bluuebunny/crossref_metadata_2025 huggingface dataset:
Post‐transcriptional regulation of the virulence‐associated enzyme AlgC by the σ22‐dependent small RNA ErsA of Pseudomonas aeruginosa
Authors: Ferrara Silvia , Carloni Sara , Fulco Roberta , Falcone Marilena , Macchi Raffaella , Bertoni Giovanni
Published: August 2014

The small RNA ErsA of Pseudomonas aeruginosa, transcribed from the same genomic context of the well‐known Escherichia coli Spot 42, has been characterized. We show that, different from Spot 42, ErsA is under the transcriptional control of the envelope stress response, which is known to impact the pathogenesis of P. aeruginosa through the activity of the alternative sigma factor σ22. The transcriptional responsiveness of ErsA RNA also spans infection‐relevant cues that P. aeruginosa can experience in mammalian hosts, such as limited iron availability, temperature shifts from environmental to body temperature and reduced oxygen conditions. Another difference between Spot 42 and ErsA is that ErsA does not seem to be involved in the regulation of carbon source catabolism. Instead, our results suggest that ErsA is linked to anabolic functions for the synthesis of exoproducts from sugar precursors. We show that ErsA directly operates in the negative post‐transcriptional regulation of the algC gene that encodes the virulence‐associated enzyme AlgC, which provides sugar precursors for the synthesis of several P. aeruginosa polysaccharides. Like ErsA, the activation of algC expression is also dependent on σ22. Altogether, our results suggest that ErsA and σ22 combine in an incoherent feed‐forward loop to fine‐tune AlgC enzyme expression.
Establishment and characterization of a novel cell line derived from thymoma with myasthenia gravis patients
Authors: Wang Guojin , Wang Yuanguo , Zhang Peng , Chen Yuan , Liu Yimei , Guo Feng , Zhang Hui
Published: August 2014

Background

Thymoma is a cancer with rare incidence, but it is a major malignancy in adult anterior mediastinum, occurring in about 40% of patients with myasthenia gravis. Because of the lack of thymic epithelial tumor cell lines, thymoma has lagged far behind other tumors in cytological studies. It is, therefore, quite necessary to establish a new thymic epithelial tumor cell line from Chinese patients to study the pathogenic mechanism and therapeutic methods.

Methods

Twenty‐three samples of tumor tissues were collected from thymoma and thymic carcinoma patients for primary culture by tissue explant, suspension cell culture method, and collagenase digestion. We detected the biological characteristics and origin of the cell line after the establishment of a novel thymoma cell line.

Results

A novel cell line, designed as Thy0517, was established from thymoma type AB with myasthenia gravis patients by tissue explant. As an immortalized cell line, it always has a stable growth cycle, and there is no change in characteristics and morphology after culturing for 18 months and passing 160 generations in vitro. The experimental data demonstrate that the cell line exhibits the growth characteristics of tumor cells, the doubling time of 37 hours, with tumorigenicity in vitro and chromosome abnormality. Immunocytochemistry indicated that the cell line positive expression of CK7, CK8/18, CK19, CK‐pan, CD24, BCL‐2, P63, Vimentin, epithelial membrane antigen and epidermal growth factor receptor, lymphocyte related antigen CD99, and TdT were negatively expressed.

Conclusions

The newly established thymic epithelial tumor cell line from Chinese patients provides a model in the study of thymoma and molecularly targeted therapies.
Roles of miR‐182 in sensory organ development and cancer
Authors: Wei Qing , Lei Rong , Hu Guohong
Published: August 2014

Micro ribonucleic acids (miRNAs) are a cluster of small non‐coding RNA molecules predicted to regulate more than 30% of coding messenger (m)RNAs in the human genome and proven to be essential in developmental and pathological processes. The miR‐182 gene was first found to be abundantly expressed in sensory organs and regulates the development of the retina and inner ear. Further studies revealed its roles in osteogenesis and T cell differentiation. In addition, the involvement of miR‐182 in cancer initiation and progression has recently been uncovered by a growing body of evidence, the majority of which supports its promoting effects in cell proliferation, angiogenesis, and invasion, as well as distant metastasis of various cancer types. Clinical analyses demonstrated the link of miR‐182 expression to poor prognosis in cancer patients. Mechanistically, multiple downstream genes including missing‐in‐metastasis, microphthalm‐associated transcription factor, FoxO1, cylindromatiosis, and others, can be targeted by miR‐182 and mediate its roles in cancer. miR‐182 is also interconnected with prominent cancer‐related signaling pathways, such as transforming growth factor beta and nuclear factor kappa beta. Interestingly, it was shown that in vivo targeting of miR‐182 prevented liver metastasis of melanoma. miR‐182 is emerging as an important regulator of malignancies, which warrants further study to establish the application potential of miR‐182 in cancer diagnosis and treatment.
Evaluation of quantitative trait loci affecting intramuscular fat and reproductive traits in pigs using marker‐assisted introgression
Authors: Sato S. , Ohnishi C. , Kikuchi T. , Kohira K. , Egawa S. , Terai S. , Nakamura T. , Arata S. , Komatsuda A. , Uemoto Y.
Published: August 2014

