bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Image Analysis of Tumour–Healthy Brain Change in Contrast Uptake Induced by Radiation
Authors: Zhang Xiaoxi , Johnson Timothy D. , Little Roderick J. A. , Cao Yue
Published: June 2010

The work is motivated by a quantitative magnetic resonance imaging study of the differential tumour–healthy tissue change in contrast uptake induced by radiation. The goal is to determine the time in which there is maximal contrast uptake (a surrogate for permeability) in the tumour relative to healthy tissue. A notable feature of the data is its spatial heterogeneity. Zhang and co-workers have discussed two parallel approaches to ‘denoise’ a single image of change in contrast uptake from baseline to one follow-up visit of interest. In this work we extend the image model to explore the longitudinal profile of the tumour–healthy tissue contrast uptake in multiple images over time. We fit a two-stage model. First, we propose a longitudinal image model for each subject. This model simultaneously accounts for the spatial and temporal correlation and denoises the observed images by borrowing strength both across neighbouring pixels and over time. We propose to use the Mann–Whitney U-statistic to summarize the tumour contrast uptake relative to healthy tissue. In the second stage, we fit a population model to the U-statistic and estimate when it achieves its maximum. Our initial findings suggest that the maximal contrast uptake of the tumour core relative to healthy tissue peaks around 3 weeks after initiation of radiotherapy, though this warrants further investigation.
Estimating the Prevalence of Sensitive Behaviour and Cheating with a Dual Design for Direct Questioning and Randomized Response
Authors: Hout Ardo van den , Böckenholt Ulf , Van Der Heijden Peter G. M.
Published: June 2010

Randomized response is a misclassification design to estimate the prevalence of sensitive behaviour. Respondents who do not follow the instructions of the design are considered to be cheating. A mixture model is proposed to estimate the prevalence of sensitive behaviour and cheating in the case of a dual sampling scheme with direct questioning and randomized response. The mixing weight is the probability of cheating, where cheating is modelled separately for direct questioning and randomized response. For Bayesian inference, Markov chain Monte Carlo sampling is applied to sample parameter values from the posterior. The model makes it possible to analyse dual sample scheme data in a unified way and to assess cheating for direct questions as well as for randomized response questions. The research is illustrated with randomized response data concerning violations of regulations for social benefit.
Treatment efficiency of combining photodynamic therapy and ionizing radiation for Bowen’s disease
Authors: Nakano A , Watanabe D , Akita Y , Kawamura T , Tamada Y , Matsumoto Y
Published: June 2010

Background  Topical 5‐aminolevulinic acid photodynamic therapy (ALA‐PDT) is widely used for treating Bowen’s disease (BD), but recurrence and tumour cell persistence after ALA‐PDT is sometimes problematic. Radiation therapy (RT) is also effective for BD, but is limited by its side‐effects, such as refractory ulcers.

Objective  The objective of the study was to observe a synergic effect of combination therapy with ALA‐PDT and RT for BD cases that did not respond effectively to prior ALA‐PDT.

Methods  Subjects were BD patients whose lesion did not show complete remission or showed recurrence after prior ALA‐PDT. A total of four cases involving four lesions were studied (three male and one female, mean age 69.5). ALA ointment (20%) was applied to the lesions. After 4 to 6 h, subjects received combination therapy consisting of excimer‐pumped dye laser radiation at 630 nm (50 J/cm2) followed by electron‐beam radiation (3 Gy). The combination therapy was repeated every 2 to 3 days for a total of four treatments. The lesions were evaluated clinically or histologically after the final combination therapy session.

Results  Following combination therapy, all of the lesions disappeared. Recurrence was not detected during the observations periods, which averaged 14.0 months in duration.

Conclusion  Our results indicate that the cure rate of BD could be improved by combination therapy with ALA‐PDT and RT. Compared with conventional RT, the synergetic effect of this therapy might reduce the dose of radiation required, thereby also reducing skin side‐effects such as refractory ulcers.
Spectrum and Frequency of SLC26A4 Mutations Among Czech Patients with Early Hearing Loss with and without Enlarged Vestibular Aqueduct (EVA)
Authors: Pourová Radka , Janoušek Petr , Jurovčík Michal , Dvořáková Marcela , Malíková Marcela , Rašková Dagmar , Bendová Olga , Leonardi Emanuela , Murgia Alessandra , Kabelka Zdenek , Astl Jaromír , Seeman Pavel
Published: June 2010

Mutations in SLC26A4 cause Pendred syndrome (PS) – hearing loss with goitre – or DFNB4 – non‐syndromic hearing loss (NSHL) with inner ear abnormalities such as Enlarged Vestibular Aqueduct (EVA) or Mondini Dysplasia (MD). We tested 303 unrelated Czech patients with early hearing loss (298 with NSHL and 5 with PS), all GJB2‐negative, for SLC26A4 mutations and evaluated their clinical and radiological phenotype. Among 115 available HRCT/MRI scans we detected three MD (2.6%), three Mondini‐like affections (2.6%), 16 EVA (13 bilateral – 19.2% and 15.6% respectively) and 61 EVA/MD‐negative scans (73.4%). We found mutation(s) in 26 patients (8.6%) and biallelic mutations in eight patients (2.7%) out of 303 tested. In 18 of 26 (69%) patients, no second mutation could be detected even using MLPA. The spectrum of SLC26A4 mutations in Czech patients is broad without any prevalent mutation. We detected 21 different mutations (four novel). The most frequent mutations were p.Val138Phe and p.Leu445Trp (18% and 8.9% of pathogenic alleles respectively). Among 13 patients with bilateral EVA, six patients (50%) carry biallelic mutations. In EVA ‐negative patients no biallelic mutations were found but 4.9% had monoallelic mutations. SLC26A4 mutations are present mostly in patients with EVA/MD and/or progressive HL and those with affected siblings.
Inflammatory chemokine release of astrocytes in vitro is reduced by all‐trans retinoic acid
Authors: Van Neerven Sabien , Regen Tommy , Wolf Dhana , Nemes Andrei , Johann Sonja , Beyer Cordian , Hanisch Uwe‐Karsten , Mey Jörg
Published: June 2010

