bluuebunny/crossref_metadata_2025 huggingface dataset:
Giant Cell Tumour of the Hamate Treated Successfully by Acrylic Cementation: A Case Report
Authors: SAKAYAMA K. , SUGAWARA Y. , KIDANI T.
Published: October 2008

We report a case of giant cell tumour (GCT) of the hamate treated by acrylic cementation. It has not recurred 3 years after surgery, and no functional impairment has been observed. We have reviewed previously reported cases of GCTs in the hamate and discuss the best management to prevent recurrence while maintaining function.
Idiopathic Carpal Tunnel Syndrome and Trigger Finger: Is There an Association?
Authors: KUMAR P. , CHAKRABARTI I.
Published: October 2008

Carpal tunnel syndrome (CTS) and trigger finger are known to occur together in association with conditions such as diabetes mellitus, rheumatoid arthritis and hypothyroidism. Although most cases that present to a hand clinic have no obvious predisposing cause, the two conditions often appear together in the same patient. We performed a prospective study of the prevalence of CTS in hospital outpatients presenting with trigger finger. Six hundred and eighty-one patients with CTS, trigger finger or both conditions were recruited prospectively. Diagnosis of both disorders was made on clinical grounds. The study group comprised 551 patients with no obvious predisposing cause. Of 211 patients with trigger finger, 91 (43%) also had CTS. This prevalence is substantially higher than the population prevalence of CTS of approximately 4%. Our data support an association between idiopathic CTS and idiopathic trigger finger and lend support to common pathophysiological factors.
Digital Oedema, Adhesion Formation and Resistance to Digital Motion after Primary Flexor Tendon Repair
Authors: CAO Y. , CHEN C. H. , WU Y. F. , XU X. F. , XIE R. G. , TANG J. B.
Published: October 2008

The development of digital oedema, adhesion formation, and resistance to digital motion at days 0, 3, 5, 7, 9 and 14 after primary flexor tendon repairs using 102 long toes of 51 Leghorn chickens was studied. Oedema presented as tissue swelling from days 3 to 7, which peaked at day 3. After day 7, oedema was manifest as hardening of subcutaneous tissue. The degree of digital swelling correlated with the resistance to tendon motion between days 3 and 7. At day 9, granulation tissues were observed around the tendon and loose adhesions were observed at day 14. Resistance to digital motion increased significantly from day 0 to day 3, but did not increase between days 3 and 9. The early postoperative changes appear to have three stages: initial (days 0–3, increasing resistance with development of oedema), delayed (days 4–7, higher resistance with continuing oedema) and late (after day 7–9, hardening of subcutaneous tissue with development of adhesions).
Image Segmentation for Evaluating Axillary Lymph Nodes
Authors: Evans Kevin D. , Sammet Steffen , Ramos Yvette , Knopp Michael V.
Published: October 2008

A review is provided of the literature that has been published on image segmentation relative to sonography. Manual and automatic techniques for partitioning a sonogram are highlighted. In addition, a preliminary set of results is provided on the interrater reliability of the manual segmentation of axillary lymph nodes that have been sonographically imaged. A correlation between sonographers conducting manual segmentation is very high ( r = 0.9 with P < .00 at the .01 alpha level). This work is set to provide additional information on lymph node cubic volume and the agreement between manual and automatic segmentation of axillary lymph nodes.
Preparation and characterisation of composite double phosphate conversion coatings on AZ91D magnesium alloy
Authors: Xu S. Q. , Li Q. , Lu Y. H. , Chen B. , Fan J. M.
Published: October 2008

A composite double zinc phosphate conversion coating was obtained via forming a hopeite crystal layer on an amorphous phosphate layer on the AZ91D magnesium alloy. The surface morphology, structure and phase composition of the composite coating were investigated by scanning electron microscopy (SEM) and X-ray diffraction (XRD). As a comparison, the single zinc phosphate coating and the bare substrate were also discussed. The phosphate crystal clusters can form on the amorphous layer densely and fine. According to the open circuit potential (OCP) and potentiodynamic polarisation curve tests, the composite phosphate conversion coating on the AZ91D magnesium alloy yielded the best protective effect compared with the single amorphous layer and crystal layer.
Effect of ultrafine grain structure on strain hardening of C–Mn steel warm rolled and subjected to intercritical annealing
Authors: Santos D. B. , Neves E. G. , Gonzalez B. M.
Published: October 2008

The behaviour during the work hardening of low carbon–manganese (0·15%C–1·39%Mn) steel with an ultrafine ferritic grain structure was investigated using Jaoul–Crussard analysis. This microstructure was produced through out quenching, warm rolling and intercritical annealing at 800°C. The steel exhibited a high strain hardening exponent and tensile strength.
Modelling strength and ductility of ultrafine grained BCC and FCC alloys using irreversible thermodynamics
Authors: Huang M. , Rivera-Díaz-del-Castillo P. E. J. , Bouaziz O. , van der Zwaag S.
Published: October 2008

A novel grain size dependent strain hardening model is derived from the theory of irreversible thermodynamics. The model yields the evolution of the dislocation densities in the grain interior and at the grain boundary, as well as their contributions to the flow stress. It is found that submicron grain sizes have a lower dislocation density in the grain interior, causing ductility to decrease greatly. The predicted stress–strain curve shapes, uniform elongation and ultimate tensile strength values for interstitial free steels (body centred cubic) and aluminium alloys (AA1100, face centred cubic) show good agreement with experimental observations.
Microstructure evolution and mechanical properties of nickel based honeycomb sandwich
Authors: Zhang Q. M. , He X. D.
Published: October 2008

