bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal circuits of fear extinction
Authors: Herry Cyril , Ferraguti Francesco , Singewald Nicolas , Letzkus Johannes J. , Ehrlich Ingrid , Lüthi Andreas
Published: February 2010

Fear extinction is a form of inhibitory learning that allows for the adaptive control of conditioned fear responses. Although fear extinction is an active learning process that eventually leads to the formation of a consolidated extinction memory, it is a fragile behavioural state. Fear responses can recover spontaneously or subsequent to environmental influences, such as context changes or stress. Understanding the neuronal substrates of fear extinction is of tremendous clinical relevance, as extinction is the cornerstone of psychological therapy of several anxiety disorders and because the relapse of maladaptative fear and anxiety is a major clinical problem. Recent research has begun to shed light on the molecular and cellular processes underlying fear extinction. In particular, the acquisition, consolidation and expression of extinction memories are thought to be mediated by highly specific neuronal circuits embedded in a large‐scale brain network including the amygdala, prefrontal cortex, hippocampus and brain stem. Moreover, recent findings indicate that the neuronal circuitry of extinction is developmentally regulated. Here, we review emerging concepts of the neuronal circuitry of fear extinction, and highlight novel findings suggesting that the fragile phenomenon of extinction can be converted into a permanent erasure of fear memories. Finally, we discuss how research on genetic animal models of impaired extinction can further our understanding of the molecular and genetic bases of human anxiety disorders.
Functional deprivation promotes amyloid plaque pathogenesis in Tg2576 mouse olfactory bulb and piriform cortex
Authors: Zhang Xue‐Mei , Xiong Kun , Cai Yan , Cai Huaibin , Luo Xue‐Gang , Feng Jia‐Chun , Clough Richard W. , Patrylo Peter R. , Struble Robert G. , Yan Xiao‐Xin
Published: February 2010

Cerebral hypometabolism and amyloid accumulation are principal neuropathological manifestations of Alzheimer’s disease (AD). Whether and how brain/neuronal activity might modulate certain pathological processes of AD are interesting topics of recent clinical and basic research in the field, and may be of potential medical relevance in regard to both the disease etiology and intervention. Using the Tg2576 transgenic mouse model of AD, this study characterized a promotive effect of neuronal hypoactivity associated with functional deprivation on amyloid plaque pathogenesis in the olfactory pathway. Unilateral naris‐occlusion caused β‐secretase‐1 (BACE1) elevation in neuronal terminals in the deprived relative to the non‐deprived bulb and piriform cortex in young adult mice. In parallel with the overall age‐related plaque development in the forebrain, locally increased BACE1 immunoreactivity co‐occurred with amyloid deposition first in the piriform cortex then within the bulb, more prominent on the deprived relative to the non‐deprived side. Biochemical analyses confirmed elevated BACE1 protein levels, enzymatic activity and products in the deprived relative to non‐deprived bulbs. Plaque‐associated BACE1 immunoreactivity in the bulb and piriform cortex was localized preferentially to swollen/sprouting glutamatergic axonal terminals, with Aβ immunoreactivity occurring inside as well as around these terminals. Together, these findings suggest that functional deprivation or neuronal hypoactivity facilitates amyloid plaque formation in the forebrain in a transgenic model of AD, which operates synergistically with age effect. The data also implicate an intrinsic association of amyloid accumulation and plaque formation with progressive axonal pathology.
Mouse strain differences in locomotor, sensitisation and rewarding effect of heroin; association with alterations in MOP‐r activation and dopamine transporter binding
Authors: Bailey Alexis , Metaxas Athanasios , Al‐Hasani Ream , Keyworth Helen L. , Forster Duncan M. , Kitchen Ian
Published: February 2010

There is growing agreement that genetic factors play an important role in the risk to develop heroin addiction, and comparisons of heroin addiction vulnerability in inbred strains of mice could provide useful information on the question of individual vulnerability to heroin addiction. This study examined the rewarding and locomotor‐stimulating effects of heroin in male C57BL/6J and DBA/2J mice. Heroin induced locomotion and sensitisation in C57BL/6J but not in DBA/2J mice. C57BL/6J mice developed conditioned place preference (CPP) to the highest doses of heroin, while DBA/2J showed CPP to only the lowest heroin doses, indicating a higher sensitivity of DBA/2J mice to the rewarding properties of heroin vs C57BL/6J mice. In order to investigate the neurobiological substrate underlying some of these differences, the effect of chronic ‘intermittent’ escalating dose heroin administration on the opioid, dopaminergic and stress systems was explored. Twofold higher μ‐opioid receptor (MOP‐r)‐stimulated [35S]GTPγS binding was observed in the nucleus accumbens and caudate of saline‐treated C57BL/6J mice compared with DBA/2J. Heroin decreased MOP‐r density in brain regions of C57BL/6J mice, but not in DBA/2J. A higher density of dopamine transporters (DAT) was observed in nucleus accumbens shell and caudate of heroin‐treated DBA/2J mice compared with heroin‐treated C57BL/6J. There were no effects on D1and D2binding. Chronic heroin administration decreased corticosterone levels in both strains with no effect of strain. These results suggest that genetic differences in MOP‐r activation and DAT expression may be responsible for individual differences in vulnerability to heroin addiction.
A role for ephrin‐As in maintaining topographic organization in register across interconnected central visual pathways
Authors: Wilks Tenelle A. , Rodger Jennifer , Harvey Alan R.
Published: February 2010