J. Neurochem. (2010) 114, 1511–1526.

The production of chemokines by astrocytes constitutes an important component of neuroinflammatory processes in the brain. As the transcriptional activator retinoic acid (RA), used for chemotherapy and dermatological applications, exerts anti‐inflammatory effects on monocytes and lymphocytes, we have tested whether the physiologically occurring isomer, all‐trans RA, affects chemokine expression by astrocytes. Under control conditions, primary cultures of murine cortical astrocytes expressed no or very low levels of CCL and CXCL chemokines. After treatment with bacterial lipopolysaccharides to simulate inflammation in vitro, we detected a strong increase in the release of CCL2 (to > 4 ng/mL in cell culture supernatant), CCL3 (> 20 ng/mL), CCL5 (> 25 ng/mL), CXCL1 (> 30 ng/mL) and CXCL2 (> 20 ng/mL). Although simultaneous exposure to RA did not significantly affect this response, 12 h pre‐treatment with 0.1 μM all‐trans RA strongly suppressed mRNA expression and protein release of all chemokines. The anti‐inflammatory activity of RA engaged RA and retinoid X receptors and correlated with a decreased expression of the lipopolysaccharides co‐receptor CD14. A minor reduction of nuclear NF‐κB was observed but not significant, activation of Jun amino‐terminal kinase, p38 and signal transducer and activator of transcription 3 were not altered by RA. The results suggest that retinoids should be further investigated as candidates for the treatment of neuroinflammation.
Development of a grape seed polyphenolic extract with anti‐oligomeric activity as a novel treatment in progressive supranuclear palsy and other tauopathies
Authors: Pasinetti Giulio Maria , Ksiezak‐Reding Hanna , Santa‐Maria Ismael , Wang Jun , Ho Lap
Published: June 2010

J. Neurochem. (2010) 114, 1557–1568.

A diverse group of neurodegenerative diseases – including progressive supranuclear palsy (PSP), corticobasal degeneration and Alzheimer’s disease among others, collectively referred to as tauopathies – are characterized by progressive, age‐dependent intracellular formations of misfolded protein aggregates that play key roles in the initiation and progression of neuropathogenesis. Recent studies from our laboratory reveal that grape seed‐derived polyphenolic extracts (GSPE) potently prevent tau fibrillization into neurotoxic aggregates and therapeutically promote the dissociation of preformed tau aggregates [J. Alzheimer’s Dis. (2009) vol. 16, pp. 433]. Based on our extensive bioavailability, bioactivity and functional preclinical studies, combined with the safety of GSPE in laboratory animals and in humans, we initiated a series of studies exploring the role of GSPE (Meganatural‐Az® GSPE) as a potential novel botanical drug for the treatment of certain forms of tauopathies including PSP, a neurodegenerative disorder involving the accumulation and deposition of misfolded tau proteins in the brain characterized, in part, by abnormal intracellular tau inclusions in specific anatomical areas involving astrocytes, oligodendrocytes and neurons [J. Neuropathol. Exp. Neurol. (2002) vol. 61, pp. 33]. In this mini‐review article, we discuss the biochemical characterization of GSPE in our laboratory and its potential preventative and therapeutic role in model systems of abnormal tau processing pertinent to PSP and related tauopathies.
Communicating through caregiver singing during morning care situations in dementia care
Authors: Hammar Lena Marmstål , Emami Azita , Engström Gabriella , Götell Eva
Published: June 2010

Scand J Caring Sci; 2011; 25; 160–168
 
Communicating through caregiver singing during morning care situations in dementia care

It is well known that persons with dementia (PWD) have problems expressing and interpreting communication, making interaction with others difficult. Interaction between PWD and their caregivers is crucial, and several strategies have been investigated to facilitate communication during caregiving. Music therapeutic caregiving (MTC) – when caregivers sing for or together with PWD during caregiving activities – has been shown to enhance communication for PWD, evoking more vitality and positive emotions. The aim of this study was to describe how PWD and their caregivers express verbal and nonverbal communication and make eye contact during the care activity ‘getting dressed’, during morning care situations without and with MTC. Findings revealed that during the situations without MTC, the caregivers led the dressing procedure with verbal instructions and body movements and seldom invited the PWD to communicate or participate in getting dressed. Patterns in responses to caregivers’ instructions included both active and compliant responses and reactions that were resistant and aggressive, confused, and disruptive. In contrast to the ‘ordinary’ morning care situation, during MTC, the caregivers seemed interested in communicating with the PWD and solicited their mutual engagement. Although verbal communication consisted of singing about things other than getting dressed, e.g. dancing, love, sailing, God, the PWD mostly responded to caregivers in a composed manner, by being active, compliant, and relaxed, though some were also resistant or incongruent. The authors conclude that MTC could be a way for PWD and their caregivers to successfully interact and co‐operate during caring situations, as it seems to evoke enhanced communication for both partners in this context.
Serpentinization as a source of energy at the origin of life
Authors: RUSSELL M. J. , HALL A. J. , MARTIN W.
Published: June 2010

