bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary airway epithelial cell culture from lung transplant recipients
Authors: Forrest I. A. , Murphy D. M. , Ward C. , Jones D. , Johnson G. E. , Archer L. , Gould F. K. , Cawston T. E. , Lordan J. L. , Corris P. A.
Published: November 2005

Long-term survival in lung transplantation is limited by the development of obliterative bronchiolitis, a condition characterised by inflammation, epithelial injury, fibroproliferation and obliteration of bronchioles leading to airflow obstruction. To investigate the role of the bronchial epithelium in the pathogenesis of obliterative bronchiolitis the current study aimed to establish primary bronchial epithelial cell cultures (PBEC) from lung allografts.

Four to six bronchial brushings were obtained from sub-segmental bronchi of lung allografts. Cells were seeded onto collagen-coated plates and grown to confluence in bronchial epithelial growth medium.

Bronchial brushings (n = 33) were obtained from 27 patients. PBECs were grown to confluence from 12 out of 33 (39%) brushings. Failure to reach confluence was due to early innate infection. Bacteria were usually isolated from both bronchoalveolar lavage and culture media, but a separate population was identified in culture media only.

Primary culture of bronchial epithelial cells from lung transplant recipients is feasible, despite a high rate of early, patient-derived infection. Latent infection of the allograft, identified only by bronchial brushings, may itself be a persistent stimulus for epithelial injury. This technique facilitates future mechanistic studies of airway epithelial responses in the pathogenesis of obliterative bronchiolitis.
Melatonin, immune function and aging
Authors: Srinivasan V , Maestroni GJM , Cardinali DP , Esquifino AI , Perumal SR Pandi , Miller SC
Published: November 2005

Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence of cancer, infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. A decrease in functional competence of individual natural killer (NK) cells is found with advancing age. Macrophages and granulocytes show functional decline in aging as evidenced by their diminished phagocytic activity and impairment of superoxide generation. There is also marked shift in cytokine profile as age advances, e.g., CD3+ and CD4+ cells decline in number whereas CD8+ cells increase in elderly individuals. A decline in organ specific antibodies occurs causing reduced humoral responsiveness. Circulating melatonin decreases with age and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes-macrophages. It also stimulates the production of NK cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from NK cells and T-helper lymphocytes also are enhanced by melatonin. Melatonin presumably regulates immune function by acting on the immune-opioid network, by affecting G protein-cAMP signal pathway and by regulating intracellular glutathione levels. Melatonin has the potential therapeutic value to enhance immune function in aged individuals and in patients in an immunocompromised state.
Comparison of laboratory and immediate diagnosis of coagulation for patients under oral anticoagulation therapy before dental surgery
Authors: Kruse-Loesler Birgit , Kelker Matthias , Kleinheinz Johannes
Published: November 2005

Background

Dental surgery can be carried out on patients under oral anticoagulation therapy by using haemostyptic measures. The aim of the study was a comparative analysis of coagulation by laboratory methods and immediate patient diagnosis on the day of the planned procedure.

Methods

On the planned day of treatment, diagnoses were carried out on 298 patients for Prothrombin Time (PT), the International Normalised Ratio (INR), and Partial Thromboplastin Time (PTT). The decision to proceed with treatment was made with an INR < 4.0 according to laboratory results.

Results

Planned treatment did not go ahead in 2.7% of cases. Postoperatively, 14.8% resulted in secondary bleeding, but were able to be treated as out-patients. 1.7% had to be treated as in-patients. The average error between the immediate diagnosis and the laboratory method: 95% confidence interval was -5.8 ± 15.2% for PT, -2.7 ± 17.9 s for PTT and 0.23 ± 0.80 for INR. The limits for concordance were 9.4 and -21.1% for PT, 15.2 and -20.5 s for PTT, and 1.03 and -0.57 for INR.

Conclusion

This study showed a clinically acceptable concordance between laboratory and immediate diagnosis for INR. Concordance for PT and PTT did not meet clinical requirements. For patients under oral anticoagulation therapy, patient INR diagnosis enabled optimisation of the treatment procedure when planning dental surgery.
Episodic memory-related activation in schizophrenia: meta-analysis
Authors: Achim Amélie M. , Lepage Martin
Published: November 2005

Background

Numerous studies have examined the neural correlates of episodic memory deficits in schizophrenia, yielding both consistencies and discrepancies in the reported patterns of results.

Aims

To identify in schizophrenia the brain regions in which activity is consistently abnormal across imaging studies of memory.

Method

Data from 18 studies meeting the inclusion criteria were combined using a recently developed quantitative meta-analytic approach.

Results

Regions of consistent differential activation between groups were observed in the left inferior prefrontal cortex, medial temporal cortex bilaterally, left cerebellum, and in other prefrontal and temporal lobe regions. Subsequent analyses explored memory encoding and retrieval separately and identified between-group differences in specific prefrontal and medial temporal lobe regions.

