bluuebunny/crossref_metadata_2025 huggingface dataset:
Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease
Authors: Yi Tangsheng , Zhao Dongchang , Lin Chia-Lei , Zhang Chunyan , Chen Ying , Todorov Ivan , LeBon Thomas , Kandeel Fouad , Forman Stephen , Zeng Defu
Published: July 2008

Th17 is a newly identified T-cell lineage that secretes proinflammatory cytokine IL-17. Th17 cells have been shown to play a critical role in mediating autoimmune diseases such as EAE, colitis, and arthritis, but their role in the pathogenesis of graft-versus-host disease (GVHD) is still unknown. Here we showed that, in an acute GVHD model of C57BL/6 (H-2b) donor to BALB/c (H-2d) recipient, IL-17−/− donor T cells manifested an augmented Th1 differentiation and IFN-γ production and induced exacerbated acute GVHD. Severe tissue damage mediated by IL-17−/− donor T cells was associated with increased Th1 infiltration, up-regulation of chemokine receptors by donor T cells, and enhanced tissue expression of inflammatory chemokines. Administration of recombinant IL-17 and neutralizing IFN-γ in the recipients given IL-17−/− donor cells ameliorated the acute GVHD. Furthermore, the regulation of Th1 differentiation by IL-17 or Th17 may be through its influence on host DCs. Our results indicate that donor Th17 cells can down-regulate Th1 differentiation and ameliorate acute GVHD in allogeneic recipients, and that treatments neutralizing proinflammatory cytokine IL-17 may augment acute GVHD as well as other inflammatory autoimmune diseases.
Soluble CD22 as a tumor marker for hairy cell leukemia
Authors: Matsushita Kakushi , Margulies Inger , Onda Masanori , Nagata Satoshi , Stetler-Stevenson Maryalice , Kreitman Robert J.
Published: July 2008

CD22 is an important immunotherapeutic target on B-cell malignancies, particularly hairy cell leukemia (HCL), but its soluble extracellular domain, sCD22, has not yet been reported in the blood. By immunoaffinity and enzyme-linked immunosorbent assay techniques using anti-CD22 monoclonal antibodies, we identified the 100-kDa extracellular domain of CD22 and an 80-kDa processed form in serum of patients with HCL. The median sCD22 level measured by enzyme-linked immunosorbent assay was 18 ng/mL for 93 patients with HCL. sCD22 levels varied from 2.1 to 163 ng/mL and were higher (P < .001) than 23 normal donors (median, 0.6 ng/mL). More than 95% of normal donors had sCD22 levels less than 1.9 ng/mL. sCD22 levels were proportional to concentrations of circulating HCL cells (P = .002), and HCL spleen size (P < .001). sCD22 levels normalized with complete but not partial response to treatment. sCD22 levels up to 300 ng/mL had less than a 2-fold effect on the cytotoxicity of the anti-CD22 recombinant immunotoxin BL22. sCD22 levels may be useful to follow in patients with HCL and may be more specific than sCD25 in patients with CD22+/CD25− disease. Trials are listed on www.cancer.gov as NCT00002765, NCT00021983, NCT00074048, NCT00085085, NCT00337311, and NCT00462189.
Methods for evaluating gene expression from Affymetrix microarray datasets
Authors: Jiang Ning , Leach Lindsey J , Hu Xiaohua , Potokina Elena , Jia Tianye , Druka Arnis , Waugh Robbie , Kearsey Michael J , Luo Zewei W
Published: July 2008

Background

Affymetrix high density oligonucleotide expression arrays are widely used across all fields of biological research for measuring genome-wide gene expression. An important step in processing oligonucleotide microarray data is to produce a single value for the gene expression level of an RNA transcript using one of a growing number of statistical methods. The challenge for the researcher is to decide on the most appropriate method to use to address a specific biological question with a given dataset. Although several research efforts have focused on assessing performance of a few methods in evaluating gene expression from RNA hybridization experiments with different datasets, the relative merits of the methods currently available in the literature for evaluating genome-wide gene expression from Affymetrix microarray data collected from real biological experiments remain actively debated.

Results

The present study reports a comprehensive survey of the performance of all seven commonly used methods in evaluating genome-wide gene expression from a well-designed experiment using Affymetrix microarrays. The experiment profiled eight genetically divergent barley cultivars each with three biological replicates. The dataset so obtained confers a balanced and idealized structure for the present analysis. The methods were evaluated on their sensitivity for detecting differentially expressed genes, reproducibility of expression values across replicates, and consistency in calling differentially expressed genes. The number of genes detected as differentially expressed among methods differed by a factor of two or more at a given false discovery rate (FDR) level. Moreover, we propose the use of genes containing single feature polymorphisms (SFPs) as an empirical test for comparison among methods for the ability to detect true differential gene expression on the basis that SFPs largely correspond tocis-acting expression regulators. The PDNN method demonstrated superiority over all other methods in every comparison, whilst the default Affymetrix MAS5.0 method was clearly inferior.