A nickel based superalloy honeycomb sandwich was manufactured by high temperature brazing. The microstructure evolution and the out of plate mechanical properties were investigated for honeycomb sandwiches aged at 1000°C in the present paper. The maximum tensile stress was 28·5 MPa and the compressive yield strength was 29·6 MPa for the original specimens. These parameters decreased to 22·9 and 20·5 MPa for specimens aged for 2 h, to 18·2 and 12·2 MPa for specimens aged for 5 h and to 20·2 and 14·3 MPa for specimens aged for 10 h respectively. With increasing aging time the tensile elongation decreased, the intermetallic compounds and the eutectic structure in the brazing region disappeared, and the solid solution approaching the matrix gradually increased.
Stratification of pediatric ALL by in vitro cellular responses to DNA double-strand breaks provides insight into the molecular mechanisms underlying clinical response
Authors: Marston Eliot , Weston Victoria , Jesson Jennifer , Maina Esther , McConville Carmel , Agathanggelou Angelo , Skowronska Anna , Mapp Katie , Sameith Katrin , Powell Judith E. , Lawson Sarah , Kearns Pamela , Falciani Francesco , Taylor Malcolm , Stankovic Tatjana
Published: October 2008

The molecular basis of different outcomes in pediatric acute lymphoblastic leukemia (ALL) remains poorly understood. We addressed the clinical significance and mechanisms behind in vitro cellular responses to ionizing radiation (IR)–induced DNA double-strand breaks in 74 pediatric patients with ALL. We found an apoptosis-resistant response in 36% of patients characterized by failure to cleave caspase-3, -7, -9, and PARP1 by 24 hours after IR and an apoptosis-sensitive response with the cleavage of the same substrates in the remaining 64% of leukemias. Resistance to IR in vitro was associated with poor early blast clearance at day 7 or 15 and persistent minimal residual disease (MRD) at day 28 of induction treatment. Global gene expression profiling revealed abnormal up-regulation of multiple prosurvival pathways in response to IR in apoptosis-resistant leukemias and differential posttranscriptional activation of the PI3-Akt pathway was observed in representative resistant cases. Importantly, pharmacologic inhibition of selected prosurvival pathways sensitized apoptosis-resistant ALL cells to IR in vitro. We suggest that abnormal prosurvival responses to DNA damage provide one of the mechanisms of primary resistance in ALL, and that they should be considered as therapeutic targets in children with aggressive disease.
Classification of drug molecules considering their IC50 values using mixed-integer linear programming based hyper-boxes method
Authors: Armutlu Pelin , Ozdemir Muhittin E , Uney-Yuksektepe Fadime , Kavakli I Halil , Turkay Metin
Published: October 2008

Background

A priori analysis of the activity of drugs on the target protein by computational approaches can be useful in narrowing down drug candidates for further experimental tests. Currently, there are a large number of computational methods that predict the activity of drugs on proteins. In this study, we approach the activity prediction problem as a classification problem and, we aim to improve the classification accuracy by introducing an algorithm that combines partial least squares regression with mixed-integer programming based hyper-boxes classification method, where drug molecules are classified as low active or high active regarding their binding activity (IC50 values) on target proteins. We also aim to determine the most significant molecular descriptors for the drug molecules.

Results

We first apply our approach by analyzing the activities of widely known inhibitor datasets including Acetylcholinesterase (ACHE), Benzodiazepine Receptor (BZR), Dihydrofolate Reductase (DHFR), Cyclooxygenase-2 (COX-2) with known IC50 values. The results at this stage proved that our approach consistently gives better classification accuracies compared to 63 other reported classification methods such as SVM, Naïve Bayes, where we were able to predict the experimentally determined IC50 values with a worst case accuracy of 96%. To further test applicability of this approach we first created dataset for Cytochrome P450 C17 inhibitors and then predicted their activities with 100% accuracy.

Conclusion

Our results indicate that this approach can be utilized to predict the inhibitory effects of inhibitors based on their molecular descriptors. This approach will not only enhance drug discovery process, but also save time and resources committed.
Genes of the most conserved WOX clade in plants affect root and flower development in Arabidopsis
Authors: Deveaux Yves , Toffano-Nioche Claire , Claisse Gaelle , Thareau Vincent , Morin Halima , Laufs Patrick , Moreau Hervé , Kreis Martin , Lecharny Alain
Published: October 2008

Background

The Wuschel related homeobox (WOX) family proteins are key regulators implicated in the determination of cell fate in plants by preventing cell differentiation. A recent WOX phylogeny, based on WOX homeodomains, showed that all of the Physcomitrella patens and Selaginella moellendorffii WOX proteins clustered into a single orthologous group. We hypothesized that members of this group might preferentially share a significant part of their function in phylogenetically distant organisms. Hence, we first validated the limits of the WOX13 orthologous group (WOX13 OG) using the occurrence of other clade specific signatures and conserved intron insertion sites. Secondly, a functional analysis using expression data and mutants was undertaken.

