bluuebunny/crossref_metadata_2025 huggingface dataset:
Occupation and skin cancer: the results of the HELIOS-I multicenter case-control study
Authors: Suárez Berta , López-Abente Gonzalo , Martínez Carmen , Navarro Carmen , Tormo Maria José , Rosso Stefano , Schraub Simon , Gafà Lorenzo , Sancho-Garnier Hélène , Wechsler Janine , Zanetti Roberto
Published: August 2007

Background

Non-melanoma skin cancer (NMSC) is the most frequent tumour among Caucasian populations worldwide. Among the risk factors associated with this tumour, there are host-related factors and several environmental agents. A greater likelihood of high exposure to physical agents (with the exception of solar radiation) and chemical agents depends on the work setting. Our objective is to evaluate the role of occupational exposures in NMSC, with special emphasis on risk factors other than solar radiation and skin type.

Methods

We analysed 1585 cases (1333 basal cell carcinoma (BCC) and 183 squamous cell carcinoma (SCC)) and 1507 controls drawn from the Helios-I multicenter study. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression mixed models.

Results

For NMSC as a whole (both histological types), miners and quarrymen, secondary education teachers, and masons registered excess risk, regardless of exposure to solar radiation and skin type (OR 7.04, 95% CI 2.44–20.31; OR 1.75, 95% CI 1.05–2.89 and OR 1.54, 95% CI 1.04–2.27, respectively). Frequency of BCC proved higher among railway engine drivers and firemen (OR 4.55; 95% CI 0.96–21.57), specialised farmers (OR 1.65; 95% CI 1.05–2.59) and salesmen (OR 3.02; 95% CI 1.05–2.86), in addition to miners and quarrymen and secondary education teachers (OR 7.96; 95% CI 2.72–23.23 and OR 1.76; 95% CI 1.05–2.94 respectively). The occupations that registered a higher risk of SCC (though not of BCC) were those involving direct contact with livestock, construction workers not elsewhere classified (OR 2.95, 95% CI 1.12–7.74), stationary engine and related equipment operators not elsewhere classified (OR 5.31, 95% CI 1.13–21.04) and masons (OR 2.55, 95% CI 1.36–4.78).

Conclusion

Exposure to hazardous air pollutants, arsenic, ionizing radiations and burns may explain a good part of the associations observed in this study. The Helios study affords an excellent opportunity for further in-depth study of physical and chemical agents and NMSC based on matrices of occupational exposure.
Methods and representativeness of a European survey in children and adolescents: the KIDSCREEN study
Authors: Berra Silvina , Ravens-Sieberer Ulrike , Erhart Michael , Tebé Cristian , Bisegger Corinna , Duer Wolfgang , von Rueden Ursula , Herdman Michael , Alonso Jordi , Rajmil Luis ,   the European KIDSCREEN group [kidscreen]
Published: August 2007

Background

The objective of the present study was to compare three different sampling and questionnaire administration methods used in the international KIDSCREEN study in terms of participation, response rates, and external validity.

Methods

Children and adolescents aged 8–18 years were surveyed in 13 European countries using either telephone sampling and mail administration, random sampling of school listings followed by classroom or mail administration, or multistage random sampling of communities and households with self-administration of the survey materials at home. Cooperation, completion, and response rates were compared across countries and survey methods. Data on non-respondents was collected in 8 countries. The population fraction (PF, respondents in each sex-age, or educational level category, divided by the population in the same category from Eurostat census data) and population fraction ratio (PFR, ratio of PF) and their corresponding 95% confidence intervals were used to analyze differences by country between the KIDSCREEN samples and a reference Eurostat population.

Results

Response rates by country ranged from 18.9% to 91.2%. Response rates were highest in the school-based surveys (69.0%–91.2%). Sample proportions by age and gender were similar to the reference Eurostat population in most countries, although boys and adolescents were slightly underrepresented (PFR <1). Parents in lower educational categories were less likely to participate (PFR <1 in 5 countries). Parents in higher educational categories were overrepresented when the school and household sampling strategies were used (PFR = 1.78–2.97).

Conclusion

School-based sampling achieved the highest overall response rates but also produced slightly more biased samples than the other methods. The results suggest that the samples were sufficiently representative to provide reference population values for the KIDSCREEN instrument.
Prevalence of overweight and obesity on the island of Ireland: results from the North South Survey of Children's Height, Weight and Body Mass Index, 2002
Authors: Whelton Helen , Harrington Janas , Crowley Evelyn , Kelleher Virginia , Cronin Michael , Perry Ivan J
Published: August 2007

Background

Childhood obesity is emerging as a major public health problem in developed and developing countries worldwide. The aim of this survey was to establish baseline data on the prevalence and correlates of overweight and obesity among children and adolescents in the Republic of Ireland (RoI) and Northern Ireland (NI).

Methods

The heights and weights of 19,617 school-going children and adolescents aged between 4 and 16 years in NI and RoI were measured using standardised and calibrated scales and measures. The participants were a representative cross-sectional sample of children randomly selected on the basis of age, gender and geographical location of the school attended. Overweight and obesity were classified according to standard IOTF criteria.

Results

Males were taller than females, children in RoI were taller than those in NI and the more affluent were taller than the less well off. The overall prevalence of overweight and obesity was higher among females than males in both jurisdictions. Overall, almost one in four boys (23% RoI and NI) and over one in four girls (28% RoI, 25% NI) were either overweight or obese. In RoI, the highest prevalence of overweight was among 13 year old girls (32%) and obesity among 7 year old girls (11%). In NI the highest prevalence of overweight and obesity were found among 11 and 8 year old girls respectively (33% and 13%).

