bluuebunny/crossref_metadata_2025 huggingface dataset:
Coeliac disease presenting as severe hypoglycaemia in youth with Type 1 diabetes
Authors: Khoury N. , Semenkovich K. , Arbeláez A. M.
Published: May 2014

Background

Coeliac disease is an autoimmune disorder classically characterized by gastrointestinal symptoms and poor growth. The disease can be difficult to recognize in patients with Type 1 diabetes mellitus. Some clinicians find treatment of the disease in asymptomatic individuals controversial.

Case reports

Two adolescent female patients with Type 1 diabetes experienced recurrent hypoglycaemic seizures. Neither patient reported gastrointestinal symptoms or poor growth. After diagnosis and treatment of coeliac disease, hypoglycaemia resolved.

Conclusion

These cases illustrate how frequent unexplained severe hypoglycaemia can be an atypical presentation of coeliac disease in youth with Type 1 diabetes. Furthermore, they emphasize the importance of screening and treatment of coeliac disease in asymptomatic patients with Type 1 diabetes. Although controversial, management of coeliac disease in these asymptomatic patients can prevent the vicious cycle of recurrent hypoglycaemia and decrease risk for morbidity and death.
Field validation supports novel niche modeling strategies in a cryptic endangered amphibian
Authors: Searcy Christopher A. , Shaffer H. Bradley
Published: May 2014

Many studies employ ecological niche models (ENMs) to predict species’ occurrences in undersampled regions, generally without field confirmation. Here, we use field surveys to test the relative utility of four potential refinements to the standard ENM approach: 1) altering model complexity based on AICc, 2) selecting background points from a biologically informed region, 3) using target‐group background to account for sampling bias in existing localities, and 4) using many rangewide localities (global model) versus fewer proximal localities (local model) to construct geographically restricted range predictions. We used Maxent to predict new localities for the California tiger salamander Ambystoma californiense, an endangered species that often goes undocumented due to its cryptic lifestyle. We followed this with a field survey of 260 previously unsampled potential breeding sites in Solano County, CA and used the resulting presence/absence data to compare all factorial combinations of the four model refinements using a new application of the Kruskal–Wallis test for ENM outputs. Our field surveys led to the discovery of 81 previously undocumented breeding localities for the California tiger salamander and demonstrated that ENMs could be significantly improved by utilizing target‐group background to account for spatial sampling bias and local models to focus model output on the subregion of the range being surveyed. Our results clearly demonstrate the potential for local models to outperform global models, and we recommend supplementing traditional Maxent global models that utilize all known localities with local models, particularly when species occupy geographically structured, heterogeneous habitat types. We also recommend using target‐group background since the improvement we observed when including it in our models was significant and very similar to that documented by previous studies. Most importantly, we emphasize the importance of field verification to enable rigorous statistical comparisons among models.
Climate change and habitat fragmentation drive the occurrence of Borrelia burgdorferi, the agent of Lyme disease, at the northeastern limit of its distribution
Authors: Simon Julie A. , Marrotte Robby R. , Desrosiers Nathalie , Fiset Jessica , Gaitan Jorge , Gonzalez Andrew , Koffi Jules K. , Lapointe Francois‐Joseph , Leighton Patrick A. , Lindsay Lindsay R. , Logan Travis , Milord Francois , Ogden Nicholas H. , Rogic Anita , Roy‐Dufresne Emilie , Suter Daniel , Tessier Nathalie , Millien Virginie
Published: May 2014

Lyme borreliosis is rapidly emerging in Canada, and climate change is likely a key driver of the northern spread of the disease in North America. We used field and modeling approaches to predict the risk of occurrence of Borrelia burgdorferi, the bacteria causing Lyme disease in North America. We combined climatic and landscape variables to model the current and future (2050) potential distribution of the black‐legged tick and the white‐footed mouse at the northeastern range limit of Lyme disease and estimated a risk index for B. burgdorferi from these distributions. The risk index was mostly constrained by the distribution of the white‐footed mouse, driven by winter climatic conditions. The next factor contributing to the risk index was the distribution of the black‐legged tick, estimated from the temperature. Landscape variables such as forest habitat and connectivity contributed little to the risk index. We predict a further northern expansion of B. burgdorferi of approximately 250–500 km by 2050 – a rate of 3.5–11 km per year – and identify areas of rapid rise in the risk of occurrence of B. burgdorferi. Our results will improve understanding of the spread of Lyme disease and inform management strategies at the most northern limit of its distribution.
Applied equine genetics
Authors: Finno C. J. , Bannasch D. L.
Published: May 2014

