bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between IRF6 SNPs and Oral Clefts in West China
Authors: Huang Y. , Wu J. , Ma J. , Beaty T.H. , Sull J.W. , Zhu L. , Lu D. , Wang Y. , Meng T. , Shi B.
Published: September 2009

Analyses of previous data have confirmed the contribution of the IRF6 gene to susceptibility to non- syndromic oral clefts (NSOC) in some populations. We tested for associations between the rs2013162, rs2235375, and rs2235371 polymorphisms in IRF6 and the risk of NSOC, using both case-parent trio and case-control designs on samples from western China. Our study group consisted of 332 persons with NSOC, their parents (289 mothers and 243 fathers for 206 complete trios for these three SNPs), and 174 control individuals. We found strong evidence of over- and under-transmission of the C allele (the Val allele) at rs2235371, and the C allele at rs2235375 in cleft case-parent trios (P = 0.013 and P = 0.000, respectively). There were significant differences in the frequency distributions of both genotypes and alleles when cases were compared with control infants at rs2235371 and rs2235375. Five specific haplotypes showed significant over- and under-transmission. These results further support a role for IRF6 variants in western Chinese populations.
Compressive Force Induces VEGF Production in Periodontal Tissues
Authors: Miyagawa A. , Chiba M. , Hayashi H. , Igarashi K.
Published: September 2009

During orthodontic tooth movement, the activation of the vascular system in the compressed periodontal ligament (PDL) is an indispensable process in tissue remodeling. We hypothesized that compressive force would induce angiogenesis of PDL through the production of vascular endothelial growth factor (VEGF). We examined the localization of VEGF in rat periodontal tissues during experimental tooth movement in vivo, and the effects of continuous compressive force on VEGF production and angiogenic activity in human PDL cells in vitro. PDL cells adjacent to hyalinized tissue and alveolar bone on the compressive side showed marked VEGF immunoreactivity. VEGF mRNA expression and production in PDL cells increased, and conditioned medium stimulated tube formation. These results indicate that continuous compressive force enhances VEGF production and angiogenic activity in PDL cells, which may contribute to periodontal remodeling, including angiogenesis, during orthodontic tooth movement.
Assessing the Relationship between Violent and Nonviolent Criminal Activity among Serious Adolescent Offenders
Authors: MacDonald John M. , Haviland Amelia , Morral Andrew R.
Published: September 2009

Understanding the progression of violent and nonviolent criminal activity remains a matter of theoretical debate. In the present study, the authors build on criminological theory and assess the extent to which the progression of violent and nonviolent criminal behaviors follows different trajectories. The authors rely on semiparametric mixture models to examine these comorbidities of offending in a longitudinal sample of delinquent adolescents. The results suggest that the trajectories of violent and nonviolent criminal offending follow similar paths over time and that membership in the chronic violent and nonviolent offender groups are associated with overlapping sets of risk factors. However, the results also indicate that at the individual level, membership in a particular nonviolent offending group does not share high concordance with membership in a particular violent offender group. These findings raise questions about the adequacy of general theories of crime progression and suggest the need to continue investigating behavioral theories that discriminate between different forms of offending.
Can Australian Universities Take Measures to Increase the Lecture Attendance of Marketing Students?
Authors: Dolnicar Sara , Kaiser Sebastian , Matus Katrina , Vialle Wilma
Published: September 2009

Lectures are a central element of traditional university learning, but Australian lecturers increasingly face very low levels of lecture attendance. A significant amount of research exists that investigates the drivers of lecture attendance. However, those studies typically study single factors in an isolated manner, thus overestimating the importance of individual factors. This study contributes to the understanding of lecture attendance (and nonattendance) by including a range of factors that potentially affect lecture attendance simultaneously, thus accounting for possible interactions between factors and identifying the key drivers of lecture attendance. The study uses a survey among all students of an Australian university to compute a regression model with the probability of lecture attendance as the dependent variable. Results indicate that only four of the factors previously investigated are significant for marketing students (i.e., the difficulty of the subject, the quality of the lecture as perceived by the student, the quality of the student as indicated by his or her average mark, and the format of the lecture), which leaves little opportunity for Australian universities to improve attendance with simple measures. Instead, the data suggest that universities need to improve the quality of lectures to achieve better attendance levels.
Independent Drilling Outperforms Conventional Transtibial Drilling in Anterior Cruciate Ligament Reconstruction
Authors: Steiner Mark E. , Battaglia Todd C. , Heming James F. , Rand Jason D. , Festa Anthony , Baria Michael
Published: September 2009

Background

Optimal tunnel placement is critical in anterior cruciate ligament reconstructive surgery, yet the method used to drill the tunnels may compromise their placement.

Hypothesis

An independent drilling method versus a conventional transtibial drilling method will place tunnels in different locations and produce reconstructions with different kinematics.

Study Design

Controlled laboratory study.

Methods

Ten pairs of knees had anterior cruciate ligament reconstructions produced by either a conventional transtibial drilling method or an independent drilling method. The location of the tunnels was recorded, and the knees were tested for laxity in the normal state, with the anterior cruciate ligament removed, and with the anterior cruciate ligament reconstructed. A surgical navigation system guided the placement of the independently drilled tunnels and measured joint laxity in response to various combinations of anterior force and rotational torques.

