bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucagon‐like peptide 1‐potentiated insulin secretion and proliferation of pancreatic β‐cells GLP‐1促进胰岛素分泌和胰岛β细胞增殖的机制
Authors: Ma Xiaosong , Guan Youfei , Hua Xianxin
Published: April 2014

Glucagon‐like peptide‐1 (GLP‐1) is the primary incretin hormone secreted from the intestine upon uptake of food to stimulate insulin secretion from pancreatic β‐cells. GLP‐1 exerts its effects by binding to its G‐protein coupled receptors and subsequently activating adenylate cyclase, leading to generation of cyclic adenosine monophosphate (cAMP). cAMP stimulates insulin secretion via activation of its effectors PKA and Epac2 in pancreatic β‐cells. In addition to its insulinotropic effects, GLP‐1 also preserves pancreatic β‐cell mass by stimulating β‐cell proliferation. Unlike the action of sulphonylureas in lowering blood glucose levels, action of GLP‐1 is affected by and interplays with glucose levels. Due to such advantages, GLP‐1‐based therapeutics have been rapidly developed and used clinically for treatment of type 2 diabetes. However, molecular mechanisms underlying how GLP‐1 potentiates diminished glucose‐stimulated insulin secretion and β‐cell proliferation under diabetic conditions are not well understood. Here, we review the actions of GLP‐1 in regulation of insulin secretion and pancreatic β‐cell proliferation.
The Effects of Accounting Standard Precision, Auditor Task Expertise, and Judgment Frameworks on Audit Firm Litigation Exposure
Authors: Grenier Jonathan H. , Pomeroy Bradley , Stern Matthew T.
Published: April 2014

Recent research suggests that adopting imprecise accounting standards elevates audit firm litigation exposure and could undermine auditor objectivity if audit firms respond by herding to industry norms. This paper reports the results of two experiments that demonstrate how audit firms can effectively mitigate the elevated litigation exposure without herding to industry norms by staffing engagements with recognized technical experts, using judgment frameworks and automated decision aids, and providing persuasive evidence of adherence to auditing standards. We find that judgment frameworks are particularly well‐suited for defending judgments under imprecise standards, and represent a cost‐effective alternative to using technical experts. However, our results also indicate that judgment frameworks may provide a safe harbor for relatively low‐quality judgments when those frameworks are used under precise standards. We discuss implications for audit firms, courts, and regulators that currently conduct or evaluate audits within and across jurisdictions where the precision of accounting standards varies considerably.
Hierarchical modelling of population growth rate from individual capture–recapture data
Authors: Tenan Simone , Pradel Roger , Tavecchia Giacomo , Igual José M. , Sanz‐Aguilar Ana , Genovart Meritxell , Oro Daniel
Published: April 2014

Estimating rates of population change is essential to achieving theoretical and applied goals in population ecology, and the Pradel (1996, Biometrics, 52: 703.) temporal symmetry method permits direct estimation and modelling of the growth rate of open populations, using capture–recapture data from marked animals.

We present a Bayesian formulation of the Pradel approach that permits a hierarchical modelling of the biological and sampling processes. Two parametrizations for the temporal symmetry likelihood are presented and implemented into a general purpose software in BUGS language.

We first consider a set of simulated scenarios to evaluate performance of a Bayesian variable selection approach to test the temporal linear trend on survival and seniority probability, population growth rate and detectability. We then provide an example application on individual detection information of three species of burrowing nesting seabirds, whose populations cannot be directly counted. For each species, we assess the strength of evidence for temporal random variation and the temporal linear trend on survival probability, population growth rate and detectability.

The Bayesian formulation provides more flexibility, by easily allowing the extension of the original fixed time effects structure to random time effects, an option that is still impractical in a frequentist framework.
Plant virus ecology and epidemiology: historical perspectives, recent progress and future prospects
Authors: Jones R.A.C.
Published: April 2014

After clarifying the relationship between the closely related concepts of ecology and epidemiology as they are used in plant virology, this article provides a historical perspective on the subject before discussing recent progress and future prospects. Ecology focuses on virus populations interacting with host populations within a variable environment, while epidemiology focuses on the complex association between virus and host plant, and factors that influence spread. The evolution and growth of plant virus ecology and epidemiology since its inception to the present day, and the major milestones in its development, are illustrated by examples from influential historical reviews published in the Annals of Applied Biology over the last 100 years. Original research papers published in the journal are used to illustrate important ecological and epidemiological principles and new developments in both fields. Both areas are multifaceted with many factors influencing host plants, and virus and vector behaviour. The highly diverse scenarios that arise from this process influence the virus population and the spatiotemporal dynamics of virus distribution and spread. The review then describes exciting progress in research in the areas of molecular epidemiology and ecology, and understanding virus–vector interactions. Application of new molecular techniques has greatly accelerated the rate of progress in understanding virus populations and the way changes in these populations influence epidemics. Viruses cause direct and plant‐mediated indirect effects on insect vectors by modifying their life cycles, fitness and behaviour, and one of the most fascinating recent fields of research concerns plant‐mediated indirect virus manipulation of insect vector behaviour that encourages virus spread. Next, the review describes the current state of knowledge about spread of plant viruses at the critical agro‐ecological interface between managed and natural vegetation. There is an urgent need to understand how viruses move in both directions between the two and be able to anticipate these kinds of events. To obtain an understanding of, and ability to foresee, such events will require a major research effort into the future. The review finishes by discussing the implications of climate change and rapid technological innovation for the types of research needed to avoid virus threats to future world food supplies and plant biodiversity. There has been lamentably little focus on research to determine the magnitude of the threat from diseases caused in diverse plant virus pathosystems under different climate change scenarios. Increasing technological innovation offers many opportunities to help ensure this situation is addressed, and provide plant virus ecology and epidemiology with a very exciting future.
Post‐operative atelectasis – a randomised trial investigating a ventilatory strategy and low oxygen fraction during recovery
Authors: EDMARK L. , AUNER U. , LINDBÄCK J. , ENLUND M. , HEDENSTIERNA G.
Published: April 2014