Genome sequencing of the domestic horse and subsequent advancements in the field of equine genomics have led to an explosion in the development of tools for mapping traits and diseases and evaluating gene expression. The objective of this review is to discuss the current progress in the field of equine genomics, with specific emphasis on assembly and analysis of the reference sequence and subsequent sequencing of a Quarter Horse mare; the genomic tools currently available to researchers and their implications in genomic investigations in the horse; the genomics of Mendelian and non‐Mendelian traits; the genomics of performance traits and considerations regarding genetic testing in the horse. The whole‐genome sequencing of a Quarter Horse mare has provided additional variants within the equine genome that extend past single nucleotide polymorphisms to include insertions/deletions and copy number variants. Equine single nucleotide polymorphism arrays have allowed for the investigation of both simple and complex genetic traits while DNA microarrays have provided a tool for examining gene expression across various tissues and with certain disease conditions. Recently, next‐generation sequencing has become more affordable and both whole‐genome DNA sequencing and transcriptome‐wide RNA sequencing are methodologies that are being applied to equine genomic research. Research in the field of equine genomics continues to expand rapidly as the cost of genotyping and sequencing decreases, resulting in a need for quality bioinformatics software and expertise to appropriately handle both the size and complexity of these data.
Epidemiology of shivering (shivers) in horses
Authors: Draper A. C. E. , Bender J. B. , Firshman A. M. , Baird J. D. , Reed S. , Mayhew I. G. , Valberg S. J.
Published: May 2014

Reasons for perfoming study

Investigating the epidemiology of shivering in horses.

Objectives

The purpose of this study was to characterise the signalment, clinical signs and management factors associated with shivering (also known as shivers), a relatively rare, poorly defined movement disorder in horses.

Study design

Web‐based case series survey and case–control study.

Methods

A Web‐based survey was used to obtain information from owners, worldwide, who suspected that their horse had shivering. Survey respondents were asked to answer standardised questions and to provide a video of the horse. Authors reviewed the surveys and videos, and horses were diagnosed with shivering if they displayed normal forward walking, with difficulty during manual lifting of the hoof and backward walking due to hyperflexion or hyperextension of the pelvic limbs. Cases confirmed by video were designated ‘confirmed shivering’, while those with compatible clinical signs but lacking video confirmation were designated ‘suspected shivering’. Owners of confirmed shivering horses were asked to provide information on 2 horses without signs of shivering (control group).

Results

Three hundred and five surveys and 70 videos were received; 27 horses were confirmed shivering (50 controls), 67 were suspected shivering and the rest had a variety of other movement disorders. Suspected shivering horses resembled confirmed shivering cases, except that the suspected shivering group contained fewer draught breeds and fewer horses with exercise intolerance. Confirmed shivering signs often began at <5 years of age and progressed in 74% of cases. Owner‐reported additional clinical signs in confirmed cases included muscle twitching (85%), muscle atrophy (44%), reduced strength (33%) and exercise intolerance (33%). Shivering horses were significantly taller (confirmed shivering, mean ∼173 cm; control horses, ∼163 cm) with a higher male:female ratio (confirmed shivering, 3.2:1 vs. control, 1.7:1). No potential triggering factors or effective treatments were reported.

Conclusions

Shivering is a chronic, often gradually progressive movement disorder that usually begins before 7 years of age and has a higher prevalence in tall male horses.
Vitiligo treatment demystified: a flowchart for stratified treatment approaches
Authors: Tung Rebecca , Le Poole I. Caroline
Published: May 2014

The recent publication by Anbar et al. in the April issue of this journal, delineating and prioritizing treatment options for vitiligo, is both timely and significant. First and foremost, this work brings to the forefront the important message that vitiligo truly is a treatable disease. All too often, patients refrain from seeking treatment as public opinion dictates that vitiligo is not an important disease, there are no effective treatments available, and insurance will not cover attempts to treat. By providing clear guidelines of treatments to be considered, practicing physicians seeing an occasional vitiligo patient will be more readily inclined to explore the possibilities currently available for enhancing the quality of life of this patient group.
Comparing and modifying penaeid beam and otter trawls to improve ecological efficiencies
Authors: McHugh M. J. , Broadhurst M. K. , Sterling D. J. , Millar R. B.
Published: May 2014

In an attempt to improve the selectivity and engineering performances of generic penaeid trawls, three established and one novel spreading‐mechanism configurations were assessed: otter boards attached (1) with and (2) without 3.15‐m sweeps to a 7.35‐m headline trawl, and a beam rigged directly to a 9.19‐m trawl (3) with and (4) without a horizontal wire and plastic streamers. Despite more surface area (7.5 vs 6.0 m2), both beam‐trawl configurations had significantly lower drag than the otter trawls (≤30%). When catches were standardised to per ha, the otter trawl with sweeps retained significantly more (1.3–2.4 times) school prawns, Metapenaeus macleayi (Haswell), than the other three configurations. Within systems, removing sweeps or adding a horizontal wire significantly reduced the unwanted catches of a key teleost (southern herring, Herklotsichthys castelnaui Ogilby) by 41 and 48%. The results illustrate the utility of simple anterior modifications for independently addressing penaeid‐trawling environmental issues.
Larval dispersal and population connectivity among a network of marine reserves
Authors: Puckett Brandon J. , Eggleston David B. , Kerr Patrick C. , Luettich Richard A.
Published: May 2014