Results

The conventional transtibial drilling method used in this study placed tibial tunnels posterior and femoral tunnels superior relative to their footprints and resulted in more vertical grafts. In contrast, the independently drilled tibial and femoral tunnels were more anterior and central in their respective footprints, resulting in more horizontal grafts. The horizontal grafts of the independent drilling method were superior to the vertical grafts of this study’s transtibial drilling method in restoring normal anterior and rotational knee laxity.

Conclusion

An independent drilling method can produce tunnels with superior function compared with tunnels produced by a conventional transtibial drilling method.

Clinical Relevance

Single-bundle anterior cruciate ligament reconstructions will be improved if grafts are centered in their anatomical insertions by an independent drilling method versus grafts placed by a conventional transtibial drilling method.
WERS the validity? a critique of the 2004 Workplace Employment Relations Survey of employees
Authors: Timming Andrew R.
Published: September 2009

The Workplace Employment Relations Survey series is a tremendously useful source of data for industrial relations researchers. But, like all large-scale secondary datasets, it has a number of structural design problems. These have not been articulated previously in much depth. Looking at the 2004 instalment of the series, this article aims to offer a critical appraisal of the survey of employees. The structure of the questionnaire and the validity of the items are critiqued. Recommendations are offered for the next edition of the Workplace Employment Relations Survey.
Gene expression profiling in rat liver treated with compounds inducing elevation of bilirubin
Authors: Hirode M , Horinouchi A , Uehara T , Ono A , Miyagishima T , Yamada H , Nagao T , Ohno Y , Urushidani T
Published: September 2009

We have constructed a large-scale transcriptome database of rat liver treated with various drugs. In an effort to identify a biomarker for the diagnosis of elevated total bilirubin (TBIL) and direct bilirubin (DBIL), we extracted 59 probe sets of rat hepatic genes from the data for seven typical drugs, gemfibrozil, phalloidin, colchicine, bendazac, rifampicin, cyclosporine A, and chlorpromazine, which induced this phenotype from 3 to 28 days of repeated administration in the present study. Principal component analysis (PCA) using these probes clearly separated dose- and time-dependent clusters in the treated groups from their controls. Eighteen more drugs in the database, reported to elevate TBIL and DBIL, were estimated by PCA using these probe sets. Of these, 12 drugs, that is methapyrilene, thioacetamide, ticlopidine, ethinyl estradiol, alpha-naphthylisothiocyanate, indomethacin, methyltestosterone, penicillamine, allyl alcohol, aspirin, iproniazid, and isoniazid were also separated from the control clusters, as were the seven typical drugs causing elevation of TBIL and DBIL. The principal component 1 (PC1) value showed high correlation with TBIL and DBIL. In the cases of colchicine, bendazac, chlorpromazine, gemfibrozil, and phalloidin, the possible elevation of TBIL and DBIL could be predicted by expression of these genes 24 h after single administration. We conclude that these identified 59 probe sets could be useful to diagnose the cause of elevation of TBIL and DBIL, and that toxicogenomics would be a promising approach for prediction of this type of toxicity.
Oxalate-mediated oxidant–antioxidant imbalance in erythrocytes: role of N-acetylcysteine
Authors: Bijarnia RK , Kaur T , Singla SK , Tandon C
Published: September 2009

The present in-vivo study was to observe the effect of N-acetylcysteine (NAC) on oxalate-induced oxidative stress on rat erythrocytes. A total of 15 Wistar rats were divided into three groups. The control group received normal saline by single intraperitoneal injection. Hyperoxaluria was induced by single intraperitoneal (i.p.) dose of sodium oxalate (70 mg/kg body weight in 0.5 mL saline) to a second group. The third group was administered single i.p. dose of NAC according to 200 mg/kg body weight dissolved in 0.5 mL saline, half an hour after oxalate dose. NAC administration normalized antioxidant enzyme activities (superoxide dismutase and catalase) and reduced malondialdehyde content (indicator of lipid peroxidation) in hyperoxaluric rat’s red blood cell (RBC) lysate. NAC administration also resulted in a significant improvement of thiol content in RBC lysate via increasing reduced glutathione content and maintaining its redox status. Oxalate-caused alteration of cholesterol/phospholipid ratio (determining membrane fluidity) was also rebalanced by NAC administration. Further, after NAC administration, electron microscopy showed improved cell morphology presenting its prophylactic properties. Above results indicate that NAC treatment is associated with an increase in plasma antioxidant capacity and a reduction in the susceptibility of erythrocyte membranes to oxidation. Thus, the study presents positive pharmacological implications of NAC against oxalate-mediated impairment of erythrocytes.
Review: Platelet Function Testing and Implications for Clinical Practice
Authors: Collet Jean-Philippe , Montalescot Gilles
Published: August 2009

