bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexually transmitted infections, benign prostatic hyperplasia and lower urinary tract symptom‐related outcomes: results from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
Authors: Breyer Benjamin N. , Huang Wen‐Yi , Rabkin Charles S. , Alderete John F. , Pakpahan Ratna , Beason Tracey S. , Kenfield Stacey A. , Mabie Jerome , Ragard Lawrence , Wolin Kathleen Y. , Grubb Robert L. , Andriole Gerald L. , Sutcliffe Siobhan
Published: January 2015

Objective

To examine whether a history of sexually transmitted infections (STIs) or positive STI serology is associated with prevalent and incident benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS)‐related outcomes in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Methods

Self‐reported history of STIs (gonorrhoea, syphilis) was ascertained at baseline, and serological evidence of STIs (Chlamydia trachomatis, Trichomonas vaginalis, human papillomavirus (HPV)‐16, HPV‐18, herpes simplex virus type 2, human herpesvirus type 8 and cytomegalovirus) was detected in baseline serum specimens. We used data collected on the baseline questionnaire, as well as results from the baseline prostate‐specific antigen (PSA) test and digital rectal examination (DRE), to define prevalent BPH/LUTS‐related outcomes as evidence of LUTS (self‐reported diagnosis of an enlarged prostate/BPH, BPH surgery or nocturia [waking ≥2 times/night to urinate]) and evidence of prostate enlargement (PSA > 1.4 ng/mL or prostate volume ≥30 mL) in men without prostate cancer. We created a similar definition of incident BPH using data from the follow‐up questionnaire completed 5–13 years after enrolment (self‐reported diagnosis of an enlarged prostate/BPH or nocturia), data on finasteride use during follow‐up, and results from the follow‐up PSA tests and DREs. We used Poisson regression with robust variance estimation to calculate prevalence ratios (PRs) in our cross‐sectional analysis of self‐reported (n = 32 900) and serologically detected STIs (n = 1 143) with prevalent BPH/LUTS, and risk ratios in our prospective analysis of self‐reported STIs with incident BPH/LUTS (n = 5 226).

Results

Generally null results were observed for associations of a self‐reported history of STIs and positive STI serologies with prevalent and incident BPH/LUTS‐related outcomes, with the possible exception of T. vaginalis infection. This STI was positively associated with prevalent nocturia (PR 1.36, 95% confidence interval (CI) 1.18–1.65), prevalent large prostate volume (PR 1.21 95% CI 1.02–1.43), and any prevalent BPH/LUTS (PR 1.32 95% CI 1.09–1.61); too few men had information on both STI serologies and incident BPH/LUTS to investigate the associations between T. vaginalis infection and incident BPH/LUTS‐related outcomes.

Conclusions

Our findings do not support associations of several known STIs with BPH/LUTS‐related outcomes, although T. vaginalis infection may warrant further study.
Management of sexual dysfunction due to central nervous system disorders: a systematic review
Authors: Lombardi Giuseppe , Musco Stefania , Kessler Thomas M. , Marzi Vincenzo Li , Lanciotti Michele , Del Popolo Giulio
Published: January 2015

Objective

To systematically review the management of sexual dysfunction due to central nervous system (CNS) disorders.

Patients and Methods

The review was done according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. Studies were identified independently by two reviewers using electronic searches of MEDLINE and OVID (from January 2004 to August 2014) and hand searches of reference lists and review articles.

Results

In patients with CNS disorders, neuro‐urological assessment is recommended for both genders before starting any treatment for sexual dysfunction. For men, blood sexual hormones evaluation is the main investigation performed before phosphodiesterase type 5 inhibitors (PDE5Is) treatment, whereas there is no consensus on routine laboratory tests for women. PDE5Is are the first‐line medical treatment for men, with the most robust data derived from patients with spinal cord injury assessed by validated questionnaires, mainly the International Index of Erectile Function‐15. There is no effective medical treatment for sexual dysfunction in women. Sacral neuromodulation for lower urinary tract dysfunction may improve sexual dysfunction in both genders.

Conclusions

Although sexual dysfunction is a major burden for patients with CNS disorders, high‐evidence level studies are rare and only available for PDE5Is treating erectile dysfunction. Well‐designed prospective studies are urgently needed for both genders.
Neotropical fish–fruit interactions: eco‐evolutionary dynamics and conservation
Authors: Correa Sandra Bibiana , Costa‐Pereira Raul , Fleming Theodore , Goulding Michael , Anderson Jill T.
Published: January 2015

Frugivorous fish play a prominent role in seed dispersal and reproductive dynamics of plant communities in riparian and floodplain habitats of tropical regions worldwide. In Neotropical wetlands, many plant species have fleshy fruits and synchronize their fruiting with the flood season, when fruit‐eating fish forage in forest and savannahs for periods of up to 7 months. We conducted a comprehensive analysis to examine the evolutionary origin of fish–fruit interactions, describe fruit traits associated with seed dispersal and seed predation, and assess the influence of fish size on the effectiveness of seed dispersal by fish (ichthyochory). To date, 62 studies have documented 566 species of fruits and seeds from 82 plant families in the diets of 69 Neotropical fish species. Fish interactions with flowering plants are likely to be as old as 70 million years in the Neotropics, pre‐dating most modern bird–fruit and mammal–fruit interactions, and contributing to long‐distance seed dispersal and possibly the radiation of early angiosperms. Ichthyochory occurs across the angiosperm phylogeny, and is more frequent among advanced eudicots. Numerous fish species are capable of dispersing small seeds, but only a limited number of species can disperse large seeds. The size of dispersed seeds and the probability of seed dispersal both increase with fish size. Large‐bodied species are the most effective seed dispersal agents and remain the primary target of fishing activities in the Neotropics. Thus, conservation efforts should focus on these species to ensure continuity of plant recruitment dynamics and maintenance of plant diversity in riparian and floodplain ecosystems.
Synthesis and Preliminary Antiviral Activities of Piperidine‐substituted Purines against HIV and Influenza A/H1N1 Infections
Authors: Kang Dongwei , Fang Zengjun , Huang Boshi , Zhang Lingzi , Liu Huiqing , Pannecouque Christophe , Naesens Lieve , De Clercq Erik , Zhan Peng , Liu Xinyong
Published: January 2015

