bluuebunny/crossref_metadata_2025_split huggingface dataset:
High expression of Lewisy/bantigens is associated with decreased survival in lymph node negative breast carcinomas
Authors: Madjd Zahra , Parsons Tina , Watson Nicholas FS , Spendlove Ian , Ellis Ian , Durrant Lindy G 
Published: July 2005

Abstract
Introduction
There is sufficient evidence that blood group related Lewis antigens are tumour-associated molecules. The Lewisy and Lewisb antigens are complex carbohydrates that are over-expressed by breast, lung, colon and ovarian cancers. The SC101 mAb is a unique Lewisy/b binding antibody that binds to native and extended Lewisy and Lewisb haptens, displaying no cross reactivity with H type 1, H type 2, Lewisx or normal blood group antigens.

Methods
Immunohistochemical detection of Lewisy/b was performed on 660 formalin-fixed, paraffin embedded breast tumour specimens using a streptavidin-biotin peroxidase technique. Tissue from these patients had previously been included in tissue microarrays. This cohort comprises a well characterized series of patients with primary operable breast cancer diagnosed between 1987 and 1992, obtained from the Nottingham Tenovus Primary Breast Carcinoma Series. This includes patients 70 years of age or less, with a mean follow up of 7 years.

Results
Of the breast carcinomas, 370 of 660 (56%) were negative for Lewisy/b expression, 110 (17%) cases showed a low level of expression (<25% of positive cells) and only 54 cases (8%) showed extensive expression of Lewisy/b (>75% of positive cells). We found significant positive associations between histological grade (p < 0.001), Nottingham Prognostic Index (p = 0.016), tumour type (p = 0.007) and the level of Lewis y/b expression. There was a significant correlation between the proportion of Lewisy/b positive tumour cells and survival in lymph-node negative patients (p = 0.006).

Conclusion
The unique epitope recognised by SC101 mAb on Lewisy/b hapten is over-expressed on breast tumour tissue compared with normal breast. In this large series of invasive breast cancers, higher expression of Lewisy/b was more often found in high grade and poor prognosis tumours compared to good prognosis cancers. Moreover, in lymph node negative breast carcinomas, over-expression of Lewisy/b hapten was associated with significantly decreased patient survival.
Tandem repeat copy-number variation in protein-coding regions of human genes
Authors: O'Dushlaine Colm T , Edwards Richard J , Park Stephen D , Shields Denis C 
Published: July 2005

Abstract
Background
Tandem repeat variation in protein-coding regions will alter protein length and may introduce frameshifts. Tandem repeat variants are associated with variation in pathogenicity in bacteria and with human disease. We characterized tandem repeat polymorphism in human proteins, using the UniGene database, and tested whether these were associated with host defense roles.

Results
Protein-coding tandem repeat copy-number polymorphisms were detected in 249 tandem repeats found in 218 UniGene clusters; observed length differences ranged from 2 to 144 nucleotides, with unit copy lengths ranging from 2 to 57. This corresponded to 1.59% (218/13,749) of proteins investigated carrying detectable polymorphisms in the copy-number of protein-coding tandem repeats. We found no evidence that tandem repeat copy-number polymorphism was significantly elevated in defense-response proteins (p = 0.882). An association with the Gene Ontology term 'protein-binding' remained significant after covariate adjustment and correction for multiple testing. Combining this analysis with previous experimental evaluations of tandem repeat polymorphism, we estimate the approximate mean frequency of tandem repeat polymorphisms in human proteins to be 6%. Because 13.9% of the polymorphisms were not a multiple of three nucleotides, up to 1% of proteins may contain frameshifting tandem repeat polymorphisms.

