bluuebunny/crossref_metadata_2025 huggingface dataset:
Plant species richness negatively affects root decomposition in grasslands
Authors: Chen Hongmei , Mommer Liesje , van Ruijven Jasper , de Kroon Hans , Fischer Christine , Gessler Arthur , Hildebrandt Anke , Scherer‐Lorenzen Michael , Wirth Christian , Weigelt Alexandra
Published: August 2016

Plant diversity enhances many ecosystem functions, including root biomass production, which drives soil carbon input. Although root decomposition accounts for a large proportion of carbon input for soil, little is known about plant diversity effect on this process. Plant diversity may affect root decomposition in two non‐exclusive ways: by providing roots of different substrate quality (e.g. root chemistry) and/or by altering the soil environment (e.g. microclimate).

To disentangle these two pathways, we conducted three decomposition experiments using a litter‐bag approach in a grassland biodiversity experiment. We hypothesized that: (i) plant species richness negatively affects substrate quality (indicated by increased C:N ratios), which we tested by decomposing roots collected from each experimental plot in one common plot; (ii) plant species richness positively affects soil environment (indicated by increased soil water content), which we tested by decomposing standardized roots in all experimental plots; (iii) the overall effect of plant species richness on root decomposition, due to the contrast between quality and environmental effects, is neutral, which we tested by decomposing community roots in their ‘home’ plots.

Plant species richness negatively affected root decomposition in all three experiments. The negative effect of plant species richness on substrate quality was largely explained by increased root C:N ratios along the diversity gradient. Functional group presence explained more variance in substrate quality than species richness. Here, the presence of grasses negatively affected substrate quality and root C:N ratios, while the presence of legumes and small herbs had positive effects. Plant species richness had a negative effect on soil environment despite its positive effect on soil water content which is known to stimulate decomposition. We argue that – instead of soil water content – a combined effect of soil temperature and seasonality might drive environmental effect of plant diversity on decomposition in our plant communities, but this remains to be tested.

Synthesis. Our results demonstrate that both substrate quality and soil environment contribute to the net negative effect of plant diversity on root decomposition. This study promotes our mechanistic understanding of increased soil carbon accumulation in more diverse grassland plant communities.
Characterization of the Bread Made with Durum Wheat Semolina Rendered Gluten Free by Sourdough Biotechnology in Comparison with Commercial Gluten‐Free Products
Authors: Rizzello Carlo Giuseppe , Montemurro Marco , Gobbetti Marco
Published: August 2016

Durum wheat semolina was fermented with sourdough lactic acid bacteria and fungal proteases aiming at a complete gluten hydrolysis. The gluten‐free (GF) semolina, added with naturally GF ingredients and structuring agents, was used to produce bread (rendered GF bread; rGFB) at industrial level. An integrated approach including the characterization of the main chemical, nutritional, structural, and sensory features was used to compare rGFB to a gluten‐containing bread and to 5 commercial naturally GF breads. High‐performance liquid chromatography was used for free amino acids (FAAs), organic acids, and ethanol analysis. A methanolic extract was used for determining total phenols and antioxidant activity. The bread characterization also included the analysis of dietary fibers, mycotoxins, vitamins, and heavy metals. Beyond chemical analysis, nutritional profile was evaluated considering the in vitro protein digestibility and the predicted glycemic index, while the instrumental texture profile analysis was performed to investigate the structure and the physical/mechanical properties of the baked goods. Beyond the huge potential of market expansion, the main advantages of durum wheat semolina rendered GF can be resumed in the high availability of FAAs, the high protein digestibility, the low starch hydrolysis index, and the better technological properties of bread compared to the commercial GF products currently present on the market. Vitamins, minerals, and dietary fiber profiles are comparable to those of gluten‐containing wheat bread. Also the sensory profile, determined by a panel test, can be considered the most similar to those of conventional baked goods, showing all the sourdough bread classic attributes.
Randomized trial assessing the safety and efficacy of sitagliptin in Chinese patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea alone or combined with metformin
Authors: Ba Jianming , Han Ping , Yuan Guoyue , Mo Zhaohui , Pan Changyu , Wu Fan , Xu Lei , Hanson Mary E. , Engel Samuel S. , Shankar R. Ravi
Published: August 2016

Background

Type 2 diabetes mellitus (T2DM) is a significant burden in China, where approximately 114 million patients have been diagnosed with diabetes. Chinese patients present with prominent β‐cell failure, with resulting deficiency in insulin secretion, particularly early phase insulin secretion leading to postprandial hyperglycemia. Sitagliptin, a selective once‐daily oral dipeptidyl peptidase‐4 inhibitor, has been shown to improve glycemic control as monotherapy and in combination with other antihyperglycemic agents, including sulfonylureas and metformin.

Methods

This was a multicenter randomized double‐blind placebo‐controlled study conducted in China. The study assessed the safety and efficacy of the addition of sitagliptin 100 mg once daily versus placebo on changes from baseline at Week 24 in HbA1c, fasting plasma glucose (FPG) and 2‐h post‐meal glucose (PMG). Patients were aged 18–79 years, had T2DM with inadequate glycemic control, and were taking a sulfonylurea, with or without metformin.

