bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of TNF‐alpha receptor type 2 protects motor neurons in a cellular model of amyotrophic lateral sclerosis and in mutant SOD1 mice but does not affect disease progression
Authors: Tortarolo Massimo , Vallarola Antonio , Lidonnici Dario , Battaglia Elisa , Gensano Francesco , Spaltro Gabriella , Fiordaliso Fabio , Corbelli Alessandro , Garetto Stefano , Martini Elisa , Pasetto Laura , Kallikourdis Marinos , Bonetto Valentina , Bendotti Caterina
Published: May 2015

Changes in the homeostasis of tumor necrosis factor α (TNFα) have been demonstrated in patients and experimental models of amyotrophic lateral sclerosis (ALS). However, the contribution of TNFα to the development of ALS is still debated. TNFα is expressed by glia and neurons and acts through the membrane receptors TNFR1 and TNFR2, which may have opposite effects in neurodegeneration. We investigated the role of TNFα and its receptors in the selective motor neuron death in ALS in vitro and in vivo. TNFR2 expressed by astrocytes and neurons, but not TNFR1, was implicated in motor neuron loss in primary SOD1‐G93A co‐cultures. Deleting TNFR2 from SOD1‐G93A mice, there was partial but significant protection of spinal motor neurons, sciatic nerves, and tibialis muscles. However, no improvement of motor impairment or survival was observed. Since the sciatic nerves of SOD1‐G93A/TNFR2−/− mice showed high phospho‐TAR DNA‐binding protein 43 (TDP‐43) accumulation and low levels of acetyl‐tubulin, two indices of axonal dysfunction, the lack of symptom improvement in these mice might be due to impaired function of rescued motor neurons. These results indicate the interaction between TNFR2 and membrane‐bound TNFα as an innovative pathway involved in motor neuron death. Nevertheless, its inhibition is not sufficient to stop disease progression in ALS mice, underlining the complexity of this pathology.

image

We show evidence of the involvement of neuronal and astroglial TNFR2 in the motor neuron degeneration in ALS. Both concur to cause motor neuron death in primary astrocyte/spinal neuron co‐cultures. TNFR2 deletion partially protects motor neurons and sciatic nerves in SOD1‐G93A mice but does not improve their symptoms and survival. However, TNFR2 could be a new target for multi‐intervention therapies.
VEHICLE ACCESS AND EXPOSURE TO NEIGHBORHOOD POVERTY: EVIDENCE FROM THE MOVING TO OPPORTUNITY PROGRAM
Authors: Dawkins Casey , Jeon Jae Sik , Pendall Rolf
Published: May 2015

The geographic determinants of social and economic opportunity have received much scholarly attention. A missing link in this body of research is an emphasis on the range of factors influencing low‐income households’ exposure to neighborhood poverty over time. This paper examines the dynamics of exposure to neighborhood poverty for Moving to Opportunity (MTO) program participants. Our paper is unique in its emphasis on the role of vehicle access as it shapes exposure to neighborhood poverty. We find that vehicle access is an important factor shaping residential spells and transitions to low‐poverty neighborhoods over time. We also find that the combined influence of a geographically‐targeted residential mobility requirement and vehicle access substantially elevates a household's likelihood of accessing and staying in a low‐poverty neighborhood. These findings suggest that residential mobility programs and similar efforts to spatially deconcentrate poverty should pay particular attention to the transportation needs of low‐income households.
Collagenase Clostridium histolyticum for the Treatment of Peyronie's Disease: The Development of This Novel Pharmacologic Approach
Authors: Gelbard Martin K. , Chagan Larisa , Tursi James P.
Published: May 2015

Introduction

The conception of collagenase Clostridium histolyticum (CCH) as treatment for Peyronie's disease (PD) was a vital first step in providing a nonsurgical, minimally invasive FDA-approved treatment for men with PD.

Aim

To review the origins, clinical research history, and ultimately FDA approval of collagenase as PD treatment.

Methods

A PubMed search using (Peyronie's or Peyronie) AND collagenase, and limited to clinical research studies, returned nine papers that were examined in the current review.

Results

Collagenase as a PD treatment arose in response to a lack of effective nonsurgical treatments and the incomplete understanding of underlying PD etiology. Awareness of dense collagen in PD scarring and parallel initial exploration of collagenase to treat herniated lumbar discs coincided with and inspired laboratory-based investigation of collagenase effects on excised PD plaque tissue. The foundational conceptual work and the critical development of purified injectable collagenase allowed the pursuit of clinical studies. Progression of clinical studies into large-scale robust trials culminated in two important outcomes: development of the first validated, PD-specific measure of psychosexual function, the Peyronie's Disease Questionnaire, and the first FDA-approved treatment for PD.

