bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing the use of nomograms by choosing threshold points in predictive models: 2012 updated Partin Tables vs a European predictive nomogram for organ‐confined disease in prostate cancer
Authors: Borque Ángel , Rubio‐Briones Jose , Esteban Luis M. , Sanz Gerardo , Domínguez‐Escrig Jose , Ramírez‐Backhaus Miguel , Calatrava Ana , Solsona Eduardo
Published: October 2013

Objectives

To implement the use of nomograms in clinical practice showing how to choose thresholds in nomograms’ predictions to select risk groups.

To validate and compare the predictive ability and clinical utility of the Hospital Universitario ‘Miguel Servet’ (HUMS) and the updated Partin Tables 2012 (PT‐2012) nomograms to predict organ‐confined disease (OCD) after radical prostatectomy (RP).

Patients and Methods

Cohort of 1285 patients with prostate cancer treated with RP at Instituto Valenciano de Oncología (IVO) between 1986 and 2011.

The predictive value of the nomograms was assessed by means of calibration curves, discrimination ability (area under the receiver operating characteristic (ROC) curve (AUC) and probability density functions).

The clinical utility was evaluated through Vickers’ decision curves and thresholds were chosen through probability density functions.

Results

The calibration curves showed a minimal underestimation in low probabilities (<20%), a minimal overestimation in high probabilities (>50%) in the HUMS nomogram and a regular minimal overestimation in the PT‐2012. Their AUC of 0.7285 (95% confidence interval [CI] 0.7010–0.7559) and 0.7288 (95%CI 0.7013–0.7562) respectively, show an adequate discrimination ability for both predictive models in the IVO cohort.

The decision curves show similar net benefits for both models.

In this study we advocate for a threshold of 53% for the identification of OCD.

Conclusions

The HUMS‐nomogram and the PT‐2012 predictions of OCD confirm their utility in a contemporary cohort of patients.

Patients with a probability of OCD >53% should be classified as OCD, helping physicians to better counsel their patients.

A selection of adequate thresholds, as presented in this paper, makes nomograms more accessible tools.
Immigrant Settlement Work in Canada: Limits and Possibilities for Professionalization
Authors: Türegün Adnan
Published: October 2013

Cet article dépeint l’émergence du travail d’établissement auprès des immigrants au Canada et explore les perspectives d'avenir de celui‐ci en tant que profession. À l'heure actuelle, le travail d'établissement comprend trois formes de pratique : (1) un travail aux contours flous; (2) une spécialité du travail social; et (3) une profession en émergence. Cet article soutient que le travail d'établissement aura probablement un avenir professionnel. Cependant, la question de savoir s'il devient une profession indépendante dépend en grande partie du régime de financement du secteur des services d'établissement. Si le régime de financement fédéral et à court terme continue d'exister, le travail d'établissement cherchera encore sa définition au sein du domaine général du travail de service social. S'il émerge un régime de financement provincial et à long terme, les perspectives d'un travail d'établissement professionnel et indépendant s'amélioreront.

This paper portrays the emergence of Canadian settlement work with immigrants and explores its prospects as an occupation. Currently, settlement work includes three forms of practice: (1) a loose occupation; (2) a specialty of social work; and (3) an emerging profession. The paper argues that settlement work is likely to have a professional future. However, whether or not it will become an independent profession depends largely on the funding regime of the settlement service sector. If the existing federal and short‐term funding regime continues, settlement work will still be trying to define itself in the broader field of social service work. If a provincial and long‐term funding regime emerges, prospects for an independent professional settlement work will improve.
CXCL1 is a negative regulator of mast cell chemotaxis to airway smooth muscle cell products in vitro
Authors: Alkhouri H. , Moir L. M. , Armour C. L. , Hughes J. M.
Published: October 2013

Background

Activated mast cells (MC) numbers on airway smooth muscle (ASM) are increased in eosinophilic asthma. In vitro, asthmatic cytokine‐stimulated ASM cell‐conditioned medium (CM) induces more MC chemotaxis than CM from nonasthmatic ASM cells. Intriguingly the nonasthmatic ASM CM inhibits MC chemotaxis to the asthmatic ASM CM. However, the inhibitory factor(s) in the nonasthmatic ASM CM is still to be identified.

Objective

To identify the factor(s) released by nonasthmatic ASM cells that inhibits MC chemotaxis.

Methods

Confluent, serum‐starved ASM cells from donors with and without asthma were stimulated with IL‐1β and T‐helper (Th)1 (TNFα and IFNγ) or Th2 (IL‐4, IL‐13) cytokines, or left unstimulated. CM samples were collected after 24 h, and a potential inhibitory factor identified using cytokine protein arrays. Its production was assessed using ELISA and RT‐PCR and inhibitory role investigated in MC chemotaxis and Ca2+ mobilization assays.

Results

Only CXCL1 was produced in greater amounts by nonasthmatic than asthmatic ASM cells following Th1 and Th2 cytokine stimulation. CXCL1 mRNA expression was also increased. Exogenous rh‐CXCL1 significantly inhibited MC intracellular Ca2+ mobilization and chemotaxis to either CXCL10, CXCL8 or CM collected from asthmatic ASM cells following Th1 or Th2 cytokine stimulation. Neutralizing CXCL1 in nonasthmatic ASM CM or blocking its receptor significantly promoted MC chemotaxis.