Platelets are key mediators in the pathophysiology of atherothrombotic disease. Inappropriate platelet activation can lead to thrombosis and ischemic events. Platelet function testing has been used to monitor patient response to antiplatelet therapy. Variability in response to antiplatelet therapy may be due in part to incomplete inhibition of targeted pathways (thromboxane A2 and adenosine diphosphate [ADP]) by currently available agents (aspirin and P2Y12 ADP receptor antagonists). Low responsiveness to antiplatelet therapy (as measured in various platelet function assays) correlates with a high rate of ischemic events. However, tailoring treatment based on platelet response remains to be definitively proven in clinical trials, correlations between assays are modest, and concordance in defining suboptimal response is poor. Additional studies are needed to determine whether changes in therapy based on results of platelet function testing improve clinical outcomes, and thus will determine whether broader use of platelet function testing in clinical practice is warranted.
The Effect of Angiotensin-Converting Enzyme Inhibitor on Hemodynamic Instability in Patients Undergoing Cardiopulmonary Bypass: Results of a Dose-Comparison Study
Authors: Shahzamani Mehran , Yousefi Zohreh , Frootaghe Azam Noori , Jafarimehr Elnaz , Froughi Mahnoosh , Tofighi Farhood , Azadani Ali N. , Pourhoseingholi Mohamad Amin , Azadani Peyman Nejatbakhsh
Published: August 2009

Background: Recently, hemodynamic instability including hypotension and its effect on the clinical outcome in patients treated with angiotensin-converting enzyme inhibitors (ACEIs) during coronary artery bypass graft (CABG) has been described. However, no analysis has examined the dose of ACEIs and its risk of hypotension. In this study, we tested the hypothesis that a higher dose of ACEIs could lead to increased episodes of hypotension.

Methods: A total of 300 patients scheduled for CABG were studied prospectively. They were divided into 3 groups according to their preoperative use of different doses of ACEIs. The demographic and medical characteristics were compared between these 3 groups. During CABG and throughout the intensive care unit (ICU), vasoconstrictors were infused in patients undergoing hypotension (mean arterial pressure [MAP] < 65 mm Hg or >30% below baseline). The predictive factors responsible for hypotension were investigated separately using univariate and multivariate logistic regression models.

Results: The 3 groups were similar with regard to the patients’ demographic and medical characteristics. The patients treated with ACEIs were more likely to develop hypotension (73% of high dose and 47% of low dose) in the operating room than those without ACEIs (30%). However, in the ICU, there was no significant association between hemodynamic changes and ACEIstreated patients. Other independent risk factors identified for hypotension were ejection fraction, history of myocardial infarction, coronary grafting count, and pump time during surgery and/or ICU admission. Conclusions: Hemodynamic changes during CABG were observed to be directly proportional to the dosage of ACEIs prescribed preoperatively.
Should the Federal Government Reallocate Funds within Federal Transfers?
Authors: Neves Sequeira Tiago , Ferreira-Lopes Alexandra
Published: August 2009

It is recognized that one of the goals of federal transfers is to provide the states with some financial leverage during recessions. Federal transfers in the United States comprise such components as retirement and disability payments for individuals, other direct payments for individuals or organizations, grants, procurement contracts, and salaries and wages. Is the composition of the federal transfers’ budget having an optimal effect on the business cycle or should the federal government reallocate some expenditure? In this article, we argue that the federal government may improve its role in stabilizing the business cycle if some reallocation is made from procurement contracts and payments for other than individuals to direct payments for individuals, grants, and disability and retirement payments.
Segregation behaviour in Nb microalloyed steels
Authors: Davis C. L. , Strangwood M.
Published: August 2009

Four continuously cast slabs from two sources were characterised by optical microscopy and scanning electron microscope energy dispersive X-ray spectroscopy (SEM-EDS) in the as cast state and after normalisation close to the Ae3 temperature. For all four slabs the composition of the majority of the slab depth (>80%) was the bulk composition and in this region microsegregation, particularly of Nb, was found to agree with predicted partition ratios from equilibrium thermodynamics. For two of the slabs, which gave final solidification as single phase austenite, equilibrium thermodynamics were also able to predict the compositional centreline macrosegregation. In the other two cases, this simple approach was not successful, which has been ascribed to solidification as a more complex phase mixture (austenite and δ-ferrite) or more complex processing during solidification (e.g. soft reduction).
Microstructure evolution model for hot strip rolling of Nb–Mo microalloyed complex phase steel
Authors: Sarkar S. , Militzer M.
Published: August 2009

A microstructure model for hot strip rolling of an Nb–Mo microalloyed complex phase steel has been proposed. The constitutive behaviour of austenite is described by the Kocks–Mecking model. The static softening kinetics is simulated by a combined recovery recrystallisation model using the law of mixtures. Ferrite transformation start is modelled with an approach that considers the early growth of corner nucleated ferrite. Bainite start is related to a critical driving pressure. Both ferrite and bainite reactions are described using the Johnson–Mehl–Avrami–Kolmogorov (JMAK) approach in combination with the additivity rule. The martensite fraction is empirically related to the carbon enrichment in austenite and is, thus, a function of the ferrite fraction formed in the final microstructure. Precipitation strengthening during coiling is simulated with a modified Shercliff–Ashby model. The microstructure models for these metallurgical phenomena have been validated with experimental studies of laboratory simulated hot strip rolling conditions and run-out table cooling strategies.
On strength of microalloyed steels: An interpretive review
Authors: DeArdo A. J. , Hua M. J. , Cho K. G. , Garcia C. I.
Published: August 2009