Conclusions

Collagenase therapy began as an attempt to modify the structure of PD-related tunica albuginea scarring, despite the lack of a fundamental understanding of the scar's origin. If we wish to advance PD treatment beyond this first effective step, the future needs to bring us full circle to the starting point: We need a greater understanding of the control of collagen deposition and wound healing in men with PD.
Rethinking ancillary relief on divorce in Ireland: the challenges and opportunities
Authors: O'Sullivan Kathryn
Published: May 2015

This paper considers the highly discretionary equitable redistribution scheme governing ancillary relief in Ireland pursuant to the Family Law (Divorce) Act 1996. The paper begins by drawing on the most up-to-data empirical data highlighting the principal difficulties inherent in the Irish ancillary relief system as currently applied and placing the spotlight firmly on the need for reform. It then considers the constitutional parameters that limit any change to the ancillary relief system applied before presenting a detailed proposal for reform. It concludes that although legislative change may be politically challenging, the commonly cited constitutional impediments to reform do not preclude the adoption of an alternative ancillary relief scheme. Instead, the paper argues that the adoption of a more rule-oriented, ‘pillared’, approach to ancillary relief provision may better resolve the challenges currently faced and ought to be afforded serious consideration in Ireland.
Atmospheric N deposition alters connectance, but not functional potential among saprotrophic bacterial communities
Authors: Freedman Zachary B. , Zak Donald R.
Published: May 2015

The use of co‐occurrence patterns to investigate interactions between micro‐organisms has provided novel insight into organismal interactions within microbial communities. However, anthropogenic impacts on microbial co‐occurrence patterns and ecosystem function remain an important gap in our ecological knowledge. In a northern hardwood forest ecosystem located in Michigan, USA, 20 years of experimentally increased atmospheric N deposition has reduced forest floor decay and increased soil C storage. This ecosystem‐level response occurred concomitantly with compositional changes in saprophytic fungi and bacteria. Here, we investigated the influence of experimental N deposition on biotic interactions among forest floor bacterial assemblages by employing phylogenetic and molecular ecological network analysis. When compared to the ambient treatment, the forest floor bacterial community under experimental N deposition was less rich, more phylogenetically dispersed and exhibited a more clustered co‐occurrence network topology. Together, our observations reveal the presence of increased biotic interactions among saprotrophic bacterial assemblages under future rates of N deposition. Moreover, they support the hypothesis that nearly two decades of experimental N deposition can modify the organization of microbial communities and provide further insight into why anthropogenic N deposition has reduced decomposition, increased soil C storage and accelerated phenolic DOC production in our field experiment.
Two glycerol uptake systems contribute to the high osmotolerance of Zygosaccharomyces rouxii
Authors: Dušková Michala , Ferreira Célia , Lucas Cândida , Sychrová Hana
Published: May 2015

The accumulation of glycerol is essential for yeast viability upon hyperosmotic stress. Here we show that the osmotolerant yeast Zygosaccharomyces rouxii has two genes, ZrSTL1 and ZrSTL2, encoding transporters mediating the active uptake of glycerol in symport with protons, contributing to cell osmotolerance and intracellular pH homeostasis. The growth of mutants lacking one or both transporters is affected depending on the growth medium, carbon source, strain auxotrophies, osmotic conditions and the presence of external glycerol. These transporters are localised in the plasma membrane, they transport glycerol with similar kinetic parameters and besides their expected involvement in the cell survival of hyperosmotic stress, they surprisingly both contribute to an efficient survival of hypoosmotic shock and to the maintenance of intracellular pH homeostasis under non‐stressed conditions. Unlike STL1 in Sa. cerevisiae, the two Z. rouxii STL genes are not repressed by glucose, but their expression and activity are downregulated by fructose and upregulated by non‐fermentable carbon sources, with ZrSTL1 being more influenced than ZrSTL2. In summary, both transporters are highly important, though Z. rouxii CBS 732T cells do not use external glycerol as a source of carbon.
Multiple modes of iron uptake by the filamentous, siderophore‐producing cyanobacterium, Anabaena sp. PCC 7120
Authors: Rudolf Mareike , Kranzler Chana , Lis Hagar , Margulis Ketty , Stevanovic Mara , Keren Nir , Schleiff Enrico
Published: May 2015

Iron is a member of a small group of nutrients that limits aquatic primary production. Mechanisms for utilizing iron have to be efficient and adapted according to the ecological niche. In respect to iron acquisition cyanobacteria, prokaryotic oxygen evolving photosynthetic organisms can be divided into siderophore‐ and non‐siderophore‐producing strains. The results presented in this paper suggest that the situation is far more complex. To understand the bioavailability of different iron substrates and the advantages of various uptake strategies, we examined iron uptake mechanisms in the siderophore‐producing cyanobacterium Anabaena sp. PCC 7120. Comparison of the uptake of iron complexed with exogenous (desferrioxamine B, DFB) or to self‐secreted (schizokinen) siderophores by Anabaena sp. revealed that uptake of the endogenous produced siderophore complexed to iron is more efficient. In addition, Anabaena sp. is able to take up dissolved, ferric iron hydroxide species (Fe′) via a reductive mechanism. Thus, Anabaena sp. exhibits both, siderophore‐ and non‐siderophore‐mediated iron uptake. While assimilation of Fe′ and FeDFB are not induced by iron starvation, FeSchizokinen uptake rates increase with increasing iron starvation. Consequently, we suggest that Fe′ reduction and uptake is advantageous for low‐density cultures, while at higher densities siderophore uptake is preferred.
The essential role of SepF in mycobacterial division
Authors: Gola Susanne , Munder Thomas , Casonato Stefano , Manganelli Riccardo , Vicente Miguel
Published: May 2015

