bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Odor Recognition: A Novel Behavioral Model for Cognitive Dysfunction in Parkinson’s Disease
Authors: Monaghan Michael M. , Leddy Lauren , Sung Mei-Li Amy , Albinson Kristin , Kubek Katie , Pangalos Menelas N. , Reinhart Peter H. , Zaleska Margaret M. , Comery Thomas A.
Published: March 2010

Background: Parkinson’s disease (PD) is a progressive neurodegenerative condition characterized by an increasing loss of dopaminergic neurons resulting in motor dysfunction. However, cognitive impairments in PD patients are a common clinical feature that has gained increased attention. Objective: The purpose of the current study was to evaluate the effects of an MPTP-induced dopaminergic lesion in mice on social odor recognition (SOR) memory. Methods: Mice were acutely treated with MPTP and evaluated for memory impairments in the SOR assay and characterized using biochemical and immunohistochemical methods approximately 2 weeks later. Results: Here we demonstrate that SOR memory is sensitive to MPTP treatment and that it correlates with multiple measures of nigrostriatal integrity. MPTP treatment of C57BL/6N mice produced a profound decrease in dopamine levels, dopamine transporter binding and tyrosine hydroxylase immunoreactivity in the striatum. These impairments in stratial dopaminergic function were blocked by pretreatment with the MAO-B inhibitor deprenyl. Changes in the dopaminergic system parallel those observed in SOR with MPTP treatment impairing recognition memory in the absence of a deficit in odor discrimination during learning. Deprenyl pretreatment blocked the MPTP-induced impairment of SOR memory. Conclusion: The use of the SOR memory model may provide a preclinical method for evaluating cognitive therapies for PD.
Cognitive Event-Related Potentials and Oscillations in the Subthalamic Nucleus
Authors: Rektor Ivan , Baláž Marek , Bočková Martina
Published: March 2010

Background: The cognitive role of the subthalamic nucleus (STN) remains largely unknown. Methods/Results: A modified protocol with a dual task elicited local field event-related potentials (ERPs) within the STN. No generators of ERPs were elicited by the standard oddball protocol in the STN (at variance with recordings from the putamen, caudate and pallidum). Repetitive transcranial magnetic stimulation (rTMS) over the right inferior frontal cortex caused a shortening of latencies of ERPs in standard and dual protocols. No changes were observable after the rTMS over the dorsolateral prefrontal cortex and sham stimulation. In the STN, only the tasks with an increased demand on executive functions produced the α-/β-event-related desynchronization/synchronization in visuomotor tasks with single letters writing. Conclusion: Our results indicate a specific, task-related involvement of the STN in the cognitive activities. Cognitive processing in the STN is possibly processed via hyperdirect cortico-STN pathway. Certain effects of deep brain stimulation surgery on cognitive performance could be explained by a direct effect on ‘cognitive’ parts of the STN.
Pharmacogenomic Protocols in CNS Disorders and Dementia
Authors: Cacabelos Ramón
Published: March 2010

The application of genomic procedures as diagnostic and therapeutic tools is a major challenge for the coming decades. Pharmacogenomic factors may account for 60–90% of drug variability in drug disposition and pharmacodynamics. About 25% of the 100 most prescribed drugs in the USA and the EU are psychotropic drugs, currently used in dementia. Approximately 60–80% of CNS drugs are metabolized via enzymes of the CYP gene superfamily; 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are major substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are major substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. About 57.76% of patients with Alzheimer’s disease are extensive metabolisers (EMs) for CYP2D6 enzymes, 31.06% are intermediate metabolisers (IMs), 5.28% are poor metabolisers (PMs), and 5.90% are ultrarapid metabolisers (UMs); 73.71% are CYP2C19-EMs, 25.12% IMs, and 1.16% PMs; 60.87% are CYP2C9-EMs, 34.16% IMs, and 4.97% PMs; 82.75% are CYP3A4/5-EMs, 15.88% IMs, and 1.37% UMs. A trigenic cluster integrating CYP2D6+CYP2C19+CYP2C9 polymorphic variants yields 82 different haplotype-like profiles, representing 36 different pharmacogenetic phenotypes in which only 26.51% of patients show a pure 3EM phenotype. These data clearly indicate that the incorporation of pharmacogenomic protocols to dementia research and clinical trials can foster therapeutics optimization by helping to develop cost-effective pharmaceuticals and improve drug efficacy and safety.
Pharmacokinetic Interaction between Indinavir and Darunavir with Low-Dose Ritonavir in Healthy Volunteers
Authors: Sekar Vanitha , Lefebvre Eric , De Marez Tine , De Pauw Martine , De Paepe Els , Vangeneugden Tony , Hoetelmans Richard M.W.
Published: March 2010

