bluuebunny/crossref_metadata_2025 huggingface dataset:
Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score
Authors: LAM JOHN S. , SELIGSON DAVID B. , YU HONG , LI AI , EEVA MERVI , PANTUCK ALLAN J. , ZENG GANG , HORVATH STEVE , BELLDEGRUN ARIE S.
Published: July 2006

OBJECTIVE

To investigate the expression and potential clinical usefulness of structure‐specific flap endonuclease 1 (FEN‐1) in human primary prostate cancer using tissue microarray technology, as FEN‐1 was recently identified to be overexpressed in CL1.1, the most aggressive clone generated from the hormone‐refractory prostate cancer cell line CL1.

MATERIALS AND METHODS

Immunohistochemistry was performed on tissue microarrays constructed from paraffin‐embedded specimens of primary prostate cancer from 246 patients who had had a radical prostatectomy. Prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal prostate epithelium were represented on the array. FEN‐1 nuclear expression was scored based on the percentage of target cells staining positively, and correlated with Gleason score, preoperative prostate‐specific antigen (PSA) level and pathological stage. The time to PSA recurrence was also analysed.

RESULTS

The mean expression of FEN‐1 was significantly higher in cancer (36.7%) than in normal (13.2%), BPH (4.5%) and PIN (15.4%) specimens (P < 0.001). FEN‐1 expression was significantly correlated with Gleason score (ó = 0.23, P = 0.002). A higher preoperative serum PSA level (P = 0.015), Gleason score ≥ 7 (P < 0.001), seminal vesicle invasion (P < 0.001) and capsular involvement (P = 0.004) were associated with PSA recurrence, whereas FEN‐1 expression was not. In a multivariate analysis, only Gleason score ≥ 7 (P < 0.001), seminal vesicle invasion (P = 0.005) and capsular involvement (P = 0.009) were retained as independent predictors for PSA recurrence.

CONCLUSIONS

FEN‐1 is overexpressed in prostate cancer compared with matched normal prostate, and its expression increases with tumour dedifferentiation, as shown by increasing Gleason score. These results suggest that FEN‐1 might be a potential marker for selecting patients at high risk, and a potential target for prostate cancer diagnosis and therapy.
Brachytherapy in men aged ≤ 54 years with clinically localized prostate cancer
Authors: MERRICK GREGORY S. , WALLNER KENT E. , BUTLER WAYNE M. , GALBREATH ROBERT W. , ALLEN ZACHARIAH A. , ADAMOVICH EDWARD , TRUE LAWRENCE
Published: July 2006

OBJECTIVE

To report the biochemical progression‐free survival (BPFS) in hormone‐naive men aged ≤ 54 years who underwent brachytherapy with or without supplemental external beam radiation therapy (EBRT), as despite favourable biochemical control rates with brachytherapy, there remains a reluctance to recommend non‐extirpative approaches for young men with clinically localized prostate cancer.

PATIENTS AND METHODS

From April 1995 to October 2002, 108 hormone‐naive patients aged ≤ 54 years (median 52 years, range 45–54) had permanent interstitial brachytherapy for clinical stage T1c‐T2c NXM0 (2002 American Joint Committee on Cancer staging) prostate cancer. No patient had a seminal vesicle biopsy or pathological lymph node staging. The mean (sd, median) follow‐up was 5.3 (1.8, 4.8) years. BPFS was defined by a prostate‐specific antigen (PSA) level of ≤ 0.40 ng/mL after the nadir. Risk groups were assigned using the Memorial Sloan‐Kettering Cancer Center criteria. Several clinical, treatment and dosimetric variables were evaluated for their effect on BPFS.

RESULTS

For the entire group, the actuarial 8‐year BPFS was 96%; for low‐ (57 men), intermediate‐ (47) and high‐ (four) risk patients, the BPFS rates were 96%, 100% and three of four, respectively. For biochemically disease‐free patients, the median PSA level after treatment was 0.05 ng/mL. In a multivariate analysis, only pretreatment PSA level predicted biochemical control, while dosimetry variables after treatment were almost statistically significant.

CONCLUSIONS

Hormone‐naive patients aged ≤ 54 years have a high probability of a good 8‐year BPFS after permanent interstitial brachytherapy with or without supplemental EBRT.
Seminal plasma magnesium and premature ejaculation: a case‐control study
Authors: ALOOSH MEHDI , HASSANI MOHAMMAD , NIKOOBAKHT MOHAMMADREZA
Published: July 2006

OBJECTIVE

To determine the relationship between premature ejaculation (PE) and serum and seminal plasma magnesium levels, in a case‐control study.

PATIENTS AND METHODS

Thirty‐eight patients referred to the authors’ urology outpatient clinic were evaluated in two groups; cases comprised 19 men complaining of PE, defined using the Diagnostic and Statistical Manual of Mental Disorders IV criteria and an intravaginal ejaculatory latency time (IELT) of <1 min, and a control group of 19 married men with a normal IELT. All men had a history taken, a systemic physical examination and laboratory studies. After organic and psychogenic disorders were excluded, the 19 patients were included in the study. Seminal plasma and serum magnesium levels were determined using atomic absorption spectrophotometry.