We investigated the effects of previously identified quantitative trait loci (QTL) in an experimental backcross (BC) between Chinese Meishan pigs and commercial Duroc pigs. We performed marker‐assisted introgression of two QTL for intramuscular fat (IMF) content (IMF population) and three QTL for reproductive traits (reproduction population) from a donor Meishan pig into a recipient Duroc pig. At the fourth BC generation of the IMF population and third BC generation of the reproduction population, carrier animals were selected for the production of animals homozygous for the QTL. Our previous studies have shown that the presence of a Meishan allele on the IMF QTL is associated with low IMF values, and the Meishan allele on the reproductive QTL is associated with large litters. In this study, the presence of a Duroc allele at the IMF QTL on SSC9 resulted in a 0.27% increase in IMF (additive effect = 0.27 ± 0.08), whereas the presence of a Meishan allele at the IMF QTL on SSC7 resulted in a 0.34% increase in IMF (additive effect = −0.34 ± 0.09). The presence of the Meishan allele at the IMF QTL on SSC7 thus had the opposite effect to our previous studies, that is, increased IMF. In the reproduction population, we observed no differences between the genotypes of the three QTL in regard to number of corpora lutea or litter size. Marker‐assisted introgression at these QTL is thus unlikely to result in an associated increase in litter size. These results show that it is possible to introgress alleles from other breeds into a selection population using molecular markers; any unexpected results might be associated with the genetic background.
Effect of ursodeoxycholic acid treatment on the altered progesterone and bile acid homeostasis in the mother‐placenta‐foetus trio during cholestasis of pregnancy
Authors: Estiú Maria C. , Monte Maria J. , Rivas Laura , Moirón Maria , Gomez‐Rodriguez Laura , Rodriguez‐Bravo Tomas , Marin Jose J.G. , Macias Rocio I.R.
Published: August 2014

Aim

Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and elevated bile acid concentrations in maternal serum. This is accompanied by an enhanced risk of intra‐uterine and perinatal complications. High concentrations of sulphated progesterone metabolites (PMS) have been suggested to be involved in the multifactorial aetiopathogenesis of ICP. The aim of this study was to investigate further the mechanism accounting for the beneficial effect of oral administration of ursodeoxycholic acid (UDCA), which is the standard treatment, regarding bile acid and PMS homeostasis in the mother‐placenta‐foetus trio.

Method

Using HPLC‐MS/MS bile acids and PMS were determined in maternal and foetal serum and placenta. The expression of ABC proteins in placenta was determined by real time quantitative PCR (RT‐QPCR) and immunofluorescence.

Results

In ICP, markedly increased concentrations of bile acids (tauroconjugates > glycoconjugates >> unconjugated), progesterone and PMS in placenta and maternal serum were accompanied by enhanced concentrations in foetal serum of bile acids, but not of PMS. UDCA treatment reduced bile acid accumulation in the mother‐placenta‐foetus trio, but had no significant effect on progesterone and PMS concentrations. ABCG2 mRNA abundance was increased in placentas from ICP patients vs. controls and remained stable following UDCA treatment, despite an apparent further increase in ABCG2.

Conclusion

UDCA administration partially reduces ICP‐induced bile acid accumulation in mothers and foetuses despite the lack of effect on concentrations of progesterone and PMS in maternal serum. Up‐regulation of placental ABCG2 may play an important role in protecting the foetus from high concentrations of bile acids and PMS during ICP.
Diagnosing and following adult patients with acute myeloid leukaemia in the genomic age
Authors: Roug Anne S. , Hansen Marcus C. , Nederby Line , Hokland Peter
Published: August 2014

The diagnosis and follow‐up process of adult patients with acute myeloid leukaemia (AML) is challenging to clinicians and laboratory staff alike. While several sets of recommendations have been published over the years, the development of high throughput screening and characterization for both genetic and epigenetic events have evolved with astonishing speed. Here we attempt to provide a practical guide to diagnose and follow adult AML patients with a focus on how to balance the wealth of information on the one hand, with the restriction put on these processes in terms of time, feasibility and economy when caring for these patients, on the other.
L‐Leucine improves the anaemia in models of Diamond Blackfan anaemia and the 5q‐ syndrome in a TP53‐independent way
Authors: Narla Anupama , Payne Elspeth M. , Abayasekara Nirmalee , Hurst Slater N. , Raiser David M. , Look A. Thomas , Berliner Nancy , Ebert Benjamin L. , Khanna‐Gupta Arati
Published: August 2014

Haploinsufficiency of ribosomal proteins (RPs) and upregulation of the tumour suppressor TP53 have been shown to be the common basis for the anaemia observed in Diamond Blackfan anaemia and 5q‐ myelodysplastic syndrome. We previously demonstrated that treatment with L‐Leucine resulted in a marked improvement in anaemia in disease models. To determine if the L‐Leucine effect was Tp53‐dependent, we used antisense MOs to rps19 and rps14 in zebrafish; expression of tp53 and its downstream target cdkn1a remained elevated following L‐leucine treatment. We confirmed this observation in human CD34+ cells. L‐Leucine thus alleviates anaemia in RP‐deficient cells in a TP53‐independent manner.
Perioperative outcomes of cytoreductive nephrectomy in the UK in 2012
Authors: Jackson Benjamin L. , Fowler Sarah , Williams Simon T. ,   the British Association of Urological Surgeons (BAUS) – Section of Oncology
Published: August 2014

Objectives

To define the perioperative morbidity and 30‐day mortality of cytoreductive nephrectomy (CN) using the British Association of Urological Surgeons (BAUS) nephrectomy dataset for 2012, the first year of public reporting of individual surgeon outcomes in the UK.

