bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteolytic processing, deubiquitinase and interferon antagonist activities of Middle East respiratory syndrome coronavirus papain-like protease
Authors: Yang Xingxing , Chen Xiaojuan , Bian Guangxing , Tu Jian , Xing Yaling , Wang Yayun , Chen Zhongbin
Published: December 2013

The emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe pulmonary disease in humans and represents the second example of a highly pathogenic coronavirus (CoV) following severe acute respiratory syndrome coronavirus (SARS-CoV). Genomic studies revealed that two viral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro), process the polyproteins encoded by the MERS-CoV genomic RNA. We previously reported that SARS-CoV PLpro acts as both deubiquitinase (DUB) and IFN antagonist, but the function of the MERS-CoV PLpro was poorly understood. In this study, we characterized MERS-CoV PLpro, which is a protease and can recognize and process the cleavage sites (CS) of nsp1-2, nsp2-3 and nsp3-4. The LXGG consensus cleavage sites in the N terminus of pp1a/1ab, which is generally essential for CoV PLpro-mediated processing, were also characterized in MERS-CoV. MERS-CoV PLpro, like human SARS-CoV PLpro and NL63-CoV PLP2, is a viral deubiquitinating enzyme. It acts on both K48- and K63-linked ubiquitination and ISG15-linked ISGylation. We confirmed that MERS-CoV PLpro acts as an IFN antagonist through blocking the phosphorylation and nuclear translocation of IFN regulatory factor 3 (IRF3). These findings indicate that MERS-CoV PLpro acts as a viral DUB and suppresses production of IFN-β by an interfering IRF3-mediated signalling pathway, in addition to recognizing and processing the CS at the N terminus of replicase polyprotein to release the non-structural proteins. The characterization of proteolytic processing, DUB and IFN antagonist activities of MERS-CoV PLpro would reveal the interactions between MERS-CoV and its host, and be applicable to develop strategies targeting PLpro for the effective control of MERS-CoV infection.
Interference with jasmonic acid-regulated gene expression is a general property of viral suppressors of RNA silencing but only partly explains virus-induced changes in plant–aphid interactions
Authors: Westwood Jack H. , Lewsey Mathew G. , Murphy Alex M. , Tungadi Trisna , Bates Anne , Gilligan Christopher A. , Carr John P.
Published: December 2013

The cucumber mosaic virus (CMV) 2b viral suppressor of RNA silencing (VSR) inhibits host responses to jasmonic acid (JA), a chemical signal regulating resistance to insects. Previous experiments with a CMV subgroup IA strain and its2bgene deletion mutant suggested that VSRs might neutralize aphid (Myzus persicae) resistance by inhibiting JA-regulated gene expression. To further investigate this, we examined JA-regulated gene expression and aphid performance inNicotiana benthamianainfected with Potato virus X, Potato virus Y, Tobacco mosaic virus and a subgroup II CMV strain, as well as in transgenic plants expressing corresponding VSRs (p25, HC-Pro, 126 kDa and 2b). All the viruses or their VSRs inhibited JA-induced gene expression. However, this did not always correlate with enhanced aphid performance. Thus, VSRs are not the sole viral determinants of virus-induced changes in host–aphid interactions and interference with JA-regulated gene expression cannot completely explain enhanced aphid performance on virus-infected plants.
Hawkish but helpful: When cultural group selection favors within-group aggression
Authors: Hanowell Ben
Published: December 2013

The origin of cooperation is a central problem in evolutionary biology and social science. Cultural group selection and parochial altruism are popular but controversial evolutionary explanations for large-scale cooperation. Proponents of the cultural group selection hypothesis argue that the human tendency to conform—a consequence of our reliance on social learning—maintained sufficient between-group variation to allow group selection (which favors altruism) to overpower individual selection (which favors selfishness), whereupon large-scale altruism could emerge. Proponents of the parochial altruism hypothesis argue that altruism could emerge in tandem with hostility toward other groups if the combination of the two traits increased success in inter-group contests. Proponents of both hypotheses assume that cooperation is altruistic and that within-group conflict is antithetical to cooperation, implying that group selection for cooperation reduces within-group conflict. Yet within-group conflict need not be antithetical to cooperation. This essay uses a mathematical model to show that selection between groups can lead to greater within-group aggression if within-group aggression enhances the value of individually costly public goods contributions. This model may help to explain cross-cultural associations between warfare, socialization for aggression, aggressive sports, and interpersonal violence among humans. It may also apply to other forms of inter-group conflict among humans. Finally, the model suggests that group selection can lead to disharmony within groups, a caveat to the use of group selection models to inform social policy.
Astrocytes engage unique molecular programs to engulf pruned neuronal debris from distinct subsets of neurons
Authors: Tasdemir-Yilmaz Ozge E. , Freeman Marc R.
Published: December 2013