Objective: To investigate the potential for a pharmacokinetic interaction between darunavir (DRV, TMC114, Prezista®), indinavir (IDV, Crixivan®) and low-dose ritonavir (RTV, Norvir®). Methods: In three 7-day sessions, 17 HIV-negative healthy volunteers received treatment A (DRV/r 400/100 mg b.i.d.), treatment B (IDV/r 800/100 mg b.i.d.) and treatment C (DRV/r 400/100 mg b.i.d. + IDV 800 mg b.i.d.). On day 7, full pharmacokinetic profiles of DRV, IDV and RTV were determined. Safety and tolerability were also assessed. Results: Based on the least-squares means ratios, the steady-state exposure (area under the curve, AUC12h) and plasma concentrations (Cmin and Cmax) of IDV were increased by 23, 125 and 8%, respectively, when DRV was co-administered. The co-administration of IDV with DRV/r resulted in increases of 24, 44 and 11% for, respectively, DRV AUC12h, Cmin and Cmax, compared with administration of DRV/r alone. Eight volunteers discontinued due to an adverse event. Overall, adverse events and laboratory abnormalities were more commonly reported during treatments including IDV. Conclusions: When used in combination with DRV/r, dose adjustment of IDV from 800 mg b.i.d. to 600 mg b.i.d. may be warranted in cases of intolerance.
Extending Combination Therapy with Peginterferon plus Ribavirin for Genotype 2 Chronic Hepatitis C Virological Responders: A Pilot Study of 7 Cases
Authors: Akuta Norio , Suzuki Fumitaka , Arase Yasuji , Hirakawa Miharu , Kawamura Yusuke , Yatsuji Hiromi , Sezaki Hitomi , Suzuki Yoshiyuki , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Saitoh Satoshi , Ikeda Kenji , Kumada Hiromitsu
Published: March 2010

Objective: In treatment-resistant patients with genotype 2 chronic hepatitis C the suitable treatment duration is still unclear. The aims were to investigate extending combination therapy with peginterferon plus ribavirin for genotype 2. Methods: 7 patients infected with genotype 2 at a high viral load and who did not achieve a sustained virological response (SVR) with the first course of 24-week IFN plus ribavirin were recruited into the study protocol with a total of 48 weeks of peginterferon plus ribavirin therapy. Results: SVR was achieved in 5 of 7 patients (71%). All 4 patients (100%) who were in relapse with the first course achieved SVR. Only 1 of 3 patients (33%) who had a non-virological response (NVR) with the first course achieved SVR. All 4 patients who had an early virological response (EVR) with the first course achieved EVR and SVR. Two of 3 patients who had no EVR with the first course also did not achieve EVR and SVR. One patient who had no EVR or a NVR during the first course achieved EVR and SVR with the second course. Conclusions: Our results suggest that extending combination therapy for genotype 2 chronic hepatitis C might be useful for patients who relapse following 24-week combination therapy.
Pharmacokinetics and Bioavailability of Moxifloxacin in Calves following Different Routes of Administrations
Authors: Goudah A. , Hasabelnaby S.
Published: March 2010

Background: Moxifloxacin is a new fourth-generation 8-methoxy fluoroquinolone developed primarily for the treatment of community-acquired pneumonia and upper respiratory tract infections. The aim of the study was to investigate the plasma pharmacokinetics characteristic of moxifloxacin in calves, after intravenous, intramuscular and subcutaneous administration of a single dose. Meanwhile, plasma protein binding and bioavailability of moxifloxacin were also estimated. Methods: Plasma concentrations of moxifloxacin were measured using a modified HPLC method, and the extent of plasma protein binding was determined in vitro using ultrafiltration. Results: Following intravenous administration, the half life of elimination, the volume of distribution at steady state and the area under the curve were 3.29 h, 0.94 l/kg and 24.72 µg·h/ml, respectively. After intramuscular and subcutaneous administration of moxifloxacin at the same dose, the peak plasma concentrations were 2.41 and 2.20 µg/ml and were obtained at 1.54 and 1.59 h, respectively. The systemic bioavailabilities were 87.19 and 75.94%, respectively. The in vitro plasma protein binding of moxifloxacin in plasma of calves was 27%. Conclusion: A high peak plasma concentration, area under the curve, rapid absorption and bioavailability following intramuscular and subcutaneous administration characterize the pharmacokinetics of moxifloxacin in calves.
Weekly Intravenous and Intraperitoneal Paclitaxel Combined with S-1 for Malignant Ascites due to Advanced Gastric Cancer
Authors: Kitayama Joji , Ishigami Hironori , Kaisaki Shoichi , Hidemura Akio , Kato Masahiro , Otani Kensuke , Kamei Takao , Soma Daisuke , Miyato Hideyo , Yamashita Hiroharu , Nagawa Hirokazu
Published: March 2010

Malignant ascites caused by gastric cancer are chemotherapy resistant and carry a poor prognosis. The efficacy of a regimen including intraperitoneal paclitaxel (PTX) was evaluated in 33 gastric cancer patients with ascetic fluid in the peritoneal cavity diagnosed with computed tomography (CT) scanning. Synchronous administration of intravenous (50 mg/m2) and intraperitoneal (20 mg/m2) PTX was performed via a subcutaneously placed intraperitoneal catheter on days 1 and 8, and S-1 was administered twice daily at 80 mg/m2/day for 14 consecutive days from day 1 to day 14, followed by 7 days of rest. The ascitic fluid volume was calculated with NIH Image J software using continuous CT images. After 2–4 treatment cycles, 23 (70%) patients showed reductions in their ascitic volumes of >50%. Ascites disappeared completely in 8 patients and were markedly reduced (to <3% of the original volume) in 4 of the 9 patients (44%) who initially had massive (>2,500 ml) ascites. Median overall survival was significantly better in patients with ascitic reduction. Weekly intravenous and intraperitoneal PTX combined with S-1 was highly effective in gastric cancer with malignant ascites. The change in ascitic fluid volumes determined by CT image measurements is a useful predictor of outcome in these patients.
Drug-Eluting Stents in Bifurcations
Authors: Guérin Patrice , Pilet Paul , Finet Gérard , Gouëffic Yann , N'Guyen Jean Michel , Crochet Dominique , Tijou Isabelle , Pacaud Pierre , Loirand Gervaise
Published: March 2010

Background—

The use of a drug-eluting stent (DES) has strongly limited the incidence of in-stent restenosis in bifurcation lesions; nevertheless, restenosis still remains a problem at the origin of the bifurcation side branch. The aim of this study is to analyze the consequences of the kissing postdilatation technique on 5 DESs, using microfocus x-ray computerized tomography and scanning electron microscopy.