Conclusion

A comprehensive assessment of seven commonly used data extraction methods based on an extensive barley Affymetrix gene expression dataset has shown that the PDNN method has superior performance for the detection of differentially expressed genes.
Assessing emergency medical care in low income countries: A pilot study from Pakistan
Authors: Razzak Junaid A , Hyder Adnan A , Akhtar Tasleem , Khan Mubashir , Khan Uzma R
Published: July 2008

Background

Emergency Medical Care is an important component of health care system. Unfortunately it is however, ignored in many low income countries. We assessed the availability and quality of facility-based emergency medical care in the government health care system at district level in a low income country – Pakistan.

Methods

We did a quantitative pilot study of a convenience sample of 22 rural and 20 urban health facilities in 2 districts – Faisalabad and Peshawar – in Pakistan. The study consisted of three separate cross-sectional assessments of selected community leaders, health care providers, and health care facilities. Three data collection instruments were created with input from existing models for facility assessment such as those used by the Joint Commission of Accreditation of Hospitals and the National Center for Health Statistics in USA and the Medical Research Council in Pakistan.

Results

The majority of respondents 43/44(98%), in community survey were not satisfied with the emergency care provided. Most participants 36/44(82%) mentioned that they will not call an ambulance in health related emergency because it does not function properly in the government system. The expenses on emergency care for the last experience were reported to be less than 5,000 Pakistani Rupees (equivalent to US$ 83) for 19/29(66%) respondents. Most health care providers 43/44(98%) were of the opinion that their facilities were inadequately equipped to treat emergencies. The majority of facilities 31/42(74%) had no budget allocated for emergency care. A review of medications and equipment available showed that many critical supplies needed in an emergency were not found in these facilities.

Conclusion

Assessment of emergency care should be part of health systems analysis in Pakistan. Multiple deficiencies in emergency care at the district level in Pakistan were noted in our study. Priority should be given to make emergency care responsive to needs in Pakistan. Specific efforts should be directed to equip emergency care at district facilities and to organize an ambulance network.
Analysis of risk factors for T. brucei rhodesiensesleeping sickness within villages in south-east Uganda
Authors: Zoller Thomas , Fèvre Eric M , Welburn Susan C , Odiit Martin , Coleman Paul G
Published: July 2008

Background

Sleeping sickness (HAT) caused byT.b. rhodesienseis a major veterinary and human public health problem in Uganda. Previous studies have investigated spatial risk factors forT.b. rhodesienseat large geographic scales, but none have properly investigated such risk factors at small scales, i.e. within affected villages. In the present work, we use a case-control methodology to analyse both behavioural and spatial risk factors for HAT in an endemic area.

Methods

The present study investigates behavioural and occupational risk factors for infection with HAT within villages using a questionnaire-based case-control study conducted in 17 villages endemic for HAT in SE Uganda, and spatial risk factors in 4 high risk villages. For the spatial analysis, the location of homesteads with one or more cases of HAT up to three years prior to the beginning of the study was compared to all non-case homesteads. Analysing spatial associations with respect to irregularly shaped geographical objects required the development of a new approach to geographical analysis in combination with a logistic regression model.

Results

The study was able to identify, among other behavioural risk factors, having a family member with a history of HAT (p = 0.001) as well as proximity of a homestead to a nearby wetland area (p < 0.001) as strong risk factors for infection. The novel method of analysing complex spatial interactions used in the study can be applied to a range of other diseases.

Conclusion

Spatial risk factors for HAT are maintained across geographical scales; this consistency is useful in the design of decision support tools for intervention and prevention of the disease. Familial aggregation of cases was confirmed forT. b. rhodesienseHAT in the study and probably results from shared behavioural and spatial risk factors amongmembers of a household.
Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patients
Authors: Rosa Alexandra , Fonseca Benedita V , Krug Tiago , Manso Helena , Gouveia Liliana , Albergaria Isabel , Gaspar Gisela , Correia Manuel , Viana-Baptista Miguel , Simões Rita Moiron , Pinto Amélia Nogueira , Taipa Ricardo , Ferreira Carla , Fontes João Ramalho , Silva Mário Rui , Gabriel João Paulo , Matos Ilda , Lopes Gabriela , Ferro José M , Vicente Astrid M , Oliveira Sofia A
Published: July 2008

Background

The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk.

Methods

We genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk.

Results

Haplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45–0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41–7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13–7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect.

Conclusion

Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample.
CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23
Authors: Michels Evi , Hoebeeck Jasmien , De Preter Katleen , Schramm Alexander , Brichard Bénédicte , De Paepe Anne , Eggert Angelika , Laureys Geneviève , Vandesompele Jo , Speleman Frank
Published: July 2008

Background

Recurrent loss of part of the long arm of chromosome 11 is a well established hallmark of a subtype of aggressive neuroblastomas. Despite intensive mapping efforts to localize the culprit 11q tumour suppressor gene, this search has been unsuccessful thus far as no sufficiently small critical region could be delineated for selection of candidate genes.