Results

The WOX13 OG contained the most conserved plant WOX proteins including the only WOX detected in the highly proliferating basal unicellular and photosynthetic organism Ostreococcus tauri. A large expansion of the WOX family was observed after the separation of mosses from other land plants and before monocots and dicots have arisen. In Arabidopsis thaliana, AtWOX13 was dynamically expressed during primary and lateral root initiation and development, in gynoecium and during embryo development. AtWOX13 appeared to affect the floral transition. An intriguing clade, represented by the functional AtWOX14 gene inside the WOX13 OG, was only found in the Brassicaceae. Compared to AtWOX13, the gene expression profile of AtWOX14 was restricted to the early stages of lateral root formation and specific to developing anthers. A mutational insertion upstream of the AtWOX14 homeodomain sequence led to abnormal root development, a delay in the floral transition and premature anther differentiation.

Conclusion

Our data provide evidence in favor of the WOX13 OG as the clade containing the most conserved WOX genes and established a functional link to organ initiation and development in Arabidopsis, most likely by preventing premature differentiation. The future use of Ostreococcus tauri and Physcomitrella patens as biological models should allow us to obtain a better insight into the functional importance of WOX13 OG genes.
Effectiveness of a mobile smoking cessation service in reaching elderly smokers and predictors of quitting
Authors: Abdullah Abu Saleh M , Lam Tai-Hing , Chan Steve KK , Leung Gabriel M , Chi Iris , Ho Winnie WN , Chan Sophia SC
Published: October 2008

Background

Different smoking cessation programmes have been developed in the last decade but utilization by the elderly is low. We evaluated a pilot mobile smoking cessation service for the Chinese elderly in Hong Kong and identified predictors of quitting.

Methods

The Mobile Smoking Cessation Programme (MSCP) targeted elderly smokers (aged 60 or above) and provided service in a place that was convenient to the elderly. Trained counsellors provided individual counselling and 4 week's free supply of nicotine replacement therapy (NRT). Follow up was arranged at 1 month by face-to-face and at 3 and 6 months by telephone plus urinary cotinine validation. A structured record sheet was used for data collection. The service was evaluated in terms of process, outcome and cost.

Results

102 governmental and non-governmental social service units and private residential homes for the elderly participated in the MSCP. We held 90 health talks with 3266 elderly (1140 smokers and 2126 non-smokers) attended. Of the 1140 smokers, 365 (32%) received intensive smoking cessation service. By intention-to-treat, the validated 7 day point prevalence quit rate was 20.3% (95% confidence interval: 16.2%–24.8%). Smoking less than 11 cigarettes per day and being adherent to NRT for 4 weeks or more were significant predictors of quitting. The average cost per contact was US$54 (smokers only); per smoker with counselling: US$168; per self-reported quitter: US$594; and per cotinine validated quitter: US$827.

Conclusion

This mobile smoking cessation programme was acceptable to elderly Chinese smokers, with quit rate comparable to other comprehensive programmes in the West. A mobile clinic is a promising model to reach the elderly and probably other hard to reach smokers.
Spatial point analysis based on dengue surveys at household level in central Brazil
Authors: Siqueira-Junior João B , Maciel Ivan J , Barcellos Christovam , Souza Wayner V , Carvalho Marilia S , Nascimento Nazareth E , Oliveira Renato M , Morais-Neto Otaliba , Martelli Celina MT
Published: October 2008

Background

Dengue virus (DENV) affects nonimunne human populations in tropical and subtropical regions. In the Americas, dengue has drastically increased in the last two decades and Brazil is considered one of the most affected countries. The high frequency of asymptomatic infection makes difficult to estimate prevalence of infection using registered cases and to locate high risk intra-urban area at population level. The goal of this spatial point analysis was to identify potential high-risk intra-urban areas of dengue, using data collected at household level from surveys.

Methods

Two household surveys took place in the city of Goiania (~1.1 million population), Central Brazil in the year 2001 and 2002. First survey screened 1,586 asymptomatic individuals older than 5 years of age. Second survey 2,906 asymptomatic volunteers, same age-groups, were selected by multistage sampling (census tracts; blocks; households) using available digital maps. Sera from participants were tested by dengue virus-specific IgM/IgG by EIA. A Generalized Additive Model (GAM) was used to detect the spatial varying risk over the region. Initially without any fixed covariates, to depict the overall risk map, followed by a model including the main covariates and the year, where the resulting maps show the risk associated with living place, controlled for the individual risk factors. This method has the advantage to generate smoothed risk factors maps, adjusted by socio-demographic covariates.

Results

The prevalence of antibody against dengue infection was 37.3% (95%CI [35.5–39.1]) in the year 2002; 7.8% increase in one-year interval. The spatial variation in risk of dengue infection significantly changed when comparing 2001 with 2002, (ORadjusted = 1.35; p < 0.001), while controlling for potential confounders using GAM model. Also increasing age and low education levels were associated with dengue infection.

Conclusion

This study showed spatial heterogeneity in the risk areas of dengue when using a spatial multivariate approach in a short time interval. Data from household surveys pointed out that low prevalence areas in 2001 surveys shifted to high-risk area in consecutive year. This mapping of dengue risks should give insights for control interventions in urban areas.
Public knowledge and attitudes towards Human Papilloma Virus (HPV) vaccination
Authors: Walsh Charlotte Devereaux , Gera Aradhana , Shah Meeraj , Sharma Amit , Powell Judy E , Wilson Sue
Published: October 2008

Background

Human Papilloma Virus (HPV) vaccine has undergone successful trials and has recently been approved for use for the primary prevention of cervical cancer. The aim of this study was to determine knowledge and attitudes towards HPV vaccination.