RESULTS

The mean (sd) plasma magnesium level was 94.7 (10.9) mg/L in the cases and 116.7 (11.6) mg/L in the controls. There was a significant relationship between seminal plasma magnesium, but not the plasma level, and PE (P < 0.001 and 0.597 respectively).

CONCLUSION

PE is significantly related with a lower level of seminal plasma magnesium. The pathological physiology of this relationship requires more investigation.
Traffic Fatalities and Public Sector Corruption
Authors: Anbarci Nejat , Escaleras Monica , Register Charles
Published: July 2006

Traffic accidents result in 1 million deaths annually worldwide, though the burden is disproportionately felt in poorer countries. Typically, fatality rates from disease and accidents fall as countries develop. Traffic deaths, however, regularly increase with income, at least up to a threshold level, before declining. While we confirm this by analyzing 1,356 country‐year observations between 1982 and 2000, our purpose is to consider the role played by public sector corruption in determining traffic fatalities. We find that such corruption, independent of income, plays a significant role in the epidemics of traffic fatalities that are common in relatively poor countries.
Institutional Quality and the Gains from Trade
Authors: Borrmann Axel , Busse Matthias , Neuhaus Silke
Published: July 2006

While theoretical models suggest that trade is likely to increase productivity and income levels, the empirical evidence is rather mixed. For some countries, trade has a strong impact on growth, whereas for other countries there is no or even a negative linkage. We examine one likely prerequisite for a welfare increasing impact of trade, that is, the role of institutional quality. Using several model specifications, including an instrumental variable approach, we identify those aspects of institutional quality that matter most for the positive linkage between trade and growth. We find that, above all, labour market regulation is the key to reducing trade‐related adjustment costs. Market entry regulations, the efficiency of the tax system, the rule of law and government effectiveness do play a role too. In essence, the results demonstrate that countries with low‐quality institutions do not benefit from trade.
Do Foreign Investors Punish Democracy? Theory and Empirics, 1984–2001
Authors: Jakobsen Jo , De Soysa Indra
Published: July 2006

Some claim that when level of property rights protection is controlled, democracy lowers foreign direct investment (FDI) to developing countries (Li and Resnick 2003). We critically examine the theoretical claims of the pessimistic arguments and show that FDI responds to preferences of countries and that democracies have a clear preference for FDI given that the scarce factor – capital – will find it harder under democracy to seek rents by raising barriers to entry. On the other hand, labor (the abundant factor in developing countries) should profit from lower barriers to capital importation. We demonstrate conclusively that the most prominent pessimistic result on democracy in the literature is simply an artefact of sample size and testing procedure. We establish robust evidence suggesting that developing country democracies actually receivehigherinflows of FDI, net of a number of control variables. Consistent with our view that host nations' attitudes are shaped by factor endowments, which in turn determine rent‐seeking, we demonstrate that governments controlled by ‘leftist’ political parties also receive more FDI than ‘centrist’ or ‘rightist’ governments among democracies. Why this should be true is not obvious from a theory based on property rights risk alone. An extended sample of LDCs and a better operationalization show that property rightsanddemocracy positively affect FDI. Our results suggest that globalization advances the fortunes of democracies in the developing world.
Group‐directed criticism in Indonesia: Role of message source and audience
Authors: Ariyanto Amarina , Hornsey Matthew J. , Gallois Cindy
Published: July 2006

Research in individualist cultures has shown that group members are more likely to agree with criticisms of their group when the criticisms are made by another ingroup member as opposed to an outgroup member (the intergroup sensitivity effect). However, evaluations of ingroup critics are often harsher when they take their comments to an outgroup audience. In light of research on facework and tolerance for dissent, it seems important to test whether these effects are generalizable to a collectivist culture. Indonesian Muslims (N = 191) received a criticism of their religion stemming either from another Muslim or a Christian, and published in either a Muslim or a Christian newspaper. Participants agreed with the comments more when they were made by an ingroup as opposed to an outgroup member. Furthermore, consistent with previous research in Australia, the effects of audience on agreement were moderated by levels of group identification. Results are discussed in relation to theory about the functional role internal critics can play in group life.
Perceiving communion in the dyadic relationship of others
Authors: Chen Sylvia Xiaohua , Bond Michael Harris , Fung Innoxa
Published: July 2006

The present research took an ecological approach to explore a relational issue in social perception − are the perceived personality characteristics of dyad members and their perceived behavioural exchanges related to perceptions of that dyad’s perceived level of friendship? To this end, observers reported on a dyad they knew well using an indigenous measure of personality perception and the Dyadic Behavioural Exchange Scale, combined with an adapted version of Hays’ Friendship Observation Checklist. Perceived similarity of personality on the dimensions of application, emotional stability (negative) and helpfulness (negative) along with the perceived level of dyadic behaviour exchange were found to be additive predictors of perceived communion or friendship strength. This interplay of personal and interpersonal processes has demonstrated the application of methodological relationalism in the social domain, and broadened the ambit of social cognition to include knowledge of relationship units of which the observer is not a member, but which plays a part in his or her social world.
Thinking groups: Rhetorical enactment of collective identity in three Israeli Kibbutzim
Authors: Asher Smadar Ben , Wagner Wolfgang , Orr Emda
Published: July 2006