Conclusions

Beneath the apparent heterogeneity of published findings on schizophrenia and memory, a consistent and robust pattern of group differences is observed as a function of memory processes.
Course and predictors of weight gain in people with first-episode psychosis treated with olanzapine or haloperidol
Authors: Zipursky Robert B. , Gu Hongbin , Green Alan I. , Perkins Diana O. , Tohen Mauricio F. , McEvoy Joseph P. , Strakowski Stephen M. , Sharma Tonmoy , Kahn René S. , Gur Raquel E. , Tollefson Gary D. , Lieberman Jeffrey A.
Published: November 2005

Background

Substantial weight gain is common with many atypical antipsychotics.

Aims

To evaluate the extent, time course and predictors of weight gain and its effect on study retention among people with first-episode psychosis treated with olanzapine or haloperidol.

Method

Survival analysis assessed time to potentially clinically significant weight gain (⩾7%) and the effect of weight gain on study retention. Weight gain during the 2-year study was summarised using last-observation-carried-forward (LOCF), observed cases and study completion approaches.

Results

After 2 years of treatment, LOCF mean weight gain was 10.2 kg (s.d.=10.1) for olanzapine (n=131) and 4.0 kg (s.d.=7.3) for haloperidol (n=132); observed cases mean weight gain was 15.4 kg (s.d.=10.0) for olanzapine and 7.5 kg (s.d.=9.2) for haloperidol. Change in body mass index was significantly predicted only by treatment group (P< 0.0001).

Conclusions

Olanzapine was associated with significantly greater weight gain than haloperidol, with both leading to greater weight gain than previously described.
Mortality in individuals who have had psychiatric treatment
Authors: Kisely Stephen , Smith Mark , Lawrence David , Maaten Sarah
Published: November 2005

Background

Most studies of mortality in psychiatric patients have investigated inpatients rather than those attending outpatient clinics or primary care, where most receive treatment.

Aims

To evaluate the mortality risk in mental illness for patients in contact with psychiatric services or primary care (n=221 048) across Nova Scotia (population 936 025).

Method

A population-based record-linkage analysis was made of the period 1995–2000, using an inception cohortto calculate mortality rate ratios.

Results

The mortality rate was 1.74, with increased ratios for all major causes of death. Male mortality was almost double that of females after controlling for demographic factors, treatment setting and place of residence. Patients of lower income, in specialist psychiatric settings, and with dementia or psychoses were also at greater risk. However, in absolute numbers, 72% of deaths occurred in patients who had only seen their general practitioner.

Conclusions

Mortality risk is increased in all psychiatric patients, not just those who have received in-patient treatment.
Cost-effectiveness of clinical interventions for reducing the global burden of bipolar disorder
Authors: Chisholm Dan , Van Ommeren Mark , Ayuso-Mateos Jose-Luis , Saxena Shekhar
Published: November 2005

Background

Bipolar disorder has been ranked seventh among the worldwide causes of non-fatal disease burden.

Aims

To estimate the cost-effectiveness of interventions for reducing the global burden of bipolar disorder.

Method

Hospital-and community-based delivery of two generic mood stabilisers (lithium and valproic acid), alone and in combination with psychosocial treatment, were modelled for 14 global sub-regions. A population model was employed to estimate the impact of different strategies, relative to no intervention. Total costs (in international dollars (I$)) and effectiveness (disability-adjusted life years (DALYs) averted) were combined to form cost-effectiveness ratios.

Results

Baseline results showed lithium to be no more costly yet more effective than valproic acid, assuming an anti-suicidal effect for lithium but not for valproic acid. Community-based treatment with lithium and psychosocial care was most cost-effective (cost per DALY averted: I$2165–6475 in developing sub-regions; I$5487–21123 in developed sub-regions).

Conclusions

Community-based interventions for bipolar disorder were estimated to be more efficient than hospital-based services, each DALY averted costing between one and three times average gross national income.
Measuring autistic traits: heritability, reliability and validity of the Social and Communication Disorders Checklist
Authors: Skuse David H. , Mandy William P. L. , Scourfield Jane
Published: November 2005

Background

Autistic traits are widely distributed in the general population, but the boundaries of the autistic spectrum are unclear. Whole-population surveys of unselected samples of children are hampered by the lack of appropriate screening instruments.

Aims

To assess whether the Social and Communication Disorders Checklist (SCDC) fulfils the need for a sensitive measure of autistic traits, which can be completed in a few minutes and which measures heritable characteristics in both males and females.

Method

A 12-item scale, the SCDC, was completed by three independent samples drawn from a twin register, a group with Turner syndrome and children with a diagnosis of autistic-spectrum disorder attending clinics. The data were used to establish the heritability reliability and validity of the checklist.

Results

Traits measured by the SCDC were highly heritable in both genders (0.74). Internal consistency was excellent (0.93) and test–retest reliability high (0.81). Discriminant validity between pervasive developmental disorder and other clinical groups was good, discrimination from non-clinical samples was better; sensitivity (0.90), specificity (0.69).

Conclusions

The SCDC is a unique and efficient first-level screening questionnaire for autistic traits.
Instability of eating disorder diagnoses: prospective study
Authors: Milos Gabriella , Spindler Anja , Schnyder Ulrich , Fairburn Christopher G.
Published: November 2005

Background

The stability of eating disorder diagnoses has received little research attention.