Conclusions

CXCL1 was a major factor regulating MC chemotaxis in vitro. Its differential release by ASM cells may explain the differences observed in MC localization to the ASM of people with and without asthma.

Clinical Relevance

CXCL1 inhibition of MC recruitment to the ASM may lead to new targets to limit asthma pathophysiology.
Profile of ocular trauma in the Solomon Islands
Authors: Baker Michelle L , Painter Geoffrey , Hewitt Alex W , Amirul Islam F M , Szetu John , Qalo Mundi , Keeffe Jill
Published: October 2013

Background

The objective of this study was to characterize the causes of ocular trauma and determine the risk factors for infection and vision loss following ocular trauma in the Solomon Islands.

Design

A prospective clinic‐based study.

Participants

A total of 507 patients with ocular trauma who were reviewed at the National Referral Hospital in Honiara or one of five provincial eye clinics were included.

Methods

An interview‐based questionnaire to determine the circumstances of ocular trauma, and an ocular examination to elicit the trauma sustained, infectious sequelae and the visual outcome.

Main Outcome Measure

Visual acuity.

Results

Males were significantly more likely to have ocular trauma than females (P = 0.01). The major cause of ocular trauma in young boys and girls was being poked by a stick, followed by lime burns in young boys. For both genders, physical violence resulted in most injuries across all adult age groups. Microbial keratitis complicated 4.4% of ocular trauma. Monocular vision impairment (<6/18) occurred in 5.5% of participants and was more likely to occur if female (P = 0.02).

Conclusions

Ocular trauma is a significant cause of visual morbidity in the Solomon Islands. The results from this prospective study provide a basis for planning blindness prevention programmes in the Western Pacific.
Curcumin Suppresses Malignant Glioma Cells Growth and Induces Apoptosis by Inhibition of SHH/GLI1 Signaling Pathway in Vitro and Vivo
Authors: Du Wen‐Zhong , Feng Yan , Wang Xiao‐Feng , Piao Xing‐Yin , Cui Yu‐Qiong , Chen Ling‐Chao , Lei Xu‐Hui , Sun Xu , Liu Xing , Wang Han‐Bing , Li Xian‐Feng , Yang Dong‐Bo , Sun Ying , Zhao Zhe‐Feng , Jiang Tao , Li Yong‐Li , Jiang Chuan‐Lu
Published: October 2013

Aims

To study the role of curcumin on glioma cells via the SHH/GLI1 pathway in vitro and vivo.

Methods

The effects of curcumin on proliferation, migration, apoptosis, SHH/GLI1 signaling, and GLI1 target genes expression were evaluated in multiple glioma cell lines in vitro. A U87‐implanted nude mice model was used to study the role of curcumin on tumor volume and the suppression efficacy of GLI1.

Results

Curcumin showed cytotoxic effects on glioma cell lines in vitro. Both mRNA and protein levels of SHH/GLI1 signaling (Shh, Smo, GLI1) were downregulated in a dose‐ and time‐dependent manner. Several GLI1‐dependent target genes (CyclinD1, Bcl‐2, Foxm1) were also downregulated. Curcumin treatment prevented GLI1 translocating into the cell nucleus and reduced the concentration of its reporter. Curcumin suppressed cell proliferation, colony formation, migration, and induced apoptosis which was mediated partly through the mitochondrial pathway after an increase in the ratio of Bax to Bcl2. Intraperitoneal injection of curcumin in vivo reduced tumor volume, GLI1 expression, the number of positively stained cells, and prolonged the survival period compared with the control group.

Conclusion

This study shows that curcumin holds a great promise for SHH/GLI1 targeted therapy against gliomas.
Enhancing ex vivo expansion of cord blood‐derived unrestricted somatic stem cells for clinical applications
Authors: Demerdash Z. , El Baz H. , Mahmoud F. , Mohamed S. , Maher K. , Gaafar T. , Shawky S. , Hassan M. , Abdelhady D. , Taha T.
Published: October 2013

Objectives

To study effects of serum‐containing medium (SCM) versus serum‐free medium (SFM) and influence of seeding density, on rate of expansion of cord blood (CB) unrestricted somatic stem cells (USSCs), as a prerequisite for evaluating their therapeutic potential in ongoing clinical trials.

Material and methods

Isolation, propagation and characterization of USSCs from CB samples were performed and followed by their passage 3 culture in SCM and SFM, at cell densities of 5, 50, 500 and 5000 cells/cm2.

Results

The cells were CD44+, CD90+, CD73+, CD105+, CD34−, CD45−, and HLA‐DR, with Oct4 & Sox2 gene expression; they were differentiated into osteoblasts and adipocytes. USSCs cultured in SCM had significantly higher population doubling levels (P < 0.01) than those cultured in SFM. Those cultured in SCM at 5 cells/cm2 and those cultured in SFM at 50 cells/cm2 had significantly higher population doubling (P < 0.01) levels than those cultured at higher cell densities.

