bluuebunny/crossref_metadata_2025 huggingface dataset:
von Economo neurones are selectively targeted in frontotemporal dementia
Authors: Santillo A. F. , Nilsson C. , Englund E.
Published: January 2013

Background

von Economo neurones (VEN) are bipolar neurones located in the anterior cingulate cortex (ACC) and the frontoinsular cortex (FI), areas affected early in behavioural variant frontotemporal dementia (bvFTD), in which VEN may constitute a selectively vulnerable cellular population.

Aim

A previous study has shown a selective loss of VEN in FTD above other neurones in the ACC of FTD. The aim of this study was to confirm this finding in a larger cohort, using a different methodology, and to examine VEN loss in relation to neuropathological severity and molecular pathology.

Methods

VEN and neighbouring neurones (NN) were quantified in layers Va and Vb of the right dorsal ACC in 21 cases of bvFTD, 10 cases of Alzheimer's disease (AD) and 10 non‐demented controls (NDC).

Results

A marked VEN reduction was seen in all FTD cases. In the neuropathologically early cases of FTD (n = 13), VEN/10 000 NN was significantly reduced by 53% compared with NDC (P < 0.001) and 41% compared with AD (P = 0.019), whereas AD patients showed a non‐significant 30% reduction of VEN/10 000 NN compared with NDC. VEN reduction was present in all protein pathology subgroups.

Discussion

In conclusion, this study confirms selective sensitivity of VEN in FTD and suggests that VEN loss is an early event in the neurodegenerative process.
Sedation practice in Nordic and non‐Nordic ICUs: a European survey
Authors: Egerod Ingrid , Albarran John W , Ring Mette , Blackwood Bronagh
Published: January 2013

Background and aims

A trend towards lighter sedation has been evident in many intensive care units (ICUs). The aims of the survey were to describe sedation practice in European ICUs and to compare sedation practice in Nordic and non‐Nordic countries.

Design and methods

A cross‐sectional survey of ICU nurses attending the fourth European federation of Critical Care Nursing associations (EfCCNa) in Denmark, 2011. Data included use of protocols; sedation, pain and delirium assessment tools; collaborative decision‐making; sedation and analgesic medications; and educational preparation related to sedation.

Results

Response rate was 42% (n = 291) from 22 countries where 53% (n = 148) used sedation protocols. Nordic nurses reported greater use of sedation (91% versus 67%, p < 0·01) and pain (91% versus 69%, p < 0·01) assessment tools than non‐Nordic nurses. Decision‐making on sedation was more inter‐professionally collaborative in Nordic ICUs (83% versus 61%, p < 0·01), units were smaller (10 versus 15 beds, p < 0·01) and nurse‐patient ratio was higher (1:1, 75% versus 26%, p < 0·01). Nordic nurses reported greater consistency in maintaining circadian rhythm (66% versus 49%, p < 0·01), less use of physical restraints (14% versus 36%, p < 0·01), less use of neuromuscular blocking agents (3% versus 16%, p < 0·01), and received more sedation education (92% versus 76%, p < 0·01). Delirium assessment was not performed systematically in most settings.

Conclusions

Organizational and contextual factors, such as ICU size, staffing ratio and inter‐professional collaboration, are contributing factors to sedation management in European ICUs. The Nordic context might be more germane to the goal of lighter sedation and better pain management.

Relevance to clinical practice

Our study raises awareness of current sedation practice, paving the way towards optimized ICU sedation management.
Sensitivity of plants to changing atmospheric CO2 concentration: from the geological past to the next century
Authors: Franks Peter J. , Adams Mark A. , Amthor Jeffrey S. , Barbour Margaret M. , Berry Joseph A. , Ellsworth David S. , Farquhar Graham D. , Ghannoum Oula , Lloyd Jon , McDowell Nate , Norby Richard J. , Tissue David T. , von Caemmerer Susanne
Published: January 2013

The rate of CO2 assimilation by plants is directly influenced by the concentration of CO2 in the atmosphere, ca. As an environmental variable, ca also has a unique global and historic significance. Although relatively stable and uniform in the short term, global ca has varied substantially on the timescale of thousands to millions of years, and currently is increasing at seemingly an unprecedented rate. This may exert profound impacts on both climate and plant function. Here we utilise extensive datasets and models to develop an integrated, multi‐scale assessment of the impact of changing ca on plant carbon dioxide uptake and water use. We find that, overall, the sensitivity of plants to rising or falling ca is qualitatively similar across all scales considered. It is characterised by an adaptive feedback response that tends to maintain 1 − ci/ca, the relative gradient for CO2 diffusion into the leaf, relatively constant. This is achieved through predictable adjustments to stomatal anatomy and chloroplast biochemistry. Importantly, the long‐term response to changing ca can be described by simple equations rooted in the formulation of more commonly studied short‐term responses.

