bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological traits affect the sensitivity of bees to land‐use pressures in European agricultural landscapes
Authors: De Palma Adriana , Kuhlmann Michael , Roberts Stuart P.M. , Potts Simon G. , Börger Luca , Hudson Lawrence N. , Lysenko Igor , Newbold Tim , Purvis Andy
Published: September 2015

Bees are a functionally important and economically valuable group, but are threatened by land‐use conversion and intensification. Such pressures are not expected to affect all species identically; rather, they are likely to be mediated by the species' ecological traits.

Understanding which types of species are most vulnerable under which land uses is an important step towards effective conservation planning.

We collated occurrence and abundance data for 257 bee species at 1584 European sites from surveys reported in 30 published papers (70 056 records) and combined them with species‐level ecological trait data. We used mixed‐effects models to assess the importance of land use (land‐use class, agricultural use‐intensity and a remotely‐sensed measure of vegetation), traits and trait × land‐use interactions, in explaining species occurrence and abundance.

Species' sensitivity to land use was most strongly influenced by flight season duration and foraging range, but also by niche breadth, reproductive strategy and phenology, with effects that differed among cropland, pastoral and urban habitats.

Synthesis and applications. Rather than targeting particular species or settings, conservation actions may be more effective if focused on mitigating situations where species' traits strongly and negatively interact with land‐use pressures. We find evidence that low‐intensity agriculture can maintain relatively diverse bee communities; in more intensive settings, added floral resources may be beneficial, but will require careful placement with respect to foraging ranges of smaller bee species. Protection of semi‐natural habitats is essential, however; in particular, conversion to urban environments could have severe effects on bee diversity and pollination services. Our results highlight the importance of exploring how ecological traits mediate species responses to human impacts, but further research is needed to enhance the predictive ability of such analyses.
The development and pilot testing of an occupational therapy group participation rating scale for inpatient mental health settings
Authors: Scanlan Justin Newton , Argent Stacey , Ayling Brooke , Mouawad Arianne , Woodward Mary
Published: September 2015

Introduction

Although group facilitation is a common task for occupational therapists in inpatient mental health settings and groups provide excellent opportunities to observe functioning, it can be difficult to report this information efficiently and effectively. To overcome these challenges, a group participating rating scale was developed. The scale was printed onto stickers so that upon completion, it could be placed directly into the medical record. This pilot study was undertaken to explore the measurement properties and construct validity of the rating scale.

Method

Data were extracted from 528 rating scales completed for 51 individuals admitted to the inpatient unit where the study was conducted. Many‐faceted Rasch analysis was used to examine several aspects of validity: rating scale validity; item functioning and person performance validity; statistical validity; and overall construct validity. In addition, to explore the capacity of the scale to detect change over time, the data were explored for differences in ratings over the course of individuals’ admissions.

Results

Rating scale functioning, item functioning and person performance validity were generally acceptable and statistical validity was good. Overall construct validity was generally acceptable, although there was a substantial ‘ceiling effect’ present. There were significant differences between ratings for individuals over time, suggesting that the scale may be effective in detecting change over time.

Conclusion

The rating scale has two main benefits: improving the quality and consistency of reporting of group participation assessment findings and the potential ability to track the quality (and quantity) of group participation over time. Other, secondary benefits included recognition of occupational therapy and reduced documentation time.
The Essays of Patrick Collinson: Or, Politics with the Religion Put Back
Authors: Shagan Ethan H.
Published: September 2015

This essay analyses Patrick Collinson's contributions as an essayist and writer of short‐form historical articles, with special attention to his concept of the ‘monarchical republic’ but more broadly focused on his vision of the interplay between religion and politics throughout his long career. It argues that Collinson saw politics as fundamentally a struggle of ideas, especially religious ideas, but that he downplayed the potential instability or violence of religious politics by emphasizing the sincerity with which early modern figures sought to reform their world. This might, the article concludes, be giving religious politics just a bit too much credit.
The Moderating Effect of Relative Performance Evaluation on the Risk Incentive Properties of Executives’ Equity Portfolios
Authors: PARK HYUNGSHIN , VRETTOS DIMITRIS
Published: September 2015

We offer evidence that the use of relative performance evaluation (RPE) in CEOs’ incentive contracts influences the effect of risk‐taking incentives on both the magnitude and composition of firm risk. We find that, when the incentive design lacks RPE features, the incentive portfolio vega motivates CEOs to increase total risk through the systematic component because it can be hedged. In contrast, when the incentive design includes RPE features, CEOs prefer idiosyncratic risk because RPE filters out the systematic component of firm performance. We also document that the use of RPE reinforces the incentive portfolio vega's effect on the total risk.
hybridcheck: software for the rapid detection, visualization and dating of recombinant regions in genome sequence data
Authors: Ward Ben J. , van Oosterhout Cock
Published: September 2015