Conclusions

For scaling up of USSCs from 106 (?) to 1012 (?) in 6 weeks, culturing of CB‐derived cells of early passage (≤P3) in SCM at low cell seeding density (5 cells/cm2) is suggested for increasing cell count with lower passaging frequency, followed by culture of expanded USSCs at 50 cells/cm2 in SFM, to avoid undesirable effects of bovine serum in clinical applications.
Sildenafil Increases Muscle Protein Synthesis and Reduces Muscle Fatigue
Authors: Sheffield‐Moore Melinda , Wiktorowicz John E. , Soman Kizhake V. , Danesi Christopher P. , Kinsky Michael P. , Dillon Edgar L. , Randolph Kathleen M. , Casperson Shannon L. , Gore Dennis C. , Horstman Astrid M. , Lynch James P. , Doucet Barbara M. , Mettler Joni A. , Ryder Jeffrey W. , Ploutz‐Snyder Lori L. , Hsu Jean W. , Jahoor Farook , Jennings Kristofer , White Gregory R. , McCammon Susan D. , Durham William J.
Published: October 2013

Reductions in skeletal muscle function occur during the course of healthy aging as well as with bed rest or diverse diseases such as cancer, muscular dystrophy, and heart failure. However, there are no accepted pharmacologic therapies to improve impaired skeletal muscle function. Nitric oxide may influence skeletal muscle function through effects on excitation‐contraction coupling, myofibrillar function, perfusion, and metabolism. Here we show that augmentation of nitric oxide‐cyclic guanosine monophosphate signaling by short‐term daily administration of the phosphodiesterase 5 inhibitor sildenafil increases protein synthesis, alters protein expression and nitrosylation, and reduces fatigue in human skeletal muscle. These findings suggest that phosphodiesterase 5 inhibitors represent viable pharmacologic interventions to improve muscle function.
Pulmonary involvement in patients with thrombotic thrombocytopenic purpura
Authors: Nokes Timothy , George James N. , Vesely Sara K. , Awab Ahmed
Published: October 2013

Objectives

To determine the frequency of pulmonary involvement in patients with thrombotic thrombocytopenic purpura (TTP).

Methods

The experience of the Oklahoma TTP‐HUS (hemolytic–uremic syndrome) Registry, a population‐based cohort of consecutive patients without selection or referral bias, 1995–2012, was analyzed. Evidence for pulmonary involvement in patients with TTP was also documented with a systematic review of published reports.

Results

Only one of 74 Registry patients with acquired severe ADAMTS13 deficiency (activity <10%) had clinically important pulmonary involvement (transient PaO2, 42 mm Hg; arterial O2 saturation, 78%; normal chest X‐ray). No clinically important pulmonary involvement occurred in the remaining 73 patients. The systematic review identified 144 articles with search terms for TTP and pulmonary involvement; seven, published 1978–2002, had evaluable individual patient data. Five articles described single patients; only one patient was documented to have severe acquired ADAMTS13 deficiency; in none of the five patients was pulmonary involvement clearly related to TTP. Two articles were case series of seven patients each; no patients had ADAMTS13 activity measured. Each of the 14 patients had potential etiologies other than TTP for pulmonary involvement.

Conclusions

Only one of 74 patients in the Oklahoma Registry had clinically important pulmonary involvement. A systematic review of published reports documented no clear evidence for pulmonary involvement resulting from TTP. Clinically important pulmonary involvement may be rare in patients with TTP because (i) pulmonary microvasculature may be inherently resistant to the formation of platelet thrombi and (ii) pulmonary function can be maintained in spite of multiple microvascular thrombi.
Short‐duration stimulation of the supplementary eye fields perturbs anti‐saccade performance while potentiating contralateral head orienting
Authors: Chapman Brendan B. , Corneil Brian D.
Published: October 2013

Many forms of brain stimulation utilize the notion of state dependency, whereby greater influences are observed when a given area is more engaged at the time of stimulation. Here, by delivering intracortical microstimulation (ICMS) to the supplementary eye fields (SEF) of monkeys performing interleaved pro‐ and anti‐saccades, we show a surprising diversity of state‐dependent effects of ICMS‐SEF. Short‐duration ICMS‐SEF passed around cue presentation selectively disrupted anti‐saccades by increasing reaction times and error rates bilaterally, and also recruited neck muscles, favoring contralateral head turning to a greater degree on anti‐saccade trials. These results are consistent with the functional relevance of the SEF for anti‐saccades. The multiplicity of stimulation‐evoked effects, with ICMS‐SEF simultaneously disrupting anti‐saccade performance and facilitating contralateral head orienting, probably reflects both the diversity of cortical and subcortical targets of SEF projections, and the response of this oculomotor network to stimulation. We speculate that the bilateral disruption of anti‐saccades arises via feedback loops that may include the thalamus, whereas neck muscle recruitment arises via feedforward polysynaptic pathways to the motor periphery. Consideration of both sets of results reveals a more complete picture of the highly complex and multiphasic response to ICMS‐SEF that can play out differently in different effector systems.
Effects of forest degradation on butterfly communities in theGwangneungForest
Authors: Lee Cheol Min , Kwon Tae‐Sung , Kim Sung‐Soo , Sohn Jeong‐Dal , Lee Bong‐Woo
Published: October 2013

This study was carried out to clarify the response of butterfly communities on forest degradation in theGwangneungForest,Korea. We monitored butterfly communities with varying degrees of human activities by conducting a line transect twice a month in 2011. A total of 70 species and 4676 individuals of butterflies were observed in four sites: natural forest (NR), two plantation forests, and theKoreanNationalArboretum (AR). The result on niche breadth, habitat breadth and habitat type of butterfly was not consistent with our predictions. Species richness of habitat type was only significantly different betweenNFandAR. Species diversity was significantly different among sites. Butterfly diversity associated with landscape patterns based on aerial photographs supported a mosaic concept. A forest management plan to conserve butterfly diversity in forests is necessary to maintain various habitats and to ensure that grasslands are protected.
An evaluation of hydrogen sulfide in orogenic gold fluids and the uncertainties associated with vapor‐rich inclusions
Authors: Mernagh T. P. , Bastrakov E. N.
Published: October 2013