A major challenge in marine ecology is describing patterns of larval dispersal and population connectivity, as well as their underlying processes. We used a biophysical model to simulate dispersal of eastern oyster, Crassostrea virginica, larvae and connectivity among a network of 10 no‐take reserves in a shallow, wind‐driven estuary to assess the relative importance of spawning location, spawning date, larval behavior, larval mortality, and adult reproductive output to predicted dispersal and connectivity patterns. The location (i.e., natal reserve) and date of spawning relative to physical processes, particularly frequency of wind reversals, were the dominant drivers of dispersal and connectivity patterns. To a lesser extent, larval behavior (i.e., 3D vertical advection and ontogenetic depth regulation) and mortality modified dispersal and connectivity, whereas spatiotemporal variability in adult reproductive output was of minimal importance. Over a 21‐day larval duration, mean dispersal distance of passive surface particles ranged from 5 to 40 km. Reserves were too small (1 km2) relative to mean dispersal distances to promote extensive local retention (median 2%) and spaced too far apart (typically ~50 km) to promote extensive inter‐reserve connectivity (median 2%). Limited connectivity and local retention may preclude the network from being self‐sustainable, thereby limiting its long‐term conservation and management benefits. In reserve systems characterized by limited connectivity, management efforts should focus on increasing connectivity by increasing the number or size of reserves to realize the benefits of improved adult demographics within reserves.
Modelling the dispersal of herring and hake larvae in the Strait of Georgia for the period 2007–2009
Authors: Snauffer Evgeniya L. , Masson Diane , Allen Susan E.
Published: May 2014

The Strait of Georgia (SoG), between Vancouver Island and mainland British Columbia, is a larval rearing ground for both hake and herring stocks, which are commercially important. Year‐to‐year variability in larval retention within the strait is examined by simulating drift tracks of larvae for these species using an ocean circulation model and a particle‐tracking model. Larvae with different vertical swimming behaviors were tracked in the springs of 2007, 2008, and 2009. Since herring larvae mostly stay near the surface, their distribution is heavily influenced by the wind. Strong winds to the north soon after the hatching period tend to wash herring larvae out of SoG and winds to the south help retain herring larvae inside the Strait. In 2007, the model indicates a massive wind‐driven export of herring larvae which may have led to the observed failure of herring production. In contrast, hake larvae reside deeper in the water column (50–200 m). Their distribution is less sensitive to surface forcing but is shaped by a deep gyre with cross‐strait currents. This study also suggests that the northern and southern SoG are weakly connected for herring larvae dispersal, which makes both regions potentially important to recruitment.
Fish determine macroinvertebrate food webs and assemblage structure in Greenland subarctic streams
Authors: González‐Bergonzoni Ivan , Landkildehus Frank , Meerhoff Mariana , Lauridsen Torben L. , Özkan Korhan , Davidson Thomas A. , Mazzeo Nestor , Jeppesen Erik
Published: May 2014

Climate warming in (sub)arctic regions is expected to increase freshwater fish overwinter survival and dispersal, potentially with strong implications for macroinvertebrate assemblage composition and ecosystem processes. Several studies worldwide have shown large effects of top predators (usually fish) on macroinvertebrates in streams. However, the influence of top predators on trophic diversity, the range of food resources exploited and trophic niche redundancy is less well studied, particularly in cold regions.

Using stable isotopes (13C and15N) and fish gut content analysis, we investigated the effect of top predators on macroinvertebrate food webs in streams in Greenland by comparing adjacent sites with and without fish (Gasterosteus aculeatus).

Food‐web metrics estimated from stable isotope data showed that the presence of fish reduced the diversity of food sources exploited by macroinvertebrates as well as their trophic diversity. In addition, fish presence increased packing and trophic redundancy of macroinvertebrate taxa in the food web, possibly due to behavioural changes in foraging activity. Furthermore, predatory macroinvertebrate taxa were unable to attain the trophic position of fish so that food webs were one trophic level longer in streams with fish. Focusing on macroinvertebrate food webs alone, predatory macroinvertebrates did not change their trophic position in the presence of fish.

Filter feeders dominated the macroinvertebrate assemblage when fish were present, while the relative abundance of collector‐gatherers was marginally higher in the fishless streams. This pattern was consistent with stronger selectivity for collector‐gatherers by fish.

Climate‐driven fish colonisation in currently fishless Greenland streams may induce a shift in macroinvertebrate food webs, with a reduction in both trophic diversity and the variety of food sources consumed. To some extent, this might counteract a change towards a broader use of food resources by macroinvertebrates that might otherwise be expected at higher temperatures. In addition, a shift in the macroinvertebrate assemblage towards dominance of filter feeders can be expected to promote an increase in periphyton biomass in streams with fish.
Dispersal distance and the pool of taxa, but not barriers, determine the colonisation of restored river reaches by benthic invertebrates
Authors: Tonkin Jonathan D. , Stoll Stefan , Sundermann Andrea , Haase Peter
Published: May 2014

Restoration is an increasingly central theme in river ecology. Recent studies have highlighted the importance of the species pool in the surrounding river network for determining colonisation of restored river reaches by both invertebrates and fish.

Using a comprehensive data set of 21 river restoration sites and 292 sites in the immediate surroundings, we tested the influence of distance to nearest colonist source on invertebrate colonisation based on a comparison of river network distances and Euclidean distances, expecting river network distances would better align with colonisation rates. We then assessed the importance of dispersal distance in relation to several other parameters, such as the number and intensity of barriers along the river network, surrounding taxon pool occupancy rate, physical characteristics of the restored sites and restoration techniques used in determining colonisation of commonly occurring benthic invertebrates.

We hypothesised that (i) distance would be critical, with colonisation of restored sites declining with increasing distance; (ii) barriers between these sites would be a minor, but taxon‐specific, influence on the colonisation; and (iii) the higher the regional pool occupancy rate of a certain taxon, the higher its probability of presence at a restored site.