The present paper reports a case study about public deliberations in three Israeli kibbutzim regarding a disputed school issue: whether to maintain a traditional in‐kibbutz high school despite a heavy financial burden or to close it and send kibbutz youths to a public regional school The results served as a demonstration of a ‘thinking group’ (i.e. of how the collective aims of a group are achieved by the coordinated rhetorical behaviour of individuals according to the formal rules of the collective deliberations). First, video‐recordings of six general assembly meetings in which the issue was discussed was analyzed as to their argumentative content. Second, the extracted arguments were presented to a sample of 342 kibbutz members to capture the distribution of opinions in the population. It is proposed that most kibbutz members were willing to preserve their collective living and saw the closure of their in‐kibbutz school as a threat to their traditional collective identity. We observed a distinct form of public rhetoric during the deliberations in the general meetings which provides a podium for the disputed opinions, preserves the kibbutz shared identity representation and avoids social friction.
Political Participation and the Workplace: The Spillover Thesis Revisited
Authors: Carter Neil
Published: July 2006

Current concern about declining public participation has ignored the potential of workplace democracy to encourage citizen involvement in political activities. Yet, Carole Pateman, in one of the classic texts of participatory democratic theory, outlines the ‘spillover thesis’, which posits a direct link between workplace participation, political efficacy and public participation. The lack of strong empirical evidence supporting this causal relationship suggests that the processes underpinning the ‘spillover thesis’, particularly between workplace participation and political efficacy, are more complex than Pateman acknowledged. A detailed review of empirical studies of worker co-operatives indicates that the ‘spillover thesis’ needs respecification to take account of seven variables that can shape the relationship between workplace participation and political efficacy. The case for supporting worker co-operatives as an institutional solution to declining public participation is weak.
The New Political Economy of Dirigisme: French Macroeconomic Policy, Unrepentant Sinning and the Stability and Growth Pact
Authors: Clift Ben
Published: July 2006

This article traces the enduring influence of the dirigiste traditions on contemporary French macroeconomic policy-making, arguing that French policy both within and towards the Stability and Growth Pact (SGP) is consistent with long-standing French dirigiste preferences and policy traditions. Specifically it explores how, within the SGP, French governments have created and defended significant fiscal policy space, and how the scope for discretionary policy-making has in fact been enhanced by the credibility accrued through European rule-based governance. Furthermore, it analyses how, in their policies towards the SGP, French governments have successfully influenced the reshaping of the fiscal policy architecture, introducing a more dirigiste interventionism in the interpretation and implementation of the SGP, loosening constraints in accordance with dirigiste preferences. French policy-makers have thus played a ‘long-run game’ with European economic governance—initially accepting ordo-liberal orthodoxy, only to subsequently ‘move the goalposts’ in a more dirigiste direction.
Privatisation in Developing Countries
Authors: Megginson William L. , Sutter Natalie L.
Published: July 2006

We survey empirical studies examining privatisation’s effects in developing economies. Most of these studies find that privatisation yields improvements in the operating and financial performance of divested firms, and only a handful document outright performance declines after privatisation. Almost all studies that examine post‐privatisation changes in output, efficiency, profitability, capital investment spending and leverage document significant increases in the first four measures and significant declines in leverage. The studies examined here are far less unanimous regarding the impact of privatisation on employment levels in privatised firms. Studies that explicitly address the sources of post‐privatisation performance improvement using data from multiple non‐transition economies tend to find stronger efficiency gains for firms in regulated industries, in firms that restructure operations after privatisation, and in countries providing greater amounts of shareholder protection.
Financial Crisis and Firm Performance: empirical evidence from Turkey
Authors: Gonenc Halit , Aybar C. Bulent
Published: July 2006

The objective of this study is to examine the impact of concentrated ownership and business group affiliation on the performance of Turkish firms during the financial crisis by controlling balance sheet currency exposure, international involvement and firm size. Our analysis focuses on a 12‐month window encapsulating the February 2001 financial crisis. Our findings show that balance sheet exposure is the key determinant of the firm performance during the crisis periods. While we find evidence that firms with higher concentrated ownership experience lower stock market performance prior and during the financial crisis, business group affiliation does not have any impact on the performance. However, there is weak evidence that stock market performance increases with the level of business group diversification.
Ownership and Control Structure as Determinants of Corporate Debt Maturity: a panel study of an emerging market
Authors: Arslan Özgür , Karan Mehmet Baha
Published: July 2006

This study highlights the corporate governance potential of debt maturity structure for Turkish firms through investigating its association with ownership and control structure. We model leverage and debt maturity as jointly endogenous under simultaneous equations framework. Firstly, we find that both concentrated ownership structure and presence of a large shareholder is directly but moderately related to corporate debt maturity. We also document that it is important for Turkish firms to match maturity of their assets with maturity of their liabilities. Our findings lend considerable support to the prediction that as firms get financially strong or have more growth opportunities they shorten their corporate debt maturity structure. Moreover, despite having a controlling large shareholder or a concentrated ownership structure, firms with growth opportunities still prefer shorter maturities in order to solve the underinvestment problems. Finally, firm size is positively associated with long‐term debt and our empirical analysis provides no evidence that taxes affect debt maturity structure.
The Payoff to America from Globalisation
Authors: Bradford Scott C. , Grieco Paul L. E. , Hufbauer Gary Clyde
Published: July 2006