Methods

To refine the critical region of 11q loss, the chromosome 11 status of 100 primary neuroblastoma tumours and 29 cell lines was analyzed using a BAC array containing a chromosome 11 tiling path. For the genes mapping within our refined region of loss, meta-analysis on published neuroblastoma mRNA gene expression datasets was performed for candidate gene selection. The DNA methylation status of the resulting candidate gene was determined using re-expression experiments by treatment of neuroblastoma cells with the demethylating agent 5-aza-2'-deoxycytidine and bisulphite sequencing.

Results

Two small critical regions of loss within 11q23 at chromosomal band 11q23.1-q23.2 (1.79 Mb) and 11q23.2-q23.3 (3.72 Mb) were identified. In a first step towards further selection of candidate neuroblastoma tumour suppressor genes, we performed a meta-analysis on published expression profiles of 692 neuroblastoma tumours. Integration of the resulting candidate gene list with expression data of neuroblastoma progenitor cells pinpointed CADM1 as a compelling candidate gene. Meta-analysis indicated that CADM1 expression has prognostic significance and differential expression for the gene was noted in unfavourable neuroblastoma versus normal neuroblasts. Methylation analysis provided no evidence for a two-hit mechanism in 11q deleted cell lines.

Conclusion

Our study puts CADM1 forward as a strong candidate neuroblastoma suppressor gene. Further functional studies are warranted to elucidate the role of CADM1 in neuroblastoma development and to investigate the possibility of CADM1 haploinsufficiency in neuroblastoma.
Suppression of local invasion of ameloblastoma by inhibition of matrix metalloproteinase-2 in vitro
Authors: Wang Anxun , Zhang Bin , Huang Hongzhang , Zhang Leitao , Zeng Donglin , Tao Qian , Wang Jianguang , Pan Chaobin
Published: July 2008

Background

Ameloblastomas are odontogenic neoplasms characterized by local invasiveness. This study was conducted to address the role of matrix metalloproteinase-2 (MMP-2) in the invasiveness of ameloblastomas.

Methods

Plasmids containing either MMP-2 siRNA or tissue inhibitor of metalloproteinase-2 (TIMP-2) cDNA were created and subsequently transfected into primary ameloblastoma cells. Zymography, RT-PCR, and Western blots were used to assess MMP-2 activity and expression of MMP-2 and TIMP-2, as well as protein levels.

Results

Primary cultures of ameloblastoma cells expressed cytokeratin (CK) 14 and 16, and MMP-2, but only weakly expressed CK18 and vimentin. MMP-2 mRNA and protein levels were significantly inhibited by RNA interference (P < 0.05). Both MMP-2 siRNA and TIMP-2 overexpression inhibited MMP-2 activity and the in vitro invasiveness of ameloblastoma.

Conclusion

These results indicate that inhibition of MMP-2 activity suppresses the local invasiveness of ameloblastoma cells. This mechanism may serve as a novel therapeutic target in ameloblastomas pursuant to additional research.
Association of loss of epithelial syndecan-1 with stage and local metastasis of colorectal adenocarcinomas: An immunohistochemical study of clinically annotated tumors
Authors: Hashimoto Yosuke , Skacel Marek , Adams Josephine C
Published: July 2008

Background

Syndecan-1 is a transmembrane proteoglycan with important roles in cell-cell and cell-extracellular matrix adhesion and as a growth factor co-receptor. Syndecan-1 is highly expressed by normal epithelial cells and loss of expression has been associated with epithelial-mesenchymal transition and the transformed phenotype. Loss of epithelial syndecan-1 has been reported in human colorectal adenocarcinomas, but whether this has prognostic significance remains undecided. Here we have examined syndecan-1 expression and its potential prognostic value with reference to a clinically annotated tissue microarray for human colon adenocarcinomas.

Methods

Syndecan-1 expression was examined by immunohistochemistry of a tissue microarray containing cores from 158 colorectal adenocarcinomas and 15 adenomas linked to a Cleveland Clinic, IRB-approved database with a mean clinical follow-up of 38 months. The Kaplan-Meier method was used to analyze the relationship between syndecan-1 expression and patient survival. Potential correlations between syndecan-1 expression and the candidate prognostic biomarker fascin were examined.

Results

Syndecan-1 is expressed at the basolateral borders of normal colonic epithelial cells. On adenocarcinoma cells, syndecan-1 was present around cell membranes and in cytoplasm. In 87% of adenocarcinomas, syndecan-1 was decreased or absent; only 13% of patients had stained for syndecan-1 on more than 75% of tumor cells. Decreased syndecan-1 correlated with a higher TNM stage and lymph node metastasis and was more common in males (p = 0.042), but was not associated with age, tumor location or Ki67 index. Reduced tumor syndecan-1 staining also correlated with upregulation of stromal fascin (p = 0.016). Stromal syndecan-1 was observed in 16.6% of tumors. There was no difference in survival between patients with low or high levels of either tumor or stromal syndecan-1.