For life to have emerged from CO2, rocks, and water on the early Earth, a sustained source of chemically transducible energy was essential. The serpentinization process is emerging as an increasingly likely source of that energy. Serpentinization of ultramafic crust would have continuously supplied hydrogen, methane, minor formate, and ammonia, as well as calcium and traces of acetate, molybdenum and tungsten, to off‐ridge alkaline hydrothermal springs that interfaced with the metal‐rich carbonic Hadean Ocean. Silica and bisulfide were also delivered to these springs where cherts and sulfides were intersected by the alkaline solutions. The proton and redox gradients so generated represent a rich source of naturally produced chemiosmotic energy, stemming from geochemistry that merely had to be tapped, rather than induced, by the earliest biochemical systems. Hydrothermal mounds accumulating at similar sites in today’s oceans offer conceptual and experimental models for the chemistry germane to the emergence of life, although the ubiquity of microbial communities at such sites in addition to our oxygenated atmosphere preclude an exact analogy.
Lifestyle impacts on the aging‐associated expression of biomarkers of DNA damage and telomere dysfunction in human blood
Authors: Song Zhangfa , Von Figura Guido , Liu Yan , Kraus Johann M. , Torrice Chad , Dillon Patric , Rudolph‐Watabe Masami , Ju Zhenyu , Kestler Hans A. , Sanoff Hanna , Lenhard Rudolph Karl
Published: June 2010

Cellular aging is characterized by telomere shortening, which can lead to uncapping of chromosome ends (telomere dysfunction) and activation of DNA damage responses. There is some evidence that DNA damage accumulates during human aging and that lifestyle factors contribute to the accumulation of DNA damage. Recent studies have identified a set of serum markers that are induced by telomere dysfunction and DNA damage, and these markers showed an increased expression in blood during human aging. Here, we investigated the influence of lifestyle factors (such as exercise, smoking, body mass) on the aging‐associated expression of serum markers of DNA damage (CRAMP, EF‐1α, stathmin, n‐acetyl‐glucosaminidase and chitinase) in comparison with other described markers of cellular aging (p16INK4a upregulation and telomere shortening) in human peripheral blood. The study shows that lifestyle factors have an age‐independent impact on the expression level of biomarkers of DNA damage. Smoking and increased body mass indices were associated with elevated levels of biomarkers of DNA damage independent of the age of the individuals. In contrast, exercise was associated with an age‐independent reduction in the expression of biomarkers of DNA damage in human blood. The expression of biomarkers of DNA damage correlated positively with p16INK4a expression and negatively with telomere length in peripheral blood T‐lymphocytes. Together, these data provide experimental evidence that both aging and lifestyle impact on the accumulation of DNA damage during human aging.
Reduction in glutamate uptake is associated with extrasynaptic NMDA and metabotropic glutamate receptor activation at the hippocampal CA1 synapse of aged rats
Authors: Potier Brigitte , Billard Jean‐Marie , Rivière Sylvain , Sinet Pierre‐Marie , Denis Isabelle , Champeil‐Potokar Gaelle , Grintal Barbara , Jouvenceau Anne , Kollen Melanie , Dutar Patrick
Published: June 2010

This study aims to determine whether the regulation of extracellular glutamate is altered during aging and its possible consequences on synaptic transmission and plasticity. A decrease in the expression of the glial glutamate transporters GLAST and GLT‐1 and reduced glutamate uptake occur in the aged (24–27 months) Sprague–Dawley rat hippocampus. Glutamatergic excitatory postsynaptic potentials recorded extracellularly in ex vivo hippocampal slices from adult (3–5 months) and aged rats are depressed by DL‐TBOA, an inhibitor of glutamate transporter activity, in an N‐Methyl‐d‐Aspartate (NMDA)‐receptor‐dependent manner. In aged but not in young rats, part of the depressing effect of DL‐TBOA also involves metabotropic glutamate receptor (mGluRs) activation as it is significantly reduced by the specific mGluR antagonist d‐methyl‐4‐carboxy‐phenylglycine (MCPG). The paired‐pulse facilitation ratio, a functional index of glutamate release, is reduced by MCPG in aged slices to a level comparable to that in young rats both under control conditions and after being enhanced by DL‐TBOA. These results suggest that the age‐associated glutamate uptake deficiency favors presynaptic mGluR activation that lowers glutamate release. In parallel, 2 Hz‐induced long‐term depression is significantly decreased in aged animals and is fully restored by MCPG. All these data indicate a facilitated activation of extrasynaptic NMDAR and mGluRs in aged rats, possibly because of an altered distribution of glutamate in the extrasynaptic space. This in turn affects synaptic transmission and plasticity within the aged hippocampal CA1 network.
Reversal of aging‐associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and NMDA receptor function
Authors: Yang Yuan‐Jian , Wu Peng‐Fei , Long Li‐Hong , Yu Dan‐Fang , Wu Wen‐Ning , Hu Zhuang‐Li , Fu Hui , Xie Na , Jin You , Ni Lan , Wang Jian‐Zhi , Wang Fang , Chen Jian‐Guo
Published: June 2010

