , Bertol Elisabetta
Published: July 2019

Through the measurement of ethyl glucuronide in hair (hETG), it is possible to assess chronic alcohol abuse over time. In this paper, we present a study on hETG in Italian prison inmates. Analyses were performed by LC‐MS according to a previously published method. Results were evaluated using the cut‐offs established by the Society of Hair Testing. Positives samples (ETG > 30 pg/mg) accounted for 6% of all subjects, with concentrations ranging from 42 pg/mg up to 270 pg/mg, abstinent subjects (ETG < 7 pg/mg) accounted for 88%, and moderate alcohol consumption (7 < ETG < 30 pg/mg) for 6% of the subjects. No females displayed ETG values above 30 pg/mg. Among positive samples, only two subjects did not declare heavy alcohol consumption and were found strongly positive at 210 and 270 pg/mg. To the best of our knowledge, this represents the first study on ETG hair concentration on prison inmates.
The Leap of the Tiger: Escaping the Middle‐income Trap to the Technological Frontier
Authors: Cherif Reda , Hasanov Fuad
Published: July 2019

The Asian miracles along with a handful of European economies and oil exporters are the few countries that reached high‐income status during 1960–2014. In contrast, many good‐performing countries such as Malaysia have been middle‐income countries for several decades despite relatively strong growth and a substantial improvement in education and export sophistication. We argue that the key factor differentiating the Asian miracles from economies like Malaysia is the creation of technologies by domestic firms and leapfrogging to the technological frontier at an early stage of development.
‘Real interest’? Understanding the 2018 Agreement to Prevent Unregulated High Seas Fisheries in the Central Arctic Ocean
Authors: Dodds Klaus
Published: July 2019

The 2018 Agreement to Prevent Unregulated High Seas Fisheries in the Central Arctic Ocean (Agreement) is a notable intervention in living resources management. The Agreement seeks to anticipate future fisheries management and serves as a reminder as how international legal frameworks such as UNCLOS ‘regionalise’ seas and oceans. But thus far analyses of the Agreement have tended to focus on its legal and managerial qualities and implications. This paper offers a different reading of the Agreement, informed by critical geopolitics, which focuses on how the Agreement actively produces ‘the Central Arctic Ocean’ (CAO) which it then seeks to manage. The Agreement will shape not only the future geopolitics of the Arctic Ocean but also the diverse array of interests held by Arctic Ocean coastal states, indigenous peoples, environmental groups and extra‐territorial parties such as China.
Optimality in prioritizing conservation projects
Authors: Hanson Jeffrey O. , Schuster Richard , Strimas‐Mackey Matthew , Bennett Joseph R.
Published: July 2019

The resources available to safeguard biodiversity are limited, and so funding must be allocated cost‐effectively. To achieve this, conservation projects—such as threatened species recovery projects, or pest management projects—are often prioritized using algorithms. Conventionally, prioritizations have been generated by ranking projects according to their cost‐effectiveness and selecting the top projects within a budget, or using backwards heuristic algorithms which iteratively remove projects until a budget is met. Yet such algorithms may not deliver optimal solutions.

We investigated the performance of exact algorithms, a class of algorithms that guarantee optimality, compared with conventional algorithms for project prioritization. Specifically, we conducted a simulation study, involving 40 conservation projects, 50 species, and 80 management actions, and a case study involving recovery projects for 62 of New Zealand’s threatened bird species. In each of these studies, we generated prioritizations by (i) exact algorithms, (ii) ranking projects using cost‐effectiveness, (iii) a backwards heuristic algorithm, and (iv) randomly funding projects. After generating the prioritizations, we evaluated their performance.

We found that exact algorithms outperform conventional algorithms for project prioritization. In the simulation study, both the ranking and backwards heuristic algorithms returned solutions that were highly suboptimal when compared with solutions by exact algorithms. In the case study, both conventional algorithms returned solutions that would be expected to result in the needless loss of millions of years of avian evolutionary history due to poor planning. Furthermore, conventional algorithms returned solutions with large amounts of unallocated funding—providing little guidance for decision makers. Despite concerns that exact algorithm solvers require an inordinate amount of time, the longest run in either study took less than three minutes.

Our results suggest that conservation agencies could benefit enormously from exact algorithms. To help make exact algorithms more accessible, we developed theoppr Rpackage (https://CRAN.R-project.org/package=oppr) which can use open‐source and commercial exact algorithm solvers to identify optimal solutions for a range of objectives and constraints. Our findings suggest that conservation plans could be substantially improved using exact algorithms, which could potentially save millions of dollars and lead to more species being saved from extinction.
Changes in presynaptic calcium signalling accompany age‐related deficits in hippocampal LTP and cognitive impairment
Authors: Pereda Daniel , Al‐Osta Ibrahim , Okorocha Albert E. , Easton Alexander , Hartell Nicholas A.
Published: July 2019