Conclusion

Syndecan-1 immunoreactivity was decreased in the majority of human colon adenocarcinomas in correlation with TNM stage and metastasis to local lymph nodes. In a small fraction of adenocarcinomas, syndecan-1 was upregulated in the local stroma. Syndecan-1 expression status did not correlate with patient survival outcomes. Combined analysis of syndecan-1 in relation to a potential prognostic biomarker, fascin, identified that loss of tumor syndecan-1 correlated significantly with strong stromal fascin staining.
Metastatic susceptibility locus, an 8p hot-spot for tumour progression disrupted in colorectal liver metastases: 13 candidate genes examined at the DNA, mRNA and protein level
Authors: Macartney-Coxson Donia P , Hood Kylie A , Shi Hong-jun , Ward Teresa , Wiles Anna , O'Connor Rosemary , Hall David A , Lea Rod A , Royds Janice A , Stubbs Richard S , Rooker Serena
Published: July 2008

Background

Mortality from colorectal cancer is mainly due to metastatic liver disease. Improved understanding of the molecular events underlying metastasis is crucial for the development of new methods for early detection and treatment of colorectal cancer. Loss of chromosome 8p is frequently seen in colorectal cancer and implicated in later stage disease and metastasis, although a single metastasis suppressor gene has yet to be identified. We therefore examined 8p for genes involved in colorectal cancer progression.

Methods

Loss of heterozygosity analyses were used to map genetic loss in colorectal liver metastases. Candidate genes in the region of loss were investigated in clinical samples from 44 patients, including 6 with matched colon normal, colon tumour and liver metastasis. We investigated gene disruption at the level of DNA, mRNA and protein using a combination of mutation, semi-quantitative real-time PCR, western blotting and immunohistochemical analyses.

Results

We mapped a 2 Mb region of 8p21-22 with loss of heterozygosity in 73% of samples; 8/11 liver metastasis samples had loss which was not present in the corresponding matched primary colon tumour. 13 candidate genes were identified for further analysis. Both up and down-regulation of 8p21-22 gene expression was associated with metastasis. ADAMDEC1 mRNA and protein expression decreased during both tumourigenesis and tumour progression. Increased STC1 and LOXL2 mRNA expression occurred during tumourigenesis. Liver metastases with low DcR1/TNFRSF10C mRNA expression were more likely to present with extrahepatic metastases (p = 0.005). A novel germline truncating mutation of DR5/TNFRSF10B was identified, and DR4/TNFRSF10A SNP rs4872077 was associated with the development of liver metastases (p = 0.02).

Conclusion

Our data confirm that genes on 8p21-22 are dysregulated during colorectal cancer progression. Interestingly, however, instead of harbouring a single candidate colorectal metastasis suppressor 8p21-22 appears to be a hot-spot for tumour progression, encoding at least 13 genes with a putative role in carcinoma development. Thus, we propose that this region of 8p comprises a metastatic susceptibility locus involved in tumour progression whose disruption increases metastatic potential.
Impact of case management by advanced practice nurses in primary care on unplanned hospital admissions: a controlled intervention study
Authors: Huws Dyfed W , Cashmore Deborah , Newcombe Robert G , Roberts Catherine , Vincent Judith , Elwyn Glyn
Published: July 2008

Background

Increasing unplanned hospital admissions disrupt planned health care, lead to additional morbidity and are expensive. A recent review found only weak evidence for case management preventing unplanned admissions, yet case management of older people is being implemented widely in the UK. We aimed to study the effect of advanced practice nurse case management on unplanned medical and geriatric hospital admission rates in patients 50 years and over, and on admission risk in a 'higher risk' sub-group of patients in the UK.

Methods

Case management by advanced practice nurses in NHS primary care practices in the Swansea Local Health Board area, Wales, UK. We conducted a prospective non-randomized controlled intervention study comparing unplanned medical and geriatric patient admissions between five intervention and thirty non-intervention practices during a pre-intervention year and an intervention year.

Results

For all lengths of stay, comparing intervention (n = 5) with non-intervention practices (n = 30) from pre-intervention to intervention year, we found that the unplanned medical and geriatric admission rate was significantly lower in the intervention group – adjusted relative risk of 0.909; relative risk reduction 9.1% (95% credible limit 0.840 to 0.984, p = 0.018); absolute risk reduction 0.99 admissions per 100 patients (95% credible limit 0.17 to 1.86, p = 0.018). For lengths of stay of one night or more we observed a stronger effect – adjusted relative risk 0.896; relative risk reduction 10.41% (95%, credible limit 0.820 to 0.979, p = 0.015). Most of the rate reduction was due to a reduction in the number of new admissions but much less so for admissions of lengths of stay of at least one night, compared to all lengths of stay. We did not find a statistically significant effect on re-admission or multiple re-admission rates in 'higher risk' patients previously admitted one or more times – adjusted relative risk of further multiple admissions per previously admitted patient 0.908 (95% credible limit 0.765, 1.077); relative risk reduction 9.3%; adjusted relative risk of total admissions per multiple admitter 0.995 (95% credible limit 0.940, 1.053) relative risk reduction 0.6%.