Conclusion
Around 1 in 20 human proteins are likely to contain tandem repeat copy-number polymorphisms within coding regions. Such polymorphisms are not more frequent among defense-response proteins; their prevalence among protein-binding proteins may reflect lower selective constraints on their structural modification. The impact of frameshifting and longer copy-number variants on protein function and disease merits further investigation.
Brief psychotherapy in Alzheimer's disease
Authors: Burns Alistair , Guthrie Else , Marino-Francis Federica , Busby Charlotte , Morris Julie , Russell Eve , Margison Frank , Lennon Sean , Byrne Jane 
Published: July 2005

BackgroundAlthough there is good evidence that interventions for carers of people with Alzheimer's disease can reduce stress, no systematic studies have investigated psychotherapeutic intervention for patients themselves. This may be important in the earlier stages of Alzheimer's disease, where insight is often preserved.AimsThe aim was to assess, in a randomised controlled trial, whether psychotherapeutic intervention could benefit cognitive function, affective symptoms and global well-being.MethodIndividuals were randomised to receive six sessions of psychodynamic interpersonal therapy or treatment as usual; cognitive function, activities of daily living, a global measure of change, and carer stress and coping were assessed prior to and after the intervention.ResultsNo improvement was found on the majority of outcome measures. There was a suggestion that therapy had improved the carers' reactions to some of the symptoms.ConclusionsThere is no evidence to support the widespread introduction of brief psychotherapeutic approaches for those with Alzheimer's disease. However, the technique was acceptable and helpful individually.
Crisis card following self-harm: 12-month follow-up of a randomised controlled trial
Authors: Evans Jonathan , Evans Mark , Morgan H. Gethin , Hayward Alan , Gunnell David 
Published: July 2005

SummaryNo intervention has been shown to be effective in preventing repetition of self-harm. In the 6-month follow-up of a large randomised controlled trial, we previously reported no effectiveness of the provision of a card offering 24-h crisis telephone consultation on repetition of self-harm. However, there was a possible benefit among those presenting following a first episode (OR=0.64, 95% CI 0.34–1.22). Here we report the 12-month follow-up of the trial. The results confirm no overall benefit of the intervention (OR=1.19, 95% CI 0.85–1.67). Among those with a first episode of self-harm, the possible benefit of the intervention had diminished (OR=0.89, 95% CI 0.52–1.52), although a modest effect cannot be excluded.
Problems with early and very early intervention in psychosis
Authors: Warner Richard 
Published: July 2005

Summary‘Early intervention’ can refer to two different approaches-intervention when the psychosis is already evident and intervention before a psychosis is fully apparent. Each carries a distinctly different set of risks. The hoped-for benefits of early intervention in a fully evident psychosis are based on research that reveals an association between intervention early in the illness and good outcome. Those suffering from a psychosis of recent onset, however, are more likely to experience a spontaneous remission of illness, and this may readily explain the observed association. Early intervention in such cases of good-prognosis psychosis may lead to unnecessary and, sometimes, protracted treatment for those who would do well with no treatment. Intervention in the supposed prodromal phase of psychosis presents more serious hazards. The screening instruments currently available are inadequate for the accurate prediction of psychosis, and the risks of negative effects for the large numbers of people who screen false-positive are considerable. These risks include unnecessary fear of illness, restriction of life goals, use of medication and their side-effects.
Early intervention in psychotic disorders: beyond debate to solving problems
Authors: Mcgorry Patrick D. 
Published: July 2005

SummaryThe challenges of early diagnosis are similar in psychiatry to the rest of medicine. For potentially severe and persistent disorders there is great value in early diagnosis, however, only under certain conditions. Early diagnosis would not be justified if there were no efficacious treatments or if such treatments provided earlier would do more harm than good for those exposed. There is growing evidence that earlier and sustained intervention improves at least short-term outcomes. However, early intervention may be iatrogenic where systems of care are poor in quality. One thing is clear, the general pattern of care is still ‘too little, too late’ even in the most affluent countries. Consistent and extensive reform of health systems, with recognition of early intervention as an increasingly evidence-based ‘best buy’, represents one of the key priorities in international mental health.
Early intervention and recovery for young people with early psychosis: consensus statement
Authors: Bertolote J. , Mcgorry P. 
Published: July 2005