Background

Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy with a combination of 1) continuous positive airway pressure (CPAP) or positive end‐expiratory pressure (PEEP) and 2) a reduced end‐expiratory oxygen concentration during recovery would reduce post‐operative atelectasis.

Methods

Sixty patients were randomized into two groups. During anaesthesia induction, inspiratory oxygen fraction (FIO2) was 1.0, and depending on weight, CPAP 6, 7 or 8 cmH2O was applied in both groups via facemask. During maintenance of anaesthesia, a laryngeal mask airway (LMA) was used, and PEEP was 6–8 cmH2O in both groups. Before removal of the LMA, FIO2 was set to 0.3 in the intervention group and 1.0 in the control group. Atelectasis was studied by computed tomography (CT) approximately 14 min post‐operatively.

Results

In one patient in the group given an FIO2 of 0.3 before removal of the LMA a CT scan could not be performed so the patient was excluded. The area of atelectasis was 5.5, 0–16.9 cm2 (median and range), and 6.8, 0–27.5 cm2 in the groups given FIO2 0.3 or FIO2 1.0 before removal of the LMA, a difference that was not statistically significant (P = 0.48). Post‐hoc analysis showed dependence of atelectasis on smoking (despite all were clinically lung healthy) and American Society of Anesthesiologists class (P = 0.038 and 0.015, respectively).

Conclusion

Inducing anaesthesia with CPAP/PEEP and FIO2 1.0 and deliberately reducing FIO2 during recovery before removal of the LMA did not reduce post‐operative atelectasis compared with FIO2 1.0 before removal of the LMA.
Insect–flower interactions: network structure in organic versus conventional vineyards
Authors: Kehinde T. , Samways M. J.
Published: April 2014

Ecosystems are made up of various mutualistic and antagonistic plant and animal interactions. These interactions are subject to various global change phenomena such as land use change and habitat modification. While the effect of environmentally friendly farming practices on the taxonomic diversity of plants and animal species has been reported, it is uncertain whether these schemes provide benefit for species interaction networks. We compared insect–flower interaction networks by analyzing important web structure indices from organic and conventional vineyards and natural vegetation sites in five different localities in the Cape Floristic Region biodiversity hotspot. Average number of insect–flower interactions was higher in organic vineyards compared with conventional vineyards and natural sites. Abundance of flowering plants contributed significantly to explain the observed difference in number of interactions in the model. Other network indices were similar between the different land use types. Our results support the importance of less intensive farming for promoting biodiversity. Approaches such as organic farming are especially beneficial for important interaction networks that drive the process of maintaining biodiversity. The potential of well‐managed vineyard ecosystems for promoting conservation of ecologically important insect–flower interactions is demonstrated.
Searching for the Optimal Rate of Medically Necessary Cesarean Delivery
Authors: Ye Jiangfeng , Betrán Ana Pilar , Guerrero Vela Miguel , Souza Joäo Paulo , Zhang Jun
Published: April 2014

Background

Over the past three decades, the World Health Organization expert panel proposed cesarean delivery rate of 10–15 percent was used as a doctrine for an optimal rate of cesarean delivery despite the lack of concrete evidence. We set out to compile cesarean delivery rates, socioeconomic indicators, and health outcomes by countries in the last three decades to explore the optimal rates for medically necessary cesarean delivery.

Methods

We selected 19 countries which have readily accessible cesarean delivery and low maternal and infant mortality, including countries in North and West Europe, North America, Australia, New Zealand, and Japan. Information on cesarean delivery rate, human development index (HDI), gross domestic products (GDP), maternal, neonatal, and infant mortality rates of each country in the past 30 years was collected from published reports. A two‐level fractional polynomial model was used to model the association between cesarean rate and mortality rates.

Results

Most of the countries have experienced sharp increases in cesarean delivery rates. Once cesarean delivery rate reached 10 percent, with adjustment for HDI and GDP, further increase in cesarean delivery rate had no impact on maternal, neonatal, and infant mortality rates.

Conclusions

Our findings corroborate the statement that a population‐level cesarean section rate above 10–15 percent is hardly justified from the medical perspective.
Editorial: e‐Research for education: Applied, methodological and critical perspectives
Authors: Markauskaite Lina , Reimann Peter
Published: April 2014

This special issue brings together a set of contributions that represent and explore the state of the art regarding the development and application of digital technology‐enhanced research approaches in educational research—e‐research for education. Over the recent years, digital technologies have enhanced various aspects of scholarly practices, such as data collection and analysis, research collaboration, and publishing. New technology‐enhanced research approaches have been emerging in a number of educational research domains, such as learning analytics, educational data mining, digital ethnography and educational informatics. Although the potential of digital approaches has been generally acknowledged, many overarching conceptual and methodological questions remain unexplored and under‐theorised. This special issue provides a landmark collection that synthesises some important empirical and methodological advances in this research field, including methodologically innovative case studies and critical analyses of overarching epistemological, methodological and practical issues that inevitably will shape future developments of this research field.
Fischer, Frank et al (2013) Grand challenges in technology enhanced learningSpringer (Berlin) isbn 978‐3‐319‐01666‐5 79 pp £44.99 http://www.springer.com/education+%26+language/learning+%26+instruction/book/978‐3‐319‐01666‐5
Authors: Laborda Jesús García
Published: April 2014

The world of education progresses by succeeding in its own challenges. This attractive volume excels in suggesting key issues that will need to be addressed in the next years by researchers, teachers and students. If you think the content of this book may be relevant, I recommend that you buy a copy for your own use.