Conclusion

Although this study reports a reduction in unplanned admission rates in the intervention practices, this appears to be only in part directly due to nurse case management: most of the reduction did not occur in multipe admitters whom were case managed. Further research is needed to explain this finding, to elucidate how best to target the attention of case managers and to examine the complexity of potential outcomes in terms of the nature and necessity of admissions and most suitable lengths-of-stay in terms of acute care or rehabilittion need.
Equity in the use of antithrombotic drugs, beta-blockers and statins among Finnish coronary patients
Authors: Manderbacka Kristiina , Keskimäki Ilmo , Reunanen Antti , Klaukka Timo
Published: July 2008

Background

Earlier studies have mainly reported the use of antithrombotic drugs, beta-blockers and statins among hospital patient populations or MI patients. This study aimed to describe the use of these drugs among middle-aged Finnish coronary patients and to identify patient groups in risk of being prescribed inadequate medication for secondary prevention of coronary heart disease.

Methods

One-year follow-up survey data from a random sample of a cohort of coronary patients were used along with register data linked to the survey. The response rate was 54% (n = 2650). The main outcome measures were use of antithrombotic drugs, beta-blockers and statins and the data were analysed using logistic regression analysis.

Results

Among men and women, respectively, 82% and 81% used beta-blockers, 95% and 89% used antithrombotic drugs, and 62% and 59% used statins. Younger men and men from higher socioeconomic groups were more likely to use statins, even after controlling for disease severity and comorbidity. In women, the age trend was reversed and no socioeconomic differences were found. Drug use increased with increased disease severity, but diabetes had only a slight effect.

Conclusion

The use of antithrombotic drugs and beta-blockers among Finnish coronary patients seemed to be rather appropriate and, to some extent, prescription practices of preventive medication varied according to patients' risk of coronary events. However, statin use was remarkably low among men with low socio-economic status, and there is need to improve preventive drug treatment among diabetic coronary patients.
A family of GFP-like proteins with different spectral properties in lancelet Branchiostoma floridae
Authors: Baumann Diana , Cook Malcolm , Ma Limei , Mushegian Arcady , Sanders Erik , Schwartz Joel , Yu C Ron
Published: July 2008

Background

Members of the green fluorescent protein (GFP) family share sequence similarity and the 11-stranded β-barrel fold. Fluorescence or bright coloration, observed in many members of this family, is enabled by the intrinsic properties of the polypeptide chain itself, without the requirement for cofactors. Amino acid sequence of fluorescent proteins can be altered by genetic engineering to produce variants with different spectral properties, suitable for direct visualization of molecular and cellular processes. Naturally occurring GFP-like proteins include fluorescent proteins from cnidarians of the Hydrozoa and Anthozoa classes, and from copepods of the Pontellidae family, as well as non-fluorescent proteins from Anthozoa. Recently, an mRNA encoding a fluorescent GFP-like protein AmphiGFP, related to GFP from Pontellidae, has been isolated from the lancelet Branchiostoma floridae, a cephalochordate (Deheyn et al., Biol Bull, 2007 213:95).

Results

We report that the nearly-completely sequenced genome of Branchiostoma floridae encodes at least 12 GFP-like proteins. The evidence for expression of six of these genes can be found in the EST databases. Phylogenetic analysis suggests that a gene encoding a GFP-like protein was present in the common ancestor of Cnidaria and Bilateria. We synthesized and expressed two of the lancelet GFP-like proteins in mammalian cells and in bacteria. One protein, which we called LanFP1, exhibits bright green fluorescence in both systems. The other protein, LanFP2, is identical to AmphiGFP in amino acid sequence and is moderately fluorescent. Live imaging of the adult animals revealed bright green fluorescence at the anterior end and in the basal region of the oral cirri, as well as weaker green signals throughout the body of the animal. In addition, red fluorescence was observed in oral cirri, extending to the tips.

Conclusion

GFP-like proteins may have been present in the primitive Metazoa. Their evolutionary history includes losses in several metazoan lineages and expansion in cephalochordates that resulted in the largest repertoire of GFP-like proteins known thus far in a single organism. Lancelet expresses several of its GFP-like proteins, which appear to have distinct spectral properties and perhaps diverse functions.

Reviewers

This article was reviewed by Shamil Sunyaev, Mikhail Matz (nominated by I. King Jordan) and L. Aravind.
Effects of antidepressant treatment on heart rate variability in major depression: A quantitative review
Authors: van Zyl Louis T , Hasegawa Takuya , Nagata Katsutaro
Published: July 2008

Background

The literature measuring effects of antidepressant and electroconvulsive therapy (ECT) for major depression on heart rate variability (HRV) in medically well individuals was reviewed.

Methods

Fourteen studies evaluating HRV were included. Twenty three pre-post or within group comparisons were available. Treatment impact on measures of HRV was pooled over studies. We examined different classes of antidepressants, and for short and long electrocardiogram (ECG) recordings separately.

Results

Tricyclic antidepressants (TCAs) were associated with declines in most measures of HRV and significant increase in heart rate (HR) in studies with short recording intervals. No significant changes were found for longer recording times.

Treatment effects with selective serotonin reuptake inhibitors (SSRIs) were more variable. Short-recording studies revealed a significant decrease in HR and an increase in one HRV measure. In two 24-hour recording studies no significant changes were observed. No relationship between ECT and HRV has been established in the literature. The effects of other drugs are reported.