Contents

Summary
1077

I.
Introduction
1078

II.
Atmospheric CO2 concentrations through time
1079

III.
Plant sensitivity to CO2 at geological timescales
1080

IV.
Plant sensitivity to CO2 over the last 200 yr
1081

V.
Increased water‐use efficiency?
1084

VI.
Simple formulation of stomatal conductance in land surface models for simulating long‐term CO2 response
1087

VII.
Conclusions
1088

Acknowledgements
1089

References
1089
Parental refusal of vaccination and transplantation listing decisions: A nationwide survey
Authors: Ladd Jennifer M. , Karkazis Katrina , Magnus David
Published: January 2013

Many professional societies and research studies recommend complete vaccination before pediatric solid organ transplantation. Nevertheless, incompletely vaccinated children often receive transplants. As the number of parents refusing to vaccinate children for nonmedical reasons increases, pediatric transplantation programs face difficult listing decisions. Given the importance of psychosocial criteria in listing decisions, this study explores how parental refusal of vaccination affects those listing decisions. Surveys were emailed to individuals at 195 pediatric solid organ transplantation programs in the United States, with a 71% response rate. Forty‐four respondents (39%) reported that their programs have had cases involving parental refusal of vaccination. In response to hypothetical scenarios, 93 respondents (82%) would list a child not vaccinated for medical reasons, whereas only 54 respondents (47%) would list a child whose parents refused vaccination. Only five respondents (4%) reported that their programs had written policies regarding parental refusal of vaccination. These data reveal inconsistencies across pediatric transplantation programs regarding how parental refusal of vaccination affects listing decisions and raise the issue of whether and how the reason for incomplete vaccination should be factored into listing decisions. We recommend further discussion and the development of written guidelines to unify programs' assessments of incompletely vaccinated pediatric transplantation candidates.
Occurrence of Potato virus Y strain PVYNTN in foundation seed potatoes in Japan, and screening for symptoms in Japanese potato cultivars
Authors: Chikh Ali M. , Karasev A. V. , Furutani N. , Taniguchi M. , Kano Y. , Sato M. , Natsuaki T. , Maoka T.
Published: January 2013

In 2008 and 2009 seasons, a sudden increase in Potato virus Y (PVY) incidence was recorded in foundation seed potatoes in Hokkaido, northern Japan. This increase was obvious during the field inspection and the postharvest indexing. Molecular typing revealed that besides the previously reported strains of PVYO and PVYNA‐N, the most common strain identified was the recombinant PVYNTN, with three characteristic recombinant junctions at the HC‐Pro, VPg and CP regions. No potato tuber necrotic ringspot disease (PTNRD) was observed in foundation seed potatoes in correlation with the presence of PVYNTN. Moreover, an isolate with a typical PVYNTN recombinant genome, namely Eu‐12Jp, did not induce PTNRD in 62 Japanese potato cultivars tested in both primarily and secondarily infected plants. Two cultivars carrying the extreme resistance gene Rychc were resistant to the infection with Eu‐12Jp, which presents potential sources of resistance to PVYNTN. Eu‐12Jp induced systemic mottle in potato cultivars Desiree and King Edward carrying resistance genes Ny and Nc, respectively, but induced a hypersensitive reaction in potato cultivar Maris Bard, with the Nz hypothetical resistance gene typical of the PVYZ strain group. Therefore, based on the genome structure and the reaction of the potato N resistance genes, Eu‐12Jp should be classified as PVYZ‐NTN, as described for isolates from Idaho, USA recently. This is the first report of PVYZ‐NTN in Japan and the sudden and increased occurrence of PVYNTN/PVYZ‐NTN represents a potential risk of PTNRD developing and increases the significance of PVY in Japan.
Improving attention control in dysphoria through cognitive training: Transfer effects on working memory capacity and filtering efficiency
Authors: Owens Max , Koster Ernst H. W. , Derakshan Nazanin
Published: January 2013

Impaired filtering of irrelevant information from working memory is thought to underlie reduced working memory capacity for relevant information in dysphoria. The current study investigated whether training‐related gains in working memory performance on the adaptive dual n‐back task could result in improved inhibitory function. Efficacy of training was monitored in a change detection paradigm allowing measurement of a sustained event‐related potential asymmetry sensitive to working memory capacity and the efficient filtering of irrelevant information. Dysphoric participants in the training group showed training‐related gains in working memory that were accompanied by gains in working memory capacity and filtering efficiency compared to an active control group. Results provide important initial evidence that behavioral performance and neural function in dysphoria can be improved by facilitating greater attentional control.
Impact of environmental parameters on coral reef development and drowning: Forward modelling of the last deglacial reefs from Tahiti (French Polynesia; IODP Expedition #310)
Authors: Seard Claire , Borgomano Jean , Granjeon Didier , Camoin Gilbert
Published: January 2013

The sedimentological and chronological analysis of the last deglacial reef sequences of Tahiti (French Polynesia), drilled during the Integrated Ocean Drilling Program Expedition 310, provide a high‐resolution data set allowing a well‐constrained forward modelling study. This study represents the first attempt to model in three dimensions the coral reef development of Tahiti during the last deglacial sea‐level rise (23 000 to 6000 cal yr bp) using the software dionisos developed by IFP Energies nouvelles. It allows the testing of the reconstructed last deglacial sea‐level curve and the different environmental parameters (for example, wave energy and sediment fluxes) that could have influenced the reef development. These last deglacial reef sequences form two prominent ridges occurring seaward of the living barrier reef that consist of successive submerged reefs. These reefs have been prone to drowning because the window of maximum carbonate production rate is inhibited by high water turbidity (sediment supply from a nearby river), shallow depth of wave action and substrate availability. These factors, combined with rapid sea‐level rise, have driven the growth of retrograding reef pinnacles. Local factors (substratum nature, sediment supply and wave energy) were the main processes that induced the drowning of the inner ridge, whereas interplay of local and global factors (acceleration of the sea‐level rise) was responsible for the drowning of the outer ridge. This particular acceleration of sea‐level rise of 16 m between 14·6 ka and 14 ka bp corresponds to meltwater pulse 1A.
Diabetes‐induced Changes in Mannan‐binding Lectin Levels and Complement Activation in a Mouse Model of Type 1 Diabetes
Authors: Østergaard J. A. , Bjerre M. , Dagnæs‐Hansen F. , Hansen T. K. , Thiel S. , Flyvbjerg A.
Published: January 2013