Jesús García Laborda
Sachs, Judyth & Parsell, Mitch ed (2014) Peer review of learning and teaching in higher educationSpringer (Berlin) isbn 978‐94‐007‐7638‐8 219 pp £90 http://www.springer.com/education+%26+language/learning+%26+instruction/book/978‐94‐007‐7638‐8
Authors: Cowan John
Published: April 2014

This clearly written and pertinent text provides a comprehensive, detailed and critical overview of current peer review practice in higher education. Its effective Introduction should enable readers to identify and move quickly to the contributions they are likely to find useful or stimulating—or both! Is the content of this book likely to be relevant to you? If it is, I recommend you buy your own copy.

John Cowan
Human DCXR – another ‘moonlighting protein’ involved in sugar metabolism, carbonyl detoxification, cell adhesion and male fertility?
Authors: Ebert Bettina , Kisiela Michael , Maser Edmund
Published: April 2014

Dicarbonyl/l‐xylulose reductase (DCXR; SDR20C1), a member of the short‐chain dehydrogenase/reductase (SDR) superfamily catalyzes the reduction of α‐dicarbonyl compounds and monosaccharides. Its role in the metabolism of l‐xylulose has been known since 1970, when essential pentosuria was found to be associated with DCXR deficiency. Despite its early discovery, our knowledge about the role of human DCXR in normal physiology and pathophysiology is still incomplete. Sporadic studies have demonstrated aberrant expression in several cancers, but their physiological significance is unknown. In reproductive medicine, where DCXR is commonly referred to as ‘sperm surface protein P34H’, it serves as marker for epididymal sperm maturation and is essential for gamete interaction and successful fertilization. DCXR exhibits a multifunctional nature, both acting as a carbonyl reductase and also performing non‐catalytic functions, possibly resulting from interactions with other proteins. Recent observations associate DCXR with a role in cell adhesion, pointing to a novel function involving tumour progression and possibly metastasis. This review summarizes the current knowledge about human DCXR and its orthologs from mouse and Caenorhabditis elegans (DHS‐21) with an emphasis on its multifunctional characteristics. Due to its close structural relationship with DCXR, carbonyl reductase 2 (Cbr2), a tetrameric enzyme found in several non‐primate species is also discussed. Similar to human DCXR, Cbr2 from golden hamster (P26h) and cow (P25b) is essential for sperm–zona pellucida interaction and fertilization. Because of the apparent similarity of these two proteins and the inconsistent use of alternative names previously, we provide an overview of the systematic classification of DCXR and Cbr2 and a phylogenetic analysis to illustrate their ancestry.
Implant success remains high despite grafting voids in the maxillary sinus
Authors: Tsai Ching‐Yu , Garaicoa‐Pazmino Carlos , Mori Kuniyasu , Benavides Erika , Kaigler Darnell , Kapila Yvonne
Published: April 2014

Objectives

Given that the nature and presence of voids present within grafted sinuses following maxillary sinus elevation procedures were not known, nor was the contribution of these factors to implant success, the purpose of this study was to investigate these parameters and their relationship to implant success.

Materials and Methods

This study evaluated data from 25 subjects who had a lateral window maxillary sinus augmentation procedure. Cone‐beam computed tomography (CBCT) was performed at baseline and 4 months after surgery. CBCT images were used to evaluate grafted sites prior to implant placement. Using CBCT images, three examiners independently measured bone‐grafted areas (BG), void areas (V), and percentage of void areas (V%) from six different sections within grafted sites. The six sections were defined as a cross‐sectional (CS) midpoint, CS mesial point, CS distal point, horizontal section (HS) low point, HS midpoint, and HS high point. Implant success was also determined.

Results

The calculated V% (V/BG) for the CS midpoint, CS mesial point, CS distal point, HS low point, HS midpoint, and HS high point were 5.30 ± 6.67%, 5.79 ± 8.51%, 6.67 ± 7.12%, 2.07 ± 2.56%, 5.30 ± 6.62%, and 4.92 ± 5.17% respectively. Implant success after 6 months of follow‐up approximated 100%.

Conclusions

Although voids within grafts varied in terms of distribution and size, the V% within the HS low point were significantly smaller compared to those within the CS midpoint and CS distal point, which had the most intra‐subject V%. Thus, more attention should be given to the distal aspect of the sinus when compacting graft materials in the lateral wall sinus augmentation procedure. Implant success was not influenced by the existence of voids as implant success remained high.
Surgery of the external nasal valve: the correlation between subjective and objective measurements
Authors: Menger D.J. , Swart K.M.A. , Nolst Trenité G.J. , Georgalas C. , Grolman W.
Published: April 2014

Objectives/hypothesis

Minimum cross‐sectional area of the nasal passage on CT (CT‐MCA) is an objective computerised determination of the minimum cross‐sectional area of the nasal passage on CT. CT‐MCA was evaluated before and after surgery on the external nasal valve using the ‘lateral crus pull‐up’ procedure (LCPU). The outcomes of CT‐MCA were compared with other currently available objective tests for nasal valve patency.

