bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of prostate size on pathological outcome and biochemical recurrence after radical prostatectomy for prostate cancer: is it correlated with serum testosterone level?
Authors: Kwon Taekmin , Jeong In Gab , You Dalsan , Park Myung‐Chan , Hong Jun Hyuk , Ahn Hanjong , Kim Choung‐Soo
Published: January 2010

Study Type – Prognosis (case series) Level of Evidence 4

OBJECTIVE

To examine whether prostate size is associated with pathological outcome and biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with prostate cancer, and to evaluate whether it is correlated with serum testosterone level.

PATIENTS AND METHODS

The study comprised 579 men treated with RP for prostate cancer between June 1991 and March 2008, with a prostate‐specific antigen level of <20 ng/mL. We assessed the associations of prostate size (volume), measured using magnetic resonance imaging, and serum testosterone concentration, with adverse pathological outcomes and BCR.

RESULTS

There was a positive correlation between preoperative prostate volume and prostate weight (r= 0.685, P < 0.001). On multivariate analysis, prostate volume was inversely associated with the outcomes of high‐grade prostate cancer (P= 0.044), extracapsular extension (P= 0.011) and BCR (P= 0.016). There was also a positive correlation between serum testosterone level and prostate volume (r= 0.136, P= 0.043). Multivariate analysis showed that lower serum testosterone levels correlated with adverse pathological stage and a pathological Gleason score of ≥8 (P= 0.042). However, there was no relationship between serum testosterone level and BCR after adjusting for covariates.

CONCLUSIONS

Men with smaller prostates had unfavourable pathological findings and were at greater risk of progression after RP. Low serum testosterone levels were not associated with tumour progression. Therefore, another mechanism, aside from hormonal factors, might be involved in unfavourable outcomes in patients with a small prostate.
Range shifts and species diversity in marine ecosystem engineers: patterns and predictions for European sedimentary habitats
Authors: Berke Sarah K. , Mahon Andrew R. , Lima Fernando P. , Halanych Kenneth M. , Wethey David S. , Woodin Sarah A.
Published: January 2010

Aim  Ecosystem engineering polychaetes in the genus Diopatra are undergoing range shifts in western Europe. Here we: (1) assess the species diversity underlying these shifts; (2) link biogeographic patterns to sea surface temperature patterns; and (3) predict possible ecosystem‐level outcomes of Diopatra's northward expansion.

Location  Western Europe.

Methods  We use molecular phylogenetic and morphological evidence to assess species diversity and biogeographic ranges. Using regression tree analyses, we assess thermal limits for two Diopatra species. We compare biogeographic patterns with historical sea surface temperature patterns to draw links between range shifts and climate change. Finally, we review published data to predict potential ecological changes as Diopatra invades new habitats.

Results  The native Diopatra neapolitana range has contracted 130 km to the south. A cryptogenic species, Diopatra sp. A, has extended the northern limit of the genus 350 km to the southern Brittany Peninsula. Both shifts can be explained by historical sea surface temperature anomalies. The Diopatra sp. A expansion is predicted to continue into the English Channel and the North Sea, introducing large tube structures to sheltered sedimentary habitats that currently lack such structures.

Main conclusions  As climate change intensifies, the sediment‐stabilizing Diopatra sp. A will invade habitats dominated by the bioturbating lugworm Arenicola marina. The resulting interaction between functionally different ecosystem engineers will probably cause ecological changes in northern European coastal waters. Existing data for Diopatra species and arenicolids suggest that the diversity and biomass of macroalgae, vascular plants, infauna and epibenthic fauna may increase, while microbial activity may decrease. Net changes in productivity will depend on the relative rates of these changes.
DELETE‐2 AND DELETE‐3 JACKKNIFE PROCEDURES FOR UNMASKING IN REGRESSION
Authors: Martin Michael A. , Roberts Steven , Zheng Letian
Published: January 2010

Single‐case deletion regression diagnostics have been used widely to discover unusual data points, but such approaches can fail in the presence of multiple unusual data points and as a result of masking. We propose a new approach to the use of single‐case deletion diagnostics that involves applying these diagnostics to delete‐2 and delete‐3 jackknife replicates of the data, and considering the percentage of times among these replicates that points are flagged as unusual as an indicator of their influence. By considering replicates that exclude certain collections of points, subtle masking effects can be uncovered.
Friendship and Delinquency: Selection and Influence Processes in Early Adolescence
Authors: Knecht Andrea , Snijders Tom A. B. , Baerveldt Chris , Steglich Christian E. G. , Raub Werner
Published: January 2010

Positive association of relevant characteristics is a widespread pattern among adolescent friends. A positive association may be caused by the selection of similar others as friends and by the deselection of dissimilar ones, but also by influence processes where friends adjust their behavior to each other. Social control theory argues that adolescents select each other as friends based on delinquency. Differential association theory, on the other hand, argues that adolescent friends influence each other's delinquency levels. We employ new statistical methods for assessing the empirical evidence for either process while controlling for the other process. These methods are based on ‘actor‐oriented’ stochastic simulation models. We analyze longitudinal data on friendship networks and delinquent behavior collected in four waves of 544 students in 21 first‐grade classrooms of Dutch secondary schools. Results indicate that adolescents select others as friends who have a similar level of delinquency compared with their own level. Estimates of the social influence parameters are not significant. The results are consistent with social control theory but provide no support for differential association theory.
The ‘Dole or Drudgery’ Dilemma: Education, the Work Ethic and Unemployment
Authors: Dunn Andrew
Published: January 2010