hybridcheck is a software package to visualize the recombination signal in large DNA sequence data set, and it can be used to analyse recombination, genetic introgression, hybridization and horizontal gene transfer. It can scan large (multiple kb) contigs and whole‐genome sequences of three or more individuals. hybridcheck is written in the r software for OS X, Linux and Windows operating systems, and it has a simple graphical user interface. In addition, the r code can be readily incorporated in scripts and analysis pipelines. hybridcheck implements several ABBA–BABA tests and visualizes the effects of hybridization and the resulting mosaic‐like genome structure in high‐density graphics. The package also reports the following: (i) the breakpoint positions, (ii) the number of mutations in each introgressed block, (iii) the probability that the identified region is not caused by recombination and (iv) the estimated age of each recombination event. The divergence times between the donor and recombinant sequence are calculated using a JC, K80, F81, HKY or GTR correction, and the dating algorithm is exceedingly fast. By estimating the coalescence time of introgressed blocks, it is possible to distinguish between hybridization and incomplete lineage sorting. hybridcheck is libré software and it and its manual are free to download from http://ward9250.github.io/HybridCheck/.
Early Secondary Neurologic Deterioration After Blunt Spinal Trauma: A Review of the Literature
Authors: Oto Brandon , Corey Domenic John , Oswald James , Sifford Derek , Walsh Brooks
Published: September 2015

Objectives

The objectives were to review published reports of secondary neurologic deterioration in the early stages of care after blunt spinal trauma and describe its nature, context, and associated risk factors.

Methods

The authors searched the MEDLINE, EMBASE, and CINAHL databases for English‐language studies. Cases were included meeting the criteria age 16 years or older, nonpenetrating trauma, and experiencing neurologic deterioration during prehospital or emergency department (ED) care prior to definitive management (e.g., discharge, spinal clearance by computed tomography, admission to an inpatient service, or surgical intervention). Results were qualitatively analyzed for characteristics and themes.

Results

Forty‐one qualifying cases were identified from 12 papers. In 30 cases, the new deficits were apparently spontaneous and were not detected until routine reassessment. In 12 cases the authors did attribute deterioration to temporally associated precipitants, seven of which were possibly iatrogenic; these included removal of a cervical collar, placement of a halo device, patient agitation, performance of flexion/extension films, “unintentional manipulation,” falling in or near the ED, and forced collar application in patients with ankylosing spondylitis. Thirteen cases occurred during prehospital care, none of them sudden and movement‐provoked, and all reported by a single study.

Conclusions

Published reports of early secondary neurologic deterioration after blunt spinal trauma are exceptionally rare and generally poorly documented. High‐risk features may include altered mental status and ankylosing spondylitis. It is unclear how often events are linked with spontaneous patient movement and whether such events are preventable.
The Association Between Emergency Department Crowding and the Disposition of Patients With Transient Ischemic Attack or Minor Stroke
Authors: Ben‐Yakov Maxim , Kapral Moira K. , Fang Jiming , Li Shudong , Vermeulen Marian J. , Schull Michael J.
Published: September 2015

Background

Emergency department (ED) crowding has been associated with adverse events, including short‐term death and hospitalization among discharged patients. The mechanisms are poorly understood, but may include altered physician decision‐making about ED discharge of higher‐risk patients. One example is patients with transient ischemic attack (TIA) and minor stroke, who are at high risk of subsequent stroke. While hospitalization is frequently recommended, little consensus exists on which patients require admission.

Objectives

The authors sought to determine the association of ED crowding with the disposition of patients with minor stroke or TIA.

Methods

This was a retrospective cohort study of prospectively collected data from the Registry of the Canadian Stroke Network at 12 EDs in Ontario, Canada, between 2003 and 2008, linked to administrative health databases. A hierarchical logistic regression model was used to determine the association between crowding at the time the patient was seen in the ED (defined as mean ED length of stay) and patient disposition (admission/discharge), after adjusting for patient and hospital‐level variables.

Results

The study cohort included 9,759 patients (4,607 with TIA and 5,152 with minor stroke); 49.5% were discharged from the ED. The mean (±SD) age of study patients was 70.78 (±13.40) years, with 52.9% being male, 37.3% arriving by emergency medical services, and 92.3% triaged as emergent or urgent. Greater severity of ED crowding was associated with a lower likelihood of discharge, regardless of ED size.

Conclusions

These results suggest that crowding may influence clinical decision‐making in the disposition of patients with TIA or minor stroke and that, as crowding worsens, the likelihood of hospitalization increases.
Anatomical Atlas of the Quail's Ear (Coturnix coturnix)
Authors: Bonsmann A. , Stoffel M. H. , Burkhart M. , Hatt J.‐M.
Published: September 2015

This study aims to enhance the anatomical knowledge of the ear of the adult quail (Coturnix coturnix) through the creation of a scaled 3D model utilizing data from micro‐CT images. In addition, 17 annotated histological sections of the quail's ear are aligned to their 3D position in the model. The resulting anatomical atlas provides an intuitive insight into the 3D anatomy and can be used for medical education. The model also allows measuring anatomical structures and can thus serve as reference for the quail's auricular anatomy and as a basis to evaluate clinical diagnostic imaging results.
Comparative Study of the Major White Matter Tracts Anatomy in Equine, Feline and Canine Brains by Use of the Fibre Dissection Technique
Authors: Pascalau R. , Aldea C. C. , Padurean V. A. , Szabo B.
Published: September 2015