The retina sends spatially ordered visual information to the superior colliculus (SC) directly and indirectly via the thalamus and primary visual cortex (V1). Gradients of Ephs and ephrins are present in all of these regions, and have been shown to be involved in establishing topography of at least some of these interconnected visual pathways. Studies in ephrin‐A knockout mice show that abnormal retinotectal termination zones (TZs) are present in a majority of mice lacking (−/−) ephrin‐A2 (57%), and ephrin‐A2 and ‐A5 (89%). A similar but seemingly less disordered pattern is detected in the retina‐to‐dorsal lateral geniculate nucleus (dLGN) and dLGN‐to‐V1 projections. Here we analyse the dLGN‐to‐V1 and V1‐to‐SC projections in ephrin‐A−/− mice to determine the extent to which topographic errors are transmitted across synaptic relays. Fluorescent tracers were injected into V1 of wild‐type (WT), ephrin‐A2−/− or ephrin‐A2A5−/− mice. We examined the number, location and size of anterograde TZs in SC, and mapped the distribution of retrogradely labelled neurons in dLGN. Compared with WT and ephrin‐A2−/− mice, the volume of individual TZs in the SC was smaller in ephrin‐A2A5−/− mice (P = 0.002). Single V1 injections labelled two foci of dLGN neurons in 70%, and two SC TZs in 80% of ephrin‐A2A5−/− mice. Abnormalities in one or other of the projections were detected in 10% of ephrin‐A2−/− mice. Importantly, there was no consistent correspondence between the organization of geniculocortical and corticotectal projections in either genotype, suggesting a role for ephrin‐As in maintaining topographic organization in register across multiple interconnected central visual pathways.
Differential regulation of mature and precursor microRNA expression by NMDA and metabotropic glutamate receptor activation during LTP in the adult dentate gyrus in vivo
Authors: Wibrand Karin , Panja Debabrata , Tiron Adrian , Ofte May L. , Skaftnesmo Kai‐O. , Lee Cherin S , Pena John T.G. , Tuschl Thomas , Bramham Clive R.
Published: February 2010

Regulation of microRNA (miRNA) expression and function in the context of activity‐dependent synaptic plasticity in the adult brain is little understood. Here, we examined miRNA expression during long‐term potentiation (LTP) in the dentate gyrus of adult anesthetized rats. Microarray expression profiling identified a subpopulation of regulated mature miRNAs 2 h after the induction of LTP by high‐frequency stimulation (HFS) of the medial perforant pathway. Real‐time polymerase chain reaction analysis confirmed modest upregulation of miR‐132 and miR‐212, and downregulation of miR‐219, while no changes occurred at 10 min post‐HFS. Surprisingly, pharmacological blockade of N‐methyl‐d‐aspartate receptor (NMDAR)‐dependent LTP enhanced expression of these mature miRNAs. This HFS‐evoked expression was abolished by local infusion of the group 1 metabotropic glutamate receptor (mGluR) antagonist, (RS)‐1‐aminoindan‐1,5‐dicarboxylic acid (AIDA). AIDA had no effect on LTP induction or maintenance, but blocked activity‐dependent depotentiation of LTP. Turning to the analysis of miRNA precursors, we show that HFS elicits 50‐fold elevations of primary (pri) and precursor (pre) miR‐132/212 that is transcription dependent and mGluR dependent, but insensitive to NMDAR blockade. Primary miR‐219 expression was unchanged during LTP. In situ hybridization showed upregulation of the pri‐miR‐132/212 cluster restricted to dentate granule cell somata. Thus, HFS induces transcription miR‐132/212 that is mGluR dependent and functionally correlated with depotentiation rather than LTP. In contrast, NMDAR activation selectively downregulates mature miR‐132, ‐212 and ‐219 levels, indicating accelerated decay of these mature miRNAs. This study demonstrates differential regulation of primary and mature miRNA expression by mGluR and NMDAR signaling following LTP induction, the function of which remains to be defined.
Fesoterodine in patients with overactive bladder syndrome: can the severity of baseline urgency urinary incontinence predict dosing requirement?
Authors: Cardozo Linda , Khullar Vik , Wang Joseph T. , Guan Zhonghong , Sand Peter K.
Published: February 2010

Study Type – Therapy (RCT) Level of Evidence 1b

OBJECTIVES

To determine whether baseline urgency urinary incontinence (UUI) episodes predict the need for increased doses of fesoterodine in patients with overactive bladder (OAB), as clinicians would benefit from data that help to predict which patients require higher doses of antimuscarinics to manage UUI episodes.

PATIENTS AND METHODS

In this pooled analysis of data from two double‐blind, placebo‐controlled trials, patients were randomized to placebo or fesoterodine 4 or 8 mg for 12 weeks and stratified into tertiles (>0–<2, 2–<4, or ≥4) according to the number of UUI episodes/24 h as recorded in 3‐day bladder diaries at baseline. The change in mean UUI episodes/24 h from baseline to end of study was assessed using analysis of covariance.

RESULTS

In a post hoc analysis of data from two clinical trials, there were significant reductions from baseline in UUI episodes for fesoterodine 4 and 8 mg vs placebo in patients (n) with >0–<2 (422), 2–<4 (424) and ≥4 (481) UUI episodes at baseline (all P < 0.01). In patients with 2–<4 and ≥4 UUI episodes at baseline, fesoterodine 8 mg gave significantly greater mean reductions (−1.92 and −4.17, respectively) vs fesoterodine 4 mg (−1.43 and −3.31) (P < 0.05). The most common adverse events were dry mouth (placebo, 8%; fesoterodine 4 mg, 19%; and 8 mg, 35%) and constipation (placebo, 2%; fesoterodine 4 mg, 5%; and 8 mg, 6%).