Mycobacteria lack several of the components that are essential in model systems as Escherichia coli or Bacillus subtilis for the formation of the divisome, a ring‐like structure assembling at the division site to initiate bacterial cytokinesis. Divisome assembly depends on the correct placement of the FtsZ protein into a structure called the Z ring. Notably, early division proteins that assist in the localisation of the Z ring to the cytoplasmic membrane and modulate its structure are missing in the so far known mycobacterial cell division machinery. To find mycobacterium‐relevant components of the divisome that might act at the level of FtsZ, a yeast two‐hybrid screening was performed with FtsZ from Mycobacterium tuberculosis. We identified the SepF homolog as a new interaction partner of mycobacterial FtsZ. Depending on the presence of FtsZ, SepF‐GFP fusions localised in ring‐like structures at potential division sites. Alteration of SepF levels in Mycobacterium smegmatis led to filamentous cells, indicating a division defect. Depletion of SepF resulted in a complete block of division. The sepF gene is highly conserved in the M. tuberculosis complex members. We therefore propose that SepF is an essential part of the core division machinery in the genus Mycobacterium.
The origins of reproductive isolation in plants
Authors: Baack Eric , Melo Maria Clara , Rieseberg Loren H. , Ortiz‐Barrientos Daniel
Published: May 2015

Reproductive isolation in plants occurs through multiple barriers that restrict gene flow between populations, but their origins remain uncertain. Work in the past decade has shown that postpollination barriers, such as the failure to form hybrid seeds or sterility of hybrid offspring, are often less strong than prepollination barriers. Evidence implicates multiple evolutionary forces in the origins of reproductive barriers, including mutation, stochastic processes and natural selection. Although adaptation to different environments is a common element of reproductive isolation, genomic conflicts also play a role, including female meiotic drive. The genetic basis of some reproductive barriers, particularly flower colour influencing pollinator behaviour, is well understood in some species, but the genetic changes underlying many other barriers, especially pollen–stylar interactions, are largely unknown. Postpollination barriers appear to accumulate at a faster rate in annuals compared with perennials, due in part to chromosomal rearrangements. Chromosomal changes can be important isolating barriers in themselves but may also reduce the recombination of genes contributing to isolation. Important questions for the next decade include identifying the evolutionary forces responsible for chromosomal rearrangements, determining how often prezygotic barriers arise due to selection against hybrids, and establishing the relative importance of genomic conflicts in speciation.

ContentsSummary968I.Introduction968II.Reproductive barriers in plants970III.Geographic patterns and the origin of reproductive isolation971IV.Genetic changes and evolutionary drivers behind reproductive isolation973V.The timing of reproductive barriers979VI.Synthesis and future directions980Acknowledgements981References981
Pinus sylvestris switches respiration substrates under shading but not during drought
Authors: Fischer Sarah , Hanf Stefan , Frosch Torsten , Gleixner Gerd , Popp Jürgen , Trumbore Susan , Hartmann Henrik
Published: May 2015

Reduced carbon (C) assimilation during prolonged drought forces trees to rely on stored C to maintain vital processes like respiration. It has been shown, however, that the use of carbohydrates, a major C storage pool and apparently the main respiratory substrate in plants, strongly declines with decreasing plant hydration. Yet no empirical evidence has been produced to what degree other C storage compounds like lipids and proteins may fuel respiration during drought.

We exposed young scots pine trees to C limitation using either drought or shading and assessed respiratory substrate use by monitoring the respiratory quotient, δ13C of respired CO2 and concentrations of the major storage compounds, that is, carbohydrates, lipids and amino acids.

Only shaded trees shifted from carbohydrate‐dominated to lipid‐dominated respiration and showed progressive carbohydrate depletion. In drought trees, the fraction of carbohydrates used in respiration did not decline but respiration rates were strongly reduced. The lower consumption and potentially allocation from other organs may have caused initial carbohydrate content to remain constant during the experiment.

Our results suggest that respiratory substrates other than carbohydrates are used under carbohydrate limitation but not during drought. Thus, respiratory substrate shift cannot provide an efficient means to counterbalance C limitation under natural drought.
Patients' participation in decision‐making in the medical field – ‘projectification’ of patients in a neoliberal framed healthcare system
Authors: Glasdam Stinne , Oeye Christine , Thrysoee Lars
Published: May 2015

This article focuses on patients' participation in decision‐making in meetings with healthcare professionals in a healthcare system, based on neoliberal regulations and ideas. Drawing on two constructed empirical cases, primarily from the perspective of patients, this article analyses and discusses the clinical practice around decision‐making meetings within a Foucauldian perspective. Patients' participation in decision‐making can be seen as an offshoot of respect for patient autonomy. A treatment must be chosen, when patients consult physicians. From the perspective of patients, there is a tendency for healthcare professionals to supply the patients with the information that they think are necessary for them to make their own decision. But patients do not always want to be a ‘customer’ in the healthcare system; they want to be a patient, consulting an expert for help and advice, which creates resistance to some parts of the decision‐making process. Both professionals and patients are subject to the structural frame of the medical field, formed of both neoliberal framework and medical logic. The decision‐making competence in relation to the choice of treatment is placed away from the professionals and seen as belonging to the patient. A ‘projectification’ of the patient occurs, whereby the patient becomes responsible for his/her choices in treatment and care and the professionals support him/her with knowledge, preferences, and alternative views, out of which he/she must make his/her own choices, and the responsibility for those choices now and in the future. At the same time, there is a tendency towards de‐professionalization. In that light, participation of patients in decision‐making can be regarded as a tacit governmentality strategy that shapes the location of responsibility between individual and society, and independent patients and healthcare professionals, despite the basically desirable, appropriate, and necessary idea of involving patients in their own situations from a humanistic perspective.
Successful combination of local flaps for large palatal fistula closure
Authors: Perry J. , Bhopal S. , Bharadwaj G. , O'Regan B.
Published: May 2015