Conclusion

These figures confirm the emergence of the obesity epidemic among children in Ireland, a wealthy country with the European Union. The results serve to underpin the urgency of implementing broad intersectoral measures to reduce calorie intake and increase levels of physical activity, particularly among children.
The efficacy of intraoperative methylene blue enemas to assess the integrity of a colonic anastomosis
Authors: Smith Stanton , McGeehin William , Kozol Robert A , Giles David
Published: August 2007

Background

Intraoperative testing of colonic anastomoses is routine in assuring anastamotic integrity. We sought to determine the efficacy of the methylene blue enema (MBE) as an intraoperative test for anastomotic leaks.

Methods

This study is a retrospective review of consecutive colonic operations performed from January 2001 to December 2004 in a community hospital setting by a general surgical group that uses the MBE exclusively. All operations featuring a colonic anastomosis and an intraoperative MBE were studied (n = 229). Intraoperative MBE via a rectal tube was used as the diagnostic test. Intraoperative leak (IOL) rate and clinically significant postoperative leak (POL) rate were the outcome measures.

Results

The IOL rate was 4.5% for proximal anastomoses, 8% for distal anastomoses, and 7% of total anastomoses. The POL rate was 3% of anastomosis. There were no other testing methods employed. There were no POLs in cases where an IOL led to concomitant intraoperative repair. POL rate for proximal anastomosis was 0.8% and for distal 3%, for stapled 1% and hand sewn 5%.

Conclusion

MBE IOL rate is comparable to published IOL rates for other methods of intraoperative testing. The MBE can be applied to proximal and distal anastomosis. Patients who were found to have an IOL, and underwent immediate repair, did not develop a clinical POL.
Observation of glycine zipper and unanticipated occurrence of ambidextrous helices in the crystal structure of a chiral undecapeptide
Authors: Acharya Rudresh , Gupta Madhvi , Ramakumar Suryanarayanarao , Ramagopal Udupi A , Chauhan Virander S
Published: August 2007

Background

The de novo design of peptides and proteins has recently surfaced as an approach for investigating protein structure and function. This approach vitally tests our knowledge of protein folding and function, while also laying the groundwork for the fabrication of proteins with properties not precedented in nature. The success of these studies relies heavily on the ability to design relatively short peptides that can espouse stable secondary structures. To this end, substitution with α, β-dehydroamino acids, especially α, β-dehydrophenylalanine (ΔPhe) comes in use for spawning well-defined structural motifs. Introduction of ΔPhe induces β-bends in small and 310-helices in longer peptide sequences.

Results

The present report is an investigation of the effect of incorporating two glycines in the middle of a ΔPhe containing undecapeptide. A de novo designed undecapeptide, Ac-Gly1-Ala2-ΔPhe3-Leu4-Gly5-ΔPhe6-Leu7-Gly8-ΔPhe9-Ala10-Gly11-NH2, was synthesized and characterized using X-ray diffraction and Circular Dichroism spectroscopic methods. Crystallographic studies suggest that, despite the presence of L-amino acid (L-Ala and L-Leu) residues in the middle of the sequence, the peptide adopts a 310-helical conformation of ambidextrous screw sense, one of them a left-handed (A) and the other a right-handed (B) 310-helix with A and B being antiparallel to each other. However, CD studies reveal that the undecapeptide exclusively adopts a right-handed 310-helical conformation. In the crystal packing, three different interhelical interfaces, Leu-Leu, Gly-Gly and ΔPhe-ΔPhe are observed between the helices A and B. A network of C-H...O hydrogen bonds are observed at ΔPhe-ΔPhe and Gly-Gly interhelical interfaces. An important feature observed is the occurrence of glycine zipper motif at Gly-Gly interface. At this interface, the geometric pattern of interhelical interactions seems to resemble those observed between helices in transmembrane (TM) proteins.

Conclusion

The present design strategy can thus be exploited in future work on de novo design of helical bundles of higher order and compaction utilizing ΔPhe residues along with GXXG motif.
Evaluation of the prevalence and economic burden of adverse drug reactions presenting to the medical emergency department of a tertiary referral centre: a prospective study
Authors: Patel KJ , Kedia MS , Bajpai D , Mehta SS , Kshirsagar NA , Gogtay NJ
Published: August 2007

Background

Adverse drug reactions (ADRs) are now recognized as an important cause of hospital admissions, with a proportion ranging from 0.9–7.9%. They also constitute a significant economic burden. We thus aimed at determining the prevalence and the economic burden of ADRs presenting to Medical Emergency Department (ED) of a tertiary referral center in India

Methods

A prospective, observational study of adult patients carried out over a 6 week period in 2005. The prevalence of ADRs, their economic burden from the hospital perspective, severity, and preventability were assessed using standard criteria.

Results

A total 6899 patients presented during the study period. Of these, 2046 were admitted for various reasons. A total of 265/6899 patients had ADRs (3.84 %). A total of 141/265 was admitted due to ADsR, and thus ADRs as a cause of admissions were 6.89% of total admissions. A majority (74.71%) were found to be of moderate severity. The most common ADRs were anti-tubercular drug induced hepatotoxicity, warfarin toxicity and chloroquine induced gastritis. The median duration of hospitalization was 5 days [95% CI 5.37, 7.11], and the average hospitalization cost incurred per patient was INR 6197/- (USD 150). Of total ADRs, 59.62% (158/265) were found to be either definitely or potentially avoidable.