CONCLUSION

Fesoterodine 4 and 8 mg significantly reduced UUI episodes vs placebo; this effect appeared to be greater with fesoterodine 8 mg in patients with ≥2 UUI episodes/24 h at baseline. Fesoterodine was well tolerated, although higher doses increased the incidence of adverse events. These findings might aid the clinical identification of patients with OAB who would most benefit from increasing the dose of fesoterodine from 4 to 8 mg.
A placebo‐controlled exploratory study investigating the efficacy and safety of the phosphodiesterase type 5 inhibitor UK‐369,003 for the treatment of men with storage lower urinary tract symptoms associated with a clinical diagnosis of overactive bladder
Authors: Giuliano Francois A. , Lamb Janice , Crossland Anna , Haughie Scott , Ellis Peter , Tamimi Nihad A.M.
Published: February 2010

Study Type – Therapy (RCT) Level of Evidence 1b

OBJECTIVES

To evaluate the efficacy and safety of the phosphodiesterase type 5 inhibitor, UK‐369,003 modified release (MR), for the treatment of storage lower urinary tract symptoms (LUTS) in men with and without erectile dysfunction (ED).

PATIENTS AND METHODS

This was a multicentre, double‐blind, placebo‐controlled, parallel‐group study conducted across 50 centres in North and South America, Europe and Australia. In all, 310 men aged ≥18 years with a clinical diagnosis of overactive bladder (OAB; voiding frequency ≥8 times/24 h, urgency episode frequency once or more per 24 h and a mean voided volume of <300 mL) and maximum urinary flow rate of >5 mL/s in a voided volume of >150 mL were stratified into two groups (with or without ED) and randomized to one of five treatment groups (10, 25, 50 or 100 mg UK‐369,003; or placebo once a day) for 12 weeks. The primary study endpoints were those derived from the bladder diary that recorded the number of voluntary urinary voids, volume of urine per void, leaks and urgency episodes over a 72‐h period, before baseline and again at 2, 4 and 12 weeks. Secondary efficacy measures included the International Prostate Symptom Score (total and storage and voiding subscores), International Index of Erectile Function–Erectile Function domain (IIEF‐EF), questions 5 and 6 of the Quality of Erection Questionnaire (QEQ), the Overactive Bladder Questionnaire Short Form, the Patient Perception of Bladder Condition, the International Consultation on Incontinence Questionnaire–Male LUTS, and the patient‐reported treatment impact questionnaire.

RESULTS

Overall, there were no clinically relevant treatment differences in voiding frequency, mean voided volume, urgency episode frequency, or nocturia frequency for any dose of UK‐369,003 MR compared with placebo. In the subset of patients with ED there were improvements in the IIEF‐EF and QEQ scores in all UK‐369,003 treatment groups compared with placebo.

CONCLUSIONS

These data provide no evidence of efficacy for UK‐369,003 in the treatment of storage LUTS in men (based on classic OAB eligibility criteria). However, although the endpoints on these classic OAB efficacy variables were negative, there is evidence to suggest a greater preference, satisfaction and willingness to use UK‐369,003 again for all treatment groups compared with placebo.
Development of a scale to assess patient misperceptions about treatment choices for localized prostate cancer
Authors: Beydoun Hind A. , Mohan Ravinder , Beydoun May A. , Davis John , Lance Raymond , Schellhammer Paul
Published: February 2010

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

OBJECTIVES

To develop a questionnaire to assess a patient’s knowledge of his cancer, understanding of treatment choices, and judgement of his survival (KUJ) with and without treatment, as treatment for localized prostate cancer (LPC) can lead to urinary, sexual and bowel side‐effects and might not improve survival in 75% of patients.

PATIENTS AND METHODS

Although >90% of patients in the USA are diagnosed with LPC, ≈94% of them choose treatment, such that newly diagnosed patients need individualized counselling to address misperceptions about the management of LPC. The internal consistency of an 18‐item KUJ scale was evaluated among 184 patients recently diagnosed with LPC at a major urology practice. Principal‐component analyses were applied for computing a KUJ index. Logistic regression modelling was used to identify predictors of the KUJ index.

RESULTS

Cronbach’s α for the KUJ scale was 0.76. Nearly half of the patients provided incorrect answers to most KUJ items. Of the patients, 68% had an income of >US$50 000 and 90% had at least high (or secondary) school literacy level. Quality‐of‐life measures suggested that most patients were physically, mentally and socially healthy. Higher education, income and functional capacity were associated with worse KUJ.

CONCLUSION

The KUJ scale is internally consistent and clinicians can use it to identify the educational needs of patients with LPC before treatment selection. Overall, patients who were socioeconomically disadvantaged and those with physical ailments were better informed about the diagnosis, treatment options and prognosis of prostate cancer.
External validation of the SEARCH model for predicting aggressive recurrence after radical prostatectomy: results from the Duke Prostate Center Database
Authors: Teeter Anna E. , Sun Leon , Moul Judd W. , Freedland Stephen J.
Published: February 2010

Study Type – Prognosis (retrospective cohort) Level of Evidence 2b

OBJECTIVE

To validate a model previously developed using the Shared Equal Access Regional Cancer Hospital (SEARCH) database to predict the risk of aggressive recurrence after surgery, defined as a prostate‐specific antigen (PSA) doubling time (DT) of <9 months, incorporating pathological stage, preoperative PSA level and pathological Gleason sum, that had an area under the curve (AUC) of 0.79 using a cohort of men from the Duke Prostate Center (DPC).