Before the recession, Labour ministers claimed that much unemployment in the UK was voluntary. While social policy authors have repeatedly countered such claims by stressing that unemployed people generally possess a strong work ethic and employment commitment, their accounts typically neglect the role that choosiness in job search behaviour plays in deciding individuals' employment status. Fifty in‐depth interviews with both unemployed and employed respondents exposed considerable diversity in attitudes towards ‘dole’ (being unemployed and claiming unemployment benefits) and ‘drudgery’ (doing less attractive jobs). The more educated were more likely to prefer ‘dole’ to ‘drudgery’ (this was also found using National Child Development Study survey data), yet they usually found jobs despite their greater choosiness. Those with very low educational attainment often desperately wanted jobs but could not find them due to their low employability – which might offer an explanation for the often replicated (yet paradoxical) finding that unemployed people generally exhibit a strong work ethic and pro‐employment attitudes and behaviours. Furthermore, the findings indicate that the scope for many Jobseeker's Allowance claimants to increase their net income by undertaking an unattractive job is greater than social policy authors often imply. The question of ‘who must do the least attractive jobs?’ has been neglected by both social policy academics and policy‐makers.
Catholicism, Job Security Regulations and Female Employment: A Micro‐level Analysis of Esping‐Andersen's Social Catholicism Thesis
Authors: Emmenegger Patrick
Published: January 2010

This article explores the religious roots of job security regulations in Western democracies by putting Esping‐Andersen's famous social Catholicism thesis to the test. Esping‐Andersen argues that due to religious socialization, Catholics exhibit more conservative family values, i.e. they tend to support the male breadwinner model. To sustain this model of family organization, Catholics are expected to support job security regulations. These regulations have been described in the literature as important determinants of gender‐segregated labour markets and low female employment rates. Data from this article show that while Catholics indeed support more conservative family models, so do Reformed Protestants and religious persons in general. Furthermore, no relationship between religious denomination and preferences for job security regulations can be observed. The analysis thus refutes Esping‐Andersen's social Catholicism thesis.
Situational Crime Prevention and Its Discontents: Rational Choice and Harm Reduction versus ‘Cultural Criminology’
Authors: Farrell Graham
Published: January 2010

In this journal, in 2007, Keith Hayward criticized situational crime prevention (SCP) and rational choice. The main thesis was that SCP cannot tackle expressive crimes of anger, hostility and excitement. The secondary thesis was that this was because the rational choice perspective cannot account for intangible aspects of offender decision‐making. Hayward's cultural criminology was offered as better explaining expressive and other crimes. The present article suggests fundamental issues may have been overlooked. Some of the many ways SCP applies to expressive and irrational crimes, and how readily they fit into the choice framework, are outlined, and a preliminary critique of Hayward's cultural criminology is offered.
Older People's Family Contacts and Long‐term Care Expenditure in OECD Countries: A Comparative Approach Using Qualitative Comparative Analysis
Authors: Haynes Philip , Hill Michael , Banks Laura
Published: January 2010

In recent decades there has been a suggestion that public and private long‐term care (LTC) expenditure might be replacing traditional family care for older people. The decline of family contact is known to be more advanced in some OECD countries than others, with southern Europe identified as where family contact is still strong. This article explores at a country level whether there is an association between levels of expenditure on long‐term care and the availability of family contacts. Qualitative Comparative Analysis is used as a comparative method, so as to use national quantitative indicators with a small sample of countries. An association between higher levels of family contact and lower levels of expenditure on LTC is suggested, but it is weakened by a number of untypical cases. Countries that defy this relationship have government care policies that seek to promote informal social care through the family contact that continues to be available. Austria, Canada, Great Britain and Japan are discussed in this context.
A‐Legality: Postnationalism and the Question of Legal Boundaries
Authors: Lindahl Hans
Published: January 2010

This paper critically examines the prevailing assumption that legal boundaries are becoming irrelevant in postnationalism. While the boundaries of the nation‐state are forfeiting some of their hold on human behaviour, postnational legal orders are simply not legal orders unless they can in some way draw the spatial, temporal, material and subjective boundaries that make it possible to qualify human behaviour as legal or illegal. This implies that reflexively constituted legal orders – whether national or postnational – must be presented as legal unities. To the extent that boundaries are the necessary condition of national and postnational legal orders, and therewith of legal unity, they also spawn the possibility of political plurality, manifested in behaviour that resists the very distinction between legality and illegality, as drawn by an order of positive law: a‐legality. Rather than signalling the demise of legal boundaries, postnationalism ushers in a novel way of dealing therewith – and with a‐legality.
The Construction of Terms of Facultative Reinsurance Contracts: is Wasa v Lexington the Exception or the Rule?
Authors: Gürses Özlem
Published: January 2010

Do reinsurers insure the liability faced by the reinsured under its original insurance contract? Where the reinsurance and direct insurance policies are written in identical terms, is it enough for the reinsured to prove its liability under the original insurance policy in order to make a successful claim against its reinsurers? These questions are crucial, because they determine whether the terms of the reinsurance are to be construed identically to those of the direct policy even though they have different governing laws. The issues came before the House of Lords in Wasa International Insurance Co Ltd v Lexington Insurance Co [2009] UKHL 40 and the answers were provided in a judgment delivered on 30 July 2009, the last day of the operation of the House of Lords as a court. This note discusses the nature of facultative reinsurance contracts in the light of their Lordships' ruling.
Shooting the past? The modernisation of Conservative Party employment relations policy under David Cameron
Authors: Williams Steve , Scott Peter
Published: January 2010