The closure of large palatal fistulae may challenge oral and maxillofacial surgeons especially when considering subsequent prosthetic requirements. Surgical procedures used to reconstruct palatal defects include prostheses, local flaps, distant flaps, bone grafting and allografts. We present a case of successful closure of a large post‐resection palatal fistula using a combination of three established techniques. Closure of the superior naso‐antral layer was completed using Fickling's inkwell technique. The resultant large defect was closed using a ‘tadpole’ rotational palatal flap combined with a buccal fat pad advancement to secure the unsupported lateral aspect of the rotation flap and remaining denuded bone of the left hard palate. The fistula remains closed four years after surgery. This report demonstrates the effective combination of three local intra‐oral flaps as a single‐stage, low‐risk method of closing a large palatal fistula.
Incidence and Predictors of Pacemaker Implantation in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: MAAN ABHISHEK , REFAAT MARWAN M. , HEIST EDWIN KEVIN , PASSERI JONATHAN , INGLESSIS IGNACIO , PTASZEK LEON , VLAHAKES GUS , RUSKIN JEREMY N. , PALACIOS IGOR , SUNDT THORALF , MANSOUR MOUSSA
Published: May 2015

Background

Transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for patients with symptomatic aortic stenosis who are at high risk for surgical aortic valve replacement. The development of conduction abnormalities is a major complication in the postprocedural period of TAVR.

Objectives

The objective of this study was to investigate the development of postprocedural conduction abnormalities and the requirement of permanent pacemaker (PPM) implantation in patients undergoing TAVR.

Methods

Data from 137 consecutive patients who underwent TAVR (Edwards SAPIEN valve, Edwards Lifesciences, Irvine, CA, USA) between June 2008 and October 2012 were reviewed. Patients with prior history of PPM (n = 27) were excluded. The role of various predictors for pacemaker implantation after TAVR, including the valve index (calculated as [valve size/left ventricular outflow tract diameter] × 100) was investigated.

Results

A total of 31/110 (28.2%) patients required implantation of a PPM after TAVR. The median time to implantation of a PPM was 5 days after the procedure. The development of postprocedural complete heart block was the most common indication for implantation of a PPM (16/31; 51.6%). On multivariate analysis, the presence of preexisting right bundle branch block (RBBB) was found to be a strong predictor of PPM implantation after TAVR (adjusted odds ratio: 4.87; 95% confidence interval: 1.29–18.46, P = 0.020). Using the receiver operated curve analysis, a cut‐off value of valve index of 128 was found to be a strong predictor for PPM implantation with a sensitivity of 73% and specificity of 61% (c statistic = 0.68).

Conclusions

This study identified the presence of prior RBBB and a valve index of 128 as important risk factors for PPM implantation after TAVR. A larger implanted valve size relative to left ventricular outflow tract diameter leads to a greater compression of the intrinsic conduction system, increasing the need for pacemaker placement.
Impact of Implantable Cardioverter Defibrillators on Survival of Patients with Centrifugal Left Ventricular Assist Devices
Authors: LEE WILLIAM , TAY ANDRE , SUBBIAH RAJESH N. , WALKER BRUCE D. , KUCHAR DENNIS L. , MUTHIAH KAVITHA , MACDONALD PETER S. , KEOGH ANNE M. , KOTLYAR EUGENE , JABBOUR ANDREW , SPRATT PHILIP , JANSZ PAUL C. , GRANGER EMILY , DHITAL KUMUD , HAYWARD CHRISTOPHER S.
Published: May 2015

Background

Both implantable cardioverter defibrillators (ICDs) and left ventricular assist devices (LVADs) have a positive impact on survival in the heart failure population. We sought to determine whether these positive effects on survival are additive or whether LVAD therapy supersedes ICD therapy.

Method

We analyzed survival data of patients implanted with nonpulsatile LVADs between October 2004 and March 2013. Survival in patients with ICDs (n = 64) was compared to those without ICDs (n = 36). Patients exited the study at the time of heart transplantation or death.

Results

A total of 100 patients underwent LVAD implantation during this time. Patients had a mean follow‐up time of 364 ± 295 days. Death occurred in 15 (38%) patients in the no ICD group versus 18 (30%) in the ICD group. Univariate analysis demonstrated a marginal early survival benefit at up to 1 year post‐LVAD implant in the ICD cohort; however, at time points greater than 1 year there was no statistically significant benefit in ICD therapy in LVAD patients (P = 0.56). Multivariate analysis did not show any significant predictor of survival. There were no patients who died of sudden cardiac death. There was no significant difference in the time to heart transplantation (443 days ± 251 no ICD vs 372 days ± 277 ICD, P = 0.37).

Conclusion

The benefit of ICD therapy in the setting of continuous flow LVAD therapy is uncertain. Although prolonged ventricular arrhythmias (VAs) may potentially impact on patient survival, LVAD therapy is beneficial in prevention of sudden cardiac death due to VAs.
Prognostic Value of a Very Prolonged Asystole during Head‐Up Tilt Test
Authors: CARVALHO MARIA SALOMÉ , REIS SANTOS KATYA , CARMO PEDRO , CAVACO DIOGO , PARREIRA LEONOR , MORGADO FRANCISCO , ADRAGÃO PEDRO
Published: May 2015

Background

Clinical significance and prognosis of a cardioinhibitory response to head‐up tilt (HUT) test with a very prolonged asystole (≥30 seconds) is poorly studied. Our aim was to evaluate the treatment (including pacemaker implantation) and prognosis (syncope recurrence, syncope‐related trauma, and overall mortality) of patients with a very prolonged asystole on a HUT test.