PATIENTS AND METHODS

Data were included from 1989 men from the DPC database who underwent RP for node‐negative prostate cancer between 1987 and 2003. Of these men, 100 had disease recurrence, with a PSADT of <9 months, while 1889 either did not have a recurrence but had ≥36 months of follow‐up or had a recurrence with a PSADT of ≥9 months. We examined the ability of the SEARCH model to predict aggressive recurrence within the DPC cohort, and examined the correlation between the predicted risk of aggressive recurrence and the actual outcome within DPC.

RESULTS

The SEARCH model predicted aggressive recurrence within DPC with an AUC of 0.82. There was a strong and significant correlation between the predicted risk of aggressive recurrence based on the SEARCH tables and the actual outcomes within DPC (r= 0.68, P < 0.001), although the model predictions tended to be slightly higher than the actual risk.

CONCLUSIONS

The SEARCH model to predict aggressive recurrence after RP predicted aggressive recurrence in an external dataset with a high degree of accuracy. These tables, now validated, can be used to help select men for adjuvant therapy and clinical trials.
Mechanisms of inhibition of human benign prostatic hyperplasia in vitro by the luteinizing hormone‐releasing hormone antagonist cetrorelix
Authors: Siejka Agnieszka , Schally Andrew V. , Block Norman L. , Barabutis Nektarios
Published: February 2010

OBJECTIVE

To assess the mechanism by which the luteinizing hormone‐releasing hormone (LHRH) antagonist cetrorelix exerts its effects in men with benign prostatic hyperplasia (BPH), as it produces a long‐lasting improvement in lower urinary tract symptoms that is only partly accounted for by the transient reduction in testosterone levels, and the beneficial results could be due to direct inhibitory effects of cetrorelix on the prostate exerted through prostatic LHRH receptors.

MATERIALS AND METHODS

Using the BPH‐1 cell line we evaluated the effects of cetrorelix in vitro on the proliferation and the expression of receptors for LHRH, epidermal growth factor (EGF), α1A‐adrenergic receptor, STAT‐3 transcription factor and the response to growth factors insulin‐like growth factor (IGF)‐1 and ‐II and fibroblast growth factor (FGF)‐2.

RESULTS

There was expression of LHRH receptors in the human BPH‐1 cell line. Cetrorelix had inhibitory effects on the proliferation rate of BPH‐1 cells, also reflected by the decrease in the expression of the proliferating cell nuclear antigen (PCNA). Cetrorelix inhibited the stimulatory effect of the growth factors IGF‐I and ‐II and FGF‐2 on the proliferation of this line. Cetrorelix also downregulated the expression of the receptors for LHRH and EGF, as well as of α1A‐adrenergic receptors, and inhibited the activation of the STAT3 transcription factor.

CONCLUSIONS

The results show that in vitro cetrorelix can directly inhibit the proliferation rate of the human BPH‐1 cell line by counteracting growth factors like IGF‐I and ‐II and FGF‐2, and downregulating the LHRH receptor and α‐adrenergic receptors, as well as transcription factors.
Association of statin and nonsteroidal anti‐inflammatory drug use with prostate cancer outcomes: results from CaPSURE
Authors: Katz Matthew S. , Carroll Peter R. , Cowan Janet E. , Chan June M. , D’Amico Anthony V.
Published: February 2010

Study Type – Prevalence (prospective cohort) Level of Evidence 1b

OBJECTIVE

To determine whether 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (statins) and nonsteroidal anti‐inflammatory drugs (NSAIDs) are associated with the risk of prostate cancer and improved survival in men with prostate cancer.

PATIENTS AND METHODS

We retrospectively examined the association between NSAID and statin use among 7042 men who underwent radical prostatectomy (RP, 4611) or radiotherapy (RT, 2431) for prostate cancer between 1990 and 2003 identified in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a primarily community‐based national prostate cancer registry. We compared clinical and sociodemographic variables by statin and NSAID use, using chi‐square tests and multinomial logistic regression. We examined associations between medications and comorbid illness with mortality using unadjusted and adjusted Cox proportional hazard models.

RESULTS

The median (range) follow‐up from treatment was 4 (0–16) years. In multivariate survival analysis, statin ‘ever‐use’ was associated with a reduced risk of all‐cause mortality (ACM) after RP (hazard ratio, HR, 0.35, 95% confidence interval, CI, 0.21–0.58) and RT (0.59, 0.37–0.94). NSAID ever‐use was also associated with a reduced risk of ACM after RP (HR 0.47, 95% CI 0.30–0.75) and RT (0.39, 0.25–0.59).

CONCLUSIONS

In a population of men with prostate cancer, statin and NSAID ever‐use were associated with a reduced risk of ACM. Our study highlights the importance of multidisciplinary survivorship care for men with prostate cancer.
Changes in symptoms of renal cell carcinoma over four decades
Authors: Sunela Kaisa L. , Kataja Matti J. , Kellokumpu‐Lehtinen Pirkko‐Liisa I.
Published: February 2010

Study Type – Symptom prevalence (case series) Level of Evidence 4

OBJECTIVE

To determine whether there has been a change in typical symptoms of renal cell carcinoma (RCC), by evaluating the symptoms of patients diagnosed during four decades, as although the increasing incidence of a diagnosis of incidental RCC has been widely reported, the change in other symptoms has not.

PATIENTS AND METHODS

The study included RCC cases diagnosed in the Pirkanmaa Hospital District between 1964 and 1997. The original medical records of 970 patients with 982 RCC tumours were analysed. Primary symptoms were recorded and changes were analysed in three groups, i.e. diagnoses made before 1980, in the 1980s and in the 1990s. Symptoms were also analysed according to stage, tumour class, gender and age.