Drawing on secondary data sources, the Conservative Party's efforts to modernise its approach to employment relations matters are discussed and critically scrutinised. Policy innovations are likely to be undermined by their mutual inconsistency with pervasive neoliberal, Eurosceptic and anti‐union values, indicating that on balance, any modernisation will be limited.
Disaffection with trade unions in China: some evidence from SOEs in the auto industry
Authors: Nichols Theo , Zhao Wei
Published: January 2010

Despite the growing research into China's industrial relations system there is remarkably little research into how China's workers regard their trade union. This article draws on over 500 interviews conducted in three SOEs in the auto industry in Hubei Province to examine this question.
Understanding organising activity among US national unions
Authors: Fiorito Jack , Jarley Paul
Published: January 2010

It is well known that US aggregate union election activity under the National Labor Relations Board (NLRB) has fallen for several years. It is also well known that NLRB win rates have increased moderately during the Sweeney era relative to the later part of the Kirkland years. This article sheds new light on organising activity and win rates, by examining these data on a national union basis. The results show that several unions, including most of the largest nationals, experienced both increases in organising activity and increased win rates for the period of 1999 to 2004 compared with the years 1990–95 (the end of the Kirkland era). While explanations of variations in inter‐union organising success remain elusive, understanding and building on the experience of these ‘resurging unions’ holds the promise of union renewal more generally.
ATF2 maintains a subset of neural progenitors through CBF1/Notch independent Hes‐1 expression and synergistically activates the expression of Hes‐1 in Notch‐dependent neural progenitors
Authors: Sanalkumar Rajendran , Indulekha Chandrasekharan Lalitha , Divya Thulasi Sheela , Divya Mundackal Sivaraman , Anto Ruby John , Vinod Balachandran , Vidyanand Sasidharan , Jagatha Balusamy , Venugopal Shalini , James Jackson
Published: January 2010

J. Neurochem. (2010) 113, 807–818.

Hes‐1 and Hes‐5 are downstream effectors of Notch signaling that are known to be involved in different aspects of neural stem cell proliferation and differentiation. Evidence has emerged that Hes‐1 expression can be regulated by alternate signaling pathways independent of canonical Notch/CBF1 interaction. This context‐dependent differential regulation of Hes‐1 expression in neural progenitor gains a lot of importance as it would help in its exponential expansion without the requirement of interaction from neighboring cells during development. Here, we have clearly demonstrated the existence of a population of neural progenitors with Notch/CBF1‐independent Hes‐1 expression in vitro. Further analysis demonstrated the role of FGF2 in activating Hes‐1 expression through the direct binding of ATF2, a JNK downstream target, on Hes‐1 promoter. This raises the possibility for the existence of two distinct populations of neural progenitors – one maintained by Hes‐1 expression exclusively through Notch‐independent mechanism and the other mediating Hes‐1 expression through both canonical Notch and FGF2‐ATF2 pathway. This alternative pathway will insure a constant expression of Hes‐1 even in the absence of canonical Notch intracellular domain‐mediated signaling, thereby maintaining a pool of proliferating neural progenitors required during development.
1‐Benzyl‐1,2,3,4‐tetrahydroisoquinoline binds with tubulin β, a substrate of parkin, and reduces its polyubiquitination
Authors: Kohta Ryuki , Kotake Yaichiro , Hosoya Takamitsu , Hiramatsu Toshiyuki , Otsubo Yuko , Koyama Hiroko , Hirokane Yuji , Yokoyama Yuichi , Ikeshoji Hirofumi , Oofusa Ken , Suzuki Masaaki , Ohta Shigeru
Published: January 2010

J. Neurochem. (2010) 114, 1291–1301.

Substances that mimic the actions of causative gene products of familial Parkinson’s disease (PD) are candidate as causative agents of idiopathic PD. 1‐Benzyl‐1,2,3,4‐tetrahydroisoquinoline (1BnTIQ), an endogenous neurotoxin, is present at three times higher levels in CSF of PD patients than in CSF of control subjects. However, the mechanism of 1BnTIQ’s neurotoxicity is unclear. In this study, we tried to identify 1BnTIQ‐binding proteins by using a diazido‐functionalized 1BnTIQ analog, 1‐(3‐azido‐5‐azidomethylbenzyl)‐1,2,3,4‐tetrahydroisoquinoline, designed and synthesized as a probe for radioisotope‐free photoaffinity labeling. One major photolabeled protein identified using this probe was tubulin β, which has been reported to be a substrate of parkin, a ubiquitin E3 ligase and a causative gene product of familial PD. Loss of function mutation of parkin is reported to result in loss of tubulin β ubiquitination. Therefore, we examined the effect of 1BnTIQ on ubiquitination of tubulin β. The polyubiquitinated tubulin β level in human neuroblastoma SH‐SY5Y cells was reduced in the presence of 1BnTIQ, even at concentrations as low as those detected in parkinsonian CSF. In vitro ubiquitination assay gave similar results. It is suggested that 1BnTIQ has the same effect on tubulin ubiquitination as does mutant parkin in familial PD. Taken together, substances which reduce polyubiquitination of tubulin such as 1BnTIQ are supposed to be candidates of etiological factors of PD.
Application of Stereo‐Digital Image Correlation to Full‐Field 3‐D Deformation Measurement of Intervertebral Disc
Authors: Spera D. , Genovese K. , Voloshin A.
Published: January 2010