Conclusion

The study shows that ADRs leading to hospitalization are frequent and constitute a significant economic burden. Training of patients and prescribers may lead to a reduction in hospitalization due to avoidable ADRs and thus lessen their economic burden.
Influence of socioeconomic factors on medically unnecessary ambulance calls
Authors: Kawakami Chihiro , Ohshige Kenji , Kubota Katsuaki , Tochikubo Osamu
Published: August 2007

Background

Unnecessary ambulance use has become a socioeconomic problem in Japan. We investigated the possible relations between socioeconomic factors and medically unnecessary ambulance calls, and we estimated the incremental demand for unnecessary ambulance use produced by socioeconomic factors.

Methods

We conducted a self-administered questionnaire-based survey targeting residents of Yokohama, Japan. The questionnaire included questions pertaining to socioeconomic characteristics, dichotomous choice method questions pertaining to ambulance calls in hypothetical nonemergency situations, and questions on the city's emergency medical system. The probit model was used to analyze the data.

Results

A total of 2,029 out of 3,363 targeted recipients completed the questionnaire (response rate, 60.3%). Probit regression analyses showed that several demographic and socioeconomic factors influence the decision to call an ambulance. Male respondents were more apt than female respondents to state that they would call an ambulance in nonemergency situations (p < 0.05). Age was an important factor influencing the hypothetical decision to call an ambulance (p < 0.05); elderly persons were more apt than younger persons to state that they would call an ambulance. Possession of a car and hesitation to use an ambulance negatively influenced the hypothetical decision to call an ambulance (p < 0.05). Persons who do not have a car were more likely than those with a car to state that they would call an ambulance in unnecessary situations.

Conclusion

Results of the study suggest that several socioeconomic factors, i.e., age, gender, household income, and possession of a car, influence a person's decision to call an ambulance in nonemergency situations. Hesitation to use an ambulance and knowledge of the city's primary emergency medical center are likely to be important factors limiting ambulance overuse. It was estimated that unnecessary ambulance use is increased approximately 10% to 20% by socioeconomic factors.
Feeding and resting behaviour of malaria vector, Anopheles arabiensis with reference to zooprophylaxis
Authors: Mahande Aneth , Mosha Franklin , Mahande Johnson , Kweka Eliningaya
Published: August 2007

Background

The most important factor for effective zooprophylaxis in reducing malaria transmission is a predominant population of a strongly zoophilic mosquito, Anopheles arabiensis. The feeding preference behaviour of Anopheline mosquitoes was evaluated in odour-baited entry trap (OBET).

Methods

Mosquitoes were captured daily using odour-baited entry traps, light traps and hand catch both indoor and in pit traps. Experimental huts were used for release and recapture experiment. The mosquitoes collected were compared in species abundances.

Results

Anopheles arabiensis was found to account for over 99% of Anopheles species collected in the study area in Lower Moshi, Northern Tanzania. In experimental release/capture trials conducted at the Mabogini verandah huts, An. arabiensis was found to have higher exophilic tendency (80.7%) compared to Anopheles gambiae (59.7%) and Culex spp. (60.8%). OBET experiments conducted at Mabogini collected a total of 506 An. arabiensis in four different trials involving human, cattle, sheep, goat and pig. Odours from the cattle attracted 90.3% (243) compared to odours from human, which attracted 9.7% (26) with a significant difference at P = 0.005. Odours from sheep, goat and pig attracted 9.7%, 7.2% and 7.3%, respectively. Estimation of HBI in An. arabiensis collected from houses in three lower Moshi villages indicated lower ratios for mosquitoes collected from houses with cattle compared to those without cattles. HBI was also lower in mosquitoes collected outdoors (0.1–0.3) compared to indoor (0.4–0.9).

Conclusion

In discussing the results, reference has been made to observation of exophilic, zoophilic and feeding tendencies of An. arabiensis, which are conducive for zooprophylaxis. It is recommended that in areas with a predominant An. arabiensis population, cattle should be placed close to dwelling houses in order to maximize the effects of zooprophylaxis. Protective effects of human from malaria can further be enhanced by keeping cattle in surroundings of residences.
Self-reported predictors of depressive symptomatology in an elderly population with type 2 diabetes mellitus: a prospective cohort study
Authors: Pawaskar Manjiri D , Anderson Roger T , Balkrishnan Rajesh
Published: August 2007

Background

The prevalence of depression increases among the elderly with chronic medical conditions like diabetes. Hence, the purpose of this study was to determine predictors of depressive symptomatology in Medicare enrolled elderly population with type 2 diabetes mellitus.

Methods

A prospective cohort study was conducted by administrating health risk assessment questionnaire to elderly (≥65 years) with type 2 diabetes. Responses were linked with administrative claim's data. Data were obtained from elderly with type 2 diabetes who were enrolled in Medicare Health Maintenance Organization (HMO) in southeastern United States. The instrument collected information related to demographics, health status, medication use, and healthcare service utilization prior to enrollment. Responses were combined with the administrative claims data of HMO to obtain information on actual utilization of healthcare resources. The Short Form Center for Epidemiologic Studies Depression scale was used to assess depressive symptoms. Multivariable logistic regression analyses were conducted to determine predictor variables.