Methods and Results—

Five different DESs (Cypher, Cypher Select, Endeavor, Taxus Express, and Taxus Liberté) were deployed using kissing postdilatation protocols in a bench-top model. For all types of DES, microfocus x-ray computerized tomography analysis showed that (1) kissing postdilatation of the stent by 2 coaxial balloons caused elliptic deformation in the proximal segment and (2) kissing postdilatation technique reduced the ratio of potential metal to artery (manufacturer’s data/calculated ratio [%]: Cypher, 12.7/8.8; Cypher Select, 13.5/10.2; Endeavor, 19.0/13.3; Taxus Express, 20.5/4.7; Taxus Liberté, 17.9/12.5) and the potential drug application to area in the proximal segment, including the ostial struts (struts adjacent to and lying around the side branch ostium) (manufacturer’s data/calculated drug application [μg/mm
2
]: Cypher, 1.4/1.0; Cypher Select, 1.4/1.1; Endeavor, 1.6/1.1; Taxus Express, 1.0/0.7; Taxus Liberté, 1.0/0.7). Scanning electron microscopy analysis showed a significantly greater coating damage to the ostial struts in all stents evaluated (
P
<0.05).

Conclusions—

Commercially available DESs subjected to simultaneous kissing balloon postdilatation in an unconstrained model may contribute to side branch ostial restenosis by proximal segment elliptic deformation and damage to the polymer coating.
Underutilization of β-Blockers in Patients Undergoing Implantable Cardioverter-Defibrillator and Cardiac Resynchronization Procedures
Authors: Hauptman Paul J. , Swindle Jason P. , Masoudi Frederick A. , Burroughs Thomas E.
Published: March 2010

Background—

Current guidelines emphasize the need for optimal medical therapy before implantation of cardiac devices (implantable cardioverter-defibrillator, cardiac resynchronization therapy). Our objective was to evaluate use of β-blockers (BB) among patients with heart failure undergoing a cardiac device procedure.

Methods and Results—

We used a large, multistate, managed-care database (January 2003 to December 2006) to identify adults admitted with an
International Classification of Diseases, Ninth Revision
(ICD-9) procedure code for cardiac device, continuous enrollment for 180 days before and 180 days after device procedure, and a primary or secondary ICD-9 diagnosis code for heart failure during that period. Our primary measures were use of BB before device procedure and changes after discharge. A total of 2766 beneficiaries (78.8% men; median age, 61 years) underwent a device procedure for primary prevention. The median number of days on BB therapy in the 90 days before device procedure was 46. Beneficiaries who did not have a pharmacy fill for BB during that time (n=925, 33.4%) were more elderly and had fewer antecedent outpatient visits with a cardiologist. There was a shift toward greater use of BB after device procedure; 83.4% had at least 1 pharmacy fill for a BB during follow-up.

Conclusions—

BB are underused before and after cardiac device procedures. There is a modest increase in use after the procedure. Strategies are required to ensure that patients are on optimal medical therapy before device therapy is selected.
Greek “Variant Literary Editions” to the Hebrew Bible?
Authors: Debel Hans
Published: March 2010

The full publication of the scrolls from the Judaean Desert has given impetus to reflections on the history and development of the biblical text during the period of Second Temple Judaism. This study critically reviews the major contributions to the debate and finally makes a plea to extent Ulrich’s hermeneutical model to some Septuagint texts that are usually not included among his “variant literary editions.” Its major arguments in this regard are that these texts witness to the same dynamic process of the organic development of Scripture, and that relegating them to the interpretational tradition merely because they are not written in Hebrew reveals an unwarranted bias towards the Masoretic Text.
Tropical–Extratropical Interactions over Southern Africa: Three Cases of Heavy Summer Season Rainfall
Authors: Hart N. C. G. , Reason C. J. C. , Fauchereau N.
Published: March 2010

The synoptic evolution of three tropical–extratropical (TE) interactions, each responsible for extreme rainfall events over southern Africa, is discussed in detail. Along with the consideration of previously studied events, common features of these heavy rainfall producing tropical temperate troughs (TTTs) over southern Africa are discussed. It is found that 2 days prior to an event, northeasterly moisture transports across Botswana, set up by the Angola low, are diverted farther south into the semiarid region of subtropical southern Africa. The TTTs reach full maturity as a TE cloud band, rooted in the central subcontinent, which is triggered by upper-level divergence along the leading edge of an upper-tropospheric westerly wave trough. Convection and rainfall within the cloud band is supported by poleward moisture transports with subtropical air rising as it leaves the continent and joins the midlatitude westerly flow. It is shown that these systems fit within a theoretical framework describing similar TE interactions found globally.