Methods and Results

A retrospective study was conducted in two centers between January 2003 and December 2013 and included a total of 2,263 consecutive HUT tests (sensitized with isosorbide dinitrate) performed in 2,247 patients with syncope of unknown etiology. Cardioinhibitory response with asystole was observed in 149 (6.6%) of these tests (44.3% women, mean age 37 ± 18 years old, 16.1% in the nonpharmacological phase), with a median duration of asystole of 10 (6–19) seconds. Very prolonged asystole (≥30 seconds) was documented in 11 (0.5%) patients (45% women; mean age 40 ± 19 years; only one in the nonpharmacological phase, 9 minutes after HUT). The longest pause lasted 63 seconds. In all patients, avoidance of triggering factors and physical counterpressure maneuvers were recommended. Telephone follow‐up was performed: in one patient, fludrocortisone was started; tilt training was conducted in one patient and none received a pacemaker. After a median follow‐up of 42 (30–76) months, four patients (36%) had syncopal recurrences, one patient had a syncope‐related injury (scalp laceration), and no patient died.
Anesthesia and organic aciduria: is the use of lactated Ringer's solution absolutely contraindicated?
Authors: Ruzkova Katerina , Weingarten Toby N. , Larson Kelly J. , Friedhoff Robert J. , Gavrilov Dimitar K. , Sprung Juraj
Published: May 2015

Background

Organic acidurias (OAs) are rare inborn errors of metabolism that can present with various neurologic manifestations, propensity for acute metabolic decompensation with anion‐gap metabolic acidosis, developmental delay, poor feeding, and failure to thrive.

Objective

In this case series, we outline the anesthetic management and perioperative outcomes of OA patients.

Methods

We reviewed demographic characteristics, comorbidities, and perioperative course of patients with four different OAs who underwent anesthetic care at our institution between January 1, 2000, and December 31, 2013.

Results

Eleven patients with OA underwent 19 anesthetic procedures, of which 13 were <2 h in duration and seven were outpatient procedures. One patient with methylmalonic acidemia developed metabolic acidosis during a 10‐h procedure with substantial blood loss but lacked evidence that this acidosis could be attributed to his underlying metabolic disease. The patients who received hydration with lactated Ringer's solution and/or nitrous oxide anesthetic had a perioperative course free of metabolic complication. Two patients died within 30 days of surgery from causes likely to be unrelated to anesthetic exposure.

Conclusions

Our patients with various forms of metabolically compensated OAs tolerated anesthetics for surgical procedures without metabolic decompensation, even when lactated Ringer's solution was used for hydration. Measures to prevent protein catabolism and intraoperative events that may precipitate metabolic acidosis, in addition to close monitoring of acid‐base status during more extensive procedures, must be part of perioperative treatment of these patients.
Stay Loyal or Exit the Party? How Openness to Experience and Extroversion Explain Vote Switching
Authors: Bakker Bert N. , Klemmensen Robert , Nørgaard Asbjørn Sonne , Schumacher Gijs
Published: May 2015

Following Hirschman, voters who are discontent with the party they voted for have two options: exit the party and vote for another or stay loyal. The inclination to exit or stay loyal is rooted in the Five Factor Model (FFM) of personality. We test our argument in two panel studies in Denmark and the United Kingdom. We find that citizens open to experience are more likely to switch parties since they are more likely to think about alternatives and take risks. Extroverts identify and commit themselves to organizations and stay loyal in Denmark, but we do not confirm this pattern in the United Kingdom. Our findings demonstrate that electoral volatility is, at least partly, rooted in personality.
Risk‐Based Decision Making for Reoccupation of Contaminated Areas Following a Wide‐Area Anthrax Release
Authors: Hamilton Michael A. , Hong Tao , Casman Elizabeth , Gurian Patrick L.
Published: May 2015

This article presents an analysis of postattack response strategies to mitigate the risks of reoccupying contaminated areas following a release of Bacillus anthracis spores (the bacterium responsible for causing anthrax) in an urban setting. The analysis is based on a hypothetical attack scenario in which individuals are exposed to B. anthracis spores during an initial aerosol release and then placed on prophylactic antibiotics that successfully protect them against the initial aerosol exposure. The risk from reoccupying buildings contaminated with spores due to their reaerosolization and inhalation is then evaluated. The response options considered include: decontamination of the buildings, vaccination of individuals reoccupying the buildings, extended evacuation of individuals from the contaminated buildings, and combinations of these options. The study uses a decision tree to estimate the costs and benefits of alternative response strategies across a range of exposure risks. Results for best estimates of model inputs suggest that the most cost‐effective response for high‐risk scenarios (individual chance of infection exceeding 11%) consists of evacuation and building decontamination. For infection risks between 4% and 11%, the preferred option is to evacuate for a short period, vaccinate, and then reoccupy once the vaccine has taken effect. For risks between 0.003% and 4%, the preferred option is to vaccinate only. For risks below 0.003%, none of the mitigation actions have positive expected monetary benefits. A sensitivity analysis indicates that for high‐infection‐likelihood scenarios, vaccination is recommended in the case where decontamination efficacy is less than 99.99%.
Risk Assessment of the Carbon Nanotube Group
Authors: Nakanishi Junko , Morimoto Yasuo , Ogura Isamu , Kobayashi Norihiro , Naya Masato , Ema Makoto , Endoh Shigehisa , Shimada Manabu , Ogami Akira , Myojyo Toshihiko , Oyabu Takako , Gamo Masashi , Kishimoto Atsuo , Igarashi Takuya , Hanai Sosuke
Published: May 2015