Patients and Methods

All nephrectomies recorded in the database in 2012 were analysed, and cytoreductive cases identified. Outcome measures were: blood loss of >1000 mL, transfusion requirement, intra‐ and postoperative complications assessed by Clavien–Dindo score, and 30‐day mortality (including failure‐to‐rescue rate). Univariate and multivariate logistic regression analysis was used to assess predictors of adverse outcomes.

Results

In all, 279 cases were undertaken by 141 surgeons in 90 centres. World Health Organization (WHO) Performance Status (PS) was 0 or 1 in 72.4% (202 cases). Open nephrectomy was performed in 59% (163 cases), with the remainder laparoscopic. The conversion rate for laparoscopy was 14% (16 cases). In all, 40 patients underwent preoperative tyrosine‐kinase inhibitor treatment. No significant differences in outcome were observed for this group. The 30‐day mortality was 1.79%. Intraoperative complications occurred in 11.9% and postoperative complications in 20.8%. Complications of Clavien–Dindo grade ≥ III occurred in 8%. Blood loss of >1000 mL occurred in 15.4% of cases and 24.1% of patients required a perioperative transfusion. Tumour of >10 cm was an independent risk factor for blood loss of >1000 mL (P = 0.021) and intraoperative complications (P = 0.021). The number of metastatic sites was an independent predictor of blood loss of >1000 mL (P = 0.001) and transfusion requirement (P = 0.026) WHO PS of ≥2 was also independently associated with intraoperative complication risk (P = 0.021).

Conclusions

CN in contemporary UK practice appears to have excellent perioperative outcomes overall. Risk factors for adverse perioperative outcomes include tumours of >10 cm, number of metastatic sites and WHO PS of ≥2. The balance of risk and benefit for CN should be carefully considered for patients with poor PS or extensive metastases.
Defining the learning curve for multiparametric magnetic resonance imaging (MRI) of the prostate using MRI‐transrectal ultrasonography (TRUS) fusion‐guided transperineal prostate biopsies as a validation tool
Authors: Gaziev Gabriele , Wadhwa Karan , Barrett Tristan , Koo Brendan C. , Gallagher Ferdia A. , Serrao Eva , Frey Julia , Seidenader Jonas , Carmona Lina , Warren Anne , Gnanapragasam Vincent , Doble Andrew , Kastner Christof
Published: August 2014

Objectives

To determine the accuracy of multiparametric magnetic resonance imaging (mpMRI) during the learning curve of radiologists using MRI targeted, transrectal ultrasonography (TRUS) guided transperineal fusion biopsy (MTTP) for validation.

Patients and Methods

Prospective data on 340 men who underwent mpMRI (T2‐weighted and diffusion‐weighted MRI) followed by MTTP prostate biopsy, was collected according to Ginsburg Study Group and Standards for Reporting of Diagnostic Accuracy standards. MRI data were reported by two experienced radiologists and scored on a Likert scale. Biopsies were performed by consultant urologists not ‘blinded’ to the MRI result and men had both targeted and systematic sector biopsies, which were reviewed by a dedicated uropathologist. The cohorts were divided into groups representing five consecutive time intervals in the study. Sensitivity and specificity of positive MRI reports, prostate cancer detection by positive MRI, distribution of significant Gleason score and negative MRI with false negative for prostate cancer were calculated. Data were sequentially analysed and the learning curve was determined by comparing the first and last group.

Results

We detected a positive mpMRI in 64 patients from Group A (91%) and 52 patients from Group E (74%). The prostate cancer detection rate on mpMRI increased from 42% (27/64) in Group A to 81% (42/52) in Group E (P < 0.001). The prostate cancer detection rate by targeted biopsy increased from 27% (17/64) in Group A to 63% (33/52) in Group E (P < 0.001). The negative predictive value of MRI for significant cancer (>Gleason 3+3) was 88.9% in Group E compared with 66.6% in Group A.

Conclusion

We demonstrate an improvement in detection of prostate cancer for MRI reporting over time, suggesting a learning curve for the technique. With an improved negative predictive value for significant cancer, decision for biopsy should be based on patient/surgeon factors and risk attributes alongside the MRI findings.
Retrospective case–control study of viral pathogen screening in proliferative verrucous leukoplakia lesions
Authors: García‐López R. , Moya A. , Bagan J.V. , Pérez‐Brocal V.
Published: August 2014

Objective

This study aimed to survey the presence of known oncoviruses in oral biopsies from patients diagnosed with the aetiologically undetermined proliferative verrucous leukoplakia and compare results to those from milder oral leukoplakia (OL) cases, oral squamous cell carcinoma, a common outcome of the lesions of interest, and healthy controls.

Design

Blind, retrospective, case–control study.

Setting

A stomatology unit in an academic Hospital and a Public Health laboratory.

Participants

Forty patients were divided in four groups. Ten patients had been diagnosed with proliferative verrucous leukoplakia, 10 with OL and 10 with OSCC, and 10 were healthy subjects.

Main outcome measures

The presence or absence of oncovirus DNA was assayed with the amplification of viral genetic markers using PCR and subsequent gel electrophoresis confirmation. Amplified fragments were sequenced and identified bioinformatically.

Results

No DNA from the herpesvirus, papillomavirus or polyomavirus species was detected in the samples.

Conclusions

No association between proliferative verrucous leukoplakia and target viruses was detected. A higher throughput viral metagenomic approach may prove valuable for future analyses, as it would not be restricted to a priori knowledge of potential targets.
Development of an ENT undergraduate curriculum using a Delphi survey
Authors: Lloyd S. , Tan Z.E. , Taube M.‐A. , Doshi J.
Published: August 2014

Objective

To determine an ENT undergraduate syllabus.