This article summarizes the economic payoff to the United States from its postwar trade opening and estimates the potential future gains from more opening going forward. To quantify these gains, we survey different methodologies and estimates. We find that trade opening since World War II has added between $800 billion to $1.4 trillion to the US economy, or about $7,000 to $13,000 per household. More speculative estimates of the potential additional gains from removing the rest of US trade barriers range from $400 billion to $1.3 trillion, or about $4,000 to $12,000 per household. Since trade opening permanently raises national income, these gains are enjoyed annually. Trade opening inevitably entails adjustment costs. We estimate that the lifetime cost of all worker dislocations that have been triggered by expanded trade in the United States could be as high as $54 billion, although probably less. Thepermanentgains from past and potential liberalization easily swamp the modest sums necessary to alleviate thetemporarypains of adjustment. In the future as in the past, free trade can significantly raise income – and quality of life – in America.
Country Competition and US Overseas Assembly
Authors: Swenson Deborah L.
Published: July 2006

To examine the role of international competition in outsourcing production decisions, I study the decisions of producers who used the U.S. Overseas Assembly Program (OAP) to conduct assembly operations in developing countries. The evidence, which is based on U.S. OAP imports between 1991 to 2000, shows that production costs and corporate tax policies both shaped production decisions. While increases in own country costs reduced the size of a developing country's OAP shipments, increases in competitor costs helped to increase a country's shipments. The effects of competitor country cost changes were relatively large, as the analysis suggests that a ten percent increase in competing country costs would increase a country's OAP outsourcing activities by 5.8 percent, while a ten percent increase in competitor country taxes would increase a country's OAP exports by 1.6 percent.
Is Robert I in hell?
Authors: Koziol Geoffrey
Published: July 2006

Can one use the most formal and formulaic type of source left us by the early Middle Ages to probe the beliefs and values of a tenth‐century leader? An enquiry into Robert of Neustria's ‘deposition’ of Charles the Simple, the importance of Saint‐Denis to Robert, and the contemporary meaning of the battle of Soissons.
Premonitory and Resolution Symptoms in Migraine: A Prospective Study in 100 Unselected Patients
Authors: Quintela E , Castillo J , Muñoz P , Pascual J
Published: July 2006

The nosology of migraine premonitory (PS) and resolution (RS) symptoms was studied in 100 migraineurs consulting their general physician. They were asked to fill in, for three attacks, a PS and RS questionnaire. ‘True’ PS/RS were those experienced the day before (or the day after) the headache had started only if they were not present in a questionnaire completed in a pain-free period. True PS and RS were experienced by 84± and 80±, respectively, of subjects for the first attack. The mean and range (per patient) of PS were 6.8 and 0–21 and of RS 4.7 and 0–15. Anxiety, phonophobia, irritability, unhappiness and yawning were the commonest PS, whereas asthenia, tiredness, somnolence and concentration difficulties were the most common RS. Gender, age and Migraine Disability Assessment scores did not influence PS and RS. Both PS and RS were more frequent in migraine with aura subjects. Patients on preventatives showed a decreased frequency of PS and, to a lesser degree, of RS. Severity of headache was associated with a higher frequency of RS. Individual RS and especially PS were quite consistent after three attacks. Almost two-thirds of the symptoms were noticed in at least two out of three attacks, while more than a half of PS and more than a quarter of RS repeated in three out of three attacks. In conclusion, around 80± of unselected migraineurs experience RS and PS. Migraine with aura and severe pain are risk factors for experiencing PS and RS, while preventatives were protective, especially for PS.
Management of Earnings and Analysts' Forecasts to Achieve Zero and Small Positive Earnings Surprises
Authors: Burgstahler David , Eames Michael
Published: July 2006

Abstract:  This paper corroborates the finding of prior studies that managers avoid reporting earnings lower than analyst forecasts (i.e., negative earnings surprises) and provides new evidence of actions contributing to this phenomenon. Specifically, we provide empirical evidence of both (1) upward management of reported earnings and (2) downward ‘management’ of analysts' forecasts to achieve zero and small positive earnings surprises. Further analysis of the components of earnings management suggests that both the operating cash flow and discretionary accruals components of earnings are managed.
Economic evaluation of alternative management methods of first‐trimester miscarriage based on results from the MIST trial
Authors: Petrou S , Trinder J , Brocklehurst P , Smith L
Published: July 2006

Objectives  To compare the cost‐effectiveness of alternative management methods of first‐trimester miscarriage.

Design  Economic evaluation conducted alongside a large randomised controlled trial (the MIST trial).

Setting  Early pregnancy assessment units of seven participating hospitals in southern England.

Sample  A total of 1200 women with a confirmed pregnancy of less than 13 weeks of gestation with a diagnosis of incomplete miscarriage or missed miscarriage.

Methods  Random allocation to expectant management, medical management or surgical management. Collection of health service and broader resource use data, unit costs for each resource item and clinical outcomes.