Circulating mannan‐binding lectin (MBL) levels are elevated in type 1 diabetes. Further, high MBL levels are associated with the development of diabetic nephropathy. In animals, a direct effect of MBL on diabetic kidney changes is observed. We hypothesized that MBL levels and detrimental complement activation increase as a consequence of diabetes. We measured plasma MBL before and 7 weeks after inducing diabetes by streptozotocin. Mice have two MBLs, MBL‐A and MBL‐C. Diabetes induction led to an increase in MBL‐C concentration, whereas no change during the study was found in the control group. The increase in MBL‐C was associated with the increasing plasma glucose levels. In accordance with the observed changes in circulating MBL levels, liver expression of Mbl2mRNA (encoding MBL‐C) was increased in diabetes. Mbl1expression (encoding MBL‐A) did not differ between diabetic and control animals. The estimated half‐life of recombinant human MBL was significantly prolonged in mice with diabetes compared with control mice. Complement activation in plasma and glomeruli did not differ between groups. We demonstrate for the first time that MBL levels increase after induction of diabetes and in parallel with increasing plasma glucose. Our findings support the previous clinical observations of increased MBL in type 1 diabetes. This change may be explained by alternations in both MBL production and turnover.
The Impact of Exercise on Suicide Risk: Examining Pathways through Depression, PTSD, and Sleep in an Inpatient Sample of Veterans
Authors: Davidson Collin L. , Babson Kimberly A. , Bonn‐Miller Marcel O. , Souter Tasha , Vannoy Steven
Published: January 2013

Suicide has a large public health impact. Although effective interventions exist, the many people at risk for suicide cannot access these interventions. Exercise interventions hold promise in terms of reducing suicide because of their ease of implementation. While exercise reduces depression, and reductions in depressive symptoms are linked to reduced suicidal ideation, no studies have directly linked exercise and suicide risk. The current study examined this association, including potential mediators (i.e., sleep disturbance, posttraumatic stress symptoms, and depression), in a sample of Veterans. SEM analyses revealed that exercise was directly and indirectly associated with suicide risk. Additionally, exercise was associated with fewer depressive symptoms and better sleep patterns, each of which was, in turn, related to lower suicide risk.
Impact of both metal composition and oxygen/nitrogen profiles on p-channel metal-oxide semiconductor transistor threshold voltage for gate last high-k metal gate
Authors: Hempel Klaus , Binder Robert , Engelmann H.-J. , Erben Elke , Metzger Joachim , Potapov Pavel , Prindle Christopher , Triyoso Dina H. , Wei Andy
Published: January 2013

As transistor size continues to shrink, SiO2/polySi has been replaced by high-k/metal gate (HKMG) to enable further scaling. Two different HKMG integration approaches have been implemented in high volume production: gate first and gate last—the latter is also known as replacement gate approach. In both integration schemes, getting the right threshold voltage (Vt) for NMOS and PMOS devices is critical. A number of recent studies have shown that Vt of devices is highly dependent on not just the as deposited material properties but also on subsequent processing steps. In this work, the authors developed an advanced high-resolution electron energy loss spectroscopy method capable of accurate measurement of material composition on device structures. Using this method, the nitrogen and oxygen concentration at the HKMG interface on p-channel field-effect transistor (PFET) transistors with slightly different metal gate stacks were studied. The authors demonstrated that the correct amount of nitrogen and oxygen at the HKMG interface is required to get the right PFET Vt.
TERT
Promoter Mutations in Familial and Sporadic Melanoma
Authors: Horn Susanne , Figl Adina , Rachakonda P. Sivaramakrishna , Fischer Christine , Sucker Antje , Gast Andreas , Kadel Stephanie , Moll Iris , Nagore Eduardo , Hemminki Kari , Schadendorf Dirk , Kumar Rajiv
Published: January 2013

Promoter Mutations and Cancer

Cancer genome sequencing projects have highlighted the pathogenic role of recurrent mutations within the protein-coding regions of genes. Now, two studies suggest that the scope of mutations in human tumors extends to gene regulatory regions. In a study of 70 melanomas,

Huang
et al.

(p.
957
, published online 24 January) found that 71% harbored one of two specific mutations in the promoter region of
TERT
, the gene coding for the catalytic subunit of telomerase, the enzyme that caps chromosome ends. Independently,

Horn
et al.

(p.
959
, published online 24 January) identified a disease-segregating germline mutation in the
TERT
promoter in a family predisposed to melanoma and found additional
TERT
promoter mutations in a high percentage of sporadic melanomas and melanoma cell lines. The mutations in both studies generated new binding sites for specific transcription factors and, in reporter assays, caused an increase in transcription.
Complete Genome Sequence of a Porcine Reproductive and Respiratory Syndrome Virus Variant with a New Deletion in the 5′ Untranslated Region
Authors: Shi Kaichuang , Tao Chun'ai , Lin Changhua , Li Gang , Li Jun
Published: January 2013