Deficits in learning and memory accompanied by age‐related neurodegenerative diseases are closely related to the impairment of synaptic plasticity. In this study, we investigated the role of thiol redox status in the modulation of the N‐methyl‐d‐aspartate receptor (NMDAR)‐dependent long‐term potentiation (LTP) in CA1 areas of hippocampal slices. Our results demonstrated that the impaired LTP induced by aging could be reversed by acute administration of reductants that can regulate thiol redox status directly, such as dithiothreitol or β‐mercaptoethanol, but not by classical anti‐oxidants such as vitamin C or trolox. This repair was mediated by the recruitment of aging‐related deficits in NMDAR function induced by these reductants and was mimicked by glutathione, which can restore the age‐associated alterations in endogenous thiol redox status. Moreover, antioxidant prevented but failed to reverse H2O2‐induced impairment of NMDAR‐mediated synaptic plasticity. These results indicate that the restoring of thiol redox status may be a more effective strategy than the scavenging of oxidants in the treatment of pre‐existing oxidative injury in learning and memory.
Sirt1’s beneficial roles in neurodegenerative diseases – a chaperonin containing TCP‐1 (CCT) connection?
Authors: Gan Bin Qi , Tang Bor Luen
Published: June 2010

Sir2/Sirt1 and its orthologues are known lifespan extension factors in several aging models from yeast to invertebrates. Sirt1 activation is also known to be beneficial and protective in both invertebrate and mammalian models of neurodegenerative disease. Sirt1’s lifespan extension effect, as well as the beneficial outcome of its activation in models of aging‐associated diseases, is often attributed to its ability to instill a gene expression profile that is pro‐survival and anti‐aging. A recent report from Nyström and colleagues showed that the yeast Sir2p affects the function of the polarisome in segregation and retrograde transport of damaged and aggregated proteins from the bud to the mother cell, thereby ensuring the generation of a ‘rejuvenated’ daughter cell. Interestingly, the role of Sir2p in this case involves deacetylation and activation of cytoplasmic chaperonin containing TCP‐1 (CCT, or TriC), thereby enhancing actin folding and polymerization. In view of a previously documented role of CCT in modulating polyglutamine‐containing protein aggregation and toxicity, we hypothesized that CCT deacetylation may also underlie Sirt1’s beneficial effects in several neurodegenerative diseases precipitated by toxic aggregates. Other than alterations in gene expression profile, another major way whereby Sirt1 activation may counter neural aging could be to promote neuronal survival via prevention of toxic aggregate formation through CCT.
MEASURING RICHNESS AND POVERTY: A MICRO DATA APPLICATION TO EUROPE AND GERMANY
Authors: Peichl Andreas , Schaefer Thilo , Scheicher Christoph
Published: June 2010

In this paper, we define a new class of richness measures. In contrast to the often used headcount, these new measures are sensitive to changes in rich individuals' incomes and, therefore, allow for a more sophisticated analysis of richness. We demonstrate the application of these new measures in analyzing the development of poverty and richness over time in Germany. Moreover, we compare Germany to many other European countries and investigate the impact of tax reforms on poverty and richness. Using these examples, we show the importance of taking the intensity of changes into account and not only the number of people beyond a given richness line (headcount). We propose to use the new measures in addition to the headcount index for a more comprehensive analysis of richness.
Primate testing of TGN1412: right target, wrong cell
Authors: Pallardy M , Hünig T
Published: June 2010

The failure of toxicity studies in non‐human primates to predict the cytokine release syndrome during a first‐in‐man study of the CD28‐specific monoclonal antibody TGN1412 has remained unexplained so far. In this issue of the BJP, work from the NIBSC first identifies the effector memory subset of human T‐lymphocytes as the most likely source of the pro‐inflammatory cytokines released during the study, and goes on to show that in cynomolgus monkeys, this subset lacks CD28, the target molecule of TGN1412. We discuss the implications for the TGN1412 catastrophe and for preclinical evaluation of biologicals in animal models in general.
Increased Prevalence of Sleep Disorders in Chronic Headache: A Case–Control Study
Authors: Sancisi Elisa , Cevoli Sabina , Vignatelli Luca , Nicodemo Marianna , Pierangeli Giulia , Zanigni Stefano , Grimaldi Daniela , Cortelli Pietro , Montagna Pasquale
Published: June 2010

Objectives.— The aim of our study was to investigate the prevalence of sleep disorders in chronic headache patients and to evaluate the role of psychiatric comorbidity in the association between chronic headache and sleep complaints.

Background.— The prevalence of sleep disorders in chronic headache has been seldom investigated, although from the earliest description chronic headache has been associated with sleep disturbances. On the contrary, mood disorders are commonly associated with both sleep disturbances and chronic headache – each of which are, in turn, core features of mood disorders. Therefore, it may be important to discriminate between sleep problems that can be attributed to a comorbid psychiatric disorder, and those specifically associated with headache. Only a few studies investigating the association of chronic headache with sleep difficulties have also taken into account to consider the possible role of anxiety and depression.

Patients and Methods.— A total of 105 consecutive patients with daily or nearly daily headache and 102 patients with episodic headache, matched by age, sex, and type of headache at onset, underwent a structured direct interview about their sleep habits and psychiatric diseases.