The loss of cognitive function accompanying healthy aging is not associated with extensive or characteristic patterns of cell death, suggesting it is caused by more subtle changes in synaptic properties. In the hippocampal CA1 region, long‐term potentiation requires stronger stimulation for induction in aged rats and mice and long‐term depression becomes more prevalent. An age‐dependent impairment of postsynaptic calcium homeostasis may underpin these effects. We have examined changes in presynaptic calcium signalling in aged mice using a transgenic mouse line (SyG37) that expresses a genetically encoded calcium sensor in presynaptic terminals. SyG37 mice showed an age‐dependent decline in cognitive abilities in behavioural tasks that require hippocampal processing including the Barnes maze, T‐maze and object location but not recognition tests. The incidence of LTP was significantly impaired in animals over 18 months of age. These effects of aging were accompanied by a persistent increase in resting presynaptic calcium, an increase in the presynaptic calcium signal following Schaffer collateral fibre stimulation, an increase in postsynaptic fEPSP slope and a reduction in paired‐pulse facilitation. These effects were not caused by synapse proliferation and were of presynaptic origin since they were evident in single presynaptic boutons. Aged synapses behaved like younger ones when the extracellular calcium concentration was reduced. Raising extracellular calcium had little effect on aged synapses but altered the properties of young synapses into those of their aged counterparts. These effects can be readily explained by an age‐dependent change in the properties or numbers of presynaptic calcium channels.
Runs of homozygosity and testicular cancer risk
Authors: Loveday C. , Sud A. , Litchfield K. , Levy M. , Holroyd A. , Broderick P. , Kote‐Jarai Z. , Dunning A. M. , Muir K. , Peto J. , Eeles R. , Easton D. F. , Dudakia D. , Orr N. , Pashayan N. ,   UK Testicular Cancer Collaboration,   The PRACTICAL Consortium, Reid A. , Huddart R. A. , Houlston R. S. , Turnbull C.
Published: July 2019

Background

Testicular germ cell tumour (TGCT) is highly heritable but > 50% of the genetic risk remains unexplained. Epidemiological observation of greater relative risk to brothers of men with TGCT compared to sons has long alluded to recessively acting TGCT genetic susceptibility factors, but to date none have been reported. Runs of homozygosity (RoH) are a signature indicating underlying recessively acting alleles and have been associated with increased risk of other cancer types.

Objective

To examine whether RoH are associated with TGCT risk.

Methods

We performed a genome‐wide RoH analysis using GWAS data from 3206 TGCT cases and 7422 controls uniformly genotyped using the OncoArray platform.

Results

Global measures of homozygosity were not significantly different between cases and controls, and the frequency of individual consensus RoH was not significantly different between cases and controls, after correction for multiple testing. RoH at three regions, 11p13‐11p14.3, 5q14.1‐5q22.3 and 13q14.11‐13q.14.13, were, however, nominally statistically significant at p < 0.01. Intriguingly, RoH200 at 11p13‐11p14.3 encompasses Wilms tumour 1 (WT1), a recognized cancer susceptibility gene with roles in sex determination and developmental transcriptional regulation, processes repeatedly implicated in TGCT aetiology.

Discussion and conclusion

Overall, our data do not support a major role in the risk of TGCT for recessively acting alleles acting through homozygosity, as measured by RoH in outbred populations of cases and controls.
A Gramscian Conjuncture in Latin America? Reflections on Violence, Hegemony, and Geographical Difference
Authors: Hesketh Chris
Published: July 2019

This article addresses whether the concepts of Antonio Gramsci still “travel” to Latin America. During the 20thcentury, Gramsci was one of the most important social theorists invoked to understand forms of social order in Latin America, as well as providing resources to reflect upon subaltern culture, resistance and the construction of alternatives. However, over the past two decades there have been several theoretical and practical challenges to the hegemony of Gramsci. These challenges are multifarious, but can be reduced to several important contentions that are explored in this article. These include the enduring role of violence, the alleged decline of ideology and finally the challenge of state‐centrism in the face of geographical difference. In the current regional conjuncture, marked by the return to power of right‐wing social forces, I therefore examine whether Gramscian concepts are still apposite for understanding the political economy of Latin America in the 21stcentury.
Blunted leptin sensitivity during hedonic overeating can be reinstated by activating galanin 2 receptors (Gal2R) in the lateral hypothalamus
Authors: Leidmaa Este , Gazea Mary , Patchev Alexandre V. , Pissioti Anna , Christian Gassen Nils , Kimura Mayumi , Liposits Zsolt , Kallo Imre , Almeida Osborne F. X.
Published: July 2019

Aim

Since foods with high hedonic value are often consumed in excess of energetic needs, this study was designed to identify the mechanisms that may counter anorexigenic signalling in the presence of hedonic foods in lean animals.

Methods

Mice, in different states of satiety (fed/fasted, or fed/fasted and treated with ghrelin or leptin, respectively), were allowed to choose between high‐fat/high‐sucrose and standard foods. Intake of each food type and the activity of hypothalamic neuropetidergic neurons that regulate appetite were monitored. In some cases, food choice was monitored in leptin‐injected fasted mice that received microinjections of galanin receptor agonists into the lateral hypothalamus.

Results

Appetite‐stimulating orexin neurons in the lateral hypothalamus are rapidly activated when lean, satiated mice consume a highly palatable food (PF); such activation (upregulated c‐Fos expression) occurred even after administration of the anorexigenic hormone leptin and despite intact leptin signalling in the hypothalamus. The ability of leptin to restrain PF eating is restored when a galanin receptor 2 (Gal2R) agonist is injected into the lateral hypothalamus.