Results

After 24 weeks, sitagliptin reduced HbA1c, FPG, and 2‐h PMG significantly more than placebo (between‐treatment differences: −0.61 %, −16.8 mg/dL, and −32.9 mg/dL, respectively; P < 0.001 for all). The addition of sitagliptin was generally well tolerated, with a comparable incidence of adverse events and drug‐related adverse events in both treatment groups. The sitagliptin group had a higher incidence of symptomatic hypoglycemia than the placebo group (25/248 [10.1 %] vs 13/249 [5.2 %], respectively; P = 0.042).

Conclusions

Sitagliptin 100 mg once daily significantly improved glycemic control in Chinese patients with T2DM who had inadequate glycemic control with sulfonylurea, with or without metformin therapy. The addition of sitagliptin was generally well tolerated. (clinicaltrials.gov: NCT01590771).
High‐throughput microsatellite genotyping in ecology: improved accuracy, efficiency, standardization and success with low‐quantity and degraded DNA
Authors: De Barba M. , Miquel C. , Lobréaux S. , Quenette P. Y. , Swenson J. E. , Taberlet P.
Published: August 2016

Microsatellite markers have played a major role in ecological, evolutionary and conservation research during the past 20 years. However, technical constrains related to the use of capillary electrophoresis and a recent technological revolution that has impacted other marker types have brought to question the continued use of microsatellites for certain applications. We present a study for improving microsatellite genotyping in ecology using high‐throughput sequencing (HTS). This approach entails selection of short markers suitable for HTS, sequencing PCR‐amplified microsatellites on an Illumina platform and bioinformatic treatment of the sequence data to obtain multilocus genotypes. It takes advantage of the fact that HTS gives direct access to microsatellite sequences, allowing unambiguous allele identification and enabling automation of the genotyping process through bioinformatics. In addition, the massive parallel sequencing abilities expand the information content of single experimental runs far beyond capillary electrophoresis. We illustrated the method by genotyping brown bear samples amplified with a multiplex PCR of 13 new microsatellite markers and a sex marker. HTS of microsatellites provided accurate individual identification and parentage assignment and resulted in a significant improvement of genotyping success (84%) of faecal degraded DNA and costs reduction compared to capillary electrophoresis. The HTS approach holds vast potential for improving success, accuracy, efficiency and standardization of microsatellite genotyping in ecological and conservation applications, especially those that rely on profiling of low‐quantity/quality DNA and on the construction of genetic databases. We discuss and give perspectives for the implementation of the method in the light of the challenges encountered in wildlife studies.
Diagnostic accuracy of Japanese posttraumatic stress measures after a complex disaster: The Fukushima Health Management Survey
Authors: Suzuki Yuriko , Yabe Hirooki , Horikoshi Naoko , Yasumura Seiji , Kawakami Norito , Ohtsuru Akira , Mashiko Hirobumi , Maeda Masaharu ,   on behalf of the Mental Health Group of the Fukushima Health Management Survey
Published: August 2016

Background

The Posttraumatic Stress Disorder (PTSD) Checklist (PCL) has been widely used among traumatized populations to screen people with PTSD; however, the Japanese version of the PCL has yet to be validated. We examined the diagnostic accuracy of the Japanese version PCL‐Specific (PCL‐S) and the abbreviated versions of the PCL‐S among the evacuees of the Fukushima Daiichi Nuclear Power Plant accident.

Methods

Fifty‐one participants were recruited from an evacuee and clinical sample. The PCL‐S, Impact of Event Scale‐Revised (IES‐R), and World Health Organization Composite International Diagnostic Interview were administered. Screening properties of the PCL‐S, IES‐R, and abbreviated PCL‐S against PTSD diagnosis, including sensitivity, specificity, and diagnostic efficiency, were calculated. Receiver operating characteristic curves were drawn, and optimal cutoff points were examined.

Results

The sensitivity, specificity, and diagnostic efficiency of the PCL‐S were 66.7%, 84.9%, and 79.2%, respectively (at 52, the area under the curve was 0.83). The cutoff point method for the PCL‐S performed better than did the symptom cluster method. The screening properties of the abbreviated versions were comparable with those of the full version.

Conclusions

The Japanese version of the PCL‐S showed moderate diagnostic accuracy and improved performance over the IES‐R for PTSD diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. The Japanese version of the PCL‐S was a reliable and valid measure, and its diagnostic accuracy was reasonable for both full and abbreviated versions.
HEDGING AND THE COMPETITIVE FIRM UNDER AMBIGUOUS PRICE AND BACKGROUND RISK
Authors: Osaki Yusuke , Wong Kit Pong , Yi Long
Published: August 2016

This paper examines the optimal production and hedging decisions of the competitive firm that possesses smooth ambiguity preferences and faces ambiguous price and background risk. The separation theorem holds in that the firm's optimal output level depends neither on the firm's attitude towards ambiguity nor on the incident to the underlying ambiguity. We derive necessary and sufficient conditions under which the full‐hedging theorem holds and thus options are not used. When these conditions are violated, we show that the firm optimally uses options for hedging purposes if ambiguity is introduced to the price and background risk by means of mean‐preserving spreads. We as such show that options play a role as a hedging instrument over and above that of futures.
Cognitive Flexibility in Young Children: Beyond Perseveration
Authors: Carroll Daniel J. , Blakey Emma , FitzGibbon Lily
Published: August 2016

Cognitive flexibility (CF) is the ability to rapidly adjust our thoughts and behaviors in response to changes around us. Although studies of preschoolers have contributed to our understanding of how this ability emerges, progress has slowed in recent years because of methodological and conceptual issues. In this article, we outline recent developments that address these issues and that have led to a more nuanced understanding of CF—particularly regarding the role of perseveration. We propose that CF is a diverse and multifaceted skill that involves more than just overcoming perseverative errors.
Weight gain in insulin‐treated patients by body mass index category at treatment initiation: new evidence from real‐world data in patients with type 2 diabetes
Authors: Paul S. K. , Shaw J. E. , Montvida O. , Klein K.
Published: August 2016

Aims

To evaluate, in patients with type 2 diabetes (T2DM) treated with insulin, the extent of weight gain over 2 years of insulin treatment, and the dynamics of weight gain in relation to glycaemic achievements over time according to adiposity levels at insulin initiation.