Abstract:  This paper presents the application of a Stereo‐Digital Image Correlation (Stereo‐DIC) based approach for full‐field deformation measurements on a porcine intervertebral disc (IVD) under in‐vitro loading. Full‐field capabilities of Stereo‐DIC provide useful information on the IVD structure‐function relationship needed for designing novel disc replacement devices on the basis of biomimetic concepts. In this work, the use of a multi‐view Stereo‐DIC system allows full‐field measurement over more than 180° of the IVD surface. This is achieved by sequentially moving a single camera through seven fixed positions in order to cover the desired angle of vision. Ad hoc data processing and merging procedures are calibrated for a cylindrical sample. Strain maps are determined for a rubber cylinder subjected to rigid‐body motions and then to uniform compression. These preliminary procedures serve to evaluate strain‐mapping errors as well as to assess repeatability and accuracy of camera re‐positioning. Once the entire procedure is verified and calibrated, a fresh porcine functional spine unit is loaded under anterior, posterior and lateral compression. From displacement maps obtained with the multi‐view set‐up, it is possible to gather information on both IVD bulging and surface strains. Results are consistent with the IVD global behaviour under standard testing protocols reported in the recent literature. Furthermore, detailed information on local variations in structural response and stiffness properties occurring when load is applied in different regions of the IVD are obtained. The present approach allows to correlate structural response with the entire 3‐D deformation and strain field and not just with a single displacement/strain component and thus it could be effectively used for explaining in‐homogeneity observed in human discs degenerative patterns.
Principal Component Analysis of Acoustic Emission Signals From Landing Gear Components: An Aid to Fatigue Fracture Detection
Authors: Eaton M. J. , Pullin R. , Hensman J. J. , Holford K. M. , Worden K. , Evans S. L.
Published: January 2010

Abstract:  This work forms part of a larger investigation into fatigue crack detection using acoustic emission (AE) during landing gear airworthiness testing. It focuses on the use of principal component analysis (PCA) to differentiate between fatigue crack propagation (FCP) signals and high levels of background noise. An artificial AE fracture source was developed and additionally five sources were used to generate differing artificial AE signals. Signals were recorded from all six artificial sources in a real landing gear component subject to no load. Furthermore, artificial FCP signals were recorded in the same component under airworthiness test load conditions. PCA was used to automatically differentiate between AE signals from different source types. Furthermore, successful separation of artificial FCP signals from a very high level of background noise was achieved. The presence of a load was observed to affect the ultrasonic propagation of AE signals.
Diminishing Efficacy of Combination Therapy, Response‐Heterogeneity, and Treatment Intolerance Limit the Attainability of Tight Risk Factor Control in Patients with Diabetes
Authors: Timbie Justin W. , Hayward Rodney A. , Vijan Sandeep
Published: January 2010

Objective.To evaluate the attainability of tight risk factor control targets for three diabetes risk factors and to assess the degree of polypharmacy required.

Data Sources/Study Setting.National Health and Nutrition Examination Survey‐III.

Study Design.We simulated a strategy of “treating to targets,” exposing subjects to a battery of treatments until low‐density lipoprotein (LDL)‐cholesterol (100 mg/dL), hemoglobin A1c (7 percent), and blood pressure (130/80 mm Hg) targets were achieved or until all treatments had been exhausted. Regimens included five statins of increasing potency, four A1c‐lowering therapies, and eight steps of antihypertensive therapy.

Data Collection/Extraction Methods.We selected parameter estimates from placebo‐controlled trials and meta‐analyses.

Principal Findings.Under ideal efficacy conditions, 77, 64, and 58 percent of subjects achieved the LDL, A1c, and blood pressure targets, respectively. Successful control depended highly on a subject's baseline number of treatments. Using the least favorable assumptions of treatment tolerance, success rates were 11–17 percentage points lower. Approximately 57 percent of subjects required five or more medication classes.

Conclusions.A significant proportion of people with diabetes will fail to achieve targets despite using high doses of multiple, conventional treatments. These findings raise concerns about the feasibility and polypharmacy burden needed for tight risk factor control, and the use of measures of tight control to assess the quality of care for diabetes.
Cue‐conditioned alcohol seeking in rats following abstinence: involvement of metabotropic glutamate 5 receptors
Authors: Adams CL , Short JL , Lawrence AJ
Published: January 2010

Background and purpose:  The current study was designed to: (i) examine whether functional interactions occur between receptors known to regulate alcohol self‐administration; and (ii) characterize relapse to alcohol seeking following abstinence.

Experimental approach:  The selective cannabinoid CB1 receptor antagonist SR141716A (0.03–1.0 mg·kg−1 i.p.) resulted in a dose‐dependent reduction in ethanol self‐administration in ethanol‐preferring Indiana‐preferring rats. SR141716A was then co‐administered with either the selective glutamate metabotropic glutamate 5 (mGlu5) receptor antagonist 3‐[(2‐methyl‐1,3‐thiazol‐4‐yl)ethynyl]pyridine (MTEP) or the selective adenosine A2A receptor antagonist SCH58261.

Key results:  When administered at individually sub‐threshold doses, a combination of SR141716A (0.1 mg·kg−1) and SCH58261 (0.5 mg·kg−1 i.p.) produced a reduction (28%) in ethanol self‐administration. Combinations of threshold doses of SR141716A (0.3 mg·kg−1) and SCH58261 (2.0 mg·kg−1, i.p.) caused an essentially additive reduction (68%) in alcohol self‐administration. A combination of individually sub‐threshold doses of CB1 and mGlu5 receptor antagonists did not affect alcohol self‐administration; however, combined threshold doses of SR141716A (0.3 mg·kg−1) and MTEP (1.0 mg·kg−1 i.p.) did reduce ethanol self‐administration markedly (80%). Cue‐conditioned alcohol seeking was attenuated by pretreatment with MTEP (1.0 mg·kg−1) co‐administered with SR141716A (0.3 mg·kg−1 i.p.). In contrast, SCH58261 (2.0 mg·kg−1) co‐administered with SR141716A (0.3 mg·kg−1 i.p.) did not reduce cue‐conditioned alcohol seeking.