In the mid-1950s, hot rolled carbon steels exhibited high carbon contents, coarse ferrite pearlite microstructures, and yield strengths near 300 MPa. Their ductility, toughness and weldability were poor. Today, a half century later, hot rolled steels can exhibit microstructures consisting of mixtures of ferrite, bainite and martensite in various proportions. These structures are very fine and can show yield strengths over 900 MPa, with acceptable levels of ductility, toughness and weldability. This advancement was made possible by the combination of improved steelmaking, microalloying technology and better rolling and cooling practices. The purpose of this paper is to chronicle some of the remarkable progress in steel alloy and process design that has resulted in this impressive achievement.
The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up
Authors: Garg Ravin J. , Kantarjian Hagop , O'Brien Susan , Quintás-Cardama Alfonso , Faderl Stefan , Estrov Zeev , Cortes Jorge
Published: September 2009

Responses can be achieved with dasatinib or nilotinib after failure of 2 prior tyrosine kinase inhibitors (TKIs). We report on 48 chronic myeloid leukemia patients sequentially treated with 3 TKIs: 34 with dasatinib after imatinib/nilotinib failure and 14 with nilotinib after imatinib/dasatinib failure. Before the third TKI, 25 patients were in chronic phase (CP), 10 in accelerated phase (AP), and 13 in blast phase (BP). Best response to third TKI in CP was 5 major molecular responses (MMR), 3 complete cytogenetic (CCyR), 2 partial cytogenetic (PCyR), 3 minor cytogenetic (mCyR), 6 complete hematologic responses (CHR), and 6 with no response (NR). In AP, 1 patient achieved MMR, 1 CCyR, 2 PCyR, 1 mCyR, 4 CHR, and 1 NR. In BP, 1 achieved MMR, 2 CCyR, 1 PCyR, 1 mCyR, 2 returned to CP, and 6 NR. Median CCyR duration was 16.3 months; 3 CP patients achieving CCyR had a response more than 12 months. Median failure-free survival was 20 months for patients in CP, 5 months in AP, and 3 months in BP. Use of second-generation TKI after failure to 2 TKIs may induce responses, but these are usually not durable except in some CP patients. New treatment options are needed.
Emerging inhaled bronchodilators: an update
Authors: Cazzola M. , Matera M. G.
Published: August 2009

Bronchodilators remain central to the symptomatic management of chronic obstructive pulmonary disease and asthma, and, for this reason and also because the patent protection of many bronchodilators has expired, several companies have reinitiated research into the field.

The only limits set for the development of a long-lasting bronchodilator with a new product profile are medical needs and marketing opportunities. The incorporation of once-daily dose administration is an important strategy for improving adherence and is a regimen preferred by most patients.

A variety of β2-agonists and antimuscarinic agents with longer half-lives and inhalers containing a combination of several classes of long-acting bronchodilator are currently under development.

The present article reviews all of the most important compounds under development, describing what has been done and discussing their genuine advantage.
Effects of exercise training in patients with idiopathic pulmonary arterial hypertension
Authors: de Man F. S. , Handoko M. L. , Groepenhoff H. , van 't Hul A. J. , Abbink J. , Koppers R. J. H. , Grotjohan H. P. , Twisk J. W. R. , Bogaard H-J. , Boonstra A. , Postmus P. E. , Westerhof N. , van der Laarse W. J. , Vonk-Noordegraaf A.
Published: August 2009

We determined the physiological effects of exercise training on exercise capacity and quadriceps muscle function in patients with idiopathic pulmonary arterial hypertension (iPAH).

In total, 19 clinically stable iPAH patients (New York Heart Association II-III) underwent a supervised exercise training programme for the duration of 12 weeks. Maximal capacity, endurance capacity and quadriceps function were assessed at baseline and after 12 weeks. In 12 patients, serial quadriceps muscle biopsies were obtained.

6-min walk distance and peak exercise capacity did not change after training. However, endurance capacity improved significantly after training, demonstrated by a shift of the anaerobic threshold to a higher workload (from 32±5 to 46±6 W; p = 0.003) together with an increase in exercise endurance time (p<0.001). Moreover, exercise training increased quadriceps strength by 13% (p = 0.005) and quadriceps endurance by 34% (p = 0.001).

Training enhanced aerobic capacity of the quadriceps, by increasing capillarisation (1.36±0.10 to 1.78±0.13 capillaries per muscle fibre; p<0.001) and oxidative enzyme activity, especially of the type-I (slow) muscle fibres. No changes were found in cross-sectional area and fibre type distribution.

Exercise training in iPAH improves exercise endurance and quadriceps muscle function, which is also reflected by structural changes of the quadriceps.
How to increase the value of randomised trials in COPD research
Authors: Puhan M. A. , Schünemann H. J.
Published: August 2009

Methodological criteria that increase the validity of randomised trials are often not considered in respiratory research, even in large chronic obstructive pulmonary disease (COPD) trials. We describe four important aspects in the design, analysis and reporting of randomised trials, selected based on their relevance to current COPD research and based on our judgments of importance for researchers and users of the literature.