Materials and methods

Patients with T2DM (n = 155 917), who commenced insulin therapy and continued it for at least 6 months, were selected from a large database of electronic medical records in the USA. Longitudinal changes in body weight and glycated haemoglobin (HbA1c) according to body mass index (BMI) category were estimated.

Results

Patients had a mean age of 59 years, a mean HbA1c level of 9.5%, and a mean BMI of 35 kg/m2 at insulin initiation. The HbA1c levels at insulin initiation were significantly lower (9.2‐9.4%) in the obese patients than in patients with normal body weight (10.0%); however, the proportions of patients with HbA1c >7.5% or >8.0% were similar across the BMI categories. The adjusted weight gain fell progressively with increasing baseline BMI category over 6, 12 and 24 months (p < .01). The adjusted changes in HbA1c were similar across BMI categories. A 1% decrease in HbA1c was associated with progressively less weight gain as pretreatment BMI rose, ranging from a 1.24 kg gain in those with a BMI <25 kg/m2 to a 0.32 kg loss in those with a BMI > 40 kg/m2.

Conclusions

During 24 months of insulin treatment, obese patients gained significantly less body weight than normal‐weight and overweight patients, while achieving clinically similar glycaemic benefits. These data provide reassurance with regard to the use of insulin in obese patients.
Gender and Disability in Male‐Dominated Occupations: A Social Relational Model
Authors: Sang Katherine J.C. , Richards James , Marks Abigail
Published: August 2016

Evidence from male‐dominated sectors points to high levels of disability and the disabling nature of working environments. However, research of this nature assumes a medical model of disability that does not account for the social construction of disability or the lived experiences of disabled employees. Using data from seven focus groups (n = 44) and semi‐structured interviews with professional transport employees with life‐long hidden ‘impairments’, including dyslexia, dyscalculia, dyspraxia, ADD/ADHD and Asperger syndrome (n = 22), this paper explores the lived experiences of men and women working in a sector traditionally dominated by men, the transport industry. Key themes include homosociality, public–private divide and the impact of changing work practices. Further, the data revealed how those with hidden ‘impairments’ in part construct their identities in relation to both non‐disabled colleagues and those considered stereotypically representing disability (wheelchair users). This study furthers understandings of the relationality of gender and disability in the workplace, and the lived experiences of disabled employees.
Training as a social purpose: are economic and social benefits delivered?
Authors: Butler Allan , Lobley Matt
Published: August 2016

This paper reports original research which measures the social and economic impact of training and skills development on individuals who participated in training provided by social purpose, nonprofit organizations. An implicit policy assumption is that such organizations contribute to social and economic regeneration. Examining the costs and benefits of training to trainees, an adapted Return on Investment methodology measures any economic benefit, while an Index of Social Benefit measures changes in individual well‐being. The results demonstrate that while changes to both the economic and social well‐being of trainees occur, it does not necessarily relate solely to the training they received. Instead, changes reflect other, often complex, aspects of trainees’ lives, although training may facilitate change. Furthermore, social purpose, nonprofit organizations need to evince the socioeconomic benefits of their training programmes to secure future funding, public or private, but proving their successful delivery may be difficult to determine.
Interactions of two odorant‐binding proteins influence insect chemoreception
Authors: Sun X. , Zeng F.‐F. , Yan M.‐J. , Zhang A. , Lu Z.‐X. , Wang M.‐Q.
Published: August 2016

It is well known that the odorant‐binding proteins (OBPs) play crucial roles in insect olfactory detection. To explore if interactions of OBPs affect olfactory coding in the rice leaffolder Cnaphalocrocis medinalis ligand‐binding experiments, molecular docking, RNA interference and electrophysiological recording were performed. The binding activity of two C. medinalis OBPs (CmedOBPs) to rice plant volatiles showed wide flexibility depending on the structure of ligands and interactions of CmedOBPs involved. The binding sites of CmedOBP2 and CmedOBP3 to rice plant volatiles were well predicted by three‐dimensional structure modelling and molecular docking experiments. In addition, the interactions of these two CmedOBPs in the perception of rice volatiles were demonstrated by RNA interference experiments. When a single double‐stranded RNA (dsRNA)‐CmedOBP2 was injected, the expression of CmedOBP2 was significantly reduced and the expression of CmedOBP3 was significantly increased, and vice versa. When both dsRNA‐CmedOBP2 and 3 were injected together, greater reduction of electroantennogram responses to rice plant volatiles was induced than that seen with individual injection of either dsRNA‐CmedOBP2 or dsRNA‐CmedOBP3. These results clearly indicate that the interactions of CmedOBP2 and CmedOBP3 have significant effects on C. medinalis during the detection of host plant volatiles.
Raising a Child with Respect
Authors: Richards Norvin
Published: August 2016

Parents whose children will become adults are expected to help them do so, as opposed to only keeping them alive while they manage it on their own. The parental help must respect the child's standing as a separate individual: our children aren't ours to shape to our design, even if our aim is to help them flourish. But then how are we to raise our children with respect for their individuality?