Results

Of 792 respondents, about 17% had depressive symptoms. Almost 96% of patients were using 1 or more antidiabetic medications. Overall, increased risk of depression was associated with lower health related quality of life (HRQoL) (OR: 0.97; 95% CI: 0.96–0.98) and higher impairments in instrumental activities of daily living (IADLs) (OR: 1.31; 95% CI: 1.14–0.52) in elderly patients. Poor health related quality of life (OR: 0.97, 95%CI: 0.95–0.99) was associated with higher risk of depression in patients on insulin therapy.

Conclusion

Impairments in daily activities and lower HRQoL were predictors of depressive symptomatology in elderly with diabetes. Determinants of depression varied according to pharmacotherapeutic class of antidiabetic medications.
A comparison of dispersing media for various engineered carbon nanoparticles
Authors: Buford Mary C , Hamilton Raymond F , Holian Andrij
Published: August 2007

Background

With the increased manufacture and use of carbon nanoparticles (CNP) there has been increasing concern about the potential toxicity of fugitive CNP in the workplace and ambient environment. To address this matter a number of investigators have conducted in vitro and in vivo toxicity assessments. However, a variety of different approaches for suspension of these particles (culture media, Tween 80, dimethyl sulfoxide, phosphate-buffered saline, fetal calf serum, and others), and different sources of materials have generated potentially conflicting outcomes. The quality of the dispersion of nanoparticles is very dependent on the medium used to suspend them, and this then will most likely affect the biological outcomes.

Results

In this work, the distributions of different CNP (sources and types) have been characterized in various media. Furthermore, the outcome of instilling the different agglomerates, or size distributions, was examined in mouse lungs after one and seven days. Our results demonstrated that CNP suspended in serum produced particle suspensions with the fewest large agglomerates, and the most uniform distribution in mouse lungs. In addition, no apparent clearance of instilled CNP took place from lungs even after seven days.

Conclusion

This work demonstrates that CNP agglomerates are present in all dispersing vehicles to some degree. The vehicle that contains some protein, lipid or protein/lipid component disperses the CNP best, producing fewer large CNP agglomerates. In contrast, vehicles absent of lipid and protein produce the largest CNP agglomerates. The source of the CNP is also a factor in the degree of particle agglomeration within the same vehicle.
Do Motor Control Genes Contribute to Interindividual Variability in Decreased Movement in Patients with Pain?
Authors: Mishra Bikash K , Wu Tianxia , Belfer Inna , Hodgkinson Colin A , Cohen Leonardo G , Kiselycznyk Carly , Kingman Albert , Keller Robert B , Yuan Qiaoping , Goldman David , Atlas Steven J , Max Mitchell B
Published: August 2007

Background:

Because excessive reduction in activities after back injury may impair recovery, it is important to understand and address the factors contributing to the variability in motor responses to pain. The current dominant theory is the “fear-avoidance model”, in which the some patients' heightened fears of further injury cause them to avoid movement. We propose that in addition to psychological factors, neurochemical variants in the circuits controlling movement and their modification by pain may contribute to this variability. A systematic search of the motor research literature and genetic databases yielded a prioritized list of polymorphic motor control candidate genes. We demonstrate an analytic method that we applied to 14 of these genes in 290 patients with acute sciatica, whose reduction in movement was estimated by items from the Roland-Morris Disability Questionnaire.

Results:

We genotyped a total of 121 single nucleotide polymorphisms (SNPs) in 14 of these genes, which code for the dopamine D2 receptor, GTP cyclohydrolase I, glycine receptor α1 subunit, GABA-A receptor α2 subunit, GABA-A receptor β1 subunit, α-adrenergic 1C, 2A, and 2C receptors, serotonin 1A and 2A receptors, cannabinoid CB-1 receptor, M1 muscarinic receptor, and the tyrosine hydroxylase, and tachykinin precursor-1 molecules. No SNP showed a significant association with the movement score after a Bonferroni correction for the 14 genes tested. Haplotype analysis of one of the blocks in the GABA-A receptor β1 subunit showed that a haplotype of 11% frequency was associated with less limitation of movement at a nominal significance level value (p = 0.0025) almost strong enough to correct for testing 22 haplotype blocks.

Conclusion:

If confirmed, the current results may suggest that a common haplotype in the GABA-A β1 subunit acts like an “endogenous muscle relaxant” in an individual with subacute sciatica. Similar methods might be applied a larger set of genes in animal models and human laboratory and clinical studies to understand the causes and prevention of pain-related reduction in movement.
Delayed Sympathetic Dependence in the Spared Nerve Injury (SNI) Model of Neuropathic Pain
Authors: Pertin Marie , Allchorne Andrew J , Beggah Ahmed T , Woolf Clifford J , Decosterd Isabelle
Published: August 2007

Background:

Clinical and experimental studies of neuropathic pain support the hypothesis that a functional coupling between postganglionic sympathetic efferent and sensory afferent fibers contributes to the pain. We investigated whether neuropathic pain-related behavior in the spared nerve injury (SNI) rat model is dependent on the sympathetic nervous system.