Main outcome measures  Costs (£, 2001–02 prices) to the health service, social services, women, carers and wider society during the first 8 weeks postrandomisation. Cost‐effectiveness estimates, expressed in terms of incremental cost per gynaecological infection prevented; cost‐effectiveness acceptability curves presented at alternative willingness‐to‐pay thresholds for preventing gynaecological infection.

Results  There was no significant difference in the incidence of gynaecological infection between groups. The net societal cost per woman was estimated at £1086.20 in the expectant group, £1410.40 in the medical group and £1585.30 in the surgical group. Expectant management had a 97.8% probability of being the most cost‐effective management method at a willingness‐to‐pay threshold of £10,000 for preventing one gynaecological infection, while medical management had a 2.2% probability of being the most cost‐effective management method. Expectant management retained the highest probability of being the most cost‐effective management method at all willingness‐to‐pay thresholds of less than £70,000 for preventing one gynaecological infection.

Conclusions  Expectant and medical management of first‐trimester miscarriage possess significant economic advantages over traditional surgical management.
Birth outcomes and pregnancy complications in women with a history of anorexia nervosa
Authors: Ekéus C , Lindberg L , Lindblad F , Hjern A
Published: July 2006

Objective  To examine birth outcomes and pregnancy complications in women with a history of anorexia nervosa.

Design  Prospective cohort study.

Setting  Nationwide study in Sweden.

Population  All primiparous women—discharged from hospital with a diagnosis of anorexia nervosa during 1973 to 1996—who gave birth during 1983 to 2002 (n= 1000) were compared with all non‐anorexia nervosa primiparous women who gave birth during the same years (n= 827 582).

Method  Register study with data from Medical Birth Registry and National Patient Discharge Register.

Main outcome measures  Pre‐eclampsia, instrumental delivery, prematurity, small for gestational age, birthweight, Apgar score and perinatal mortality.

Results  Main birth outcome measures in women with a history of anorexia nervosa were very similar to the main population. The only observed differences were a slightly lower mean birthweight and lower adjusted odds ratios for instrumental delivery in the anorexia nervosa group compared with the main population. Neither severity of the disease nor a shorter recovery phase after first hospitalisation was related to pregnancy complications or birth outcomes.

Conclusion  A history of anorexia nervosa was not associated with negative birth outcomes. Thus, special obstetric monitoring of pregnant women with history of anorexia nervosa does not seem to be warranted in a country with a satisfactory maternity surveillance.
Cannabinoid receptors in human astroglial tumors
Authors: Held‐Feindt Janka , Dörner Lutz , Sahan Gülcan , Mehdorn H. Maximilian , Mentlein Rolf
Published: July 2006

In animal models, cannabinoids are reported to inhibit the growth of tumors, including gliomas. These effects have been claimed to be mediated via cannabinoid receptors 1 and 2 (CB1, CB2). To elucidate a possible relevance for treatment of human gliomas, we investigated receptor subtype expression in surgical material of solid human astrocytomas, gliomas and cultivated glioma cells by quantitative reverse transcriptase polymerase chain reaction, western blot and immunohistochemistry and assayed their functionality. In normal brain, cultivated glioma cells and solid tumors, CB1 mRNA was expressed to a much greater extent than CB2, which in some samples was even undetectable. Expression of both receptor subtypes was unrelated to malignancy, varied between patients, and was not significantly increased in relation to normal brain tissues. In normal brain, CB1 protein was localized on astroglial and other cell types; in gliomas, it was found on astroglial/glioma cells. CB2 protein was detected on microglial cells/macrophages but rarely on astroglial cells. Functionally, CB1 receptor agonists reduced elevated cyclic AMP levels and slightly reduced proliferation of glioma cells in vitro, but did not induce apoptosis. We conclude that cannabinoid therapy of human gliomas targets not only receptors on tumor, but also on other cell types. Therefore, complex and potential side‐effects should be considered carefully.
Down‐regulation of vesicular glutamate transporters precedes cell loss and pathology in Alzheimer's disease
Authors: Kirvell Sara L. , Esiri Margaret , Francis Paul T.
Published: July 2006

Alzheimer's disease (AD) is characterized pathologically by plaques, tangles, and cell and synapse loss. As glutamate is the principle excitatory neurotransmitter of the CNS, the glutamatergic system may play an important role in AD. An essential step in glutamate neurotransmission is the concentration of glutamate into synaptic vesicles before release from the presynaptic terminal. Recently a group of proteins responsible for uptake has been identified – the vesicular glutamate transporters (VGLUTs). The generation of antibodies has facilitated the study of glutamatergic neurones. Here, we used antibodies to the VGLUTs together with immunohistochemistry and western blotting to investigate the status of glutamatergic neurones in temporal, parietal and occipital cortices of patients with AD; these regions were chosen to represent severely, moderately and mildly affected regions at the end stage of the disease. There was no change in expression of the synaptic markers in relation to total protein in the temporal cortex, but a significant reduction in synaptophysin and VGLUT1 was found in both the parietal and occipital cortices. These changes were found to relate to the number of tangles in the temporal cortex. There were no correlations with either mental test score or behaviour syndromes, with the exception of depression.
Altered signaling pathways underlying abnormal hippocampal synaptic plasticity in the Ts65Dn mouse model of Down syndrome
Authors: Siarey Richard J. , Kline‐Burgess Angelina , Cho Madelaine , Balbo Andrea , Best Tyler K. , Harashima Chie , Klann Eric , Galdzicki Zygmunt
Published: July 2006