According to Matthew Clayton, doing so requires refraining from attempting to provide our child with any values that reasonable persons would dispute. According to Harry Brighouse and Adam Swift, it doesn't require that: parents have a right to try to instil values, including disputable ones, because they must have this right if families are to enjoy ‘family relationship goods’. I argue against Clayton's position, and against Brighouse and Swift's. I introduce a different approach, and flesh it out in light of a difficulty it faces. I then return to the initial problem, identifying some ways in which the approach I've offered explains how to raise one's child with respect.
MicroRNA‐203 mimics age‐related aortic smooth muscle dysfunction of cytoskeletal pathways
Authors: Nicholson Christopher J. , Seta Francesca , Lee Sophie , Morgan Kathleen G.
Published: August 2016

Increased aortic stiffness is a biomarker for subsequent adverse cardiovascular events. We have previously reported that vascular smooth muscle Src‐dependent cytoskeletal remodelling, which contributes to aortic plasticity, is impaired with ageing. Here, we use a multi‐scale approach to determine the molecular mechanisms behind defective Src‐dependent signalling in an aged C57BL/6 male mouse model. Increased aortic stiffness, as measured in vivo by pulse wave velocity, was found to have a comparable time course to that in humans. Bioinformatic analyses predicted several miRs to regulate Src‐dependent cytoskeletal remodelling. qRT‐PCR was used to determine the relative levels of predicted miRs in aortas and, notably, the expression of miR‐203 increased almost twofold in aged aorta. Increased miR‐203 expression was associated with a decrease in both mRNA and protein expression of Src, caveolin‐1 and paxillin in aged aorta. Probing with phospho‐specific antibodies confirmed that overexpression of miR‐203 significantly attenuated Src and extracellular signal regulated kinase (ERK) signalling, which we have previously found to regulate vascular smooth muscle stiffness. In addition, transfection of miR‐203 into aortic tissue from young mice increased phenylephrine‐induced aortic stiffness ex vivo, mimicking the aged phenotype. Upstream of miR‐203, we found that DNA methyltransferases (DNMT) 1, 3a, and 3b are also significantly decreased in the aged mouse aorta and that DNMT inhibition significantly increases miR‐203 expression. Thus, the age‐induced increase in miR‐203 may be caused by epigenetic promoter hypomethylation in the aorta. These findings indicate that miR‐203 promotes a re‐programming of Src/ERK signalling pathways in vascular smooth muscle, impairing the regulation of stiffness in aged aorta.
Nuclear Power and the Mob: Extortion in Japan
Authors: Ramseyer J. Mark
Published: August 2016

Nuclear reactors entail massive nontransferrable site‐specific investments. The resulting appropriable quasi‐rents offer the mob a lucrative target. In exchange for large fees, it can either promise to “protect” the utility (and silence the reactor's local opponents) or “extort” from it (and desist from inciting those opponents). Using prefecture‐level Japanese panel data covering the years 1980 to 2010, I find that extortion rates rise when a utility announces plans to build a reactor. The evidence is consistent with a straightforward account: once news about a utility's plans to build a new reactor leaks, the mob moves in to appropriate the large quasi‐rents from the utility, and stays to do what it does everywhere else—extort regular payments from local businesses.
Isolation, identification and characterisation of ballan wrasse Labrus bergylta plasma pigment
Authors: Clark W. , Leclercq E. , Migaud H. , Nairn J. , Davie A.
Published: August 2016

This study confirmed that observations of blue‐green colouration in plasma fractions of the ballan wrasse Labrus bergylta were caused by the linear tetra‐pyrrole biliverdin and that the molecule was of the physiologically relevant IXα isomer. Accumulation appears driven by chromogenic association with an unknown protein moiety which precludes enzymatic reduction and would suggest active management. It was demonstrated that the pigment did not fluctuate relative to ontogeny, or indeed binary gender in the species of interest, but mobilisation and depletion in the subset of individuals undergoing sex change at the time of study supports a potential association with gender inversion processes. It is of note that although biliverdin does have some effect on external colouration, the evidence is indicative that crypsis is a supplementary function thus other factors must be considered.
Comparative analyses within Gyrodactylus (Platyhelminthes: Monogenea) mitochondrial genomes and conserved polymerase chain reaction primers for gyrodactylid mitochondrial DNA
Authors: Ye F , Easy R H , King S D , Cone D K , You P
Published: August 2016

In this study, we describe the complete mitochondrial genomes of Gyrodactylus brachymystacis and Gyrodactylus parvae infecting rainbow trout (Oncorhynchus mykiss) and the invasive topmouth gudgeon (Pseudorasbora parva), respectively. The two circular genomes have a common genome organization found in other Gyrodactylus species. Comparative analyses of mitochondrial genomes from six Gyrodactylus species were carried out to determine base composition, codon usage, transfer RNA and ribosomal RNA genes, major non‐coding regions, and nucleotide diversity within the genus. We also provide the first universal models of the secondary structures of rrnS and rrnL for this group thereby promoting utilization of these genetic markers. Universal primers provided herein can be used to obtain more mitochondrial information for pathogen identification and may reveal different levels of molecular phylogenetic inferences for this lineage.
Microwave dehydration of apple fruit: Investigation of drying efficiency and energy costs
Authors: Hazervazifeh Amin , Moghaddam Parviz A. , Nikbakht Ali M.
Published: August 2016