Results.— In total, 80 out of 105 patients with chronic headache received a diagnosis of medication overuse headache, 21 patients were classified as chronic migraine and 4 as chronic tension‐type headache without drug overuse.

Patients.— Patients with chronic headache showed a high prevalence of insomnia, daytime sleepiness, and snoring with respect to controls (67.7% vs 39.2%, 36.2% vs 23.5%, and 48.6% vs 37.2%, respectively). Forty‐five patients with chronic headache (42.9%) had psychiatric comorbidity (anxiety and/or depressive disorders), vs 27 episodic headache patients (26.5%). Multivariate analysis disclosed that low educational level, lower mean age at headache onset, and insomnia are independently associated with chronic headache.

Conclusions.— Patients with chronic headache had a high prevalence of sleep complaints. Insomnia may thus represent an independent risk factor for headache chronification. Recognition of sleep disorders, alone or in association with depression or anxiety, may be useful in episodic headache patients to prevent chronification.
Efficacy of individual nucleic acid amplification testing in reducing the risk of transfusion‐transmitted hepatitis B virus infection in Switzerland, a low‐endemic region
Authors: Stolz Martin , Tinguely Caroline , Graziani Mauro , Fontana Stefano , Gowland Peter , Buser Andreas , Michel Martine , Canellini Giorgia , Züger Max , Schumacher Philippe , Lelie Nico , Niederhauser Christoph
Published: June 2010

BACKGROUND: The risk of transfusion‐transmitted hepatitis B virus (HBV) in Switzerland by testing blood donors for hepatitis B surface antigen (HBsAg) alone has been historically estimated at 1:160,000 transfusions. The Swiss health authorities decided not to introduce mandatory antibody to hepatitis B core antigen (anti‐HBc) testing but to evaluate the investigation of HBV nucleic acid testing (NAT).

STUDY DESIGN AND METHODS: Between June 2007 and February 2009, a total of 306,000 donations were screened routinely for HBsAg and HBV DNA by triplex individual‐donation (ID)‐NAT (Ultrio assay on Tigris system, Gen‐Probe/Novartis Diagnostics). ID‐NAT repeatedly reactive donors were further characterized for HBV serologic markers and viral load by quantitative polymerase chain reaction. The relative sensitivity of screening for HBsAg, anti‐HBc, and HBV DNA was assessed. The residual HBV transmission risk of NAT with or without anti‐HBc and HBsAg was retrospectively estimated in a mathematical model.

RESULTS: From the 306,000 blood donations, 31 were repeatedly Ultrio test reactive and confirmed HBV infected, of which 24 (77%) and 27 (87%) were HBsAg and anti‐HBc positive, respectively. Seven HBV‐NAT yields were identified (1:44,000), two pre‐HBsAg window period (WP) donations (1:153,000) and five occult HBV infections (1:61,000). Introduction of ID‐NAT reduced the risk of HBV WP transmission in repeat donors from 1:95,000 to 1:296,000.

CONCLUSIONS: Triplex NAT screening reduced the HBV WP transmission risk approximately threefold. NAT alone was more efficacious than the combined use of HBsAg and anti‐HBc. The data from this study led to the decision to introduce sensitive HBV‐NAT screening in Switzerland. Our findings may be useful in designing more efficient and cost‐effective HBV screening strategies in low‐prevalence countries.
Intergenerational Considerations Affecting the Future of Nuclear Power: Equity as a Framework for Assessing Fuel Cycles
Authors: Taebi Behnam , Kadak Andrew C.
Published: June 2010

Alternative fuel cycles are being considered in an effort to prolong uranium fuel supplies for thousands of years to come and to manage nuclear waste. These strategies bring with them different benefits and burdens for the present generation and for future generations. In this article, we present a method that provides insight into future fuel cycle alternatives and into the conflicts arising between generations within the framework of intergenerational equity. A set of intersubjective values is drawn from the notion of sustainable development. By operationalizing these values and mapping out their impacts, value criteria are introduced for the assessment of fuel cycles, which are based on the distribution of burdens and benefits between generations. The once‐through fuel cycle currently deployed in the United States and three future fuel cycles are subsequently assessed according to these criteria. The four alternatives are then compared in an integrated analysis in which we shed light on the implicit tradeoffs made by decisionmakers when they choose a certain fuel cycle. When choosing a fuel cycle, what are the societal costs and burdens accepted for each generation and how can these factors be justified? This article presents an integrated decision‐making method, which considers intergenerational aspects of such decisions; this method could also be applied to other technologies.
Self‐Organizing Policy Networks: Risk, Partner Selection, and Cooperation in Estuaries
Authors: Berardo Ramiro , Scholz John T.
Published: June 2010

Policy actors seek network contacts to improve individual payoffs in the institutional collective action dilemmas endemic to fragmented policy arenas. The risk hypothesis argues that actors seek bridging relationships (well‐connected, popular partners that maximize their access to information) when cooperation involves low risks, but seek bonding relationships (transitive, reciprocal relationships that maximize credibility) when risks of defection increase. We test this hypothesis in newly developing policy arenas expected to favor relationships that resolve low‐risk dilemmas. A stochastic actor‐based model for network evolution estimated with survey data from 1999 and 2001 in 10 U.S. estuaries finds that actors do tend to select popular actors as partners, which presumably creates a centralized bridging structure capable of efficient information transmission for coordinating policies even without any government mandate. Actors also seek reciprocal bonding relationships supportive of small joint projects and quickly learn whether or not to trust their partners.
Pacing Maneuver in the Diagnosis of the Mechanism of Supraventricular Tachycardia
Authors: BHATTACHARYA SANJOY , SABA SAMIR
Published: June 2010