Design

Two round Delphi survey.

Setting

Email questionnaire.

Participants

Stakeholders with a vested interest in ENT undergraduate education.

Main outcomes measured

Mode and median scores for 232 learning outcomes.

Results

The individual learning objectives that scored most highly were related to history taking and examination, red flag symptoms, common ENT conditions including all forms of otitis, acute and chronic rhinosinusitis, thyroid disease, pharyngeal infection and airway compromise and formulation of differential diagnoses.

Conclusions

Using a Delphi technique, a structured, evidence‐based curriculum has been developed. This should assist those medical schools who do not currently have ENT in their curriculum but wish to reinstate it to produce a high quality teaching programme. It may also assist those medical schools who do have ENT in their curriculum to continue to develop their curriculum.
Pollution, habitat loss, fishing, and climate change as critical threats to penguins
Authors: Trathan Phil N. , García‐Borboroglu Pablo , Boersma Dee , Bost Charles‐André , Crawford Robert J. M. , Crossin Glenn T. , Cuthbert Richard J. , Dann Peter , Davis Lloyd Spencer , De La Puente Santiago , Ellenberg Ursula , Lynch Heather J. , Mattern Thomas , Pütz Klemens , Seddon Philip J. , Trivelpiece Wayne , Wienecke Barbara
Published: August 2014

Cumulative human impacts across the world's oceans are considerable. We therefore examined a single model taxonomic group, the penguins (Spheniscidae), to explore how marine species and communities might be at risk of decline or extinction in the southern hemisphere. We sought to determine the most important threats to penguins and to suggest means to mitigate these threats. Our review has relevance to other taxonomic groups in the southern hemisphere and in northern latitudes, where human impacts are greater. Our review was based on an expert assessment and literature review of all 18 penguin species; 49 scientists contributed to the process. For each penguin species, we considered their range and distribution, population trends, and main anthropogenic threats over the past approximately 250 years. These threats were harvesting adults for oil, skin, and feathers and as bait for crab and rock lobster fisheries; harvesting of eggs; terrestrial habitat degradation; marine pollution; fisheries bycatch and resource competition; environmental variability and climate change; and toxic algal poisoning and disease. Habitat loss, pollution, and fishing, all factors humans can readily mitigate, remain the primary threats for penguin species. Their future resilience to further climate change impacts will almost certainly depend on addressing current threats to existing habitat degradation on land and at sea. We suggest protection of breeding habitat, linked to the designation of appropriately scaled marine reserves, including in the High Seas, will be critical for the future conservation of penguins. However, large‐scale conservation zones are not always practical or politically feasible and other ecosystem‐based management methods that include spatial zoning, bycatch mitigation, and robust harvest control must be developed to maintain marine biodiversity and ensure that ecosystem functioning is maintained across a variety of scales.

Contaminación, Pérdida de Hábitat, Pesca y Cambio Climático como Amenazas Críticas para los Pingüinos
Use of structured expert judgment to forecast invasions by bighead and silver carp in Lake Erie
Authors: Wittmann Marion E. , Cooke Roger M. , Rothlisberger John D. , Rutherford Edward S. , Zhang Hongyan , Mason Doran M. , Lodge David M.
Published: August 2014

Identifying which nonindigenous species will become invasive and forecasting the damage they will cause is difficult and presents a significant problem for natural resource management. Often, the data or resources necessary for ecological risk assessment are incomplete or absent, leaving environmental decision makers ill equipped to effectively manage valuable natural resources. Structured expert judgment (SEJ) is a mathematical and performance‐based method of eliciting, weighting, and aggregating expert judgments. In contrast to other methods of eliciting and aggregating expert judgments (where, for example, equal weights may be assigned to experts), SEJ weights each expert on the basis of his or her statistical accuracy and informativeness through performance measurement on a set of calibration variables. We used SEJ to forecast impacts of nonindigenous Asian carp (Hypophthalmichthysspp.) in Lake Erie, where it is believed not to be established. Experts quantified Asian carp biomass, production, and consumption and their impact on 4 fish species if Asian carp were to become established. According to experts, in Lake Erie Asian carp have the potential to achieve biomass levels that are similar to the sum of biomasses for several fishes that are harvested commercially or recreationally. However, the impact of Asian carp on the biomass of these fishes was estimated by experts to be small, relative to long term average biomasses, with little uncertainty. Impacts of Asian carp in tributaries and on recreational activities, water quality, or other species were not addressed. SEJ can be used to quantify key uncertainties of invasion biology and also provide a decision‐support tool when the necessary information for natural resource management and policy is not available.

El Uso de Juicio Experto Estructurado para Predecir Invasiones de Carpas Asiáticas en el Lago Erie
Foundational Tuning: How Infants' Attention to Speech Predicts Language Development
Authors: Vouloumanos Athena , Curtin Suzanne
Published: August 2014

Orienting biases for speech may provide a foundation for language development. Although human infants show a bias for listening to speech from birth, the relation of a speech bias to later language development has not been established. Here, we examine whether infants' attention to speech directly predicts expressive vocabulary. Infants listened to speech or non‐speech in a preferential listening procedure. Results show that infants' attention to speech at 12 months significantly predicted expressive vocabulary at 18 months, while indices of general development did not. No predictive relationships were found for infants' attention to non‐speech, or overall attention to sounds, suggesting that the relationship between speech and expressive vocabulary was not a function of infants' general attentiveness. Potentially ancient evolutionary perceptual capacities such as biases for conspecific vocalizations may provide a foundation for proficiency in formal systems such language, much like the approximate number sense may provide a foundation for formal mathematics.
Sequencing approaches in cancer treatment
Authors: Sekar D. , Thirugnanasambantham K. , Hairul Islam V. I. , Saravanan S.
Published: August 2014