The GX1002 strain is a highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) characterized by a continuous 2-nucleotide deletion at positions 119 and 120 in the 5′ untranslated region. This differs from prevalent HP-PRRSVs in China, which have a deletion of only 1 nucleotide at position 119. Here we report the complete genome sequence of the GX1002 strain.
The value of history and goals of care with code status; even in an emergency setting
Authors: Irfan Affan , Hublikar Siddharth , Cho Jae Hyung , Hill John
Published: January 2013

This is a case report involving an elderlyJehovah's Witness woman with a history of chronic anaemia who suffers cardiac arrest and is resuscitated. This case illustrates, even in an emergency setting, (1) the value of obtaining relevant history, (2) addressing code status within the framework of achievable goals of care and (3) the need to revise both history and goals of care, as more information becomes available. We also propose aspects of this discussion that would benefit from future research.
Thrombolysis in submassive pulmonary embolism, prudent or puerile?
Authors: Rehman Aamer , Yousaf Shafaq , Chugh Atul
Published: January 2013

Pulmonary embolism (PE) remains one of the leading causes of cardiovascular mortality. The safety and efficacy of thrombolytic therapy using tissue-type plasminogen activator (tPA) for acute PE in clinical practice remain unclear. We describe a case of life-threatening submassive PE causing extreme refractory hypoxaemia, where thrombolysis was successfully administered. Current consensus suggests that patients with features of hemodynamic instability as a result of an acute PE, that is, massive PE, should receive thrombolysis. Patients, not in shock however, but with evidence of right-ventricular (RV) dysfunction echocardiographically, that is, submassive PE may also benefit. Serum troponin and brain-type natriuretic peptide have been suggested as biomarkers of RV injury that may identify a subset of submassive PE patients who may particularly benefit from thrombolytic therapy. The clinical response of this patient to thrombolysis is important, as it may identify a subgroup of patients with submassive PE who warrant this intervention.
Extrinsic colonic obstruction by congenital fibrous band in an infant
Authors: Catania Vincenzo Davide , Olivieri Claudio , Nanni Lorenzo , Pintus Claudio
Published: January 2013

The finding of a congenital fibrous band during laparotomy for intestinal obstruction is extremely rare. Preoperative diagnosis is challenging and no characteristic radiological findings have been described. We report the case of a premature baby in whom incomplete intestinal obstruction was due to a congenital band originating from the duodeno-jejunal flexure and extending across the ascending colon.
Orbital varix thrombosis: a rare cause of unilateral proptosis
Authors: Wade Ryckie George , Maddock Thomas B , Ananth Srinivasan
Published: January 2013

Orbital varices are thin walled, low flow, distensible veins which may rarely present with periorbital pain, proptosis or visual loss. Most orbital varices may be managed conservatively and only warrant surgery in the presence of recurrent thrombosis, disfiguring proptosis or acute visual loss. This report concerns an 84-year-old Caucasian woman who was admitted following a fall and noted to have isolated proptosis of the right eye, with vertical diplopia. All biochemical and haematological investigations were normal. A CT scan of the orbits demonstrated a serpiginous soft tissue mass within the superior portion of the right orbit, consistent with a thrombosed orbital varix. Conservative management was agreed with prism glasses and ophthalmological follow-up.
Unforeseen renal pathological findings in a patient with type 2 cardiorenal syndrome who died after 4 years of continuous ambulatory peritoneal dialysis
Authors: Matsui Masaru , Okayama Satoshi , Samejima Kenichi , Saito Yoshihiko
Published: January 2013

A man in his 30s with dilated cardiomyopathy was admitted to our hospital with heart failure exacerbation. Despite optimal medical treatment, his renal function progressively declined to end-stage renal failure. Type 2 cardiorenal syndrome (CRS) was diagnosed and continuous ambulatory peritoneal dialysis was started. He died of a brainstem infarction 4 years later. Postmortem renal pathology revealed no significant changes in the glomeruli except for shrinkage, normal arterioles and focal degeneration of the tubules with peritubular fibrosis. This suggests that renal replacement therapy can be withdrawn from some patients with type 2 CRS.
Denervation of the ear and the ‘folding flower’ illusion
Authors: Williams David Bruce
Published: January 2013

Following acute denervation of the ear, I experienced altered cutaneous sensory perception analogous to that reported by patients after limb amputation. This suggests that any sudden, complete loss of somaesthetic sensation can result in cortical reorganisation reflecting lost peripheral input. Although the short time course of the phenomenon suggests an initial functional reorganisation, it does not preclude longer time course structural alterations at multiple levels of the nervous system.
Understanding barriers to sexual health service access among substance-misusing women on the South East coast of England
Authors: Edelman Natalie Lois , Patel Harish , Glasper Anthony , Bogen-Johnston Leanne
Published: January 2013

Objectives

Evidence suggests substance-misusing women (SMW) experience disproportionate sexual health morbidity and poor uptake of interventions including contraception and cervical screening, yet there has been little investigation of sexual health service access issues for this population.

Methods

Twenty women with problem drug use in Hastings in South East England, UK participated in a one-to-one interview with a researcher to explore experiences and beliefs surrounding access to a range of sexual health service interventions. Transcripts were open-coded and themes were elicited and organised concerning barriers to access.

Results

Drug-use lifestyles, trauma and low self-worth framed the lives of SMW and hindered sexual health service access through: depleted practical and emotional resources to enable attendance; high perceived emotional cost of discussing sexual histories, and coping with tests and unfavourable results; and low anticipated value of sexual health interventions due to low perception and minimisation of risk and perceived incompatibility between drug use and sexual well-being.