Raman spectroscopy has been used to obtain the concentration of H2S in individual fluid inclusions in the Archean Missouri gold deposit in Western Australia. These results indicated that the gas phase of Type III, vapor‐rich fluid inclusions from the Missouri gold deposit contained highly variable CO2/CH4 ratios and mole fractions of H2S up to 0.0018. There is good agreement between the calculated and empirically estimated H2S contents at 300°C and 200 MPa. The measured H2S concentrations can be explained by the proposed equilibrium with pyrite in the vicinity of or along the pyrite‐pyrrhotite sulfide buffer. In this study, optical methods were used for estimating the volume fractions of vapor and liquid (where observable) in inclusions at room temperature. To investigate the uncertainty associated with these measurements, where no aqueous phase was observed in an inclusion, we have calculated its bulk composition both without liquid water and also by assuming that there was a 0.5 μm film of liquid water on the walls of the inclusion. Calculations of bulk densities were found to be considerably higher for inclusions with liquid water when compared with vapor‐only inclusions. To investigate the error associated with undetected water in vapor‐rich inclusions, numerical experiments were completed for a number of fluid compositions in the H2O‐CH4‐CO2‐H2S compositional space, both for a regular compositional grid and for a set of specific fluid compositions derived from the visual observations and Raman measurements. Using this approach, the bulk compositions of fluid inclusions were calculated in equilibrium with the pyrite‐pyrrhotite buffer within the temperature‐pressure range of 270 to 360°C and approximately 40 to 260 MPa. The numerical modeling has also shown that variations in calculated H2S concentrations of up to two orders of magnitude may arise due to errors associated with visual estimates of volume fractions in vapor‐rich inclusions. To reduce this source of error, bulk inclusion compositions should be checked by other analytical methods, where possible.
Reduced Threshold for Inhibitory Homeostatic Responses in Migraine Motor Cortex? A tDCS/TMS Study
Authors: Cosentino Giuseppe , Brighina Filippo , Talamanca Simona , Paladino Piera , Vigneri Simone , Baschi Roberta , Indovino Serena , Maccora Simona , Alfonsi Enrico , Fierro Brigida
Published: October 2013

Background and Objective

Neurophysiological studies in migraine have reported conflicting findings of either cortical hyper‐ or hypoexcitability. In migraine with aura (MwA) patients, we recently documented an inhibitory response to suprathreshold, high‐frequency repetitive transcranial magnetic stimulation (hf‐rTMS) trains applied to the primary motor cortex, which is in contrast with the facilitatory response observed in the healthy subjects. The aim of the present study was to support the hypothesis that in migraine, because of a condition of basal increased cortical responsivity, inhibitory homeostatic‐like mechanisms of cortical excitability could be induced by high magnitude stimulation. For this purpose, the hf‐rTMS trains were preconditioned by transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique able to modulate the cortical excitability state.

Methods

Twenty‐two MwA patients and 20 patients with migraine without aura (MwoA) underwent trains of 5‐Hz repetitive transcranial magnetic stimulation at an intensity of 130% of the resting motor threshold, both at baseline and after conditioning by 15 minutes of cathodal or anodal tDCS. Motor cortical responses to the hf‐rTMS trains were compared with those of 14 healthy subjects.

Results

We observed abnormal inhibitory responses to the hf‐rTMS trains given at baseline in both MwA and MwoA patients as compared with the healthy subjects (P < .00001). The main result of the study was that cathodal tDCS, which reduces the cortical excitability level, but not anodal tDCS, which increases it, restored the normal facilitatory response to the hf‐rTMS trains in both MwA and MwoA.

Conclusions

The present findings strengthen the notion that, in migraine with and without aura, the threshold for inducing inhibitory mechanisms of cortical excitability might be lower in the interictal period. This could represent a protective mechanism counteracting cortical hyperresponsivity. Our results could be helpful to explain some conflicting neurophysiological findings in migraine and to get insight into the mechanisms underlying recurrence of the migraine attacks.
Quality of Life and Health‐Related Disability in Children With Migraine
Authors: Ferracini Gabriela Natália , Dach Fabíola , Speciali José Geraldo
Published: October 2013

Objective

To determine whether migraine interferes with health‐related quality of life (HRQL) and the degree of disability caused by this condition in the daily life of children of both genders aged 6‐12 years.

Background

Migraine is a chronic disease with recurrent symptoms that lead to a reduction of daily activity during the crises and during the intercritical periods, with an impact on HRQL.

Methods

The sample consisted of 50 children with migraine without aura being treated at a childhood headache outpatient clinic (study group) and 50 children with no history of headache selected at a pediatric outpatient clinic (control group). The Pediatric Migraine Disability Score questionnaire was applied to the study group in order to determine the disability provoked by headache in daily life, and the Pediatric Quality of Life Inventory4.0 was applied to both groups to determine HRQL.

Results

Children with migraine were absent from school activities, did not perform household tasks, and did not participate in leisure activities for 23.9 days, on average, during the last 3 months because of migraine. Disability was absent or mild in 38% of the children, whereas 14% showed severe disability. HRQL was similar in both groups regarding self‐evaluation, whereas it was perceived as being worse by the parents of children with migraine. Children with migraine had a worse school and emotional quality of life as determined by self‐perception. According to the perception of the parents, children with migraine had a worse general, physical, and psychosocial quality of life. Absenteeism from school activities, household tasks, and leisure was not correlated with HRQL.