Use of sequencing approaches is an important aspect in the field of cancer genomics, where next‐generation sequencing has already been utilized for targeting oncogenes or tumour‐suppressor genes, that can be sequenced in a short time period. Alterations such as point mutations, insertions/deletions, copy number alterations, chromosomal rearrangements and epigenetic changes are encountered in cancer cell genomes, and application of various NGS technologies in cancer research will encounter such modifications. Rapid advancement in technology has led to exponential growth in the field of genomic analysis. The $1000 Genome Project (in which the goal is to sequence an entire human genome for $1000), and deep sequencing techniques (which have greater accuracy and provide a more complete analysis of the genome), are examples of rapid advancements in the field of cancer genomics. In this mini review, we explore sequencing techniques, correlating their importance in cancer therapy and treatment.
Diabetes and breast cancer in Taiwanese women: a detection bias?
Authors: Tseng Chin‐Hsiao
Published: August 2014

Purpose

To evaluate whether diabetes is a risk factor for breast cancer considering confounders and potential detection examinations.

Methods

National Health Insurance data on 501 747 women without breast cancer were retrieved. Three‐year cumulative incidence (2003–2005) and risk ratios (RRs) between diabetic and nondiabetic women were calculated. Potential detection examinations were compared between diabetic and nondiabetic women by chi‐square test. Odds ratios (ORs) were estimated by logistic regression for diabetes status/duration with and without adjustment for potential detection examinations and confounders.

Results

The crude RR (95% confidence interval [CI]) for all ages, and age groups < 50, 50–64 and ≥ 65 years, was 2·62 (2·31–2·91), 2·69 (2·11–3·44), 1·39 (1·15–1·68) and 1·37 (1·03–1·84), respectively. Patients with diabetes more frequently received potential detection examinations than nondiabetes (17·5% vs. 7·4%, P‐value < 0·001). The unadjusted OR (95% CI) for breast cancer for diabetes status (yes vs. no) was 2·63 (2·31–2·98) and was significant for any diabetes duration. The OR for diabetes status was 1·81 (95% CI: 1·59–2·06) after adjustment for potential detection examinations. In models adjusted for potential detection examinations, age, living region, occupation, comorbidities and used medications, OR for diabetes status attenuated to 1·13 (95% CI 0·96–1·32, P‐value = 0·14) and none was significant for any diabetes duration. Potential detection examinations were associated with a fivefold to sevenfold higher risk in various models, indicating a strong impact of detection bias.

Conclusions

An association between diabetes and breast cancer is observed, but this can be due to potential detection bias and confounders.
Optical coherence tomography in patients with a history of juvenile multiple sclerosis reveals early retinal damage
Authors: Huhn K. , Lämmer R. , Oberwahrenbrock T. , Lämmer A. , Waschbisch A. , Gosar D. , Brandt A. , Paul F. , Linker R. A. , Lee D.‐H.
Published: August 2014

Background and purpose

Some 3%−10% of patients with multiple sclerosis (MS) experience disease onset before the age of 18 years (‘early’ onset MS, EOMS). Optical coherence tomography is a non‐invasive method to measure retinal nerve fibre layer thickness (RNFLT) and total macular volume (TMV) and may be useful to differentiate axonal and neuronal damage in the retina of patients with a history of EOMS. Here RNFLT and TMV in EOMS patients after a mean disease duration of 11.6 years were compared with patients with age‐ or disease‐duration‐matched later onset MS (LOMS) and healthy controls (HCs).

Methods

In this observational cross‐sectional study at two German academic MS centres, RNFLT and TMV were measured by spectral‐domain optical coherence tomography in 32 HCs, 36 EOMS (mean age at onset 15.5 ± 2.0 years) and 58 LOMS patients.

Results

In comparison with HCs, EOMS patients displayed a significant reduction of RNFLT and TMV independently of a history of optic neuritis. In particular, RNFLT loss in EOMS was similar to that in LOMS and TMV loss was slightly higher compared with disease‐duration‐matched LOMS. In a generalized estimating model, the EOMS group also displayed a similar correlation between disease duration and RNFLT or TMV loss to LOMS patients.

Conclusions

These data argue for a significant amount of axonal and neuronal damage in the retina of EOMS patients and may provide a structural basis for the observation that EOMS patients reach states of irreversible disability at a younger age than patients with LOMS.
Serum proteomic analysis of a pre‐symptomatic multiple sclerosis cohort
Authors: Wallin M. T. , Oh U. , Nyalwidhe J. , Semmes J. , Kislinger T. , Coffman P. , Kurtzke J. F. , Jacobson S.
Published: August 2014

Background and purpose

Susceptibility to multiple sclerosis (MS) is determined by environmental and genetic factors, but the cause remains unknown. Changes to the proteome prior to first symptom onset may reflect the underlying pathophysiology of the disease.

Methods

This preliminary study utilized pre‐symptomatic and post‐symptomatic serum from a sample of 100 incident population‐based US military veterans with MS along with 100 matched healthy controls. All samples were obtained from the Department of Defense Serum Repository. Multidimensional protein identification technology tandem mass spectrometry analysis was performed on tryptic peptides of lectin‐captured glycosylated serum proteins following albumin/immunoglobulin G depletion. Identified proteins were analyzed with the Ingenuity Pathway Analysis program.