Limitations

Few studies measure the effects of treatment of depression on HRV. Existing studies have generally used very small samples, employing a variety of measurements and methodologies.

Conclusion

We confirm that TCAs are associated with a large decrease in HRV and increase HR. However, data for SSRIs is not clear. Although the effect of SSRIs on HRV is weaker than for TCAs, evidence shows that SSRIs are associated with a small decrease in HR, and an increase in one measure of HRV. The use of TCAs in depression leads to changes in HRV that are associated with increased risk of mortality.
Jejunal perforation caused by a feeding jejunostomy tube: a case report
Authors: Stylianides Nicholas A , Date Ravindra S , Pursnani Kishor G , Ward Jeremy B
Published: July 2008

Introduction

Percutaneous endoscopic gastrostomy and feeding jejunostomy are used for providing long-term nutritional support to patients with neurological disorders. Various mechanical complications of these procedures are described.

Case presentation

We report a case of a 17-year-old boy with cerebral injury who had a percutaneous endoscopic gastrostomy tube changed to a feeding jejunostomy tube. Twenty-four hours later he developed abdominal pain and became clinically septic. A contrast study through the feeding tube and a subsequent computed tomography scan did not reveal any intra-abdominal pathology. At laparotomy it was discovered that the tip of the feeding tube had perforated through the jejunal wall and was lying outside the lumen. This was successfully treated by re-inserting a feeding jejunostomy tube distally and closure of the perforation and previous FJ site

Conclusion

We suggest that the threshold for contrast studies and operative intervention should be low in neurologically impaired patients to avoid the delay in treatment of tube-related complications.
DM, but not cathepsin L, is required to control an aerosol infection withMycobacterium tuberculosis
Authors: Nepal Rajeev Mani , Vesosky Bridget , Turner Joanne , Bryant Paula
Published: July 2008

Antigen presentation by class II MHC molecules in the uninfected host is a multi-step process involving key functions provided by specific cathepsins (Cat) and the peptide editor DM. Herein, we examined the requirement for each of these components in mice to control a low-dose aerosol infection with Mycobacterium tuberculosis (MTB). Mice lacking Cat B, -L, or -S were similar to wild-type in their ability to control the growth and dissemination of MTB. In contrast, DM−/− mice failed to limit MTB growth and showed ∼100-fold higher bacterial burden in the lung and spleen (5–6 weeks postinfection) as compared with wild-type and Cat-deficient mice. Histopathology revealed impaired cellular recruitment and altered granuloma formation in the lungs of MTB-infected DM−/− mice. Moreover, despite impaired thymic selection in Cat L−/− and DM−/− mice, MTB-specific CD4+ T cells were elicited only in the former. The lower numbers of MTB-specific CD4+ T cells available in Cat L−/− mice as compared with wild-type animals were sufficient to control MTB growth and dissemination. In addition, DM−/− macrophages infected with MTB in vitro were unable to stimulate pathogen-specific T cells. The data indicate that the majority of antigens derived from MTB are loaded onto nascent class II MHC molecules via the classical DM-dependent pathway.
Prediction of Survival in Multiple Myeloma Based on Gene Expression Profiles Reveals Cell Cycle and Chromosomal Instability Signatures in High-Risk Patients and Hyperdiploid Signatures in Low-Risk Patients: A Study of the Intergroupe Francophone du Myélome
Authors: Decaux Olivier , Lodé Laurence , Magrangeas Florence , Charbonnel Catherine , Gouraud Wilfried , Jézéquel Pascal , Attal Michel , Harousseau Jean-Luc , Moreau Philippe , Bataille Régis , Campion Loïc , Avet-Loiseau Hervé , Minvielle Stéphane
Published: July 2008

Purpose

Survival of patients with multiple myeloma is highly heterogeneous, from periods of a few weeks to more than 10 years. We used gene expression profiles of myeloma cells obtained at diagnosis to identify broadly applicable prognostic markers.

Patients and Methods

In a training set of 182 patients, we used supervised methods to identify individual genes associated with length of survival. A survival model was built from these genes. The validity of our model was assessed in our test set of 68 patients and in three independent cohorts comprising 853 patients with multiple myeloma.

Results

The 15 strongest genes associated with the length of survival were used to calculate a risk score and to stratify patients into low-risk and high-risk groups. The survival-predictor score was significantly associated with survival in both the training and test sets and in the external validation cohorts. The Kaplan-Meier estimates of rates of survival at 3 years were 90.5% (95% CI, 85.6% to 95.3%) and 47.4% (95% CI, 33.5% to 60.1%), respectively, in our patients having a low risk or high risk independently of traditional prognostic factors. High-risk patients constituted a homogeneous biologic entity characterized by the overexpression of genes involved in cell cycle progression and its surveillance, whereas low-risk patients were heterogeneous and displayed hyperdiploid signatures.