Study design

Prospective cohort study.

Methods

This study included 34 patients undergoing surgery on the external nasal valve with the use of the LCPU technique. CT‐MCA was performed before and after surgery and compared with the subjective perception of nasal passage using the Nasal Obstruction Symptom Evaluation (NOSE) scale and with objective tests such as acoustic rhinometry (A‐MCA), rhinomanometry (NAR) and peak nasal inspiratory flow (PNIF).

Results

This study showed a significant correlation between CT‐MCA and the NOSE scale, PNIF and NAR. Paired‐samples t‐tests showed significant improvement after surgery on CT‐MCA, PNIF and the NOSE scale. Multiple linear regression analysis showed that PNIF, CT‐MCA and NAR were significantly associated with the NOSE scale.

Conclusion

CT‐MCA and PNIF were both significantly correlated and associated with the patient's subjective perception of nasal passage. The surgical procedure, the ‘lateral crus pull‐up’, showed a significant improvement in the postoperative result both subjectively and objectively.
Trefoil factor peptides in serum and sputum from subjects with asthma and COPD
Authors: Viby Niels‐Erik , Pedersen Lars , Lund Thomas Kromann , Kissow Hannelouise , Backer Vibeke , Nexø Ebba , Thim Lars , Poulsen Steen Seier
Published: April 2014

Objective

Trefoil factor peptides (TFF) are secreted onto mucosal surfaces together with mucins and occur in high concentrations in pulmonary secretions from patients with chronic obstructive pulmonary disease (COPD). In the present study, we aimed to explore the concentrations of the peptides in serum and sputum in patients with COPD.

Materials and Methods

Thirty‐five individuals were included in the study, including 11 healthy individuals, 13 indivials with asthma and 11 individuals with COPD. TFF1, TFF2 and TFF3 were measured by enzyme‐linked immunosorbent assay (ELISA) in sputum induced by hypertonic saline inhalation and in serum. Total protein content in sputum was also determined.

Results

In the sputum samples from COPD patients, we observed an eightfold higher concentration of TFF1 and a fivefold higher concentration of TFF3 compared with controls. In the serum samples from COPD patients, we observed three‐, three‐ and twofold higher concentrations of TFF1, TFF2 and TFF3 respectively compared with controls.

Conclusions

There is increased secretion of TFF peptides in the lungs of patients with COPD, as well as significant increases in serum levels. This suggests a role for TFF peptides in the pathogenesis of pulmonary diseases with mucus hypersecretion.
Expression of beclin 1 in non‐small cell lung cancer: an immunohistochemical study
Authors: Lv Zhi‐qiang , Han Jing‐jing , Liu Ye‐qing , Wang Li‐li , Tang Qiong‐lan , Sun Qing , Li Hai‐gang
Published: April 2014

Background

Cigarette smoking causes a variety of adverse human health effects, including lung cancer. The molecular events associated with smoke‐induced carcinogenesis are thought to be related in part to autophagy. Beclin 1 is an important autophagy‐related protein involved in cell death and cell survival.

Aim

The purpose of this investigation was to determine the beclin 1 protein and its association with cigarette smoke and the mutation of epidermal growth factor receptor (EGFR) in non‐small cell lung cancer (NSCLC).

Material and methodology

Our study included 108 cases of non‐small cell lung cancer who were admitted in our hospital. The beclin 1 protein was detected by immunohistochemistry and EGFR mutation by direct sequencing.

Results

Beclin 1 expression could be detected in 15 (13.9%) of 108 specimens. These studies investigated that beclin 1 expression was associated with heavy smoking, the gender and the histological type of NSCLC (P = 0.023, 0.035 and 0.039). No association of beclin 1 with EGFR mutation was found (P > 0.05).

Conclusion

The results from these experiments indicate that heavy smoking may induce the beclin 1 protein in NSCLC.
Typical or atypical pneumonia and severe acute respiratory symptoms in PICU
Authors: Hon Kam Lun , Leung Agnes S. Y. , Cheung Kam Lau , Fu Antony C. , Chu Winnie Chiu Wing , Ip Margaret , Chan Paul K. S.
Published: April 2014

Background and Aims

Mycoplasma pneumoniae (MP) is a common childhood pathogen associated with atypical pneumonia (AP). It is often a mild disease and seldom results in paediatric intensive care (PICU) admission. In 2003, World Health Organization (WHO) coined the word SARS (severe acute respiratory syndrome) in patients with severe acute respiratory symptoms (sars) for an outbreak of AP in Hong Kong due to a novel coronavirus. In 2012, another outbreak of coronavirus AP occurred in the Middle East. Confusing case definitions such as MERS (Middle East respiratory syndrome) and SARI (severe acute respiratory infections) were coined. This paper aims to present a case of MP with sars, ARDS, pneumonia and pleural effusion during the MERS epidemics, and review the incidence and mortality of severe AP with MP.

Methods

We presented a case of MP with sars, acute respiratory distress syndrome (ARDS), pneumonia and pleural effusion during the MERS epidemics, and performed a literature review on the incidence and mortality of severe AP with MP requiring PICU care.