Overall, taxon pool occupancy rate was the most important driver of colonisation likelihood, followed by distance to nearest source, with the first kilometre particularly important. The effect of barriers was minor but significant, and taxon identity had no effect on the predictive ability of the model. Factors associated with the restoration projects such as techniques used and physical characteristics had minor influences, being completely outweighed by taxon pool and dispersal‐related factors.

To gauge the likelihood of successful outcomes of habitat restoration projects, we suggest it is important to assess regional taxon pools and ensure distances between healthy populations are minimised. These results clearly emphasise the importance of spatial planning for restoration projects.
Climate change and Southern Ocean ecosystems I: how changes in physical habitats directly affect marine biota
Authors: Constable Andrew J. , Melbourne‐Thomas Jessica , Corney Stuart P. , Arrigo Kevin R. , Barbraud Christophe , Barnes David K. A. , Bindoff Nathaniel L. , Boyd Philip W. , Brandt Angelika , Costa Daniel P. , Davidson Andrew T. , Ducklow Hugh W. , Emmerson Louise , Fukuchi Mitsuo , Gutt Julian , Hindell Mark A. , Hofmann Eileen E. , Hosie Graham W. , Iida Takahiro , Jacob Sarah , Johnston Nadine M. , Kawaguchi So , Kokubun Nobuo , Koubbi Philippe , Lea Mary‐Anne , Makhado Azwianewi , Massom Rob A. , Meiners Klaus , Meredith Michael P. , Murphy Eugene J. , Nicol Stephen , Reid Keith , Richerson Kate , Riddle Martin J. , Rintoul Stephen R. , Smith Walker O. , Southwell Colin , Stark Jonathon S. , Sumner Michael , Swadling Kerrie M. , Takahashi Kunio T. , Trathan Phil N. , Welsford Dirk C. , Weimerskirch Henri , Westwood Karen J. , Wienecke Barbara C. , Wolf‐Gladrow Dieter , Wright Simon W. , Xavier Jose C. , Ziegler Philippe
Published: May 2014

Antarctic and Southern Ocean (ASO) marine ecosystems have been changing for at least the last 30 years, including in response to increasing ocean temperatures and changes in the extent and seasonality of sea ice; the magnitude and direction of these changes differ between regions around Antarctica that could see populations of the same species changing differently in different regions. This article reviews current and expected changes inASOphysical habitats in response to climate change. It then reviews how these changes may impact the autecology of marine biota of this polar region: microbes, zooplankton, salps, Antarctic krill, fish, cephalopods, marine mammals, seabirds, and benthos. The general prognosis forASOmarine habitats is for an overall warming and freshening, strengthening of westerly winds, with a potential pole‐ward movement of those winds and the frontal systems, and an increase in ocean eddy activity. Many habitat parameters will have regionally specific changes, particularly relating to sea ice characteristics and seasonal dynamics. Lower trophic levels are expected to move south as the ocean conditions in which they are currently found move pole‐ward. For Antarctic krill and finfish, the latitudinal breadth of their range will depend on their tolerance of warming oceans and changes to productivity. Ocean acidification is a concern not only for calcifying organisms but also for crustaceans such as Antarctic krill; it is also likely to be the most important change in benthic habitats over the coming century. For marine mammals and birds, the expected changes primarily relate to their flexibility in moving to alternative locations for food and the energetic cost of longer or more complex foraging trips for those that are bound to breeding colonies. Few species are sufficiently well studied to make comprehensive species‐specific vulnerability assessments possible. Priorities for future work are discussed.
Field practice study of half‐dose sorafenib treatment on safety and efficacy for hepatocellular carcinoma: A propensity score analysis
Authors: Morimoto Manabu , Numata Kazushi , Kondo Masaaki , Kobayashi Satoshi , Ohkawa Shinichi , Hidaka Hisashi , Nakazawa Takahide , Okuwaki Yusuke , Okuse Chiaki , Matsunaga Kotaro , Suzuki Michihiro , Morita Satoshi , Taguri Masataka , Tanaka Katsuaki
Published: May 2014

Aim

Patients with hepatocellular carcinoma (HCC) who receive an initial full dose of sorafenib (800 mg/day) often require a decreased dose (400 mg/day) or discontinuation of therapy because of severe adverse events. We conducted a retrospective analysis of patients with HCC to compare the safety and efficacy of full‐ to half‐dose sorafenib.

Methods

We reviewed the medical records of 218 consecutive patients with intermediate or advanced stage HCC who received half (n = 73) or full‐dose sorafenib (n = 145) between 2009 and 2012 at four institutions. A propensity score‐matching analysis was used to adjust for potential bias.

Results

Multivariate logistic regression analysis showed that increased age was an independent factor for the selection of initial half‐dose sorafenib (odds ratio, 1.10; 95% confidence interval, 1.05–1.15; P < 0.001). Fifty‐eight patients each in the half‐dose and full‐dose groups were selected for propensity score matching. The incidence of grade 3–4 severe adverse effects was lower in the half‐dose group (47.4% vs 66.7%, P = 0.037). In contrast, the median progression‐free survival (PFS) and overall survival (OS) rates were not significantly different (half‐dose group, 3.8 and 10.2 months; full‐dose group, 2.5 and 8.8 months; P = 0.143 and 0.911, respectively).