SummaryInternational declarations that articulate core values, goals and standards have played an important role in enhancing the quality of care in a number of areas of medicine. This document attempts this task for early intervention in psychotic disorders. It was originally inspired by the St Vincents declaration on the care of diabetes and carefully developed by David Shiers and Jo Smith with support from the Initiative to Reduce the Impact of Schizophrenia, National Institute for Mental Health in England and Rethink, resulting in the UK-focused Newcastle Declaration. The World Health Organization and the International Early Psychosis Association then collaborated to produce an international version of the declaration, which articulates the universal principles of early intervention and tries to blend these with local capacities and cultural diversity.
Pathways to care for first-episode psychosis in an early detection healthcare sector
Authors: Johannessen Jan Olav , Larsen Tor K. , Joa Inge , Melle Ingrid , Friis Svein , Opjordsmoen Stein , Rund Bjørn Rishovd , Simonsen Erik , Vaglum Per , Mcglashan Thomas H. 
Published: July 2005

BackgroundEarly detection programmes aim to reduce the duration of untreated psychosis (DUP) by public education and by prompt access to treatment via active outreach detection teams.AimsTo determine whether those with first-episode psychosis in an early detection healthcare area with existing referral channels differ from those who access care via detection teams.MethodThose with first-episode psychosis recruited via detection teams were compared with those accessing treatment via conventional channels, at baseline and after 3 months of acute treatment.ResultsPatients recruited via detection teams are younger males with a longer DUP a less dramatic symptom picture and better functioning; however they recover more slowly, and have more symptoms at 3-month follow-up.ConclusionsAfter establishing low threshold active case-seeking detection teams, we found clear differences between those patients entering treatment via detection teams v. those obtaining treatment via the usual channels. Such profiling may be informative for early detection service development.
Prepsychotic phase of schizophrenia and related disorders: recent progress and future opportunities
Authors: Phillips Lisa J. , Mcgorry Patrick D. , Yung Alison R. , Mcglashan Thomas H. , Cornblatt Barbara , Klosterkötter Joachim 
Published: July 2005

BackgroundClinical and research focus has recently shifted from established psychotic disorders to first-episode psychosis and the prepsychotic phase of illness.AimsTo describe the principles, progress and dilemmas associated with the prospective detection, engagement and treatment of young people at risk of developing a psychotic disorder.MethodStrategies to identify young people at heightened risk of a psychotic disorder are described. Preventive interventions and results of their evaluation are provided.ResultsWell-validated criteria for identifying young people at heightened risk of psychosis have been developed, evidence of the efficacy of various psychological and pharmacological interventions in preventing progression has accumulated and progress towards the identification of clinical and neurobiological predictors of transition to acute psychosis has been made.ConclusionsThe detection, monitoring and treatment of young people in the prepsychotic phase is a growth area in psychiatry. The ethical considerations about treatment options, treatment of minors and provision of information about risk status must be treated with sensitivity if the potential benefit to many young people and their families is to be realised.
Role of distress in delusion formation
Authors: Hanssen Manon , Krabbendam Lydia , De Graaf Ron , Vollebergh Wilma , Van Os Jim 
Published: July 2005

BackgroundContemporary cognitive psychological theories suggest that distress plays a mediating role in delusion formation.AimsTo study the amplifying role of distress from early perceptual intrusions to delusion formation.MethodA general population sample of 7076 individuals was interviewed with the Composite International Diagnostic Interview (CIDI) in 1996 (baseline), 1997 (T1) and 1999 (T2). At T2, clinicians also scored the Brief Psychiatric Rating Scale (BPRS) item ‘unusual thought content’. Analyses compared hallucinatory experiences with and without subjective distress at baseline for risk of delusion formation at follow-up.ResultsIndividuals experiencing hallucinations with distress, compared with those without distress had a fourfold increased risk of subsequent delusion formation.ConclusionsThis finding corroborates the hypothesis that distress associated with early perceptual intrusions serves as a catalyst in the development of delusions.
Implementing cognitive-behavioural therapy for first-episode psychosis
Authors: Addington Jean , Gleeson John 
Published: July 2005