Conclusion

Hedonically‐loaded foods interrupt the inhibitory actions of leptin on orexin neurons and interfere with the homeostatic control of feeding. Overeating of palatable foods can be curtailed in lean animals by activating Gal2R in the lateral hypothalamus.
Systematic review with meta‐analysis: risk of new onset IBD with the use of anti‐interleukin‐17 agents
Authors: Yamada Akihiro , Wang Jingzhou , Komaki Yuga , Komaki Fukiko , Micic Dejan , Sakuraba Atsushi
Published: July 2019

Background

New onset IBD has been reported with the use of anti‐IL‐17 agents, but it remains unclear to what extent this is attributed to treatment or to underlying disease.

Aim

To evaluate the risk of new onset IBD with the use of anti‐IL‐17 agents

Methods

Electronic databases were searched for randomised controlled trials (RCT) of anti‐IL‐17 agents (brodalumab, ixekizumab and secukinumab). Risk of new onset IBD was compared to placebo by Mantel‐Haenszel (MH) risk difference (RD). Sensitivity analyses including meta‐analysis using fixed‐effect model, MH and Peto odds ratio and MH risk ratio were performed due to incidence of rare adverse events. The risk of diarrhoea was also assessed due to the possibility of underdiagnosis of IBD.

Results

Thirty‐eight RCTs including 16 690 patients treated with anti‐IL‐17 agents were included. Twelve cases of new onset IBD were reported with anti‐IL‐17 agents in five studies, whereas no cases were reported with placebo. There was no difference in the risk of developing new onset IBD with anti‐IL‐17 agents compared to placebo (MH RD 0.00062, 95% CI −0.00072‐0.0021, P = 0.35). Sensitivity analyses demonstrated no consistent risk with any method. There was no difference in the risk of diarrhoea (MH RD 0.0013, 95% CI −0.0014‐0.0041, P = 0.34).

Conclusions

New onset IBD with the use of anti‐IL‐17 agents was rare. Interpretation of the results needs caution due to the presence of many zero‐event studies.
ANOTHER ONE BITES THE DUST: QUALITY CONTROL AND FIRING TECHNOLOGY IN THE PRODUCTION OF MEDIEVAL GREYWARE CERAMICS IN CATALONIA, SPAIN
Authors: Travé Allepuz E. , Quinn P. S. , Álvaro Rueda K.
Published: July 2019

The following study sheds new light on the quality control procedures of ancient potters by comparing cooking vessels exported from the medieval kiln‐site of Cabrera d'Anoia (Barcelona) with ‘wasters' that were discarded at source. The firing temperature of examined sherds indicates that only pots subjected to a maximum temperature of 800–850°C were offered for sale. The potters at Cabrera d'Anoia appear to have been fully aware of the optimal balance between thermal and physical shock resistance of vessels fired within this range and strived to control firing in order to achieve better products than that of competing workshops.
Effects of physically effective fiber in diets based on rice straw and cassava pulp on chewing activity, ruminal fermentation, milk production, and digestibility in dairy cows
Authors: Kaeokliang Ornvimol , Kawashima Tomoyuki , Narmseelee Ramphrai , Butcha Patima , Sunato Supakit , Thinowong Anusorn , Jindatajak Yaungyote
Published: July 2019

The objective of this study was to evaluate the effects of physically effective neutral detergent fiber (peNDF) in rice straw and cassava pulp diets on the chewing activity, ruminal fermentation, milk production, and digestibility in low‐producing dairy cows. Eight lactating Holstein crossbred cows were randomly divided into two groups in a crossover design with two dietary treatments over two 21‐day periods. The difference in peNDF contents was achieved by balancing the ratio of rice straw, cassava pulp, and concentrate. The high cassava pulp diet had 15.5% peNDF and the low cassava pulp diet had 20.2% peNDF. The results showed that feeding the low cassava pulp diet increased the concentrations of milk protein, milk fat, solids‐not‐fat, and total solids in the milk. In contrast, the dry matter intake, milk yield, lactose content, chewing activity, nutrient digestibility, ruminal fermentation, and pH were not affected by treatments.
Predation by carpet pythons (Morelia spilota) is an important cause of mortality in a free‐living koala (Phascolarctos cinereus) population in South East Queensland
Authors: Robbins Amy , Loader Joanne , de Villiers Deidre , Beyer Hawthorne L. , Hanger Jonathan
Published: July 2019