Uplift forcing for the extreme rainfall of each event is investigated. Unsurprisingly, quasigeostrophic uplift is found to dominate in the midlatitudes with convective processes strongest in the subtropics. Rainfall in the semiarid interior of South Africa appears to be a result of quasigeostrophically triggered convection.

Investigation of TTT formation in the context of planetary waves shows that early development is sometimes associated with previous anticyclonic wave breaking south of the subcontinent, with full maturity of TTTs occurring as a potential vorticity trough approaches the continent from the west. Sensitivity to upstream wave perturbations and effects on anticyclonic wave breaking in the South Indian Ocean are also observed.
On the Orthogonalization of Bred Vectors
Authors: Keller Jan D. , Hense Andreas , Kornblueh Luis , Rhodin Andreas
Published: March 2010

The key to the improvement of the quality of ensemble forecasts assessing the inherent flow uncertainties is the choice of the initial ensemble perturbations. To generate such perturbations, the breeding of growing modes approach has been used for the past two decades. Here, the fastest-growing error modes of the initial model state are estimated. However, the resulting bred vectors (BVs) mainly point in the phase space direction of the leading Lyapunov vector and therefore favor one direction of growing errors. To overcome this characteristic and obtain growing modes pointing to Lyapunov vectors different from the leading one, an orthogonalization implemented as a singular value decomposition based on the similarity between the BVs is applied. This transformation is similar to that used in the ensemble transform technique currently in operational use at NCEP but with certain differences in the metric used and in the implementation. In this study, results of this approach using BVs generated in the Ensemble Forecasting System (EFS) based on the global numerical weather prediction model GME of the German Meteorological Service are presented. The gain in forecast performance achieved with the orthogonalized BV initialization is shown by using different probabilistic forecast scores evaluating ensemble reliability, variance, and resolution. For a 3-month period in summer 2007, the results are compared to forecasts generated with simple BV initializations of the same ensemble prediction system as well as operational ensemble forecasts from ECMWF and NCEP. The orthogonalization vastly improves the GME–EFS scores and makes them competitive with the two other centers.
Delays and User Performance in Human-Computer-Network Interaction Tasks
Authors: Caldwell Barrett S. , Wang Enlie
Published: March 2010

Objective: This article describes a series of studies conducted to examine factors affecting user perceptions, responses, and tolerance for network-based computer delays affecting distributed human-computer-network interaction (HCNI) tasks. Background: HCNI tasks, even with increasing computing and network bandwidth capabilities, are still affected by human perceptions of delay and appropriate waiting times for information flow latencies. Method: Conducted were 6 laboratory studies with university participants in China (Preliminary Experiments 1 through 3) and the United States (Experiments 4 through 6) to examine users’ perceptions of elapsed time, effect of perceived network task performance partners on delay tolerance, and expectations of appropriate delays based on task, situation, and network conditions. Results: Results across the six experiments indicate that users’ delay tolerance and estimated delay were affected by multiple task and expectation factors, including task complexity and importance, situation urgency and time availability, file size, and network bandwidth capacity. Results also suggest a range of user strategies for incorporating delay tolerance in task planning and performance. Conclusion: HCNI user experience is influenced by combinations of task requirements, constraints, and understandings of system performance; tolerance is a nonlinear function of time constraint ratios or decay. Application: Appropriate user interface tools providing delay feedback information can help modify user expectations and delay tolerance. These tools are especially valuable when delay conditions exceed a few seconds or when task constraints and system demands are high. Interface designs for HCNI tasks should consider assistant-style presentations of delay feedback, information freshness, and network characteristics. Assistants should also gather awareness of user time constraints.
Modeling of Hybrid Composite Foams
Authors: Desai Amit A. , Nutt Steven R. , Alonso María Virginia
Published: March 2010

An analysis of variance was applied to model the mechanical properties of hybrid foams. The controlled variable used in the study was the fiber weight fraction of glass and aramid fibers, and all foam samples were of similar density (∼250 kg/m3). The responses analyzed were elastic modulus and strength for compressive and shear loading. The microstructure of the hybrid foam samples was examined and the effects of fiber type on the cell geometry and distribution were studied. The results showed that each fiber type in hybrid foam had significant effects on the compression and shear properties and the fiber weight fraction affected the isotropy of the properties. The utilization of a statistical model for predicting hybrid composite foam properties is an appropriate tool that affords a global perspective of the influence of process variables on foam properties.
Decision Making and Aggression in Forensic Psychiatric Inpatients
Authors: Bass Stephanie L.S. , Nussbaum David
Published: March 2010

This study provides initial empirical support for a novel neurobiological decision-making model proposed by Nussbaum (2005), applied to an aggression typology (Nussbaum, Saint-Cyr, & Bell, 1997). The Iowa Gambling Task (IGT; Bechara, Damasio, Damasio, & Anderson, 1994) was analyzed for forensic inpatients using both the traditional method of scoring reflecting motivational decision making and a novel method developed by Yechiam, Busemeyer, Stout, and Bechara (2005) that provides scores for three cognitive decision-making components: attention, learning, and response-choice consistency. Predatory seclusions were predicted by traditional motivational scoring of the IGT but not by the cognitive scores. Conversely, Irritable seclusions were predicted only by the cognitive scoring system. Based on these findings, the utilization of the aggression typology and the inclusion of these clinical measures could enhance and refine violent risk assessment, suggest specific treatment targets for different aggression types, and monitor responses to interventions prior to release into the community.
Hemiatrophy of the Spinal Cord in a Patient With Mucopolysaccharidosis Type IIIB
Authors: Samia Pauline , Wieselthaler Nicky , van der Watt George F. , Wilmshurst Jo M.
Published: March 2010