We have developed a series of N2‐(1‐(substituted‐aryl)piperidin‐4‐yl)‐N6‐mesityl‐9H‐purine‐2,6‐diamine derivatives as potent antiviral agents. Preliminary biological evaluation indicated that nearly half of them possessed remarkable HIV inhibitory potencies in cellular assays. In particular, FZJ13 appeared to be the most notable one, which displayed anti‐HIV‐1 activity compared to 3TC. Moreover, an unexpected finding was that FZJ05 displayed significant potency against influenza A/H1N1 (strain A/PR/8/34) in Madin–Darby canine kidney cells with EC50 values much lower than those of ribavirin, amantadine, and rimantadine. The results suggest that these novel purine derivatives have the potential to be further developed as new therapeutic agents against HIV‐1 or influenza virus.
Infant gut microbiota and food sensitization: associations in the first year of life
Authors: Azad M. B. , Konya T. , Guttman D. S. , Field C. J. , Sears M. R. , HayGlass K. T. , Mandhane P. J. , Turvey S. E. , Subbarao P. , Becker A. B. , Scott J. A. , Kozyrskyj A. L. ,   the CHILD Study Investigators
Published: January 2015

Background

The gut microbiota is established during infancy and plays a fundamental role in shaping host immunity. Colonization patterns may influence the development of atopic disease, but existing evidence is limited and conflicting.

Objective

To explore associations of infant gut microbiota and food sensitization.

Methods

Food sensitization at 1 year was determined by skin prick testing in 166 infants from the population‐based Canadian Healthy Infant Longitudinal Development (CHILD) study. Faecal samples were collected at 3 and 12 months, and microbiota was characterized by Illumina 16S rRNA sequencing.

Results

Twelve infants (7.2%) were sensitized to ≥ 1 common food allergen at 1 year. Enterobacteriaceae were overrepresented and Bacteroidaceae were underrepresented in the gut microbiota of food‐sensitized infants at 3 months and 1 year, whereas lower microbiota richness was evident only at 3 months. Each quartile increase in richness at 3 months was associated with a 55% reduction in risk for food sensitization by 1 year (adjusted odds ratio 0.45, 95% confidence interval 0.23–0.87). Independently, each quartile increase in Enterobacteriaceae/Bacteroidaceae ratio was associated with a twofold increase in risk (2.02, 1.07–3.80). These associations were upheld in a sensitivity analysis among infants who were vaginally delivered, exclusively breastfed and unexposed to antibiotics. At 1 year, the Enterobacteriaceae/Bacteroidaceae ratio remained elevated among sensitized infants, who also tended to have decreased abundance of Ruminococcaceae.

Conclusions and Clinical Relevance

Low gut microbiota richness and an elevated Enterobacteriaceae/Bacteroidaceae ratio in early infancy are associated with subsequent food sensitization, suggesting that early gut colonization may contribute to the development of atopic disease, including food allergy.
Neutrophil extracellular trap formation is associated with autophagy-related signalling in ANCA-associated vasculitis
Authors: Tang S , Zhang Y , Yin S-W , Gao X-J , Shi W-W , Wang Y , Huang X , Wang L , Zou L-Y , Zhao J-H , Huang Y-J , Shan L-Y , Gounni A S , Wu Y-Z , Zhang J-B
Published: January 2015

Increasing evidence indicates that aberrant neutrophil extracellular trap (NET) formation could contribute to the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Recent research has provided evidence that a novel type of ANCA autoantibody, anti-lysosomal membrane protein-2 (LAMP-2) antibody, may have a pathogenic role in AAV. We have shown previously that anti-LAMP-2 antibody-stimulated NET formation contains autoantigens and anti-microbial peptides. The current study sought to determine whether LAMP-2, as a novel antigen of ANCA, was present on NETs in AAV patients, the influence of the anti-LAMP-2 antibody on the neutrophil apoptosis rate and the role of autophagy in anti-LAMP-2 antibody-induced NET formation. NET formation was assessed using immunofluorescence microscopy, scanning electron microscopy or live cell imaging. The neutrophil apoptosis rate was analysed using fluorescence activated cell sorting (FACS). Autophagy was detected using LC3B accumulation and transmission electron microscopy. The results showed that enhanced NET formation, which contains LAMP-2, was observed in kidney biopsies and neutrophils from AAV patients. The apoptosis rate decreased significantly in human neutrophils stimulated with anti-LAMP-2 antibody, and this effect was attenuated by the inhibitors of autophagy 3-methyladenine (3MA) and 2-morpholin-4-yl-8-phenylchromen-4-one (LY294002). The anti-LAMP-2 antibody-stimulated NET formation was unaffected by benzyloxycarbonyl-Val- Ala-Asp (OMe)-fluoromethylketone (zVAD-fmk) and necrostatin-1 (Nec-1), which are inhibitors of apoptosis and necrosis, respectively, but was inhibited by 3MA and LY294002. Moreover, the proportion of LC3BI that was converted to LC3BII increased significantly (P = 0·0057), and massive vacuolizations that exhibited characteristics typical of autophagy were detected in neutrophils stimulated with anti-LAMP-2 antibody. Our results provide further evidence that autophagy is involved in ANCA-induced NET formation in human neutrophils.
Low myocardial glucose uptake in Turner syndrome is unaffected by growth hormone: a randomized, placebo‐controlled FDG‐PET study
Authors: Trolle Christian , Hjerrild Britta , Mortensen Kristian Havmand , Knorr Sine , Søndergaard Hanne Maare , Christiansen Jens Sandahl , Gravholt Claus Højbjerg
Published: January 2015