Conclusions

A range of practical, social and emotional barriers to sexual health service access exist for this population, presenting a context from within which use of services may come at considerable personal cost to SMW. Interventions addressing anticipated stigma and emotional, hygiene and fiscal concerns are warranted for this population.
Theoretical investigation of the absorption spectra and singlet-triplet energy gap of positively charged tetraphenylporphyrins as potential photodynamic therapy photosensitizers
Authors: Mazzone Gloria , Russo Nino , Sicilia Emilia
Published: January 2013

DFT and TD-DFT calculations have been performed on a series of positively charged tetraphenylporphyrins with the aim to check whether these compounds can be used as photosensitizers in photodynamic therapy (PDT). Absorption spectra and singlet-triplet energy gaps have been computed by using the BP86, PBE0, and ωB97XD exchange-correlation functionals. Polarizable continuum model (PCM) has been used to take into account solvent effects. A careful analysis has been made on the Q-band, localized in the near-red visible region of the spectrum, since it plays a fundamental role in the drug design of new photodynamic therapy photosensitizers. Our results show that all the examined molecules have an adsorption band that falls in the so-called therapeutic window and possess a singlet-triplet energy gap able to promote the excitation of molecular oxygen from its ground triplet to the excited singlet state. The use of the ωB97XD exchange correlation functional, which accounts for dispersion interactions, allows calculating excitation energy values close to the experimental values.
QM/MM MD and free energy simulations of the methylation reactions catalyzed by protein arginine methyltransferase PRMT3
Authors: Chu Yuzhuo , Li Guohui , Guo Hong
Published: January 2013

Protein arginine N-methyltransferases (PRMTs) catalyze the transfer of methyl group(s) from S-adenosyl-l-methionine (AdoMet) to the guanidine group of arginine residue in abundant eukaryotic proteins. Two major types of PRMTs have been identified in mammalian cells. Type I PRMTs catalyze the formation of asymmetric ω-NG, NG-dimethylarginine (ADMA), while Type II PRMTs catalyze the formation of symmetric ω-NG, N′G-dimethylarginine (SDMA). The two different methylation products (ADMA or SDMA) of the substrate could lead to different biological consequences. Although PRMTs have been the subject of extensive experimental investigations, the origin of the product specificity remains unclear. In this study, quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) and free energy simulations are performed to study the reaction mechanism for one of Type I PRMTs, PRMT3, and to gain insights into the energetic origin of its product specificity (ADMA). Our simulations have identified some important interactions and proton transfers involving the active site residues. These interactions and proton transfers seem to be responsible, at least in part, in making the Nη2 atom of the substrate arginine the target of the both 1st and 2nd methylations, leading to the asymmetric dimethylation product. The simulations also suggest that the methyl transfer and proton transfer appear to be somehow concerted processes and that Glu326 is likely to function as the general base during the catalysis.
Effects of exercise on monocrotaline-induced changes in right heart function and pulmonary artery remodeling in rats
Authors: Colombo Rafael , Siqueira Rafaela , Becker Cristiano Urbano , Fernandes Tânia Gatelli , Pires Karla Maria , Valença Samuel Santos , Souza-Rabbo Maristela Padilha , Araujo Alex Sander , Belló-Klein Adriane
Published: January 2013

Pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) is an experimental protocol of right heart failure. We analyzed the role of exercise training on the right ventricle structure and function, pulmonary artery remodeling, and GSK-3β expression. Rats were divided among the following groups: sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), and trained monocrotaline (TM). Rats underwent exercise training for a period of 5 weeks, with 3 weeks post-MCT injection. Rats in the SM and TM groups presented with an increase in right ventricle hypertrophy indexes and lung congestion. The right ventricular end diastolic pressure (RVEDP), right ventricular systolic pressure (RVSP), and its minimum and maximal pressure derivates were increased in the SM and TM groups. The right ventricle interstitial volume pulmonary artery thickness and p-GSK-3β/GSK-3β were increased in the MCT groups as compared with the control groups. The TM group had a reduction in interstitial volume, p-GSK-3β/GSK-3β ratio, pulmonary artery thickness, RVEDP, and an increase in intramyocardial vessels volume as compared with the SM group. The overall results have shown that the exercise protocol used promoted positive changes in right ventricle and pulmonary artery remodeling. These observations also suggest that structural remodeling may be influenced by signaling proteins, such as GSK-3β.
INITIAL PUBLIC OFFERINGS AND PRE-IPO SHAREHOLDERS: ANGELS VERSUS VENTURE CAPITALISTS
Authors: JOHNSON WILLIAM C. , SOHL JEFFREY E.
Published: January 2013

At the time of an initial public offering, shares in a firm are typically held by venture capitalists, insiders, corporate investors and angel investors. We examine the role of angel investors in the IPO process. We find that angel investors provide equity capital in industries venture capitalists are less likely to serve and that shareholders in angel backed IPO firms are more likely to sell their shares at the time of the offering. Where venture capital backed IPO firms have higher underpricing, angel backed IPO firms do not, implying that angels may be the preferred investors for early-stage firms.
THE ROLE OF INFORMATION DISCLOSURE IN CLIMATE MITIGATION POLICY
Authors: COHEN MARK A. , VISCUSI W. KIP
Published: January 2013