The main incentive in processing fruits such as apple is reduction of losses and gaining added value. In this research, drying kinetics and drying efficiency of Golden Delicious apple slices are investigated using hot air flow and uniform microwave drying. Microwave power levels, 500, 1,000, 1,500, and 2,000 W, air temperatures, 40, 50, 60, and 70°C and air velocities, 0.5, 1, 1.5, and 2 ms−1 were selected. Results revealed that microwave dehydration is highly time‐efficient with 80% reduction of processing time, compared to hot air method. Highest value of drying efficiency was found in microwave method and it was reduced by 99% in the case of hot air drying. Energy costs to cover the drying process were decreased by 60% when the microwave method was used. Technically speaking, microwave drying resolves insufficiency of hot air method along with a significant enhancement of drying rate, drying efficiency and energy economy.

Practical applications

Drying of agricultural commodities is known as a main challenge in the processing industry regarding the waste reduction, longer shelf time, easier transportation, and storage. The main technique in this regard is currently hot air convection method which suffers energy consumption and surface hardening. Reduction of drying time and energy consumption with simultaneous enhancement of drying efficiency and energy economy are well known features in modern drying technologies such as microwave method. However, microwave systems are rarely utilized in industry, because of lack of operating information and high‐tech hardware issues. Application of microwave technology in dehydration of apple fruits can result in significant improvement in the processing economy. Volumetric and uniform heating as the primary benefit of microwave drying can be mentioned as an undeniable incentive to producers, processors and industrialists. Additionally, investigation of kinetics of drying is the first step for dryer design or scale‐up.
Characterization of fibrosis changes in chronic hepatitis C patients after virological cure: A systematic review with meta‐analysis
Authors: Liu Zhipeng , Wei Xuewu , Chen Ting , Huang Chuhong , Liu Haiyan , Wang Yan
Published: August 2016

Background and Aim

Virological cure becomes available for most patients with chronic hepatitis C (CHC), but residual fibrosis can be an independent risk factor for liver‐related complications. We aimed to characterize fibrosis change in CHC patients achieved virological cure.

Methods

We did a systematic literature search for studies that had pre and post‐treatment evaluations of histologic fibrosis in CHC patients with sustained virological response (SVR). We identified the association of SVR with the incidence, extent, and velocity of fibrosis change.

Results

Overall, 3243 patients were included. Interferon‐based regimens were used for all the patients, achieving a median SVR prevalence of 36.2%. Biopsy interval ranged from 1 to 10 years. Mean baseline fibrosis score (METAVIR) was 2.3 points. Compared with non‐SVR patients, SVR patients could have higher incidence of fibrosis regression (35.1% vs 17.0%; OR: 3.3; P < 0.001), regardless of baseline fibrosis severity, way of biopsy evaluation, treatment regimen, or study design, and could have more extent of reduction (−0.31 points vs −0.00 points; P = 0.004). Baseline advanced fibrosis (F > 2) was associated with more rapid regression in both SVR and non‐SVR patients (P < 0.05 for both). SVR patients could have lower incidence of fibrosis progression and maintenance than non‐SVR patients by 4.8% versus 23.1% (OR: 0.20; P = 0.008) and 42.9% versus 55.2% (OR: 0.53; P < 0.001), respectively.

Conclusions

There could be a favorable characteristic of fibrosis regression in SVR patients. However, residential fibrosis may remain an issue because of a non‐ignorable prevalence of fibrosis maintenance among these patients.
Evaluation of transient elastography in assessing liver fibrosis in patients with autoimmune hepatitis
Authors: Xu Qinyu , Sheng Li , Bao Han , Chen Xiaoyu , Guo Canjie , Li Hai , Ma Xiong , Qiu Dekai , Hua Jing
Published: August 2016

Background and Aim

Transient elastography (TE) can reliably stage liver fibrosis via liver stiffness measurement (LSM) in chronic liver disease. However, the accuracy of TE for assessment of liver fibrosis in patients with autoimmune hepatitis (AIH) is still limited. We evaluate TE in staging liver fibrosis in AIH patients and compare with other noninvasive diagnostic tools.

Methods

A total of 100 patients with biopsy‐proven AIH were included. The correlation between LSM and fibrosis stage was analyzed using Spearman correlation test. The optimal cut‐off values of LSM were calculated for predicting individual fibrosis stages using receiver‐operating characteristic curve. The diagnostic accuracy of LSM for severe fibrosis was compared with those of serum biochemical scores.

Results

Median LSM in AIH patients was higher than that of healthy controls (11.2 ± 8.2 kPa vs 4.3 ± 1.4 kPa, P < 0.01). LSM had significant correlation with fibrosis (r = 0.752, P < 0.01) and increased progressively with increasing fibrosis stages in AIH patients. AUROC values of LSM for stages F ≥ 2, F ≥ 3, and F4 were 0.878 (95%CI: 0.789–0.967), 0.883 (0.820–0.946), and 0.914 (0.852–0.976), respectively. The optimal cut‐off values of LSM for fibrosis stages F ≥ 2, F ≥ 3, and F4 were 6.45, 8.75, and 12.50 kPa, respectively. LSM was superior to APRI score and FIB‐4 score in detecting severe fibrosis (F ≥ 3). Serum ALT levels had minor effect on LSM values.