Results:

Permanent chemical sympathectomy was achieved by daily injection of guanethidine (50 mg/kg s.c.) from age P8 to P21. SNI was performed at adulthood followed by 11 weeks of mechanical and thermal hypersensitivity testing. A significant but limited effect of the sympathectomy on SNI-induced pain sensitivity was observed. The effect was delayed and restricted to cold allodynia-like behavior: SNI-related cold scores were lower in the sympathectomized group compared to the control group at 8 and 11 weeks after the nerve injury but not before. Mechanical hypersensitivity tests (pinprick and von Frey hair threshold tests) showed no difference between groups during the study period. Concomitantly, pericellular tyrosine-hydroxylase immunoreactive basket structures were observed around dorsal root ganglia (DRG) neurons 8 weeks after SNI, but were absent at earlier time points after SNI and in sham operated controls.

Conclusion:

These results suggest that the early establishment of neuropathic pain-related behavior after distal nerve injury such as in the SNI model is mechanistically independent of the sympathetic system, whereas the system contributes to the maintenance, albeit after a delay of many weeks, of response to cold-related stimuli.
Remission by composite scores in rheumatoid arthritis: are ankles and feet important?
Authors: Kapral Theresa , Dernoschnig Florian , Machold Klaus P , Stamm Tanja , Schoels Monika , Smolen Josef S , Aletaha Daniel
Published: August 2007

Current treatment strategies aim to achieve clinical remission in order to prevent the long-term consequences of rheumatoid arthritis (RA). Several composite indices are available to assess remission. All of them include joint counts as the assessment of the major 'organ' involved in RA, but some employ reduced joint counts, such as the 28-joint count, which excludes ankles and feet.

The aim of the present study was to determine the relevance of excluding joints of the ankles and feet in the assessment of RA disease activity and remission. Using a longitudinal observational RA dataset, we analyzed 767 patients (80% female, 60% rheumatoid factor-positive), for whom joint counts had been recorded at 2,754 visits. We determined the number of affected joints by the 28-JC and the 32-JC, the latter including ankles and combined metatarso-phalangeal joints (as a block on each side).

Several findings were supportive of the validity of the 28-joint count: (a) Absence of joint swelling on the 28-joint scale had a specificity of 98.1% and a positive predictive value (PPV) of 94.1% for the absence of swelling also on the 32-joint scale. For absence of tender joints, the specificity and PPV were 96.1% and 91.7%, respectively. (b) Patients with swollen or tender joints in the 32-JC, despite no joint activity in the 28-JC, were clearly different with regard to other disease activity measures. In particular, the patient global assessment of disease activity was higher in these individuals. Thus, the difference in the joint count was not relevant for composite disease activity assessment. (c) The disease activity score based on 28 joints (DAS28) may reach levels higher than 2.6 in patients with feet swelling since these patients often have other findings that raise DAS28. (d) The frequency of remission did not change when the 28-JC was replaced by 32-JC in the composite indices. (e) The changes in joint activity over time were almost identical in longitudinal analysis.

The assessment of the ankles and feet is an important part in the clinical evaluation of patients with RA. However, reduced joint counts are appropriate and valid tools for formal disease activity assessment, such as done in composite indices.
Risk factors associated with the loss of cartilage volume on weight-bearing areas in knee osteoarthritis patients assessed by quantitative magnetic resonance imaging: a longitudinal study
Authors: Pelletier Jean-Pierre , Raynauld Jean-Pierre , Berthiaume Marie-Josée , Abram François , Choquette Denis , Haraoui Boulos , Beary John F , Cline Gary A , Meyer Joan M , Martel-Pelletier Johanne
Published: August 2007

The objective of this study was to identify, on a symptomatic knee osteoarthritis (OA) cohort, the risk factors associated with the progression of the disease. More specifically, we investigated the correlation between knee cartilage volume loss from subregions over the span of 24 months by means of quantitative magnetic resonance imaging (qMRI) with demographic, clinical, radiological, and MRI structural changes.

A cohort of 107 patients with knee OA selected from a large trial evaluating the effect of a bisphosphonate underwent x-rays and MRI of the knee at baseline and 24 months. Joint space width (JSW) and joint space narrowing (JSN) and cartilage volume loss over time in subregions of the tibial plateaus and femoral condyles were quantitated. Structural changes in the subchondral bone (hypersignal) and in the menisci (tear and extrusion) were also evaluated.

The greatest cartilage volume loss was found in the medial compartment, and risk factors included female gender, JSW, meniscal lesions, and bone changes at baseline. Subregion analysis revealed that the greatest cartilage volume loss at 24 months was found in the central area of the medial tibial plateau (15%; p < 0.0001) and of the medial femoral condyle (12%; p < 0.0001). These findings were associated with the presence at baseline of meniscal extrusion, particularly severe meniscal extrusion, medial and severe meniscal tear, bone hypersignal, high body mass index (BMI), smaller JSW, increases in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and patient global scores over time, and greater JSN. Parameters predicting medial central femoral condyle cartilage volume loss at 24 months were lateral meniscal tear, SF-36 and BMI at baseline, and JSN. At the medial central tibial plateau, the parameters were severe meniscal extrusion, severe lateral meniscal tear, and bone hypersignal in the lateral compartment at baseline, and WOMAC pain change.