The authors describe a girl with mucopolysaccharidosis type IIIB (Sanfilippo disease). She presented with speech delay, macrocephaly, and left lower limb hypoatrophy. Her brain and spinal cord imaging revealed diffuse cystic brain lesions and hemiatrophy of her spinal cord on the left (thoracic levels 11/12). She had marked reduction of her α-N-acetylglucosaminidase activity assay consistent with the diagnosis of mucopolysaccharidosis type IIIB. Mutational analysis showed 2 mutations on exon 6 of the α-N-acetylglucosaminidase gene, both of which were identified in her parents. At 10 years of age the girl had minor learning difficulties and mild behavioral problems. Her spinal cord hemiatrophy, in association with mucopolysaccharidosis type III, has not previously been described in the literature.
Study of Aromatic Polyimides Containing Cyano Groups
Authors: Bacosca Irina , Hamciuc Elena , Bruma Maria , Ronova Inga A.
Published: March 2010

Aromatic polyimides containing cyano groups have been synthesized by solution polycondensation reaction of an aromatic diamine having cyano and ether groups, with various aromatic dianhydrides containing flexible groups such as carbonyl and hexafluoroisopropylidene. The properties of these polyimides were compared with those of related polymers based on rigid aromatic dianhydrides, such as biphenyltetracarboxylic and pyromellitic dianhydride, and the same cyano containing diamine. The polymers were easily soluble in polar organic solvents, such as N-methylpyrrolidinone, N, N-dimethylacetamide and N, N-dimethylformamide and exhibited remarkable film forming ability, except for polyimide derived from pyromellitic dianhydride. They showed high thermal stability, with initial decomposition temperature being above 400 °C and glass transition temperature in the range of 210—260 °C. Conformational rigidity parameters of these polymers have been calculated by Monte Carlo method with allowance for hindered rotation. Several physical properties such as solubility and glass transition temperature are discussed in relation to the structure of the polymers and rigidity of their chains. The calculation of parameters of conformational rigidity showed that the glass transition temperature values (220—230 °C) increase with the increase of the rigidity. The polymers based on pyromellitic dianhydride form a separate group having the glass transition temperature values above 250 °C.
Phosphorus-containing Polysulfones - A Comparative Study
Authors: Hoffmann Thorsten , Pospiech Doris , Häußler Liane , Sahre Karin , Komber Hartmut , Harnisch Christina , Auf Der Landwehr Maria , Schäfer Alexander , Döring Manfred
Published: March 2010

A comparative study of the influence of 2-(10-oxo-10H-9-oxa-10 λ5-phosphaphenanthrene10-yl)-benzene-1,4-diol (DOPO-HQ) and 2-(2,8-dimethyl-10-oxo-10H-10 λ5-phenoxaphosphine-10-yl)benzene-1,4-diol (DPPO-HQ) on their ability to form polysulfones (PSU) with 4,4′ -difluorodiphenylsulfone (DFDPS) as well as the properties of the aromatic phosphorus-containing polysulfones (P-PSU) is reported. These properties are also compared to bisphenol A-based polysulfone. Both diols have the phosphorus unit as substituent and differ in the number of oxygen atoms within the environment of the phosphorus changing from DOPO-HQ (phosphinate structure, Ar2 OP(=O)) to DPPO-HQ (phosphine oxide structure, Ar3PO). The nucleophilic aromatic polycondensation was carried out successfully using both phosphorus-containing aromatic diols instead of bisphenol A and was followed by ATR-FTIR in-line monitoring. The use of DPPO-HQ decreased the number of side reactions and enhanced slightly the molecular weight. The thermal stability of DPPO-HQ-based PSU is slightly better than DOPO-HQ-based PSU. Thermal decomposition schemes for PSU and for both P-PSUs are proposed based on thermogravimetric analysis and Pyrolysis GC-MS results.
Quantitative analysis of climate versus human impact on sediment yield since the Lateglacial: The Sarliève palaeolake catchment (France)
Authors: Macaire Jean-Jacques , Fourmont Agathe , Argant Jacqueline , Bréhéret Jean-Gabriel , Hinschberger Florent , Trément Frédéric
Published: March 2010