The spatial anatomy of the white matter tracts is a subject of growing interest not only for researchers but also for clinicians. Imagistic methods have some limitations so that they should be confronted with dissection studies. The aim of this paper was to provide a three‐dimensional view of the major white matter tracts in equine, feline and canine brains by use of the fibre dissection technique. Twenty cerebral hemispheres (six equine, four feline and 10 canine brains) were prepared according to the Klingler method. Stepwise mediolateral and lateromedial blunt dissections were performed using wooden sticks and spatulas. The lateromedial dissection was followed by the opening of the lateral ventricle. The use of the same multi‐stage procedures resulted in a comparable exposure of the major association, projection and commissural fibres and their spatial relation with the lateral ventricle. To conclude, the proposed techniques are reproducible in equine, feline and canine brains and they can be successfully used for teaching, training or research in the field of neurobiology.
A reduced risk of stroke with lithium exposure in bipolar disorder: a population‐based retrospective cohort study
Authors: Lan Chen‐Chia , Liu Chia‐Chien , Lin Ching‐Heng , Lan Tzuo‐Yun , McInnis Melvin G , Chan Chin‐Hong , Lan Tsuo‐Hung
Published: September 2015

Objectives

The risk of stroke is increased in patients with bipolar disorder. Lithium exhibits neuroprotective effects but the association between lithium use and the risk of stroke is unknown.

Methods

A population‐based retrospective cohort study was conducted by utilizing the National Health Insurance Research Database in Taiwan. Subjects who had first been diagnosed with bipolar disorder between 2001 and 2006 were identified. A propensity score (PS) for receiving lithium was calculated with variables of age, gender, and comorbidities. The patients with bipolar disorder receiving lithium within the period from diagnosis through to December 2011 were designated as the lithium group (n = 635). A 1:2 ratio was used to select PS‐matched subjects with bipolar disorder without lithium use (n = 1,250). Multivariate Cox proportional hazards regression models were used to explore the association, rather than causal inference, of lithium exposure and the risk of stroke.

Results

Of the 1,885 subjects, 86 (4.6%) experienced stroke, including 2.8% of the lithium group and 5.4% of the non‐lithium group. Lithium use was associated with a significantly reduced risk of stroke [hazard ratio (HR) = 0.39, 95% confidence interval (CI): 0.22–0.68]. Reduced risks of stroke were also associated with the highest cumulative lithium dose [≥720 defined daily dose (DDD), HR = 0.25, 95% CI: 0.10–0.59], the longest cumulative exposure period (≥720 days, HR = 0.20, 95% CI: 0.06–0.64), and the highest exposure rate (≥2 DDD/day, HR = 0.39, 95% CI: 0.21–0.70).

Conclusions

Lithium use was significantly related to a reduced risk of stroke in patients with bipolar disorder.
Parametric Modeling of Quantile Regression Coefficient Functions
Authors: Frumento Paolo , Bottai Matteo
Published: September 2015

Estimating the conditional quantiles of outcome variables of interest is frequent in many research areas, and quantile regression is foremost among the utilized methods. The coefficients of a quantile regression model depend on the order of the quantile being estimated. For example, the coefficients for the median are generally different from those of the 10th centile. In this article, we describe an approach to modeling the regression coefficients as parametric functions of the order of the quantile. This approach may have advantages in terms of parsimony, efficiency, and may expand the potential of statistical modeling. Goodness-of-fit measures and testing procedures are discussed, and the results of a simulation study are presented. We apply the method to analyze the data that motivated this work. The described method is implemented in the qrcm R package.
Characterization of 12 GnRH peptide agonists – a kinetic perspective
Authors: Nederpelt Indira , Georgi Victoria , Schiele Felix , Nowak‐Reppel Katrin , Fernández‐Montalván Amaury E. , IJzerman Adriaan P. , Heitman Laura H.
Published: September 2015

Background and Purpose

Drug‐target residence time is an important, yet often overlooked, parameter in drug discovery. Multiple studies have proposed an increased residence time to be beneficial for improved drug efficacy and/or longer duration of action. Currently, there are many drugs on the market targeting the gonadotropin‐releasing hormone (GnRH) receptor for the treatment of hormone‐dependent diseases. Surprisingly, the kinetic receptor‐binding parameters of these analogues have not yet been reported. Therefore, this project focused on determining the receptor‐binding kinetics of 12 GnRH peptide agonists, including many marketed drugs.

Experimental Approach

A novel radioligand‐binding competition association assay was developed and optimized for the human GnRH receptor with the use of a radiolabelled peptide agonist, [125I]‐triptorelin. In addition to radioligand‐binding studies, a homogeneous time‐resolved FRET Tag‐lite™ method was developed as an alternative assay for the same purpose.

Key Results

Two novel competition association assays were successfully developed and applied to determine the kinetic receptor‐binding characteristics of 12 high‐affinity GnRH peptide agonists. Results obtained from both methods were highly correlated. Interestingly, the binding kinetics of the peptide agonists were more divergent than their affinities with residence times ranging from 5.6 min (goserelin) to 125 min (deslorelin).

