bluuebunny/crossref_metadata_2025 huggingface dataset:
Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI – Mel.A.) [ISRCTN75125874]
Authors: Chiarion-Sileni Vanna , Del Bianco Paola , Romanini Antonella , Guida Michele , Paccagnella Adriano , Dalla Palma Maurizio , Naglieri Emanuele , Ridolfi Ruggero , Silvestri Barbara , Michiara Maria , De Salvo Gian Luca
Published: March 2006

Background

High-dose interferon alfa-2b (IFNalfa-2b), according to the ECOG 1684 schedule, is the only approved adjuvant treatment for stage III melanoma patients by the FDA and EMEA. However, the risk/benefit profile has been questioned limiting its world-wide use. In the late nineties, the Italian Melanoma Inter-group started a spontaneous randomized clinical trial (RCT) to verify if a more intense, but shorter than the ECOG 1684 regimen, could improve survival without increasing the toxicity profile. The safety analysis in the first 169 patients who completed the treatment is here described.

Methods

Stage III melanoma patients were randomized to receive IFNalfa-2b 20 MU/m2/d intravenously (IV) 5 days/week × 4 weeks, repeated for three times on weeks 9 to 12, 17 to 20, 25 to 28 (Dose-Dense/Dose-Intense, DD/DI, arm), or IFNalfa-2b 20 MU/m2/d IV 5 days/week × 4 weeks followed by 10 MU/m2 subcutaneously (SC) three times per week × 48 weeks (High Dose Interferon, HDI, arm). Toxicity was recorded and graded, according to the WHO criteria, as the worst grade that occurred during each cycle.

Results

The most common toxicities in both arms were flu-like and gastrointestinal symptoms, leukopenia, liver and neuro-psichiatric morbidities; with regard to severe toxicity, only leukopenia was statistically more frequent in DD/DI arm than in HDI arm (24% vs 9%) (p = 0.0074), yet, this did not cause an increase in the infection risk. Discontinuation of treatment, due to toxicity, was observed in 13 and 17% of the patients in the DD/DI and HDI arm, respectively. The median actual dose intensity delivered in the DD/DI arm (36.4 MU/m2/week) was statistically higher than that delivered in the HDI arm (30.7 MU/m2/week) (p = 0.003).

Conclusion

Four cycles of intravenous high-dose IFNalfa-2b can be safely delivered with an increase in the median dose intensity. Efficacy results from this trial are eagerly awaited.
Inhibitors of apoptosis proteins in human cervical cancer
Authors: Espinosa Magali , Cantú David , Herrera Norma , Lopez Carlos M , De la Garza Jaime G , Maldonado Vilma , Melendez-Zajgla Jorge
Published: March 2006

Background

It has been shown that IAPs, in particular XIAP, survivin and c-IAP1, are overexpressed in several malignancies. In the present study we investigate the expression of c-IAP1, c-IAP2, XIAP and survivin and its isoforms in cervical cancer.

Methods

We used semiquantitative RT-PCR assays to analyze 41 cancer and 6 normal tissues. The study included 8 stage I cases; 16 stage II; 17 stageIII; and a control group of 6 samples of normal cervical squamous epithelial tissue.

Results

c-IAP2 and XIAP mRNA levels were similar among the samples, cervical tumors had lower c-IAP1 mRNA levels. Unexpectedly, a clear positive association was found between low levels of XIAP and disease relapse. A log-rank test showed a significant inverse association (p= 0.02) between XIAP expression and tumor aggressiveness, as indicated by disease relapse rates. There were no statistically significant differences in the presence or expression levels of c-IAP1 and c-IAP2 among any of the clinical variables studied. Survivin and its isoforms were undetectable in normal cervical tissues, in contrast with the clear upregulation observed in cancer samples. We found no association between survivin expression and age, clinical stage, histology or menopausal state. Nevertheless, we found that adenocarcinoma tumors expressed higher levels of survivin 2B and DeltaEx3 (p= 0.001 andp= 0.04 respectively, by Kruskal-Wallis). A multivariate Cox's partial likelihood-based analysis showed that only FIGO stage was an independent predictor of outcome.

Conclusion

There are no differences in the expression of c-IAP2 and XIAP between normal vs. cancer samples, but XIAP expression correlate in cervical cancer with relapse of this disease in the patients. Otherwise, c-IAP1 was downregulated in the cervical cancer samples. The expression of survivin was upregulated in the patients with cervical cancer. We have found that adenocarcinoma presented higher levels of survivin isoforms 2B and DeltaEx3.
Prognostic significance of HER3 and HER4 protein expression in colorectal adenocarcinomas
Authors: Kountourakis Panteleimon , Pavlakis Kitty , Psyrri Amanda , Rontogianni Dimitra , Xiros Nikolaos , Patsouris Efstratios , Pectasides Dimitrios , Economopoulos Theofanis
Published: March 2006

Background

Colorectal cancer remains a major cause of cancer mortality in the Western world. A limited number of studies has been conducted in respect of Her-3 and Her-4 expression and their correlation with clinical parameters and prognosis in colorectal carcinomas . In this study we sought to determine the pattern and the prognostic significance of HER-3 and HER-4 in colorectal adenocarcinoma.