Information disclosure policies represent an additional policy mechanism that can be used to foster reductions in greenhouse gas emissions. These informational efforts could be either mandatory or voluntary, but in each case government regulation could play a productive role by establishing common structures for the information and providing criteria to ensure the accuracy and credibility of the information. Unlike most previous uses of environmental information disclosure, such as the Toxic Release Inventory and pesticide warnings, carbon footprint labeling does not communicate information about immediate private benefits. While considerable insight can be gleaned by examining the principles for effective warnings generally, additional research would further our understanding of how to best design a successful information effort directed at varied future environmental benefits. Care is needed as green labeling may distort consumer decisions if undue prominence is given to environmental consequences as compared to other valued attributes, such as safety.
Diffusion of Ar in K-feldspar: Present and absent
Authors: Villa Igor M.
Published: January 2013

The mechanisms of Ar release from K-feldspar samples in laboratory experiments and during their geological history are assessed here. Modern petrology clearly established that the chemical and isotopic record of minerals is normally dominated by aqueous recrystallization. The laboratory critique is trickier, which explains why so many conflicting approaches have been able to survive long past their expiration date. Current models are evaluated for self-consistency, especially Arrhenian non-linearity which leads to paradoxes. The models’ testable geological predictions suggest that temperature-based downslope extrapolations often overestimate observed geological Ar mobility substantially. An updated interpretation is based on the unrelatedness of geological behaviour to laboratory experiments. The isotopic record of K-feldspar in geological samples is not a unique function of temperature, as recrystallization promoted by aqueous fluids is the predominant mechanism controlling isotope transport. K-feldspar should therefore be viewed as a hygrochronometer. Laboratory degassing proceeds from structural rearrangements and phase transitions such as are observed
in situ
at high temperature in Na and Pb feldspars. These effects violate the mathematics of an inert Fick's Law matrix and preclude downslope extrapolation. The similar upward-concave non-linear shapes of Arrhenius trajectories of many silicates, hydrous and anhydrous, are likely common manifestations of structural rearrangements in silicate structures.
Molecular Basis of Asbestos-Induced Lung Disease
Authors: Liu Gang , Cheresh Paul , Kamp David W.
Published: January 2013

Asbestos causes asbestosis and malignancies by molecular mechanisms that are not fully understood. The modes of action underlying asbestosis, lung cancer, and mesothelioma appear to differ depending on the fiber type, lung clearance, and genetics. After reviewing the key pathologic changes following asbestos exposure, we examine recently identified pathogenic pathways, with a focus on oxidative stress. Alveolar epithelial cell apoptosis, which is an important early event in asbestosis, is mediated by mitochondria- and p53-regulated death pathways and may be modulated by the endoplasmic reticulum. We review mitochondrial DNA (mtDNA)-damage and -repair mechanisms, focusing on 8-oxoguanine DNA glycosylase, as well as cross talk between reactive oxygen species production, mtDNA damage, p53, OGG1, and mitochondrial aconitase. These new insights into the molecular basis of asbestos-induced lung diseases may foster the development of novel therapeutic targets for managing degenerative diseases (e.g., asbestosis and idiopathic pulmonary fibrosis), tumors, and aging, for which effective management is lacking.
Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts
Authors: Chen Yishi , Chitapanarux Taned , Wu Jianfeng , Soon Russell K. , Melton Andrew C. , Yee Hal F.
Published: January 2013

Contraction of intestinal myofibroblasts (IMF) contributes to the development of strictures and fistulas seen in inflammatory bowel disease, but the mechanisms that regulate tension within these cells are poorly understood. In this study we investigated the role of nitric oxide (NO) signaling in C-type natriuretic peptide (CNP)-induced relaxation of IMF. We found that treatment with ODQ, a soluble guanylyl cyclase (sGC) inhibitor, or NG-nitro-l-arginine (l-NNA) or NG-monomethyl-l-arginine (l-NMMA), inhibitors of NO production, all impaired the relaxation of human and mouse IMF in response to CNP. ODQ, l-NNA, and l-NMMA also prevented CNP-induced elevations in cGMP concentrations, and l-NNA or l-NMMA blocked CNP-induced decreases in myosin light phosphorylation. IMF isolated from transgenic mice deficient in inducible nitric oxide synthase (iNOS) had reduced relaxation responses to CNP compared with IMF from control mice and were insensitive to the effects of ODQ, l-NNA, and l-NMMA on CNP treatment. Together these data indicate that stimulation of sGC though NO produced by iNOS activation is required for maximal CNP-induced relaxation in IMF.
Targeting IGF-IR with Ganitumab Inhibits Tumorigenesis and Increases Durability of Response to Androgen-Deprivation Therapy in VCaP Prostate Cancer Xenografts
Authors: Fahrenholtz Cale D. , Beltran Pedro J. , Burnstein Kerry L.
Published: January 2013