Conclusion

Although migraine was a cause of school absenteeism, most of the children with migraine showed little or no disability regarding daily life activities and their quality of life was similar to that of children without headache.
Granuloma annulare as a possible new adverse effect of topiramate
Authors: Cassone Giulia , Tumiati Bruno
Published: October 2013

Background

Granuloma annulare (GA) is a relatively common, self‐limiting condition that can be associated with disorders such as diabetes mellitus, malignancy, and thyroid disease, and with the use of some drugs. Topiramate is approved for the prevention of migraine. Its adverse effects include somnolence, fatigue, paresthesia, anorexia and weight loss, and other abnormalities.

Objectives

We report a 50‐year‐old woman in whom topiramate at 50 mg/d was initiated in January 2010.

Case report

One month after starting topiramate, the patient presented with painless nodules on the left ankle, which later spread to the left leg. Histopathology of a punch biopsy revealed lymphohistiocytic infiltrate, collagen degeneration, and mucin deposition, all of which are characteristic of GA. Two weeks after the discontinuation of topiramate, the lesion resolved. Two years later, the patient resumed topiramate. Two weeks later, a new GA appeared in the same area and disappeared within a few weeks of discontinuation of the drug.

Conclusions

Associations between the use of topiramate and a GA‐like reaction have been reported in recent years. Based on the present case, it would appear that an actual association between GA and topiramate is possible given that: (i) the GA appeared only after the initiation of topiramate; (ii) the GA resolved after the discontinuation of topiramate; (iii) the GA reappeared with the resumption of topiramate in the same area and with the same characteristics as previously; and (iv) the lesion healed after topiramate was suspended.
Improvement in the lag phase estimation of individual cells that have survived mild heat treatment
Authors: Aguirre Juan S. , Monis Almira , García de Fernando Gonzalo D.
Published: October 2013

The effect of heat on the variability of lag phase of single cells was investigated. In addition, three alternatives on the lag phase determination were analysed, considering different approaches to estimate the inoculum size: samples with growth contained one initial cell (1C), the average of the truncated Poisson distribution of the number of cells (TP) or the number of cells given by the Poisson function (P). Increasing the intensity of the treatment lengthened the lag phase of survivors and increased its variability. In addition, the comparisons between the lag phase assuming the approaches 1C and P, and TP and P, usually differed significantly in the absence of heat treatment, but not when heat was applied. 1C and TP approaches were never significantly different. The assumption that growth starts from one cell is appropriate when lag phases are long, but it can lead to errors when growth conditions are optimal.
A Survey ofL1Regression
Authors: Vidaurre Diego , Bielza Concha , Larrañaga Pedro
Published: October 2013

L1regularization, or regularization with anL1penalty, is a popular idea in statistics and machine learning. This paper reviews the concept and application ofL1regularization for regression. It is not our aim to present a comprehensive list of the utilities of theL1penalty in the regression setting. Rather, we focus on what we believe is the set of most representative uses of this regularization technique, which we describe in some detail. Thus, we deal with a number ofL1‐regularized methods for linear regression, generalized linear models, and time series analysis. Although this review targets practice rather than theory, we do give some theoretical details aboutL1‐penalized linear regression, usually referred to as the least absolute shrinkage and selection operator (lasso).
A Multiplicity of Worlds: Other Habitable Planets
Authors: Rushby Andrew
Published: October 2013

The first planet orbiting another star was discovered in 1995. Since then some of Earth's most sensitive and far-seeing eyes have been picking out alien worlds from across the vast gulf of space, at a steadily increasing pace. Most found so far are very large, very hot and not at all similar to Earth. But how representative is today's sample of extrasolar planets? And are Earth-like planets likely to be found close enough for us to signal to them? Andrew Rushby gives some surprising answers.
Repeated and predictable patterns of ecotypic differentiation during a biological invasion: lake–stream divergence in parapatricSwiss stickleback
Authors: Lucek K. , Sivasundar A. , Roy D. , Seehausen O.
Published: October 2013

The relative importance of ecological selection and geographical isolation in promoting and constraining genetic and phenotypic differentiation among populations is not always obvious. Interacting with divergent selection, restricted opportunity for gene flow may in some cases be as much a cause as a consequence of adaptation, with the latter being a hallmark of ecological speciation. Ecological speciation is well studied in parts of the native range of the three‐spined stickleback. Here, we study this process in a recently invaded part of its range. Switzerland was colonized within the past 140 years from at least three different colonization events involving different stickleback lineages. They now occupy diverse habitats, ranging from small streams to the pelagic zone of large lakes. We use replicated systems of parapatric lake and stream populations, some of which trace their origins to different invasive lineages, to ask (i) whether phenotypic divergence occurred among populations inhabiting distinct habitats, (ii) whether trajectories of phenotypic divergence follow predictable parallel patterns and (iii) whether gene flow constrains divergent adaptation or vice versa. We find consistent phenotypic divergence between populations occupying distinct habitats. This involves parallel evolution in several traits with known ecological relevance in independent evolutionary lineages. Adaptive divergence supersedes homogenizing gene flow even at a small spatial scale. We find evidence that adaptive phenotypic divergence places constraints on gene flow over and above that imposed by geographical distance, signalling the early onset of ecological speciation.
Incipient post‐zygotic barrier in a model system of ecological speciation with gene flow
Authors: Sá‐Pinto A. , Martínez‐Fernández M. , López‐Fernández C. , Ferreira Z. , Pereira R. , Gosálvez J. , Rolán‐Alvarez E.
Published: October 2013