Conclusions and Implications

Our research provides new insights by incorporating kinetic, next to equilibrium, binding parameters in current research and development that can potentially improve future drug discovery targeting the GnRH receptor.
Review: Alternatives to inpatient care for children and adolescents with mental health disorders
Authors: Kwok Ka Ho Robin , Yuan Sze Ngar Vanessa , Ougrin Dennis
Published: September 2015

Background

Intensive community services may provide an alternative to inpatient care but there is little systematic evidence of their efficacy. This article provides a systematic review of randomized controlled trials (RCTs) reporting efficacy of intensive community services versus inpatient care in youth.

Method

Data sources were identified by searching Medline, PsychINFO and EMBASE databases as of December 2014. RCTs comparing intensive community services versus inpatient care in children and adolescents (through age 18) were included.

Results

Six unique RCTs including 569 youth were identified. The RCTs examined the efficacy of specialist outpatient treatment, multisystemic therapy, day patient treatment, intensive home treatment and supported discharge services versus inpatient care. Using intensive community services was associated with clinical improvements similar to inpatient care in most studies. Where differences in clinical outcomes existed, they tended to favour intensive community treatment. Using intensive community services was associated with shorter hospitalizations, lower costs and greater patient satisfaction. There were no independent replications of the results. Few studies investigated the use of intensive community treatment as an alternative to inpatient care in children and adolescents with severe immediate risk to self and others.

Conclusions

Intensive community services appear to be a viable alternative to inpatient care. Independent replication of results achieved by specific intensive community treatment models is a research priority.
Clinical significance of tumor‐infiltrating immune cells focusing on BTLA and Cbl‐b in patients with gallbladder cancer
Authors: Oguro Seiji , Ino Yoshinori , Shimada Kazuaki , Hatanaka Yutaka , Matsuno Yoshihiro , Esaki Minoru , Nara Satoshi , Kishi Yoji , Kosuge Tomoo , Hiraoka Nobuyoshi
Published: September 2015

The host immune system plays a significant role in tumor control, although most cancers escape immune surveillance through a variety of mechanisms. The aim of the present study was to evaluate the clinicopathological significance of a novel co‐inhibitory receptor, B and T lymphocyte attenuator (BTLA), the anergy cell marker Casitas–B‐lineage lymphoma protein‐b (Cbl‐b), and clinical implications of tumor‐infiltrating immune cells in gallbladder cancer (GBC) tissues. We investigated 211 cases of GBC, 21 cases of chronic cholecystitis (CC), and 11 cases of xanthogranulomatous cholecystitis (XGC) using immunohistochemistry to detect tissue‐infiltrating immune cells and their expression of BTLA and Cbl‐b, and carried out correlation and survival analyses. The density of infiltrating T cells was significantly higher in CC and XGC than in GBC. The density ratio of BTLA+ cells to CD8+ T cells (BTLA/CD8) and that of Cbl‐b+ cells to CD8+T cells (Cbl‐b/CD8) were significantly higher in GBC than in CC and XGC. The FOXP3/CD4, BTLA/CD8, and Cbl‐b/CD8 ratios were significantly correlated with each other, and also with malignant phenotypes. Survival analyses revealed that a lower density of tumor‐infiltrating CD8+ cells, and higher Foxp3/CD4, BTLA/CD8, and Cbl‐b/CD8 ratios were significantly associated with shorter overall survival and disease‐free survival in GBC patients. Multivariate analyses showed that M factor, perineural invasion, BTLA/CD8, and Cbl‐b/CD8 were closely associated with shorter overall survival. These findings suggest that higher ratios of BTLA/CD8 and Cbl‐b/CD8 are independent indicators of unfavorable outcome in GBC patients, and that upregulation of BTLA in cancer tissues is involved in inhibition of antitumor immunity.
Near‐infrared fluorescence laparoscopy‐ technical description of PINPOINT® a novel and commercially available system
Authors: Fengler J.
Published: September 2015

The PINPOINT Endoscopic Fluorescence Imaging System is a high‐definition video laparoscopy system for conventional white light laparoscopic visualization and for near‐infrared fluorescence imaging with indocyanine green (ICG). This manuscript describes it's technical characteristics and performance capabilities.
Beyond the ‘raw’ and the ‘cooked’: a history of fortified blended foods
Authors: Scott‐Smith Tom
Published: September 2015

This paper offers a history of fortified blended foods, a humanitarian product that first emerged in the middle of the twentieth century. Tracing its emergence and development, the paper argues that this food was the product of four key historical trends: (i) the search for a compact and efficient diet in the wake of the Second World War; (ii) the high modernist movement that saw science and technology as a way to improve on traditional foods; (iii) the state‐led industrialisation of the development decades oriented around the notion of a worldwide ‘protein gap’; and (iv) the legacy of ‘productivist’ agriculture in the United States, generating massive surpluses in certain crops that had to be adapted creatively for a multitude of uses. The paper positions fortified blended foods in these broader historical processes, and asserts that humanitarian techniques are very much rooted in cultural, political, and social conditions.
Banking and Insurance Recapitalization During the 2007–2009 Credit Crisis
Authors: Cybo‐Ottone Alberto , Savorelli Lorenzo
Published: September 2015