Precise neural circuit assembly is achieved by initial overproduction of neurons and synapses, followed by refinement through elimination of exuberant neurons and synapses. Glial cells are the primary cells responsible for clearing neuronal debris, but the cellular and molecular basis of glial pruning is poorly defined. Here we show that Drosophila larval astrocytes transform into phagocytes through activation of a cell-autonomous, steroid-dependent program at the initiation of metamorphosis and are the primary phagocytic cell type in the pupal neuropil. We examined the developmental elimination of two neuron populations—mushroom body (MB) γ neurons and vCrz+ neurons (expressing Corazonin [Crz] neuropeptide in the ventral nerve cord [VNC])—where only neurites are pruned or entire cells are eliminated, respectively. We found that MB γ axons are engulfed by astrocytes using the Draper and Crk/Mbc/dCed-12 signaling pathways in a partially redundant manner. In contrast, while elimination of vCrz+ cell bodies requires Draper, elimination of vCrz+ neurites is mediated by Crk/Mbc/dCed-12 but not Draper. Intriguingly, we also found that elimination of Draper delayed vCrz+ neurite degeneration, suggesting that glia promote neurite destruction through engulfment signaling. This study identifies a novel role for astrocytes in the clearance of synaptic and neuronal debris and for Crk/Mbc/dCed-12 as a new glial pathway mediating pruning and reveals, unexpectedly, that the engulfment signaling pathways engaged by glia depend on whether neuronal debris was generated through cell death or local pruning.
ArabidopsisChlorophyll Biosynthesis: An Essential Balance between the Methylerythritol Phosphate and Tetrapyrrole Pathways
Authors: Kim Se , Schlicke Hagen , Van Ree Kalie , Karvonen Kristine , Subramaniam Anant , Richter Andreas , Grimm Bernhard , Braam Janet
Published: December 2013

Chlorophyll, essential for photosynthesis, is composed of a chlorin ring and a geranylgeranyl diphosphate (GGPP)–derived isoprenoid, which are generated by the tetrapyrrole and methylerythritol phosphate (MEP) biosynthesis pathways, respectively. Although a functional MEP pathway is essential for plant viability, the underlying basis of the requirement has been unclear. We hypothesized that MEP pathway inhibition is lethal because a reduction in GGPP availability results in a stoichiometric imbalance in tetrapyrrolic chlorophyll precursors, which can cause deadly photooxidative stress. Consistent with this hypothesis, lethality of MEP pathway inhibition in Arabidopsis thaliana by fosmidomycin (FSM) is light dependent, and toxicity of MEP pathway inhibition is reduced by genetic and chemical impairment of the tetrapyrrole pathway. In addition, FSM treatment causes a transient accumulation of chlorophyllide and transcripts associated with singlet oxygen-induced stress. Furthermore, exogenous provision of the phytol molecule reduces FSM toxicity when the phytol can be modified for chlorophyll incorporation. These data provide an explanation for FSM toxicity and thereby provide enhanced understanding of the mechanisms of FSM resistance. This insight into MEP pathway inhibition consequences underlines the risk plants undertake to synthesize chlorophyll and suggests the existence of regulation, possibly involving chloroplast-to-nucleus retrograde signaling, that may monitor and maintain balance of chlorophyll precursor synthesis.
Arabidopsis Kelch Repeat F-Box Proteins Regulate Phenylpropanoid Biosynthesis via Controlling the Turnover of Phenylalanine Ammonia-Lyase
Authors: Zhang Xuebin , Gou Mingyue , Liu Chang-Jun
Published: December 2013

Phenylalanine ammonia-lyase (PAL) catalyzes the first rate-limiting step in the phenylpropanoid pathway, which controls carbon flux to a variety of bioactive small-molecule aromatic compounds, and to lignin, the structural component of the cell wall. PAL is regulated at both the transcriptional and translational levels. Our knowledge about the transcriptional regulation of PAL is relatively comprehensive, but our knowledge of the molecular basis of the posttranslational regulation of PAL remains limited. Here, we demonstrate that the Arabidopsis thaliana Kelch repeat F-box (KFB) proteins KFB01, KFB20, and KFB50 physically interact with four PAL isozymes and mediate their proteolytic turnover via the ubiquitination-26S proteasome pathway. The KFB genes are differentially expressed in Arabidopsis tissues and respond to developmental and environmental cues. Up- or downregulation of their expression reciprocally affects the stability of the PAL enzymes, consequently altering the levels of phenylpropanoids. These data suggest that the KFB-mediated protein ubiquitination and degradation regulates the proteolysis of PALs, thus posttranslationally regulating phenylpropanoid metabolism. Characterizing the KFB-mediated proteolysis of PAL enzymes may inform future strategies for manipulating the synthesis of bioactive phenolics.
How effective are agri‐environment schemes for protecting and improving herpetofaunal diversity in Australian endangered woodland ecosystems?
Authors: Michael Damian R. , Wood Jeffrey T. , Crane Mason , Montague‐Drake Rebecca , Lindenmayer David B.
Published: December 2013

Agricultural intensification is a major cause of reptile and amphibian decline world‐wide, prompting concern on how to best protect biodiversity in commodity production landscapes and meet global food demands. Agri‐environment schemes (AES) attempt to integrate biodiversity conservation in agricultural landscapes but are often compromised by a lack of baseline data, monitoring and evaluation. Few studies have examined the benefits of AES in protecting biodiversity relative to the wider farming landscape, and no studies have explicitly quantified the effectiveness of AES to increase herpetofaunal diversity.

To examine whether AES protect and increase herpetofauna, we established a landscape‐wide biodiversity monitoring programme in threatened semi‐arid and temperate woodland communities in south‐eastern Australia.