RESULTS

The incidence of haematuria (P < 0.01) and an increased erythrocyte sedimentation rate (P < 0.001) decreased, but there was no change in other symptoms. Incidental diagnoses increased from 12% to 19% (P < 0.01). Less chronic or systemic symptoms were noted more recently. Stage and tumour class were highly correlated with symptoms: systemic symptoms increased (24% in stage I to 72% in stage IV, a highly statistically significant increase) and asymptomatic tumours became rarer (27% in stage I to 8% in stage IV, again a highly significant increase) with increasing stage. Haematuria was more common in male patients, anaemia and flank pain in women. Elderly patients were more often asymptomatic than younger patients, with 70–79‐year‐olds being the least symptomatic.

CONCLUSIONS

Incidental cases of RCC have recently become more common. Haematuria, hypersedimentation, chronic and systemic symptoms have decreased. Stage, tumour class, gender and age are correlated with symptoms.
Institutional Investors and Institutional Environment: A Comparative Analysis and Review
Authors: Johnson Richard A. , Schnatterly Karen , Johnson Scott G. , Chiu Shih‐Chi
Published: February 2010

abstract

We provide a review of the literature surrounding institutional investor classifications, and we extend this research by examining the aforementioned classification systems and relate this to the three predominant financial systems (market‐based, family‐centred, and bank‐centred systems). After integrating this literature we propose that future research can contribute to the corporate governance field in three main ways: through improved measurement of the central constructs, through more complex research designs (through moderated and/or longitudinal relationships), and through asking new types of questions. We suggest several questions and approaches for future research on institutional investors and their interrelationship with country financial systems.
THE INFLUENCE OF VOLUNTEERS, DONATIONS AND PUBLIC SUBSIDIES ON THE WAGE LEVEL OF NONPROFIT WORKERS: EVIDENCE FROM AUSTRIAN MATCHED DATA
Authors: Haider Astrid , Schneider Ulrike
Published: February 2010

ABSTRACT**:  In this article we add to the literature analyzing wages in the nonprofit sector by estimating a wage function based on employer‐employee matched data for Austria. We concentrate on the influence of voluntary contributions on the wage level of paid workers. By using a quantile regression approach we find that the existence of volunteers reduces the wages of paid employees in nonprofit organizations. The number of volunteers does not have an influence on the wage level. Donations have a small but positive effect for higher income groups only. Public subsidies increase wages of all paid workers in a nonprofit organization.
FRONTIER EFFICIENCY MEASUREMENT IN DEPOSIT‐TAKING FINANCIAL MUTUALS: A REVIEW OF TECHNIQUES, APPLICATIONS, AND FUTURE RESEARCH DIRECTIONS
Authors: Worthington Andrew C.
Published: February 2010

ABSTRACT**:  Despite the global importance of mutuals in financial services, and the universal need to measure and improve organizational efficiency in all deposit‐taking institutions, it is only relatively recently that the most advanced econometric and mathematical programming frontier techniques have been applied. This paper provides a synoptic survey of the comparatively few empirical analyses of frontier efficiency measurement in deposit‐taking financial mutuals, comprising savings and loans, building societies and credit unions in Australia, the UK, and the USA. Both estimation and measurement techniques and the determinants of efficiency are examined. Particular focus is placed on how the results of these studies may help inform regulatory policy and managerial behaviour.
SUNK COSTS OF CAPITAL AND THE FORM OF ENTERPRISE: INVESTOR‐OWNED FIRMS AND WORKER‐OWNED FIRMS*
Authors: Mikami Kazuhiko , Tanaka Satoru
Published: February 2010

ABSTRACT**:  This paper examines implications of sunk costs of capital for efficient forms of enterprise. It is assumed that firm owners and outside traders are asymmetrically informed of venture risks, and that there are sunk costs associated with investment in physical and human capital. We then make an efficiency comparison between investor‐owned and worker‐owned firms. We find that the firm is efficient when it is owned by the input supplier (the investor or worker) who incurs large sunk costs. This is because such an input supplier can credibly signal to the other input supplier that he in fact has a safe project. An empirical study based on the Japanese manufacturing industry seems to support the theoretical result.
Famine as agricultural catastrophe: the crisis of 1622–4 in east Lancashire
Authors: HOYLE R. W.
Published: February 2010

This article argues that historians have paid insufficient attention to the agrarian roots of early modern English famines. While not dismissing the insights arising from entitlements theory, the article takes issue with recent writings that have explained the famine of 1622–3 in north‐west England as an entitlements crisis. It offers new empirical evidence from an estate in east Lancashire to demonstrate the scale of the crisis in the early 1620s, using estate accounts to produce new price data and estimates of productivity. On the basis of oat tithe data, the scale of the shortfall in foodstuffs in the harvest of 1621 is demonstrated as being probably in the region of a third; that of the following year has to be inferred from price data. The evidence shows that the crisis was not limited to the arable economy, but was followed by an extensive restocking of the pastoral economy. The article therefore makes a contribution to the growing interest in weather as an exogenous factor.
Clinical features of non‐hypertensive lobar intracerebral hemorrhage related to cerebral amyloid angiopathy
Authors: Hirohata M. , Yoshita M. , Ishida C. , Ikeda S. I. , Tamaoka A. , Kuzuhara S. , Shoji M. , Ando Y. , Tokuda T. , Yamada M.
Published: February 2010

Background and purpose:  The present study aims to clarify the clinical features of non‐hypertensive cerebral amyloid angiopathy‐related lobar intracerebral hemorrhage (CAA‐L‐ICH).