Minimum rates of solid (SSY) and dissolved (DSY) sediment yield (SY) were evaluated in t/km 2 per yr from sediments stored in the Sarliève palaeolake (French Massif Central) for seven phases of the Lateglacial and Holocene up to the seventeenth century. The catchment (29 km2), mainly formed of limestones and marls, is located in an area rich in archaeological sites in the Massif Central. The respective impacts of human activities and climate on SY were compared by quantification of human settlements through archaeological survey and palynological data. During the Lateglacial and early Holocene up to about 7500 yr cal. BP, variations in SSY and DSY rates were mainly related to climate change with higher rates during colder periods (Younger Dryas and Preboreal) and lower rates during warmer periods (Bölling-Alleröd and Boreal). However, CF1 tephra fallout induced a sharp increase in SY during the Alleröd. During the middle and late Holocene after 7500 yr cal. BP, SSY and DSY greatly increased (by factors of 6.5 and 2.8, respectively), particularly during the Final Neolithic at about 5300 yr cal. BP when the climate became cooler and more humid. After this date, at least 75% of the SSY increase and more than 90% of the DSY increase resulted from human activities, but SSY rates showed little variation during Protohistoric and Historic Times up to the seventeenth century. SSY and DSY rates and DSY/SSY ratio indicate that catchment soils began to form during the Lateglacial and Preboreal, thickened considerably during the Boreal and Atlantic, finally thinning (rejuvenation) mainly as the result of human-induced erosion during the sub-Boreal and sub-Atlantic. Increased mechanical erosion during the late Holocene also induced an increase in chemical erosion.
Nausea and Vomiting in Advanced Cancer
Authors: Sik Kim Ang  , Shoemaker Laura K. , Davis Mellar P.
Published: March 2010

Nausea and vomiting are relatively common in advanced cancer and is dreaded more than pain by patients. The history, pattern of nausea and vomiting, associated symptoms, and physical examination provides clues as to etiology and may guide therapy. Continuous severe nausea unrelieved by vomiting is usually caused by medications or metabolic abnormalities, while nausea relieved by vomiting or induced by eating is usually due to gastroparesis, gastric outlet obstruction, or small bowel obstruction. Drug choices are empiric or based on etiology. Metoclopramide has the greatest evidence for efficacy followed by phenothiazines and tropisetron. Corticosteroids have not been effective in randomized trials except in the case of bowel obstruction. Treatment of nausea unresponsive to first-line medications involves rotation to medications which bind to multiple receptors (broad-spectrum antiemetics), the addition of another antiemetic to a narrow-spectrum antiemetic (a serotonin receptor antagonist such as tropisetron to a phenothiazine), rotation to a different class of antiemetic (tropisetron for a phenothiazine), or in-class drug rotation. Venting gastrostomy, octreotide, and corticosteroids will reduce nausea and vomiting associated with malignant bowel obstruction.
The Relationships Between Time Usage During Instrumental Lessons and Preservice Teachers’ Self-Evaluations
Authors: Dorfman Jay
Published: March 2010

The purpose of this study was to investigate the relationships between proportions of time spent on particular pedagogical behaviors and preservice teachers’ perceptions of their own teaching, as measured by reflective self-evaluations. Preservice teachers ( N = 9) taught and video recorded small-group instrumental music lessons and completed a reflective self-evaluation form while watching the video.The video footage was coded for time spent on physical space setup, talk, modeling, and student performance. Correlation statistics indicated relationships between several components of the reflection form and time spent on various activities during the lesson. Possible reasons for these correlations are examined, and suggestions are provided for modification of the undergraduate methods curricula based on the findings.
Venture Capital and Underserved Communities
Authors: Sass Rubin Julia
Published: March 2010

Access to equity capital is critical for the growth of businesses, especially for young companies, which lack the cash flows necessary to repay loans. To meet this need, a thriving venture capital industry has evolved, fostering job creation, economic growth, and innovation in the United States. Not all companies, however, have been equally able to access such investments. Firms owned by women and people of color and those located in rural and distressed urban regions of the country have been underserved by the venture capital industry. This note analyzes the factors responsible for this and proposes policies designed to ensure a more equitable economic landscape.
Visceral Adiposity, Insulin Resistance, and Type 2 Diabetes
Authors: Griffith Michelle L. , Younk Lisa M. , Davis Stephen N.
Published: March 2010

The worldwide prevalence of obesity and obesity-related diseases continues to rise. Insulin resistance, the metabolic syndrome, and type 2 diabetes are all associated with obesity. Visceral fat is now recognized to have metabolic, endocrine, and immune functions; increased visceral adiposity enhances the risk of metabolic and cardiovascular disorders. Potential mechanisms of this increased risk may include increased free fatty acid release and alterations in adipokines. Lifestyle interventions resulting in weight loss and loss of visceral fat can have a significant impact on cardiometabolic risk. Bariatric surgery has also been shown to improve insulin resistance, type 2 diabetes, and other comorbidities of obesity. Several medical therapies for type 2 diabetes or obesity also show promise for an impact on visceral adiposity-related comorbidities.
Enhancing Childhood Obesity Treatment
Authors: Panzer Barry M.
Published: March 2010

Despite numerous and varied programs to treat childhood obesity, there is only limited progress in reducing the prevalence of this disorder. The epidemic, first labeled more than a decade ago, persists. This article suggests that part of the lack of success is due to the failure to recognize the variety of obesity profiles, as well as practitioner adherence to an ineffective treatment paradigm. Clinicians should consider family-based behavior modification combined with diet and exercise to be a primary intervention and develop treatment strategies to match obesity subgroups.
Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity
Authors: Liu Xiangdong , Shin Niu , Koblish Holly K. , Yang Gengjie , Wang Qian , Wang Kathy , Leffet Lynn , Hansbury Michael J. , Thomas Beth , Rupar Mark , Waeltz Paul , Bowman Kevin J. , Polam Padmaja , Sparks Richard B. , Yue Eddy W. , Li Yanlong , Wynn Richard , Fridman Jordan S. , Burn Timothy C. , Combs Andrew P. , Newton Robert C. , Scherle Peggy A.
Published: March 2010