Conclusions and implications:  Adenosine A2A and cannabinoid CB1 receptors regulated alcohol self‐administration additively, but combined low‐dose antagonism of these receptors did not prevent cue‐conditioned alcohol seeking after abstinence. In contrast, combined low‐dose antagonism of mGlu5 and CB1 receptors did prevent relapse‐like alcohol seeking after abstinence, suggesting a prominent role for mGlu5 receptors in this paradigm.
Rimonabant (SR141716) induces metabolism and acquisition of fertilizing ability in human sperm
Authors: Aquila S , Guido C , Santoro A , Gazzerro P , Laezza C , Baffa MF , Andò S , Bifulco M
Published: January 2010

Background and purpose:  The endocannabinoid system and the cannabinoid CB1 receptor have been identified in human sperm, and it is well known that endocannabinoids have pronounced adverse effects on male and female reproduction. In order to elucidate further the pathophysiological role of the endocannabinoid system in male fertility, we investigated the activity of the CB1 receptor antagonist rimonabant (SR141716) on the fertilizing ability of human sperm.

Experimental approach:  We evaluated in vitro the effects of rimonabant on motility, survival, capacitation, acrosin activity and metabolism of human sperm. Particularly, capacitation was studied by using three different approaches: intracellular free Ca2+ content assay, cholesterol efflux assay and protein tyrosine phosphorylation analysis.

Key results:  Rimonabant significantly increased sperm motility and viability through the induction of pAkt and pBcl2, key proteins of cell survival and metabolism, and it induced acrosome reaction and capacitation as well. Rimonabant reduced the triglyceride content of sperm, while enhancing lipase and acyl‐CoA dehydrogenase activities, implying an overall lipolytic action in these cells. Rimonabant also affected sperm glucose metabolism by decreasing phosphorylation of glycogen synthase kinase 3 and increasing glucose‐6‐phosphate dehydrogenase activity, suggesting a role in inducing sperm energy expenditure. Intriguingly, agonism at the CB1 receptor, with an anandamide analogue or a selective inhibitor of fatty acid amide hydrolase, produced opposing effects on human sperm functions.

Conclusions and implications:  Our data suggest that blockade of the CB1 receptor by rimonabant induces the acquisition of fertilizing ability and stimulates energy expenditure in human sperm.
The role of kinin B1 and B2 receptors in the scratching behaviour induced by proteinase‐activated receptor‐2 agonists in mice
Authors: Costa Robson , Manjavachi Marianne N , Motta Emerson M , Marotta Denise M , Juliano Luiz , Torres Hugo A , Pesquero João B , Calixto João B.
Published: January 2010

Background and purpose:  Activation of the proteinase‐activated receptor‐2 (PAR‐2) induces scratching behaviour in mice. Here, we have investigated the role of kinin B1 and B2 receptors in the pruritogenic response elicited by activators of PAR‐2.

Experimental approach:  Scratching was induced by an intradermal (i.d.) injection of trypsin or the selective PAR‐2 activating peptide SLIGRL‐NH2 at the back of the mouse neck. The animals were observed for 40 min and their scratching response was quantified.

Key results:  I.d. injection of trypsin or SLIGRL‐NH2 evoked a scratching behaviour, dependent on PAR‐2 activation. Mice genetically deficient in kinin B1 or B2 receptors exhibited reduced scratching behaviour after i.d. injection of trypsin or SLIGRL‐NH2. Treatment (i.p.) with the non‐peptide B1 or B2 receptor antagonists SSR240612 and FR173657, respectively, prevented the scratching behaviour caused by trypsin or SLIGRL‐NH2. Nonetheless, only treatment i.p. with the peptide B2 receptor antagonist, Hoe 140, but not the B1 receptor antagonist (DALBK), inhibited the pruritogenic response to trypsin. Hoe 140 was also effective against SLIGRL‐NH2‐induced scratching behaviour when injected by i.d. or intrathecal (i.t.) routes. Also, the response to SLIGRL‐NH2 was inhibited by i.t. (but not by i.d.) treatment with DALBK. Conversely, neither Hoe 140 nor DALBK were able to inhibit SLIGRL‐NH2‐induced scratching behaviour when given intracerebroventricularly (i.c.v.).

Conclusions and implications:  The present results demonstrated that kinins acting on both B1 and B2 receptors played a crucial role in controlling the pruriceptive signalling triggered by PAR‐2 activation in mice.
Home and Community‐Based Medicaid Options for Dependent Older Floridians
Authors: Golden Adam G. , Roos Bernard A. , Silverman Michael A. , Beers Mark H.
Published: January 2010

In an era of widespread state budget constraints, Florida has been increasingly challenged to provide long‐term care services to a growing population of older dependent persons. The high costs of nursing home care have led the state to implement care management alternatives that offer potential for cost savings along with greater consumer satisfaction through maintenance of community residence. Although these alternative care approaches represent important opportunities to contain costs, it is equally important that professional care providers and policymakers understand how such programs operate. Here the Florida experience with eight home and community‐based waiver models, in addition to the Program of All‐Inclusive Care for the Elderly, are summarized and a comparative analysis offered that may enlighten the efforts of other states to establish cost‐effective and attractive care management models.
Eslicarbazepine Acetate: A Well-Kept Secret?
Authors: Ben-Menachem Elinor
Published: January 2010

Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Treatment in Adults with Refractory Partial-Onset Seizures: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase III Study. Elger C, Halász P, Maia J, Almeida L, Soares-da-Silva P, BIA-2093-301 Investigators Study Group. Epilepsia 2009;50(3):454–463. PURPOSE: To study the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy for refractory partial seizures in adults with ≥4 partial-onset seizures (simple or complex, with or without secondary generalization) per 4 weeks despite treatment with 1–2 antiepileptic drugs (AEDs). METHODS: This multicenter, parallel-group study had an 8-week, single-blind, placebo baseline phase, after which patients were randomized to placebo ( n = 102) or once-daily ESL 400 mg ( n = 100), 800 mg ( n = 98), or 1,200 mg ( n = 102) in the double-blind treatment phase. ESL starting dose was 400 mg; thereafter, ESL was titrated at weekly 400-mg steps to the full maintenance dose (12 weeks). RESULTS: Seizure frequency adjusted per 4 weeks over the maintenance period (primary endpoint) was significantly lower than placebo in the ESL 1,200-mg ( p = 0.0003) and 800-mg ( p = 0.0028) groups [analysis of covariance (ANCOVA) of log-transformed seizure frequency]. Responder rate was 20% (placebo), 23% (400 mg), 34% (800 mg), and 43% (1,200 mg). Median relative reduction in seizure frequency was 16% (placebo), 26% (400 mg), 36% (800 mg), and 45% (1,200 mg). The most frequent concomitant AEDs were carbamazepine (56–62% of patients), lamotrigine (25–27%), and valproic acid (22–28%). Similar efficacy results were obtained in patients administered ESL with or without carbamazepine as concomitant AED. Discontinuation rates caused by adverse events (AEs) were 3.9% (placebo), 4% (400 mg), 8.2% (800 mg), and 19.6% (1,200 mg). AEs in >10% of any group were dizziness, headache, and diplopia. Most AEs were mild or moderate. DISCUSSION: ESL, 800 and 1,200 mg once-daily, was well tolerated and more effective than placebo in patients who were refractory to treatment with one or two concomitant AEDs.
When Should Corpus Callosotomy be Offered as Palliative Therapy?
Authors: Abou-Khalil Bassel W.
Published: January 2010

Long-Term Seizure Outcome after Corpus Callosotomy: A Retrospective Analysis of 95 Patients. Tanriverdi T, Olivier A, Poulin N, Andermann F, Dubeau F. J Neurosurg 2009;110(2):332–342. OBJECT: The authors report long-term follow-up seizure outcome in patients who underwent corpus callosotomy during the period 1981–2001 at the Montreal Neurological Institute. METHODS: The records of 95 patients with a minimum follow-up of 5 years (mean 17.2 years) were retrospectively evaluated with respect to seizure, medication outcomes, and prognostic factors on seizure outcome. RESULTS: All patients had more than one type of seizure, most frequently drop attacks and generalized tonic-clonic seizures. The most disabling seizure type was drop attacks, followed by generalized tonic–clonic seizures. Improvement was noted in several seizure types and was most likely for generalized tonic–clonic seizures (77.3%) and drop attacks (77.2%). Simple partial, generalized tonic, and myoclonic seizures also benefited from anterior callosotomy. The extent of the callosal section was correlated with favorable seizure outcome. The complications were mild and transient and no death was seen. CONCLUSIONS: This study confirms that anterior callosotomy is an effective treatment in intractable generalized seizures that are not amenable to focal resection. When considering this procedure, the treating physician must thoroughly assess the expected benefits, limitations, likelihood of residual seizures, and the risks, and explain them to the patient, his or her family, and other caregivers.
Aging Models of Acute Seizures and Epilepsy
Authors: Kelly Kevin M.
Published: January 2010

Aged animals have been used by researchers to better understand the differences between the young and the aged brain and how these differences may provide insight into the mechanisms of acute seizures and epilepsy in the elderly. To date, there have been relatively few studies dedicated to the modeling of acute seizures and epilepsy in aged, healthy animals. Inherent challenges to this area of research include the costs associated with the purchase and maintenance of older animals and, at times, the unexpected and potentially confounding comorbidities associated with aging. However, recent studies using a variety of in vivo and in vitro models of acute seizures and epilepsy in mice and rats have built upon early investigations in the field, all of which has provided an expanded vision of seizure generation and epileptogenesis in the aged brain. Results of these studies could potentially translate to new and tailored interventional approaches that limit or prevent the development of epilepsy in the elderly.
Herbs and Spices: Unexpected Sources of Antiepileptogenic Drug Treatments?
Authors: Wong Michael
Published: January 2010

Protective Effect of Resveratrol Against Kainate-Induced Temporal Lobe Epilepsy in Rats. Wu Z, Xu Q, Zhang L, Kong D, Ma R, Wang L. Neurochem Res 2009;34(8):1393–1400. Resveratrol (Res) is a phytoalexin produced naturally by several plants, which has multifunctional effects such as neuroprotection, anti-inflammatory, and anti-cancer. The present study was to evaluate a possible anti-epileptic effect of Res against kainate-induced temporal lobe epilepsy (TLE) in rat. We performed behavior monitoring, intracranial electroencepholography (IEEG) recording, histological analysis, and Western blotting to evaluate the anti-epilepsy effect of Res in kainate-induced epileptic rats. Res decreased the frequency of spontaneous seizures and inhibited the epileptiform discharges. Moreover, Res could protect neurons against kainate-induced neuronal cell death in CA1 and CA3a regions and depressed mossy fiber sprouting, which are general histological characteristics both in TLE patients and animal models. Western blot revealed that the expression level of kainate receptors (KARs) in hippocampus was reduced in Res-administrated rats compared to that in epileptic ones. These results suggest that Res is a potent anti-epilepsy agent, which protects against epileptogenesis and progression of the kainate-induced TLE animal.