Conclusion

Propensity score‐matched analyses indicate that initial half‐dose sorafenib treatment led to fewer severe adverse effects and a comparable survival benefit compared with a full dose in select patients with HCC, particularly for those of advanced age.
Construction and Contestation: Toward a Unifying Methodology for Borderlands History
Authors: Orsi Jared
Published: May 2014

Borderlands history is a burgeoning field that churns out dozens of important monographs every year. Despite their individual insights, these works collectively lack conceptual glue to hold them together as a field. Using US‐Mexican border historiography as a case study, this article synthesizes recent scholarship to extract an emerging but as yet not fully articulated methodology that unites much of the field's scholarship of the last decade. Regardless of their individual time, place, or subject matter emphases, the works considered here share common starting questions that inquire what borders are present in any historical context and what their origins and consequences are. The keystone of the methodology is a dialect through which borderlands historians understand borders to be constructed, contested, reconstructed, and ultimately unfinished and unstable. Borderlands historians extend their analysis to include the mental categories with which people have historically made sense of their worlds, and they employ innovative narrative structures that integrate large and small spatial and geographical scales into coherent stories. As a research field seeking to explain the origins and evolution of national and other borders, borderlands history explores one of the most important developments of modern history. As a teaching field that introduces students to the history of boundary making and crossing, borderlands history helps prepare them for twenty‐first‐century world citizenship.
Canadian Political History and Ideas: Intersections and Influences
Authors: Anderson Kevin
Published: May 2014

Over the last two decades, traditionally minded historians have argued that the rise of social and cultural history has fragmented Canadian history and caused the decline of Canadian political history. Despite these claims, current Canadian political history is proving to be a dynamic field that embraces the methodological and theoretical innovations of social and cultural history by incorporating gender, class, race and ethnicity as categories of analysis to create a “new political history.” However, the “new political history” in Canada has neglected to integrate the history of ideas. Studying the history of ideas in Canadian political history could expand the discipline beyond the current trends that include highly individualised political biography and studies emphasising politics, the state and ideology within Ian McKay's potentially reductive liberal order framework. Supplementing the “new political history” with the history of ideas, influenced by the work of Michael Freeden, would allow innovative analyses of institutional and popular politics to accompany the voices of elite political figures.
Telegraphy and Journalism in Colonial India, c. 1830s to 1900s
Authors: Bonea Amelia
Published: May 2014

This essay argues that a focus on technologies of communication such as the electric telegraph helps us to rethink the historiography of the press in colonial India by drawing attention to the ‘moments of transition’ of the 19th century and questioning dominant narratives of a media revolution spurred by telegraphy. It also enables us to overcome some of the limitations of previous nation‐centric research by recovering the networks of technology and news which integrated newspapers during this period and providing insights into the development of news reporting in 19th‐century India.
Immunohistochemistry in the diagnosis of papillary lesions of the breast
Authors: Tse Gary M , Ni Yun‐Bi , Tsang Julia Y S , Shao Mu‐Min , Huang Yu‐Hua , Luo Ming‐Hua , Lacambra Maribel D , Yamaguchi Rin , Tan Puay‐Hoon
Published: May 2014

Aims

Many immunohistochemical markers have been studied for differentiating papillary lesions. However, their differentiating power has not been evaluated comprehensively. Additionally, assessment of some markers will require the difficult task of identifying different cell types. In the current study, we aimed to devise a simple papillary panel which can aid in diagnosis irrespective of architectural pattern and cell type differentiation.

Methods and results

Immunohistochemical analysis of papillary lesions using myoepithelial markers [p63 and smooth muscle actin (SMA)], high molecular weight cytokeratins (HMWCKs: CK5, CK5/6, CK14 and 34βE12), hormone receptors (ER and PR) and neuroendocrine markers (chromogranin and synaptophysin) was performed. Among them, neuroendocrine markers showed high specificity but low sensitivity. HMWCK specificity was better than that for myoepithelial markers. Homogeneous staining pattern for hormonal receptors rather than their percentage positivity was more effective in identifying malignant lesions. Negative staining for two or more of HMWCKs, namely CK5/6, CK14 and 34βE12, achieved the best overall specificity and sensitivity of 87.8% and 94.1%, respectively, irrespective of the architecture. Their discriminatory power was validated with an independent cohort of core needle biopsies.

Conclusions

A marker panel with HMWCKs could be used in differentiating papillary lesions irrespective of architectural pattern or cell type differentiation.
Epstein–Barr virus‐associated lymphoepithelioma‐like cholangiocarcinoma: a rare variant of intrahepatic cholangiocarcinoma with favourable outcome
Authors: Chan Anthony W H , Tong Joanna H M , Sung Mandy Y M , Lai Paul B S , To Ka‐Fai
Published: May 2014

Aims

Lymphoepithelioma‐like cholangiocarcinoma (LELCC) is a rare variant of intrahepatic cholangiocarcinoma (IHCC). Only 16 cases have reported previously in the literature, and about 62.5% of these cases were associated with Epstein–Barr virus (EBV).