This study assessed the health risks via inhalation and derived the occupational exposure limit (OEL) for the carbon nanotube (CNT) group rather than individual CNT material. We devised two methods: the integration of the intratracheal instillation (IT) data with the inhalation (IH) data, and the “biaxial approach.” A four‐week IH test and IT test were performed in rats exposed to representative materials to obtain the no observed adverse effect level, based on which the OEL was derived. We used the biaxial approach to conduct a relative toxicity assessment of six types of CNTs. An OEL of 0.03 mg/m3 was selected as the criterion for the CNT group. We proposed that the OEL be limited to 15 years. We adopted adaptive management, in which the values are reviewed whenever new data are obtained. The toxicity level was found to be correlated with the Brunauer‐Emmett‐Teller (BET)‐specific surface area (BET‐SSA) of CNT, suggesting the BET‐SSA to have potential for use in toxicity estimation. We used the published exposure data and measurement results of dustiness tests to compute the risk in relation to particle size at the workplace and showed that controlling micron‐sized respirable particles was of utmost importance. Our genotoxicity studies indicated that CNT did not directly interact with genetic materials. They supported the concept that, even if CNT is genotoxic, it is secondary genotoxicity mediated via a pathway of genotoxic damage resulting from oxidative DNA attack by free radicals generated during CNT‐elicited inflammation. Secondary genotoxicity appears to involve a threshold.
Index for Predicting Insurance Claims from Wind Storms with an Application in France
Authors: Mornet Alexandre , Opitz Thomas , Luzi Michel , Loisel Stéphane
Published: May 2015

For insurance companies, wind storms represent a main source of volatility, leading to potentially huge aggregated claim amounts. In this article, we compare different constructions of a storm index allowing us to assess the economic impact of storms on an insurance portfolio by exploiting information from historical wind speed data. Contrary to historical insurance portfolio data, meteorological variables show fewer nonstationarities between years and are easily available with long observation records; hence, they represent a valuable source of additional information for insurers if the relation between observations of claims and wind speeds can be revealed. Since standard correlation measures between raw wind speeds and insurance claims are weak, a storm index focusing on high wind speeds can afford better information. A storm index approach has been applied to yearly aggregated claim amounts in Germany with promising results. Using historical meteorological and insurance data, we assess the consistency of the proposed index constructions with respect to various parameters and weights. Moreover, we are able to place the major insurance events since 1998 on a broader horizon beyond 40 years. Our approach provides a meteorological justification for calculating the return periods of extreme‐storm‐related insurance events whose magnitude has rarely been reached.
The Relationship Between Volume Overload in End‐Stage Renal Disease and Obstructive Sleep Apnea
Authors: Roumelioti Maria‐Eleni , Brown Lee K. , Unruh Mark L.
Published: May 2015

Obstructive sleep apnea (OSA) is common, underdiagnosed, and undertreated among patients with end‐stage renal disease (ESRD). As in all cases, pathogenesis of OSA is related to repeated upper airway (UA) occlusion or narrowing, but in ESRD, additional contributory factors likely include uremic destabilization of central respiratory control and anatomic changes in the UA related to fluid status. Pulmonary congestion is common in acute and chronic kidney failure and is a consequence of cardiomyopathy and fluid overload, two potentially reversible risk factors. Emerging evidence suggests that volume overload also reduces the UA caliber. The diminution in UA area as well as destabilization of ventilatory control in ESRD have been postulated as causes of increased OSA prevalence and severity in these patients, and creates a vicious cycle wherein OSA exacerbates fluid overload disorders such as in congestive heart failure (CHF) and ESRD, which then further worsen OSA. Dialysis modalities may differ in their effects on volume status, the accumulation of uremic toxins, and acid–base status, and as a consequence, on the emergence and severity of OSA. Given the contribution of excess fluid to both the severity of nocturnal hypoxia and UA narrowing, establishing and maintaining dry weight is of particular importance when managing OSA in ESRD. Clinical trials to determine the extent to which more aggressive fluid removal in ESRD patients may alleviate OSA are needed.
Effects of acute, intermittent exercise in hypoxic environments on the release of cardiac troponin
Authors: Li F. , Hu Y. , Nie J. , Fu F.H.
Published: May 2015