Background

An unfavourable cardiovascular and metabolic phenotype causes threefold excess mortality in Turner syndrome (TS), and perturbed cardiac substrate metabolism is increasingly recognized as a common component of cardiovascular and metabolic diseases. We therefore hypothesized that myocardial glucose uptake (MGU) is reduced in TS and that growth hormone (GH) treatment improves MGU. To this end, this controlled trial elucidates MGU in TS and the impact of 6 months of growth hormone treatment on MGU.

Methods and Results

Women with TS (n = 9) were examined at baseline, sequentially treated with either Norditropin® SimpleXx or placebo and re‐examined after 6 months. MGU and myocardial blood flow (MBF) were measured using 2‐deoxy‐2‐[18F]fluoro‐D‐glucose positron emission tomography (FDG‐PET) during a hyperinsulinaemic euglycaemic clamp (at baseline and 6 months). Blood pressure measurement, blood sampling, echocardiography and dual energy X‐ray absorptiometry scan were also performed. Age‐matched female controls (n = 9) were examined once. Baseline MGU was reduced in TS (0·24 ± 0·08 vs. 0·36 ± 0·13 μmol/g/min in controls; P = 0·036) despite similar insulin sensitivity (whole body glucose uptake (M‐value): 9·69 ± 1·86 vs. 9·86 ± 2·58 mg/(min*kg) in controls; P = 0·9). Six months of GH carried no impact on MGU (0·25 ± 0·08 vs. 0·26 ± 0·12 μmol/g/min in the placebo group; P = 0·8). Plasma glucose, low‐density cholesterol and triglycerides increased, while M‐value and exercise capacity decreased during 6 months of GH treatment.

Conclusion

MGU is reduced in TS despite normal insulin sensitivity. GH treatment does not alter MGU despite decreased whole body insulin sensitivity. A perturbed cardiac glucose uptake appears to be a feature of TS.
Compound IMM‐H004, a Novel Coumarin Derivative, Protects against CA1 Cell Loss and Spatial Learning Impairments Resulting from Transient Global Ischemia
Authors: Zuo Wei , Zhang Wei , Han Ning , Chen Nai‐Hong
Published: January 2015

Aims

Compound IMM‐H004 (7‐hydroxy‐5‐methoxy‐4‐methyl‐3‐[4‐methylpiperazin‐1‐yl]‐2H‐chromen‐2‐one) is a new synthetic derivative of coumarin, and previous studies showed that it exhibited antioxidant and neuroprotective roles in focal cerebral ischemia. However, we know little about the compound's function in transient global ischemia. This study is to investigate whether compound IMM‐H004 can protect against transient global ischemic injury.

Methods

Four‐vessel occlusion (4VO) rat model was induced for a 20‐min occlusion and different times of reperfusion to mimic transient global cerebral ischemia. IMM‐H004 (3, 6, 9 mg/kg) or Edaravone (6 mg/kg) was administered after 30 min of reperfusion. Morris water maze tests were used to estimate the ability of spatial learning and memory. Nissl staining, TUNEL assay and Immunoblot for Bax/Bcl‐2 and activated caspase‐3 were used to detect hippocampal neuron injury. Immunoblot for PSD‐95 and synapsin 1, and electron microscopy were used to observe synaptic function.

Results

Compared with vehicle group, IMM‐H004 significantly improved the spatial learning performance and exhibited less CA1 neurons loss. The expressions of Bax/Bcl‐2 and activated caspase‐3 were decreased. IMM‐H004 also ameliorated synaptic structure, decreased PSD‐95 and increased synapsin 1 expression.

Conclusion

These findings suggested that IMM‐H004 exerted neuroprotective role in global ischemia by reducing apoptosis and maintaining the integrity of synaptic structure.
Global conservation status of sponges
Authors: Bell James J. , McGrath Emily , Biggerstaff Andrew , Bates Tracey , Cárdenas César A. , Bennett Holly
Published: January 2015

Sponges are important for maintaining ecosystem function and integrity of marine and freshwater benthic communities worldwide. Despite this, there has been no assessment of their current global conservation status. We assessed their status, accounting for the distribution of research effort; patterns of temporal variation in sponge populations and assemblages; the number of sponges on threatened species lists; and the impact of environmental pressures. Sponge research effort has been variable; marine sponges in the northeastern Atlantic and Mediterranean and freshwater sponges in Europe and North America have received the most attention. Although sponge abundance has increased in some locations since 1990, these were typically on coral reefs, in response to declines in other benthic organisms, and restricted to a few species. Few data were available on temporal trends in freshwater sponge abundance. Despite over 8500 described sponge species, only 20 are on threatened species lists, and all are marine species from the northeastern Atlantic and Mediterranean. Of the 202 studies identified, the effects of temperature, suspended sediment, substratum loss, and microbial pathogens have been studied the most intensively for marine sponges, although responses appear to be variable. There were 20 studies examining environmental impacts on freshwater sponges, and most of these were on temperature and heavy metal contamination. We found that most sponges do not appear to be threatened globally. However, little information is available for most species and more data are needed on the impacts of anthropogenic‐related pressures. This is a critical information gap in understanding sponge conservation status.