Methods

Semi-structured interview and questionnaire delivered in a street survey. Standardised HPV-related statements used to measure HPV knowledge and attitudes to vaccination. The setting was three different areas of Birmingham, to target a mix of social class and ethnicity. The sample population was composed of 16–54 year olds.

Results

A total of 420 participants were recruited. Poor knowledge of HPV and its links with cervical cancer were observed. 81% had a knowledge score of zero. Knowledge about HPV was associated with different ethnic group and socio-economic group. The majority (88%) of participants were in favour of vaccination, with 83.6% indicating that they would allow a child under their care to be vaccinated.

Conclusion

Initial responses to the proposed HPV vaccination within the UK public are favourable. However, knowledge levels are poor and media and health professional promotion are required to raise awareness.
Duplex scan in patients with clinical suspicion of deep venous thrombosis
Authors: de Oliveira Aguinaldo , França Graciliano J , Vidal Enrique A , Stalke Paulo SDB , Baroncini Liz AV
Published: October 2008

Background

The incidence of deep venous thrombosis is 0.6/1000 habitants and when symptomatic its diagnosis by duplex scan has 100% sensitivity and 98% specificity.

Objectives

The aim of this study was to evaluate the findings of the duplex scan in patients with clinical suspicion of deep venous thrombosis.

Methods

239 consecutive outpatients (59.2 ± 18.6 years, 164 female) were evaluated by duplex scan.

Results

According to symptoms 101 (42.3%) were related to the right lower limb; 113 (47.3%) to the left lower limb; and 25 were related to both lower limbs. Forty-eight patients presented a normal duplex scan. Venous thrombosis was found in 117 patients (0.49; CI 0.43–0.55): 75 with deep venous thrombosis (DVT), 22 with superficial venous thrombosis (SVT) and 20 with both DVT and SVT. Other pathologies were found in 74 patients. Among patients with DVT the most involved veins were below the knee. Among patients with SVT, 20 (47.6%) showed progression to the deep venous system: 9 (45%) by perforans veins; in 6 by saphenous-femoral junction (30%); and in 5 (25%) by saphenous-popliteal junction.

Conclusion

Deep venous and superficial venous thromboses were diagnosed in 49% of cases. In 30.9% of cases, the duplex scan indicated other pathologies.
Improved proteome coverage by using iTRAQ labelling and peptide OFFGEL fractionation
Authors: Ernoult Emilie , Gamelin Erick , Guette Catherine
Published: October 2008

Background

The development of mass spectrometric techniques and fractionation methods now allows the investigation of very complex protein mixtures ranging from subcellular structures to tissues. Nevertheless, this work is particularly difficult due to the wide dynamic range of protein concentration in eukaryotic tissues. In this paper, we present a shotgun method whereby the peptides are fractionated using OFFGEL electrophoresis after iTRAQ labelling.

Results

We demonstrated that iTRAQ peptide labelling enhances MALDI ionisation and that the OFFGEL fractionation of the labelled peptides introduces a supplementary criterion (pI) useful for validation and identification of proteins. We showed that iTRAQ samples allowed lower-concentrated proteins identification in comparison with free-labelled samples.

Conclusion

The combined use of iTRAQ labelling and OFFGEL fractionation allows a considerable increase in proteome coverage of very complex samples prepared from total cell extracts and supports the low-concentrated protein identification.
The Children's Eating Behaviour Questionnaire: factorial validity and association with Body Mass Index in Dutch children aged 6–7
Authors: Sleddens Ester FC , Kremers Stef PJ , Thijs Carel
Published: October 2008

Background

The Children's Eating Behaviour Questionnaire (CEBQ) is a parent-report measure designed to assess variation in eating style among children. In the present study we translated the CEBQ and examined its factor structure in a sample of parents of 6- and 7-year-old children in the Netherlands. Additionally, associations between the mean scale scores of the instrument and children's body mass index (BMI) were assessed.

Methods

In total, 135 parents of primary school children aged 6 and 7 completed the questionnaire (response rate 41.9%). Children's BMI was converted into standardised z-scores, adjusted for child gender and age to examine the association between mean scale scores and child weight status.

Results

Results generally confirmed the theoretical factor structure, with acceptable internal reliability and between-subscale correlations. Linear regression analyses revealed that BMI z-scores were positively associated with the 'food approach' subscales of the CEBQ (food responsiveness, enjoyment of food, emotional overeating) (β's 0.15 to 0.22) and negatively with 'food avoidant' subscales (satiety responsiveness, slowness in eating, emotional undereating, and food fussiness) (β's -0.09 to -0.25). Significant relations with child BMI z-scores were found for food responsiveness (p = 0.02), enjoyment of food (p = 0.03), satiety responsiveness (p = 0.01) and slowness in eating (p = 0.01).