With 31 species recorded, regional herpetofaunal diversity was relatively high, whereas local diversity was low. Herpetofaunal richness and reptile assemblage structure did not differ significantly between sites under AES and sites managed for livestock production. A gradient in species richness as a function of time‐since‐management intervention was not evident, although the abundance of one lizard species increased under vegetation management. Reptile richness and frog abundance differed significantly among vegetation types.

Herpetofaunal richness was positively related to native plant richness and bare ground cover, whereas Boulenger's skink Morethia boulengeri was negatively affected by bare ground cover. The ragged snake‐eyed skink Cryptoblepharus pannosus was positively related to the amount of woody debris.

Synthesis and applications. In this system, strong habitat specificity implies local‐scale management interventions under agri‐environment schemes (AES) may not significantly increase herpetofaunal diversity in the short term. Vegetation management is likely to increase the abundance of common lizard species rather than increase local species richness due to barrier effects. Future incentive schemes should focus on improving habitat connectivity, enhancing pasture condition and increasing woody debris in the agricultural matrix to dissolve dispersal barriers and mitigate the legacy of historical land‐use practices. We propose that AES, which manage mosaics of intergrading vegetation types at multiple spatial scales, will protect maximum herpetofaunal diversity. These recommendations have implications for AES world‐wide, many of which currently do not adequately address the habitat requirements of herpetofauna.
Effects of experimental warming on nitrogen concentration and biomass of forage plants for an arctic herbivore
Authors: Doiron Madeleine , Gauthier Gilles , Lévesque Esther
Published: December 2013

In many arctic herbivores, the growth of young depends upon a synchrony between hatching date and seasonal change in plant nutritive quality. If plants respond more quickly than herbivores to climate warming, this may cause a mismatch between the availability of high‐quality food and the hatching of young. This study examines the impact of experimental warming on the main food plants of an arctic herbivore, the greater snow goose (Chen caerulescens atlanticaL.) breeding on Bylot Island, Nunavut, Canada.

During summers 2007–2009, we increased the temperature using small glasshouses (open‐top chambers, OTC) in two habitats, wetlands and mesic tundra. Every 10 days, we measured above‐ground plant biomass and a proxy of nutritive quality, nitrogen concentration, of graminoid plants in warmed and control plots from snowmelt in June until late July.

Open‐top chambers increased mean maximum temperature by up to 2.0 °C in wetlands and 4.6 °C in mesic tundra. Annual warming significantly increased biomass of graminoids by up to 29% in wetlands and 20% in mesic tundra. There was no difference in nitrogen concentration of the four plant species sampled (Dupontia fisheri, Eriophorum scheuchzeri, Arctagrostis latifolia and Luzula spp.) early in the season, but the seasonal decline in nitrogen occurred more rapidly in warmed than in control plots (10% to 14% less nitrogen in warmed plots in July). This effect was consistent across the 3 years of the experiment and independent of annual variation in plant phenology. There was either a weak positive effect or no effect of the warming treatment on the nitrogen biomass of plants depending on species or period of the season.

Synthesis. Our results show that warming speeds up plant phenology and the seasonal decline in nutritive quality for arctic herbivores. Because young herbivores like geese are highly sensitive to the nitrogen concentration of their food, a warmer climate will likely reduce their growth. Climate warming may therefore have a negative impact on the population dynamic of arctic herbivores by reducing the quality of their summer forage.
The Impact of Electronic Health Records on Workflow and Financial Measures in Primary Care Practices
Authors: Fleming Neil S. , Becker Edmund R. , Culler Steven D. , Cheng Dunlei , McCorkle Russell , Graca Briget da , Ballard David J.
Published: December 2013

Objective

To estimate a commercially available ambulatory electronic health record's (EHR's) impact on workflow and financial measures.

Data Sources/Study Setting

Administrative, payroll, and billing data were collected for 26 primary care practices in a fee‐for‐service network that rolled out an EHR on a staggered schedule from June 2006 through December 2008.

Study Design

An interrupted time series design was used. Staffing, visit intensity, productivity, volume, practice expense, payments received, and net income data were collected monthly for 2004–2009. Changes were evaluated 1–6, 7–12, and >12 months postimplementation.

Data Collection/Extraction Methods

Data were accessed through a SQLserver database, transformed into SAS®, and aggregated by practice. Practice‐level data were divided by full‐time physician equivalents for comparisons across practices by month.

Principal Findings

Staffing and practice expenses increased following EHR implementation (3 and 6 percent after 12 months). Productivity, volume, and net income decreased initially but recovered to/close to preimplementation levels after 12 months. Visit intensity did not change significantly, and a secular trend offset the decrease in payments received.

Conclusions

Expenses increased and productivity decreased following EHR implementation, but not as much or as persistently as might be expected. Longer term effects still need to be examined.
The Medicare Electronic Health Record Incentive Program: Provider Performance on Core and Menu Measures
Authors: Wright Adam , Feblowitz Joshua , Samal Lipika , McCoy Allison B. , Sittig Dean F.
Published: December 2013

Objective

To measure performance by eligible health care providers on CMS's meaningful use measures.