Indoleamine 2,3-dioxygenase-1 (IDO1; IDO) mediates oxidative cleavage of tryptophan, an amino acid essential for cell proliferation and survival. IDO1 inhibition is proposed to have therapeutic potential in immunodeficiency-associated abnormalities, including cancer. Here, we describe INCB024360, a novel IDO1 inhibitor, and investigate its roles in regulating various immune cells and therapeutic potential as an anticancer agent. In cellular assays, INCB024360 selectively inhibits human IDO1 with IC50 values of approximately 10nM, demonstrating little activity against other related enzymes such as IDO2 or tryptophan 2,3-dioxygenase (TDO). In coculture systems of human allogeneic lymphocytes with dendritic cells (DCs) or tumor cells, INCB024360 inhibition of IDO1 promotes T and natural killer (NK)–cell growth, increases IFN-γ production, and reduces conversion to regulatory T (Treg)–like cells. IDO1 induction triggers DC apoptosis, whereas INCB024360 reverses this and increases the number of CD86high DCs, potentially representing a novel mechanism by which IDO1 inhibition activates T cells. Furthermore, IDO1 regulation differs in DCs versus tumor cells. Consistent with its effects in vitro, administration of INCB024360 to tumor-bearing mice significantly inhibits tumor growth in a lymphocyte-dependent manner. Analysis of plasma kynurenine/tryptophan levels in patients with cancer affirms that the IDO pathway is activated in multiple tumor types. Collectively, the data suggest that selective inhibition of IDO1 may represent an attractive cancer therapeutic strategy via up-regulation of cellular immunity.
MyD88-dependent TLR4 signaling is selectively impaired in alveolar macrophages from asymptomatic HIV+ persons
Authors: Tachado Souvenir D. , Li Xin , Bole Medhavi , Swan Katharine , Anandaiah Asha , Patel Naimish R. , Koziel Henry
Published: March 2010

Alveolar macrophages (AMs) are the predominant effector cell in the lungs and contribute to a critical first line of defense against bacterial pathogens through recognition by pattern recognition receptors such as Toll-like receptor 4 (TLR4). TLR4-mediated tumor necrosis factor α (TNFα) release is significantly impaired in HIV+ macrophages, but whether HIV impairs myeloid differentiation factor 88 (MyD88)–dependent and/or MyD-independent TLR4 signaling pathways in human macrophages is not known. Comparing human U937 macrophages with HIV+ U1 macrophages (HIV-infected U937 subclone), the current study shows that HIV infection is associated with impaired macrophage TLR4-mediated signaling, specifically targeting the MyD88-dependent TLR4-mediated signaling pathway (reduced MyD88–interleukin-1 receptor–associated kinase [IRAK] interaction, IRAK phosphorylation, nuclear factor [NF]–κB nuclear translocation, and TNFα release) while preserving the MyD88-independent TLR4-mediated signaling pathway (preserved STAT1 phosphorylation, interferon regulatory factor [IRF] nuclear translocation, and interleukin-10 [IL-10] and RANTES release). Extracellular TLR4 signaling complex was intact (similar levels of CD14 and MD2), and similar patterns of response were observed in clinically relevant AMs from healthy and asymptomatic HIV+ persons at high clinical risk of pneumonia. Taken together, these data support the concept that chronic HIV infection is associated with specific and targeted disruption of critical macrophage TLR4 signaling, which in turn may contribute to disease pathogenesis of bacterial pneumonia.
Development of O-antigen gene cluster-specific PCRs for rapid typing six epidemic serogroups of Leptospira in China
Authors: Cai Cheng-Song , Zhu Yong-Zhang , Zhong Yi , Xin Xiao-Fang , Jiang Xiu-Gao , Lou Xiao-Li , He Ping , Qin Jin-Hong , Zhao Guo-Ping , Wang Sheng-Yue , Guo Xiao-Kui
Published: March 2010

Background

Leptospira is the causative agent of leptospirosis. The O-antigen is the distal part of the lipopolysaccharide, which is a key component of outer membrane of Gram-negative bacteria and confers serological specificity. The epidemiology and clinical characteristics of leptospirosis are relative to the serology based taxonomic unit. Identification of Leptospira strains by serotyping is laborious and has several drawbacks.

Results

In this study, the O-antigen gene clusters of four epidemic Leptospira serogroups (serogroup Canicola, Autumnalis, Grippotyphosa and Hebdomadis) in China were sequenced and all genes were predicted in silico. Adding published sequences of two serogroups, Icterohaemorrhagiae (strain Lai and Fiocruz L1-130) and Sejroe (strain JB197 and L550), we identified six O-antigen-specific genes for six epidemic serogroups in China. PCR assays using these genes were developed and tested on 75 reference strains and 40 clinical isolates.

Conclusion

The results show that the PCR-based assays can be reliable and alternative means for rapid typing of these six serogroups of Leptospira.
Polymorphisms in IL-1β, vitamin D receptor Fok1, and Toll-like receptor 2 are associated with extrapulmonary tuberculosis
Authors: Motsinger-Reif Alison A , Antas Paulo RZ , Oki Noffisat O , Levy Shawn , Holland Steven M , Sterling Timothy R
Published: March 2010

Background

Human genetic variants may affect tuberculosis susceptibility, but the immunologic correlates of the genetic variants identified are often unclear.