Results

In early 2013, an 11‐year‐old girl presented with sars, ARDS (acute respiratory distress syndrome), right‐sided pneumonia and pleural effusion. She was treated with multiple antibiotics. Streptococcus pneumoniae was not isolated in this girl with ‘typical’ pneumonia by symptomatology and chest radiography, but tracheal aspirate identified MP instead. The respiratory equations are computed with PaO2/FiO2 consistent with severe lung injury. Literature on the incidence and mortality of severe AP with MP requiring PICU care is reviewed. Six, 165 and 293 articles were found when PubMed (a service of the U.S. National Library of Medicine) was searched for the terms ‘mycoplasma’ and ‘ICU’, ‘mycoplasma’ and ‘mortality’, and ‘mycoplasma' and ‘severe’. Mortality and PICU admission associated with MP is general low and rarely reported. Experimental and clinical studies have suggested that the pathogenesis of lung injuries in MP infection is associated with a cell‐mediated immune reaction, and high responsiveness to corticosteroid therapy has been reported especially for severe disease. Management of severe mycoplasma infection in the PICU includes general cardiopulmonary support and specific antimicrobial treatment. Macrolide resistance genotypes have been detected.

Conclusion

We urge health organizations to refrain from the temptation of coining unnecessary new terminology to describe essentially the same conditions each and every time when outbreaks of AP occur.
Risk Tolerance among National Longitudinal Survey of Youth Participants: The Effects of Age and Cognitive Skills
Authors: Mandal Bidisha , Roe Brian E.
Published: April 2014

We analyse how age and cognitive skills are related to risk tolerance among respondents to the National Longitudinal Survey of Youth between 1993 and 2006. Older individuals display lower risk tolerance than younger individuals, though as the panel ages from their early thirties to their mid‐forties, differences in risk tolerance between the oldest and youngest individuals narrow, while panel‐average risk tolerance declines. In contrast to other studies, we find that cognitive skill measured during respondents' teenage years is related to risk tolerance in a non‐linear fashion, where respondents with the lowest and highest skills reveal the greatest risk tolerance.
Dothistroma septosporum on firs (Abies spp.) in the northern Baltics
Authors: Drenkhan R. , Adamson K. , Jürimaa K. , Hanso M.
Published: April 2014

In the spring of 2008, Dothistroma septosporum, a damaging quarantine pathogen of pine foliage, was documented in Järvselja (southeastern Estonia), apparently for the first time, on white fir (Abies concolor). Thus, a new host species and genus for the fungus were recorded. Infection of white fir by D. septosporum, and also of some other fir species, was monitored annually on a transect proceeding from southeastern Estonia to northern Latvia. As a result, D. septosporum was detected also on silver fir (Abies alba). It is not clear why this fungus with a worldwide distribution appeared on this new host genus definitely in northern Europe.
Family‐focused therapy for individuals at clinical high risk for psychosis: treatment fidelity within a multisite randomized trial
Authors: Marvin Sarah E. , Miklowitz David J. , O'Brien Mary P. , Cannon Tyrone D.
Published: April 2014

Aim

Family psychoeducation is an effective adjunct to pharmacotherapy in delaying relapse among patients with schizophrenia and bipolar disorder. This study tested the treatment adherence and competence of newly trained clinicians to an adaptation of family‐focused therapy for individuals at clinical high risk for psychosis (FFT‐CHR).

Methods

The sample included 103 youth or young adults (ages 12–30 years) who had attenuated positive symptoms of psychosis. Families participated in a randomized trial comparing two psychosocial interventions: FFT‐CHR (18 sessions over 6 months) and enhanced care (EC; 3 sessions over 1 month). Following a 1.5‐day training seminar, 24 clinicians from eight study sites received teleconference supervision in both treatment protocols for the 2‐year study period. Treatment fidelity was rated with the 13‐item Therapy Competence and Adherence Scales, Revised.

Results

Supervisors classified 90% of treatment sessions as above acceptable fidelity thresholds (ratings of 5 or better on a 1–7 scale of overall fidelity). As expected, fidelity ratings indicated that FFT‐CHR included a greater emphasis on communication and problem‐solving skills training than EC, but ratings of non‐specific clinician skills, such as maintaining rapport and appropriately pacing sessions, did not differ between conditions. Treatment fidelity was not related to the severity of symptoms or family conflict at study entry.

Conclusions

FFT‐CHR can be administered with high levels of fidelity by clinicians who receive training and supervision. Future studies should examine whether there are more cost‐effective methods for training, supervising and monitoring the fidelity of FFT‐CHR.
Disease stage determines the efficacy of treatment of a paediatric neurodegenerative disease
Authors: Hassiotis Sofia , Beard Helen , Luck Amanda , Trim Paul J. , King Barbara , Snel Marten F. , Hopwood John J. , Hemsley Kim M.
Published: April 2014