Data Source

Medicare Electronic Health Record Incentive Program Eligible Professionals Public Use File (PUF), which contains data on meaningful use attestations by 237,267 eligible providers through May 31, 2013.

Study Design

Cross‐sectional analysis of the 15 core and 10 menu measures pertaining to use of EHR functions reported in the PUF.

Principal Findings

Providers in the dataset performed strongly on all core measures, with the most frequent response for each of the 15 measures being 90–100 percent compliance, even when the threshold for a particular measure was lower (e.g., 30 percent). PCPs had higher scores than specialists for computerized order entry, maintaining an active medication list, and documenting vital signs, while specialists had higher scores for maintaining a problem list, recording patient demographics and smoking status, and for providing patients with an after‐visit summary. In fact, 90.2 percent of eligible providers claimed at least one exclusion, and half claimed two or more.

Conclusions

Providers are successfully attesting to CMS's requirements, and often exceeding the thresholds required by CMS; however, some troubling patterns in exclusions are present. CMS should raise program requirements in future years.
Clinical Benefits of Electronic Health Record Use: National Findings
Authors: King Jennifer , Patel Vaishali , Jamoom Eric W. , Furukawa Michael F.
Published: December 2013

Objective

To assess whether physicians' reported electronic health record (EHR) use provides clinical benefits and whether benefits depend on using an EHR meeting Meaningful Use criteria or length of EHR experience.

Data Source

The 2011 Physician Workflow study, representative of U.S. office‐based physicians.

Study Design

Cross‐sectional data were used to examine the association of EHR use with enhanced patient care overall and nine specific clinical benefits.

Principal Findings

Most physicians with EHRs reported EHR use enhanced patient care overall (78 percent), helped them access a patient's chart remotely (81 percent), and alerted them to a potential medication error (65 percent) and critical lab values (62 percent). Between 30 and 50 percent of physicians reported that EHR use was associated with clinical benefits related to providing recommended care, ordering appropriate tests, and facilitating patient communication. Using EHRs that met Meaningful Use criteria and having 2 or more years of EHR experience were independently associated with reported benefits. Physicians with EHRs meeting Meaningful Use criteria and longer EHR experience were most likely to report benefits across all 10 measures.

Conclusions

Physicians reported EHR use enhanced patient care overall. Clinical benefits were most likely to be reported by physicians using EHRs meeting Meaningful Use criteria and longer EHR experience.
The Association between EHRs and Care Coordination Varies by Team Cohesion
Authors: Graetz Ilana , Reed Mary , Shortell Stephen M. , Rundall Thomas G. , Bellows Jim , Hsu John
Published: December 2013

Objective

To examine whether primary care team cohesion changes the association between using an integrated outpatient‐inpatient electronic health record (EHR) and clinician‐rated care coordination across delivery sites.

Study Design

Self‐administered surveys of primary care clinicians in a large integrated delivery system, collected in 2005 (N = 565), 2006 (N = 678), and 2008 (N = 626) during the staggered implementation of an integrated EHR (2005–2010), including validated questions on team cohesion. Using multivariable regression, we examined the combined effect of EHR use and team cohesion on three dimensions of care coordination across delivery sites: access to timely and complete information, treatment agreement, and responsibility agreement.

Principal Findings

Among clinicians working in teams with higher cohesion, EHR use was associated with significant improvements in reported access to timely and complete information (53.5 percent with EHR vs. 37.6 percent without integrated‐EHR), agreement on treatment goals (64.3 percent vs. 50.6 percent), and agreement on responsibilities (63.9 percent vs. 55.2 percent, all p < .05). We found no statistically significant association between use of the integrated‐EHR and reported care coordination in less cohesive teams.

Conclusion

The association between EHR use and reported care coordination varied by level of team cohesion. EHRs may not improve care coordination in less cohesive teams.
A Statewide Assessment of Electronic Health Record Adoption and Health Information Exchange among Nursing Homes
Authors: Abramson Erika L. , McGinnis Sandra , Moore Jean , Kaushal Rainu ,   HITEC investigators
Published: December 2013

Objective

To determine rates of electronic health record (EHR) adoption and health information exchange (HIE) among New York State (NYS) nursing homes.

Data Sources/Study Setting

Primary data collected from a novel survey administered between November 2011 and March 2012 to all NYS nursing homes.

Study Design

We used a cross‐sectional study design to assess level of EHR implementation, automation of key functionalities, participation in HIE, and barriers to adoption.

Data Collection/Extraction Methods

We used descriptive statistics to characterize rates of EHR adoption and participation in HIE and logistic regression to identify nursing home characteristics associated with EHR adoption and HIE.

Principal Findings

We received responses from 375 of 632 nursing homes (59.3 percent). Of respondents, almost one in five (n = 66, 18.0 percent) reported having a fully implemented and operational EHR and a majority (n = 192, 54.4 percent) reported electronically exchanging information. Nursing homes with 100–159 beds were significantly less likely than other facilities to have implemented or be in the process of implementing an EHR (p = .011).