Koalas (Phascolarctos cinereus) are experiencing significant declines across the northern part of their range. However, unbiased, population‐level estimates of mortality are rarely reported, as it's difficult to quantify causes of mortality robustly in this cryptic species. We aimed to determine the relative importance of carpet python (Morelia spilota) predation in a free‐living koala population and describe the characteristic pathological findings during necropsy. In total, 503 koalas were captured, underwent veterinary examination and telemetric tagging, and were monitored after release over a four‐year period. Mortalities were detected when activity data reported by K‐Tracker® biotelemetry collars indicated low or zero activity, or during routine field monitoring events. Experienced koala veterinarians performed thorough, standardised necropsy examinations on retrieved carcasses to determine causes of death. The three, sometimes subtle, cardinal signs used to definitively diagnose carpet python‐caused deaths of koalas were a U‐shaped primary bite site, slicking of the fur by python saliva (particularly around the face), and diffuse, uniform pulmonary congestion. We found that carpet pythons were important predators of koalas, second only to wild dogs (dingoes and dingo hybrids (Canis familiaris dingo)), accounting for 11.6% of predation deaths and 7.2% of total deaths. Less than half (38%) of the koalas killed by carpet pythons were ingested. Though carpet pythons are known predators of koalas, their relative importance as a cause of mortality hasn't previously been recognised. Population viability analyses and conservation management plans benefit from robust cause‐of‐death data collected during longitudinal monitoring studies, requiring telemetry methods that facilitate rapid detection of mortalities.
Identification of Chlamydia gallinacea in a parrot and in free‐range chickens in Australia
Authors: Stokes HS , Martens JM , Chamings A , Walder K , Berg ML , Segal Y , Bennett ATD
Published: July 2019

Chlamydia gallinacea is a recently described bacterial species in a genus known to infect and cause disease in animals and humans. Our report describes the identification of C. gallinacea infection in free‐range laying chickens (Gallus gallus) in Australia, and the identification of C. gallinacea infection in a parrot, a wild Australian galah (Eolophus roseicapillus). There is currently little knowledge of the effects of C. gallinacea infection on avian hosts, but it has been linked to respiratory disease in humans and could potentially cause similar disease in other species. Our report highlights the need for further study and surveillance of Chlamydia species in both wild and domestic hosts in Australia.
Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU‐285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignancies
Authors: Weisberg Ellen , Meng Chengcheng , Case Abigail E. , Sattler Martin , Tiv Hong L. , Gokhale Prafulla C. , Buhrlage Sara J. , Liu Xiaoxi , Yang Jing , Wang Jinhua , Gray Nathanael , Stone Richard M. , Adamia Sophia , Dubreuil Patrice , Letard Sebastien , Griffin James D.
Published: July 2019

Mutations in two type‐3 receptor tyrosine kinases (RTKs), KIT and FLT3, are common in both acute myeloid leukaemia (AML) and systemic mastocytosis (SM) and lead to hyperactivation of key signalling pathways. A large number of tyrosine kinase inhibitors (TKIs) have been developed that target either FLT3 or KIT and significant clinical benefit has been demonstrated in multiple clinical trials. Given the structural similarity of FLT3 and KIT, it is not surprising that some of these TKIs inhibit both of these receptors. This is typified by midostaurin, which has been approved by the US Food and Drug Administration for mutant FLT3‐positive AML and for KIT D816V‐positive SM. Here, we compare the in vitro activities of the clinically available FLT3 and KIT inhibitors with those of midostaurin against a panel of cells expressing a variety of oncogenic FLT3 or KIT receptors, including wild‐type (wt) FLT3, FLT3‐internal tandem duplication (ITD), FLT3 D835Y, the resistance mutant FLT3‐ITD+ F691L, KIT D816V, and KIT N822K. We also examined the effects of these inhibitors in vitro and in vivo on cells expressing mutations in c‐CBL found in AML that result in hypersensitization of RTKs, such as FLT3 and KIT. The results show a wide spectrum of activity of these various mutations to these clinically available TKIs.
Blood eosinophil count correlates with severity of respiratory failure in life‐threatening asthma and predicts risk of subsequent exacerbations
Authors: Yii Anthony C.A. , Tay Tunn‐Ren , Puah Ser Hon , Lim Hui‐Fang , Li Andrew , Lau Priscilla , Tan Raeann , Neo Lay‐Ping , Chung Kian Fan , Koh Mariko S.
Published: July 2019

Background

An elevated blood eosinophil count when asthma is stable predicts exacerbations and therapeutic response to corticosteroids or biologics targeting eosinophils. Few studies have examined the prognostic value of blood eosinophils measured at exacerbation.

Aim

To elucidate the relationship between a spot blood eosinophil count–measured at the onset of a life‐threatening asthma exacerbation–with indices of exacerbation severity and risk of subsequent exacerbations.

Methods

Real‐world, retrospective review of all life‐threatening asthma cases admitted at 4 public hospitals in Singapore between 2011‐2015. We assessed the trends and correlations between blood eosinophil count on admission with arterial blood gas values, duration of mechanical ventilation, and risk of death, hypoxic ischemic encephalopathy or respiratory arrest. Risk of future exacerbations among survivors was modelled using Cox regression and survival curves.

Results

There were 376 index life‐threatening exacerbations with median blood eosinophil count (5‐95th percentiles) of 0.270 × 109/L (0‐1.410 × 109/L). Arterial pH decreased and PCO2 increased with increasing eosinophil count. Duration of mechanical ventilation and risk of death, hypoxic ischaemic encephalopathy or respiratory arrest did not vary with eosinophils. Among 329 survivors who were followed‐up over a median of 52 months, blood eosinophils ≥1.200 × 109/L was associated with an increased hazard of emergency visits and/or admissions for asthma (hazard ratio 1.8, 95% confidence interval 1.1‐2.9, P = .02).