The role of post‐zygotic isolation in nonallopatric ecological speciation is still mostly unknown and information on the nature and strength of these barriers in well‐known speciation models is essential for a deeper understanding of such processes. The Galician ecotypes of the marine snail Littorina saxatilis represent one of the best studied cases of nonallopatric ecological speciation. Here, we test the existence of incipient post‐zygotic isolation by comparing the fertility of male hybrids with that of both pure forms [ridged and banded (RB) and smooth and unbanded (SU) ecotypes]. We analysed the degree of sperm DNA fragmentation (SDF) of individuals morphologically classified as RB, SU and hybrids, sampled from two locations. SDF analyses were chosen to study sperm quality because, in other animal species, SDF rates correlate with important parameters for speciation research, such as fertilization and abortion rates and viability of adult progeny. In the present work, hybrids showed significantly higher SDF rates than RB and SU males in one location and significantly higher variances in both locations. These results suggest the existence of an incipient post‐zygotic barrier, the strength of which may vary across the Galician shore, and highlight the potential of SDF analyses for speciation research.
A Statistical Analysis of Prices of Electrical and Electronic Equipment after the Introduction of the WEEE Directive
Authors: Favot Marinella , Marini Alfio
Published: October 2013

In January 2003, the European Union (EU) issued a directive on e‐waste (waste from electrical and electronic equipment; WEEE) to deal with increasing quantities and the included hazardous components. The WEEE Directive is based on the principle of extended producer responsibility, which shifts the responsibility for end of life of products away from municipalities toward producers. This led some researchers to state that, in theory, the costs of waste treatment are passed on to consumers in terms of higher prices. This work addresses two fundamental questions: (1) Did the introduction of the WEEE Directive increase consumer prices of electrical and electronic equipment (EEE)? and (2) how much is this price increase? We carry out, for the first time in the literature, a quantitative research on price variation of the vast majority of EEE sold in the EU after the introduction of producers’ financial responsibility. The panel data include 972 price level indices, namely, six categories of EEE for 27 member states for six years. The main result is that the average variation of the prices for each category of EEE investigated actually increased and the variation was between 0.71% and 3.88%, depending on the specific category of EEE. The average increase of 2.19% is in line with the previous studies that estimated the impact of the WEEE Directive up to a 3% increase of the product price. The t‐test performed on the data shows a good statistical significance, which strengthens the relevance of the results. Finally, future directions for research are included.
Immunocytochemical characterisation of olfactory ensheathing cells of zebrafish
Authors: Lazzari Maurizio , Bettini Simone , Franceschini Valeria
Published: October 2013

Continuous lifelong neurogenesis is typical of the vertebrate olfactory system. The regenerative ability of olfactory receptor neurons is dependent on the glial cell type specific to the olfactory pathway, designated ‘olfactory ensheathing cells’. Several studies to date have focused on mammalian olfactory ensheathing cells, owing to their potential roles in cell‐based therapy for spinal cord injury repair. However, limited information is available regarding this glial cell type in non‐mammalian vertebrates, particularly anamniotes. In the current immunocytochemical study, we analysed the features of olfactory ensheathing cells in the zebrafish, Danio rerio. Fish provide a good model for studying glial cells associated with the olfactory pathway of non‐mammalian vertebrates. In particular, zebrafish has numerous valuable features that enable its use as a prime model organism for genetic, neurobiological and developmental studies, as well as toxicology and genomics research. Paraffin sections from decalcified heads of zebrafish were processed immunocytochemically to detect proteins used in the research on mammalian olfactory ensheathing cells, including glial fibrillary acid protein (GFAP), S100, neural cell adhesion molecule (NCAM), polysialylated NCAM (PSA‐NCAM), vimentin (VIM), p75NTR and galactin (Gal)‐1. Notably, GFAP, S100, NCAM and Gal‐1 were clearly observed, whereas no vimentin staining was detected. Weak immunostaining for PSA‐NCAM and p75NTR was evident. Moreover the degree of marker expression was not uniform in various tracts of the zebrafish olfactory pathway. The immunostaining patterns of the zebrafish olfactory system are distinct from those of other fish to some extent, suggesting interspecific differences. We also showed that the olfactory pathway of zebrafish expresses markers of mammalian olfactory ensheathing cells. The olfactory systems of vertebrates have similarities but there are also marked variations between them. The issue of whether regional and interspecific differences in immunostaining patterns of olfactory pathway markers have functional significance requires further investigation.
Clinical efficacy of new aloe vera‐ and myrrh‐based oral mucoadhesive gels in the management of minor recurrent aphthous stomatitis: a randomized, double‐blind, vehicle‐controlled study
Authors: Mansour Ghada , Ouda Soliman , Shaker Ahmed , Abdallah Hossam M.
Published: October 2013

Objective

To evaluate the clinical efficacy, and safety of newly customized natural oral mucoadhesive gels, containing either aloe vera or myrrh as active ingredients, in the management of minor recurrent aphthous stomatitis (MiRAS).