Conclusions

Our findings present an important systematic look at EHR adoption and HIE by NYS nursing homes. Although the nursing home sector has been reported to lag in health information technology adoption, our results are encouraging. However, they suggest much room for growth and highlight the need for targeted initiatives to achieve more widespread adoption in this important health care sector.
Where Are We on the Diffusion Curve? Trends and Drivers of Primary Care Physicians' Use of Health Information Technology
Authors: Audet Anne‐Marie , Squires David , Doty Michelle M.
Published: December 2013

Objective

To describe trends in primary care physicians' use of health information technology (HIT) between 2009 and 2012, examine practice characteristics associated with greater HIT capacity in 2012, and explore factors such as delivery system and payment reforms that may affect adoption and functionality.

Data

We used data from the 2012 and 2009 Commonwealth Fund International Health Policy Surveys of Primary Care Physicians. The data were collected in both years by postal mail between March and July among a nationally representative sample of primary care physicians in the United States.

Study Design

We compared primary care physicians' HIT capacity in 2009 and 2012. We employed multivariable logistic regression to analyze whether participating in an integrated delivery system, sharing resources and support with other practices, and being eligible for financial incentives were associated with greater HIT capacity in 2012.

Principal Findings

Primary care physicians' HIT capacity has significantly expanded since 2009, although solo practices continue to lag. Practices that are part of an integrated delivery system or share resources with other practices have higher rates of electronic medical record (EMR) adoption, multifunctional HIT, electronic information exchange, and electronic access for patients. Receiving or being eligible for financial incentives is associated with greater adoption of EMRs and information exchange.

Conclusions

Federal efforts to increase adoption have coincided with a rapid increase in HIT capacity. Delivery system and payment reforms and federally funded extension programs could offer promising pathways for further diffusion.
The Health IT Regional Extension Center Program: Evolution and Lessons for Health Care Transformation
Authors: Lynch Kimberly , Kendall Mat , Shanks Katherine , Haque Ahmed , Jones Emily , Wanis Maggie G. , Furukawa Michael , Mostashari Farzad
Published: December 2013

Objective

Assess the Regional Extension Center (REC) program's progress toward its goal of supporting over 100,000 providers in small, rural, and underserved practices to achieve meaningful use (MU) of an electronic health record (EHR).

Data Sources/Study Setting

Data collected January 2010 through June 2013 via monitoring and evaluation of the 4‐year REC program.

Study Design

Descriptive study of 62 REC programs.

Data Collection/Extraction Methods

Primary data collected from RECs were merged with nine other datasets, and descriptive statistics of progress by practice setting and penetration of targeted providers were calculated.

Principal Findings

RECs recruited almost 134,000 primary care providers (PCPs), or 44 percent of the nation's PCPs; 86 percent of these were using an EHR with advanced functionality and almost half (48 percent) have demonstrated MU. Eighty‐three percent of Federally Qualified Health Centers and 78 percent of the nation's Critical Access Hospitals were participating with an REC.

Conclusions

RECs have made substantial progress in assisting PCPs with adoption and MU of EHRs. This infrastructure supports small practices, community health centers, and rural and public hospitals to use technology for care delivery transformation and improvement.
Reliability of a standardized test in Swedish for evaluation of reading performance in healthy eyes. Interchart and test–retest analyses
Authors: Thaung Jörgen , Olseke Kjell , Ahl Johan , Sjöstrand Johan
Published: December 2013

Purpose

The purpose of our study was to establish a practical and quick test for assessing reading performance and to statistically analyse interchart and test–retest reliability of a new standardized Swedish reading chart system consisting of three charts constructed according to the principles available in the literature.

Methods

Twenty‐four subjects with healthy eyes, mean age 65 ± 10 years, were tested binocularly and the reading performance evaluated as reading acuity, critical print size and maximum reading speed. The test charts all consist of 12 short text sentences with a print size ranging from 0.9 to −0.2 logMAR in approximate steps of 0.1 logMAR. Two testing sessions, in two different groups (C1 and C2), were under strict control of luminance and lighting environment. Reading performance tests with chart T1, T2 and T3 were used for evaluation of interchart reliability and test data from a second session 1 month or more apart for the test–retest analysis.

Results

The testing of reading performance in adult observers with short sentences of continuous text was quick and practical. The agreement between the tests obtained with the three different test charts was high both within the same test session and at retest.

Conclusion

This new Swedish variant of a standardized reading system based on short sentences and logarithmic progression of print size provides reliable measurements of reading performance and preliminary norms in an age group around 65 years. The reading test with three independent reading charts can be useful for clinical studies of reading ability before and after treatment.
Deep sclerectomy in normal‐tension glaucoma with and without mitomycin‐c
Authors: Suominen Sakari , Harju Mika , Kurvinen Leena , Vesti Eija
Published: December 2013

Purpose

To compare the outcome of deep sclerectomy (DS) with and without mitomycin‐C (MMC) in patients with normal‐tension glaucoma (NTG).

Methods

We prospectively analysed the results of 37 eyes of 37 consecutive patients with NTG (age; mean ± SD; 64 ± 7 years) who underwent DS with a collagen implant. Patients were randomized to the MMC and non‐MMC groups. Subconjunctival MMC (0.4 mg/ml for 3 min) was used intraoperatively in 15 of 37 eyes. We defined total success as 25% reduction in intraocular pressure (IOP) without medication. Follow‐up time was 12 months.