The Ts65Dn mouse model of Down syndrome (DS) has an extra segment of chromosome (Chr.) 16 exhibits abnormal behavior, synaptic plasticity and altered function of several signaling molecules. We have further investigated signaling pathways that may be responsible for the impaired hippocampal plasticity in the Ts65Dn mouse. Here we report that calcium/calmodulin‐dependent protein kinase II (CaMKII), phosphatidylinositol 3‐kinase (PI3K)/Akt, extracellular signal‐regulated kinase (ERK), protein kinase A (PKA) and protein kinase C (PKC), all of which have been shown to be involved in synaptic plasticity, are altered in the Ts65Dn hippocampus. We found that the phosphorylation of CaMKII and protein kinase Akt was increased, whereas ERK was decreased. Activities of PKA and PKC were decreased. Furthermore, abnormal PKC activity and an absence of the increase in Akt phosphorylation were demonstrated in the Ts65Dn hippocampus after high‐frequency stimulation that induces long‐term potentiation. Our findings suggest that abnormal synaptic plasticity in the Ts65Dn hippocampus is the result of compensatory alterations involving the glutamate receptor subunit GluR1 in either one or more of these signaling cascades caused by the expression of genes located on the extra segment of Chr. 16.
Unconventional neuroprotection against Ca2+‐dependent insults by metalloporphyrin catalytic antioxidants
Authors: Tauskela Joseph S. , Brunette Eric , Kiedrowski Lech , Lortie Karine , Hewitt Melissa , Morley Paul
Published: July 2006

We evaluated whether both inert and catalytically active metalloporphyrin antioxidants,meso‐substituted with either phenyl‐based orN‐alkylpyridinium‐based groups, suppress Ca2+‐dependent neurotoxicity in cell culture models of relevance to cerebral ischemia. Representatives from both metalloporphyrin classes, regardless of antioxidant strength, protected cultured cortical neurons or PC‐12 cultures against the Ca2+ionophores ionomycin or A23187, by suppressing neurotoxic Ca2+influx. Some metalloporphyrins suppressed excitotoxic Ca2+influx indirectly induced by the Ca2+ionophores in cortical neurons. Metalloporphyrins did not quench intracellular fluorescence, suggesting localization to the plasma membrane interface and/or interference with Ca2+ionophores. Metalloporphyrins suppressed ionomycin‐induced Mn2+influx, but did not protect cortical neurons against pyrithione, a Zn2+ionophore. In other Ca2+‐dependent paradigms, Ca2+influx via plasma membrane depolarization, but not through reversal of plasmalemmal Na+/Ca2+exchangers, was modestly suppressed by MnIIImeso‐tetrakis(4‐benzoic acid)porphyrin (MnIIITBAP) or by an inert analog, ZnIITBAP. MnIIITBAP and ZnIITBAP potently protected cortical neurons against long‐duration oxygen–glucose deprivation (OGD), performed in the presence of antagonists of NMDA, α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate and L‐type voltage‐gated Ca2+channels, raising the possibility of an unconventional mode of blockade of transient receptor protein melastatin 7 channels by a metalloTBAP family of metalloporphyrins. The present study extends the range of Ca2+‐dependent insults for which metalloporphyrins demonstrate unconventional neuroprotection. MetalloTBAPs appear capable of targeting an OGD temporal continuum.
Protean agonism of the lysophosphatidic acid receptor‐1 with Ki16425 reduces nerve growth factor‐induced neurite outgrowth in pheochromocytoma 12 cells
Authors: Moughal Noreen A. , Waters Catherine M. , Valentine William J. , Connell Michelle , Richardson Jill C. , Tigyi Gabor , Pyne Susan , Pyne Nigel J.
Published: July 2006

We report here a novel role for the constitutively active lysophosphatidic acid receptor‐1 (LPA1) receptor in providing Gβγ subunits for use by the Trk A receptor. This enhances the ability of nerve growth factor (NGF) to promote signalling and cell response. These conclusions were based on three lines of evidence. Firstly, the LPA1 receptor was co‐immunoprecipitated with the Trk A receptor from lysates, suggesting that these proteins form a complex. Secondly, Ki16425, a selective protean agonist of the LPA1 receptor, decreased constitutive basal and LPA‐induced LPA1 receptor‐stimulated GTPγS binding. Ki16425 reduced the LPA‐induced activation of p42/p44 mitogen activated protein kinase (MAPK), while acting as a weak stimulator of p42/p44 MAPK on its own, properties typical of a protean agonist. Significantly, Ki16425 also reduced the NGF‐induced stimulation of p42/p44 MAPK and inhibited NGF‐stimulated neurite outgrowth. Thirdly, the over‐expression of the C‐terminal GRK‐2 peptide, which sequesters Gβγ subunits, reduced the NGF‐induced activation of p42/p44 MAPK. In contrast, the stimulation of PC12 cells with LPA leads to a predominant Giα2‐mediated Trk A‐independent activation of p42/p44 MAPK, where Gβγ subunits play a diminished role. These findings suggest a novel role for the constitutively active LPA1 receptor in regulating NGF‐induced neuronal differentiation.
Molecular phylogeny of treecreepers (Certhia) detects hidden diversity†
Authors: TIETZE DIETER THOMAS , MARTENS JOCHEN , SUN YUE‐HUA
Published: July 2006