Estado Global de la Conservación de Esponjas
Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products – Part 2: Echinacea purpurea–Lavandula angustifolia
Authors: Gangemi Sebastiano , Minciullo Paola L. , Miroddi Marco , Chinou Ioanna , Calapai Gioacchino , Schmidt Richard J.
Published: January 2015

This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph has been produced. Part 2: Echinacea purpurea Moench–Lavandula angustifolia Mill.
Mapping perceptions of species' threats and population trends to inform conservation efforts: the Bornean orangutan case study
Authors: Abram Nicola K. , Meijaard Erik , Wells Jessie A. , Ancrenaz Marc , Pellier Anne‐Sophie , Runting Rebecca K. , Gaveau David , Wich Serge , Nardiyono  , Tjiu Albertus , Nurcahyo Anton , Mengersen Kerrie
Published: January 2015

Aim

We demonstrate a robust approach for predicting and mapping threats and population trends of wildlife species, invaluable for understanding where to target conservation resources. We used the endangered Bornean orangutan (Pongo pygmaeus) as our case study to facilitate and strengthen conservation efforts by the Indonesian government to stabilize populations by 2017.

Location

Kalimantan, Indonesian Borneo.

Methods

Local knowledge of threats to orangutan populations was gathered through questionnaire interviews in 531 villages (512 in Kalimantan) within known orangutan range. These data were integrated with 39 environmental/socio‐economic spatial variables using boosted regression tree modelling to predict threat levels and population trends across Kalimantan and to identify key combinations of threats and trends that can help to direct appropriate conservation actions.

Results

Nineteen percentage of villages surveyed in Kalimantan reported human–orangutan conflicts. High‐predicted conflict likelihood was extensive, strongly associated with road density (very low or high) and temperature seasonality. Recent orangutan killings were reported in 23% of villages. High killing risk was highly associated with greater surrounding orangutan habitat and for villages more than 60 km from oil palm plantations. Killings by respondents were reported in 20% of villages with higher likelihoods associated with greater range in rainfall and temperature, and higher proportion of Christian believers. Orangutan populations were predicted to decline/become locally extinct across the majority of their range in Kalimantan over the next decade, with few regions predicted to support stable populations.

Main conclusions

Human–orangutan conflicts and killings occur extensively in Kalimantan, with many populations at risk of decline or localized extinctions. Effective conservation actions are therefore urgently needed. Our approach better informs conservation managers in understanding the extent, spatial patterns and drivers of threats to endangered species such as the orangutan. This is essential to better design management strategies that can minimize or avert the species' decline.
Effects of terrestrial–aquatic connectivity on an estuarine turtle
Authors: Isdell Robert E. , Chambers Randolph M. , Bilkovic Donna M. , Leu Matthias
Published: January 2015

Aim

Estuaries world‐wide have been modified or fragmented due to human stressors in their terrestrial and aquatic components. Estuary fragmentation often results in reductions in species richness, diversity and connectivity. Effects of human modification on estuaries have been well studied, but less is known about how land use alters connectivity of the terrestrial–aquatic ecotone. We studied the relationship between terrestrial–aquatic connectivity and the distribution of an estuarine turtle, diamondback terrapin (Malaclemys terrapin).

Location

Chesapeake Bay, Virginia, USA.

Methods

We conducted diamondback terrapin surveys at 165 sites from late spring to mid‐summer in 2012 and 2013. We evaluated associations between terrapin occurrence, land use, salt marsh, shoreline armouring and crabbing intensity in concentric–circular neighbourhoods ranging from 0.27 to 2 km to cover daily and annual terrapin movements. We used occupancy modelling and model averaging to identify key terrestrial and aquatic variables explaining heterogeneity in terrapin occupancy. We evaluated the final model with an independent data set and identified occurrence thresholds for key variables.

Results

Diamondback terrapin occupy areas with ≥ 10% of marsh within a 750‐m neighbourhood, ≤ 17% armoured shoreline within a 1‐km neighbourhood, ≤ 20% of agriculture within a 500‐m neighbourhood, ≤ 33% low‐density housing within a 270‐m neighbourhood and ≤ 9 active crab pots within a 270‐m neighbourhood. Our model performed well when evaluated with an independent data set.

Main conclusions

We are the first to identify thresholds and quantify negative associations between the distribution of diamondback terrapin and alterations to terrestrial–aquatic connectivity from land development, shoreline armouring, and fishing activity. Because diamondback terrapin responses are reflective of changes in coastal habitats, especially marshes, terrapin occurrence can be used to direct wetlands conservation and restoration efforts.
Scientists and software – surveying the species distribution modelling community
Authors: Ahmed Sadia E. , McInerny Greg , O'Hara Kenton , Harper Richard , Salido Lara , Emmott Stephen , Joppa Lucas N.
Published: January 2015

Aim

Software use is ubiquitous in the species distribution modelling (SDM) domain; nearly every scientist working on SDM either uses or develops specialist SDM software; however, little is formally known about the prevalence or preference of one software over another. We seek to provide, for the first time, a ‘snapshot’ of SDM users, the methods they use and the questions they answer.