Pacing and entrainment maneuvers are essential for establishing the mechanism of supraventricular tachycardia (SVT), but may fail to do so if the SVT terminates or if pacing results in atrioventricular (AV) dissociation as opposed to entrainment of the arrhythmia. We present an unusual case of typical AV nodal reentrant tachycardia (AVNRT) with high degree AV block in which the diagnosis was confirmed using a novel maneuver consisting of simultaneous atrial and ventricular (A + V) pacing. The reproducible response to A + V pacing at varying cycle lengths established the diagnosis of AVNRT in this case. (PACE 2011; 34:e90–e93)
Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer
Authors: Chiche Johanna , Brahimi‐Horn M. Christiane , Pouysségur Jacques
Published: June 2010

Introduction

Intracellular pH regulation controls energy balance and cell proliferation: chemical and biological proof of principle

Oncogene activation and transformation cause acidosis

Hypoxia promotes acidosis by shifting from oxidative phosphorylation to glycolytic metabolism

Hypoxia enhances the expression and activity of pHi‐regulating systems to promote cell survival and invasion

Strategies taking advantage of changes in the oxygen level, energy balance and pH homeostasis to target primary tumours and metastases

Conclusion

Maintenance of cellular pH homeostasis is fundamental to life. A number of key intracellular pH (pHi) regulating systems including the Na+/H+ exchangers, the proton pump, the monocarboxylate transporters, the HCO3− transporters and exchangers and the membrane‐associated and cytosolic carbonic anhydrases cooperate in maintaining a pHi that is permissive for cell survival. A common feature of tumours is acidosis caused by hypoxia (low oxygen tension). In addition to oncogene activation and transformation, hypoxia is responsible for inducing acidosis through a shift in cellular metabolism that generates a high acid load in the tumour microenvironment. However, hypoxia and oncogene activation also allow cells to adapt to the potentially toxic effects of an excess in acidosis. Hypoxia does so by inducing the activity of a transcription factor the hypoxia‐inducible factor (HIF), and particularly HIF‐1, that in turn enhances the expression of a number of pHi‐regulating systems that cope with acidosis. In this review, we will focus on the characterization and function of some of the hypoxia‐inducible pH‐regulating systems and their induction by hypoxic stress. It is essential to understand the fundamentals of pH regulation to meet the challenge consisting in targeting tumour metabolism and acidosis as an anti‐tumour approach. We will summarize strategies that take advantage of intracellular and extracellular pH regulation to target the primary tumour and metastatic growth, and to turn around resistance to chemotherapy and radiotherapy.
STIM proteins: integrators of signalling pathways in development, differentiation and disease
Authors: Johnstone Lorna S. , Graham Sarah J. L. , Dziadek Marie A.
Published: June 2010

Introduction

Part I: STIM proteins

Part II: STIM proteins and the regulation of cell physiology and pathology

Part III: invertebrate animal models of STIM deficiency

Part IV: conclusions and future perspectives

The stromal interaction molecules STIM1 and STIM2 are endoplasmic reticulum Ca2+ sensors, serving to detect changes in receptor‐mediated ER Ca2+ store depletion and to relay this information to plasma membrane localized proteins, including the store‐operated Ca2+ channels of the ORAI family. The resulting Ca2+ influx sustains the high cytosolic Ca2+ levels required for activation of many intracellular signal transducers such as the NFAT family of transcription factors. Models of STIM protein deficiency in mice, Drosophila melanogaster and Caenorhabditis elegans, in addition to the phenotype of patients bearing mutations in STIM1 have provided great insight into the role of these proteins in cell physiology and pathology. It is now becoming clear that STIM1 and STIM2 are critical for the development and functioning of many cell types, including lymphocytes, skeletal and smooth muscle myoblasts, adipocytes and neurons, and can interact with a variety of signalling proteins and pathways in a cell‐ and tissue‐type specific manner. This review focuses on the role of STIM proteins in development, differentiation and disease, in particular highlighting the functional differences between STIM1 and STIM2.
Association between periodontal condition and use of tongue piercing: a case–control study
Authors: Pires Ivana Lucia Oliveira , Cota Luís Otávio Miranda , Oliveira Ana Cristina Borges , Costa José Eustaquio , Costa Fernando Oliveira
Published: June 2010

Pires ILO, Cota LOM, Oliveira ACB, Costa JE, Costa FO. Association between periodontal condition and use of tongue piercing: a case–control study. J Clin Periodontol 2010; 37: 712‐718 doi: 10.1111/j.1600-051X.2010.01584.x.

Objective: This cross‐sectional study aimed to evaluate the periodontal status and risk factors for gingival recession in individuals with tongue piercings.

Methods: Sixty cases (individuals with tongue piercings) and 120 controls (non‐users) in Brazil, between 13 and 28 years of age, from both genders and a mix of races were selected. The clinical evaluation of patient oral health records included periodontal parameters and the presence of tooth fracture. Cases and controls were compared with demographic, behavioural and clinical variables of interest. Risk variables for the occurrence of gingival recession were identified in multivariate regression models, with linear and logistic regressions.