We sequenced a part of the mitochondrial cytochrome‐b gene from the seven treecreeper species, including 18 subspecies, to reconstruct the phylogeny of the genusCerthia. Species status of all seven species could be affirmed.Certhia discolor,C. himalayana,C.nipalensis, andC.tianquanensis, the species with relatively small distribution ranges in southeast Asia and simple territorial song, are found at the base of all phylogenetic trees, although without good support. A comparatively recent sister species ofC. tianquanensisisC. nipalensis, replacingC. discoloras closest relative.Certhia familiaris,C. brachydactylaandC. americanaform a derived set of species (again only weak support). The closest relative ofC. americanaisC. brachydactyla. TheC. familiarissubtree is deeply split into two well‐defined population groups: a Eurasian group including populations in northern China (Qinling range northward and all Eurasia) and a Sino‐Himalayan group (Himalayas and China excluding northern China). In accordance with acoustic characters, the three subspecieshodgsoni,mandelliiandkhamensisof the Sino‐Himalayan group are combined and elevated to species rank:Certhia hodgsoni.Certhia discolor manipurensisis deeply split from nominatediscoloras well, and is also promoted to species level. WithinC. brachydactyla(western palearctic) and withinC. hodgsoni(Himalayas, China) several populations form well‐supported separate lineages that diverged quite recently and represent subspecies level. In all other species, molecular–genetic and vocal characters support traditional species delimitation.
Behavioural and ecological correlates of natural hybridization in birds
Authors: RANDLER CHRISTOPH
Published: July 2006

Hybridization and speciation are central to evolutionary biology. Although birds have been studied more thoroughly than any other vertebrate class, there have still been few macro‐evolutionary analyses. Here, I present results based on 65 phylogenetically independent hybrid types from the western Palearctic, focusing on behavioural and ecological correlates of hybridization. The main results are as follows. (1) Hybrids that are easier to detect were more often reported. (2) A positive correlation exists between population size (mean of both parent species) and the number of hybrids. After accounting for these confounding variables in a General Linear Model, I found (3) that sympatric species pairs produced fewer hybrids than did parapatric species pairs and (4) pairs with at least one of the parent species reported as endangered produced a greater number of hybrids whereas (5) species pairs with high male parental (paternal) care produced fewer hybrids. Other variables were excluded by a stepwise procedure in the following order: sexual dichromatism; body weight differences; publication bias. Phylogenetic information was available for a small number of hybrids but did not influence the results.
Nest survival and productivity of the critically endangered Sociable Lapwing Vanellus gregarius
Authors: WATSON M. , WILSON J. M. , KOSHKIN M. , SHERBAKOV B. , KARPOV F. , GAVRILOV A. , SCHIELZETH H. , BROMBACHER M. , COLLAR N. J. , CRESSWELL W.
Published: July 2006

The Sociable Lapwing Vanellus gregarius is a critically endangered species, probably declining from 5000 pairs to 500 pairs in 11 years. Fieldwork was conducted at two sites in Kazakhstan, May–August 2004, to identify causes of the species’ decline. In total, 58 nests and a minimum of 36 broods in 16 colonies were found: colonies consisted of 1–8 nests that were on average 154 m apart, with 2.1 km between colonies. Although classified as biparental, the total proportion of time both parents spent incubating was low (77 ± 2% se, n = 13 nests). Daily survival rates (Mayfield method) were very low during incubation (0.943 ± 0.009 se) but high during the chick stage (0.986 ± 0.004 se); incubation and chick‐stage durations were found to be 28.5 and 29 days, respectively, so that the overall probability of any breeding attempt fledging chicks was 0.124 (0.055–0.274 95% confidence interval). A breeding attempt that produced fledglings, fledged 2.2 ± 0.2 se chicks (n = 26) on average. Observed productivity predicted the population decline over the last 11 years well (using the maximum number of nesting attempts per pair of 1.4 that could have occurred in this study, and assuming an adult and first‐year survival rate of 0.74 and 0.60, respectively, based on the means for Northern Lapwing Vanellus vanellus and Golden Plover Pluvialis apricalia). Nest survival during incubation (controlling for colony effects) may have been longer for nests in predominantly Artemisia rather than grass habitat. Mean nest survival for a colony was higher in areas with more bare ground and more nest predators, suggesting that predators were relatively unimportant in nest (egg or chick) mortality, but was lower in areas with high numbers of cattle, suggesting that trampling was important (64% of known‐cause nest failures, n = 11, were trampled). Nests were preferentially sited in areas of Artemisia, where there was greater dung abundance, and probably shorter vegetation, suggesting that highly grazed vegetation is important for nesting. Chicks preferentially selected areas with a lower percentage of bare ground and possibly taller vegetation, suggesting that more vegetated areas are important for chicks. The results suggest that low egg survival due to nesting in areas of high grazer density may be responsible for the Sociable Lapwing's decline. Although grazers may create suitable vegetation for initial nesting, if those grazers remain at high density as in anthropogenic systems then they may reduce nest survival, probably through trampling. Experimentally maintaining grazing early but reducing it later in the breeding season is the logical first step in managing the species to increase egg survival and so to increase productivity.
Experimental tail elongation in male Barn SwallowsHirundo rusticareduces provisioning of young, but only in second broods
Authors: CUERVO JOSÉ J. , MØLLER ANDERS P.
Published: July 2006