The purpose of this study was to examine the effects of acute, intermittent exercise performed in hypoxic environments on the release of cardiac troponin (cTn). Ten well‐trained, male marathon runners (22.1 ± 2.6 years, 64.0 ± 4.9 kg and 177.3 ± 3.9 cm) completed three intermittent exercise protocols under normoxic (trial N) and hypoxic (trial AH and RH) conditions. In trial N, the fraction of inspiration oxygen (FIO2) was 21.0% and exercise intensity was 90% and 50% normoxic velocity of VO2max (vVO2max). In trial AH, FIO2 was 14.4% (simulated altitude of 3000 m) and exercise intensity was 90% and 50% normoxic vVO2max. In trial RH, FIO2 was 14.4% and exercise intensity was 90% and 50% hypoxic vVO2max. High‐sensitivity cardiac troponin T (hs‐cTnT) and cardiac troponin I (cTnI) were measured pre‐ and 0, 2, 4, and 24 h post‐exercise. Hs‐cTnT was elevated in all three trials, peaking at 2 to 4 h and returning to the baseline 24 h post‐exercise. CTnI increased in trial AH, peaking at 2 to 4 h and returning below the detection limit 24 h post‐exercise. It is concluded that the stimulus of hypoxia did not in and of itself induce more cTn to be released, but exercise intensity could affect this response in hypoxic environments.
From Official Supervision to Self‐monitoring: Privatizing Supervision of Private Social Care Services in Finland
Authors: Kotkas Toomas
Published: May 2015

In October 2011, a new Act on Private Social Care Services came into force in Finland. The Act included a provision on a ‘self‐monitoring plan’. According to the provision, providers of private social care services are required to draw up a self‐monitoring plan and to follow its realization. The plan must be kept publicly on view so that clients and their relatives can also keep an eye on the realization of self‐monitoring. In this article, self‐monitoring is first explained and then briefly analyzed against the background of a wider theoretical discussion on accountability. It is argued that the introduction of client involvement in the supervision of private social care services represents a new mechanism of accountability that is typical of the Post‐Keynesian welfare state. Because public authorities are no longer able to supervise the growing number of private social care service providers, the responsibility has been partly shifted to service providers themselves as well as to clients. However, it is argued that the idea of self‐monitoring lends itself poorly to ‘delegated’ private social care services, i.e. to services that are outsourced to private service suppliers. Supervision of private social care service providers should not be too eagerly delegated to service providers themselves, or to clients, because we are here dealing with the constitutional right to adequate social care services. Client involvement also involves numerous practical problems, as shown at the end of the article.
Students' Alternate Conceptions on Acids and Bases
Authors: Pan Hanqing , Henriques Laura
Published: May 2015

Knowing what students bring to the classroom can and should influence how we teach them. This study is a review of the literature associated with secondary and postsecondary students' ideas about acids and bases. It was found that there are six types of alternate ideas about acids and bases that students hold. These are: macroscopic properties of acids and bases, microscopic properties of acids and bases, neutralization, acid strength, pH, and titration.
Antimalarial drugs inhibit PI3P production
Authors: VanHook Annalisa M.
Published: May 2015

A mutation that thwarts the ability of an antimalarial drug to inhibit production of a signaling lipid confers drug resistance to the parasite
Plasmodium falciparum
.
Hypoxia, myelin, and the neonatal brain
Authors: Ferrarelli Leslie K.
Published: May 2015

Myelination defects associated with premature birth may be ameliorated by drugs that activate GABA receptors.
Effects of Surotomycin on Clostridium difficile Viability and Toxin Production
In Vitro
Authors: Bouillaut Laurent , McBride Shonna , Sorg Joseph A. , Schmidt Diane J. , Suarez José M. , Tzipori Saul , Mascio Carmela , Chesnel Laurent , Sonenshein A. L.
Published: May 2015

The increasing incidence and severity of infection by
Clostridium difficile
have stimulated attempts to develop new antimicrobial therapies. We report here the relative abilities of two antibiotics (metronidazole and vancomycin) in current use for treating
C. difficile
infection and of a third antimicrobial, surotomycin, to kill
C. difficile
cells at various stages of development and to inhibit the production of the toxin proteins that are the major virulence factors. The results indicate that none of the drugs affects the viability of spores at 8× MIC or 80× MIC and that all of the drugs kill exponential-phase cells when provided at 8× MIC. In contrast, none of the drugs killed stationary-phase cells or inhibited toxin production when provided at 8× MIC and neither vancomycin nor metronidazole killed stationary-phase cells when provided at 80× MIC. Surotomycin, on the other hand, did kill stationary-phase cells when provided at 80× MIC but did so without inducing lysis.
Direct Administration in the Respiratory Tract Improves Efficacy of Broadly Neutralizing Anti-Influenza Virus Monoclonal Antibodies
Authors: Leyva-Grado Victor H. , Tan Gene S. , Leon Paul E. , Yondola Mark , Palese Peter
Published: May 2015

The emergence of influenza virus strains resistant to approved neuraminidase inhibitors and the time constrains after infection when these drugs can be effective constitute major drawbacks for this class of drugs. This highlights a critical need to discover new therapeutic agents that can be used for the treatment of influenza virus-infected patients. The use of broadly neutralizing anti-influenza monoclonal antibodies (MAbs) has been sought as an alternative immunotherapy against influenza infection. Here, we tested in mice previously characterized broadly neutralizing anti-hemagglutinin (HA) stalk MAbs prophylactically and therapeutically using different routes of administration. The efficacy of treatment against an influenza H1N1 pandemic virus challenge was compared between two systemic routes of administration, intraperitoneal (i.p.) and intravenous (i.v.), and two local routes, intranasal (i.n.) and aerosol (a.e.). The dose of MAb required for prophylactic protection was reduced by 10-fold in animals treated locally (i.n. or a.e.) compared with those treated systemically (i.p. or i.v.). Improved therapeutic protection was observed in animals treated i.n. on day 5 postinfection (60% survival) compared with those treated via the i.p. route (20% survival). An increase in therapeutic efficacy against other influenza virus subtypes (H5N1) was also observed when a local route of administration was used. Our findings demonstrate that local administration significantly decreases the amount of broadly neutralizing monoclonal antibody required for protection against influenza, which highlights the potential use of MAbs as a therapeutic agent for influenza-associated disease.
Inhibition of Aminoglycoside Acetyltransferase Resistance Enzymes by Metal Salts
Authors: Li Yijia , Green Keith D. , Johnson Brooke R. , Garneau-Tsodikova Sylvie
Published: May 2015