Methods

We studied HER-3 and HER-4 protein expression in106 paraffin embedded specimens of primary colorectal tumors using immunohistochemistry. The pattern and protein expression levels of HER-3 and HER-4 were correlated with several clinical and pathological parameters.

Results

HER-3 staining displayed membranous and cytoplasmic expression pattern in 18 (17%) and 30 samples (28,3%), respectively. HER-4 membranous and cytoplasmic expression was found in 20 (18,9%) and 32 samples (30,2%), respectively. Specimens regarded as positive for HER-3 cytoplasmic expression were associated with moderate tumor grade (p = 0,032) and older median age (p = 0,010). Specimens regarded as positive for HER-4 membranous protein expression were associated with involved lymphnodes (p = 0,0003). Similar results were obtained when considering Her-3 and Her-4 protein expression irrespective of their cellular localization. There was no correlation between the expression of HER-3 and HER-4 and patients outcome.

Conclusion

HER-4 membranous protein expression was found to predict for lymph nodes positivity in this cohort of patients with colorectal cancer.HER-4 expression status may identify tumors with aggressive biological behavior and increased metastatic potential.
Cough and reflux esophagitis in children: their co-existence and airway cellularity
Authors: Chang Anne B , Cox Nancy C , Faoagali Joan , Cleghorn Geoffrey J , Beem Christopher , Ee Looi C , Withers Geoffrey D , Patrick Mark K , Lewindon Peter J
Published: March 2006

Background

There are no prospective studies that have examined for chronic cough in children without lung disease but with gastroesophageal reflux (GER). In otherwise healthy children undergoing flexible upper gastrointestinal endoscopy (esophago-gastroscopy), the aims of the study were to (1) define the frequency of cough in relation to symptoms of GER, (2) examine if children with cough and reflux esophagitis (RE) have different airway cellularity and microbiology in bronchoalveolar lavage (BAL) when compared to those without.

Methods

Data specific for chronic cough (>4-weeks), symptoms of GER and cough severity were collected. Children aged <16-years (n = 150) were defined as 'coughers' (C+) if a history of cough in association with their GER symptoms was elicited before BAL were obtained during elective esophago-gastroscopy. Presence of esophagitis on esophageal biopsies was considered reflux esophagitis positive (E+).

Results

C+ (n = 69) were just as likely as C- (n = 81) to have esophagitis, odds ratio 0.87 (95%CI 0.46, 1.7). Median neutrophil percentage in BAL was significantly different between groups; highest in C+E- (7, IQR 28) and lowest in C-E+ (5, IQR 6). BAL positive bacterial culture occurred in 20.7% and were more likely present in current coughers (OR 3.37, 95%CI 1.39, 8.08). Airway neutrophilia (median 20%, IQR 34) was significantly higher in those with BAL positive bacterial cultures than those without (5%, 4; p = 0.0001).

Conclusion

In children without lung disease, the common co-existence of cough with symptoms of GER is independent of the occurrence of esophagitis. Airway neutrophilia when present in these children is more likely to be related to airway bacterial infection and not to esophagitis.
Relation between awareness of circulatory disorders and smoking in a general population health examination
Authors: John Ulrich , Meyer Christian , Hanke Monika , Völzke Henry , Schumann Anja
Published: March 2006

Background

Little is known about proportions of smokers who maintain smoking after they are aware of a circulatory disorder. The goal was to analyze the extent to which the number of circulatory disorders may be related to being a current smoker.

Methods

Cross-sectional survey study with a probability sample of residents in Germany investigated in health examination centers. Questionnaire data of 3,778 ever smoking participants aged 18 – 79 were used, questions included whether the respondent had ever had hypertension, myocardial infarction, other coronary artery disease, heart failure, stroke, other cerebrovascular disease, peripheral vascular disease, and venous thrombosis. Logistic regression was calculated for circulatory disorders and their number with current smoking as the dependent variable, and odds ratios (OR) are presented adjusted for physician contact, inpatient treatment, smoking cessation counseling, heavy smoking, exercise, overweight and obesity, school education, sex and age.

Results

Among ever smokers who had 1 circulatory disorder, 52.1 % were current smokers and among those who reported that they had 3 or more circulatory disorders 28.0 % were current smokers at the time of the interview. The adjusted odds of being a current smoker were lower for individuals who had ever smoked in life and had 2 or more central circulatory disorders, such as myocardial infarction, heart failure or stroke, than for ever smokers without central circulatory disorder (2 or more disorders: adjusted OR 0.6, 95 % confidence interval, CI, 0.4 to 0.8).