Curcumin Protects Against Electrobehavioral Progression of Seizures in the Iron-Induced Experimental Model of Epileptogenesis. Jyoti A, Sethi P, Sharma D. Epilepsy Behav 2009;14(2):300–308. The purpose of the study was to investigate whether dietary intake of curcumin can inhibit the onset and progression of seizures and their associated pathophysiology in experimental FeCl3-induced epileptogenesis. Curcumin was considered for this study because it can cross the blood–brain barrier and bind redox-active metal ions. It is also well known for its antioxidative, anticancer, and anti-inflammatory properties. In the present study, seizures were induced by intracortical injection of FeCl3 into young rats. Synchronized video/EEG recordings were obtained to diagnose the progression of seizures. Short-term treatment with a curcumin-supplemented diet (1500 ppm w/w) significantly inhibited the onset of grade III and IV seizures in rats with iron-induced epilepsy. The lower dose of curcumin (500 ppm) was not effective in inhibiting grade III seizures, but retarded the onset and progression of generalized seizures. The seizure-suppressing potential of curcumin is explained by the observed biochemical, behavioral, and ultrastructural results. Our results indicate that curcumin significantly prevents generalization of electroclinical seizure activity as well as the pathogenesis associated with iron-induced epileptogenesis.
Magnetic resonance imaging diagnosis of iron overload in a leukemic patient after allogeneic hematopoietic stem cell transplantation
Authors: Tan Cher Heng , Marcal Leonardo , Tan Dongfeng , Patnana Madhavi
Published: January 2010

BACKGROUND: Iron overload (IO) is increasingly recognized as a common cause of hepatic dysfunction in leukemic patients who have undergone allogeneic hematopoietic stem cell transplantation. Magnetic resonance imaging (MRI) is a noninvasive method of making the diagnosis.

CASE REPORT: A patient with acute lymphocytic leukemia presented with severe liver dysfunction during salvage chemotherapy for leukemia relapse after undergoing allogeneic hematopoietic stem cell transplantation. The liver dysfunction was originally attributed to graft‐versus‐host disease; however, findings on MRI and liver biopsy were consistent with hepatic IO.

CONCLUSIONS: As illustrated by our case, MRI can be a reliable, noninvasive modality that should be employed in the work‐up of these patients.
The aptamer ARC1779 blocks von Willebrand factor–dependent platelet function in patients with thrombotic thrombocytopenic purpura ex vivo
Authors: Mayr Florian B. , Knöbl Paul , Jilma Bernd , Siller‐Matula Jolanta M. , Wagner Patricia G. , Schaub Robert G. , Gilbert James C. , Jilma‐Stohlawetz Petra
Published: January 2010

BACKGROUND: In thrombotic thrombocytopenic purpura (TTP), ultralarge von Willebrand factor (VWF) multimers bind platelet (PLT) glycoprotein Ib and lead to the formation of disseminated fibrin‐poor, VWF‐rich PLT thrombi. The aptamer ARC1779 blocks binding of the VWF A1 domain to PLT glycoprotein Ib. We evaluated whether ARC1779 inhibits the excessive VWF activity and VWF‐mediated PLT function in patients with TTP.

STUDY DESIGN AND METHODS: We studied the ex vivo concentration response curves for ARC1779 on PLT function analyzer (PFA‐100, Dade Behring) and cone‐and‐plate analyzer (CPA, Impact‐R) PLT function tests, agonist‐induced PLT aggregation, and VWF activity of TTP patients (n = 11, three in acute phase and eight in remission) and healthy controls (n = 44).

RESULTS: VWF activity and VWF‐dependent PLT plug formation were increased in TTP patients relative to healthy controls, but agonist‐induced PLT aggregation was not. ARC1779 blocked collagen/adenosine 5′‐diphosphate (ADP)‐induced PLT plug formation as measured by PFA‐100 with an inhibitory concentration (IC)100 of approximately 1 µg/mL in citrate‐anticoagulated samples and approximately 3 to 4 µg/mL in hirudin‐anticoagulated samples. A similar concentration of ARC1779 was necessary to block shear‐dependent PLT adhesion in both TTP patients and healthy controls using the CPA assay (IC100 of approx. 1 µg/mL for both). ARC1779 blocked VWF activity with an IC90 of approximately 3 to 4 µg/mL in all subjects, but did not inhibit PLT aggregation by ADP, collagen, or arachidonic acid even at concentrations much greater than those that fully inhibited VWF‐dependent PLT function.

CONCLUSIONS: ARC1779 potently and specifically inhibits VWF activity and VWF‐dependent PLT function. ARC1779 may be a promising novel therapeutic for the treatment of TTP.
Conversion to the buffy coat method and quality of frozen plasma derived from whole blood donations in Canada
Authors: Sheffield William P. , Bhakta Varsha , Jenkins Craig , Devine Dana V.
Published: January 2010

BACKGROUND: Canada converted from the platelet‐rich plasma (PRP) method to the buffy coat (BC) method of processing whole blood donations between 2006 and 2008. We measured coagulation variables in plasma units during this transition, in 2006 (PRP only), 2007 (BC and PRP), and 2008 (BC only) to test the hypothesis that this conversion would not affect frozen plasma (FP) quality.