Conclusion

The results support the use of the CEBQ as a psychometrically sound tool for assessing children's eating behaviours in Dutch children and the study demonstrates its applicability in overweight-related studies.
Anti-HTLV antibody profiling reveals an antibody signature for HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)
Authors: Burbelo Peter D , Meoli Elise , Leahy Hannah P , Graham Jhanelle , Yao Karen , Oh Unsong , Janik John E , Mahieux Renaud , Kashanchi Fatah , Iadarola Michael J , Jacobson Steven
Published: October 2008

Background

HTLV-I is the causal agent of adult T cell leukemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Biomarkers are needed to diagnose and/or predict patients who are at risk for HAM/TSP or ATLL. Therefore, we investigated using luciferase immunoprecipitation technology (LIPS) antibody responses to seven HTLV-I proteins in non-infected controls, asymptomatic HTLV-I-carriers, ATLL and HAM/TSP sera samples. Antibody profiles were correlated with viral load and examined in longitudinal samples.

Results

Anti-GAG antibody titers detected by LIPS differentiated HTLV-infected subjects from uninfected controls with 100% sensitivity and 100% specificity, but did not differ between HTLV-I infected subgroups. However, anti-Env antibody titers were over 4-fold higher in HAM/TSP compared to both asymptomatic HTLV-I (P< 0.0001) and ATLL patients (P< 0.0005). Anti-Env antibody titers above 100,000 LU had 75% positive predictive value and 79% negative predictive value for identifying the HAM/TSP sub-type. Anti-Tax antibody titers were also higher (P< 0.0005) in the HAM/TSP compared to the asymptomatic HTLV-I carriers. Proviral load correlated with anti-Env antibodies in asymptomatic carriers (R= 0.76), but not in HAM/TSP.

Conclusion

These studies indicate that anti-HTLV-I antibody responses detected by LIPS are useful for diagnosis and suggest that elevated anti-Env antibodies are a common feature found in HAM/TSP patients.
The association of elevated reactive oxygen species levels from neutrophils with low-grade inflammation in the elderly
Authors: Ogawa Kishiko , Suzuki Katsuhiko , Okutsu Mitsuharu , Yamazaki Kyoko , Shinkai Shoji
Published: October 2008

Background

Reactive oxygen species (ROS), including free radicals, oxygen ions, and peroxides, are implicated in cell damage. The objective of this study was to investigate whether the spontaneous production of ROS from neutrophils changes with age and is associated with the conventional inflammatory markers.

Results

Thirty-seven elderly subjects (median age, 87, range 70–95 years) and 22 young subjects (median age, 26, range 21–37 years) participated in this study. Circulating levels of C-reactive protein, serum amyloid A, tumor necrosis factor-α, interleukin (IL)-1, IL-6, IL-8, monocyte chemotactic protein-1, and heat shock protein (HSP)70 were measured with enzyme-linked immunosorbent assays. The N-formyl-methionyl-leucyl-phenylalanine and lipopolysaccharide-stimulated ROS of neutrophils were quantified by flow cytometry. Both spontaneous ROS production and circulating levels of inflammatory markers were higher in the elderly group than in the younger group. In addition, spontaneous ROS production by neutrophils was negatively associated with HSP70 in plasma. We could not find the association between spontaneous ROS production by neutrophils and the other inflammatory markers including cytokines.

Conclusion

The results suggest that spontaneous ROS production from neutrophils may increase with age and represent the different aspect of age-associated immune dysregulation.
Molecular characterization and complete genome sequence of avian paramyxovirus type 4 prototype strain duck/Hong Kong/D3/75
Authors: Nayak Baibaswata , Kumar Sachin , Collins Peter L , Samal Siba K
Published: October 2008

Background

Avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds throughout the world. All APMVs, except avian metapneumovirus, are classified in the genus Avulavirus of the family Paramyxoviridae. At present, the APMVs of genus Avulavirus are divided into nine serological types (APMV 1–9). Newcastle disease virus represents APMV-1 and is the most characterized among all APMV types. Very little is known about the molecular characteristics and pathogenicity of APMV 2–9.

Results

As a first step towards understanding the molecular genetics and pathogenicity of APMV-4, we have sequenced the complete genome of APMV-4 strain duck/Hong Kong/D3/75 and determined its pathogenicity in embryonated chicken eggs. The genome of APMV-4 is 15,054 nucleotides (nt) in length, which is consistent with the "rule of six". The genome contains six non-overlapping genes in the order 3'-N-P/V-M-F-HN-L-5'. The genes are flanked on either side by highly conserved transcription start and stop signals and have intergenic sequences varying in length from 9 to 42 nt. The genome contains a 55 nt leader region at 3' end. The 5' trailer region is 17 nt, which is the shortest in the family Paramyxoviridae. Analysis of mRNAs transcribed from the P gene showed that 35% of the transcripts were edited by insertion of one non-templated G residue at an editing site leading to production of V mRNAs. No message was detected that contained insertion of two non-templated G residues, indicating that the W mRNAs are inefficiently produced in APMV-4 infected cells. The cleavage site of the F protein (DIPQR↓F) does not conform to the preferred cleavage site of the ubiquitous intracellular protease furin. However, exogenous proteases were not required for the growth of APMV-4 in cell culture, indicating that the cleavage does not depend on a furin site.