Lysosomal storage disorders are a large group of inherited metabolic conditions resulting from the deficiency of proteins involved in lysosomal catabolism, with resulting accumulation of substrates inside the cell. Two‐thirds of these disorders are associated with a neurodegenerative phenotype and, although few therapeutic options are available to patients at present, clinical trials of several treatments including lysosomal enzyme replacement are underway. Although animal studies indicate the efficacy of pre‐symptomatic treatment, it is largely unknown whether symptomatic disease‐related pathology and functional deficits are reversible. To begin to address this, we used a naturally‐occurring mouse model with Sanfilippo syndrome (mucopolysaccharidosis type IIIA) to examine the effectiveness of intracisternal cerebrospinal fluid enzyme replacement in early, mid‐ and symptomatic disease stage mice. We observed a disease‐stage‐dependent treatment effect, with the most significant reductions in primary and secondary substrate accumulation, astrogliosis and protein aggregate accumulation seen in mucopolysaccharidosis type IIIA mice treated very early in the disease course. Affected mice treated at a symptomatic age exhibited little change in these neuropathological markers in the time‐frame of the study. Microgliosis was refractory to treatment regardless of the age at which treatment was instigated. Although longer‐term studies are warranted, these findings indicate the importance of early intervention in this condition.
Role of ictal baseline shifts and ictal high‐frequency oscillations in stereo‐electroencephalography analysis of mesial temporal lobe seizures
Authors: Wu Shasha , Kunhi Veedu Hari Prasad , Lhatoo Samden D. , Koubeissi Mohamad Z. , Miller Jonathan P. , Lüders Hans O.
Published: April 2014

Objective

To assess the role of ictal baseline shifts (IBS) and ictal high‐frequency oscillations (iHFOs) in intracranial electroencephalography (EEG) presurgical evaluation by analysis of the spatial and temporal relationship of IBS, iHFOs with ictal conventional stereo‐electroencephalography (icEEG) in mesial temporal lobe seizures (MTLS).

Methods

We studied 15 adult patients with medically refractory MTLS who underwent monitoring with depth electrodes. Seventy‐five ictal EEG recordings at 1,000 Hz sampling rate were studied. Visual comparison of icEEG, IBS, and iHFOs were performed using Nihon‐Kohden Neurofax systems (acquisition range 0.016–300 Hz). Each recorded ictal EEG was analyzed with settings appropriate for displaying icEEG, IBS, and iHFOs.

Results

IBS and iHFOs were observed in all patients and in 91% and 81% of intracranial seizures, respectively. IBS occurred before (22%), at (57%), or after (21%) icEEG onset. In contrast, iHFOs occurred at (30%) or after (70%) icEEG onset. The onset of iHFOs was 11.5 s later than IBS onset (p < 0.0001). All of the earliest onset of IBS and 70% of the onset of iHFOs overlapped with the ictal onset zone (IOZ). Compared with iHFOs, interictal HFOs (itHFOs) were less correlated with IOZ. In contrast to icEEG, IBS and iHFOs had smaller spatial distributions in 70% and 100% of the seizures, respectively. An IBS dipole was observed in 66% of the seizures. Eighty‐seven percent of the dipoles had a negative pole at the anterior/medial part of amygdala/hippocampus complex (A‐H complex) and a positive pole at the posterior/lateral part of the A‐H complex.

Significance

The results suggest that evaluation of IBS and iHFOs, in addition to routine icEEG, helps in more accurately defining the IOZ. This study also shows that the onset and the spatial distribution of icEEG, IBS, and iHFOs do not overlap, suggesting that they reflect different cellular or network dynamics.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
The cognitive profile of occipital lobe epilepsy and the selective association of left temporal lobe hypometabolism with verbal memory impairment
Authors: Knopman Alex A. , Wong Chong H. , Stevenson Richard J. , Homewood Judi , Mohamed Armin , Somerville Ernest , Eberl Stefan , Wen Lingfeng , Fulham Michael , Bleasel Andrew F.
Published: April 2014

We investigated the cognitive profile of structural occipital lobe epilepsy (OLE) and whether verbal memory impairment is selectively associated with left temporal lobe hypometabolism on [18F]‐fluorodeoxyglucose positron emission tomography (FDG‐PET). Nine patients with OLE, ages 8–29 years, completed presurgical neuropsychological assessment. Composite measures were calculated for intelligence quotient (IQ), speed, attention, verbal memory, nonverbal memory, and executive functioning. In addition, the Wisconsin Card Sorting Test (WCST) was used as a specific measure of frontal lobe functioning. Presurgical FDG‐PET was analyzed with statistical parametric mapping in 8 patients relative to 16 healthy volunteers. Mild impairments were evident for IQ, speed, attention, and executive functioning. Four patients demonstrated moderate or severe verbal memory impairment. Temporal lobe hypometabolism was found in seven of eight patients. Poorer verbal memory was associated with left temporal lobe hypometabolism (p = 0.002), which was stronger (p = 0.03 and p = 0.005, respectively) than the association of left temporal lobe hypometabolism with executive functioning or with performance on the WCST. OLE is associated with widespread cognitive comorbidity, suggesting cortical dysfunction beyond the occipital lobe. Verbal memory impairment is selectively associated with left temporal lobe hypometabolism in OLE, supporting a link between neuropsychological dysfunction and remote hypometabolism in focal epilepsy.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Low‐density lipoprotein receptor is a calcium/magnesium sensor – role of LR4 and LR5 ion interaction kinetics in low‐density lipoprotein release in the endosome
Authors: Martínez‐Oliván Juan , Rozado‐Aguirre Zuriñe , Arias‐Moreno Xabier , Angarica Vladimir E. , Velázquez‐Campoy Adrián , Sancho Javier
Published: April 2014