Results

The mean preoperative IOP was significantly reduced from 15.2 ± 2.8 mmHg to 9.3 ± 2.7 (p < 0.001) in the MMC group after 12‐month follow‐up and from 15.1 ± 2.9 mmHg to 11.8 ± 2.0 (p < 0.001) in the non‐MMC group. At 12 months, the mean IOP was significantly lower in the MMC group (p = 0.003) compared with the non‐MMC group. Total success was achieved in 10 of 15 eyes (67%) in MMC group and in nine of 22 eyes (41%) in non‐MMC group (p = 0.12). The number of glaucoma medications was decreased from 2.2 ± 0.8 to 0.5 ± 1.2 in MMC group (p = 0.001) and from 2.6 ± 1.0 to 0.5 ± 0.7 in non‐MMC group (p < 0.001). Goniopuncture was performed in seven eyes (47%) in the MMC group, compared with 16 eyes (73%) in the non‐MMC group (p = 0.13). IOP < 10 mmHg was achieved in seven of 15 eyes in the MMC group and in two of 22 in the non‐MMC group (p = 0.009). Complication rate was low, and no difference between groups was evident.

Conclusion

Deep sclerectomy seems to be effective and safe in reducing IOP in patients with NTG. Intraoperative use of MMC results in lower postoperative IOP 12‐month postoperatively without increased rate of complications.
Analysis of HER2 status in breast carcinoma by fully automated HER2 fluorescence in situ hybridization (FISH): comparison of two immunohistochemical tests and manual FISH
Authors: Yoon Nara , Do In‐Gu , Cho Eun Yoon
Published: December 2013

Easy and accurate HER2 testing is essential when considering the prognostic and predictive significance of HER2 in breast cancer. The use of a fully automated, quantitative FISH assay would be helpful to detect HER2 amplification in breast cancer tissue specimens with reduced inter‐laboratory variability. We compared the concordance of HER2 status as assessed by an automated FISH staining system to manual FISH testing. Using 60 formalin‐fixed paraffin‐embedded breast carcinoma specimens, we assessed HER2 immunoexpression with two antibodies (DAKO HercepTest and CB11). In addition, HER2 status was evaluated with automated FISH using the Leica FISH System for BOND and a manual FISH using the Abbott PathVysion DNA Probe Kit. All but one specimen were successfully stained using both FISH methods. When the data were divided into two groups according to HER2/CEP17 ratio, positive and negative, the results from both the automated and manual FISH techniques were identical for all 59 evaluable specimens. The HER2 and CEP17 copy numbers and HER2/CEP17 ratio showed great agreement between both FISH methods. The automated FISH technique was interpretable with signal intensity similar to those of the manual FISH technique. In contrast with manual FISH, the automated FISH technique showed well‐preserved architecture due to low membrane digestion. HER2 immunohistochemistry and FISH results showed substantial significant agreement (κ = 1.0, p < 0.001). HER2 status can be reliably determined using a fully automated HER2 FISH system with high concordance to the well‐established manual FISH method. Because of stable signal intensity and high staining quality, the automated FISH technique may be more appropriate than manual FISH for routine applications.
Drug Dosing in Patients with Renal Insufficiency in a Hospital Setting using Electronic Prescribing and Automated Reporting of Estimated Glomerular Filtration Rate
Authors: Nielsen Anita L. , Henriksen Daniel P. , Marinakis Christianna , Hellebek Annemarie , Birn Henrik , Nybo Mads , Søndergaard Jens , Nymark Anita , Pedersen Court
Published: December 2013

In patients with impaired renal function, drug dose adjustment is often required. Non‐adherence to clinical prescribing recommendations may result in severe adverse events. In previous studies, the prevalence rate of non‐adherence to recommended dosing has been reported to be 19–67%. Using the clinical support system Renbase® as reference, we investigated the use and dosing of drugs in patients with impaired renal function in a university hospital setting using electronic prescription and automatic reporting of estimated glomerular filtration rate (eGFR). In all, 232 patients with an eGFR in the range of 10–49 ml/min./1.73 m2 were included. We identified 436 episodes with administration of renal risk drugs (prescribed to 183 patients): 410 drugs required dose adjustment according to the eGFR and 26 should be avoided. In total, the use or dosing of 66 (15%) of the 436 renal risk drugs was not in agreement with recommendations in Renbase®. This reflects less disagreement with expert guidelines than reported previously, indicating a possible beneficial effect of electronic prescribing and reporting of eGFR. However, we also found that disagreement to some extent reflected inappropriate drug use. We conclude that despite implementation of electronic prescribing and automated reporting of eGFR, patients with renal insufficiency may still be exposed to inappropriate drug use, with potential increased risk of adverse effects. Initiatives to reduce medication errors such as the use of electronic decision support systems should be explored.
School ethnic diversity and students' interethnic relations
Authors: Thijs Jochem , Verkuyten Maykel
Published: December 2013

Background and aims

School ethnic desegregation has been a topic of strong societal and educational concern. Research has examined the effects of ethnic school composition on students' interethnic relations with diverging outcomes and sometimes inconsistent results. In this review paper, we provide an assessment of this literature to explain why and when school desegregation might improve or worsen ethnic relations and to identify important future research directions.