SummarySignificant symptomatic improvement after a first episode of psychosis is not matched by a similar improvement in functional outcome. Thus, increased attention has been given to psychological intervention, in particular cognitive-behavioural therapy (CBT), with the hope of enhancing functional recovery. Outcome trials of CBT for schizophrenia are few, in particular for the first episode, and have been occasionally criticised for their lack of significance compared with supportive therapies. We describe a modular CBT approach for those with a first episode of psychosis that addresses adaptation as well as both functional and symptomatic outcome and one that parallels the theoretical shift in CBT that has occurred in the last decade. Guidelines for integrating CBT into an early psychosis service are presented.
Rational pharmacotherapy in early psychosis
Authors: Remington Gary 
Published: July 2005

BackgroundAn increased focus in research specific to first-episode schizophrenia has provided a rapidly growing body of evidence that can be directly translated to clinical practice.AimsTo provide clinical recommendations specific to effective pharmacotherapy of first-episode schizophrenia.MethodEvidence from clinical trials focused on the first-episode population is combined with data from other areas of investigation.ResultsIn first-episode psychosis, when to initiate treatment is not always clear, being intimately linked to challenges regarding early detection and diagnosis. There may be differences in antipsychotic dosing, patterns of response and sensitivity to side-effects. Adherence appears to be even more problematic at this stage.ConclusionsClinicians currently treating early psychosis have considerably more information to guide their decision-making. However, the speed at which the field is growing is a reminder totreatthis knowledge as a work in progress.
Integrated treatment of first-episode psychosis: effect of treatment on family burden
Authors: Jeppesen Pia , Petersen Lone , Thorup Anne , Abel Maj-Britt , ⊘ehlenschlæger Johan , Christensen Torben Ø. , Krarup Gertrud , Hemmingsen Ralf , J⊘rgensen Per , Nordentoft Merete 
Published: July 2005

BackgroundThe families of patients with first-episode psychosis often play a major role in care and often experience lack of support.AimsTo determine the effect of integrated treatment v. standard treatment on subjective burden of illness, expressed emotion (EE), knowledge of illness and satisfaction with treatment in key relatives of patients with a first episode of schizophrenia-spectrum disorder.MethodPatients with ICD-10 schizophrenia-spectrum disorders (first episode) were randomly assigned to integrated treatment or to standard treatment. Integrated treatment consisted of assertive community treatment, psychoeducational multi-family groups and social skills training. Key relatives were assessed with the Social Behaviour Assessment Schedule (SBAS, burden of illness), the 5-min speech sample (EE), and a multiple choice questionnaire at entry and after 1 year.ResultsRelatives in integrated treatment felt less burdened and were significantly more satisfied with treatment than relatives in standard treatment. There were no significant effects of intervention groups on knowledge of illness and EE.ConclusionsThe integrated treatment reduced family burden of illness and improved satisfaction with treatment.
Improving 1-year outcome in first-episode psychosis
Authors: Petersen Lone , Nordentoft Merete , Jeppesen Pia , ⊘hlenschlæger Johan , Thorup Anne , Christensen Torben Østergaard , Krarup Gertrud , Dahlstr⊘m Jytte , Haastrup Bodil , J⊘rgensen Per 
Published: July 2005