First, to optimally control for confounding, where confounding refers to a factor that is associated with an exposure or intervention and influences the outcome, a clear definition of the main relationship between treatment and the primary outcome as well as identification of measurable confounders is required. In addition to randomisationper seas the key method to protect against confounding, restriction (excluding patients with specific characteristics that may introduce confounding), stratification (separate randomisation of patients with specific characteristics) and statistical adjustment are means to be considered to optimally control for confounding that simple randomisation may not achieve.

Secondly, the selection of the primary outcome should be guided by the importance to patients. Secondary outcomes provide hypotheses about the effects observed for the primary outcome and can provide important data for systematic reviews and meta-analyses, but should be interpreted with caution in single trials.

Thirdly, in study power calculations, not only the actual sample size, but the number of events, has a large influence on the power of the study and, often, unrealistic assumptions about event rates are made to increase the feasibility of trials.

Finally, essential steps to transfer results from research to practice include complete reporting of trials and developing tools, such as decision aids, to support patients and physicians in their shared decision making.
Comparison of spirometry criteria for the diagnosis of COPD: results from the BOLD study
Authors: Vollmer W. M. , Gíslason Þ. , Burney P. , Enright P. L. , Gulsvik A. , Kocabas A. , Buist A. S.
Published: August 2009

Published guidelines recommend spirometry to accurately diagnose chronic obstructive pulmonary disease (COPD). However, even spirometry-based COPD prevalence estimates can vary widely. We compared properties of several spirometry-based COPD definitions using data from the international Burden of Obstructive Lung Disease (BOLD)study.

14 sites recruited population-based samples of adults aged ≥40 yrs. Procedures included standardised questionnaires and post-bronchodilator spirometry. 10,001 individuals provided usable data.

Use of the lower limit of normal (LLN) forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio reduced the age-related increases in COPD prevalence that are seen among healthy never-smokers when using the fixed ratio criterion (FEV1/FVC <0.7) recommended by the Global Initiative for Chronic Obstructive Lung Disease. The added requirement of an FEV1either <80% predicted or below the LLN further reduced age-related increases and also led to the least site-to-site variability in prevalence estimates after adjusting for potential confounders. Use of the FEV1/FEV6ratio in place of the FEV1/FVC yielded similar prevalence estimates.

Use of the FEV1/FVC<LLN criterion instead of the FEV1/FVC <0.7 should minimise known age biases and better reflect clinically significant irreversible airflow limitation. Our study also supports the use of the FEV1/FEV6as a practical substitute for the FEV1/FVC.
Pulmonary arterial hypertension in paediatric and adult patients with congenital heart disease
Authors: Gatzoulis M. A. , Alonso-Gonzalez R. , Beghetti M.
Published: August 2009

Pulmonary arterial hypertension (PAH) commonly arises in patients with congenital heart disease (CHD). Greater numbers of patients with PAH associated with CHD (PAH-CHD) are now surviving into adulthood, many with increasingly complex cardiac defects. Patients with cardiac defects which result in left-to-right shunting are at risk of developing PAH, owing to the increased shear stress and circumferential stretch induced by increased pulmonary blood flow, which leads to endothelial dysfunction and progressive vascular remodelling and, thus, increased pulmonary vascular resistance. Although PAH-CHD shares similar lung histology with idiopathic PAH, differences do exist between these aetiologies. Management of PAH-CHD can involve surgical correction of the cardiac defect and/or treatment of the PAH, depending on the underlying cardiac defect and status of disease progression. Transplantation surgery can be curative but is not without limitations. The timing of intervention in patients with PAH-CHD is important, but the optimums are sometimes difficult to define, with limited robust data to inform management decisions. Uncontrolled studies suggest that prostacyclin analogues and phosphodiesterase type-5 inhibitors may have benefits in advanced pulmonary vascular disease. In the only randomised controlled trial dedicated to end-stage PAH-CHD, bosentan significantly reduced pulmonary vascular resistance and significantly increased 6-minute walk distance without compromising peripheral oxygen saturation, in patients with Eisenmenger syndrome. These data suggest that targeted therapies are beneficial in the PAH-CHD population, and warrant further research.
The use of combination therapy in pulmonary arterial hypertension: new developments
Authors: Galiè N. , Negro L. , Simonneau G.
Published: August 2009

There is a strong clinical rationale for combination therapy in pulmonary arterial hypertension (PAH), as several pathological pathways have been implicated in its pathogenesis and no single agent has yet been shown to deliver completely satisfactory results. Registry data indicate that use of combination therapy is in fact common in existing clinical practice, even though support has been largely empirical or derived from small-scale observational studies. Data from large, adequately powered, randomised controlled trials of combination therapy in PAH are now emerging and suggest that combination therapy may be clinically beneficial. Studies of bosentan in combination with prostanoids and phosphodiesterase (PDE)-5 inhibitors show consistent evidence of improvements in exercise capacity compared with placebo. Similar improvements have been observed with PDE-5 inhibitors in combination with prostanoids. The appropriate timing of combination therapy requires further evaluation but goal-oriented therapy using combinations of oral and inhaled drugs has been shown to provide acceptable long-term results in patients with advanced PAH. Monitoring should be performed regularly and be based on repeatable, noninvasive, measurable parameters that have prognostic value.
Pulmonary veno-occlusive disease misdiagnosed as idiopathic pulmonary arterial hypertension
Authors: Palazzini M. , Manes A.
Published: August 2009

A 27-yr-old female with a 6-month diagnosis of idiopathic pulmonary arterial hypertension (PAH) confirmed elsewhere was referred to our centre with worsening dyspnoea.