Results

The mean intervals between first symptom onset and the collection of pre‐symptomatic and post‐symptomatic sera were −6.0 and +1.1 years, respectively. Pre‐symptomatic proteins from the MS group were differentially regulated compared with both control groups indicating that proteomic changes are detected prior to symptom onset. Pathway analysis showed that proteins involved in the complement and coagulation pathways and lipid transport are significantly altered in the serum of subjects with MS compared with healthy donors.

Conclusions

Compared with healthy controls, differential proteomic changes were noted in the serum of patients with MS that preceded the onset of symptomatic disease. Further work is in progress to confirm or refute these findings.
Up Close: Family Therapy Challenges and Innovations Around the World
Authors: Roberts Janine , Abu‐Baker Khawla , Diez Fernández Cristina , Chong Garcia Nelly , Fredman Glenda , Kamya Hugo , Martín Higarza Yolanda , Fortes de Leff Jacqueline , Messent Philip , Nakamura Shin‐Ichi , Torun Reid Fatma , Sim Timothy , Subrahmanian Chitra , Zevallos Vega Roxana
Published: August 2014

Family therapists from 10 different countries (China, India, Israel including Palestinian citizens, Japan, Mexico, Peru, Spain, Turkey, Uganda, and the United Kingdom) describe systemic therapy in their contexts and current innovative work and challenges. They highlight the importance of family therapy continuing to cut across disciplines, the power of systems ideas in widely diverse settings and institutions (such as courts, HIV projects, working with people forced into exile), extensive new mental health initiatives (such as in Turkey and India), as well as the range of family therapy journals available (four alone in Spain). Many family therapy groups are collaborating across organizations (especially in Asia) and the article presents other ideas for connections such as a clearing house to inexpensively translate family therapy articles into other languages.
Resolving regulatory uncertainty: legislative language for potentially invasive bioenergy feedstocks
Authors: Quinn Lauren D. , Scott Elise C. , Endres A. Bryan , Barney Jacob N. , Voigt Thomas B. , McCubbins James
Published: August 2014

Concerns about invasions by novel bioenergy feedstocks are valid, given the parallels between the traits of energy crops and those of many common invasive plants. As the bioenergy industry is poised to introduce nonnative bioenergy crops to large acreages in the United States under state and federal mandates, it is important to consider these concerns – and not simply in an academic sense. Instead, the prevention of invasions should be codified in statutes and regulations pertaining to bioenergy production on both the state and federal level. Unfortunately, this is not occurring regularly or consistently at this time. The few existing regulations that do consider invasiveness in bioenergy systems suffer from vague terminology that could have major economic, environmental, and legal consequences. Here, we discuss existing regulatory challenges and provide solutions to address invasion potential of bioenergy crops. We provide model definitions and provisions to be included in revised or new state and federal regulations, including an invasion risk assessment process, a permit and bond system for high‐risk crops, and a risk mitigation provision for all novel crops. Our proposal provides a consistent and transparent system that will allow the industry to move forward with minimal risk of invasion by novel feedstocks.
Biochar mineralization and priming effect on SOM decomposition in two European short rotation coppices
Authors: Ventura Maurizio , Alberti Giorgio , Viger Maud , Jenkins Joseph R. , Girardin Cyril , Baronti Silvia , Zaldei Alessandro , Taylor Gail , Rumpel Cornelia , Miglietta Franco , Tonon Giustino
Published: August 2014

As studies on biochar stability in field conditions are very scarce, the carbon sequestration potential of biochar application to agricultural soils remains uncertain. This study assessed the stability of biochar in field conditions, the effect of plant roots on biochar stability and the effect of biochar on original soil organic matter (SOM) decomposition in two (Italy and United Kingdom) short rotation coppice systems (SRCs), using continuous soil respiration monitoring and periodic isotopic (δ13CO2) measurements. When root growth was excluded, only 7% and 3% of the biochar carbon added was decomposed after 245 and 164 days in Italy and United Kingdom sites respectively. In the presence of roots, this percentage was increased to 9% and 8%, suggesting a small positive priming effect of roots on biochar decomposition. A decreased decomposition rate of original SOM was observed at both sites after biochar incorporation, suggesting a protective effect of biochar on SOM. This study supports the carbon sequestration potential of biochar and highlights the role of root activity on biochar decomposition, questioning the applicability of laboratory incubation studies to assess biochar stability.
Safety and efficacy of a von Willebrand factor/factor VIII concentrate (Wilate®): a single centre experience
Authors: Batty P. , Chen Y. ‐H. , Bowles L. , Hart D. P. , Platton S. , Pasi K. J.
Published: August 2014