Methods

We conducted a pilot case-control study to identify genetic variants associated with extrapulmonary tuberculosis in patients with previously characterized immune defects: low CD4+ lymphocytes and low unstimulated cytokine production. Two genetic association approaches were used: 1) variants previously associated with tuberculosis risk; 2) single nucleotide polymorphisms (SNPs) in candidate genes involved in tuberculosis pathogenesis. Single locus association tests and multifactor dimensionality reduction (MDR) assessed main effects and multi-locus interactions.

Results

There were 24 extrapulmonary tuberculosis cases (18 black), 24 pulmonary tuberculosis controls (19 black) and 57 PPD+ controls (49 black). In approach 1, 22 SNPs and 3 microsatellites were assessed. In single locus association tests, interleukin (IL)-1β +3953 C/T was associated with extrapulmonary tuberculosis compared to PPD+ controls (P = 0.049). Among the sub-set of patients who were black, genotype frequencies of the vitamin D receptor (VDR) Fok1 A/G SNP were significantly different in extrapulmonary vs. pulmonary TB patients (P = 0.018). In MDR analysis, the toll-like receptor (TLR) 2 microsatellite had 76% prediction accuracy for extrapulmonary tuberculosis in blacks (P = 0.002). In approach 2, 613 SNPs in 26 genes were assessed. None were associated with extrapulmonary tuberculosis.

Conclusions

In this pilot study among extrapulmonary tuberculosis patients with well-characterized immune defects, genetic variants in IL-1β, VDR Fok1, and TLR2 were associated with an increased risk of extrapulmonary disease. Additional studies of the underlying mechanism of these genetic variants are warranted.
Construct validation of a non-exercise measure of cardiorespiratory fitness in older adults
Authors: Mailey Emily L , White Siobhan M , Wójcicki Thomas R , Szabo Amanda N , Kramer Arthur F , McAuley Edward
Published: March 2010

Background

Cardiorespiratory fitness (CRF) is associated with a decreased risk of all-cause mortality but is rarely assessed in medical settings due to burdens of time, cost, risk, and resources. The purpose of this study was to test the construct validity of a regression equation developed by Jurca and colleagues (2005) to estimate CRF without exercise testing in community dwelling older adults.

Methods

Participants (n = 172) aged 60 to 80 years with no contraindications to submaximal or maximal exercise testing completed a maximal graded exercise test (GXT) and the submaximal Rockport 1-mile walk test on separate occasions. Data included in the regression equation (age, sex, body mass index, resting heart rate, and physical activity) were obtained via measurement or self-report. Participants also reported presence of cardiovascular conditions.

Results

The multiple R for the regression equation was .72, p < .001 and CRF estimated from this equation was significantly correlated with the MET value from the GXT (r = 0.66) and with CRF estimated from submaximal field testing (r = 0.67). All three CRF indices were significantly and inversely associated with reporting more cardiovascular conditions.

Conclusions

This research provides preliminary evidence that a non-exercise estimate of CRF is at least as valid as field test estimates of CRF and represents a low-risk, low-cost, and expedient method for estimating fitness in older adults.
The development of a web- and a print-based decision aid for prostate cancer screening
Authors: Dorfman Caroline S , Williams Randi M , Kassan Elisabeth C , Red Sara N , Dawson David L , Tuong William , Parker Elizabeth R , Ohene-Frempong Janet , Davis Kimberly M , Krist Alexander H , Woolf Steven H , Schwartz Marc D , Fishman Mary B , Cole Carmella , Taylor Kathryn L
Published: March 2010

Background

Whether early detection and treatment of prostate cancer (PCa) will reduce disease-related mortality remains uncertain. As a result, tools are needed to facilitate informed decision making. While there have been several decision aids (DAs) developed and tested, very few have included an exercise to help men clarify their values and preferences about PCa screening. Further, only one DA has utilized an interactive web-based format, which allows for an expansion and customization of the material. We describe the development of two DAs, a booklet and an interactive website, each with a values clarification component and designed for use in diverse settings.

Methods

We conducted two feasibility studies to assess men's (45-70 years) Internet access and their willingness to use a web- vs. a print-based tool. The booklet was adapted from two previous versions evaluated in randomized controlled trials (RCTs) and the website was created to closely match the content of the revised booklet. Usability testing was conducted to obtain feedback regarding draft versions of the materials. The tools were also reviewed by a plain language expert and the interdisciplinary research team. Feedback on the content and presentation led to iterative modifications of the tools.

Results

The feasibility studies confirmed that the Internet was a viable medium, as the majority of men used a computer, had access to the Internet, and Internet use increased over time. Feedback from the usability testing on the length, presentation, and content of the materials was incorporated into the final versions of the booklet and website. Both the feasibility studies and the usability testing highlighted the need to address men's informed decision making regarding screening.

Conclusions

Informed decision making for PCa screening is crucial at present and may be important for some time, particularly if a definitive recommendation either for or against screening does not emerge from ongoing prostate cancer screening trials. We have detailed our efforts at developing print- and web-based DAs to assist men in determining how to best meet their PCa screening preferences. Following completion of our ongoing RCT designed to test these materials, our goal will be to develop a dissemination project for the more effective tool.

Trial Registration

NCT00623090