At the beginning of the breeding season, the outermost tail feathers of 31 male Barn SwallowsHirundo rusticawere either shortened by 20 mm, elongated by 20 mm or left unmanipulated. In first broods, the number of feeding bouts (per nestling per hour) by males and females did not differ significantly among experimental groups. However, in second broods, males with elongated tails fed their nestlings less often than males with shortened or unmanipulated tails. Male tail elongation may have been detrimental to flight, making capture of insects more difficult. Females paired to long‐tailed males did not compensate for this reduction in feeding by males and their nestlings received less food. Neither feeding rates nor brood size differed significantly between first and second broods. Variation in abundance of large insects at different times of the day (high around noon and low in the morning and afternoon) matched variation in feeding rates, supporting the importance of large insects in the Barn Swallow diet. Different feeding rate patterns in first and second broods by males with elongated tails could have at least three explanations: (1) such males were able to adjust their parental effort to some extent, temporarily compensating for an imposed handicap; (2) they were more sensitive than males in the other experimental groups to late season food shortage (a decrease in numbers of large insects, the main Barn Swallow prey, was observed as the season progressed); and (3) they were more sensitive than males in the other experimental groups to the deterioration in their physical condition after first broods.
Is Some Provider Advice on Smoking Cessation Better Than No Advice? An Instrumental Variable Analysis of the 2001 National Health Interview Survey
Authors: Bao Yuhua , Duan Naihua , Fox Sarah A.
Published: July 2006

Research Objective. To estimate the effect of provider advice in routine clinical contacts on patient smoking cessation outcome.

Data Source. The Sample Adult File from the 2001 National Health Interview Survey. We focus on adult patients who were either current smokers or quit during the last 12 months and had some contact with the health care providers or facilities they most often went to for acute or preventive care.

Study Design. We estimate a joint model of self‐reported smoking cessation and ever receiving advice to quit during medical visits in the past 12 months. Because providers are more likely to advise heavier smokers and/or patients already diagnosed with smoking‐related conditions, we use provider advice for diet/nutrition and for physical activity reported by the same patient as instrumental variables for smoking cessation advice to mitigate the selection bias. We conduct additional analyses to examine the robustness of our estimate against the various scenarios by which the exclusion restriction of the instrumental variables may fail.

Principal Findings. Provider advice doubles the chances of success in (self‐reported) smoking cessation by their patients. The probability of quitting by the end of the 12‐month reference period increased from 6.9 to 14.7 percent, an effect that is of both statistical (p<.001) and clinical significance.

Conclusions. Provider advice delivered in routine practice settings has a substantial effect on the success rate of smoking cessation among smoking patients. Providing advice consistently to all smoking patients, compared with routine care, is more effective than doubling the federal excise tax and, in the longer run, likely to outperform some of the other tobacco control policies such as banning smoking in private workplaces.
How Do Doctors in Different Countries Manage the Same Patient? Results of a Factorial Experiment
Authors: McKinlay John , Link Carol , Arber Sara , Marceau Lisa , O'Donnell Amy , Adams Ann
Published: July 2006

Objective.To determine the relative contributions of: (1) patient attributes; (2) provider characteristics; and (3) health care systems to health care disparities in the management of coronary heart disease (CHD) and depression.

Data Sources/Study Setting.Primary experimental data were collected in 2001–2 from 256 randomly sampled primary care providers in the U.S. (Massachusetts) and the U.K. (Surrey, Southeast London, and the West Midlands).

Study Design.Two factorial experiments were conducted in which physicians were shown, in random order, two clinically authentic videotapes of “patients” presenting with symptoms strongly suggestive of CHD and depression. “Patient” characteristics (age, gender, race, and socioeconomic status [SES]) were systematically varied, permitting estimation of unconfounded main effects and the interaction of patient, provider, and system‐level influences.

Data Collection/Data Extraction Methods.Analysis of variance was used to measure provider decision‐making outcomes, including diagnosis, information seeking, test ordering, prescribing behavior, lifestyle recommendations, and referrals/follow‐ups.

Principal Findings.There is a high level of consistency in decision making for CHD and depression between the U.S. and the U.K. Most physicians in both countries correctly identified conditions depicted in the vignettes, although U.S. doctors engage in more information seeking, are more likely to prescribe medications, and are more certain of their diagnoses than their U.K. counterparts. The absence of any national differences in test ordering is consistent for both of the medical conditions depicted. U.K. physicians, however, were more likely than U.S. physicians to make lifestyle recommendations for CHD and to refer those patients to other providers.

Conclusions.Substantively, these findings point to the importance of patient and provider characteristics in understanding between‐country differences in clinical decision making. Methodologically, our use of a factorial experiment highlights the potential of these methods for health services research—especially the estimation of the influence of patient attributes, provider characteristics, and between‐country differences in the quality of medical care.