Methods and results

We present the largest series (seven cases) of LELCC with descriptions of clinical and pathological characteristics, investigations of aberrant DNA methylation and mutation analyses of EGFR and KRAS. The evaluation also included 11 cases of stage‐matched conventional IHCC for comparison.

Results

All seven patients of LELCC were female and had stage I disease. LELCC had significantly better 2‐ and 5‐year overall survival than IHCC (100% versus 52.8%, and 100% versus 13.2%, respectively, P = 0.003). All seven LELCCs were EBV‐associated and composed exclusively of adenocarcinoma with varied glandular differentiation, dense lymphoplasmacytic infiltrate, and variable expression of biliary‐type cytokeratins (CK7 and CK19) and stemness markers (CD133 and EpCAM). Gene hypermethylation was more frequent in LELCC than IHCC. CRBPI (85.7% versus 9.1%, P < 0.003) and CRBPIV (85.7% versus 0%, P < 0.001) showed statistically higher methylation frequencies in LELCC than IHCC. No LELCC harboured any EGFR or KRAS mutation.

Conclusion

Epstein–Barr virus‐associated LELCC is a variant of IHCC, characterized by marked female predominance, favourable overall survival and distinctively frequent DNA hypermethylation.
HIV/hepatitis C virus coinfection management: changing guidelines and changing paradigms
Authors: Cooper CL , Klein MB
Published: May 2014

Objectives

The aim of the study was to consider the impact of new direct‐acting antiviral (DAA) regimens on hepatitis C virus (HCV) treatment in HIV/HCV coinfection.

Methods

Current coinfection guidelines were reviewed and the impact of recent DAA publications evaluating HIV‐coinfected individuals was considered.

Results

Current coinfection guidelines recommend HIV antiretroviral therapy initiation prior to HCV antiviral therapy. New all‐oral, combination antiviral therapy composed of one or more DAAs with or without ribavirin will change this paradigm. As these regimens are better tolerated, it will be possible to offer nearly all HCV‐infected patients antiviral therapy, including those with HIV infection. All‐oral regimens may impact the incidence of HCV infection by providing a treatment option that can be safely and broadly utilized in high‐risk populations with the benefits of curing individual patients and addressing broader public health concerns related to HCV.

Conclusions

HCV infection treatment should no longer be a secondary consideration restricted to the minority of HIV/HCV‐coinfected patients.
Evidence for aldosterone‐dependent growth of renal cell carcinoma
Authors: King Sharon , Bray Susan , Galbraith Sarah , Christie Lesley , Fleming Stewart
Published: May 2014

The aim if this study was to investigate the hypothesis that K‐RAS 4A is upregulated in a mineralocorticoid‐dependent manner in renal cell carcinoma and that this supports the proliferation and survival of some renal cancers. Expression of the K‐RAS in renal tumour tissues and cell lines was examined by real‐time PCR and Western blot and mineralocorticoid receptor, and its gatekeeper enzyme 11β‐hydroxysteroid dehydrogenase‐2 was examined by immunocytochemistry on a tissue microarray of 27 cases of renal cell carcinoma. Renal cancer cells lines 04A018 (RCC4 plus VHL) and 04A019 (RCC4 plus vector alone) were examined for the expression of K‐RAS4A and for the effect on K‐RAS expression of spironolactone blockade of the mineralocorticoid receptor. K‐RAS4A was suppressed by siRNA, and the effect on cell survival, proliferation and activation of the Akt and Raf signalling pathways was investigated in vitro. K‐RAS4A was expressed in RCC tissue and in the renal cancer cell lines but K‐RAS was downregulated by spironolactone and upregulated by aldosterone. Spironolactone treatment and K‐RAS suppression both led to a reduction in cell number in vitro. Both Akt and Raf pathways showed activation which was dependent on K‐RAS expression. K‐RAS expression in renal cell carcinoma is at least partially induced by aldosterone. Aldosterone supports the survival and proliferation of RCC cells by upregulation of K‐RAS acting through the Akt and Raf pathways.
Living in supportive housing for people with serious mental illness: A paradoxical everyday life
Authors: Bengtsson‐Tops Anita , Ericsson Ulf , Ehliasson Kent
Published: May 2014

Since the closure of large psychiatric institutions, various types of community‐based supportive housing for people with serious mental illness (SMI) have been developed. There is currently limited knowledge about users' experiences of living in supportive housing. The aim of the present study was to describe user experiences of living in supportive housing for people withSMI. Twenty‐nine people living in such facilities participated in open, qualitative interviews. Data were subjected to latent content analysis. Three main themes emerged from this analysis: (i) having a nest, which included the subthemes of a place to rest and having someone to attach to; (ii) being part of a group, with the subthemes of being brought together and a community spirit; and (iii) leading an oppressive life, including the subthemes of questioning one's identity, sense of inequality, and a life of gloom. It could be concluded that user experiences of living in supportive housing are complex and paradoxical. In order to provide supportive housing, staff need to recognize and work within social group processes, and perform continual and structural evaluations of users' social and emotional needs.
Clinical severity of rhinovirus/enterovirus compared to other respiratory viruses in children
Authors: Asner Sandra A. , Petrich Astrid , Hamid Jemila S. , Mertz Dominik , Richardson Susan E. , Smieja Marek
Published: May 2014

Background

Human rhinovirus/enterovirus (HRV/ENT) infections are commonly identified in children with acute respiratory infections (ARIs), but data on their clinical severity remain limited.