Conclusions

Transient elastography is an accurate and reliable noninvasive tool in assessing liver fibrosis in AIH. Hepatic inflammatory activity had no significant effect on LSM determination.
Randomized clinical trial comparing 10‐ or 14‐day sequential therapy and 10‐ or 14‐day concomitant therapy for the first line empirical treatment of Helicobacter pylori infection
Authors: Park Sung Min , Kim Joon Sung , Kim Byung‐Wook , Ji Jeong‐Seon , Choi Hwang
Published: August 2016

Background and Aim

Whether concomitant therapy is superior to sequential therapy (ST) as first‐line therapy of Helicobacter pylori in areas with high clarithromycin resistance remains controversial. The aim of this study was to compare the efficacy and tolerability of 10‐ or 14‐day ST with 10‐ or 14‐day concomitant therapy (CT).

Methods

This was a prospective randomized study comparing 10‐ or 14‐day ST with 10‐ or 14‐day CT. The ST‐10 and ST‐14 groups received pantoprazole 40 mg and amoxicillin 1 g twice a day for the first 5 and 7 days followed by pantoprazole 40 mg, clarithromycin 500 mg, and metronidazole 500 mg twice a day for the remaining 5 and 7 days, respectively. The CT‐10 and CT‐14 groups received pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 and 14 days, respectively.

Results

Three hundred forty‐one patients were randomly allocated to the four groups. The modified intention‐to‐treat eradication rates of ST‐10, ST‐14, CT‐10, and CT‐14 were 91.7%, 91.2%, 94.2%, and 98.5%, respectively. The corresponding per protocol eradication rates were 91.4%, 91.0%, 95.6%, and 98.5%. There was no difference in compliance and adverse events in the four groups. Eradication rates increased sequentially with statistical significance in the following order: ST‐10, ST‐14, CT‐10, and CT‐14 (P = 0.044).

Conclusions

All four regimens achieved eradication rates >90% in per protocol analyses in a country with high clarithromycin resistance. There was no difference in tolerability among the four regimens.
Frontotemporal dementia: from molecular mechanisms to therapy
Authors: Haass Christian , Neumann Manuela
Published: August 2016

Frontotemporal dementia (FTD) is a heterogeneous clinical syndrome characterized by frontotemporal lobar degeneration (FTLD). Neuropathologically, FTLD is characterized by abnormal protein deposits and almost all cases can now be classified into three major molecular subgroups based on specific accumulating proteins with the most common being FTLD‐tau and FTLD‐TDP (accounting for ~40% and 50%, respectively) and FTLD‐FET (accounting for ~5–10%). In this special issue, the molecular and genetic basics as well as clinical approaches and therapeutics are reviewed in a series of articles.

image

This article is part of the Frontotemporal Dementia special issue.
A Review of Factors Influencing Maturation of Atlantic Salmon, Salmo salar, with Focus on Water Recirculation Aquaculture System Environments
Authors: Good Christopher , Davidson John
Published: August 2016

Sexual maturation of Atlantic salmon, Salmo salar, is a complex process, with many variables having the capacity to influence the timing and prevalence of maturation and acting as promoters and/or inhibitors of sexual development. Precocious maturation has the capacity to seriously impact production in commercial aquaculture settings, and in response there has been a significant amount of research devoted to understanding this issue in order to develop remedial strategies. Very little research has been conducted specifically examining salmon maturation in land‐based, closed containment water recirculation aquaculture systems, which have recently received attention as an alternative technology for the sustainable production of market‐size Atlantic salmon. Unfortunately, the nascent closed containment salmon industry has thus far experienced high levels of precocious maturation, for reasons that are presently unclear. Given the economic challenges facing the closed containment industry's expansion, it is imperative that best management practices be developed to reduce economic losses from early maturation, in order to assist the sustainable growth of farmed Atlantic salmon production. This review provides a brief summary of published research on factors associated with early salmonid maturation, as well as information from research examining maturation and growout performance of Atlantic salmon in closed containment aquaculture systems.
Initiation time of renal replacement therapy on patients with acute kidney injury: A systematic review and meta‐analysis of 8179 participants
Authors: Wang Caixia , Lv Lin‐Sheng , Huang Hui , Guan Jianqiang , Ye Zengchun , Li Shaomin , Wang Yanni , Lou Tanqi , Liu Xun
Published: August 2016

The early initiation of renal replacement therapy has been recommended for patients with acute renal failure by some studies, but its effects on mortality and renal recovery are unknown. We conducted an updated meta‐analysis to provide quantitative evaluations of the association between the early initiation of renal replacement therapy and mortality for patients with acute kidney injury. After applying inclusion/exclusion criteria, 51 studies, including 10 randomized controlled trials, with a total of 8179 patients were analyzed. Analysis of the included trials showed that patients receiving early renal replacement therapy had a 25% reduction in all‐cause mortality compared to those receiving late renal replacement therapy (risk ratio [RR] 0.75, 95% CI [0.69, 0.82]). We also noted a 30% increase in renal recovery (RR 1.30, 95% CI [1.07, 1.56]), a reduction in hospitalization of 5.84 days (mean difference [MD], 95% CI [–10.27, –1.41]) and a reduction in the duration of mechanical ventilation of 2.33 days (MD, 95% CI [–3.40, –1.26]) in patients assigned to early renal replacement therapy. The early initiation of renal replacement therapy was associated with a decreased risk of all‐cause mortality compared with the late initiation of RRT in patients with acute kidney injury. These findings should be interpreted with caution given the heterogeneity between studies. Further studies are needed to identify the causes of mortality and to assess whether mortality differs by dialysis dose.
Multi‐inhibitor prodrug constructs for simultaneous delivery of anti‐inflammatory agents to mustard‐induced skin injury
Authors: Lacey Carl J. , Wohlman Irene , Guillon Christophe , Saxena Jaya , Fianu‐Velgus Cynthia , Aponte Erik , Young Sherri C. , Heck Diane E. , Joseph Laurie B. , Laskin Jeffrey D. , Heindel Ned D.
Published: August 2016