Meniscal damage and bone changes are the features most closely associated with the greatest subregional cartilage volume loss. Interestingly, for the first time, JSN was strongly associated with cartilage loss in the central areas of plateaus and condyles. This study also further confirms the correlation between cartilage volume loss and JSN and symptomatic changes at 24 months.
A novel approach for prediction of tacrolimus blood concentration in liver transplantation patients in the intensive care unit through support vector regression
Authors: Van Looy Stijn , Verplancke Thierry , Benoit Dominique , Hoste Eric , Van Maele Georges , De Turck Filip , Decruyenaere Johan
Published: August 2007

Introduction

Tacrolimus is an important immunosuppressive drug for organ transplantation patients. It has a narrow therapeutic range, toxic side effects, and a blood concentration with wide intra- and interindividual variability. Hence, it is of the utmost importance to monitor tacrolimus blood concentration, thereby ensuring clinical effect and avoiding toxic side effects. Prediction models for tacrolimus blood concentration can improve clinical care by optimizing monitoring of these concentrations, especially in the initial phase after transplantation during intensive care unit (ICU) stay. This is the first study in the ICU in which support vector machines, as a new data modeling technique, are investigated and tested in their prediction capabilities of tacrolimus blood concentration. Linear support vector regression (SVR) and nonlinear radial basis function (RBF) SVR are compared with multiple linear regression (MLR).

Methods

Tacrolimus blood concentrations, together with 35 other relevant variables from 50 liver transplantation patients, were extracted from our ICU database. This resulted in a dataset of 457 blood samples, on average between 9 and 10 samples per patient, finally resulting in a database of more than 16,000 data values. Nonlinear RBF SVR, linear SVR, and MLR were performed after selection of clinically relevant input variables and model parameters. Differences between observed and predicted tacrolimus blood concentrations were calculated. Prediction accuracy of the three methods was compared after fivefold cross-validation (Friedman test and Wilcoxon signed rank analysis).

Results

Linear SVR and nonlinear RBF SVR had mean absolute differences between observed and predicted tacrolimus blood concentrations of 2.31 ng/ml (standard deviation [SD] 2.47) and 2.38 ng/ml (SD 2.49), respectively. MLR had a mean absolute difference of 2.73 ng/ml (SD 3.79). The difference between linear SVR and MLR was statistically significant (p < 0.001). RBF SVR had the advantage of requiring only 2 input variables to perform this prediction in comparison to 15 and 16 variables needed by linear SVR and MLR, respectively. This is an indication of the superior prediction capability of nonlinear SVR.

Conclusion

Prediction of tacrolimus blood concentration with linear and nonlinear SVR was excellent, and accuracy was superior in comparison with an MLR model.
Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study
Authors: Zappitelli Michael , Washburn Kimberly K , Arikan Ayse A , Loftis Laura , Ma Qing , Devarajan Prasad , Parikh Chirag R , Goldstein Stuart L
Published: August 2007

Introduction

Serum creatinine is a late marker of acute kidney injury (AKI). Urine neutrophil gelatinase-associated lipocalin (uNGAL) is an early marker of AKI, where the timing of kidney injury is known. It is unknown whether uNGAL predicts AKI in the general critical care setting. We assessed the ability of uNGAL to predict AKI development and severity in critically ill children.

Methods

This was a prospective cohort study of critically ill children. Children aged between 1 month and 21 years who were mechanically ventilated and had a bladder catheter inserted were eligible. Patients with end-stage renal disease or who had just undergone kidney transplantation were excluded. Patients were enrolled within 24 to 48 hours of initiation of mechanical ventilation. Clinical data and serum creatinine were collected daily for up to 14 days from enrollment, and urine was collected once daily for up to 4 days for uNGAL measurement. AKI was graded using pRIFLE (pediatric modified Risk, Injury, Failure, Loss, End Stage Kidney Disease) criteria. Day 0 was defined as the day on which the AKI initially occurred, and pRIFLEmax was defined as the worst pRIFLE AKI grade recorded during the study period. The χ2 test was used to compare associations between categorical variables. Mann-Whitney and Kruskal-Wallis tests were used to compare continuous variables between groups. Diagnostic characteristics were evaluated by calculating sensitivity and specificity, and constructing receiver operating characteristic curves.

Results

A total of 140 patients (54% boys, mean ± standard deviation Pediatric Risk of Mortality II score 15.0 ± 8.0, 23% sepsis) were included. Mean and peak uNGAL concentrations increased with worsening pRIFLEmax status (P < 0.05). uNGAL concentrations rose (at least sixfold higher than in controls) in AKI, 2 days before and after a 50% or greater rise in serum creatinine, without change in control uNGAL. The parameter uNGAL was a good diagnostic marker for AKI development (area under the receiver operating characteristic curve [AUC] 0.78, 95% confidence interval [CI] 0.62 to 0.95) and persistent AKI for 48 hours or longer (AUC 0.79, 95% CI 0.61 to 0.98), but not for AKI severity, when it was recorded after a rise in serum creatinine had occurred (AUC 0.63, 95% CI 0.44 to 0.82).

Conclusion

We found uNGAL to be a useful early AKI marker that predicted development of severe AKI in a heterogeneous group of patients with unknown timing of kidney injury.
Human subtelomeric duplicon structure and organization
Authors: Ambrosini Anthony , Paul Sheila , Hu Sufen , Riethman Harold
Published: August 2007

Background

Human subtelomeric segmental duplications ('subtelomeric repeats') comprise about 25% of the most distal 500 kb and 80% of the most distal 100 kb in human DNA. A systematic analysis of the duplication substructure of human subtelomeric regions was done in order to develop a detailed understanding of subtelomeric sequence organization and a nucleotide sequence-level characterization of subtelomeric duplicon families.