Objectives

We compared the clinical severity of HRV/ENT to respiratory syncytial virus (RSV), influenza A/B (FLU), and other common respiratory viruses in children.

Patients/Methods

Retrospective study of children with ARIs and confirmed single positive viral infections on mid‐turbinate swabs by molecular assays. Outcome measures included hospital admission and, for inpatients, a composite endpoint consisting of intensive care admission, hospitalization >5 days, oxygen requirements or death.

Results

A total of 116 HRV/ENT, 102 RSV, 99 FLU, and 64 other common respiratory viruses were identified. Children with single HRV/ENT infections presented with significantly higher rates of underlying immunosuppressive conditions compared to those with RSV (37·9% versus 13·6%; P < 0·001), FLU (37·9% versus 22%; P = 0·018) or any other single viral infection (37·9% versus 22·5%; P = 0·024). In multivariable analysis adjusted for underlying conditions and age, children with HRV/ENT infections had increased odds of hospitalization compared to children with RSV infections (OR 2·6; 95% CI 1·4, 4·8; P < 0·003) or FLU infections (OR 3·0; 95% CI 1·6, 5·8; <0·001) and increased odds of severe clinical disease among inpatients (OR 3·0; 95% CI 1·6,5·6; P = 0·001) when compared to those with FLU infections.

Conclusions

Children with HRV/ENT had a more severe clinical course than those with RSV and FLUA/B infections and often had significant comorbidities. These findings emphasize the importance of considering HRV/ENT infection in children presenting with severe acute respiratory tract infections.
Cardiorespiratory Changes and Pain Response of Lift Laparoscopy Compared to Capnoperitoneum Laparoscopy in Dogs
Authors: Fransson Boel A. , Grubb Tamara L. , Perez Tania E. , Flores Krystina , Gay John M.
Published: May 2014

Objective

To compare intraoperative physiologic variables and post‐operative pain associated with lift laparoscopy and conventional capnoperitoneum laparoscopy.

Study Design

Prospective randomized case controlled study.

Animals

Healthy dogs (n = 30).

Methods

Dogs having laparoscopic ovariohysterectomy were randomly assigned to lift laparoscopy (n = 14) or capnoperitoneum (16) laparoscopy. Physiologic variables measured intraoperatively were documented. Postoperatively, pain response was assessed in a blinded fashion using the short Glasgow pain scale and von Frey filament aesthesiometry.

Results

Lift laparoscopy was associated with less frequency of hypercapnia, required less anesthetic gas, and was not more time‐consuming or painful than capnoperitoneum laparoscopy.

Conclusions

Lift laparoscopy is a feasible alternative to capnoperitoneum laparoscopy, especially in dogs where pressurized capnoperitoneum is not desired.
Altered gene expression signature of early stages of the germ line supports the pre‐meiotic origin of human spermatogenic failure
Authors: Bonache S. , Algaba F. , Franco E. , Bassas L. , Larriba S.
Published: May 2014

The molecular basis of spermatogenic failure (SpF) is still largely unknown. Accumulating evidence suggests that a series of specific events such as meiosis, are determined at the early stage of spermatogenesis. This study aims to assess the expression profile of pre‐meiotic genes of infertile testicular biopsies that might help to define the molecular phenotype associated with human deficiency of sperm production. An accurate quantification of testicular mRNA levels of genes expressed in spermatogonia was carried out by RT‐qPCR in individuals showing SpF owing to germ cell maturation defects, Sertoli cell‐only syndrome or conserved spermatogenesis. In addition, the gene expression profile of SpF was compared with that of testicular tumour, which is considered to be a severe developmental disease of germ cell differentiation. Protein expression from selected genes was evaluated by immunohistochemistry. Our results indicate that SpF is accompanied by differences in expression of certain genes associated with spermatogonia in the absence of any apparent morphological and/or numerical change in this specific cell type. In SpF testicular samples, we observed down‐regulation of genes involved in cell cycle (CCNE1 and POLD1), transcription and post‐transcription regulation (DAZL, RBM15 and DICER1), protein degradation (FBXO32 and TM9SF2) and homologous recombination in meiosis (MRE11A and RAD50) which suggests that the expression of these genes is critical for a proper germ cell development. Interestingly, a decrease in the CCNE1, DAZL, RBM15 and STRA8 cellular transcript levels was also observed, suggesting that the gene expression capacity of spermatogonia is altered in SpF contributing to an unsuccessful sperm production. Altogether, these data point to the spermatogenic derangement being already determined at, or arising in, the initial stages of the germ line.
Why Should We Save Nature's Hidden Gems?
Authors: Parsons Glenn
Published: May 2014

Aesthetic preservation is the idea of sparing natural areas from development because of their aesthetic value. In this article I discuss a problem for aesthetic preservation that I call the ‘hidden gems problem’: in certain cases, the natural area under consideration is so remote and/or fragile that few people can actually experience it. In these cases, it becomes unclear how nature's aesthetic value can justify its preservation when development promises practical human benefits. After rejecting some potential responses to the hidden gems problem, I offer a different solution. I argue that we have an aesthetic reason to preserve nature's hidden gems because they are required to produce ‘true judges’ of aesthetic value, who are capable of improving the general quality of taste for landscape. I develop this argument using the example of recent preservationist efforts to save the isolated landscape of Sable Island, Nova Scotia.
Successful human long‐term application of in situ bone tissue engineering
Authors: Horch Raymund E. , Beier Justus P. , Kneser Ulrich , Arkudas Andreas
Published: May 2014