The low‐density lipoprotein receptor (LDLR) captures circulating lipoproteins and delivers them in the endosome for degradation. Its function is essential for cholesterol homeostasis, and mutations in the LDLR are the major cause of familiar hypercholesterolemia. The release of LDL is usually attributed to endosome acidification. As the pH drops, the affinity of the LDLR/LDL complex is reduced, whereas the strength of a self‐complex formed between two domains of the receptor (i.e. the LDL binding domain and the β‐propeller domain) increases. However, an alternative model states that, as a consequence of a drop in both pH and Ca2+ concentration, the LDLR binding domain is destabilized in the endosome, which weakens the LDLR/LDL complex, thus liberating the LDL particles. In the present study, we test a key underlying assumption of the second model, namely that the lipoprotein binding repeats of the receptor (specifically repeats 4 and 5, LR4 and LR5) rapidly sense endosomal changes in Ca2+ concentration. Our kinetic and thermodynamic analysis of Ca2+ and Mg2+ binding to LR4 and LR5, as well as to the tandem of the two (LR4–5), shows that both repeats spontaneously release Ca2+ in a time scale much shorter than endosomal delivery of LDL, thus acting as Ca2+ sensors that become unfolded under endosomal conditions. Our analysis additionally explains the lower Ca2+ affinity of repeat LR4, compared to LR5, as arising from a very slow Ca2+ binding reaction in the former, most likely related to the lower conformational stability of apolipoprotein LR4, compared to apolipoprotein LR5, as determined from thermal unfolding experiments and molecular dynamics simulations.
Impact of paralarvae and juveniles feeding environment on the neon flying squid (Ommastrephes bartramii) winter–spring cohort stock
Authors: Nishikawa Haruka , Igarashi Hiromichi , Ishikawa Yoichi , Sakai Mitsuo , Kato Yoshiki , Ebina Masahito , Usui Norihisa , Kamachi Masafumi , Awaji Toshiyuki
Published: April 2014

In this study, we found that there were significant positive correlations between the catch per unit effort (CPUE, a squid abundance index) for the neon flying squid (Ommastrephes bartramii) winter–spring cohort and the satellite‐derived chlorophyll a concentrations in their spawning grounds located at 140–160°E where 21°C < sea surface temperature < 25°C from February to May. The spawning grounds of the winter–spring cohort are located in a quiet stream region, and a particle tracking experiment, based on the velocity field obtained from an ocean data assimilation system, showed that paralarvae and juveniles aged <90 days remained in their spawning grounds and the chlorophyll a concentration in their habitat had a significant positive correlation with the CPUE. A backward particle tracking experiment also showed that the chlorophyll a concentration in the spawning grounds had a significant positive correlation with the autumn–winter mixed layer depth. Based on these results, we hypothesize that the CPUE interannual variability is caused by variations in the feeding environment of the paralarvae and juveniles, which may be linked to autumn–winter mixed layer depth variations.
Reliability and validity of a novel Haemophilia‐specific Self‐Efficacy Scale
Authors: Lock J. , Raat H. , Peters M. , Tamminga R. Y. J. , Leebeek F. W. G. , Moll H. A. , Cnossen M. H.
Published: April 2014

Higher self‐efficacy in chronic disease patients is associated with higher development of self‐management skills and increased quality‐of‐life. Quantification and monitoring of self‐efficacy is therefore of importance. Self‐efficacy in haemophilia patients has received little attention due to lack of standardized scales. To validate the novel Haemophilia‐specific Self‐Efficacy Scale (HSES) in haemophilia patients on prophylactic home treatment, haemophilia patients aged 1–18 years on prophylactic treatment ≥1 year were included from three Dutch Haemophilia Treatment Centres. The HSES consists of 12 items, relating to perceptions of the ability to function on a day‐to‐day basis with regard to patient's disease. Retest was performed in a subsample. Validity was proven by the General Self‐Efficacy Scale and by the health‐related quality‐of‐life assessment tool Haemo‐QoL. Data were analysed from 53 children (response 75%), with a mean age of 9.8 years (SD 4.0). Mean total scale score of HSES was 55.5 (SD 4.7; range 38–60), with a ceiling effect of 17%. The HSES showed adequate internal consistency (Cronbach's alpha 0.72) and good test–retest reliability (Intra‐Class‐Correlation coefficient 0.75; P < 0.01; n = 37). The convergent validity was adequate as haemophilia‐specific self‐efficacy correlated significantly with general self‐efficacy (r = 0.38; P < 0.01). High HSES scores correlated significantly with quality‐of‐life as measured by the Haemo‐QoL (r = −0.42; P ≤ 0.01). The novel HSES is a reliable and valid tool to assess self‐efficacy in paediatric haemophilia patients on prophylactic home treatment. High self‐efficacy correlated with higher quality‐of‐life, further underlining the importance to standardly assess, monitor and improve self‐efficacy.
Low expression of BARX2 in human primary hepatocellular carcinoma correlates with metastasis and predicts poor prognosis
Authors: Zhang Yi , Zhang Jia‐Xing , Huang Lin‐Lin , He Long‐Jun , Liao Yi‐Ji , Lai Ying‐Rong , Deng Hai‐Xia , Tian Xiao‐Peng , Kung Hsiang Fu , Xie Dan , Zhu Sen‐Lin
Published: April 2014

Aim

The homeobox gene Barx2 was recently identified as a regulator of ovarian and breast cancer; however, the expression level of BARX2 and its significance in hepatocellular carcinoma (HCC) remain unknown.

Methods

Protein and mRNA expression levels of Barx2 were examined using Western blotting and real‐time PCR respectively, in paired HCC tissue and matched adjacent non‐cancerous tissue from 12 patients. The expression levels of epithelial–mesenchymal transition (EMT) markers were also detected in relation to BARX2 expression. Lastly, immunohistochemistry for BARX2 was also performed on a tissue microarray containing 231 HCC tissue samples.