This paper explores the feedback loop between the intensity of financial intermediary recapitalization and a number of measures of credit and liquidity risk. We cover the entire 2007–2009 subprime crisis with a sample that includes the 97 largest banks and insurance companies on both sides of the Atlantic. We model the intensity of recapitalization by implementing a scale measure inspired by the Corrective Action system used by U.S. banking regulators. The proposed ordering starts with inaction, followed by dividend cuts, to issues of new equity, to bailouts. Our risk measures include toxic asset exposures, credit default swap spreads, and Merton‐style probabilities of default. We show that there is a monotone relationship between the intensity of risk and the intensity of recapitalization across all firms and jurisdictions in the sample. We are able to simplify the large heterogeneity of regulations and business models across sectors and countries within a fairly simple and general classification scheme. This scheme distinguishes between individual bailouts, targeted at bankruptcy prevention, and more nuanced collective bailouts, which were more related to the prevention of systemic risk arising from potentially solvent institutions.
Friend or foe: inter‐specific interactions and conflicts of interest within the family
Authors: DE GASPERIN ORNELA , KILNER REBECCA M.
Published: September 2015

1. Interactions between species can vary from mutually beneficial to evolutionarily neutral to antagonistic, even when the same two species are involved. Similarly, social interactions between members of the same species can lie on a spectrum from conflict to cooperation.

2. The aim of the present study was to investigate whether variation in the two types of social behaviour are interconnected. Is the fitness of the various classes of social partner within species (such as parent and offspring, or male and female) differently affected by interactions with a second species? Moreover, can inter‐specific interactions influence the outcome of social interactions within species?

3. The present experiments focus on the interactions between the burying beetleNicrophorus vespilloidesHerbst and the phoretic mitePoecilochirus carabiG.Canestrini &R.Canestrini. The approach was to measure the fitness of burying beetle mothers, fathers, and offspring after reproduction, which took place either in the presence or absence of mites.

4. We found that male, female, and larval burying beetles derive contrasting fitness costs and benefits from their interactions with the mite, despite sharing a common family environment. From the mite's perspective, its relationship with the burying beetle can, therefore, be simultaneously antagonistic, neutral, and possibly even mutualistic, depending on the particular family member involved. We also found that mites can potentially change the outcome of evolutionary conflicts within the family.

5. We conclude that inter‐specific interactions can explain some of the variation in social interactions seen within species. It is further suggested that intra‐specific interactions might contribute to variation in the outcome of interactions between species.
Plenty more fish in the sea?
Authors: Watson Reg A , Pitcher Tony J , Jennings Simon
Published: September 2015

Only in the last century did humans overwhelmingly accept that fisheries resources are finite. Consequently, ‘there are more fish still in the sea than ever came out of it’ served as a popular metaphor for unbounded expectations for half a millennium, expectations that also extended to use of the planet in general. By reconstructing historical fishing back 1200 years, we identify when this metaphor actually ceased to be true. For some of our most important stocks, it has not been true for centuries, although surprisingly, for fishes globally, it applied until the last century. We demonstrate, however, that there can still be ‘plenty more fish in the sea’ and that with effective management they provide a continuous flow of benefits for our future.
Death in the fast lane: what's next for necroptosis?
Authors: Oberst Andrew
Published: September 2015

Necroptosis is a form of programmed cell death that is both mechanistically and morphologically distinct from apoptosis, the canonical mechanism of cell suicide. Although early descriptions of necroptosis date back decades, the last 5 years have seen a proliferation of studies of this process. This surge in interest has included the recent publication of several excellent, in‐depth reviews of the literature [Chan FK‐M et al. (2014) Annu Rev Immunol 33, 141210135520002; Weinlich R & Green DR (2014) Mol Cell 56, 469–480; Silke J et al. (2015) Nat Immunol 16, 689–697; Linkermann A & Green DR (2014) N Engl J Med 370, 455–465]. Rather than contribute another summary to this well‐summarized field, in this Minireview I will briefly discuss key recent findings, then touch on some of the major outstanding questions – the known unknowns – that remain.
TheTCP1γ subunit ofLeishmania donovaniforms a biologically active homo‐oligomeric complex
Authors: Bhaskar   , Mitra Kalyan , Kuldeep Jitendra , Siddiqi Mohammad Imran , Goyal Neena
Published: September 2015

Chaperonins are a class of molecular chaperons that encapsulate nascent or stress‐denatured proteins and assist their intracellular assembly and folding in anATP‐dependent manner. The ubiquitous eukaryotic chaperonin,TCP1 ring complex is a hetero‐oligomeric complex comprising two rings, each formed of eight subunits that may have distinct substrate recognition andATPhydrolysis properties. InLeishmania, only theTCP1γ subunit has been cloned and characterized. It exhibited differential expression at various growth stages of promastigotes. In the present study, we expressed theTCP1γ subunit inEscherichia colito investigate whether it forms chaperonin‐like complexes and plays a role in protein folding. LdTCP1γ formed high‐molecular‐weight complexes withinE. colicells as well as inLeishmaniacell lysates. The recombinant protein is arranged into two back‐to‐back rings of seven subunits each, as predicted by homology modelling and observed by negative staining electron microscopy. This morphology is consistent with that of the oligomeric double‐ring group I chaperonins found in mitochondria. The LdTCP1γ homo‐oligomeric complex hydrolysedATP, and was active as assayed by luciferase refolding. Thus, the homo‐oligomer performs chaperonin reactions without partner subunit(s). Further, co‐ immunoprecipitation studies revealed that LdTCP1γ interacts with actin and tubulin proteins, suggesting that the complex may have a role in maintaining the structural dynamics of the cytoskeleton of parasites.
Effects of nutrient supplementation on host‐pathogen dynamics of the amphibian chytrid fungus: a community approach
Authors: Buck Julia C. , Rohr Jason R. , Blaustein Andrew R.
Published: September 2015