On examination, the patient had low systemic oxygen saturation despite high oxygen flow and reduced exercise capacity. Haemodynamics were indicative of severe pre-capillary PAH. High-resolution computed tomography revealed diffuse ground-glass opacity with thickening interlobular septa, and haemosiderin-laden macrophages were identified by bronchoalveolar lavage. Based on clinical and diagnostic findings, the patient was re-diagnosed with pulmonary veno-occlusive disease (PVOD).

Treatment with high-dose diuretics and the endothelin-receptor antagonist bosentan improved the patient's exercise capacity, haemodynamics and quality of life. However, 1 yr later there was a progressive, slow deterioration in the patient's functional capacity and oxygen saturation, and inhaled prostanoid and oxygen therapy were initiated. Despite some subjective improvements, the patient's haemodynamics and oxygen saturation continued to decline and she underwent lung transplantation.

This case emphasises that PVOD is an under-recognised and often misdiagnosed form of pulmonary hypertension. Therefore, accurate diagnosis of PVOD requires comprehensive clinical and diagnostic work-up. While lung transplantation remains the treatment of choice for patients with PVOD, targeted therapies for PAH in addition to high doses of diuretics merit evaluation.
Short-Term Synaptic Plasticity in the Nociceptive Thalamic-Anterior Cingulate Pathway
Authors: Shyu Bai-Chuang , Vogt Brent A
Published: September 2009

Background

Although the mechanisms of short- and long-term potentiation of nociceptive-evoked responses are well known in the spinal cord, including central sensitization, there has been a growing body of information on such events in the cerebral cortex. In view of the importance of anterior cingulate cortex (ACC) in chronic pain conditions, this review considers neuronal plasticities in the thalamocingulate pathway that may be the earliest changes associated with such syndromes.

Results

A single nociceptive electrical stimulus to the sciatic nerve induced a prominent sink current in the layer II/III of the ACC in vivo, while high frequency stimulation potentiated the response of this current. Paired-pulse facilitation by electrical stimulation of midline, mediodorsal and intralaminar thalamic nuclei (MITN) suggesting that the MITN projection to ACC mediates the nociceptive short-term plasticity. The short-term synaptic plasticities were evaluated for different inputs in vitro where the medial thalamic and contralateral corpus callosum afferents were compared. Stimulation of the mediodorsal afferent evoked a stronger short-term synaptic plasticity and effectively transferred the bursting thalamic activity to cingulate cortex that was not true for contralateral stimulation. This short-term enhancement of synaptic transmission was mediated by polysynaptic pathways and NMDA receptors. Layer II/III neurons of the ACC express a short-term plasticity that involves glutamate and presynaptic calcium influx and is an important mechanism of the short-term plasticity.

Conclusion

The potentiation of ACC neuronal activity induced by thalamic bursting suggest that short-term synaptic plasticities enable the processing of nociceptive information from the medial thalamus and this temporal response variability is particularly important in pain because temporal maintenance of the response supports cortical integration and memory formation related to noxious events. Moreover, these modifications of cingulate synapses appear to regulate afferent signals that may be important to the transition from acute to chronic pain conditions associated with persistent peripheral noxious stimulation. Enhanced and maintained nociceptive activities in cingulate cortex, therefore, can become adverse and it will be important to learn how to regulate such changes in thalamic firing patterns that transmit nociceptive information to ACC in early stages of chronic pain.
Ixodes ricinus ticks are reservoir hosts for Rickettsia helvetica and potentially carry flea-borne Rickettsia species
Authors: Sprong Hein , Wielinga Peter R , Fonville Manoj , Reusken Chantal , Brandenburg Afke H , Borgsteede Fred , Gaasenbeek Cor , van der Giessen Joke WB
Published: September 2009

Background

Hard ticks have been identified as important vectors of rickettsiae causing the spotted fever syndrome. Tick-borne rickettsiae are considered to be emerging, but only limited data are available about their presence in Western Europe, their natural life cycle and their reservoir hosts. Ixodes ricinus, the most prevalent tick species, were collected and tested from different vegetation types and from potential reservoir hosts. In one biotope area, the annual and seasonal variability of rickettsiae infections of the different tick stages were determined for 9 years.

Results

The DNA of the human pathogen R. conorii as well as R. helvetica, R. sp. IRS and R. bellii-like were found. Unexpectedly, the DNA of the highly pathogenic R. typhi and R. prowazekii and 4 other uncharacterized Rickettsia spp. related to the typhus group were also detected in I. ricinus. The presence of R. helvetica in fleas isolated from small rodents supported our hypothesis that cross-infection can occur under natural conditions, since R. typhi/prowazekii and R. helvetica as well as their vectors share rodents as reservoir hosts. In one biotope, the infection rate with R. helvetica was ~66% for 9 years, and was comparable between larvae, nymphs, and adults. Larvae caught by flagging generally have not yet taken a blood meal from a vertebrate host. The simplest explanation for the comparable prevalence of R. helvetica between the defined tick stages is, that R. helvetica is vertically transmitted through the next generation with high efficiency. The DNA of R. helvetica was also present in whole blood from mice, deer and wild boar.