Aims

To examine the course of the full range of clinical eating disorders.

Method

A sample of 192 women with a current DSM–IV eating disorder (55 with anorexia nervosa, 108 with bulimia nervosa and 29 with eating disorder not otherwise specified) were assessed three times over 30 months using a standardised interview.

Results

Although the overarching category of ‘eating disorder’ was relatively stable, the stability of the three specific eating disorder diagnoses was low, with just a third of participants retaining their original diagnosis. This was due only in part to remission since the remission rate was low across all three diagnoses.

Conclusions

There is considerable diagnostic flux within the eating disorders but a low overall remission rate. This suggests that underpinning their psychopathology may be common biological and psychological causal and maintaining processes.
Validity of the construct of post-traumatic stress disorder in a low-income country
Authors: Mehta Khyati , Vankar Ganpat , Patel Vikram
Published: November 2005

The validity of the clinical construct of post-traumatic stress disorder (PTSD) has been questioned in non-Western cultures. This report describes in-depth interviews exploring the experiences of women who were traumatised by the communal riots in Ahmedabad, India, in March 2002. Three specific narratives are presented which describe experiences that closely resemble re-experiencing, avoidance and hyperarousal. Thus, symptoms described as characteristic features of PTSD in biomedical classifications are clearly expressed by the women in our study, and are attributed by them to trauma and grief. We conclude that PTSD may be a relevant clinical construct in the Indian context.
Psychiatric in-patients receive fewer greetings cards than other in-patients
Authors: Lankappa Sudheer , Spence Sean A.
Published: November 2005

Aims and Method

Greetings cards (wishing patients well) appear less abundant on psychiatric wards than other in-patient facilities. We tested this hypothesis in three cross-sectional surveys of teaching hospitals in Sheffield.

Results

On each occasion, psychiatric wards contained significantly fewer card recipients (χ2 test, P<0.001). Individual recipients in psychiatric wards received significantly fewer cards than recipients in general hospitals (Kruskal–Wallis test, P<0.05).

Clinical Implications

Although receiving a card might seem a trivial matter, it nevertheless denotes the outcome of an altruistic act, which may be appreciated by its recipient. Psychiatric in-patients receive fewer such acts of kindness than other in-patients. These data concur with other recent reports suggesting that the stigma of mental illness extends to expressions of altruism.
New long-stay patients in a psychiatric admission ward setting
Authors: Cowan Colin , Walker Philippa
Published: November 2005

Aims and Method

This is a descriptive study of the admissions of new long-stay patients and their outcome in a district with minimal access to longer-stay in-patient beds. Cases were identified through an ongoing in-patient census and information was gathered by retrospective case-note review.

Results

Thirty-nine new long-stay admissions were identified. High rates of living alone, early readmission following previous discharge and use of the Mental Health Act 1983 were noted. The 39 admissions occupied 12% of the unit's capacity. Four patients returned to a family residence but 27 went into residential or in-patient care. Of those discharged to settings not providing patient care, 48% were readmitted in the year after discharge.

Clinical Implications

New long-stay admissions continue to absorb a high proportion of the bed resources of an in-patient unit for their numbers and these patients are at risk of unsuccessful discharge.
Service innovations: Is there a market for neuropsychiatry? A year in the life of a district-based neuropsychiatry service
Authors: Barrett K. , Sudharsan S.
Published: November 2005

Aims and Method

This paper describes the clinical activity of a district neuropsychiatry service over a 1-year period. The data presented are drawn from a clinical database with individuals classified according to the following diagnostic groups: acquired brain injury, early-onset dementia, Huntington's disease, epilepsy, other neurological disorders, developmental disorders and non-organic disorders. Information is presented on out-patient case-load, new out-patient referrals, general hospital referrals and in-patient admissions.

Results

The total out-patient case-load was 451; 189 new out-patient and 99 liaison referrals were seen and 90 individuals were admitted. Acquired brain injury was the most common neurological diagnosis in all groups.

Clinical Implications

The demand for this service indicates that there is a market for neuropsychiatry, even at a district level, and particularly in the management of the sequelae of acquired brain injury.
Partners in Care: Staywell Support Group for patients. In the beginning was an idea
Authors: Burton Sandra , Blaj Adrian
Published: November 2005

Motto: With perseverance a blade of glass splits rocks

(Chinese proverb).