Conclusion

Gene expression–based survival prediction and molecular features associated with high-risk patients may be useful for developing prognostic markers and may provide basis to treat these patients with new targeted antimitotics.
Breast Cancer Onset in Twins and Women With Bilateral Disease
Authors: Hartman Mikael , Hall Per , Edgren Gustaf , Reilly Marie , Lindstrom Linda , Lichtenstein Paul , Kaprio Jaakko , Skytthe Axel , Peto Julian , Czene Kamila
Published: July 2008

Purpose

Little is known of the onset of breast cancer in high-risk populations. We investigated the risk of breast cancer in twin sisters and in the contralateral breast taking family history into consideration.

Patients and Methods

We analyzed a Scandinavian population-based cohort of 2,499 female twin pairs, in which at least one had a diagnosis of breast cancer and estimated the risk of breast cancer in the sister. Using a total of 11 million individuals in Sweden with complete family links, we identified 93,448 women with breast cancer and estimated the risk of a bilateral breast cancer.

Results

The incidence of breast cancer in twin sisters of breast cancer patients was 0.64% per year and 0.42% per year in mono- and dizygotic twin sisters, respectively. In comparison, the risk of familial (affected first-degree relative) and nonfamilial bilateral breast cancer was 1.03% per year and 0.68% per year, respectively. Contrary to the risk of unilateral disease, the risk of cancer in the nonaffected twin and the opposite breast was not affected by age or time since first event. The relative risk of familial bilateral cancer was 52% higher (incidence rate ratio [IRR] = 1.52; 95% CI, 1.42 to 1.64) and the relative risk in the dizygotic twin sister was 25% lower (IRR = 0.75; 95% CI, 0.61 to 0.91) compared with the risk of nonfamilial bilateral cancer.

Conclusion

The elevated risk of breast cancer in high-risk groups is little affected by age and time since diagnosis. Our findings suggest that susceptible groups of women might have already aggregated genetic prerequisites for breast cancer.
Phase II Study of Erlotinib in Recurrent or Metastatic Endometrial Cancer: NCIC IND-148
Authors: Oza Amit M. , Eisenhauer Elizabeth A. , Elit Laurie , Cutz Jean-Claude , Sakurada Akira , Tsao Ming S. , Hoskins Paul J. , Biagi Jim , Ghatage Prafull , Mazurka John , Provencher Diane , Dore Naomi , Dancey Janet , Fyles Anthony
Published: July 2008

Purpose

Epidermal growth factor receptor (EGFR) overexpression is common in endometrial cancers and may have a major role in tumor growth and progression. Erlotinib is an orally active, selective inhibitor of EGFR tyrosine kinase activity.

Patients and Methods

A multinomial design two-stage phase II study was performed to evaluate single-agent activity of erlotinib in women with advanced endometrial cancer with recurrent or metastatic disease who were chemotherapy naïve and had received up to one line of prior hormonal therapy. Erlotinib was administered at daily dose of 150 mg. Archival tumor tissue was analyzed for EGFR expression by immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH). Mutational status of EGFR was determined in responders.

Results

Thirty-two of 34 entered patients are assessable for response. Treatment was well tolerated and severe toxicity infrequent, with the only grade 4 toxicity being an elevation of transaminases (AST). There were four confirmed partial responses (PRs; 12.5%; 95% CI, 3.5% to 29%) lasting 2 to 36 months. Fifteen patients had stable disease (SD), with median duration of 3.7 months (range, 2 to 12 months). EGFR expression was analyzed in thirty patients; 19 were positive, nine were negative, and two were not assessable. Of the 19 patients who were EGFR positive, three had PR (16%), seven SD, and eight progressive disease, and one was not assessable. No mutations were identified in responders. FISH showed no correlation of response with gene amplification.

Conclusion

Erlotinib is well tolerated with an overall objective response rate of 12.5%. Molecular analysis did not identify EGFR mutations in responders or correlation of response with gene amplification.
Power diagrams and interaction processes for unions of discs
Authors: Møller Jesper , Helisová Kateřina
Published: July 2008

We study a flexible class of finite-disc process models with interaction between the discs. We let 𝒰 denote the random set given by the union of discs, and use for the disc process an exponential family density with the canonical sufficient statistic depending only on geometric properties of 𝒰 such as the area, perimeter, Euler-Poincaré characteristic, and the number of holes. This includes the quermass-interaction process and the continuum random-cluster model as special cases. Viewing our model as a connected component Markov point process, and thereby establishing local and spatial Markov properties, becomes useful for handling the problem of edge effects when only 𝒰 is observed within a bounded observation window. The power tessellation and its dual graph become major tools when establishing inclusion-exclusion formulae, formulae for computing geometric characteristics of 𝒰, and stability properties of the underlying disc process density. Algorithms for constructing the power tessellation of 𝒰 and for simulating the disc process are discussed, and the software is made public available.
Length and surface area estimation under smoothness restrictions
Authors: Pateiro-López Beatriz , Rodríguez-Casal Alberto
Published: July 2008

The problem of estimating the Minkowski content L0(G) of a body G ⊂ ℝd is considered. For d = 2, the Minkowski content represents the boundary length of G. It is assumed that a ball of radius r can roll inside and outside the boundary of G. We use this shape restriction to propose a new estimator for L0(G). This estimator is based on the information provided by a random sample, taken on a square containing G, in which we know whether a sample point is in G or not. We obtain the almost sure convergence rate for the proposed estimator.
Index policies for discounted bandit problems with availability constraints
Authors: Dayanik Savas , Powell Warren , Yamazaki Kazutoshi
Published: July 2008