Tissue Engineering (TE) and Regenerative Medicine (RM) have gained much popularity because of the tremendous prospects for the care of patients with tissue and organ defects. To overcome the common problem of donor‐site morbidity of standard autologous bone grafts, we successfully combined tissue engineering techniques for the first time with the arteriovenous loop model to generate vascularized large bone grafts. We present two cases of large bone defects after debridement of an osteomyelitis. One of the defects was localized in the radius and one in the tibia. For osseus reconstruction, arteriovenous loops were created as vascular axis, which were placed in the bony defects. In case 1, the bone generation was achieved using cancellous bone from the iliac crest and fibrin glue and in case 2 using a clinically approved β‐tricalciumphosphate/hydroxyapatite (HA), fibrin glue and directly auto‐transplanted bone marrow aspirate from the iliac crest. The following post‐operative courses were uneventful. The final examinations took place after 36 and 72 months after the initial operations. Computer tomogrphy (CT), membrane resonance imaging (MRI) and doppler ultrasound revealed patent arterio‐venous (AV) loops in the bone grafts as well as completely healed bone defects. The patients were pain‐free with normal ranges of motion. This is the first study demonstrating successfully axially vascularized in situ tissue engineered bone generation in large bone defects in a clinical scenario using the arteriovenous loop model without creation of a significant donor‐site defect utilizing TE and RM techniques in human patients with long‐term stability.
Effect of rhBMP‐2 dose on bone formation/maturation in a rat critical‐size calvarial defect model
Authors: Pelaez Manuel , Susin Cristiano , Lee Jaebum , Fiorini Tiago , Bisch Frederick C. , Dixon Douglas R. , McPherson James C. , Buxton Amanda N. , Wikesjö Ulf M.E.
Published: May 2014

Background

Application of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) has been associated with significant adverse events in craniofacial settings, including swelling and seroma formation. Recent work has demonstrated an inverse relationship between bone formation/maturation and rhBMP‐2 dose, frequency/severity of adverse events increasing with rising dose.

Objective

The objective of this study was to determine the most effective dose for rhBMP‐2 soak‐loaded onto an absorbable collagen sponge (ACS) carrier for bone formation/maturation using an established defect model.

Methods

One hundred sixty‐eight outbred male Sprague‐Dawley rats, age 11–13 weeks, weight 325–375 g randomized into seven groups of 24 subdivided into groups of eight, were used to provide radiographic and light microscopy observations of bone formation/maturation and aberrant healing events at 2, 4 and 8 weeks following application of rhBMP‐2/ACS into critical‐size, ø8‐mm, through‐through, calvarial osteotomy defects for a dose of 1.25, 2.5, 5.0, 10.0 and 20.0 μg rhBMP‐2/defect, or serve as ACS or sham‐surgery controls.

Results

rhBMP‐2 dosages ≥2.5 μg/defect showed histological defect closure >90% within 2 weeks, and complete resolution within 4 weeks. Adverse healing events including swelling, excessive bone formation or seroma formation could not be determined with certainty in this defect model. Notably ACS control sites showed complete defect closure at the 8‐week healing interval.

Conclusions

rhBMP‐2/ACS accelerates local bone formation in the rat critical‐size through‐through calvarial defect model once reaching an osteoinductive dose threshold. This threshold may already be reached at a 1.25‐/2.5‐μg dose in this model. No further enhancement to bone formation/maturation may be observed adding rhBMP‐2 above the 2.5‐μg dose. The 1.25–20.0 μg dose range did not invoke appreciable aberrant healing events.
Systematic Evaluation of Uncertainty in Material Flow Analysis
Authors: Laner David , Rechberger Helmut , Astrup Thomas
Published: May 2014

Material flow analysis (MFA) is a tool to investigate material flows and stocks in defined systems as a basis for resource management or environmental pollution control. Because of the diverse nature of sources and the varying quality and availability of data, MFA results are inherently uncertain. Uncertainty analyses have received increasing attention in recent MFA studies, but systematic approaches for selection of appropriate uncertainty tools are missing. This article reviews existing literature related to handling of uncertainty in MFA studies and evaluates current practice of uncertainty analysis in MFA. Based on this, recommendations for consideration of uncertainty in MFA are provided. A five‐step framework for uncertainty handling is outlined, reflecting aspects such as data quality and goal/scope of the MFA. We distinguish between descriptive (quantification of material turnover in a region) and exploratory MFA (identification of critical parameters and system behavior). Whereas mathematically simpler concepts focusing on data uncertainty characterization are appropriate for descriptive MFAs, statistical approaches enabling more‐rigorous evaluation of uncertainty and model sensitivity are needed for exploratory MFAs. Irrespective of the level of sophistication, lack of information about MFA data poses a major challenge for meaningful uncertainty analysis. The step‐wise framework suggested here provides a systematic way to consider available information and produce results as precise as the data warrant.