Conclusion

Phylogenic analysis of the nucleotide sequences of viruses of all five genera of the family Paramyxoviridae showed that APMV-4 is more closely related to the APMVs than to other paramyxoviruses, reinforcing the classification of all APMVs in the genus Avulavirus of the family Paramyxoviridae.
Acute and late toxicity in prostate cancer patients treated by dose escalated intensity modulated radiation therapy and organ tracking
Authors: Ghadjar Pirus , Vock Jacqueline , Vetterli Daniel , Manser Peter , Bigler Roland , Tille Jan , Madlung Axel , Behrensmeier Frank , Mini Roberto , Aebersold Daniel M
Published: October 2008

Background

To report acute and late toxicity in prostate cancer patients treated by dose escalated intensity-modulated radiation therapy (IMRT) and organ tracking.

Methods

From 06/2004 to 12/2005 39 men were treated by 80 Gy IMRT along with organ tracking. Median age was 69 years, risk of recurrence was low 18%, intermediate 21% and high in 61% patients. Hormone therapy (HT) was received by 74% of patients. Toxicity was scored according to the CTC scale version 3.0. Median follow-up (FU) was 29 months.

Results

Acute and maximal late grade 2 gastrointestinal (GI) toxicity was 3% and 8%, late grade 2 GI toxicity dropped to 0% at the end of FU. No acute or late grade 3 GI toxicity was observed. Grade 2 and 3 pre-treatment genitourinary (GU) morbidity (PGUM) was 20% and 5%. Acute and maximal late grade 2 GU toxicity was 56% and 28% and late grade 2 GU toxicity decreased to 15% of patients at the end of FU. Acute and maximal late grade 3 GU toxicity was 8% and 3%, respectively. Decreased late ≥ grade 2 GU toxicity free survival was associated with higher age (P = .025), absence of HT (P = .016) and higher PGUM (P < .001).

Discussion

GI toxicity rates after IMRT and organ tracking are excellent, GU toxicity rates are strongly related to PGUM.
Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin
Authors: Shin Thuzar M , Isas J Mario , Hsieh Chia-Ling , Kayed Rakez , Glabe Charles G , Langen Ralf , Chen Jeannie
Published: October 2008

Background

The multifunctional protein vitronectin is present within the deposits associated with Alzheimer disease (AD), age-related macular degeneration (AMD), atherosclerosis, systemic amyloidoses, and glomerulonephritis. The extent to which vitronectin contributes to amyloid formation within these plaques, which contain misfolded, amyloidogenic proteins, and the role of vitronectin in the pathophysiology of the aforementioned diseases is currently unknown. The investigation of vitronectin aggregation is significant since the formation of oligomeric and fibrillar structures are common features of amyloid proteins.

Results

We observed vitronectin immunoreactivity in senile plaques of AD brain, which exhibited overlap with the amyloid fibril-specific OC antibody, suggesting that vitronectin is deposited at sites of amyloid formation. Of particular interest is the growing body of evidence indicating that soluble nonfibrillar oligomers may be responsible for the development and progression of amyloid diseases. In this study we demonstrate that both plasma-purified and recombinant human vitronectin readily form spherical oligomers and typical amyloid fibrils. Vitronectin oligomers are toxic to cultured neuroblastoma and retinal pigment epithelium (RPE) cells, possibly via a membrane-dependent mechanism, as they cause leakage of synthetic vesicles. Oligomer toxicity was attenuated in RPE cells by the anti-oligomer A11 antibody. Vitronectin fibrils contain a C-terminal protease-resistant fragment, which may approximate the core region of residues essential to amyloid formation.

Conclusion

These data reveal the propensity of vitronectin to behave as an amyloid protein and put forth the possibilities that accumulation of misfolded vitronectin may contribute to aggregate formation seen in age-related amyloid diseases.
Red blood cell transfusion within the first 24 hours of admission is associated with increased mortality in the pediatric trauma population: a retrospective cohort study
Authors: Stone Taylor J , Riesenman Paul J , Charles Anthony G
Published: October 2008

Background

Allogeneic red blood cell transfusion is associated with increased morbidity and mortality in adult trauma patients. Although studies have suggested that the adoption of a more restrictive transfusion strategy may be safely applied to critically ill adult and all-cause critically ill pediatric patients, recent developments in our understanding of the negative consequences of red blood cell transfusion have focused almost entirely on adult populations, while the applicability of these findings to the pediatric population remains poorly defined. The object of this study was to evaluate the effect of red blood cell transfusion within the first 24 hours following admission on mortality in pediatric trauma patients treated at our institution.

Results

Age, race, and mechanism of injury did not differ between transfused and non-transfused groups, although there were significantly more female patients in the transfusion group (51 vs. 37%; p < 0.01). Shock index (pulse/systolic blood pressure), injury severity score, and new injury severity score were all significantly higher in the transfused group (1.21 vs. 0.96, 26 vs. 10, and 33 vs. 13 respectively; all p ≤ 0.01). Patients who received a red blood cell transfusion experienced a higher mortality compared to the non-transfused group (29% vs. 3%; p < 0.001). When attempting to control for injury severity, goodness-of-fit analysis revealed a poor fit for the statistical model preventing reliable conclusions about the contribution of red blood cell transfusion as an independent predictor of mortality.