Over 3 years ago a former in-patient of mine walked quietly into my clinic and asked my opinion in respect of her desire to put something back into the system which helped her to recover. I instantly thought that this was a brilliant idea; a support group run by the patients for the patients! People around me remained sceptical about this project and simply thought the project was doomed to failure from the start as there was no known long-term successful precedent. Then I thought of the idea behind the enormously successful Alcoholics Anonymous self-help organisation founded in the USA by two alcoholic men, a surgeon and stockbroker. The result was impressive – I only wish that this project would find deep resonance in a few dedicated hearts and spread nationally. For those who want to read further about this against-all-the-odds journey, I stop myself and let Sandra tell the story about the origin of the Staywell Support Group.
Active ERK1 is dimerized in vivo: bisphosphodimers generate peak kinase activity and monophosphodimers maintain basal ERK1 activity
Authors: Philipova Rada , Whitaker Michael
Published: November 2005

ERK1 and ERK2 are widely involved in cell signalling. Using a recombinant approach, it has been shown that exogenous ERK2 is capable of dimerization and that preventing dimerization reduces its nuclear accumulation on stimulation. Dimerization occurs on phosphorylation; the dimer partner of phosphorylated ERK2 may be either phosphorylated or unphosphorylated. It has been assumed that monophosphodimers are hemiactive. Here we show that ERK1 is capable of dimerization both in vivo and in vitro. Dimerization of human recombinant ERK1 in vitro requires both ERK1 phosphorylation and cellular cofactor(s); it leads to the formation of a high molecular weight complex that can be dissociated by treatment with β-mercaptoethanol. We demonstrate for the first time in both sea urchin embryos and human cells that native ERK forms dimers and that high ERK kinase activity is largely associated with bisphosphodimers, not with monophosphodimers or phosphorylated monomers. The activity of the bisphosphodimer is about 20-fold higher than that of the phosphorylated monomer in vitro and the bisphosphodimer shows 5- to 7-fold higher in vivo activity than the basal activity attributable to the monophosphodimer. Thus phosphorylation of both partners in the dimer is a hallmark of ERK activation. Judgments made about ERK kinase activity associated with phosphorylated monomers are at best a proxy for ERK activity.
TLS facilitates transport of mRNA encoding an actin-stabilizing protein to dendritic spines
Authors: Fujii Ritsuko , Takumi Toru
Published: November 2005

TLS (translocation in liposarcoma), an RNA-binding protein, was originally identified as a heterogeneous ribonuclear protein (hnRNP). Recently, we showed that TLS is localized in neuronal dendrites of mouse hippocampal neurons and is translocated to the spines, where local translation takes place, in an mGluR5 activation-dependent manner. However, the specific role of TLS has not been clarified. TLS-null neurons display abnormal spine morphology, suggesting that TLS-deficiency may impair activity-dependent actin reorganization in spines. To address this issue, we screened for mouse brain transcripts by their in vitro binding to TLS, and identified RNAs that associate with TLS, including mRNAs encoding actin-related proteins such as actin-stabilizing protein Nd1-L. Nd1-L transcripts were increased in the dendrites upon mGluR activation and significantly reduced in TLS-null dendrites. Overexpression of Nd1-L in mouse hippocampal neurons prevented damage to spine structure caused by actin destabilization. Our results demonstrate that TLS associates with mRNA encoding an actin-related protein and may be involved in actin reorganization in spines.
Postoperative care after varicose vein surgery: patient-based questionnaire
Authors: Tang T , Boyle J R , Gaunt M E , Varty K
Published: November 2005

Objective: Practical advice given postoperatively to varicose vein patients remains subjective. They are encouraged to walk in their stockings or bandages as much as possible. The aim of this study was to investigate if this is a realistic request.

Methods: A postal questionnaire was given to all patients undergoing varicose vein surgery from July 2003. The questionnaire referred to the following issues: pain scores, walking ability, stairs, driving, return to work, dressings and stockings.

Results: A total of 93 patients replied, of which 55 (59%) were women and the mean age was 52 years (range 23–83). Of the patients who replied, 66 (71%) had a unilateral procedure and 13 (14%) had recurrent varicose veins. A total of 65 (70%) underwent a high tie, strip and avulsions, 16 (17%) underwent a short saphenous tie, nine (10%) underwent ligation of both saphenous systems and three (3%) underwent avulsions alone. Pain scores were low (3/10), resolving completely after nine days on average. Despite this, 89% of patients could only walk around the garden or block in the first week. After two weeks, normal activities were possible but most patients remained off work for three weeks. Stockings were a problem for 49 (53%) patients.

Conclusions: Although we would like all our patients to mobilize early after varicose vein surgery, the traditional long walk is unrealistic. Support stockings cause difficulties in over half the patients. Postoperative care and advice for varicose vein surgery need re-thinking.
Temporary caval filter in the prevention of pulmonary embolism during delivery and postpartum
Authors: Pagliariccio G , Carbonari L , Grilli Cicilioni C , Angelini A , Gatta E , Curatola A , Alo′ F P
Published: November 2005

Objectives: The treatment of deep vein thrombosis (DVT) of the lower limbs during pregnancy remains controversial. There are a lot of problems related to anticoagulant therapy for the safety of the fetus; the use of caval filters rarely appears in the literature and it is not yet codified. So the choice of the right treatment is often difficult.

The authors review their experience with a prophylactic use of a temporary caval filter for patients with proximal DVT of the last period of pregnancy, in order to avoid the inherent risk of major pulmonary embolism during delivery and postpartum.

Methods: Ten women with proximal DVT were treated. The diagnosis was performed by Doppler ultrasonography (DU) and magnetic resonance (MR). At the end of pregnancy, a temporary caval filter (eight Prolyser and two Tempofilter) was percutaneously inserted under X-ray control. The patients were then subjected to a planned caesarean section. After 15 days, all filters were removed after a phlebography to check the absence of clots.