Prostate cancer is the most commonly diagnosed malignancy in men. While tumors initially respond to androgen-deprivation therapy, the standard care for advanced or metastatic disease, tumors eventually recur as castration-resistant prostate cancer (CRPC). Upregulation of the insulin-like growth factor receptor type I (IGF-IR) signaling axis drives growth and progression of prostate cancer by promoting proliferation, survival, and angiogenesis. Ganitumab (formerly AMG 479) is a fully human antibody that inhibits binding of IGF-I and IGF-II to IGF-IR. We evaluated the therapeutic value of ganitumab in several preclinical settings including androgen-dependent prostate cancer, CRPC, and in combination with androgen-deprivation therapy. Ganitumab inhibited IGF-I–induced phosphorylation of the downstream effector AKT and reduced proliferation of multiple androgen-dependent and castration-resistant human prostate cancer cell lines in vitro. Ganitumab inhibited androgen-dependent VCaP xenograft growth and increased tumor-doubling time from 2.3 ± 0.4 weeks to 6.4 ± 0.4 weeks. Ganitumab blocked growth of castration-resistant VCaP xenografts for over 11.5 weeks of treatment. In contrast, ganitumab did not have appreciable effects on the castration-resistant CWR-22Rv1 xenograft model. Ganitumab was most potent against VCaP xenografts when combined with complete androgen-deprivation therapy (castration). Tumor volume was reduced by 72% after 4 weeks of treatment and growth suppression was maintained over 16 weeks of treatment. These data suggest that judicious use of ganitumab particularly in conjunction with androgen-deprivation therapy may be beneficial in the treatment of prostate cancer. Mol Cancer Ther; 12(4); 394–404. ©2013 AACR.
Incidence and Prevalence of Multiple Sclerosis in the Americas: A Systematic Review
Authors: Evans Charity , Beland Sarah-Gabrielle , Kulaga Sophie , Wolfson Christina , Kingwell Elaine , Marriott James , Koch Marcus , Makhani Naila , Morrow Sarah , Fisk John , Dykeman Jonathan , Jetté Nathalie , Pringsheim Tamara , Marrie Ruth Ann
Published: January 2013

Background: The incidence and prevalence of multiple sclerosis (MS) varies considerably around the world. No previous study has performed a comprehensive review examining the incidence and prevalence of MS across the Americas. The purpose of this study was to systematically review and assess the quality of studies estimating the incidence and/or prevalence of MS in North, Central and South American regions. Methods: A comprehensive literature search was performed using MEDLINE and EMBASE from January 1985 to January 2011. Search terms included ‘multiple sclerosis’, ‘incidence’, ‘prevalence’ and ‘epidemiology’. Only full-text articles published in English or French were included. Study quality was assessed using an assessment tool based on recognized guidelines and designed specifically for this study. Results: A total of 3,925 studies were initially identified, with 31 meeting the inclusion criteria. The majority of studies examined North American regions (n = 25). Heterogeneity was high among all studies, even when stratified by country. Only half of the studies reported standardized rates, making comparisons difficult. Quality scores ranged from 3/8 to 8/8. Conclusion: This review highlights the gaps that still exist in the epidemiological knowledge of MS in the Americas, and the inconsistencies in methodologies and quality among the published studies. There is a need for future studies of MS prevalence and incidence to include uniform case definitions, employ comparable methods of ascertainment, report standardized results, and be performed on a national level. Other factors such as sex distribution, ethnic make-up and population lifestyle habits should also be considered.
Prevalence of Cerebral Palsy in Quebec: Alternative Approaches
Authors: Oskoui M. , Joseph L. , Dagenais L. , Shevell M.
Published: January 2013

Aim: To provide an estimate of the period prevalence of cerebral palsy (CP) in the province of Quebec. Methods: Children with CP were identified from three consecutive birth cohorts (1999–2001) from the Quebec CP Registry, covering 6 of the 17 administrative health regions of the province. Two inferential approaches were applied for period prevalence estimation, frequentist and bayesian. Results: 228 children were identified with CP. Using a frequentist approach, the overall prevalence of CP was 1.84 per 1,000 children aged 9–11 years living in those areas in 2010 (95% CI 1.60–2.08). Using a bayesian approach taking into account the uncertainty about the registry’s sensitivity in capturing all cases, the overall prevalence is higher at 2.30 per 1,000 children with a 95% CI (1.99–2.65). Conclusion: Using a bayesian approach to adjust for the registry’s known high specificity and lower sensitivity, the prevalence estimate is in concordance with worldwide estimates and estimates using administrative databases in western Canadian provinces. Future studies are needed to validate the diagnosis of CP within administrative databases and to evaluate possible regional trends across Canada in both prevalence and health service utilization, which may highlight disparities in healthcare delivery.
Diffusion Tensor Imaging Findings of Optic Radiation in Patients with Putaminal Hemorrhage
Authors: Seo Jeong Pyo , Choi Byung Yeon , Chang Chul Hoon , Jung Young Jin , Byun Woo Mok , Kim Seong Ho , Kwon Yong-Hyun , Jang Sung Ho
Published: January 2013

Objectives: Little is known about optic radiation (OR) injury in intracerebral hemorrhage (ICH). We attempted to investigate OR injury in patients with ICH by diffusion tensor imaging (DTI). Methods: Forty-three consecutive patients with putaminal hemorrhage and 40 normal healthy control subjects were recruited. DTI data were acquired at the beginning of rehabilitation (average 34 days after onset). DTI-Studio software was used to reconstruct the OR. Fractional anisotropies (FA) and fiber numbers of the ORs were measured. FA values and fiber numbers of affected ORs were described as abnormal when they were more than 2.5 SD lower than those of normal controls. Results: Thirty (70%) of the 43 patients showed an OR abnormality in the affected hemisphere. In 13 (30%) patients, the affected OR was disrupted or nonreconstructable. On the other hand, of the 20 patients with preserved OR integrity, 14 (33%) had a low FA value and 3 (7%) a low FA and fiber number. The other 13 (30%) of the 43 patients had no abnormal OR findings. Conclusion: Seventy percent of patients showed any abnormality of OR in the affected hemisphere on DTI. This result suggests that patients with putaminal hemorrhage are at high risk of OR injury.
Effects of Imidazoline and Non-Imidazoline α-Adrenergic Agents on Rabbit Platelet Aggregation
Authors: Yokota Shin-ichi , Hikasa Yoshiaki , Mizushima Hitomi
Published: January 2013