Results

The extent of nucleotide sequence divergence within subtelomeric duplicon families varies considerably, as does the organization of duplicon blocks at subtelomere alleles. Subtelomeric internal (TTAGGG)n-like tracts occur at duplicon boundaries, suggesting their involvement in the generation of the complex sequence organization. Most duplicons have copies at both subtelomere and non-subtelomere locations, but a class of duplicon blocks is identified that are subtelomere-specific. In addition, a group of six subterminal duplicon families are identified that, together with six single-copy telomere-adjacent segments, include all of the (TTAGGG)n-adjacent sequence identified so far in the human genome.

Conclusion

Identification of a class of duplicon blocks that is subtelomere-specific will facilitate high-resolution analysis of subtelomere repeat copy number variation as well as studies involving somatic subtelomere rearrangements. The significant levels of nucleotide sequence divergence within many duplicon families as well as the differential organization of duplicon blocks on subtelomere alleles may provide opportunities for allele-specific subtelomere marker development; this is especially true for subterminal regions, where divergence and organizational differences are the greatest. These subterminal sequence families comprise the immediate cis-elements for (TTAGGG)n tracts, and are prime candidates for subtelomeric sequences regulating telomere-specific (TTAGGG)n tract length in humans.
Using comparative genomics to reorder the human genome sequence into a virtual sheep genome
Authors: Dalrymple Brian P , Kirkness Ewen F , Nefedov Mikhail , McWilliam Sean , Ratnakumar Abhirami , Barris Wes , Zhao Shaying , Shetty Jyoti , Maddox Jillian F , O'Grady Margaret , Nicholas Frank , Crawford Allan M , Smith Tim , de Jong Pieter J , McEwan John , Oddy V Hutton , Cockett Noelle E ,   the International Sheep Genomics Consortium
Published: August 2007

Background

Is it possible to construct an accurate and detailed subgene-level map of a genome using bacterial artificial chromosome (BAC) end sequences, a sparse marker map, and the sequences of other genomes?

Results

A sheep BAC library, CHORI-243, was constructed and the BAC end sequences were determined and mapped with high sensitivity and low specificity onto the frameworks of the human, dog, and cow genomes. To maximize genome coverage, the coordinates of all BAC end sequence hits to the cow and dog genomes were also converted to the equivalent human genome coordinates. The 84,624 sheep BACs (about 5.4-fold genome coverage) with paired ends in the correct orientation (tail-to-tail) and spacing, combined with information from sheep BAC comparative genome contigs (CGCs) built separately on the dog and cow genomes, were used to construct 1,172 sheep BAC-CGCs, covering 91.2% of the human genome. Clustered non-tail-to-tail and outsize BACs located close to the ends of many BAC-CGCs linked BAC-CGCs covering about 70% of the genome to at least one other BAC-CGC on the same chromosome. Using the BAC-CGCs, the intrachromosomal and interchromosomal BAC-CGC linkage information, human/cow and vertebrate synteny, and the sheep marker map, a virtual sheep genome was constructed. To identify BACs potentially located in gaps between BAC-CGCs, an additional set of 55,668 sheep BACs were positioned on the sheep genome with lower confidence. A coordinate conversion process allowed us to transfer human genes and other genome features to the virtual sheep genome to display on a sheep genome browser.

Conclusion

We demonstrate that limited sequencing of BACs combined with positioning on a well assembled genome and integrating locations from other less well assembled genomes can yield extensive, detailed subgene-level maps of mammalian genomes, for which genomic resources are currently limited.
RASTA-Bacteria: a web-based tool for identifying toxin-antitoxin loci in prokaryotes
Authors: Sevin Emeric W , Barloy-Hubler Frédérique
Published: August 2007

Toxin/antitoxin (TA) systems, viewed as essential regulators of growth arrest and programmed cell death, are widespread among prokaryotes, but remain sparsely annotated. We present RASTA-Bacteria, an automated method allowing quick and reliable identification of TA loci in sequenced prokaryotic genomes, whether they are annotated open reading frames or not. The tool successfully confirmed all reported TA systems, and spotted new putative loci upon screening of sequenced genomes. RASTA-Bacteria is publicly available at http://genoweb.univ-rennes1.fr/duals/RASTA-Bacteria.
Exon expression profiling reveals stimulus-mediated exon use in neural cells
Authors: McKee Adrienne E , Neretti Nicola , Carvalho Luis E , Meyer Clifford A , Fox Edward A , Brodsky Alexander S , Silver Pamela A
Published: August 2007

Background:

Neuronal cells respond to changes in intracellular calcium ([Ca2+]i) by affecting both the abundance and architecture of specific mRNAs. Although calcium-induced transcription and transcript variation have both been recognized as important sources of gene regulation, the interplay between these two phenomena has not been evaluated on a genome-wide scale.

Results:

Here, we show that exon-centric microarrays can be used to resolve the [Ca2+]i-modulated gene expression response into transcript-level and exon-level regulation. Global assessments of affected transcripts reveal modulation within distinct functional gene categories. We find that transcripts containing calcium-modulated exons exhibit enrichment for calcium ion binding, calmodulin binding, plasma membrane associated, and metabolic proteins. Additionally, we uncover instances of regulated exon use in potassium channels, neuroendocrine secretory proteins and metabolic enzymes, and demonstrate that regulated changes in exon expression give rise to distinct transcript variants.