Location

Global.

Methods

We conducted a survey of over 300 SDM scientists to capture a snapshot of the community and used an extensive literature search of SDM papers in order to investigate the characteristics of the SDM community and its interactions with software developers in terms of co‐authoring research publications.

Results

Our results show that those members of the community who develop software and who are directly connected with developers are among the most highly connected and published authors in the field. We further show that the two most popular softwares for SDM lie at opposite ends of the ‘use‐complexity’ continuum.

Main conclusion

Given the importance of SDM research in a changing environment, with its increasing use in the policy domain, it is vital to be aware of what software and methodologies are being implemented. Here, we present a snapshot of the SDM community, the software and the methods being used.
Signal clarity: an account of the variability in infant quantity discrimination tasks
Authors: Cantrell Lisa , Boyer Ty W. , Cordes Sara , Smith Linda B.
Published: January 2015

Infants have shown variable success in quantity comparison tasks, with infants of a given age sometimes successfully discriminating numerical differences at a 2:3 ratio but requiring 1:2 and even 1:4 ratios of change at other times. The current explanations for these variable results include the two‐systems proposal – a theoretical framework that suggests that there are multiple systems at play and that these systems do not communicate early in infancy, leading to failure in certain numerical comparisons. An alternative proposal is that infants may be attending to continuous extent dimensions in these tasks rather than number per se. However, neither of these two main proposals is independently capable of accounting for the previously published data. Recently the Signal Clarity Hypothesis was proposed to account for and predict the variability (Cantrell & Smith, 2013). According to this hypothesis, infants’ variable success may be understood from a framework of statistical learning taken together with the signal‐to‐noise ratio generated by control procedures in habituation tasks. Here we test specific predictions made by the Signal Clarity Hypothesis. Across four experiments assessing 9‐month old discriminations of small and large sets (2 vs. 4 and 3 vs. 4), we demonstrate that infant success can be predicted by this novel approach and, further, that infants may discriminate smaller ratios of change than previously believed (3:4 numerical change and 2:3 cumulative area change).
Effect of canagliflozin on serum uric acid in patients with type 2 diabetes mellitus
Authors: Davies M. J. , Trujillo A. , Vijapurkar U. , Damaraju C. V. , Meininger G.
Published: January 2015

Hyperuricaemia is associated with an increased risk of gout, kidney stones and cardiovascular disease. The present post hoc analysis of pooled data from four placebo‐controlled phase III studies assessed the effect of canagliflozin, a sodium‐glucose co‐transporter 2 inhibitor, on serum uric acid levels in patients with type 2 diabetes mellitus (T2DM) and in a subset of patients with hyperuricaemia [defined as baseline serum uric acid ≥475 µmol/l (∼8 mg/dl)]. At week 26, canagliflozin 100 and 300 mg were associated with a ∼13% reduction in serum uric acid compared with placebo. In the subset of patients with hyperuricaemia, placebo‐subtracted percent reductions in serum uric acid were similar to those in the overall cohort. More patients in the hyperuricaemic group achieved a serum uric acid level of <360 µmol/l (∼6 mg/dl) with both canagliflozin 100 mg (23.5%) and 300 mg (32.4%) compared with placebo (3.1%). Incidences of gout and kidney stones were low and similar across groups. In conclusion, canagliflozin treatment decreased serum uric acid in patients with T2DM, including those with baseline hyperuricaemia.
Looking for a Needle in a Haystack: Revisiting the Cross‐country Causes of the 2008–9 Crisis by Bayesian Model Averaging
Authors: Ho Tai‐kuang
Published: January 2015

In this paper we explore the cross‐country variation in the output impact of the global financial crisis in 2008–9. We use the extensive dataset of Rose and Spiegel but control for the problems of model uncertainty and outliers by using a variety of Bayesian model averaging techniques. We find first that cross‐country differences in crisis intensity can be explained by macroeconomic vulnerabilities. Second, ignoring model uncertainty can lead to incorrect inferences. Third, international trade linkages do matter.
Characterization of Left Atrial Mechanics in Hypertrophic Cardiomyopathy and Essential Hypertension Using Vector Velocity Imaging
Authors: Badran Hala Mahfouz , Faheem Naglaa , Elnoamany Mohamed Fahmy , Kenawy Asma , Yacoub Magdi
Published: January 2015

Background

Systemic hypertension (HTN) and hypertrophic cardiomyopathy (HCM) may be associated with left atrial (LA) dilation, but whether LA functional abnormalities are characteristic to each disease or not, is unknown. The aim of this study was to characterize LA mechanical changes in patients with HTN and HCM using vector velocity imaging (VVI).

Methods

VVI‐derived longitudinal LA function was acquired from apical views in 76 CM patients, 33 hypertension patients and 30 age‐matched controls. Peak atrial longitudinal strain (ɛsys), atrial strain rate during systole (SRsys), early diastole (SRe), and late diastole (SRa) were measured (corresponding to LA reservoir, conduit and contractile functions, respectively). Similar parameters were used to assess left ventricular (LV) function.