Results

We observed that BARX2 expression was lower in HCC tissues compared to matching adjacent non‐cancerous tissue. The low expression level of BARX2 was significantly correlated with metrics of tumor size, tumor differentiation, clinical stage, metastasis and relapse. Furthermore, the patients with low BARX2 expression had adverse survival outcomes. Importantly, multivariate Cox regression analysis revealed that low BARX2 expression was an independent marker for lower overall survival (P = 0.007). Moreover, a significant negative relationship was observed between the expression of BARX2 and markers of EMT.

Conclusion

These findings provide evidence that the low expression level of BARX2 in HCC is significantly correlated with tumor metastasis, and that BARX2 may be an independent prognostic biomarker for patients with HCC.
Decreased expression of P54nrb/NonO correlates with collagen deposition and fibrosis in human aortic dissection
Authors: Ren Zongli , Wang Zhiwei , Hu Zhipeng , Hu Xiaoping , Zhang Hao , Wu Hongbing , Hu Rui , Liu Huan
Published: April 2014

Aims

Aortic dissection (AD) is characterized by changes in the extracellular matrix, including fibrosis with collagen production. P54nrb/NonO is known to be involved in collagen formation. In this study, we examined whether AD is associated with abnormal P54nrb/NonO expression.

Methods and results

Aortic specimens and serum were obtained from 10 patients with AD and 10 controls. In‐vitro cultures of vascular smooth muscle cells (VSMCs) and adventitial fibroblasts (AFs) were obtained from organ donors. P54nrb/NonO protein and mRNA levels were determined by Western blot, immunohistochemistry and quantitative real‐time reverse transcription–polymerase chain reaction (quantitative real‐time RT–PCR). To evaluate collagen expression, we stained tissue sections with Masson's trichrome. Serum concentration of TNF‐α was determined by enzyme‐linked immunosorbent assay (ELISA). Aortic P54nrb/NonO protein and mRNA were decreased in AD patients, compared with controls. Decreased P54nrb/NonO mRNA correlated significantly with increased collagen deposition and fibrosis in AD aortas. In VSMCs and AFs from normal human aortas, P54nrb/NonO was expressed strongly and localized to the nucleus.

Conclusions

Patients with AD exhibited significantly decreased expression of P54nrb/NonO. The significant correlation between P54nrb/NonO and collagen may point to novel thinking about collagen metabolism research in AD aorta.
Hemicraniectomy for Malignant Middle Cerebral Artery Infarction: Current Status and Future Directions
Authors: Neugebauer Hermann , Jüttler Eric
Published: April 2014

Malignant middle cerebral artery infarction is a life-threatening sub-type of ischemic stroke that may only be survived at the expense of permanent disability. Decompressive hemicraniectomy is an effective surgical therapy to reduce mortality and improve functional outcome without promoting most severe disability. Evidence derives from three European randomized controlled trials in patients up to 60 years. The recently finished DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY – II trial gives now high-level evidence for the effectiveness of decompressive hemicraniectomy in patients older than 60 years. Nevertheless, pressing issues persist that need to be answered in future clinical trials, e.g. the acceptable degree of disability in survivors of malignant middle cerebral artery infarction, the importance of aphasia, and the best timing for decompressive hemicraniectomy. This review provides an overview of the current diagnosis and treatment of malignant middle cerebral artery infarction with a focus on decompressive hemicraniectomy and outlines future perspectives.
Prevalence of Stroke and Coexistent Conditions: Disparities between Indigenous and Nonindigenous Western Australians
Authors: Katzenellenbogen Judith M. , Knuiman Matthew W. , Sanfilippo Frank M. , Hobbs Michael S. T. , Thompson Sandra C.
Published: April 2014

Background

Worldwide, the prevalence of stroke is poorly described in indigenous populations, despite high stroke burden. This paper reports the average point prevalence of hospitalized stroke and coexistent conditions (2007–2011) in indigenous and nonindigenous people in Western Australia, the largest and most sparsely populated Australian jurisdiction.

Methods

Using state-wide linked hospital and mortality data, indigenous and nonindigenous prevalent stroke cases (aged 25–84 years) were identified after reviewing stroke admissions over a fixed 20-year look-back period. Prevalent cases were those alive at midyear of each study year. The 2007–2011 period prevalence was a weighted average of annual prevalence. Histories of 11 comorbidities were identified using the 20-year look-back period.

Results

Indigenous cases comprised 5% of the average 13 591 annual prevalent cases. Indigenous patients were more likely to be younger, female, and have unknown stroke type. Indigenous prevalence was higher at every age. The age-standardized prevalence in indigenous men (33·7 per 1000; 95% confidence interval 31·9–35·4) was 3.7 times greater than in nonindigenous men (9·1 per 1000; 95% confidence interval 9·0–9·2). The corresponding estimates for women were 27·1 per 1000 (25·7–28·4) and 6·1 per 1000 (6·0–6·2) (ratio = 4·4). The percentage with selected comorbid conditions was substantially higher for indigenous patients.

Conclusions

The high stroke prevalence in indigenous Western Australians, coupled with clinical complexity from comorbid conditions, requires access to culturally appropriate medical, rehabilitation, and logistical support. Intensified primary and secondary prevention is needed to reduce the impact of stroke on indigenous people.