Methods:  We investigated clinical, laboratory, and neuroimaging findings in 41 patients (30, women; 11, men) with pathologically supported CAA‐L‐ICH from 303 non‐hypertensive Japanese patients aged ≥55, identified via a nationwide survey as symptomatic CAA‐L‐ICH.

Results:  The mean age of patients at onset of CAA‐L‐ICH was 73.2 ± 7.4 years; the number of patients increased with age. The corrected female‐to‐male ratio for the population was 2.2, with significant female predominance. At onset, 7.3% of patients received anti‐platelet therapy. In brain imaging studies, the actual frequency of CAA‐L‐ICHs was higher in the frontal and parietal lobes; however, after correcting for the estimated cortical volume, the parietal lobe was found to be the most frequently affected. CAA‐L‐ICH recurred in 31.7% of patients during the average 35.3‐month follow‐up period. The mean interval between intracerebral hemorrhages (ICHs) was 11.3 months. The case fatality rate was 12.2% at 1 month and 19.5% at 12 months after initial ICH. In 97.1% of patients, neurosurgical procedures were performed without uncontrollable intraoperative or post‐operative hemorrhage.

Conclusions:  Our study revealed the clinical features of non‐hypertensive CAA‐L‐ICH, including its parietal predilection, which will require further study with a larger number of patients with different ethnic backgrounds.
Changes in nutritional status and body composition during enzyme replacement therapy in adult‐onset type II glycogenosis
Authors: Ravaglia S. , Danesino C. , Moglia A. , Costa A. , Cena H. , Maccarini L. , Carlucci A. , Pichiecchio A. , Bini P. , De Filippi P. , Rossi M.
Published: February 2010

Background:  In adult glycogen storage disease type II (GSDII), a single‐gene mutation causes reduction of the lysosomal enzyme acid alpha‐glucosidse. This produces a chronic proximal myopathy with respiratory involvement. Enzyme replacement treatment (ERT) has recently become available and is expected to improve muscle strength. This should result in increased lean body mass. In this study we evaluate body composition and nutritional status in GSDII, and assess whether these parameters changed during treatment.

Methods:  Seventeen patients with late‐onset GSDII, aged 52.6 ± 16.8 years, received ERT for >18 months. Dietary habits and metabolic profiles of glucids, lipids, and proteins were assessed. Body composition was calculated using anthropometry and bioelectrical impedence analysis.

Results:  On inclusion, we found increased fat mass (FM) in five patients in severe disease stage; all had normal body mass index (BMI). FM correlated inversely, and lean mass (LM) directly, with creatine kinase, prealbumin and albumin levels. After treatment, BMI and FM significantly increased, while LM only showed a trend toward increase. Prealbumin and albumin levels increased as early as after the first months of ERT.

Discussion:  Body mass index value may underestimate FM in patients in severe stage of disease, due to altered body composition. In severely affected patients, laboratory parameters revealed a relative protein malnutrition, that was reversed by ERT, this reflecting restoration of normal muscle metabolic pathways. Increased BMI may indicate a reduction in energy consumption during exercise or respiration, along with clinical improvement.
Prevalence of depression in amyotrophic lateral sclerosis and other motor disorders
Authors: Taylor L. , Wicks P. , Leigh P. N. , Goldstein L. H.
Published: February 2010

Background:  Research suggests the prevalence of severe depression in ALS is <20%. In contrast, studies have reported that severe depression affects 40–50% of patients with other neurodegenerative motor conditions (e.g. multiple sclerosis, Parkinson’s disease and Huntington’s disease). The comparison with such disorders has generated a clinical impression that patients with ALS have surprisingly low rates of depression. However, comparisons with such disorders do not take into account the markedly different pathological, physical and behavioural profiles associated with these disorders. To assess further the extent to which ALS is associated with a low prevalence of depression, we compared the prevalence of depression in patients with ALS to that in patients with neuromuscular disorders with more comparable disease profiles.

Methods:  The Beck Depression Inventory‐II (BDI‐II), the Major Depression Inventory (MDI), the Hospital Anxiety and Depression Scale (HADS) and the ALS Functional Rating Scale‐Revised were sent to 212 patients from a tertiary referral Motor Nerve Clinic in London, UK.

Results:  Data were obtained from 51 people with ALS and 39 with other neuromuscular disorders. The non‐ALS group included patients diagnosed with disorders that are characterized by motor neurone dysfunction and/or a decline in everyday function. Analyses revealed no between‐group differences on severity and prevalence rates of depression according to the BDI‐II, HADS Depression Subscale and MDI.

Conclusions:  Our findings do not support the impression that patients with ALS have lower rates of depression than patients with other varied neuromuscular disorders.
Governing Ourselves: Citizen Participation and Governance in Barcelona and Manchester
Authors: BLAKELEY GEORGINA
Published: February 2010

Barcelona and Manchester have become paradigmatic examples of ‘governance‐beyond‐the‐state’, ‘new localism’ or ‘local state entrepreneurialism’. Whatever the label, citizen participation has become a key feature of governance in each city. This article argues that a useful way of understanding the developing relationship between governance and citizen participation is through the analytical perspective of governmentality. This perspective illuminates two paradoxes that characterize the new governance arrangements in these two European cities. The first paradox is that the power of the state is not necessarily diminished despite the emerging plurality of actors involved in governance. The second paradox lies in the fact that the spread of participatory practices as an integral element of new modes of governance does not necessarily lead to citizen empowerment.