Results: The case group presented a higher prevalence and severity of gingival recession when compared with the control group. Individuals with tongue piercings presented an 11 times greater chance for the occurrence of gingival recession in the anterior lingual mandibular region as compared with controls (OR=11.0, 95% CI 5.02–24.09). The presence of gingival recession in the anterior lingual mandibular region was associated with the use of piercings, age, male gender and bleeding on probing.

Conclusions: The use of tongue piercings was strongly associated with the occurrence of gingival recession in the anterior lingual mandibular region.
Single amino acid repeats in signal peptides
Authors: Łabaj Paweł P. , Leparc Germán G. , Bardet Anaïs F. , Kreil Günther , Kreil David P.
Published: June 2010

There has been an increasing interest in single amino acid repeats ever since it was shown that these are the cause of a variety of diseases. Although a systematic study of single amino acid repeats is challenging, they have subsequently been implicated in a number of functional roles. In general surveys, leucine runs were among the most frequent. In the present study, we present a detailed investigation of repeats in signal peptides of secreted and type I membrane proteins in comparison with their mature parts. We focus on eukaryotic species because single amino acid repeats are generally rather rare in archaea and bacteria. Our analysis of over 100 species shows that repeats of leucine (but not of other hydrophobic amino acids) are over‐represented in signal peptides. This trend is most pronounced in higher eukaryotes, particularly in mammals. In the human proteome, although less than one‐fifth of all proteins have a signal peptide, approximately two‐thirds of all leucine repeats are located in these transient regions. Signal peptides are cleaved early from the growing polypeptide chain and then degraded rapidly. This may explain why leucine repeats, which can be toxic, are tolerated at such high frequencies. The substantial fraction of proteins affected by the strong enrichment of repeats in these transient segments highlights the bias that they can introduce for systematic analyses of protein sequences. In contrast to a general lack of conservation of single amino acid repeats, leucine repeats were found to be more conserved than the remaining signal peptide regions, indicating that they may have an as yet unknown functional role.
Injections of Adipose Tissue-Derived Stem Cells and Stem Cell Lysate Improve Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury
Authors: Albersen Maarten , Fandel Thomas M. , Lin Guiting , Wang Guifang , Banie Lia , Lin Ching-Shwun , Lue Tom F.
Published: June 2010

Introduction

Erectile dysfunction (ED) remains a major complication after radical prostatectomy. The use of adipose tissue-derived stem cells (ADSCs) has shown promising results for the treatment of ED. However, the mechanisms of action for stem cell therapy remain controversial, with increasing evidence pointing to paracrine pathways.

Aim

To determine the effects and to identify the mechanism of action of ADSC and ADSC-derived lysate in a rat model of cavernous nerve (CN) crush injury.

Methods

Thirty-two male Sprague-Dawley rats were randomly divided into four equal groups: one group underwent sham operation, while three groups underwent bilateral CN crush. Crush-injury groups were treated at the time of injury with intracavernous injection of ADSC, lysate, or vehicle only (injured controls). Erectile function was assessed by CN electrostimulation at 4 weeks. Penile tissue was collected for histology.

Main Outcome Measures

Intracavernous pressure increase upon CN stimulation; neuronal nitric oxide synthase (nNOS) content in the dorsal penile nerve; smooth muscle content, collagen content, and number of apoptotic cells in the corpus cavernosum.

Results

Both ADSC and lysate treatments resulted in significant recovery of erectile function, as compared with vehicle treatment. nNOS content was preserved in both the ADSC and lysate group, with significantly higher expression compared with vehicle-treated animals. There was significantly less fibrosis and a significant preservation of smooth muscle content in the ADSC and lysate groups compared with injured controls. The observed functional improvement after lysate injection supports the hypothesis that ADSCs act through release of intracellular preformed substances or by active secretion of certain biomolecules. The underlying mechanism of recovery appears to involve neuron preservation and cytoprotection by inhibition of apoptosis.

Conclusions

Penile injection of both ADSC and ADSC-derived lysate can improve recovery of erectile function in a rat model of neurogenic ED.
HLA alleles and fissured tongue
Authors: Kalifatidis A. , Albanidou‐Farmaki E. , Daniilidis M. , Markopoulos A. K. , Karyotis N. , Antoniades D. Z.
Published: June 2010

The aim of this study was to investigate the linkage between HLA and fissured tongue. Sixty‐ nine individuals with fissured tongue and 125 healthy volunteers were typed for HLA‐DRB1*. The results showed increased frequency of HLA‐DRB1*08 (P < 0.001), HLA‐DRB1*14 (P < 0.01), HLA‐DRB1*11 (P < 0.05) and HLA‐DRB1*16 (P < 0.05), while HLA‐DRB1*03 and HLA‐DRB1*07 frequency was decreased (P < 0.05).
Chimeras, Moral Status, and Public Policy: Implications of the Abortion Debate for Public Policy on Human/Nonhuman Chimera Research
Authors: Streiffer Robert
Published: June 2010