Conclusion:

Our findings connect extracellular stimuli to specific exon behavior, and suggest that changes in transcript and exon abundance are reflective of a coordinated gene expression response to elevated [Ca2+]i. The technology we describe here lends itself readily to the resolution of stimulus-induced gene expression at both the transcript and exon levels.
Regulation of skeletogenic differentiation in cranial dermal bone
Authors: Abzhanov Arhat , Rodda Stephen J. , McMahon Andrew P. , Tabin Clifford J.
Published: August 2007

Although endochondral ossification of the limb and axial skeleton is relatively well-understood, the development of dermal (intramembranous) bone featured by many craniofacial skeletal elements is not nearly as well-characterized. We analyzed the expression domains of a number of markers that have previously been associated with endochondral skeleton development to define the cellular transitions involved in the dermal ossification process in both chick and mouse. This led to the recognition of a series of distinct steps in the dermal differentiation pathways, including a unique cell type characterized by the expression of both osteogenic and chondrogenic markers. Several signaling molecules previously implicated in endochondrial development were found to be expressed during specific stages of dermal bone formation. Three of these were studied functionally using retroviral misexpression. We found that activity of bone morphogenic proteins (BMPs) is required for neural crest-derived mesenchyme to commit to the osteogenic pathway and that both Indian hedgehog (IHH) and parathyroid hormone-related protein (PTHrP, PTHLH)negatively regulate the transition from preosteoblastic progenitors to osteoblasts. These results provide a framework for understanding dermal bone development with an aim of bringing it closer to the molecular and cellular resolution available for the endochondral bone development.
Redefining the role of ectoderm in somitogenesis: a player in the formation of the fibronectin matrix of presomitic mesoderm
Authors: Rifes Pedro , Carvalho Lara , Lopes Catarina , Andrade Raquel P. , Rodrigues Gabriela , Palmeirim Isabel , Thorsteinsdóttir Sólveig
Published: August 2007

The absence of ectoderm impairs somite formation in cultured presomitic mesoderm (PSM) explants, suggesting that an ectoderm-derived signal is essential for somitogenesis. Here we show in chick that the standard enzymatic treatments used for explant isolation destroy the fibronectin matrix surrounding the anterior PSM, which fails to form somites when cultured for 6 hours. By contrast, explants isolated with collagenase retain their fibronectin matrix and form somites under identical culture conditions. The additional presence of ectoderm enhances somite formation, whereas endoderm has no effect. Furthermore, we show that pancreatin-isolated PSM explants cultured in fibronectin-supplemented medium, form significantly more somites than control explants. Interestingly, ectoderm is the major producer of fibronectin (Fn1) transcripts, whereas all but the anterior-most region of the PSM expresses the fibronectin assembly receptor, integrinα5 (Itga5). We thus propose that the ectoderm-derived fibronectin is assembled by mesodermal α5β1 integrin on the surface of the PSM. Finally, we demonstrate that inhibition of fibronectin fibrillogenesis in explants with ectoderm abrogates somitogenesis. We conclude that a fibronectin matrix is essential for morphological somite formation and that a major, previously unrecognised role of ectoderm in somitogenesis is the synthesis of fibronectin.
Heterosexual HIV transmission dynamics: implications for prevention and control
Authors: Chin James , Bennett Anthony
Published: August 2007

Understanding the epidemiologic definition of epidemic versus non-epidemic spread of an infectious disease agent and the different patterns of heterosexual HIV transmission are needed to fully understand the low potential for heterosexual HIV epidemics in most heterosexual populations. Epidemic sexual HIV transmission can occur only in populations where there are large numbers of persons who have unprotected sex with multiple and concurrent sex partners. How high HIV prevalence may reach in these populations depends on the size and overlap of sex networks, and the prevalence of facilitating and protective factors that can greatly increase or limit the amount of infected blood and sexual fluids exchanged during intercourse. The wide difference in potentials for heterosexual HIV epidemics that exists within and between countries must be recognized, accepted and monitored in order to design and focus prevention strategies where they are most needed and most effective.
The frequency of high-grade intraepithelial neoplasia in anal/perianal warts is higher than previously recognized
Authors: McCloskey J C , Metcalf C , French M A , Flexman J P , Burke V , Beilin L J
Published: August 2007

A retrospective review of the prevalence of intraepithelial neoplasia (IN) in surgically removed perianal/anal warts from December 1995 to December 2004 was undertaken in patients referred to the Sexual Health Clinic at Royal Perth Hospital. Data were analysed from 115 men and 38 women, 29 of whom had HIV infection (27 men and two women). Perianal/anal IN within the warts was found in 78% (52% high grade) of men with HIV infection. In men without HIV infection, the overall rate of IN within warts was 33% (20% high grade). The IN rate was 8.3% for HIV-negative women (2.8% high grade). Rates of IN within perianal/anal warts in men with or without HIV infection are higher than previously reported, and suggest the likelihood of a substantial increase in the future incidence of anal cancer. The association between IN and genital warts needs to be further studied.
Methaemoglobinaemia causing progressive dyspnoea and cyanosis during treatment of Pneumocystis jirovecii pneumonia
Authors: Hamill Matthew , Harte Derval , Miller Robert F
Published: August 2007

An HIV-infected man became increasingly breathless and cyanosed while receiving clindamycin and primaquine treatment for Pneumocystis jirovecii pneumonia. He was found to have 11.4% methaemoglobinaemia and recovered with conservative management.