Results

LV mass and LA volume index were higher in HCM and HTN than in controls. Both LA Reservoir function (LA ɛsys SRsys) and conduit function (SRe) were more declined in HCM patients, in comparison to HTN patients and controls (P < 0.0001),whereas conduit function was the only function deteriorated in the HTN group. LA contractile function was preserved among patient groups. In HCM, LV ɛsys and SRa [P < 0.001] are independent predictors for LA ɛsys. While in hypertension, only LVMI is an independent predictor for LA dysfunction (P < 0.01). By receiver operating characteristic analyses, only atrial reservoir function was extrapolative and appeared to be accurate in discriminating HCM from both hypertension and controls, with LA ɛsys ≤ 33% being more sensitive (71.8%) and specific (75%).

Conclusions

Response of LA mechanics to pathologic hypertrophy is entirely different. In HCM LA reservoir and conduit functions are more deteriorated and related to the severity of phenotype, while in hypertension the conduit function is chiefly affected and LA dysfunction is linked to a more advanced disease.
Dose‐adjusted arsenic trioxide for acute promyelocytic leukaemia in chronic renal failure
Authors: Firkin Frank , Roncolato Fernando , Ho Wai Khoon
Published: January 2015

Objective

To determine the potential for arsenic trioxide (ATO) to be safely and effectively incorporated into induction therapy of newly diagnosed acute promyelocytic leukaemia (APL) in patients with severe chronic renal failure (CRF) by reduction of the ATO dosage to compensate for reduced renal elimination of arsenic in CRF.

Patients and methods

Two of the four CRF patients with APL in the study were dialysis‐dependent, and two had eGFRs of 18 and 19 mL/min/1.73 m2. ATO dosage schedules were adjusted to obtain comparable whole‐blood arsenic levels to those in APL patients with normal renal function who achieved molecular remission (MR) while receiving 10 mg ATO daily for 28 d.

Results

Average ATO administered per day in CRF patients ranged from 36 to 50% of the ATO administered to APL patients with normal renal function. No clinically significant cardiac, hepatic or other toxicities were detected. RT‐PCR‐negative MR was achieved after one treatment course in two patients and after two courses in the others. Relapse‐free survival is 155, 60, 43 and 5 months.

Conclusion

The observations in this pilot study have demonstrated whole‐blood arsenic levels can provide a guide to adjustments of ATO dosage schedules that permit safe and effective therapeutic outcomes in APL patients with severely compromised renal function.
Cellularity, characteristics of hematopoietic parameters and prognosis in myelodysplastic syndromes
Authors: Schemenau Jennifer , Baldus Stephan , Anlauf Martin , Reinecke Petra , Braunstein Stefan , Blum Sabine , Nachtkamp Kathrin , Neukirchen Judith , Strup Corinna , Aul Carlo , Haas Rainer , Gattermann Norbert , Germing Ulrich
Published: January 2015

Background

Myelodysplastic syndromes (MDS) present with a normo‐ or hyperplastic bone marrow in most cases. We aimed at a characterization of patients with different types of cellularity.

Methods

We assessed marrow cellularity both by histology and cytology in 1270 patients and analyzed hematologic, cytogenetic, and prognostic parameters accordingly.

Results

The concordance of the assessment of cellularity differed dramatically between histology and cytology as only 36.5% were described as hypocellular by both methods (P < 0.0005) (hypocellular 16.4%, normocellular 23.3%, hypercellular 60.3%). There were no major differences with regard to hematopoietic insufficiency. The presence of fibrosis was associated to hypercellular bone marrow. Median survival differed from 38 months in hypocellular, 42 months in normocellular, and 25 months in hypercellular MDS (P < 0.0005). AML progression rates were 33% for hypercellular MDS after 2 yr, whereas hypo‐ and normocellular had a progression rate of 19% after 2 yr (P = 0.018). IPSS and IPSS‐R were able to identify different risk groups within all three cellularity groups.

Conclusion

Based on our data, hypocellular patients obviously do not present as a separate entity, as there were no striking differences with regard to cytogenetics and WHO types. Assessment of cellularity should be performed by histopathology.
Predominant female care in the beetle Lethrus apterus with supposedly biparental care
Authors: Kosztolányi András , Nagy Nikoletta , Kovács Tibor , Barta Zoltán
Published: January 2015

Although intensive care for offspring by both parents is rare in arthropods, it occurs in some species including the beetle Lethrus apterus. According to previous publications, in this species the male collects leaves, which are used by the female to form balls in the underground nest burrow. These balls serve as food for the hatched offspring. Most knowledge about the behavior of this species is based on information collected more than a century ago. Therefore, we investigated above‐ground breeding behavior and the status of nest burrows of this beetle in its natural habitat in Hungary. Our results suggest that contrary to previously documented cases, above‐ground parental care, i.e. the collection of leaves, is done predominantly not by the males but the females. Further research is needed to understand the role of the sexes in parental care in this species and to explain the discrepancy between the previously documented cases and the results we report here.
Dynamic directed interictal connectivity in left and right temporal lobe epilepsy
Authors: Coito Ana , Plomp Gijs , Genetti Mélanie , Abela Eugenio , Wiest Roland , Seeck Margitta , Michel Christoph M. , Vulliemoz Serge
Published: January 2015

Objective

There is increasing evidence that epileptic activity involves widespread brain networks rather than single sources and that these networks contribute to interictal brain dysfunction. We investigated the fast‐varying behavior of epileptic networks during interictal spikes in right and left temporal lobe epilepsy (RTLEandLTLE) at a whole‐brain scale using directed connectivity.