A multiarmed bandit problem is studied when the arms are not always available. The arms are first assumed to be intermittently available with some state/action-dependent probabilities. It is proven that no index policy can attain the maximum expected total discounted reward in every instance of that problem. The Whittle index policy is derived, and its properties are studied. Then it is assumed that the arms may break down, but repair is an option at some cost, and the new Whittle index policy is derived. Both problems are indexable. The proposed index policies cannot be dominated by any other index policy over all multiarmed bandit problems considered here. Whittle indices are evaluated for Bernoulli arms with unknown success probabilities.
Exponential utility indifference valuation in two Brownian settings with stochastic correlation
Authors: Frei Christoph , Schweizer Martin
Published: July 2008

We study the exponential utility indifference valuation of a contingent claim B in an incomplete market driven by two Brownian motions. The claim depends on a nontradable asset stochastically correlated with the traded asset available for hedging. We use martingale arguments to provide upper and lower bounds, in terms of bounds on the correlation, for the value VB of the exponential utility maximization problem with the claim B as random endowment. This yields an explicit formula for the indifference value b of B at any time, even with a fairly general stochastic correlation. Earlier results with constant correlation are recovered and extended. The reason why all this works is that, after a transformation to the minimal martingale measure, the value VB enjoys a monotonicity property in the correlation between tradable and nontradable assets.
Using systematic sampling selection for Monte Carlo solutions of Feynman-Kac equations
Authors: Gentil Ivan , Rémillard Bruno
Published: July 2008

While the convergence properties of many sampling selection methods can be proven, there is one particular sampling selection method introduced in Baker (1987), closely related to ‘systematic sampling’ in statistics, that has been exclusively treated on an empirical basis. The main motivation of the paper is to start to study formally its convergence properties, since in practice it is by far the fastest selection method available. We will show that convergence results for the systematic sampling selection method are related to properties of peculiar Markov chains.
Importance sampling and the two-locus model with subdivided population structure
Authors: Griffiths Robert C. , Jenkins Paul A. , Song Yun S.
Published: July 2008

The diffusion-generator approximation technique developed by De Iorio and Griffiths (2004a) is a very useful method of constructing importance-sampling proposal distributions. Being based on general mathematical principles, the method can be applied to various models in population genetics. In this paper we extend the technique to the neutral coalescent model with recombination, thus obtaining novel sampling distributions for the two-locus model. We consider the case with subdivided population structure, as well as the classic case with only a single population. In the latter case we also consider the importance-sampling proposal distributions suggested by Fearnhead and Donnelly (2001), and show that their two-locus distributions generally differ from ours. In the case of the infinitely-many-alleles model, our approximate sampling distributions are shown to be generally closer to the true distributions than are Fearnhead and Donnelly's.
Boundary behavior and product-form stationary distributions of jump diffusions in the orthant with state-dependent reflections
Authors: Piera Francisco J. , Mazumdar Ravi R. , Guillemin Fabrice M.
Published: July 2008

In this paper we consider reflected diffusions with positive and negative jumps, constrained to lie in the nonnegative orthant of ℝn. We allow for the drift and diffusion coefficients, as well as for the directions of reflection, to be random fields over time and space. We provide a boundary behavior characterization, generalizing known results in the nonrandom coefficients and constant directions of the reflection case. In particular, the regulator processes are related to semimartingale local times at the boundaries, and they are shown not to charge the times the process expends at the intersection of boundary faces. Using the boundary results, we extend the conditions for product-form distributions in the stationary regime to the case when the drift and diffusion coefficients, as well as the directions of reflection, are random fields over space.
Dynamic Distributed Scheduling in Random Access Networks
Authors: Stolyar Alexander L.
Published: July 2008

We consider a model of random access (slotted-aloha-type) communication networks of general topology. Assuming that network links receive exogenous arrivals of packets for transmission, we seek dynamic distributed random access strategies whose goal is to keep all network queues stable. We prove that two dynamic strategies, which we collectively call queue length based random access (QRA), ensure stability as long as the rates of exogenous arrival flows are within the network saturation rate region. The first strategy, QRA-I, can be viewed as a random-access-model counterpart of the max-weight scheduling rule, while the second strategy, QRA-II, is a counterpart of the exponential (EXP) rule. The two strategies induce different dynamics of the queues in the fluid scaling limit, which can be exploited for the quality-of-service control in applications.
Polynomial-Rate Convergence to the Stationary State for the Continuum-Time Limit of the Minority Game
Authors: Ortisi Matteo
Published: July 2008

In this paper we show that the continuum-time version of the minority game satisfies the criteria for the application of a theorem on the existence of an invariant measure. We consider the special case of a game with a ‘sufficiently’ asymmetric initial condition, where the number of possible choices for each individual isS= 2 and Γ < +∞. An upper bound for the asymptotic behavior, as the number of agents grows to infinity, of the waiting time for reaching the stationary state is then obtained.