Subjects and Methods

Ninety subjects with MiRAS were recruited from Oral Medicine Clinic, at Faculty of Dentistry, King Abdulaziz University, Saudi Arabia, for this randomized, double‐blind, placebo‐controlled study. Two new natural gels, containing aloe vera and myrrh, were prepared in a concentration of (0.5% w/w), in addition to a plain mucoadhesive gel used as a placebo. Patients with fresh ulcers (<48‐h duration) were instructed to apply either one of the three gels four times a day for a period of 5 days. Clinical efficacy was investigated in the form of changes in ulcer size, pain intensity, erythema, and exudation at days 4 and 6 of study entry. Participants were interviewed for the emergence of any side effects.

Results

76.6% of patients using aloe gel showed complete ulcer healing, 86.7%, and 80% of them revealed subsidence of erythema and exudation, respectively, especially at day 6 visit, whereas 76.7% of myrrh‐treated patients revealed almost absence of pain at day 6. No side effects were encountered with the use of any of the three gels.

Conclusion

The new formulated aloe‐ and myrrh‐based gels proved to be effective in topical management of MiRAS. Aloe was superior in decreasing ulcer size, erythema, and exudation; whereas myrrh resulted in more pain reduction.
Automatic and Deliberate Affective Associations with Sexual Stimuli in Women with Lifelong Vaginismus Before and After Therapist-Aided Exposure Treatment
Authors: Melles Reinhilde J. , ter Kuile Moniek M. , Dewitte Marieke , van Lankveld Jacques J.D.M. , Brauer Marieke , de Jong Peter J.
Published: October 2013

Introduction

The intense fear response to vaginal penetration in women with lifelong vaginismus, who have never been able to experience coitus, may reflect negative automatic and deliberate appraisals of vaginal penetration stimuli which might be modified by exposure treatment.

Aims

The aim of this study is to examine whether (i) sexual stimuli elicit relatively strong automatic and deliberate threat associations in women with vaginismus, as well as relatively negative automatic and deliberate global affective associations, compared with symptom-free women; and (ii) these automatic and more deliberate attitudes can be modified by therapist-aided exposure treatment.

Methods

A single target Implicit Association Test (st-IAT) was used to index automatic threat associations, and an Affective Simon Task (AST) to index global automatic affective associations. Participants were women with lifelong vaginismus (N = 68) and women without sexual problems (N = 70). The vaginismus group was randomly allocated to treatment (n = 34) and a waiting list control condition (n = 34).

Main Outcome Measures

Indices of automatic threat were obtained by the st-IAT and automatic global affective associations by the AST, visual analogue scales (VAS) were used to assess deliberate appraisals of the sexual pictures (fear and global positive affect).

Results

More deliberate fear and less global positive affective associations with sexual stimuli were found in women with vaginismus. Following therapist-aided exposure treatment, the strength of fear was strongly reduced, whereas global positive affective associations were strengthened. Automatic associations did not differ between women with and without vaginismus and did not change following treatment.

Conclusions

Relatively stronger negative (threat or global affect) associations with sexual stimuli in vaginismus appeared restricted to the deliberate level. Therapist-aided exposure treatment was effective in reducing subjective fear of sexual penetration stimuli and led to more global positive affective associations with sexual stimuli. The impact of exposure might be further improved by strengthening the association between vaginal penetration and positive affect (e.g., by using counter-conditioning techniques).
The Contribution of Vascular Smooth Muscle to Aortic Stiffness Across Length Scales
Authors: Saphirstein Robert J. , Morgan Kathleen G.
Published: October 2013

The operation of the cardiovascular system in health and disease is inherently mechanical. Clinically, aortic stiffness has proven to be of critical importance as an early biomarker for subsequent cardiovascular disease; however, the mechanisms involved in aortic stiffening are still unclear. The etiology of aortic stiffening with age has been thought to primarily involve changes in extracellular matrix protein composition and quantity, but recent studies suggest a significant involvement of the differentiated contractile vascular smooth muscle cells in the vessel wall. Here, we provide an overview of vascular physiology and biomechanics at different spatial scales. The processes involved in aortic stiffening are examined with particular attention given to recent discoveries regarding the role of vascular smooth muscle.
Three‐Dimensional Reconstruction of Neovasculature in Solid Tumors and Basement Membrane Matrix Using Ex Vivo X‐ray Microcomputed Tomography
Authors: Lee Seunghyung , Barbe Mary F. , Scalia Rosario , Goldfinger Lawrence E.
Published: October 2013

Objective

To create accurate, high‐resolution 3D reconstructions of neovasculature structures in xenografted tumors and Matrigel plugs for quantitative analyses in angiogenesis studies in animal models.

Methods

The competent neovasculature within xenografted solid tumors or Matrigel plugs in mice was perfused with Microfil, a radioopaque, hydrophilic polymerizing contrast agent, by systemic perfusion of the blood circulation via the heart. The perfused tumors and plugs were resected and scanned by X‐ray micro‐CT to generate stacks of 2D images showing the radioopaque material. A nonbiased, precise postprocessing scheme was employed to eliminate background X‐ray absorbance from the extravascular tissue. The revised binary image stacks were compiled to reveal the Microfil‐casted neovasculature as 3D reconstructions. Vascular structural parameters were calculated from the refined 3D reconstructions using the scanner software.

Results

Clarified 3D reconstructions were sufficiently precise to allow measurements of vascular architecture to a diametric limit of resolution of 3 μm in tumors and plugs.