Methods

In 16 patients, 8 withLTLEand 8 withRTLE, we estimated the electrical source activity in 82 cortical regions of interest (ROIs) using high‐density electroencephalography (EEG), individual head models, and a distributed linear inverse solution. A multivariate, time‐varying, and frequency‐resolved Granger‐causal modeling (weighted Partial Directed Coherence) was applied to the source signal of allROIs. A nonparametric statistical test assessed differences between spike and baseline epochs. Connectivity results between RTLE and LTLE were compared betweenRTLEandLTLEand with neuropsychological impairments.

Results

Ipsilateral anterior temporal structures were identified as key drivers for both groups, concordant with the epileptogenic zone estimated invasively. We observed an increase in outflow from the key driver already before the spike. There were also important temporal and extratemporal ipsilateral drivers in both conditions, and contralateral only inRTLE. A different network pattern betweenLTLEandRTLEwas found: inRTLEthere was a much more prominent ipsilateral to contralateral pattern than inLTLE. Half of theRTLEpatients but none of theLTLEpatients had neuropsychological deficits consistent with contralateral temporal lobe dysfunction, suggesting a relationship between connectivity changes and cognitive deficits.

Significance

The different patterns of time‐varying connectivity inLTLEandRTLEsuggest that they are not symmetrical entities, in line with our neuropsychological results. The highest outflow region was concordant with invasive validation of the epileptogenic zone. This enhanced characterization of dynamic connectivity patterns could better explain cognitive deficits and help the management of epilepsy surgery candidates.
Pediatric refractory epilepsy: A decision analysis comparing medical versus surgical treatment
Authors: Sánchez Fernández Iván , An Sookee , Loddenkemper Tobias
Published: January 2015

Objectives

To quantify the life expectancy of surgically eligible children with refractory epilepsy comparing two treatment strategies: medical treatment only versus epilepsy surgery.

Methods

Decision analysis model populated with available parameters from the literature. One‐ and two‐way sensitivity analyses and second‐order Monte Carlo simulations evaluated the robustness of the results across wide variations of the input parameters. The time horizon was lifetime and the main outcome was life expectancy.

Results

Across the range of pediatric ages, epilepsy surgery yielded a higher life expectancy. For a cohort of 10‐year‐old children with refractory epilepsy, the gain in life expectancy with epilepsy surgery (compared to medical treatment only) was 5.9 years for temporal epilepsy and 5.6 years for extratemporal epilepsy. One‐ and two‐way sensitivity analyses and second‐order Monte Carlo simulations demonstrated the robustness of results across a wide variation of input parameters. There was no adjustment for quality of life, but we estimated the percentage of life expectancy spent in seizure freedom. For a cohort of 10‐year‐old patients with refractory epilepsy: (1) in temporal lobe epilepsy, epilepsy surgery yielded 48.9% of life expectancy years in seizure freedom while medical treatment yielded 14.3%; and (2) in extratemporal epilepsy, epilepsy surgery yielded 43.0% of life expectancy years in seizure freedom while medical treatment yielded 14.3%.

Significance

Epilepsy surgery yields a substantially higher life expectancy than continued medical treatment for surgically eligible children with refractory epilepsy. This conclusion remains robust across a wide range of parameter variations.
Lysosomes and unfolded protein response, determinants of differential resistance of melanoma cells to vinca alkaloids
Authors: Vincent Laure‐Anais , Attaoua Chaker , Bellis Michel , Rozkydalova Lucie , Hadj‐Kaddour Kamel , Vian Laurence , Cuq Pierre
Published: January 2015

On account of its strong ability to become chemoresistant after a primary response to drugs, malignant melanoma (MM) remains a therapeutic challenge. This study focuses on acquired resistance to vinca alkaloids (VAs) using VA‐resistant MM cell lines (CAL1R‐VCR, CAL1R‐VDS, and CAL1R‐VRB), established by long‐term continuous exposure of parental CAL1‐wt cells to vincristine (VCR), vindesine (VDS), or vinorelbine (VRB), respectively. Transcriptomic profiling using rma and rdam methods led to distinguish two cell groups: CAL1R‐VCR and CAL1R‐VDS, CAL1R‐VRB, and CAL1‐wt. mgsa of the specifically altered genes in the first group evidenced the GO terms ‘lysosomal lumen’ and ‘vacuolar lumen’ linked to underexpressed genes, and ‘endoplasmic reticulum (ER) stress response’ associated with overexpressed genes. A specific reduction of lysosomal enzymes, independent of acidic vacuole organelle (AVO) turnover, was observed (LTG probe) in CAL1R‐VCR and CAL1R‐VDS cells. It was associated with the specific lowering of cathepsin B and L, known to be involved in the lysosomal pathway of apoptosis. Confirming gene profiling, the same groups (CAL1R‐VCR and CAL1R‐VDS, CAL1‐wt and CAL1R‐VRB) could be distinguished regarding the VA‐mediated changes on mean size areas and on acidic compartment volumes. These two parameters were reduced in CAL1R‐VCR and CAL1R‐VDS cells, suggesting a smaller AVO accumulation and thus a reduced sensitivity to lysosomal membrane permeabilization‐mediated apoptosis. In addition, ‘ER stress response’ inhibition by tauroursodeoxycholic acid induced a higher VA sensitization of the first cell group. In conclusion, lysosomes and unfolded protein response could be key determinants of the differential resistance of MM to VAs.
The conformational plasticity of eukaryotic RNA‐dependent ATPases
Authors: Ozgur Sevim , Buchwald Gretel , Falk Sebastian , Chakrabarti Sutapa , Prabu Jesuraj Rajan , Conti Elena
Published: January 2015