Summary

von Willebrand disease (VWD) is the commonest inherited bleeding disorder. Management of major surgery or bleeding often requires treatment with a plasma‐derived (pd) VWF/FVIII containing concentrate. Wilate® is a dual‐virally inactivated pd‐concentrate, produced specifically for the treatment of VWD, containing physiological (1:1) ratios of VWF: FVIII. We reviewed efficacy and safety of Wilate® usage (2007–2012) at our centre including 2 years following product switching the majority of patients. Clinical and laboratory data of all adult patients treated with Wilate® during the study period were evaluated. Fifty four patients used 3 972 150 IU of Wilate® (1378 infusions) between 1/3/07 and 1/5/12. Efficacy was rated as being excellent or good in 94% of surgical episodes (n = 70; 34 patients) and 98% of bleeding/traumatic episodes (n = 46; 25 patients). Eight patients (2 636 100 IU) were managed on home treatment regimens. Two patients switched to Wilate® prophylaxis in the evaluation period, demonstrating similar efficacy to a previous product. Incremental recoveries (n = 37) were 2.24 IU dL−1 per IU kg−1 for FVIII:C, 2.39 IU dL−1 per IU kg−1 for VWF:Ag and 1.88 IU dL−1 per IU kg−1 for VWF:RCo. Six adverse events occurred in six patients (11.1% patients) over 1378 infusions (0.44%). Half of these were retrospectively felt to be infusion speed related. No notable accumulation of FVIII was seen in patients treated for ≥3 days. There was no treatment failure, thrombosis, transfusion transmitted infection or inhibitory VWF antibodies seen. Our findings confirm safety and efficacy of Wilate® in an adult VWD population with lack of notable FVIII accumulation.
Piperacillin/tazobactam‐induced neurotoxicity in a hemodialysis patient: A case report
Authors: Neves Precil Diego M. M. , Freitas Fernanda M. , Kojima Christiane A. , Carmello Beatriz L. , Bazan Rodrigo , Barretti Pasqual , Martin Luis C.
Published: August 2014

Antibiotics are potentially a cause of neurotoxicity in dialysis patients, the most common are the beta‐lactams as ceftazidime and cefepime, and few cases have been reported after piperacillin/tazobactam use. This report presents a case of a hypertensive and diabetic 67‐year‐old woman in regular hemodialysis, which previously had a stroke. She was hospitalized presenting pneumonia, which was initially treated with cefepime. Two days after treatment, she presented dysarthria, left hemiparesis, ataxia, and IX and X cranial nerves paresis. Computed tomography showed no acute lesions and cefepime neurotoxicity was hypothesized, and the antibiotic was replaced by piperacillin/tazobactam. The neurologic signs disappeared; however, 4 days after with piperacillin/tazobactam treatment, the neurological manifestations returned. A new computed tomography showed no new lesions, and the second antibiotic regimen withdrawn. After two hemodialysis sessions, the patient completely recovered from neurological manifestations. The patient presented sequentially neurotoxicity caused by two beta‐lactams antibiotics. This report meant to alert clinicians that these antibiotics have dangerous neurological effects in chronic kidney disease patients.
Myofibroblasts from salivary gland adenoid cystic carcinomas promote cancer invasion by expressing MMP2 and CXCL12
Authors: Guan Haijie , Tan Jie , Zhang Fuyin , Gao Lu , Bai Liang , Qi Dongyuan , Dong Hui , Zhu Lei , Li Xiaojie , Liu Tingjiao
Published: August 2014

Objectives

Salivary gland adenoid cystic carcinoma (ACC) is one of the most common malignant tumours in the oral and maxillofacial region, and has high aggressive potential. Tumour and stroma interactions are critical in determining the biological characteristics of malignancy. The aim of this study was to investigate the presence of myofibroblasts and their roles in the invasive characteristics of ACC.

Methods and results

Immunohistochemistry was used to detect the expression of vimentin (VIM), α‐smooth muscle actin (α‐SMA), matrix metalloproteinase 2 (MMP2) and CD34 in ACCs and normal salivary gland controls. A significant difference in α‐SMA expression was found between normal controls and ACCs, suggesting the presence of myofibroblasts in ACCs. Immunohistochemical staining also demonstrated higher MMP2 expression in the stroma of ACCs than in the controls (P < 0.001). Primary culture of myofibroblasts from one ACC showed great invasive activity, with high expression of MMP2 and C‐X‐C motif chemokine 12 (CXCL12) by reverse transcription polymerase chain reaction (RT‐PCR) analysis.

Conclusions

This study demonstrated the presence of myofibroblasts in ACC. Myofibroblasts might be related to the aggressive growth behaviour of ACC, owing to their high levels of expression of MMP2 and CXCL12.
Engineering High Permeability:Mn–Zn andNi–Zn Ferrites
Authors: Kumar Surender , Shinde Tukaram , Vasambekar Pramod
Published: August 2014

Magnetic properties of polycrystalline spinel ferrites are of significant interest in scientific community. Of all, initial permeability is most important magnetic property for device fabrication.Mn–Zn andNi–Zn ferrites are commercially most successful class of ferrites. Ferrites accommodate variety of cations in interstitial sites; type of cations, their occupancy at interstitial sites, grain size, pores, defects, or other imperfections in ferrites regulate their response to external magnetic stimulus. These factors are influenced by composition and preparation method. The failure of initial permeability of ferrites, to withstand variation in frequency of applied signal has fueled intense efforts in scientific community to optimize frequency stability of permeability. Therefore, improvement in their permeability is important from commercial perspective, and it further enables deeper insight into the dynamical link between microstructure and magnetic properties. This work presents a review of initial permeability inMn–Zn andNi–Zn ferrites with a focus on influence of intrinsic factors and frequency of applied signal. The work is an analytical assessment to provide framework for engineering high permeability in ferrites.
Lightning Rods in the Local Moral Economy: Debating Unauthorized Migrants' Deservingness in Israel
Authors: Willen Sarah S.
Published: August 2014