Background/Aims: Imidazoline α2-adrenergic agents exert complex effects on mammalian platelet aggregation. Although non-adrenergic, imidazoline (I) receptors have been revealed in human platelets, there is limited information about imidazoline’s action on platelet aggregation. This study aimed to investigate aggregatory and anti-aggregatory effects of various imidazoline or non-imidazoline α-adrenergic agents on rabbit platelets. Methods: Aggregatory responses of agents on rabbit platelets were examined by turbidimetric method. Radioligand binding assay to platelet I1 and I2 receptors was performed using [3H]-clonidine and [3H]-idazoxan, respectively. Results: Aggregation was not induced by α-adrenoceptor agonists alone. Adrenaline and noradrenaline produced dose-dependent potentiation of ADP- or collagen-induced aggregation. Imidazoline adrenoceptor agonists clonidine and p-aminoclonidine also potentiated ADP-induced platelet aggregation. The α2-adrenoceptor antagonists and/or certain imidazoline adrenergic agents inhibited adrenaline-potentiated aggregation in a dose-dependent manner, whereas α1-adrenoceptor antagonists and non-imidazoline α-adrenergic agents were either ineffective or less effective in inhibiting adrenaline-potentiated aggregation. Rabbit platelets did not have I1 receptors, but had I2 receptors, indicating that adrenaline-potentiated platelet aggregation was inhibited by idazoxan, but not by imidazoline compounds clonidine and oxymetazoline. Conclusions/Implications: These results demonstrated that α2-adrenoceptor-blocking agents and/or imidazoline α-adrenergic agents effectively inhibit adrenaline-potentiated platelet aggregation. It is proposed that imidazoline structure in part plays a role in the inhibition of adrenaline-potentiated aggregation.
Gene Polymorphisms of Interleukin-10 and Tumor Necrosis Factor-α Are Associated with Contrast-Induced Nephropathy
Authors: Chang Chao-Fu , Lu Tse-Min , Yang Wu-Chang , Lin Shing-Jong , Lin Chih-Ching , Chung Ming-Yi
Published: January 2013

Background/Aims: Contrast-induced nephropathy (CIN) is the third most common cause of hospital-acquired acute renal failure. However, the pathogenesis of CIN remains unclear. This study evaluated the role of anti-inflammatory cytokine interleukin-10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) gene polymorphisms as CIN susceptibility markers after percutaneous coronary intervention (PCI). Methods: Four IL-10 tag SNPs (rs1554286, rs3021094, rs3790622, rs1800896) and three TNF-α tag SNPs (rs1799964, rs1800630, rs1800629) were analyzed by MALDI-TOF mass spectrometry in 53 CIN patients and 455 control subjects. Serum IL-10 and TNF-α were detected using ELISA. Results: When compared to controls, the CIN patients showed increased frequencies of CC (rs1554286) and AG+GG (rs1800896) genotypes in IL-10 and GA+AA (rs1800629) genotype in TNF-α (OR = 2.24 (1.13–4.44), p = 0.018; OR = 2.61 (1.30–5.26), p = 0.005, and OR = 2.11 (1.08–4.09), p = 0.025, respectively). Baseline serum IL-10 levels in CIN patients were significantly lower (1.02 ± 1.14 vs. 2.78 ± 4.73 pg/ml, p = 0.008). Patients with CIN had a higher rate of decline in renal function than those without CIN (0.89 ± 1.67 vs. 0.30 ± 0.95 ml/min/1.73 m2 per month, p = 0.002). Significantly higher rates of decline in creatinine clearance were noted in patients with TNF-α (rs1800629) GA+AA than GG genotype (0.88 ± 1.83 vs. 0.36 ± 0.70, p = 0.03), and with IL-10 (rs1800896) AG+GG than AA genotype (1.28 ± 2.14 vs. 0.33 ± 0.90, p < 0.001). Conclusions: Gene polymorphisms of IL-10 and TNF-α are associated with CIN risk and long-term renal outcome after PCI. More prospective studies are needed to confirm our results.
Development of polymorphic microsatellite loci markers for the Asp viper (Vipera aspis) using high-throughput sequencing and their use for other European vipers
Authors: Geser Silvia , Kaiser Laura , Zwahlen Valérie , Ursenbacher Sylvain
Published: January 2013

The Asp viper (Vipera aspis) is a highly endangered species in the Swiss Plateau and in the Jura Mountains of Switzerland. In the past, numerous populations disappeared due to human activities, but currently the trend is reversed and several locations seem favourable for this species. However, it is not known if the remaining populations are still genetically variable and viable. In this study, 12 new microsatellite loci markers were developed for Vipera aspis using Next Generation Sequencing (NGS) techniques (454 sequencing). All markers proved to be polymorphic with 2-9 alleles. When cross-tested with two Eurasian widespread viper species, 8 of the newly developed loci provided reliable amplification for V. berus and 3 loci for V. ammodytes.
Feature Integration across Multimodal Perception and Action: A Review
Authors: Zmigrod Sharon , Hommel Bernhard
Published: January 2013

The human brain is facing a continuous stream of stimulus information delivered by multiple modalities and sensory channels and processed in distinct cortical regions. We discuss recent empirical and theoretical developments in addressing the question of how this distributed information is integrated into coherent representations (the so-called binding problem) with an emphasis on the principles and constraints underlying the integration of multiple (rather than redundant) features across different sensory modalities and across perception and action planning.