Conclusion

Red blood cell transfusion within the first 24 hours following admission is associated with an increase in mortality in pediatric trauma patients. The potential contribution of red blood cell transfusion as an independent predictor of hospital mortality could not be assessed from our single-institution trauma registry. A review of state-wide or national trauma databases may be necessary to obtain adequate statistical confidence.
The role of casein in supporting the operation of surface bound kinesin
Authors: Verma Vivek , Hancock William O , Catchmark Jeffrey M
Published: October 2008

Microtubules and associated motor proteins such as kinesin are envisioned for applications such as bioseparation and molecular sorting to powering hybrid synthetic mechanical devices. One of the challenges in realizing such systems is retaining motor functionality on device surfaces. Kinesin motors adsorbed onto glass surfaces lose their functionality or ability to interact with microtubules if not adsorbed with other supporting proteins. Casein, a milk protein, is commonly used in microtubule motility assays to preserve kinesin functionality. However, the mechanism responsible for this preservation of motor function is unknown. To study casein and kinesin interaction, a series of microtubule motility assays were performed where whole milk casein, or its αs1 and αs2, β or κ subunits, were introduced or omitted at various steps of the motility assay. In addition, a series of epifluorescence and total internal reflection microscopy (TIRF) experiments were conducted where fluorescently labeled casein was introduced at various steps of the motility assay to assess casein-casein and casein-glass binding dynamics. From these experiments it is concluded that casein forms a bi-layer which supports the operation of kinesin. The first tightly bound layer of casein mainly performs the function of anchoring the kinesin while the second more loosely bound layer of casein positions the head domain of the kinesin to more optimally interact with microtubules. Studies on individual casein subunits indicate that β casein was most effective in supporting kinesin functionality while κ casein was found to be least effective.
Expression-based Pathway Signature Analysis (EPSA): Mining publicly available microarray data for insight into human disease
Authors: Tenenbaum Jessica D , Walker Michael G , Utz Paul J , Butte Atul J
Published: October 2008

Background

Publicly available data repositories facilitate the sharing of an ever-increasing amount of microarray data. However, these datasets remain highly underutilized. Reutilizing the data could offer insights into questions and diseases entirely distinct from those considered in the original experimental design.

Methods

We first analyzed microarray datasets derived from known perturbations of specific pathways using the samr package in R to identify specific patterns of change in gene expression. We refer to these pattern of gene expression alteration as a "pathway signatures." We then used Spearman's rank correlation coefficient, a non-parametric measure of correlation, to determine similarities between pathway signatures and disease profiles, and permutation analysis to evaluate false discovery rate. This enabled detection of statistically significant similarity between these pathway signatures and corresponding changes observed in human disease. Finally, we evaluated pathway activation, as indicated by correlation with the pathway signature, as a risk factor for poor prognosis using multiple unrelated, publicly available datasets.

Results

We have developed a novel method, Expression-based Pathway Signature Analysis (EPSA). We demonstrate that ESPA is a rigorous computational approach for statistically evaluating the degree of similarity between highly disparate sources of microarray expression data. We also show how EPSA can be used in a number of cases to stratify patients with differential disease prognosis. EPSA can be applied to many different types of datasets in spite of different platforms, different experimental designs, and different species. Applying this method can yield new insights into human disease progression.

Conclusion

EPSA enables the use of publicly available data for an entirely new, translational purpose to enable the identification of potential pathways of dysregulation in human disease, as well as potential leads for therapeutic molecular targets.
Photosensitivity, corneal scarring and developmental delay: Xeroderma Pigmentosum in a tropical country
Authors: Halpern James , Hopping Bryan , Brostoff Joshua M
Published: October 2008

We present the case of an 8 year-old girl in a developing country with significant corneal scarring and multiple cutaneous skin lesions in sun-exposed areas. Neuro-developmental delay had been present since 3 months of age, and taken as a whole the consensus was that this clinical picture was consistent with Xeroderma Pigmentosum (XP). We highlight the difficulties encountered due to the lack of diagnostic and treatment modalities for this child, and offer a brief review of XP, including emerging treatments that show potential.
Effects of cyclophosphamide on pulmonary function in patients with scleroderma and interstitial lung disease: a systematic review and meta-analysis of randomized controlled trials and observational prospective cohort studies
Authors: Nannini Carlotta , West Colin P , Erwin Patricia J , Matteson Eric L
Published: October 2008

Introduction

The purpose of the present study was to systematically review the effect of cyclophosphamide treatment on pulmonary function in patients with systemic sclerosis and interstitial lung disease.

Methods

The primary outcomes were the mean change in forced vital capacity and in diffusing capacity for carbon monoxide after 12 months of therapy in patients treated with cyclophosphamide.

Results

Three randomized clinical trials and six prospective observational studies were included for analysis. In the pooled analysis, the forced vital capacity and the diffusing capacity for carbon monoxide predicted values after 12 months of therapy were essentially unchanged, with mean changes of 2.83% (95% confidence interval = 0.35 to 5.31) and 4.56% (95% confidence interval = -0.21 to 9.33), respectively.