Conclusion

Besides R. helvetica, unexpected rickettsiae are found in I. ricinus ticks. We propose that I. ricinus is a major reservoir host for R. helvetica, and that vertebrate hosts play important roles in the further geographical dispersion of rickettsiae.
Rare and unusual dementias
Authors: Gupta Susham , Fiertag Olivia , Warner James
Published: August 2009

Over 95% of cases of dementia are attributable to Alzheimer's disease, vascular, Lewy body and frontotemporal dementia, and a few other common causes. In this article we consider some of the rare and unusual causes that account for the remaining 5%. Categorising them according to aetiological group (degenerative, vascular and infectious causes, and human prion diseases), we discuss the presentation of these forms and reasons for variations in estimated prevalence rates in the general population.
Hoarding behaviour: building up the ‘R factor’
Authors: Gaston Romina Lopez , Kiran-Imran Farida , Hassiem Fairooz , Vaughan John
Published: August 2009

Hoarding seems to be a non-specific symptom, as it has been associated with a wide range of psychiatric disorders. Validating hoarding as pathological is controversial and its nosological status remains unresolved. ‘Diogenes syndrome’ has been paradigmatic in this area, but its clinical use seems limited. Hoarding is not explicitly covered in either DSM–IV or ICD–10 and literature suggests that diagnosis of mental illness may consequently be missed in this population. In the context of these theoretical uncertainties, clinicians still need to accurately assess and treat patients who show hoarding behaviour. To this end, we summarise the available evidence, and present assessment and management algorithms together with a multicomponent psychological intervention that aims to teach patients to successfully apply the three Rs (reduce, recycle, reuse).
Assessment of personality disorder
Authors: Banerjee Penny J. M. , Gibbon Simon , Huband Nick
Published: August 2009

In 2003 the Department of Health, in conjunction with the National Institute for Mental Health in England, outlined the government's plan for the provision of mental health services for people with a diagnosis of personality disorder. This emphasised the need for practitioners to have skills in identifying, assessing and treating these disorders. It is important that personality disorders are properly assessed as they are common conditions that have a significant impact on an individual's functioning in all areas of life. Individuals with personality disorder are more vulnerable to other psychiatric disorders, and personality disorders can complicate recovery from severe mental illness. This article reviews the classification of personality disorder and some common assessment instruments. It also offers a structure for the assessment of personality disorder.
In defence of professional judgement
Authors: Downie Robin , Macnaughton Jane
Published: August 2009

A judgement may be defined as an assertion made with evidence or good reason in a context of uncertainty. In psychiatry the uncertainty is inherent in the professional context and the evidence derives from academic literature and scientific studies as they are applied to a specific patient. The nature of the uncertainty and the factors that should inform professional judgement are explored in this article. Professional judgement currently faces two serious challenges: an obsession with numbers, which comes from within medicine, and the ‘patient choice’ agenda, which is politically inspired and comes from outside medicine. In this article we strive to defend professional judgement in the clinic against both challenges.
Buprenorphine prescription, misuse and service provision: a global perspective
Authors: Ho Roger Chun Man , Chen Kai Yang , Broekman Birit , Mak Anselm
Published: August 2009

Buprenorphine, a partial μ-opioid agonist and κ-opioid antagonist, is recommended as safe and effective maintenance treatment for opioid dependence. It offers the possibility of management in primary care settings. However, its prescription has led to diversion for illicit recreational use and resulted in medical complications and, rarely, fatal overdose in combination with other sedatives. The outcome of buprenorphine maintenance programmes varies from country to country and it is determined by the local therapeutic traditions, regulatory restrictions and existing service provision for opioid misusers. This article addresses the pharmacology of buprenorphine, the benefits and drawbacks of its prescription, service provision for opioid misuse around the world, policy recommendations, and prescribing training requirements.
Brain morphology and neurological soft signs in adolescents with first-episode psychosis
Authors: Janssen Joost , Diaz-Caneja Angeles , Reig Santiago , Bombín Igor , Mayoral María , Parellada Mara , Graell Montserrat , Moreno Dolores , Zabala Arantzazu , Vazquez Veronica García , Desco Manuel , Arango Celso
Published: August 2009

Background

Adolescents with first-episode psychosis have increased severity of neurological soft signs when compared with controls, but it is unclear whether increased severity of neurological soft signs is an expression of specific structural brain deficits.

Aims

To examine whether increased severity of neurological soft signs was associated with decreased brain volumes in adolescents with first-episode psychosis.

Method

Brain scans were obtained for 70 adolescents (less than 18 years of age) with first-episode psychosis (duration of positive symptoms less than 6 months). Volumes were assessed using voxel-based morphometry and through segmentation of anatomical structures.

Results

Increased severity of sensory integration neurological soft signs correlated with smaller right and left thalamus volume, whereas increased severity of sequencing of complex motor acts neurological soft signs correlated with smaller right caudate volume.