Anthropogenic stressors may influence hosts and their pathogens directly or may alter host–pathogen dynamics indirectly through interactions with other species. For example, in aquatic ecosystems, eutrophication may be associated with increased or decreased disease risk. Conversely, pathogens can influence community structure and function and are increasingly recognised as important members of the ecological communities in which they exist.

In outdoor mesocosms, we experimentally manipulated nutrients (nitrogen and phosphorus) and the presence of a fungal pathogen, Batrachochytrium dendrobatidis (Bd), and examined the effects on Bd abundance on larval amphibian hosts (Pseudacris regilla: Hylidae), amphibian traits and community dynamics. We predicted that resource supplementation would mitigate negative effects of Bd on tadpole growth and development and that indirect effects of treatments would propagate through the community.

Nutrient additions caused changes in algal growth, which benefitted tadpoles through increased mass, development and survival. Bd‐exposed tadpoles metamorphosed sooner than unexposed individuals, but their mass at metamorphosis was not affected by Bd exposure. We detected additive rather than interactive effects of nutrient supplementation and Bd in this experiment.

Nutrient supplementation was not a significant predictor of infection load of larval amphibians. However, a structural equation model revealed that resource supplementation and exposure of amphibians to Bd altered the structure of the aquatic community. This is the first demonstration that sublethal effects of Bd on amphibians can alter aquatic community dynamics.
Helicobacter pylori HP0425 Targets the Nucleus with DNase I‐Like Activity
Authors: Kim Jung‐Min , Choe Min‐Ho , Asaithambi Killivalavan , Song Jae‐Young , Lee Yong Seok , Lee Je Chul , Seo Ji‐Hyun , Kang Hyung‐Lyun , Lee Kon Ho , Lee Woo‐Kon , Cho Myung‐Je , Rhee Kwang‐Ho , Youn Hee‐Shang , Baik Seung‐Chul
Published: September 2015

Background and Aims

Nuclear targeting of bacterial proteins has a significant impact on host cell pathology. Helicobacter pylori have many nuclear targeting proteins that translocate into the nucleus of host cells. H. pylori HP0425, annotated as hypothetical, has a nuclear localization signal (NLS) sequence, but its function has not been demonstrated. The aim of this experiment was to address the nuclear translocation of HP0425 and determine the effect of HP0425 pathology on host cells.

Materials and Methods

To investigate the nuclear localization of HP0425, it was expressed in AGS and MKN‐1 cells as a GFP fusion protein (pEGFP–HP0425), and its localization was analyzed by confocal microscopy. Recombinant HP0425 (rHP0425) protein was overproduced as a GST fusion protein in Escherichia coli and purified by glutathione‐affinity column chromatography. Purified rHP0425 was examined for cytotoxicity and DNase activity.

Results

The pEGFP–HP0425 fluorescence was expressed in the nucleus and cytosol fraction of cells, while it was localized in the cytoplasm in the negative control. This protein exhibited DNase activity under various conditions, with the highest DNase activity in the presence of manganese. In addition, the rHP0425 protein efficiently decreased cell viability in a concentration‐dependent manner.

Conclusions

These results suggest that HP0425 carrying a nuclear localization signal sequence translocates into the nucleus of host cells and degrades genomic DNA by DNase I‐like enzymatic activity, which is a new pathogenic strategy of H. pylori in the host.
Estimated cost per HIV infection diagnosed through routine HIV testing offered in acute general medical admission units and general practice settings in England
Authors: Ong KJ , Thornton AC , Fisher M , Hutt R , Nicholson S , Palfreeman A , Perry N , Stedman‐Bryce G , Wilkinson P , Delpech V , Nardone A
Published: September 2015

Objectives

Following national guidelines to expand HIV testing in high‐prevalence areas in England, a number of pilot studies were conducted in acute general medical admission units (ACUs) and general practices (GPs) to assess the feasibility and acceptability of testing in these settings. The aim of this study was to estimate the cost per HIV infection diagnosed through routine HIV testing in these settings.

Methods

Resource use data from four 2009/2010 Department of Health pilot studies (two ACUs; two GPs) were analysed. Data from the pilots were validated and supplemented with information from other sources. We constructed possible scenarios to estimate the cost per test carried out through expanded HIV testing in ACUs and GPs, and the cost per diagnosis.