Moral status is the moral value that something has in its own right, independently of the interests or concerns of others. Research using human embryonic stem cells (hESCs) implicates issues about moral status because the current method of extracting hESCs involves the destruction of a human embryo, the moral status of which is contested. Moral status issues can also arise, however, when hESCs are transplanted into embryonic or fetal animals, thereby creating human/ nonhuman stem cell chimeras (“chimeras” for short). In particular, one concern about chimera research is that it could confer upon an animal the moral status of a normal human adult, but then impermissibly fail to accord the animal the protections it merits in virtue of its enhanced status. Understanding the public policy implications of this ethical conclusion is complicated by the fact that certain views about the moral status of the embryo cannot legitimately be used to justify public policy decisions. Arguments like those employed in the abortion debate for the conclusion that abortion should be legally permissible even if abortion is not morally permissible also support, to a more limited degree, a liberal policy on hESC research involving the creation of chimeras.
Translating Stem Cell Research: Challenges at the Research Frontier
Authors: Magnus David
Published: June 2010

There are many kinds of clinical trials. The regulatory framework within which most drug development takes place appears to be the one that is to be applied to the development of novel stem cell-based clinical trials. In the standard drug development model, appropriate pre-clinical research is conducted (largely based upon non-human animal models), and investigators or research sponsors (typically a company) submit an investigational new drug (IND) application to the Food and Drug Administration (FDA).

If approved, typical clinical trials start with Phase I, which is usually a trial (with a small number of participants) to determine the maximum tolerable dose of a drug. Phase I trials are often referred to as “safety studies” because the primary goal of Phase I research is to determine if an intervention is safe (not whether it works).
Damage Control: Unintended Pregnancy in the United States Military
Authors: Ponder Kathryn L. , Nothnagle Melissa
Published: June 2010

Military reproductive health policies affect large numbers of women. In 2006 servicewomen numbered nearly 350,000 and comprised 14.5% of active-duty forces and 17.4% of the reserve force. In addition, approximately 165,000 female dependents of active duty military personnel and 157,000 female dependents of reserve duty personnel are between the ages of 12 and 22 and are eligible for military health care services. Dependents of military personnel are eligible for military health care coverage until age 21, or up to the age of 23 if considered a full-time student.

About 10% of active duty female servicemembers become pregnant each year. Pregnant servicewomen are considered non-deployable and are usually not assigned to overseas commands. Pregnant women in the Army, the service branch with the greatest number of women on active duty, can choose to remain on active duty, request temporary leave from service, or request separation from service. Separation options include either discharge, honorable or uncharacterized depending on rank, or transfer to individual ready reserve.
Teaching Health Law
Authors: Apel Susan B.
Published: June 2010

Interdisciplinary teaching can be a hard sell to the legal academic community. Over almost three decades, I have spoken at conferences on a variety of subjects. When I have presented on this particular topic, however, I have drawn my most meager crowds. Is it because we think interdisciplinary pedagogy is a bad idea, that we are ill-equipped, or that it is generally too difficult to do successfully? After a dozen years of creating and teaching an interdisciplinary course in law and medicine, I confess that it is now my other, law-only courses that I feel I have to justify. Why is an interdisciplinary approach to teaching law the exception rather than the rule?

My path to creating an interdisciplinary course in law and medicine (MedLaw) began indirectly and with impatience at my own teaching of family law. I had been a professor of family law for decades, and I had developed a sophisticated set of simulations that asked students to negotiate a settlement in a marital dissolution case.
Surgical treatment of osteomyelitis and sequestration of the ilium by a cranial partial hemipelvectomy in an alpaca cria
Authors: Bischofberger AS , Dart CM , Dart AJ
Published: June 2010

A 12‐week‐old female alpaca cria weighing 10 kg presented with a 2‐month history of left hindlimb lameness associated with osteomyelitis and sequestration of the shaft and wing of the left ilium. The affected segment of the ilium was surgically removed. Bacteriological culture revealed a small number of mixed aerobic and anaerobic bacteria. The cria recovered well, was discharged from the hospital 8 days after surgery and was paddock sound without complications 8 months later. Osteomyelitis and sequestration of long bones has been reported in alpacas, but further investigation is necessary to define the prevalence and pathogenesis and to develop specific recommendations for prevention and treatment.
Commissurotomy for improving access to the oral cavity of the wombat
Authors: Wilson GJ , Gillett A
Published: June 2010

Wombats are a grazing marsupial with a diet rich in silicates, which is highly abrasive and results in a higher rate of tooth attrition than in other grazing marsupials such as kangaroos. Any interference in the natural wear process, such as malocclusion or loss of teeth, causes overgrowth of teeth. The small mouth opening of the wombat makes access to the caudal mouth difficult and overgrowth of cheek teeth can be difficult to treat effectively. This case report describes a technique that greatly improves access to allow dental treatment of all overgrown teeth with minimal complications.
Thoracoscopic‐assisted lung lobectomy in the dog: report of two cases
Authors: Laksito MA , Chambers BA , Yates GD
Published: June 2010

The benefits and application of thoracoscopy with selective ventilation, as an adjunct to thoracotomy, in facilitating pleural exploration and lung lobectomy in two dogs are presented. Similar thoracoscopic‐assisted procedures are commonly used in human patients because there is better exposure and they are technically less demanding than thoracoscopy alone, while causing less postoperative morbidity than conventional thoracotomy. There are no previous reports of thoracoscopic‐assisted surgery in the veterinary literature. In the cases described, thoracoscopic‐assisted mini‐thoracotomy was an effective, minimally‐invasive approach for ipsilateral hemithorax exploration and lung lobectomy.