Conclusions

Cyclophosphamide treatment in patients with systemic sclerosis-related interstitial lung disease does not result in clinically significant improvement of pulmonary function.
Association of a single nucleotide polymorphism in growth differentiate factor 5 with congenital dysplasia of the hip: a case-control study
Authors: Dai Jin , Shi Dongquan , Zhu Pengsheng , Qin Jianghui , Ni Haijian , Xu Yong , Yao Chen , Zhu Lunqing , Zhu Hongtao , Zhao Baocheng , Wei Jia , Liu Baorui , Ikegawa Shiro , Jiang Qing , Ding Yitao
Published: October 2008

Introduction

Congenital dysplasia of the hip is an abnormal seating of the femoral head in the acetabulum, mainly caused by shallow acetabulum and lax joint capsule. Genetic factors play a considerable role in the pathogenesis of congenital dysplasia of the hip. The gene growth differentiate factor 5 (GDF5) has been implicated in skeletal development and joint morphogenesis in humans and mice. A functional single nucleotide polymorphism (SNP) in the 5'-untranslated region of GDF5 (rs143383) was reported to be associated with osteoarthritis susceptibility. As a key regulator in morphogenesis of skeletal components and soft tissues in and around the joints, GDF5 may be involved in the aetiology and pathogenesis of congenital dysplasia of the hip. Our objective is to evaluate if the GDF5 SNP is associated with congenital dysplasia of the hip in people of Han Chinese origin.

Methods

The GDF5 SNP was genotyped in 338 children with congenital dysplasia of the hip and 622 control subjects.

Results

The SNP was significantly associated with congenital dysplasia of the hip (p = 0.0037; odds ration (OR) = 1.40; 95% confidence interval (CI) = 1.11 to 1.75). A significant difference was detected in female samples when stratified by gender (p = 0.0053; OR = 1.46; 95% CI = 1.21 to 1.91), and in hip dislocation when stratified by severity (p = 0.0078; OR = 1.43; 95% CI = 1.11 to 1.85).

Conclusions

Our results indicate that GDF5 is important in the aetiology of congenital dysplasia of the hip. To the authors' knowledge this is the first time that a definite association with the congenital dysplasia of the hip susceptibility has been detected.
A modeling study of preprocessing considerations for reverse-time migration
Authors: Jones Ian F.
Published: October 2008

Much of the thinking behind conventional geophysical processing assumes that we wanted to image energy that propagates down from the surface of the earth, scatters from a reflector or diffractor, and then propagates back up to the recording surface without being reflected by any other feature. Such travel paths conform to the assumptions of one-way wave propagation, and most contemporary migration schemes are designed to image such data. In addition, the moveout behavior of these primary reflection events in the various prestack domains is well understood, and many of our standard data-preprocessing techniques relied on the assumption that this behavior adequately describes the events we wanted to preserve for imaging. As a corollary, events that do not conform to this prescribed behavior are classified as noise, and many of our standard preprocessing techniqueswere designed to remove them. We assessed the kinematics of moveout behavior of events that arise from two-way wave propagation and the effect of certain preprocessing techniques on those events. This was of interest to us because the recent rapid increase in available cost-effective computing power has enabled industrial implementation of migration algorithms—particularly reverse-time migration—that in principle can image events that reflect more than once on their way from source to receiver. We used 2D synthetic data to show that some conventional data-processing steps—particularly those used in suppression of complex reverberations (“multiples”)—remove nonreverberatory primary events from seismic reflection data. Specifically, they remove events that have repeated or turning reflections in the subsurface (such as double-bounce arrivals) but that otherwise are imageable using reverse-time migration.
Randomized Trial of Postoperative Reirradiation Combined With Chemotherapy After Salvage Surgery Compared With Salvage Surgery Alone in Head and Neck Carcinoma
Authors: Janot François , de Raucourt Dominique , Benhamou Ellen , Ferron Christophe , Dolivet Gilles , Bensadoun René-Jean , Hamoir Marc , Géry Bernard , Julieron Morbize , Castaing Marine , Bardet Etienne , Grégoire Vincent , Bourhis Jean
Published: October 2008

Purpose

Full-dose reirradiation combined with chemotherapy has been shown to be feasible after salvage surgery with acceptable toxicity. The Groupe d’Etude des Tumeurs de la Tête et du Cou and Groupe d’Oncologie Radiothérapie Tête Et Cou groups performed a randomized study to assess its efficacy.

Patients and Methods

Between 1999 and 2005, 130 patients with head and neck cancer were treated with salvage surgery and randomly assigned to full-dose reirradiation combined with chemotherapy (RT arm) or to observation (a “wait and see” approach; WS arm). Eligibility criteria were recurrence or a second primary tumor in a previously irradiated area, no major sequelae resulting from the first radiotherapy, good general condition, no distant metastasis, and salvage surgery with macroscopic complete resection. Patients in the RT arm received 60 Gy over 11 weeks combined with concomitant fluorouracil and hydroxyurea.

Results

Sixty-five patients were randomly assigned to each arm. There was no imbalance in the distribution of the main tumor and patients characteristics. The most serious acute toxicity in the RT arm was mucositis, attaining grade 3 or 4 in 28% of patients. At 2 years, 39% of patients in the RT arm and 10% in the WS arm experienced grade 3 or 4 late toxicity according to Radiation Therapy Oncology Group criteria (P = .06). Disease-free survival (DFS) was significantly improved in the RT arm, with a hazard ratio of 1.68 (95% CI, 1.13 to 2.50; P = .01), but overall survival (OS) was not statistically different.

Conclusion

Full-dose reirradiation combined with chemotherapy after salvage surgery significantly improved DFS, but had no significant impact on OS. An increase in both acute and late toxicity was observed.