Conclusion

In this study of life‐threatening asthma, we found that a spot blood eosinophil count correlates with severity of respiratory failure and predicts risk of subsequent exacerbations.
Heterozygous CTNNB1 and TBX4 variants in a patient with abnormal lung growth, pulmonary hypertension, microcephaly, and spasticity
Authors: Karolak Justyna A. , Szafranski Przemyslaw , Kilner David , Patel Chirag , Scurry Bonnie , Kinning Esther , Chandler Kate , Jhangiani Shalini N. , Coban Akdemir Zeynep H. , Lupski James R. , Popek Edwina , Stankiewicz Paweł
Published: July 2019

The canonical wingless (Wnt) and fibroblast growth factor (FGF) signaling pathways involving CTNNB1 and TBX4, respectively, are crucial for the regulation of human development. Perturbations of these pathways and disruptions from biological homeostasis have been associated with abnormal morphogenesis of multiple organs, including the lung. The aim of this study was to identify the underlying genetic cause of abnormal lung growth, pulmonary hypertension (PAH), severe microcephaly, and muscle spasticity in a full‐term newborn, who died at 4 months of age due to progressively worsening PAH and respiratory failure. Family trio exome sequencing showed a de novo heterozygous nonsense c.1603C>T (p.Arg535*) variant in CTNNB1 and a paternally inherited heterozygous missense c.1198G>A (p.Glu400Lys) variant in TBX4, both predicted to be likely deleterious. We expand the phenotypic spectrum associated with CTNNB1 and TBX4 variants and indicate that they could act synergistically to produce a distinct more severe phenotype. Our findings further support a recently proposed complex compound inheritance model in lethal lung developmental diseases and the contention that dual molecular diagnoses can parsimoniously explain blended phenotypes.
Prednisone‐free maintenance immunosuppression in obese kidney transplant recipients
Authors: Matas Arthur J. , Vock David M.
Published: July 2019

Obese transplant recipients (BMI ≥ 30 kg/m2) have decreased posttransplant patient and graft survival compared with their nonobese counterparts. At the same time, many prednisone‐related side effects (eg, new‐onset diabetes) are similar to those associated with obesity. Using SRTR data, we studied outcomes associated with prednisone‐free maintenance immunosuppression (rapid discontinuation of prednisone—RDP). Between January 1, 2000, and December 31, 2014, 44 635 first transplant recipients with BMI ≥ 30 kg/m2 had a first kidney transplant (28 176 DD; 16 459, LD); 12,994 (29%) were discharged from the hospital on a prednisone‐free protocol. We compared outcomes to those discharged on a protocol incorporating maintenance prednisone (intention‐to‐treat analysis). RDP‐treated obese first DD recipients had significantly better patient survival (HR, 0.88; CI, 0.81‐0.96) and graft survival (HR, 0.93; CI, 0.88‐0.99) compared with their counterparts on maintenance immunosuppression. Although not statistically significant, the same trends were seen for LD recipients. For both DD and LD recipients, there was no difference between groups for death‐censored graft survival, suggesting that the benefit of RDP was due to improved patient survival. Our findings suggest that kidney transplant recipients with BMI ≥ 30 kg/m2 benefit from a protocol that incorporates RDP.
Differentiation between duodenal neoplasms and non‐neoplasms using magnifying narrow‐band imaging – Do we still need biopsies for duodenal lesions?
Authors: Yamasaki Yasushi , Takeuchi Yoji , Kanesaka Takashi , Kanzaki Hiromitsu , Kato Minoru , Ohmori Masayasu , Tonai Yusuke , Hamada Kenta , Matsuura Noriko , Iwatsubo Taro , Akasaka Tomofumi , Hanaoka Noboru , Higashino Koji , Uedo Noriya , Ishihara Ryu , Okada Hiroyuki , Iishi Hiroyasu
Published: July 2019

Objectives

Endoscopic biopsies for nonampullary duodenal epithelial neoplasms (NADENs) can induce submucosal fibrosis, making endoscopic resection difficult. However, no biopsy‐free method exists to distinguish between NADENs and non‐neoplasms. We developed a diagnostic algorithm for duodenal neoplasms based on magnifying endoscopy findings and evaluated the model's diagnostic ability.

Methods

Magnified endoscopic images and duodenal lesion histology were collected consecutively between January 2015 and April 2016. Diagnosticians classified the surface patterns as pit, groove or absent. In cases of nonvisible surface patterns, the vascular pattern was evaluated to determine regularity or irregularity. The correlation between our algorithm (pit‐type or absent with irregular vascular pattern) and the lesion histology were evaluated. Four evaluators, who were blinded to the histology, also classified the endoscopic findings and evaluated the diagnostic performance and interobserver agreement.

Results

Endoscopic images of 114 lesions were evaluated (70 NADENs and 44 non‐neoplasms, 31 in the superior and 83 in the descending and horizontal duodenum). Of the NADEN surface patterns, 88% (62/70) were pit‐type, while 79% (35/44) of the non‐neoplasm surface patterns were groove‐type. Our diagnostic algorithm for differentiating NADENs from non‐neoplasms was high (sensitivity 96%, specificity 95%) in the descending and horizontal duodenum. The evaluators’ diagnostic performances were also high, and interobserver agreement for the algorithm was good between each diagnostician and evaluator (κ = 0.60–0.76).