STUDY DESIGN AND METHODS: Fresh‐frozen plasma (FFP; frozen within 8 hr of collection) or FP (frozen within 24 hr of collection) units were shipped on dry ice from 12 plasma manufacturing sites, thawed, and characterized using an automated coagulation analyzer, at a single testing site.

RESULTS: FP made by the BC method (FP‐BC) exhibited fibrinogen, Factor (F)V, ABO‐matched FVIII, and antithrombin levels at least as high as FP made by the PRP method (FP‐PRP) and supported global clotting, as measured by prothrombin time or activated partial thromboplastin time, to an indistinguishable extent as FP‐PRP. FP‐BC and FP‐PRP did not differ in ABO‐matched FVIII levels, but both contained 30% to 35% less FVIII than FFP. There was no discernible effect of the site of manufacturing on plasma quality. FP‐BC units leukoreduced by centrifugation contained more FV activity than those leukoreduced by filtration, but the difference was unlikely to be of clinical significance.

CONCLUSION: Our data suggest that no reduction in FP quality, at least in the characteristics we tested, accompanied the switch from the PRP to the BC method processing of whole blood donations in Canada.
Prevalence of HLA antibodies in remotely transfused or alloexposed volunteer blood donors
Authors: Kakaiya Ram M. , Triulzi Darrell J. , Wright David J. , Steele Whitney R. , Kleinman Steven H. , Busch Michael P. , Norris Philip J. , Hillyer Christopher D. , Gottschall Jerome L. , Rios Jorge A. , Carey Patricia , Glynn Simone A.
Published: January 2010

BACKGROUND: HLA antibody testing of previously transfused or pregnant donors may help reduce the risk of transfusion‐related acute lung injury (TRALI). However, the prevalence of HLA antibodies in transfused donors has not been well characterized.

STUDY DESIGN AND METHODS: Transfusion and pregnancy history was obtained from consenting donors. HLA Class I and II antibody testing was performed by multiantigen bead Luminex platform. Cutoff values for Class I and II antibodies used normalized background ratios of 10.8 and 6.9, respectively. Linear probability models were used to evaluate potential associations between HLA alloimmunization and donor characteristics.

RESULTS: A total of 7920 donors (2086 males and 5834 females) were tested. HLA antibody prevalence did not significantly differ between 895 transfused (1.7%) and 1138 nontransfused males (1.0%; odds ratio [OR], 1.75; 95% confidence interval [CI], 0.80‐3.82]. Prevalence in 45 transfused nulliparous females (4.4%; 95% CI, 0.1%‐11.8%) was not different from the 1.6% prevalence in 1732 nontransfused nulliparous females (OR, 2.94; 95% CI, 0.68‐12.74). Transfused parous females had higher prevalence than nontransfused counterparts (p = 0.004; OR, 1.39; 95% CI, 1.07‐1.80). In a linear probability model, the estimated additive risk of transfusion‐induced alloimmunization was only 0.8% (95% CI, −0.2% to 1.8%; p = 0.10). Donor transfusion history showed that 58% of transfusions occurred more than 10 years previously.

CONCLUSION: Transfused volunteer blood donors do not appear to have a significantly higher prevalence of HLA antibodies than their nontransfused counterparts. Thus, in an effort to reduce TRALI risk, ascertaining past history of transfusion and testing these donors for HLA antibodies is not necessary.
Neonatal alloimmune thrombocytopenia caused by an antibody specific for a newly identified allele of human platelet antigen‐7
Authors: Koh Yangsook , Taniue Atsuko , Ishii Hiroyuki , Matsuyama Nobuki , Amakishi Etsuko , Hayashi Tomoya , Furuta Rika A. , Fukumori Yasuo , Hirayama Fumiya , Yoshimura Keiji , Nagamine Tomoko , Tamai Susumu , Nakano Susumu
Published: January 2010

BACKGROUND:Neonatal alloimmune thrombocytopenia (NAIT) is a neonatal disorder characterized by maternal alloimmunization against fetal platelet (PLT) antigens inherited from the father. A healthy 30‐year‐old Japanese woman (Hit) gave birth to her second child after an uneventful pregnancy. Nine hours after birth, the infant presented with severe petechiae and a PLT count of 6 × 109/L.

STUDY DESIGN AND METHODS:To elucidate the maternal cause of NAIT in the infant, serologic and genetic studies, including PLT genotyping and sequence‐based analysis, were conducted. Additionally, serologic screening for the new PLT antigen was performed.

RESULTS:Serum from the NAIT infant's mother contained antibodies directed against a human PLT antigen (HPA) of the newborn. Using five‐cell‐lineage flow cytometry, we localized the antigen to a PLT glycoprotein (GP). Subsequent monoclonal antibody immobilization of PLT antigen assay and PLT immunofluorescence inhibition experiments localized the antigen to the GPIIIa subunit of the GPIIb/IIIa complex. GPIIIa localization was confirmed by sequence‐based typing studies, which identified a 1297C>T (407proline>serine substitution) mutation on the ninth exon of the GPIIIa gene. This mutation identified the third allele of HPA‐7. Anti‐Hitareacted with mutated GPIIIa‐transfected cells but not with stable transfectants expressing wild‐type GPIIIa. Serologic screening for Hitain the Japanese population revealed a phenotypic frequency of approximately 0.0015.

CONCLUSIONS:We identified a new third allele of HPA‐7, which is characterized by a 1297C>T mutation in the GPIIIa gene. This 1297C>T allele was found in 0.15% of the Japanese population. An antibody against this antigen could be the cause of severe NAIT.