RNA helicases are present in all domains of life and participate in almost all aspects of RNA metabolism, from transcription and processing to translation and decay. The diversity of pathways and substrates that they act on is reflected in the diversity of their individual functions, structures, and mechanisms. However, RNA helicases also share hallmark properties. At the functional level, they promote rearrangements of RNAs and RNP particles by coupling nucleic acid binding and release with ATP hydrolysis. At the molecular level, they contain two domains homologous to the bacterial RecA recombination protein. This conserved catalytic core is flanked by additional domains, which typically regulate the ATPase activity in cis. Binding to effector proteins targets or regulates the ATPase activity in trans. Structural and biochemical studies have converged on the plasticity of RNA helicases as a fundamental property that is used to control their timely activation in the cell. In this review, we focus on the conformational regulation of conserved eukaryotic RNA helicases.
Cyclic fracture behaviour of 20MnMoNi55 steel at room and elevated temperatures
Authors: Chowdhury T. , Sivaprasad S. , Bar H. N. , Tarafder S. , Bandyopadhyay N. R.
Published: January 2015

Cyclic fracture behaviour of 20MnMoNi55 steel has been evaluated at room temperature and elevated temperature of 300 °C. Fracture resistance at elevated temperature was found to be lower than that at room temperature. The deterioration in fracture resistance was due to dynamic strain ageing. Cyclic loading amplitude and frequency were also found to have an influence on fracture resistance. The features of the stretch zone during cyclic fracture were different from those at monotonic fracture. Stretch zone dimensions were found to be insensitive to cyclic load amplitudes whereas marginally affected by frequency of load cycles under dynamic strain ageing conditions.
Enhancing the TurtleWatch product for leatherback sea turtles, a dynamic habitat model for ecosystem‐based management
Authors: Howell Evan A. , Hoover Aimee , Benson Scott R. , Bailey Helen , Polovina Jeffrey J. , Seminoff Jeffrey A. , Dutton Peter H.
Published: January 2015

Fishery management measures to reduce interactions between fisheries and endangered or threatened species have typically relied on static time‐area closures. While these efforts have reduced interactions, they can be costly and inefficient for managing highly migratory species such as sea turtles. The NOAA TurtleWatch product was created in 2006 as a tool to reduce the rates of interactions of loggerhead sea turtles with shallow‐set longline gear deployed by the Hawaii‐based pelagic longline fishery targeting swordfish. TurtleWatch provides information on loggerhead habitat and can be used by managers and industry to make dynamic management decisions to potentially reduce incidentally capturing turtles during fishing operations. TurtleWatch is expanded here to include information on endangered leatherback turtles to help reduce incidental capture rates in the central North Pacific. Fishery‐dependent data were combined with fishing effort, bycatch and satellite tracking data of leatherbacks to characterize sea surface temperature (SST) relationships that identify habitat or interaction ‘hotspots’. Analysis of SST identified two zones, centered at 17.2° and 22.9°C, occupied by leatherbacks on fishing grounds of the Hawaii‐based swordfish fishery. This new information was used to expand the TurtleWatch product to provide managers and industry near real‐time habitat information for both loggerheads and leatherbacks. The updated TurtleWatch product provides a tool for dynamic management of the Hawaii‐based shallow‐set fishery to aid in the bycatch reduction of both species. Updating the management strategy to dynamically adapt to shifts in multi‐species habitat use through time is a step towards an ecosystem‐based approach to fisheries management in pelagic ecosystems.
Re‐evaluating the effect of wind on recruitment inGulf ofMaineAtlanticCod (Gadus morhua) using an environmentally‐explicit stock recruitment model
Authors: Hare Jonathan A. , Brooks Elizabeth N. , Palmer Michael C. , Churchill James H.
Published: January 2015

A previous study documented a correlation betweenAtlanticCod (Gadus morhua) recruitment in theGulf ofMaine and an annual index of the north component ofMay winds. This correlation was supported by modeling studies that indicated strong recruitment ofGulf ofMaineAtlanticCod results from high retention of spring‐spawned larvae in years when winds were predominately out of the north, which favor downwelling. We re‐evaluated this relationship using updated recruitment estimates and found that the correlation decreased between recruitment and wind. The original relationship was largely driven by two recruitment estimates, one of which (2005 year‐class) was highly uncertain because it was near the terminal year of the assessment. With additional data, the updated assessment estimated lower recruitment for the 2005 year‐class, which consequently lowered the correlation between recruitment and wind. We then investigated whether an environmentally‐explicit stock recruit function that incorporated an annual wind index was supported by either the original or updated assessment output. Although incorporation of the annual wind index produced a better fitting model, the uncertainty in the estimated parameters and the implied unexploited conditions were not appropriate for providing management advice. These results suggest the need for caution in the development of environmentally‐explicit stock recruitment relationships, in particular when basing relationships and hypotheses on recruitment estimates from the terminal years of stock assessment models. More broadly, this study highlights a number of sources of uncertainty that should be considered when analyzes are performed on the output of stock assessment models.