Results: The mean time of X-ray exposure was about 1 min and 30 s. None of the patients suffered a major pulmonary embolism. All fetuses were born without problems or malformations. There were no complications related to the filters. No caval thrombosis or filters clots were found at the phlebography. The follow-up registered no pulmonary embolism episodes.

Conclusions: The use of a temporary caval filter in pregnancy is safe and does not introduce any additional risk. It could be suggested for pregnant patients with proximal DVT beginning in the last period of pregnancy.
Perforator of the popliteal fossa and short saphenous vein insufficiency
Authors: De Palma M , Carandina S , Mazza P , Fortini P , Legnaro A , Palazzo A , Liboni A , Zamboni P
Published: November 2005

Objectives: To assess the preoperative frequency of reflux from the perforator of the popliteal fossa (PPF) in cases of short saphenous vein insufficiency.

Methods: Short saphenous vein insufficiency cases were carefully investigated in 590 consecutive patients affected by primary chronic venous insufficiency. PPF was identified in accordance with anatomical criteria translated in ultrasonic anatomy. Reflux was elicited in standing both by squeezing and active manoeuvres.

Results: Short saphenous vein insufficiency occurred in 77/590 cases (13%). In 15/77 cases (19%) short saphenous insufficiency was fed by reflux from the PPF, with a competent saphenopopliteal junction, and this finding was confirmed at surgical exploration. PPF superficial outlet was found on the inferior aspect of the short saphenous main trunk (type 1 presentation, 11 cases) and on a varicous tributary (type 2, four cases).

Conclusions: PPF is a neglected entity, but often is the only source of the reflux in the short saphenous vein system. The lack of preoperative awareness of its presence could lead to an increased rate of saphenopopliteal recurrences, especially in case of type 1 presentation.
Informed consent: what do we tell patients about the risk of fatal pulmonary embolism after varicose vein surgery?
Authors: Srilekha A , Karunanithy N , Corbett C R R
Published: November 2005

Objective: To obtain an estimate of the frequency of fatal pulmonary embolism (PE) after varicose vein surgery.

Methods: Firstly by analysis of official statistics and secondly by a postal questionnaire to surgeons carrying out varicose vein surgery. The response rate from the questionnaire was 68% (391/576). Surgeons were asked if they had encountered PE after varicose vein surgery, whether the outcome was fatal and how many years they had spent in the specialty. Further calculations were based on data obtained from the Vascular Society of Great Britain and Ireland that suggest that on average about 120 cases are operated per year per consultant surgeon.

Results: Analysis of the statistics available from official sources suggested that the risk of fatal PE after varicose vein surgery is about 1 in 15,000. Respondents to the questionnaire reported a total of 396 pulmonary emboli, of which 73 were fatal. From the questionnaire, we estimate that between one in three and one in four surgeons will encounter a fatality in the course of a full career. From knowledge of the length of time spent in the specialty by our respondents and using the figure of 120 operated cases per consultant per year, we obtained a higher estimate of the risk of fatal PE, around one in 10,000 cases.

Conclusions: While the methods used to collect these figures are imperfect and open to criticism, they suggest a risk between one in 10,000 and one in 15,000. We think it is reasonable, when obtaining consent, to warn patients of the very small risk of fatal PE, using the more pessimistic figure of one in 10,000.
Determinants of the Differences in Ldl-Cholesterol After Initiation of Statin Treatment
Authors: Caspard Herve , Chan Arnold K , Walker Alexander M
Published: November 2005

Background:

Randomized clinical trials may not accurately predict drug benefit in clinical practice because the patients and conditions of therapy almost always differ between those settings.

Objective:

To determine whether differences in low-density lipoprotein cholesterol (LDL-C) time curves between clinical trial results and usual care experience after initiation of statin therapy could be explained fully in terms of observable characteristics of patients and practice in usual care.

Methods:

We compared LDL-C measurements for 3 years after initiation of statin treatment in individuals enrolled in a health maintenance organization (HMO), with enrollees in the active treatment arm of the CARE (Cholesterol and Recurrent Events) trial. Analysis of the determinants of variation in LDL-C in the HMO cohort was used to adjust the crude results to the distribution of patient and treatment characteristics in the trial.

Results:

The mean percent decrease in LDL-C was lower in the HMO cohort (n = 1245) than in the clinical trial at the end of each 6-month period, with the difference diminishing over time. Adjustment of the HMO time curve to the baseline characteristics of the clinical trial cohort did not significantly change the mean estimates at any time point. Assuming optimal adherence in the HMO cohort raised the curve over time, with 95% confidence intervals including the means observed in CARE after 18 months. Fixing treatment to pravastatin 40 mg/day, as in CARE, brought the estimates in the HMO cohort very close to those of the clinical trial, with 95% confidence intervals including the means observed in CARE at all time points.