BackgroundBecause early illness course and outcome may affect the long-term outcome of schizophrenia-spectrum disorders, it is especially important to address poor outcome in this early critical period.AimsTo evaluate whether integrated treatment compared with standard treatment reduced the proportion of patients with poor clinical and social outcome after 1 year.MethodA total of 547 patients with first-episode psychosis were included in the study, 275 randomly assigned to integrated treatment and 272 to standard treatment. Measures assessed psychotic symptoms and social functioning.ResultsThere was a significant beneficial effect of integrated treatment v. standard treatment on ‘any poor outcome’. Integrated treatment had a significantly better effect on ‘any poor outcome’ in patients with schizophrenia compared with patients in standard treatment.ConclusionsThe integrated treatment significantly reduced the proportion of patients with poor clinical and social outcome compared with standard treatment.
Conflict of interest in psychiatry
Authors: Ahmer Syed , Arya Pradeep , Anderson Duncan , Faruqui Rafey 
Published: July 2005

Aims and MethodTo study the association between study support and outcome in randomised controlled trials (RCTs) of psychotropic drugs, we reviewed all RCTs published in four psychiatry journals over a 5-year period. Chi-squared tests were used to analyse the association between RCT support and outcome, and logistic regression to determine which variable best predicted outcome.ResultsA significantly higher proportion of manufacturer-supported RCTs (125/138, 91%, 95% CI 88–93) had a positive outcome than non-manufacturer-supported RCTs (39/50, 78%, 95% CI 72–84; P=0.02). Having an employee author almost guaranteed a positive outcome (56/58, 97%, 95% CI 94–99).Clinical ImplicationsOutcomes of drug RCTs have a significant association with support by the manufacturer of the experimental drug. Systematic reviews and meta-analyses based on these RCTs may be biased in favour of newer drugs.
Development of Peptide Antagonists for the Androgen Receptor Using Combinatorial Peptide Phage Display
Authors: Chang Ching-yi , Abdo Jennifer , Hartney Tanya , McDonnell Donald P. 
Published: July 2005

Abstract
Under the auspices of the Nuclear Receptor Signaling Atlas (NURSA) , we have undertaken to evaluate the feasibility of targeting nuclear receptor-coactivator surfaces for new drug discovery. The underlying objective of this approach is to provide the research community with reagents that can be used to modulate the transcriptional activity of nuclear receptors. Using combinatorial peptide phage display, we have been able to develop peptide antagonists that target specific nuclear receptor (NR)-coactivator binding surfaces. It can be appreciated that reagents of this nature will be of use in the study of orphan nuclear receptors for whom classical ligands have not yet been identified. In addition, because the interaction of coactivators with the receptor is an obligate step for NR transcriptional activity, it is anticipated that peptides that block these interactions will enable the definition of the biological and pharmacological significance of individual NR-coactivator interactions. In this report, we describe the use of this approach to develop antagonists of the androgen receptor by targeting its coactivator-binding pocket and their use to study the coactivator-binding surface of this receptor. Based on our findings, we believe that molecules that function by disrupting the androgen receptor-cofactor interactions will have use in the treatment of prostate cancer.
Weight Gain Trends Across Sociodemographic Groups in the United States
Authors: Truong Khoa Dang , Sturm Roland 
Published: July 2005

Objectives. To better understand health disparities, we compared US weight gain trends across sociodemographic groups between 1986 and 2002. Methods. We analyzed mean and 80th-percentile body mass index (BMI), calculated from self-reported weight and height, for subpopulations defined by education, relative income, race/ethnicity, and gender. Data were from the Behavioral Risk Factor Surveillance System, a random-digit-dialed telephone survey (total sample=1.88 million adult respondents). Results. Each sociodemographic group experienced generally similar weight gains. We found no statistically significant difference in increase in mean BMI by educational attainment, except that individuals with a college degree gained less weight than did others. The lowest-income group gained as much weight on average as the highest-income group, but lowest-income heavier individuals (80th percentile of BMI) gained weight faster than highest-income heavier individuals. We found no differences across racial/ethnic groups except that non-Hispanic Blacks gained more weight than other groups. Women gained more weight than men. Conclusions. We found fewer differences, especially by relative income and education, in weight gain across subpopulations than we had expected. Women and non-Hispanic Blacks gained weight faster than other groups.