Results

In the pilots, cost per test ranged from £8.55 to £13.50, and offer time and patient uptake were 2 minutes and 90% in ACUs, and 5 minutes and 60% in GPs, respectively. In scenario analyses we fixed offer time, diagnostic test cost and uptake rate at 2 minutes, £6 and 80% for ACUs, and 5 minutes, £9.60 and 40% for GPs, respectively. The cost per new HIV diagnosis at a positivity of 2/1000 tests conducted was £3230 in ACUs and £7930 in GPs for tests performed by a Band 3 staff member, and £5940 in ACUs and £18 800 in GPs for tests performed by either hospital consultants or GPs.

Conclusions

Expanded HIV testing may be more cost‐efficient in ACUs than in GPs as a consequence of a shorter offer time, higher patient uptake, higher HIV positivity and lower diagnostic test costs. As cost per new HIV diagnosis reduces at higher HIV positivity, expanded HIV testing should be promoted in high HIV prevalence areas.
The Czech Republic experience in a corneal clinic
Authors: Liskova P.
Published: September 2015

The spectrum of monogenic corneal disorders identified in the Czech Republic is diverse. We have observed some of the rare disorders, such as cornea plana, megalocornea, Harboyan syndrome and brittle cornea syndrome, in Czech patients. We have also observed a founder effect for posterior polymorphous corneal dystrophy, which appears to have the highest worldwide prevalence in the Czech Republic. Molecular genetic confirmatory testing can be performed in settings with limited laboratory diagnostic services either on a research basis or via research collaborations. Experience from the Czech Republic suggests that monogenic corneal disorders, particularly those that are non‐syndromic, are under‐diagnosed.
Benign or malignant? Clinical features
Authors: Lasudry J.
Published: September 2015

Despite the fact that the majority of eyelid tumours are benign, proper management in daily practice requires to detect the malignant ones. A few clinical behaviour criteria are usually examined to support the hypothesis of a malignancy, e.g. the rate of growth, associated inflammation or pigmentation, a cystic structure, ulceration, madarosis, etc. However most are of limited reliability. The course will review the most typical presentation scenarios of common eyelid tumours. In any case of doubt, biopsy is recommended, which is readily done in the outpatient setting, in order to reach a pathologic diagnosis, and draw the appropriate management plan.
Adaptive Optics
Authors: Paques M.
Published: September 2015

During dry age‐related macular degeneration (ARMD), adaptive optics (AO) en face flood imaging improves the resolution of drusens and of pigmentary changes and hence of the progression of atrophic lesions. In addition, AO revealed the presence of numerous migrating hyporeflective clumps, which are most likely melanin‐loaded cells (MLCs). Time‐lapse imaging demonstrates a high kinetic activity of these MLCs, that appear to migrate subretinally because the photoreceptors are visible over them. The linear velocity of MLCs peakee at ~1 µm/day, hence they can be tracked only if there is a short ionterval of time between imaging sessions. As many adjacent MLCs are seen to migrate in opposite direction, there appears to be no migrating scheme. Such subretinal migration of MLCs occurs throughout the posterior pole, in atrophic as well as in nonatrophic areas. It is likely that these MLCs correspond to the hyperreflective dots reported by optical coherence tomography. The nature of these cells and their role in the process of ARMD remains to be clarified. Nevertheless, we believe that this finding may have important consequences for the understanding and monitoring of dry ARMD, as well as for the validation of experimental models of ARMD.
Cases
Authors: Black G.C. , Hall G. , Ramsden S.
Published: September 2015

Within the context of the Ophthalmic Genetic Clinic, the diagnosis of Inherited Eye Diseases (IED) requires an integrated approach. This can not only determine clinical management and treatment, but also direct genetic counselling, which is valuable both for the patient and relevant to their wider family. Such an approach requires an accurate history (including a detailed three generation family history), as well as detailed clinical examination, imaging and investigation. Increasingly, such an process requires the integration of genomic testing via Next Generation Sequencing with can include multigene panels, clinical exomes or even whole genome sequencing. The presentation will include a range of examples to span the breadth of IED including developmental disorders (such as microphthalmia/anophthalmia and congenital cataract), anterior segment disorders as well as inherited retinal disorders (both childhood and adult onset). This will illustrate the power of a multidisciplinary and integrated apporach to the diagnosis of IED.
Gene panels and genomic testing for childhood cataract and lens dislocation disorders
Authors: Black G.C. , Hall G. , Ramsden S. , Lloyd I.C.
Published: September 2015

Congenital cataract (CC) affects 3–5 individuals per 10,000 and is a significant cause of lifelong visual disability worldwide. Highly heterogeneous, CC may be isolated or may form one manifestation of a multisystemic condition. It is estimated that around 50% of bilateral CC cases have a genetic basis, with well over 100 genes implicated in their underlying etiology. Consequently, the identification and characterisation of CC is not equivalent to making a clinical diagnosis on which is based care planning, genetic counselling and non‐ocular management. Until recently, clinical investigation of patients with CC has been based upon an iterative, clinically‐driven process that is expensive, time‐consuming and inefficient. The advent of Next Generation Sequencing promises to provide a platform upon which can be built a unified approach to diagnosis. We, and others, have shown that such an approach can identify the molecular basis of CC and other lens‐related disorders such as lens subluxation in the majority (over 70% in our series) of cases. When applied early in the diagnostic pathway this can direct ongoing management, improve outcomes for pathents, and direct genetic counselling for families with CC.
Masquerade syndromes in children
Authors: Desjardins L. , Cassoux N.
Published: September 2015

In children the main diagnosis problem are represented by retinoblastoma and rhabdomyosarcoma.