Conclusions

Ex vivo micro‐CT can be used for 3D reconstruction and quantitative analysis of neovasculature including microcirculation in solid tumors and Matrigel plugs. This method can be generally applied for reconstructing and measuring vascular structures in three dimensions.
An anaerobic bacterium, Bacteroides thetaiotaomicron, uses a consortium of enzymes to scavenge hydrogen peroxide
Authors: Mishra Surabhi , Imlay James A.
Published: October 2013

Obligate anaerobes are periodically exposed to oxygen, and it has been conjectured that on such occasions their low‐potential biochemistry will predispose them to rapid ROS formation. We sought to identify scavenging enzymes that might protect the anaerobe Bacteroides thetaiotaomicron from the H2O2 that would be formed. Genetic analysis of eight candidate enzymes revealed that four of these scavenge H2O2 in vivo: rubrerythrins 1 and 2, AhpCF, and catalase E. The rubrerythrins served as key peroxidases under anoxic conditions. However, they quickly lost activity upon aeration, and AhpCF and catalase were induced to compensate. The AhpCF is an NADH peroxidase that effectively degraded low micromolar levels of H2O2, while the catalytic cycle of catalase enabled it to quickly degrade higher concentrations that might arise from exogenous sources. Using a non‐scavenging mutant we verified that endogenous H2O2 formation was much higher in aerated B. thetaiotaomicron than in Escherichia coli. Indeed, the OxyR stress response to H2O2 was induced when B. thetaiotaomicron was aerated, and in that circumstance this response was necessary to forestall cell death. Thus aeration is a serious threat for this obligate anaerobe, and to cope it employs a set of defences that includes a repertoire of complementary scavenging enzymes.
Review: Iron metabolism and the role of iron in neurodegenerative disorders
Authors: Hadzhieva M. , Kirches E. , Mawrin C.
Published: October 2013

Iron plays a role for the biogenesis of two important redox‐reactive prosthetic groups of enzymes, iron sulphur clusters (ISC) and heme. A part of these biosynthetic pathways takes plays in the mitochondria. While several important proteins of cellular iron uptake and storage and of mitochondrial iron metabolism are well‐characterized, limited knowledge exists regarding the mitochondrial iron importers (mitoferrins). A disturbed distribution of iron, hamperedFe‐dependent biosynthetic pathways and eventually oxidative stress resulting from an increased labile iron pool are suggested to play a role in several neurodegenerative diseases.Friedreich's ataxia is associated with mitochondrial iron accumulation and hamperedISC/heme biogenesis due to reduced frataxin expression, thus representing a monogenic mitochondrial disorder, which is clearly elicited solely by a disturbed iron metabolism. Less clear are the controversially discussed impacts of iron dysregulation and iron‐dependent oxidative stress in the most common neurodegenerative disorders, i.e.Alzheimer's disease (AD) andParkinson's disease (PD). Amyotrophic lateral sclerosis (ALS) may be viewed as a disease offering a better support for a direct link between iron, oxidative stress and regional neurodegeneration. Altogether, despite significant progress in molecular knowledge, the true impact of iron on the sporadic forms ofAD,PDandALSis still uncertain. Here we summarize the current knowledge of iron metabolism disturbances in neurodegenerative disorders.
Assessment of Ventricular Tachycardia Scar Substrate by Intracardiac Echocardiography
Authors: HUSSEIN AYMAN , JIMENEZ ALEJANDRO , AHMAD GHADA , MESUBI OLUROTIMI , KLEIN THOMAS , GURM GAGANDEEP , BECK HIROKO , SHAMS OMAR , SEE VINCENT , SALIARIS ANASTASIOS , SHOROFSKY STEPHEN , DICKFELD TIMM
Published: October 2013

Background

Intracardiac echocardiography (ICE) is increasingly used to guide complex ablation procedures. This study aimed to assess the scar substrate of ventricular tachycardia (VT) by ICE in patients undergoing VT ablation.

Methods

In 22 patients undergoing VT ablation (10 ischemic, 12 nonischemic), the Biosense CARTOSOUND module (Biosense Webster, Diamond Bar, CA, USA) was used for three‐dimensional reconstruction of the ventricles. The characteristics and appearance with ICE imaging of voltage‐defined scar zones (bipolar voltage <0.5 mV), border zones (0.5–1.5 mV), and normal myocardium (>1.5 mV) on electroanatomic maps were evaluated. The standard image analysis software Image J (National Institutes of Health, Bethesda, MD, USA) was used to analyze signal intensity (mean pixel signal intensity unit [SIU]) and heterogeneity (standard deviation of signal intensity in analyzed area) on ICE images.

Results

A total of 83 myocardial areas were analyzed from two‐dimensional ICE images (15 scars, 31 border zones, and 37 normal). Voltage‐defined scar zones had increased signal intensities compared to border zones (149 SIU vs 104 SIU, P < 0.0001) and normal myocardium (88 SIU, P < 0.0001). Border zones were more likely to have heterogeneous densities compared to normal myocardium (standard deviation of signal intensity 20 SIU vs 12 SIU, P < 0.0001). In receiver‐operator characteristic analyses, signal intensity ≥137 SIU differentiated scar from nonscar zones (area under curve 0.91, P < 0.0001). Software‐based color enhancement of areas with signal intensity ≥137 SIU allowed identification of the VT substrate in all 15 patients with voltage‐defined scar zones.

Conclusions

ICE provides important information about the VT anatomical substrate and may have potential to identify areas of scarred myocardium.