Approach

We discuss different theoretical perspectives predicting positive versus negative aspects of school ethnic diversity: intergroup contact theory and the perspectives of group threat and power differences. Subsequently, we consider a number of school and educational characteristics that can moderate the impact of ethnic diversity on students' interethnic relations and that could be considered in future research. Furthermore, we discuss the need for studying underlying psychological and social processes as well as the importance of investigating interethnic relations in combination with academic adjustment.

Conclusions

School ethnic diversity is not enough to promote interethnic tolerance. It is important to examine diversity in relation to other aspects of the school environment that may influence how students respond to the ethnic diversity within school. Important factors to consider are the presence of multicultural education and inclusive school identities, student–teacher relationships, and peer norms and networks, but also the role of parents and of peer relations outside the school context.
Struggling Against the ‘Worst‐Case Scenario’? Strategic Conflicts and Realignments of the Feminist Movement in the Context of the 2006 Nicaraguan Elections
Authors: LACOMBE DELPHINE
Published: December 2013

This article analyses the debates that took place within the Nicaraguan feminist movement during 2006. In the months before the election of Daniel Ortega, a new feminist organisation, the Autonomous Women's Movement (MAM), was created. Its members decided to ally themselves with the Sandinista Renewal Movement (MRS), which shared the priority of avoiding the return to power of the Sandinista National Liberation Front (FSLN), because they considered it to be the ‘worst‐case scenario’. This article explains these processes. It studies their consequences for other feminist groupings and the relevance of the revolutionary referent for the strategic divergences within the movement.
Percutaneous neuromodulation of the posterior tibial nerve for the treatment of faecal incontinence – mid‐term results: is retreatment required?
Authors: de la Portilla F. , Laporte M. , Maestre M. V. , Díaz‐Pavón J. M. , Gollonet J. L. , Palacios C. , Vázquez‐Monchul J. M. , García‐Cabrera A. M. , Jiménez‐Rodríguez R. M. , Sánchez Gil J. M.
Published: December 2013

Aim

Posterior tibial nerve stimulation (PTNS) has emerged in recent years as a therapy for faecal incontinence. Its long‐term effectiveness is yet to be established, along with what the form of retreatment should be in the event of loss of effectiveness. The present study aimed to establish the mid‐term results to identify the proportion of patients who may need further treatment, and if so when.

Method

A prospective study including 30 patients was conducted at an academic hospital. The patients underwent 12 weekly outpatient treatment sessions, each lasting 30 min (first PTNS phase). Neuromodulation was discontinued in those patients who did not have a 40% decrease in their pretreatment Wexner score. Patients having a better than 40% response were offered another 12‐week course of complete treatment (second PTNS phase), following which they received no further PTNS treatment (phase without PTNS) but were assessed at 6 months and 2 years.

Results

All patients finished the first phase and 22/30 patients continued to the second phase. During this phase 11 patients showed an improved Wexner score (baseline/first phase/second phase: 14.3 ± 4.2 vs 9.9 ± 5.4 vs 6.8 ± 5.4). After a 6‐month period without any treatment, the score was still improved in 11/30 patients (9.1 ± 6.2). At 2 years there was improvement in 16/30 patients (8.8 ± 7.1). There was a significant improvement in three variables of the quality of life questionnaire: lifestyle, coping behaviour and embarrassment.

Conclusion

The response to first and second phase PTNS was maintained for up to 2 years. Retreatment was not required in about half of patients, even when they had finished the treatment 6 months or 2 years previously.
Pulse granuloma of the lip: morphologic clues in its differential diagnosis
Authors: Fernandez‐Flores Angel , Saeb‐Lima Marcela
Published: December 2013

Pulse granuloma is not a common condition in cutaneous pathology. In diagnosing this condition, it is essential to determine if the foreign fragmented bodies are really vegetable parts. Certain vegetable structures, such as hyaline rings, have been clearly emphasized in the literature. However, other vegetable parts can show certain morphologic similarities with animal structures, especially if observed in a fragmented biopsy, as is the case with the pericarp (which can mimic the cuticle of a maggot) or the endosperm (which can mimic the fat cells of the larva). Herein, we present a case of pulse granuloma involving the lip, an uncommon location for this condition. We also describe the histopathologic appearance of experimentally obtained maggots and pupae, as well as that of several vegetable seeds. We compare some of the vegetable and animal structures and emphasize the differential diagnosis between them.
Etiology of impaired selective motor control: emerging evidence and its implications for research and treatment in cerebral palsy
Authors: Cahill‐Rowley Katelyn , Rose Jessica
Published: December 2013

Selective motor control (SMC) impairment involves movement patterns dominated by flexor or extensor synergies that interfere with functional movements in children with cerebral palsy (CP). Emerging evidence on neural correlates of impaired SMC has important implications for etiology and for the treatment for children with CP. Early evidence on the microstructure of brain white matter assessed with diffusion tensor imaging in adult patients after stroke suggests that the rubrospinal tract may compensate for injury to the corticospinal tract. Furthermore, the observed changes on diffusion tensor imaging corresponded to the degree of SMC impairment. The rubrospinal tract may provide imperfect compensation in response to corticospinal tract injury, resulting in diminished SMC. Cortical mapping evidence in stroke patients indicates that loss of SMC is also associated with increased overlap of joint representation in the sensorimotor cortices. The severity of SMC impairment can be assessed with the recently developed Selective Control Assessment of the Lower Extremity, a validated observation‐based measure designed for children with spastic CP. Recent advances in neuroimaging and assessment of SMC provide an opportunity to better understand the etiology and impact of impaired SMC, which may ultimately guide strategic treatment for children with CP.
Alopecia areata and vitiligo – Partners in crime or a case of false alibis
Authors: Tobin Desmond J.
Published: December 2013