Retinoblastoma can sometimes present as an inflammatory disease with conjunctival and orbital inflammatory reactions. Some tumors can be the cause of major vascular dilatation and exudation which can simulate coats disease. Diffuse infiltrating retinoblastoma can simulate uveitis. All these aspects will be described extensively. One has to keep in mind the necessity of complete fundus examination in case of strabismus or leukocoria. In case of unilateral retinal detachment or uveitis, the possibility of retinoblastoma should always be ruled out before any surgery.

Rhabdomyosarcoma usually presents like a rapid exophtalmia with inflammation but can also appear as a conjunctival or palpebral mass. It should not be mistaken for infectious disease and orbital biopsy should be performed promptly.
The corpus callosum in human binocularity and strabismus
Authors: Ten Tusscher M.
Published: September 2015

Intercortical visual transfer has been shown important in mammalian binocularity. The present study aims at demonstrating intercortical visual callosal transfer in 16 human subjects using DTI, fMRI and connectivity. With fMRI brain activation was analysed during central and peripheral retinal stimulation. These were compared with right and left sided stimuli during RE and LE fixation. Results were analysed in a 2 × 2 × 2 ANOVA with p = 0.005. Callosal fiber tracts were visualised with DTI. With fMRI it showed that RE fixation is associated more with significant signal changes in the corpus callosum, both with right and left V1 co‐activation. Connectivity from the left V1 showed mostly de‐activation in the corpus callosum and activation if the eye is stimulated from the contralateral central area of the visual field. Callosal activity is associated stronger with stimulation of the temporal central retina and right eye fixation. The stronger trigger from the right eye is likely due to ocular dominance: during central stimulation of the temporal retina of the RE, activation in the left V1 is associated with de‐activation in the corpus callosum.
ANGIO‐OCT and DMLA (diagnosis and post‐treatment follow‐up)
Authors: Coscas G. , Lupidi M. , Coscas F.
Published: September 2015

To compare the OCT Angiography (OCT‐A) findings to the traditional multimodal imaging (TMI) in patients with exudative AMD (eAMD) in terms of diagnosis and treatment decision.

80 eyes of 73 consecutive eAMD patients diagnosed with different types of CNV were enrolled. The data obtained from the TMI, based on Fluorescein Angiography (FA), Indocyanine green angiography (ICGA) and OCT, were compared with the ones achieved by OCT‐A (Spectralis, Heidelberg Engineering, Heidelberg, Germany). The lesion's activity in TMI was established according to leakage on FA, evidence of CNV network on ICGA and fluid accumulation on OCT, while in OCT‐A was based on the shape, the branching pattern, the anastomoses, the vessel termini and the perilesional hypo‐intense halo. Both OCT‐A and TMI allowed the recognition of 5 types of neovascularization (Type I, Type II, Mixed Type I‐II, CRA, AMD‐related polyps).

The two methods achieved the same diagnosis in 95% of cases. The percentage of full agreement in determining the CNV activity between the two imaging protocols was 92.5%.

Our study highlights the capability of OCT‐A to diagnose, determine the type, grade the activity and guide the treatment of a choroidal neovascular lesion in an eAMD patient.
Differential diagnosis of papilloedema
Authors: Kawasaki A.
Published: September 2015

Optic disc swelling is a non‐specific manifestation of injury to the intraorbital portion of the optic nerve, the nerve head (or disc). By convention, the term “papilledema” refers to optic disc edema that is due to increased intracranial pressure. Increased intracranial pressure typically causes bilateral swelling of the optic discs, although asymmetry in the degree of disc edema is not uncommon. Truly unilateral papilledema is rare. In most cases of papilledema (increased intracranial pressure), visual function is relatively preserved. This lecture will present the differential diagnosis of patients who present with bilateral disc edema of unknown etiology and discuss how to distinguish those who have true papilledema of increased intracranial pressure.
Neuro‐ophthalmic considerations and investigations
Authors: Kawasaki A.
Published: September 2015

Unexplained visual loss is a challenging clinical situation. It is important to distinguish underlying occult pathology from visual loss without organic basis. Even trickier are patients in whom concurrent organic disease does exist but the degree of visual dysfunction is exaggerated, leading to the false notion of malingering. This lecture examines some objectives techniques for discerning visual function in the patient with medically unexplained visual loss.
Optic nerve hypoplasia: Evaluation and genetic considerations
Authors: Yu‐Wai‐Man P.
Published: September 2015

The minimum prevalence of optic nerve hypoplasia has been estimated at 1 in 10,000 and unlike other causes of childhood blindness, the incidence of this congenital disorder is still increasing in the developed world. From a practical point of view, children with optic nerve hypoplasia need to be properly evaluated given the strong association with a number of developmental brain abnormalities and potentially life‐threatening neuroendocrine dysfunction. This presentation will also review the complex aetiology and emerging genetic basis for this important cause of visual impairment in young children.