Barcelone et Manchester sont désormais des exemples paradigmatiques de ‘gouvernance au‐delà de l’État’, de ‘nouveau localisme’ ou d’‘entrepreneurialisme de l’État local’. Quelle que soit l’étiquette, la participation citoyenne est devenue un trait caractéristique de la gouvernance de chaque ville. Pour comprendre le lien qui se tisse entre gouvernance et participation citoyenne, on adoptera avec profit la perspective analytique de la gouvernementalité. En effet, celle‐ci éclaire deux paradoxes propres aux nouveaux dispositifs de gouvernance dans ces deux villes européennes: le premier paradoxe est que la puissance de l’État n’est pas forcément diminuée malgré la multiplication des acteurs impliqués dans la gouvernance; le second tient au fait que la propagation des pratiques participatives, en tant que composante des nouveaux modes de gouvernance, ne conduit pas forcément à une autonomie accrue des habitants.
Discrete–continuous analysis of optimal equipment replacement
Authors: Yatsenko Yuri , Hritonenko Natali
Published: February 2010

In operations research, the equipment replacement process is usually modeled in discrete time. An alternative approach is represented by continuous‐time vintage capital models that explicitly involve the equipment lifetime and are described by nonlinear integral equations. The paper introduces and analyzes a model that unites both these approaches. The structure of optimal replacement, transition, and long‐term dynamics, and clustering and splitting of replaced machines are discussed and illustrated with numeric examples. Equipment splitting is demonstrated when the optimal equipment lifetime increases.
Analysis of some representative geomorphosites in the Bucegi Mountains: between scientific evaluation and tourist perception
Authors: Comănescu Laura , Nedelea Alexandru
Published: February 2010

Geomorphosites are landforms that have acquired, in time, a certain value (scientific, cultural, aesthetic, ecological and/or economic). This article presents a statistical analysis of the results obtained during our evaluation of geomorphosites, including their associated value in the minds of tourists. The Bucegi Mountains were considered to be an appropriate study area given their great variety in geomorphosites and their accessibility (the highest infrastructure density in the whole Carpathian area). We selected, catalogued and evaluated the best‐known geomorphosites in the Bucegi Mountains without making it our goal to map them. Tourists' opinions were assessed by questionnaire and the data obtained were statistically processed.
An Australian and New Zealand survey of practice of the use of oxytocin at elective caesarean section
Authors: MOCKLER Joanne C. , MURPHY Deirdre J. , WALLACE Euan M.
Published: February 2010

Background:  The use of oxytocin to prevent postpartum haemorrhage at elective caesarean section is largely based on evidence derived from vaginal births. Overseas studies indicate wide variation in practice with regard to specific doses of oxytocin administered at caesarean section. No such surveys have been undertaken in Australia or New Zealand.

Aims:  To survey and report Australian and New Zealand practice regarding oxytocin administration at elective caesarean section.

Methods:  A structured questionnaire was posted to Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists resident in Australia and New Zealand.

Results:  One thousand five hundred and forty‐seven questionnaires were distributed, of which 890 (58%) were returned. Of these, 700 Fellows, 600 from Australia and 100 from New Zealand, currently practiced obstetrics. Almost all Fellows, 686 (98%), reported that they administered an oxytocin bolus at elective caesarean section, most commonly 10 IU (n = 460) or 5 IU (n = 220). The choice of bolus dose was related to country, duration and type (private or public) of practice. A majority of Fellows, 683 (98%), used an additional oxytocin infusion, either routinely or selectively. A total of 68 different regimens were reported. The single most common regimen was 40 IU oxytocin in 1000 mL administered over four hours, used by 255 Fellows (37%).

Conclusions:  There are wide variations in the usage of oxytocin at elective caesarean section in Australia and New Zealand, most likely due to a lack of high level evidence to guide practice. Appropriately designed clinical trials are needed to provide evidence to support future practice.
Women who miscarry: The effectiveness and clinical utility of the Kessler 10 questionnaire in screening for ongoing psychological distress
Authors: STALLMAN Helen M. , McDERMOTT Brett M. , BECKMANN Michael M. , KAY WILSON M. , ADAM Kareen
Published: February 2010

Background:  Early pregnancy loss has been linked to enduring psychological morbidity.

Aims:  This study aimed to investigate the utility of the Kessler 10 (K10) questionnaire as a brief screening instrument to identify women at risk for the development of psychiatric diagnoses three months post‐miscarriage.

Method:  Participants were 117 consecutive women presenting at a public hospital emergency department and receiving a diagnosis of miscarriage.

Main outcome measures:  K10 screen for psychological distress and the Structured Clinical Interview for DSM Disorders to determine psychiatric diagnoses.

Results:  A majority of women (81.2%) experienced elevated levels of distress initially, 24.8% in the very high range. They were not at increased risk of psychiatric diagnoses at three months compared with the general population; however, they were significantly more likely to report subsyndromal symptoms at this time compared with the general population. The baseline K10 score was the only significant predictor of distress at follow‐up (r = 0.45, P < 0.001). The receiver operating characteristic curve shows that a cut‐off of 14 on the K10 has suitable sensitivity (97%) and specificity (82%) for predicting ongoing psychological distress in women who miscarry.

Conclusions:  The K10 is effective in identifying women at risk for ensuring psychological symptoms following miscarriage.
Informing policy for the Australian context – Costs, outcomes and cost savings of prenatal carrier screening for cystic fibrosis
Authors: MAXWELL Susannah , BRAMELD Kate , YOUNGS Leanne , GEELHOED Elizabeth , O’LEARY Peter
Published: February 2010

Aims:  To examine the costs, outcomes and cost savings of three models of prenatal cystic fibrosis (CF) carrier screening compared to no screening from a public health sector perspective.