Conclusion

Diagnostic performance of our algorithm sufficiently enabled eliminating endoscopic biopsies for diagnosing the descending and horizontal duodenum.
Adaptive functional reorganization in amyotrophic lateral sclerosis: coexisting degenerative and compensatory changes
Authors: Abidi M. , de Marco G. , Couillandre A. , Feron M. , Mseddi E. , Termoz N. , Querin G. , Pradat P. ‐F. , Bede P.
Published: July 2019

Background and purpose

Considerable functional reorganization takes place in amyotrophic lateral sclerosis (ALS) in face of relentless structural degeneration. This study evaluates functional adaptation in ALS patients with lower motor neuron predominant (LMNp) and upper motor neuron predominant (UMNp) dysfunction.

Methods

Seventeen LMNp ALS patients, 14 UMNp ALS patients and 14 controls participated in a functional magnetic resonance imaging study. Study‐group‐specific activation patterns were evaluated during preparation for a motor task. Connectivity analyses were carried out using the supplementary motor area (SMA), cerebellum and striatum as seed regions and correlations were explored with clinical measures.

Results

Increased cerebellar, decreased dorsolateral prefrontal cortex and decreased SMA activation were detected in UMNp patients compared to controls. Increased cerebellar activation was also detected in UMNp patients compared to LMNp patients. UMNp patients exhibit increased effective connectivity between the cerebellum and caudate, and decreased connectivity between the SMA and caudate and between the SMA and cerebellum when performing self‐initiated movement. In UMNp patients, a positive correlation was detected between clinical variables and striato‐cerebellar connectivity.

Conclusions

Our findings indicate that, despite the dysfunction of SMA–striatal and SMA–cerebellar networks, cerebello‐striatal connectivity increases in ALS indicative of compensatory processes. The coexistence of circuits with decreased and increased connectivity suggests concomitant neurodegenerative and adaptive changes in ALS.
In situ antioxidant activity of a dermo‐cosmetic product: A randomized controlled clinical study
Authors: Ribet Virginie , Nobile Vincenzo , Rossi Ana Beatris
Published: July 2019

Ultraviolet light enhances the generation of reactive oxygen species that are responsible for skin photoageing. The aim of this randomized, vehicle‐ and active‐controlled double‐blind, intra‐individual monocentric study was to evaluate in situ the antioxidant activity of a dermo‐cosmetic product in photoaged skin. Twenty healthy volunteers had defined skin areas randomized to receive a topical product containing 3 antioxidants (pre‐tocopheryl®, retinaldehyde and glycylglycine ole‐amide), its vehicle and a positive antioxidant control cream. The products were applied daily for 30‐day period. The skin areas were exposed to a controlled dose of UVA rays, and the skin oxidative status was evaluated 4 and 24 hours post‐UVA exposure at D0 (basal value) and after 15 and 30 days of product application. Skin layers were collected by stripping, and antioxidant capacity was measured using the ferric reducing ability of a plasma assay. Lipid peroxidation (LPO) was assessed using the malonyldialdehyde test. The tested product significantly improved the skin antioxidant capacity after 15 and 30 days and significantly decreased the basal level of the skin LPO. The skin LPO level significantly decreased 4 and 24 hours after UVA exposure at 15 and 30 days. These findings were comparable to positive control treated sites and were significantly different from the vehicle and untreated sites. This minimally invasive methodology enabled a quantitative evaluation of potent antioxidant activity in situ in the stratum corneum reflecting real‐life skin conditions and confirming the benefits of the topical application of a product containing 3 antioxidants in the prevention of UVA‐induced oxidative damage.
Seborrheic dermatitis—Looking beyond Malassezia
Authors: Wikramanayake Tongyu C. , Borda Luis J. , Miteva Mariya , Paus Ralf
Published: July 2019

Seborrhoeic Dermatitis (SD) is a very common chronic and/or relapsing inflammatory skin disorder whose pathophysiology remains poorly understood. Yeast of the genus Malassezia has long been regarded as a main predisposing factor, even though causal relationship has not been firmly established. Additional predisposing factors have been described, including sebaceous activity, host immunity (especially HIV infection), epidermal barrier integrity, skin microbiota, endocrine and neurologic factors, and environmental influences. Genetic studies in humans and mouse models—with particularly interesting insights from examining the Mpzl3 knockout mice and their SD‐like skin phenotype, and patients carrying a ZNF750 mutation—highlight defects in host immunity, epidermal barrier and sebaceous activity. After synthesizing key evidence from the literature, we propose that intrinsic host factors, such as changes in the amount or composition of sebum and/or defective epidermal barrier, rather than Malassezia, may form the basis of SD pathobiology. We argue that these intrinsic changes provide favourable conditions for the commensal Malassezia to over‐colonize and elicit host inflammatory response. Aberrant host immune activity or failure to clear skin microbes may bypass the initial epidermal or sebaceous abnormalities. We delineate specific future clinical investigations, complemented by studies in suitable SD animal models, that dissect the roles of different epidermal compartments and immune components as well as their crosstalk and interactions with the skin microbiota during the process of SD. This research perspective beyond the conventional Malassezia‐centric view of SD pathogenesis is expected to enable the development of better therapeutic interventions for the management of recurrent SD.
Climate change alters elevational phenology patterns of the European spruce bark beetle (Ips typographus)
Authors: Jakoby Oliver , Lischke Heike , Wermelinger Beat
Published: July 2019