It has long been appreciated in science that correlation does not imply causation. However, with any logical fallacy, simply spotting that the reasoning behind an argument is faulty does not imply that the resulting conclusion is false. Thus, I begin the tricky business of exploring the basis upon which researchers and clinicians are often tempted to conclude that two medical conditions (here alopecia areata and vitiligo), with some striking resemblances, are in fact related. This is relevant, particularly if assumptions of shared aetiology (and to some extent shared pathomechanism) encourage a common strategy to finding a treatment or cure.
Melanocortin 1 receptor and skin pathophysiology: beyond colour, much more than meets the eye
Authors: García‐Borrón José Carlos , Olivares Concepción
Published: December 2013

The melanocortin 1 receptor (MC1R), a G protein‐coupled receptor preferentially expressed in melanocytes, mediates the pigmentary effects of α melanocyte‐stimulating hormone (αMSH). MC1R is also expressed in other cutaneous cell types, particularly keratinocytes and dermal fibroblasts, suggesting non‐pigmentary actions of the αMSH/MC1R system. Böhm and Stegemann now report a dramatic effect of mouse Mc1r functional status on susceptibility to skin fibrosis and collagen types I and III metabolism, in a study combining the powerful mouse model provided by the natural Mc1re/e knockout and an established model of skin fibrosis. The study underscores the antifibrotic role for the skin αMSH/MC1R system.
Fatigue crack growth rates of API X70 pipeline steel in a pressurized hydrogen gas environment
Authors: Drexler E. S. , Slifka A. J. , Amaro R. L. , Barbosa N. , Lauria D. S. , Hayden L. E. , Stalheim D. G.
Published: December 2013

Hydrogen is known to have a deleterious effect on most engineering alloys. It has been shown repeatedly that the strength of steels is inversely related to the ductility of the material in hydrogen gas. However, the fatigue properties with respect to strength are not as well documented or understood. Here, we present the results of tests of the fatigue crack growth rate (FCGR) on API X70 from two sources. The two materials were tested in air, 5.5 and 34 MPa pressurized hydrogen gas, and at both 1 and 0.1 Hz. At these hydrogen pressures, the FCGR increases above that of air for all values of the stress intensity factor range (ΔK) greater than ~7 MPa · m1/2. The effect of hydrogen is particularly sensitive at values of ΔK below ~15 MPa · m1/2. That is, for values of ΔK between 7 and 15 MPa · m1/2, the FCGR rapidly increases from approximately that found in air to as much as two orders of magnitude above that in air. Above 15 MPa · m1/2, the FCGR remains approximately one to two orders of magnitude higher than that of air.
Introduction of imperfections in the cubic mesh of the truss‐like discrete element method
Authors: Iturrioz I. , Riera J. D. , Miguel L. F. F.
Published: December 2013

In the present version of the truss‐like discrete element method (DEM), masses are considered lumped at nodal points and interconnected by means of unidimensional elements with arbitrary constitutive relations. In previous studies of non‐homogeneous concrete cubic samples subjected to nominally uniaxial tension, it was verified that numerical predictions of fracture using DEM models are feasible and yield results that are consistent with the experimental evidence so far available, including the prediction of size and strain rate effects. In the DEM formulation, material failure under compression is assumed to occur by indirect tension. In previous simulations, it was verified that the response is satisfactorily modelled up to the peak load, when a sudden collapse usually occurs, characteristic of fragile behaviour. On the other hand, experimental stress versus displacement curves observed in small specimens subjected to compression typically present a softening branch, in part due to sliding with friction of the fractured parts of the specimens. A second deficiency of DEM models with a perfectly cubic mesh is that the best correlations with experimental results are obtained with material parameters that differ in tension and compression. This paper examines another cause of the excessively fragile behaviour of DEM predictions of the response of concrete elements subjected to nominally uniaxial compression, which is due to the regularity of the perfect cubic mesh, unable to capture nonlinear stability effects in the material. It is shown herein that the introduction of small perturbations of the DEM regular mesh significantly improves the predicting capability of the model and in addition allows adopting a unique set of material properties, which are independent of the nature of the loading.
Notch stress analyses of high‐frequency mechanical impact‐improved welds by using ρf = 1 mm and ρf = ρ + 1 mm approaches
Authors: Yildirim H. C. , Marquis G. B.
Published: December 2013

This paper presents further assessments of the previously reported round‐robin fatigue data obtained from high‐frequency mechanical impact (HFMI)‐improved longitudinal welds. A detailed statistical analyses of geometry measurements of HFMI‐treated weld toe profiles are presented. The fatigue analyses based on notch stress as defined by the International Institute of Welding are performed using the finite element method. Notch stresses are assessed based on both the fictitious weld toe radius and the addition of measured actual notch radius to the fictitious radius. While no large differences are observed between the results of methods, the former one is found to be more practical and faster to implement from the end‐user point of view.