Methods:  A decision tree was generated to estimate costs and outcomes for each screening model for a hypothetical cohort of 38 000 pregnancies. Sensitivity analysis assessed the impact of model parameter variation.

Results:  Under baseline assumptions, the initial annual cost to provide a prenatal CF carrier‐screening programme is Au$5.32 million, Au$3.35 million and $2.93 million for one‐step, two‐step simultaneous and two‐step sequential screening respectively. Annual costs are significantly lower for an established programme. No screening model provides a net saving over a lifetime horizon; however, the results were sensitive to variation in lifetime cost of care, screening test costs and number of pregnancies per carrier couple.

Conclusions:  Under some scenarios, prenatal CF carrier screening is cost saving to the health system; however, this is not conclusive and depends on several factors. Cost remains a potential barrier due to the substantial level of funding required in the short term. Feasibility and psychosocial, ethical and legal implications of screening need to be considered. Additionally, consultation is required with the Australian community on the acceptability and/or desire for prenatal CF carrier screening.
Lifestyle factors in people seeking infertility treatment – A review
Authors: ANDERSON Kirsty , NISENBLAT Vicki , NORMAN Rob
Published: February 2010

Background: Clinical infertility is a prevalent problem with significant financial and psychosocial costs. Modifiable lifestyle factors exist that may affect a person’s time to conception and their chance of having a healthy, live birth. However, no guideline delineates what preconception advice should be offered to people presenting for infertility treatment.

Aim: The aim of this article is to review the literature regarding modifiable lifestyle factors in people seeking infertility treatment.

Results: A person’s time to pregnancy and their chance of having a healthy, live birth may be affected by factors such as weight, vitamin and iodine intake, alcohol and caffeine consumption, smoking, substance abuse, stress, environmental pollutants, vaccinations and oxidative stress.

Conclusions: Advice on modifiable lifestyle factors should be given to people presenting for infertility treatment to help them make positive changes that may improve their chances of pregnancy and delivering a healthy, live baby. Developing a guideline for this would be a prudent step towards helping clinicians to implement this aspect of preconception care.
MIS 3 marine and lacustrine sediments at Kriegers Flak, southwestern Baltic Sea
Authors: ANJAR JOHANNA , LARSEN NICOLAJ KROG , BJÖRCK SVANTE , ADRIELSSON LENA , FILIPSSON HELENA L.
Published: February 2010

Anjar, J., Larsen, N. K., Björck, S., Adrielsson, L. & Filipsson, H. L. 2010: MIS 3 marine and lacustrine sediments at Kriegers Flak, southwestern Baltic Sea. Boreas, 10.1111/j.1502‐3885.2010.00139.x. ISSN 0300‐9483.

Sediment cores from the Kriegers Flak area in the southwestern Baltic Sea show a distinct lithological succession, starting with a lower diamict that is overlain by a c. 10 m thick clay unit that contains peat, gyttja and other organic remains. On top follows an upper diamict that is inter‐layered with sorted sediments and overlain by an upward‐coarsening sequence with molluscs. In this paper we focus on the clay unit, which has been subdivided into three subunits: (A) lower clay with benthic foraminifera and with diamict beds in the lower part; (B) thin beds of gyttja and peat, which have been radiocarbon‐dated to 31–35 14C kyr BP (c. 36–41 cal. kyr BP); and (C) upper clay unit. Based on the preliminary results we suggest the following depositional model: fine‐grained sediments interbedded with diamict in the lower part (subunit A) were deposited in a brackish basin during a retreat of the Scandinavian Ice Sheet, probably during the Middle Weichselian. Around 40 kyr BP the area turned into a wetland with small ponds (subunit B). A transgression, possibly caused by the damming of the Baltic Basin during the Kattegat advance at 29 kyr BP, led to the deposition of massive clay (subunit C). The data presented here provide new information about the paleoenvironmental changes occurring in the Baltic Basin following the Middle Weichselian glaciation.
Effects of Habitat Fragmentation on Effective Dispersal of Florida Scrub‐Jays
Authors: COULON AURÉLIE , FITZPATRICK JOHN W. , BOWMAN REED , LOVETTE IRBY J.
Published: February 2010

Abstract: Studies comparing dispersal in fragmented versus unfragmented landscapes show that habitat fragmentation alters the dispersal behavior of many species. We used two complementary approaches to explore Florida Scrub‐Jay (Aphelocoma cœrulescens) dispersal in relation to landscape fragmentation. First, we compared dispersal distances of color‐marked individuals in intensively monitored continuous and fragmented landscapes. Second, we estimated effective dispersal relative to the degree of fragmentation (as inferred from two landscape indexes: proportion of study site covered with Florida Scrub‐Jay habitat and mean distance to nearest habitat patch within each study site) by comparing genetic isolation‐by‐distance regressions among 13 study sites having a range of landscape structures. Among color‐banded individuals, dispersal distances were greater in fragmented versus continuous landscapes, a result consistent with other studies. Nevertheless, genetic analyses revealed that effective dispersal decreases as the proportion of habitat in the landscape decreases. These results suggest that although individual Florida Scrub‐Jays may disperse farther as fragmentation increases, those that do so are less successful as breeders than those that disperse short distances. Our study highlights the importance of combining observational data with genetic inferences when evaluating the complex biological and life‐history implications of dispersal.