Conclusions:

Treatment selection, dosing, and adherence under usual care were the primary reasons for which improvements in LDL-C in practice fell short of expectations that are based on clinical trial findings for statin therapy. Beginning with a low dose of statins and titrating to a satisfactory response can delay effective treatment by 18 months or more. Poor adherence accounts for a further substantial shortfall from maximal effect. Differences between trial populations and the general population of statin users with respect to age, gender, and baseline LDL-C have no measurable impact on discrepancies between predicted and observed LDL-C improvement in usual practice.
Neuronal Signals in the Monkey Basolateral Amygdala during Reward Schedules
Authors: Sugase-Miyamoto Yasuko , Richmond Barry J.
Published: November 2005

The amygdala is critical for connecting emotional reactions with environmental events. We recorded neurons from the basolateral complex of two monkeys while they performed visually cued schedules of sequential color discrimination trials, with both valid and random cues. When the cues were valid, the visual cue, which was present throughout each trial, indicated how many trials remained to be successfully completed before a reward. Seventy-six percent of recorded neurons showed response selectivity, with the selectivity depending on some aspects of the current schedule. After a reward, when the monkeys knew that the upcoming cue would be valid, 88 of 246 (36%) neurons responded between schedules, seemingly anticipating the receiving information about the upcoming schedule length. When the cue appeared, 102 of 246 (41%) neurons became selective, at this point encoding information about whether the current trial was the only trial required or how many more trials are needed to obtain a reward. These cue-related responses had a median latency of 120 ms (just between the latencies in inferior temporal visual area TE and perirhinal cortex). When the monkey was releasing a touch bar to complete the trial correctly, 71 of 246 (29%) neurons responded, with responses in the rewarded trials being similar no matter which schedule was ending, thus being sensitive to the reward contingency. Finally, 39 of 246 (16%) neurons responded around the reward. We suggest that basolateral amygdala, by anticipating and then delineating the schedule and representing reward contingency, provide contextual information that is important for adjusting motivational level as a function of immediate behavior goals.
Soluble β-Amyloid1-40Induces NMDA-Dependent Degradation of Postsynaptic Density-95 at Glutamatergic Synapses
Authors: Roselli F. , Tirard M. , Lu J. , Hutzler P. , Lamberti P. , Livrea P. , Morabito M. , Almeida O. F. X.
Published: November 2005

Amyloid-β (Aβ) has been implicated in memory loss and disruption of synaptic plasticity observed in early-stage Alzheimer's disease. Recently, it has been shown that soluble Aβ oligomers target synapses in cultured rat hippocampal neurons, suggesting a direct role of Aβ in the regulation of synaptic structure and function. Postsynaptic density-95 (PSD-95) is a postsynaptic scaffolding protein that plays a critical role in synaptic plasticity and the stabilization of AMPA (AMPARs) and NMDA (NMDARs) receptors at synapses. Here, we show that exposure of cultured cortical neurons to soluble oligomers of Aβ1-40reduces PSD-95 protein levels in a dose- and time-dependent manner and that the Aβ11-40-dependent decrease in PSD-95 requires NMDAR activity. We also show that the decrease in PSD-95 requires cyclin-dependent kinase 5 activity and involves the proteasome pathway. Immunostaining analysis of cortical cultured neurons revealed that Aβ treatment induces concomitant decreases in PSD-95 at synapses and in the surface expression of the AMPAR glutamate receptor subunit 2. Together, these data suggest a novel pathway by which Aβ triggers synaptic dysfunction, namely, by altering the molecular composition of glutamatergic synapses.
Expression of Spinal NMDA Receptor and PKCγ after Chronic Morphine Is Regulated by Spinal Glucocorticoid Receptor
Authors: Lim Grewo , Wang Shuxing , Zeng Qing , Sung Backil , Yang Liling , Mao Jianren
Published: November 2005

Spinal NMDA receptor (NMDAR), protein kinase C (PKC), and glucocorticoid receptor (GR) have all been implicated in the mechanisms of morphine tolerance; however, how these cellular elements interact after chronic morphine exposure remains unclear. Here we show that the expression of spinal NMDAR and PKCγ after chronic morphine is regulated by spinal GR through a cAMP response element-binding protein (CREB)-dependent pathway. Chronic morphine (10 μg, i.t.; twice daily for 6 d) induced a time-dependent upregulation of GR, the NR1 subunit of NMDAR, and PKCγ within the rat's spinal cord dorsal horn. This NR1 and PKCγ upregulation was significantly diminished by intrathecal coadministration of morphine with the GR antagonist RU38486 or a GR antisense oligodeoxynucleotide. Intrathecal coadministration of morphine with an adenylyl cyclase inhibitor (2′,5′-dideoxyadenosine) or a protein kinase A inhibitor (H89) also significantly attenuated morphine-induced NR1 and PKCγ expression, whereas intrathecal treatment with an adenylyl cyclase activator (forskolin) alone mimicked morphine-induced expression of GR, NR1, and PKCγ. Moreover, the expression of phosphorylated CREB was upregulated within the spinal cord dorsal horn after chronic morphine, and a CREB antisense oligodeoxynucleotide coadministered intrathecally with morphine prevented the upregulation of GR, NR1, and PKCγ. These results indicate that spinal GR through the cAMP-CREB pathway played a significant role in NMDAR and PKCγ expression after chronic morphine exposure. The data suggest that genomic interaction among spinal GR, NMDAR, and PKCγ may be an important mechanism that contributes to the development of morphine tolerance.
Gastrin-Releasing Peptide Promotes Suprachiasmatic Nuclei Cellular Rhythmicity in the Absence of Vasoactive Intestinal Polypeptide-VPAC2Receptor Signaling
Authors: Brown Timothy M. , Hughes Alun T. , Piggins Hugh D.
Published: November 2005

Vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP) acting via the VPAC2receptor and BB2receptors, respectively, are key signaling pathways in the suprachiasmatic nuclei (SCN) circadian clock. Transgenic mice lacking the VPAC2receptor (Vipr2-/-) display a continuum of disrupted behavioral rhythms with only a minority capable of sustaining predictable cycles of rest and activity. However, electrical or molecular oscillations have not yet been detected in SCN cells from adultVipr2-/-mice. Using a novel electrophysiological recording technique, we found that in brain slices from wild-type and behaviorally rhythmicVipr2-/-mice, the majority of SCN neurons we detected displayed circadian firing patterns with estimated periods similar to the animals' behavior. In contrast, in slices from behaviorally arrhythmicVipr2-/-mice, only a small minority of the observed SCN cells oscillated. Remarkably, exogenous GRP promoted SCN cellular rhythms inVipr2-/-mouse slices, whereas blockade of BB2receptors suppressed neuronal oscillations. In wild-type mice, perturbation of GRP-BB2signaling had few effects on SCN cellular rhythms, except when VPAC2receptors were blocked pharmacologically. These findings establish that residual electrical oscillations persist in the SCN ofVipr2-/-mice and reveal a potential new role for GRP-BB2signaling within the circadian clock.
Influence of Landscape‐Scale Factors in Limiting Brook Trout Populations in Pennsylvania Streams
Authors: Kocovsky Patrick M. , Carline Robert F.
Published: November 2005

Landscapes influence the capacity of streams to produce trout through their effect on water chemistry and other factors at the reach scale. Trout abundance also fluctuates over time; thus, to thoroughly understand how spatial factors at landscape scales affect trout populations, one must assess the changes in populations over time to provide a context for interpreting the importance of spatial factors. We used data from the Pennsylvania Fish and Boat Commission's fisheries management database to investigate spatial factors that affect the capacity of streams to support brook trout Salvelinus fontinalis and to provide models useful for their management. We assessed the relative importance of spatial and temporal variation by calculating variance components and comparing relative standard errors for spatial and temporal variation. We used binary logistic regression to predict the presence of harvestable‐length brook trout and multiple linear regression to assess the mechanistic links between landscapes and trout populations and to predict population density. The variance in trout density among streams was equal to or greater than the temporal variation for several streams, indicating that differences among sites affect population density. Logistic regression models correctly predicted the absence of harvestable‐length brook trout in 60% of validation samples. The r2‐value for the linear regression model predicting density was 0.3, indicating low predictive ability. Both logistic and linear regression models supported buffering capacity against acid episodes as an important mechanistic link between landscapes and trout populations. Although our models fail to predict trout densities precisely, their success at elucidating the mechanistic links between landscapes and trout populations, in concert with the importance of spatial variation, increases our understanding of factors affecting brook trout abundance and will help managers and private groups to protect and enhance populations of wild brook trout.
Growth of Larval to Juvenile Green Sturgeon in Elevated Temperature Regimes
Authors: Allen Peter J. , Nicholl Mary , Cole Stephanie , Vlazny Amy , Cech Joseph J.
Published: November 2005

To determine the effect of high river temperatures on post‐yolk‐sac larval to early juvenile green sturgeonAcipenser medirostris, growth rates at elevated and cycling temperature regimes were measured. Water temperatures were chosen based on temperature regimes in their highly altered natal rivers. Post‐yolk‐sac fish (15 d after hatching) were placed into twenty‐four 60‐L tanks. Fish were kept on a natural photoperiod, receiving continuous well water and aeration and ad libitum commercial rations. Significant differences were found between final wet weights, total lengths, and specific growth rates (at 24°C and at cycling 19–24°C > 19°C) because of increases in food consumption, despite increases in activity (both significantly greater at 24°C than at 19–24°C or 19°C). Elevated and cycling temperatures in the 19–24°C range do not adversely affect juveniles (body size range, ∼0.1–10 g), when abundant food and oxygen are available.
Design and construction of the Sail Bridge, Swansea, UK
Authors: Sanders P. A. , Firth I. P. T.
Published: November 2005

This paper describes the design and construction of the Sail Bridge over the River Tawe at Swansea, South Wales. This pedestrian bridge represented a key element in the regeneration of the disused docks area, unlocking the potential for the new Port Tawe Innovation Village under development by the Welsh Development Agency. The development of the design and construction from planning stage through to completion of construction is discussed. This includes the selection of the bridge form along with the use of computer modelling techniques to develop the complex geometry, fabrication and bridge erection issues, aerodynamic investigations and the design of tuned mass dampers to control potential pedestrian-induced vibrations.
Performance of a stress-laminated-timber arch bridge
Authors: Kermani A. , Freedman G.
Published: November 2005