Aminoglycosides (AGs) are clinically relevant antibiotics used to treat infections caused by both Gram-negative and Gram-positive bacteria, as well as
Mycobacteria
. As with all current antibacterial agents, resistance to AGs is an increasing problem. The most common mechanism of resistance to AGs is the presence of AG-modifying enzymes (AMEs) in bacterial cells, with AG acetyltransferases (AACs) being the most prevalent. Recently, it was discovered that Zn
2+
metal ions displayed an inhibitory effect on the resistance enzyme AAC(6′)-Ib in
Acinetobacter baumannii
and
Escherichia coli
. In this study, we explore a wide array of metal salts (Mg
2+
, Cr
3+
, Cr
6+
, Mn
2+
, Co
2+
, Ni
2+
, Cu
2+
, Zn
2+
, Cd
2+
, and Au
3+
with different counter ions) and their inhibitory effect on a large repertoire of AACs [AAC(2′)-Ic, AAC(3)-Ia, AAC(3)-Ib, AAC(3)-IV, AAC(6′)-Ib′, AAC(6′)-Ie, AAC(6′)-IId, and Eis]. In addition, we determine the MIC values for amikacin and tobramycin in combination with a zinc pyrithione complex in clinical isolates of various bacterial strains (two strains of
A. baumannii
, three of
Enterobacter cloacae
, and four of
Klebsiella pneumoniae
) and one representative of each species purchased from the American Type Culture Collection.
Development of Gendine-Coated Cannula for Continuous Subcutaneous Insulin Infusion for Extended Use
Authors: Jamal Mohamed A. , Garoge Kumait , Rosenblatt Joel S. , Hachem Ray Y. , Raad Issam I.
Published: May 2015

Continuous subcutaneous insulin infusion (CSII) using pumps is a widely used method for insulin therapy in patients with diabetes mellitus. Among the major factors that usually lead to the discontinuation of CSII are CSII set-related issues, including infection at the infusion site. The American Diabetic Association currently recommends rotating sites every 2 to 3 days. This recommendation adds cost and creates inconvenience. Therefore, in order to prevent infections and extend the duration between insertion site changes, we developed a Teflon cannula coated with a combination of gentian violet and chlorhexidine (gendine) and tested its antimicrobial efficacy against different pathogens. The cannulas were coated with gendine on the exterior surface and dried. The efficacy and durability of gendine-coated cannulas were determined against methicillin-resistant
Staphylococcus aureus
,
Staphylococcus epidermidis
, methicillin-susceptible
S. aureus
,
Streptococcus pyogenes
, vancomycin-resistant enterococci,
Escherichia coli
,
Pseudomonas aeruginosa
,
Candida albicans
, and
Candida glabrata
using a biofilm colonization method. The cytotoxicity of gendine was assessed against mouse fibroblast cell lines. The gendine-coated cannulas showed complete prevention of biofilm colonization of all organisms tested for up to 2 weeks (
P
< 0.0001) compared to that with the uncoated control. A gendine-coated catheter against mouse fibroblast cells was shown to be noncytotoxic. Our
in vitro
results show that a novel gendine cannula is highly effective in completely inhibiting the biofilm of multidrug-resistant pathogens for up to 2 weeks and may have potential clinical applications, such as prolonged use, cost reduction, and lower infection rate.
Mutational Analysis of the Chlamydia muridarum Plasticity Zone
Authors: Rajaram Krithika , Giebel Amanda M. , Toh Evelyn , Hu Shuai , Newman Jasmine H. , Morrison Sandra G. , Kari Laszlo , Morrison Richard P. , Nelson David E.
Published: May 2015

Pathogenically diverseChlamydiaspp. can have surprisingly similar genomes.Chlamydia trachomatisisolates that cause trachoma, sexually transmitted genital tract infections (chlamydia), and invasive lymphogranuloma venereum (LGV) and the murine strainChlamydia muridarumshare 99% of their gene content. A region of high genomic diversity betweenChlamydiaspp. termed the plasticity zone (PZ) may encode niche-specific virulence determinants that dictate pathogenic diversity. We hypothesized that PZ genes might mediate the greater virulence and gamma interferon (IFN-γ) resistance ofC. muridarumcompared toC. trachomatisin the murine genital tract. To test this hypothesis, we isolated and characterized a series ofC. muridarumPZ nonsense mutants. Strains with nonsense mutations in chlamydial cytotoxins,guaBA-add, and a phospholipase D homolog developed normally in cell culture. Two of the cytotoxin mutants were less cytotoxic than the wild type, suggesting that the cytotoxins may be functional. However, none of the PZ nonsense mutants exhibited increased IFN-γ sensitivity in cell culture or were profoundly attenuated in a murine genital tract infection model. Our results suggest thatC. muridarumPZ genes are transcribed—and some may produce functional proteins—but are dispensable for infection of the murine genital tract.