The molecular pathology of sulfur mustard injury is complex, with at least nine inflammation‐related enzymes and receptors upregulated in the zone of the insult. A new approach wherein inhibitors of these targets have been linked by hydrolyzable bonds, either one to one or via separate preattachment to a carrier molecule, has been shown to significantly enhance the therapeutic response compared with the individual agents. This article reviews the published work of the authors in this drug development domain over the last 8 years.
Technical Note: Development of a 3D printed subresolution sandwich phantom for validation of brain SPECT analysis
Authors: Negus Ian S. , Holmes Robin B. , Jordan Kirsty C. , Nash David A. , Thorne Gareth C. , Saunders Margaret
Published: August 2016

Purpose:

To make an adaptable, head shaped radionuclide phantom to simulate molecular imaging of the brain using clinical acquisition and reconstruction protocols. This will allow the characterization and correction of scanner characteristics, and improve the accuracy of clinical image analysis, including the application of databases of normal subjects.

Methods:

A fused deposition modeling 3D printer was used to create a head shaped phantom made up of transaxial slabs, derived from a simulated MRI dataset. The attenuation of the printed polylactide (PLA), measured by means of the Hounsfield unit on CT scanning, was set to match that of the brain by adjusting the proportion of plastic filament and air (fill ratio). Transmission measurements were made to verify the attenuation of the printed slabs. The radionuclide distribution within the phantom was created by adding 99mTc pertechnetate to the ink cartridge of a paper printer and printing images of gray and white matter anatomy, segmented from the same MRI data. The complete subresolution sandwich phantom was assembled from alternate 3D printed slabs and radioactive paper sheets, and then imaged on a dual headed gamma camera to simulate an HMPAO SPECT scan.

Results:

Reconstructions of phantom scans successfully used automated ellipse fitting to apply attenuation correction. This removed the variability inherent in manual application of attenuation correction and registration inherent in existing cylindrical phantom designs. The resulting images were assessed visually and by count profiles and found to be similar to those from an existing elliptical PMMA phantom.

Conclusions:

The authors have demonstrated the ability to create physically realistic HMPAO SPECT simulations using a novel head‐shaped 3D printed subresolution sandwich method phantom. The phantom can be used to validate all neurological SPECT imaging applications. A simple modification of the phantom design to use thinner slabs would make it suitable for use in PET.
Histone deacetylase 3 supports endochondral bone formation by controlling cytokine signaling and matrix remodeling
Authors: Carpio Lomeli R. , Bradley Elizabeth W. , McGee-Lawrence Meghan E. , Weivoda Megan M. , Poston Daniel D. , Dudakovic Amel , Xu Ming , Tchkonia Tamar , Kirkland James L. , van Wijnen Andre J. , Oursler Merry Jo , Westendorf Jennifer J.
Published: August 2016

Histone deacetylase 3 prevents chondrocytes from producing inflammatory mediators that prevent bone development.
Papers of note in
Science
Authors: VanHook Annalisa M.
Published: August 2016

This week’s articles explain how sunflowers track the Sun’s movement, a human mutation that links necroptosis to neurodegeneration, and why proteasome inhibitors work.
Comment on “SUMO deconjugation is required for arsenic-triggered ubiquitylation of PML”
Authors: Ferhi Omar , Pérès Laurent , Tessier Sarah , de Thé Hugues , Lallemand-Breitenbach Valérie
Published: August 2016

A switch in the SUMO isoforms conjugated to Lys
65
in the oncoprotein PML-RARA is not required for its arsenic-induced degradation.
Preclinical Profile and Clinical Efficacy of a Novel Hepatitis C Virus NS5A Inhibitor, EDP-239
Authors: Owens Christopher M. , Brasher Bradley B. , Polemeropoulos Alex , Rhodin Michael H. J. , McAllister Nicole , Peng Xiaowen , Wang Ce , Ying Lu , Cao Hui , Lawitz Eric , Poordad Fred , Rondon Juan , Box Terry D. , Zeuzem Stefan , Buggisch Peter , Lin Kai , Qiu Yao-Ling , Jiang Lijuan , Colvin Richard , Or Yat Sun
Published: August 2016