For the past three years the authors have been involved in the optimisation of the performance of stress-laminated-timber arch (SLTA) structures by utilising the strength properties of timber in an arching action for use as vehicle and pedestrian bridges. During this time over 20 permanent bridges have been built and eight have been load tested. The overall aim of this extensive research programme has been to develop structural uses for low-grade, UK-grown, timber and it has been shown that arches, using timber in compression, are an extremely effective technique for bridges. Timber structures have a very high sustainability value while being low cost and employing less early capital. These bridges on public roads can help increase public confidence in timber as a viable structural material. As part of a series of field and laboratory tests on SLTA bridges, a 20 m span arch bridge was designed and constructed at the Glentress Forestry Commission site near Peebles, in August 2004. The bridge has since been subjected to a series of extensive static and dynamic loads evaluating its response to crowd and vandal loadings. The results have confirmed predictions that the strength and stiffness of this type of construction was well beyond the strength normally expected from a slender timber structure. This paper details the construction and compares the analysis, design and load testing of the latest 20 m span full-scale SLTA test bridge at Glentress. The extensive testing programme, augmented by analytical work, aims to develop reliable design guidelines for arch structures using UK softwood.
Human–structure dynamic interaction in footbridges
Authors: Živanović S. , Pavic A. , Reynolds P.
Published: November 2005

Dynamic load induced in the vertical direction by a single person walking across a footbridge structure is usually modelled as a resonant harmonic force. A comparison between modal responses generated by this harmonic force and a walking force measured on a treadmill confirmed that using the harmonic force is justifiable in the case of walking across a structure that does not vibrate perceptibly. It is further shown that using this harmonic force for predicting the response of a perceptibly vibrating footbridge can significantly overestimate the real footbridge response and therefore its degree of liveliness. This is because of the inability of pedestrians to keep pacing steadily when perceiving strong vibrations. A methodology for systematic comparison of the measured and simulated responses is proposed with the aim of identifying vibration levels which disturb normal walking. On two footbridges investigated this level was 0·33 m/s2 and 0·37 m/s2, in both cases being lower than the levels allowed by the current British footbridge design code. Finally, the observed effect of losing steady walking step can be expressed via either increased damping or modified harmonic dynamic force over time periods when test subjects lose their step. The average increase in the damping over the analysed time periods of imperfect walking was up to 10 times higher than the damping of an empty footbridge.
Efficient dynamic performance assessment of a footbridge
Authors: Brownjohn J. M. W. , Middleton C.
Published: November 2005

The dynamic performance of footbridges has become a significant concern in recent years, resulting in increasing demand for assessment of the performance of new and existing footbridges subject to pedestrian loading scenarios far more complex than the existing code provisions. Performance assessment typically involves predictions based on numerical simulations using finite-element representations and pedestrian load models, possibly followed by experimental assessment under normal and limiting load conditions. As dynamic performance is strongly related to all the modal parameters of the bridge, namely modal frequency, damping, shape and mass, their reliable identification for modes to be involved in pedestrian-induced response is central to assessment. The paper describes an efficient procedure for assessing dynamic characteristics and performance using a combination of visual survey, finite-element modelling and brief and unobtrusive dynamic testing, followed by short observation of pedestrian-induced response and finite-element model updating for evaluating other loading scenarios. The procedure involves minimal effort for maximum effect, generating a reliable analytical representation for response simulation and checking the serviceability of the bridge. The procedure has been tested using an existing non-problematic bridge, as described here, before being used on new structures.
Footbridge over the Sant Adria Marina in Barcelona, Spain
Authors: Aparicio Á. C. , Ramos G.
Published: November 2005

This paper presents a description of a continuous truss footbridge comprising two spans, one of 140 m and the other 50 m. The bridge crosses the Sant Adria Marina, close to Barcelona. The width of the deck is 6 m and the depth of the two trusses, which form the bridge, range between 6 and 10 m. Main innovations are the use of recycled aggregates for concrete in the approach slab deck, the use of silica fume concrete for the pavement which performs well from the strength, durability and aesthetic points of view and the formal exploration of irregular longitudinal layouts in truss bridges. This formal exploration resulted in the creation of an internal space extremely pleasant for people and avoiding any tunnel sensation. Moreover, the absence of dynamic loads and the light live load allowed the trusses to be designed without using gusset plates.
Design for enhanced marine habitats in coastal structures
Authors: Li B. , Reeve D. E. , Fleming C. A.
Published: November 2005

A study to investigate the feasibility of modifying the current engineering design of coastal structures, in order to enhance their ability to provide marine habitats is described. In particular, a detailed account of the wave modelling undertaken to develop guidelines for the conceptual design of structures that can enhance the marine habitat is presented. Illustrative examples are used to demonstrate how wave and flow modelling can be used, in conjunction with ecological and engineering constraints, to derive performance design curves for different defence scheme layouts. Conclusions and implications for the design of future schemes are discussed.