The European spruce bark beetle Ips typographus is the most important insect pest in Central European forests. Under climate change, its phenology is presumed to be changing and mass infestations becoming more likely. While several studies have investigated climate effects across a latitudinal gradient, it remains an open question how phenology will change depending on elevation and topology. Knowing how an altered climate is likely to affect bark beetle populations, particularly across diverse topographies and elevations, is essential for adaptive management. We developed a time‐varying distributed delay model to predict the phenology of I. typographus. This approach has the particular advantage of capturing the variability within populations and thus representing its stage structure at any time. The model is applied for three regional climate change scenarios, A1B, A2 and RCP3PD, to the diverse topography of Switzerland, covering a large range of elevations, aspects and slopes. We found a strong negative relationship between voltinism and elevation. Under climate change, the model predicts an increasing number of generations over the whole elevational gradient, which will be more pronounced at low elevations. In contrast, the pre‐shift in spring swarming is expected to be greater at higher elevations. In comparison, the general trend of faster beetle development on steep southern slopes is only of minor importance. Overall, the maximum elevation allowing a complete yearly generation will move upwards. Generally, the predicted increase in number of generations, earlier spring swarming, more aggregated swarming, together with a projected increase in drought and storm events, will result in a higher risk of mass infestations. This will increase the pressure on spruce stands particularly in the lowlands and require intensified management efforts. It calls for adapted long‐term silvicultural strategies to mitigate the loss of ecosystem services such as timber production protection against rockfall and avalanches and carbon storage.
Estimating aboveground net biomass change for tropical and subtropical forests: Refinement of IPCC default rates using forest plot data
Authors: Requena Suarez Daniela , Rozendaal Danaë M. A. , De Sy Veronique , Phillips Oliver L. , Alvarez‐Dávila Esteban , Anderson‐Teixeira Kristina , Araujo‐Murakami Alejandro , Arroyo Luzmila , Baker Timothy R. , Bongers Frans , Brienen Roel J. W. , Carter Sarah , Cook‐Patton Susan C. , Feldpausch Ted R. , Griscom Bronson W. , Harris Nancy , Hérault Bruno , Honorio Coronado Eurídice N. , Leavitt Sara M. , Lewis Simon L. , Marimon Beatriz S. , Monteagudo Mendoza Abel , Kassi N'dja Justin , N'Guessan Anny Estelle , Poorter Lourens , Qie Lan , Rutishauser Ervan , Sist Plinio , Sonké Bonaventure , Sullivan Martin J. P. , Vilanova Emilio , Wang Maria M. H. , Martius Christopher , Herold Martin
Published: July 2019

As countries advance in greenhouse gas (GHG) accounting for climate change mitigation, consistent estimates of aboveground net biomass change (∆AGB) are needed. Countries with limited forest monitoring capabilities in the tropics and subtropics rely on IPCC 2006 default ∆AGB rates, which are values per ecological zone, per continent. Similarly, research into forest biomass change at a large scale also makes use of these rates. IPCC 2006 default rates come from a handful of studies, provide no uncertainty indications and do not distinguish between older secondary forests and old‐growth forests. As part of the 2019 Refinement to the 2006 IPCC Guidelines for National Greenhouse Gas Inventories, we incorporate ∆AGB data available from 2006 onwards, comprising 176 chronosequences in secondary forests and 536 permanent plots in old‐growth and managed/logged forests located in 42 countries in Africa, North and South America and Asia. We generated ∆AGB rate estimates for younger secondary forests (≤20 years), older secondary forests (>20 years and up to 100 years) and old‐growth forests, and accounted for uncertainties in our estimates. In tropical rainforests, for which data availability was the highest, our ∆AGB rate estimates ranged from 3.4 (Asia) to 7.6 (Africa) Mg ha−1 year−1 in younger secondary forests, from 2.3 (North and South America) to 3.5 (Africa) Mg ha−1 year−1 in older secondary forests, and 0.7 (Asia) to 1.3 (Africa) Mg ha−1 year−1 in old‐growth forests. We provide a rigorous and traceable refinement of the IPCC 2006 default rates in tropical and subtropical ecological zones, and identify which areas require more research on ∆AGB. In this respect, this study should be considered as an important step towards quantifying the role of tropical and subtropical forests as carbon sinks with higher accuracy; our new rates can be used for large‐scale GHG accounting by governmental bodies, nongovernmental organizations and in scientific research.
Preparation and identification of angiotensin I‐converting enzyme inhibitory peptides from sweet potato protein by enzymatic hydrolysis under high hydrostatic pressure
Authors: Nazir Muhammad Amer , Mu Tai‐Hua , Zhang Miao
Published: July 2019