EDP-239, a novel hepatitis C virus (HCV) inhibitor targeting nonstructural protein 5A (NS5A), has been investigated
in vitro
and
in vivo
. EDP-239 is a potent, selective inhibitor with potency at picomolar to nanomolar concentrations against HCV genotypes 1 through 6. In the presence of human serum, the potency of EDP-239 was reduced by less than 4-fold. EDP-239 is additive to synergistic with other direct-acting antivirals (DAAs) or host-targeted antivirals (HTAs) in blocking HCV replication and suppresses the selection of resistance
in vitro
. Furthermore, EDP-239 retains potency against known DAA- or HTA-resistant variants, with half-maximal effective concentrations (EC
50
s) equivalent to those for the wild type. In a phase I, single-ascending-dose, placebo-controlled clinical trial, EDP-239 demonstrated excellent pharmacokinetic properties that supported once daily dosing. A single 100-mg dose of EDP-239 resulted in reductions in HCV genotype 1a viral RNA of >3 log
10
IU/ml within the first 48 h after dosing and reductions in genotype 1b viral RNA of >4-log
10
IU/ml within 96 h. (This study has been registered at ClinicalTrials.gov under identifier NCT01856426.)
Meckel's diverticular perforation presenting as acute abdomen in the second trimester of pregnancy
Authors: Ahmed Z , Chhabra S , Kankaria J , Jenaw RK
Published: August 2016

Meckel's diverticular perforation is a rare cause of acute abdomen during pregnancy. We report the case of a 24-year-old woman at 24 weeks of gestation who presented with abdominal pain for 4 days accompanied with abdominal distension, tenderness and guarding in right lower quadrant. Ultrasonography was inconclusive. The patient underwent exploratory laparotomy with the clinical suspicion of appendicular perforation peritonitis. Intraoperatively, a perforated Meckel's diverticulum was detected. Owing to gross contamination of the peritoneal cavity, a diverticulectomy with ileostomy was performed. She had a normal full-term vaginal delivery, and ileostomy was reversed 1 month after delivery. The physiological and anatomical changes in pregnancy can make a straightforward clinical diagnosis difficult. A high index of suspicion is required to prevent delay in diagnosis and surgical intervention, which could prove detrimental to the mother and fetus.
Sands subjected to repetitive vertical loading under zero lateral strain: accumulation models, terminal densities, and settlement
Authors: Chong Song-Hun , Santamarina J. Carlos
Published: August 2016

Geosystems often experience numerous loading cycles. Plastic strain accumulation during repetitive mechanical loads can lead to shear shakedown or continued shear ratcheting; in all cases, volumetric strains diminish as the specimen evolves towards terminal density. Previously suggested models and new functions are identified to fit plastic strain accumulation data. All accumulation models are formulated to capture terminal density (volumetric strain) and either shakedown or ratcheting (shear strain). Repetitive vertical loading tests under zero lateral strain conditions are conducted using three different sands packed at initially low and high densities. Test results show that plastic strain accumulation for all sands and density conditions can be captured in the same dimensionless plot defined in terms of the initial relative density, terminal density, and ratio between the amplitude of the repetitive load and the initial static load. This observation allows us to advance a simple but robust procedure to estimate the maximum one-dimensional settlement that a foundation could experience if subjected to repetitive loads.
Temporally stable, weak genetic structuring in brackish water northern pike (Esox lucius) in the Baltic Sea indicates a contrasting divergence pattern relative to freshwater populations
Authors: Wennerström Lovisa , Olsson Jens , Ryman Nils , Laikre Linda
Published: August 2016

Understanding spatiotemporal population genetic patterns is important for conservation management of ecologically and socioeconomically important species. This is particularly so in species-poor environments such as the brackish Baltic Sea. We examined over 600 northern pike (Esox lucius), a coastal predator and treasured sport fish, collected over major parts of the Baltic Sea coastline. We found low genetic divergence among populations, indicating a contrasting genetic structure of brackish water coastal spawners compared with previous reports on anadromous Baltic pike migrating up freshwater streams for spawning. A pattern of genetic isolation by distance either over shortest waterway or primarily along the mainland coast with islands as stepping stones suggested that gene flow is primarily taking place among neighboring populations, possibly with some migration over open water. Temporal data showed a stable genetic structure over a decade. Within a single sampling year, however, spatial divergence was larger during spawning than feeding season, indicating increased mixing of populations during the feeding season. Management should assure connectivity among brackish spawning grounds and large population sizes at identified core areas.
The interglacial of the Nar Valley, Norfolk
Authors: Stevens Leonora Ann
Published: August 2016

The geology and palaeobotany of the Pleistocene deposits in the Nar Valley, Norfolk, have been investigated. A low till is overlain by interglacial sediments consisting of lacustrine beds underlying an estuarine clay. These are covered by an upper till and glacial gravel.

The pollen analysis of the lacustrine sediments shows an early phase of park-tundra and then, due to an amelioration in the climate, the expansion of the mixed oak forest suggesting that the climate was at least as warm as at the present day. The pollen in the estuarine clay traces the decline of this forest and the increase in coniferous trees, indicating that the marine transgression took place after the climatic optimum.

The tills are defined and correlated with others in East Anglia by a comparison of the texture, erratics and the preferred orientation of the stones. The Jurassic erratics and the westerly preferred orientation of the stones indicate that the lower till was deposited during the Lowestoft Advance, while the upper till has a N.-S. preferred orientation comparable to the Gipping Advance.

This correlation of the tills indicates that the Nar Valley interglacial sediments are in a stratigraphical position similar to that of the Hoxne interglacial beds. The similarities between the vegetational successions of these two deposits is further evidence that the Nar Valley interglacial beds are of Great (Hoxnian, Elster/Saale) Interglacial age.

Both the pollen diagrams and the marine faunas of the Nar Valley and Clacton estuarine clays are very similar. These deposits, however, occur at different heights above sea level, and this is attributed to some relative vertical movement since their deposition.