Conclusions

Neurological soft signs may be an easy-to-assess marker of region-specific structural brain deficits in adolescents with first-episode psychosis.
Adverse reactions to antidepressants
Authors: Uher Rudolf , Farmer Anne , Henigsberg Neven , Rietschel Marcella , Mors Ole , Maier Wolfgang , Kozel Dejan , Hauser Joanna , Souery Daniel , Placentino Anna , Strohmaier Jana , Perroud Nader , Zobel Astrid , Rajewska-Rager Aleksandra , Dernovsek Moica Z. , Larsen Erik Roj , Kalember Petra , Giovannini Caterina , Barreto Mara , McGuffin Peter , Aitchison Katherine J.
Published: August 2009

Background

Adverse drug reactions are important determinants of non-adherence to
antidepressant treatment but their assessment is complicated by overlap
with depressive symptoms and lack of reliable self-report measures.

Aims

To evaluate a simple self-report measure and describe adverse reactions
to antidepressants in a large sample.

Method

The newly developed self-report Antidepressant Side-Effect Checklist and
the psychiatrist-rated UKU Side Effect Rating Scale were repeatedly
administered to 811 adult participants with depression in a
part-randomised multicentre open-label study comparing escitalopram and
nortriptyline.

Results

There was good agreement between self-report and psychiatrists' ratings.
Most complaints listed as adverse reactions in people with depression
were more common when they were medication-free rather than during their
treatment with antidepressants. Dry mouth (74%), constipation (33%) and
weight gain (15%) were associated with nortriptyline treatment. Diarrhoea
(9%), insomnia (36%) and yawning (16%) were more common during treatment
with escitalopram. Problems with urination and drowsiness predicted
discontinuation of nortriptyline. Diarrhoea and decreased appetite
predicted discontinuation of escitalopram.

Conclusions

Adverse reactions to antidepressants can be reliably assessed by
self-report. Attention to specific adverse reactions may improve
adherence to antidepressant treatment.
Imaginal desensitisation plus motivational interviewing for
pathological gambling: randomised controlled trial
Authors: Grant Jon E. , Donahue Christopher B. , Odlaug Brian L. , Kim Suck Won , Miller Michael J. , Petry Nancy M.
Published: August 2009

Sixty-eight individuals were randomised to either six sessions of imaginal
desensitisation plus motivational interviewing (IDMI) or Gamblers Anonymous.
Individuals assigned to IDMI had significantly greater reductions in
Yale–Brown Obsessive Compulsive Scale Modified for Pathological Gambling
total scores, gambling urges and gambling behaviour. People who failed to
respond to Gamblers Anonymous reported significantly greater reduction in
pathological gambling symptoms following later assignment to IDMI.
Abstinence was achieved by 63.6% during the acute IDMI treatment period.
Adherence to substitute opioid prescribing: survey of inner-London drug services
Authors: Dunn John , Haskew Michael , Pant Anshuman
Published: August 2009

Aims and Method

To investigate non-adherence to substitute opioid treatment, using a cross-sectional study design, with 630 patients from three London community drug services. Adherence was measured as the number of doses collected from the pharmacy as a proportion of the total number of doses stipulated on the prescription during a 28-day period and was further investigated through laboratory urine drug screens.

Results

Overall, 30.5% (n= 191) of individuals failed to pick up at least one dose of medication from the pharmacy over 1 month, but only 1.6% (n= 10) missed 50% or more of their doses. Non-adherence was associated with supervised consumption, more frequent pick-up, shorter duration of treatment, younger age, a lower dose of methadone and a recent urinalysis result positive for opiates.

Clinical Implications

Treatment services need to monitor levels of adherence to treatment and develop strategies to improve it so that treatment can be optimised effectively.
From a sector-based service model to a functional one: qualitative study of staff perceptions
Authors: Khandaker Golam , Cherukuru Srinivasarao , Dibben Claire , Ray Manaan Kar
Published: August 2009

Aims and Method

An increasing number of mental health trusts in the UK are replacing the geographically sectorised model of service delivery with a functional one. We conducted a qualitative study of staff perception concerning this reorganisation in our Trust, to inform effective change management locally and elsewhere.

Results

Perceived benefits were quick decision-making, positive risk management and improvement in clinical leadership. Dedicated consultant time would lead to improvements in junior doctor training. Concerns included lack of continuity of care, disagreement between teams and de-skilling of staff. Communication was seen as the key to overcoming these difficulties.

Clinical Implications

Detailed communication from management about the practicalities and reasons for change could facilitate effective transition.
Marx and Contemporary Models of Socialist Economy
Authors: Elliott John E.
Published: September 2009

John Elliott is Professor of Economics at the University of Southern California.
Think Locally, Act Locally: Spillovers, Spillbacks, and Efficient Decentralized Policymaking
Authors: Ogawa Hikaru , Wildasin David E
Published: September 2009

We analyze models with interjurisdictional spillovers among heterogeneous jurisdictions, such as CO2emissions that affect the global environment. Each jurisdiction's emissions depend upon the local stock of capital, which is inter-jurisdictionally mobile and subject to local taxation. In important cases, decentralized policymaking leads to efficient resource allocation, even in the complete absence of corrective interventions by higher-level governments or coordination of policy through Coasian bargaining. In particular, even when the preferences and production technologies differ among the agents, the decentralized system can result in globally efficient allocation. (JEL D62, H23, H73, H87, Q58)