Sweet potato protein hydrolysates (SPPH) with angiotensin I‐converting enzyme (ACE) inhibitory activity were prepared by papain, pepsin and alcalase under high hydrostatic pressure (HHP, 100–300 MPa). HHP significantly increased degree of hydrolysis (DH), nitrogen recovery (NR) and molecular weight (MW) <3 kDa fractions contents of SPPH by all three enzymes (P < 0.05). MW < 3 kDa peptide fractions from SPPH by alcalase under 100 MPa showed the highest ACE inhibitory activity (IC50 value 32.24 µg mL−1), and was subjected to purification and identification by semi‐preparative RP‐HPLC and LC‐MS/MS. Fifty‐four peptides ranged from 501.28 to 1958.88 Da with 5–18 amino acids were identified and matched sporamin A and B sequences. Five identified peptides with sequences of VSAIW, AIWGA, FVIKP, VVMPSTF and FHDPMLR displayed good ACE inhibitory activity with the contribution of Val, Trp, Phe and Arg. Thus, SPPH by enzymatic hydrolysis under HHP can be potentially used in functional food.
Risks of interstitial cystitis among patients with systemic lupus erythematosus: A population‐based cohort study
Authors: Wen Jen‐Yu , Lo Tsia‐Shu , Chuang Yao‐Chi , Ho Chung‐Han , Long Cheng‐Yu , Law Kim‐Seng , Tong Yat‐Ching , Wu Ming‐Ping
Published: July 2019

Objective

To investigate whether the risk of interstitial cystitis increases among the patients with systemic lupus erythematosus.

Methods

This was a nationwide population‐based cohort study. Data were obtained from the National Health Insurance Research Database in Taiwan. Women aged >18 years newly diagnosed as systemic lupus erythematosus during 2001–2008 were identified as the control group. The comparison included individuals randomly selected from the National Health Insurance Research Database in the year of 2000, by matching one systemic lupus erythematosus participant with eight non‐systemic lupus erythematosus participants with sex and age. These participants were followed up until being diagnosed as interstitial cystitis, or the end of 2011. Women diagnosed with lupus cystitis were excluded from this study.

Results

This study included 7240 women with systemic lupus erythematosus and 57 920 women without systemic lupus erythematosus as controls. The incidence rate of interstitial cystitis was significantly higher in the systemic lupus erythematosus group, with an incidence rate ratio of 2.26 (95% confidence interval 1.57–3.27, P < 0.0001). After adjustment, the risk increased by 2.45‐fold (adjusted hazard ratio 2.45, 95% confidence interval 1.57–3.27, P < 0.05). Age as a factor increases incidence rate ratios among all age groups, 2.12‐, 3.32‐ and 4.65‐fold. Age ≥45 years had an increased adjusted hazard ratio (2.07, 95% confidence interval 1.37–3.13, P < 0.05). Comorbidities, for example, hypertension, diabetes mellitus, dyslipidemia and renal disease, were insignificant.

Conclusions

This is the first population‐based cohort study showing a higher incidence of interstitial cystitis among patients with systemic lupus erythematosus. These findings support the concordance of interstitial cystitis with autoimmune diseases, and the temporal relationship to develop interstitial cystitis in patients with systemic lupus erythematosus.
Linguistic Constraints on Statistical Computations
Authors: Bonatti Luca L. , Peña Marcela , Nespor Marina , Mehler Jacques
Published: July 2019

Speech is produced mainly in continuous streams containing several words. Listeners can use the transitional probability (TP) between adjacent and non-adjacent syllables to segment “words” from a continuous stream of artificial speech, much as they use TPs to organize a variety of perceptual continua. It is thus possible that a general-purpose statistical device exploits any speech unit to achieve segmentation of speech streams. Alternatively, language may limit what representations are open to statistical investigation according to their specific linguistic role. In this article, we focus on vowels and consonants in continuous speech. We hypothesized that vowels and consonants in words carry different kinds of information, the latter being more tied to word identification and the former to grammar. We thus predicted that in a word identification task involving continuous speech, learners would track TPs among consonants, but not among vowels. Our results show a preferential role for consonants in word identification.
Nutritional and mineral content of prickly pear cactus: A highly water‐use efficient forage, fodder and food species
Authors: Mayer Jesse A. , Cushman John C.
Published: July 2019

Increased demand for food requires us to investigate livestock forage and fodder crops that can be grown over a wide range of locations where their cultivation will not compete with that of the food supply. A large portion of the southwestern United States consists of underutilized semi‐arid land. Crops typically used for livestock fodder or forage have high‐water demands that make them uneconomical or unsustainable for semi‐arid and arid regions. The growth rate and low‐input requirements of prickly pear cactus (Opuntia ficus‐indica) make it an excellent candidate for forage or fodder supplementation or replacement in these regions. Previous reports about forage quality data on Opuntia have been scattered across multiple locations, growing conditions and cultivars. Here, we report on the forage quality and mineral content of Opuntia ficus‐indica grown under both field and greenhouse conditions. Crude protein was 71 and 264 g/kg of dry mass for field and greenhouse conditions, respectively. Field‐grown plants showed higher acid and neutral detergent fibre content than greenhouse‐grown plants reflecting higher cellulose, hemicellulose and lignin accumulation. Nutritional values were also compared to requirements of cattle to determine what deficiencies might need to be addressed through supplementation. These data suggest that Opuntia can be used in combination with other feed sources to reduce the demand of resource‐intensive forage crops for raising livestock in dryland areas.