Localized debates about who unauthorized migrants are and what they do, or do not, deserve unfold in a culturally specific register that is deeply charged with emotion and moral valuation. Structuring such debates are vernacular discursive frames that emerge from, and reflect, a common “local moral economy.” Taking Israel as case study, this article examines six elements of the country's local moral economy – biopolitical logic, historical memory, political emotion, popularized religion, an ideology of “fruitful multiplication,” and hasbara (“public diplomacy”/propaganda) – and explores their impact on public debates about unauthorized and irregular forms of migration. Here, as elsewhere, conventionalized distinctions that frame much migration scholarship – e.g. “economic” vs. “political” migrants, “migrant workers” vs. “refugees,” even the terms “authorized” and “unauthorized” themselves – bear but limited salience. Migration researchers who hope to influence local policy debates must recognize the weight and influence of local moral economies, and the chasms that divide vernacular from conventionalized frames. Achieving this sort of nuanced understanding is, at root, an ethnographic challenge.
Immunomodulatory oligonucleotides inhibit neutrophil migration by decreasing the surface expression of interleukin‐8 and leukotriene B4 receptors
Authors: Admyre Charlotte , Axelsson Lars‐Göran , von Stein Oliver , Zargari Arezou
Published: August 2014

Neutrophils play important roles in many inflammatory diseases. The migration of neutrophils to the inflammatory site is tightly regulated by specific chemokines, of which interleukin‐8 (IL‐8) and leukotriene B4 (LTB4) constitute key mediators by binding to the surface receptors CXCR1/2 and BLT1, respectively. Oligonucleotides (ODN) containing CpG motifs mediate potent immunomodulatory effects through binding to Toll‐like receptor 9. So far, knowledge on how ODN can affect neutrophil migration during inflammation is lacking. This study demonstrates that several novel CpG ODN significantly down‐regulate the surface expression of CXCR1/2 and BLT1. In addition, the ODN significantly blocked IL‐8‐induced and LTB4‐induced neutrophil migration in vitro, as well as leucocyte migration in vivo demonstrated in mice by intravital microscopy and in a model of airway inflammation. The down‐regulation of CXCR1 is rapid, occurring 15 min after ODN stimulation, and can be mediated through an endosomally independent mechanism. Inhibition of the IL‐8 and LTB4 pathways may provide new opportunities of therapeutic intervention using ODN to reduce neutrophil infiltration during inflammation.
Bringing in State Regulations, Private Brokers, and Local Employers: A Meso-Level Analysis of Labor Trafficking in Israel
Authors: Kemp Adriana , Raijman Rebeca
Published: August 2014

This article examines the intersection of state policies, private brokers and local employers that fuels trafficking practices and forced labor of legal labor migrants. Focusing on the Israeli case of labor migration, we offer a meso-level institutional analysis of the modes by which private brokers's actions combine with state regulations and policies in creating labor trafficking. More specifically, we stress the active role official labor migration schemes play in the growth of a private brokerage sector driven by profit considerations and in the privatization of state capacities regarding migration control and management. Our analysis demonstrates how systemic features – and not necessarily or solely criminal activities – catalyze trafficking practices taking place first and foremost within the realm of legal migration.
Formation of Ferroelectric Phases in Sb–S–I Glasses
Authors: Savytskii Dmytro , Atwater Katherine , Dierolf Volkmar , Jain Himanshu
Published: August 2014

We have investigated devitrification of glasses within infrared transmitting xSbSI–(100 − x)Sb2S3 pseudo‐binary series, which forms SbSI and Sb2S3 ferroelectric crystal phases. Differential scanning calorimetry (DSC) and X‐ray powder diffraction results show unusual behavior for the formation of the SbSI phase, which occurs by two parallel processes: one‐dimensional crystallization at low temperature which starts from the sample surface, and three‐dimensional bulk crystallization that continues the transformation to crystalline state at higher temperatures. The ratio of the intensities of the high‐temperature exothermal peak to the low‐temperature peak in DSC scans increases as the particle size and heating rate are increased. In contrast to the SbSI phase, the temperature of crystallization for the Sb2S3 phase does not depend on the particle size. Models are proposed for the origin of the various crystallization mechanisms.
Microwave Dielectric Properties and Thermally Stimulated Depolarization Currents of MgF2‐Doped Diopside Ceramics
Authors: Zhang Jie , Zhou Yuanyuan , Peng Bin , Xie Zhenkun , Zhang Xiaohua , Yue Zhenxing
Published: August 2014

A new low‐fired dielectric material derived from CaMg0.9Zn0.1Si2O6 (CMZS) ceramics with high quality factor was synthesized by solid‐state reaction method. The effects of MgF2 addition on the sinterability, phase composition, crystal defects, and microwave dielectric properties of CMZS were investigated. MgF2 was proved not only to lower the sintering temperature to ~1000°C but also to remarkably modify the microwave dielectric properties of CMZS. In addition to the main diopside phase, forsterite was identified as the secondary phase in all MgF2‐doped samples. Dielectric temperature spectra showed that MgF2 induced significant dielectric relaxations associated with oxygen vacancy defects to CMZS. Thermally stimulated depolarization current was, therefore, considered to obtain the defects associated with extrinsic microwave dielectric loss mechanisms. Compared with undoped CMZS, although the concentration of oxygen vacancies showed a notable increase in the 5 wt% MgF2‐doped CMZS, the Q×f values were still improved. Here, with proper MgF2‐doping, it demonstrated that the microwave dielectric loss was basically influenced by phase composition. The excellent characteristics of εr = 7.78, Q×f = 151 800 GHz, and τf = −26.40 ppm/°C were achieved from the 5 wt% MgF2‐doped specimens sintered at 1000°C.