Conclusion

Among those with central circulatory disorders, there is a substantial portion of individuals who smoke despite their disease. The data suggest that only a portion of smokers among the general population seems to be discouraged from smoking by circulatory disorders or its accompanying cognitive or emotional processes.
Risk behaviors of 15–21 year olds in Mexico lead to a high prevalence of sexually transmitted infections: results of a survey in disadvantaged urban areas
Authors: Gutierrez Juan-Pablo , Bertozzi Stefano M , Conde-Glez Carlos J , Sanchez-Aleman Miguel-Angel
Published: March 2006

Background

Due to the fact that adolescents are more likely to participate in high-risk behaviors, this sector of the population is particularly vulnerable to contracting sexually transmitted infections (STIs) and resultant health problems.

Methods

A survey was carried out among adolescents from poor homes in 204 small-urban areas of Mexico. Information was collected in relation to risk behaviors and socio-economic environment. A sub-group of the participants also provided blood and urine samples which were analyzed to detect sexually transmitted infections.

Results

The presence of Chlamydia was detected in nearly 8% of participants who had stated that they were sexually active (18%) and approximately 12% were positive for herpes type 2-specific antibodies. For both, a greater proportion of girls resulted positive compared to boys. The presence of these biological outcomes of sexual risk behavior was associated with other risk behaviors (smoking), but not with self-reported indicators of protected sex (reported use of condom during most recent sexual activity).

Conclusion

The results presented in this study show a startlingly high prevalence of HSV-2 among sexually active Mexican adolescents in poor urban areas, suggesting that this group has participated to a great extent in risky sexual practices. The relationships between socioeconomic environment and adolescent risk behavior need to be better understood if we are to design preventive interventions that modify the determinants of risk behaviors.
An analysis of factors that influence personal exposure to toluene and xylene in residents of Athens, Greece
Authors: Alexopoulos Evangelos C , Chatzis Christos , Linos Athena
Published: March 2006

Background

Personal exposure to pollutants is influenced by various outdoor and indoor sources. The aim of this study was to evaluate the exposure of Athens citizens to toluene and xylene, excluding exposure from active smoking.

Methods

Passive air samplers were used to monitor volunteers, their homes and various urban sites for one year, resulting in 2400 measurements of toluene and xylene levels. Since both indoor and outdoor pollution contribute significantly to human exposure, volunteers were chosen from occupational groups who spend a lot of time in the streets (traffic policemen, bus drivers and postmen), and from groups who spend more time indoors (teachers and students). Data on individual and house characteristics were obtained using a questionnaire completed at the beginning of the study; a time-location-activity diary was also completed daily by the volunteers in each of the six monitoring campaigns.

Results

Average personal toluene exposure varied over the six monitoring campaigns from 53 to 80 μg/m3. Urban and indoor concentrations ranged from 47 – 84 μg/m3 and 30 – 51 μg/m3, respectively. Average personal xylene exposure varied between 56 and 85 μg/m3 while urban and indoor concentrations ranged from 53 – 88 μg/m3 and 27 – 48 μg/m3, respectively. Urban pollution, indoor residential concentrations and personal exposures exhibited the same pattern of variation during the measurement periods. This variation among monitoring campaigns might largely be explained by differences in climate parameters, namely wind speed, humidity and amount of sunlight.

Conclusion

In Athens, Greece, the time spent outdoors in the city center during work or leisure makes a major contribution to exposure to toluene and xylene among non-smoking citizens. Indoor pollution and means of transportation contribute significantly to individual exposure levels. Other indoor residential characteristics such as recent painting and mode of heating used might also contribute significantly to individual levels. Groups who may be subject to higher exposures (e.g. those who spent more time outdoors because of occupational activities) need to be surveyed and protected against possible adverse health effects.
In vitro gentamicin release from commercially available calcium-phosphate bone substitutes influence of carrier type on duration of the release profile
Authors: Stallmann Hein P , Faber Chris , Bronckers Antonius LJJ , Nieuw Amerongen Arie V , Wuisman Paul IJM
Published: March 2006

Background

Polymethyl-methacrylate (PMMA) beads releasing antibiotics are used extensively to treat osteomyelitis, but require surgical removal afterwards because they do not degrade.

Methods

As an alternative option, this report compares the in vitro gentamicin release profile from clinically used, biodegradable carrier-materials: six injectable cements and six granule-types. Cement cylinders and coated granules containing 3% gentamicin were submerged in dH2O and placed in a 48-sample parallel drug-release system. At regular intervals (30, 90, 180 min. and then every 24 h, for 21 days), the release fluid was exchanged and the gentamicin concentration was measured. The activity of released gentamicin was tested on Staphylococcus aureus.

Results

All combinations showed initial burst-release of active gentamicin, two cements had continuous-release (17 days). The relative release of all cements (36–85%) and granules (30–62%) was higher than previously reported for injectable PMMA-cements (up to 17%) and comparable to other biodegradable carriers. From the cements residual gentamicin could be extracted, whereas the granules released all gentamicin that had adhered to the surface.

Conclusion

The high release achieved shows great promise for clinical application of these biodegradable drug-carriers. Using the appropriate combination, the required release profile (burst or sustained) may be achieved.
Effectiveness of a tailor-made intervention for pregnancy-related pelvic girdle and/or low back pain after delivery: Short-term results of a randomized clinical trial [ISRCTN08477490]
Authors: Bastiaenen Caroline HG , de Bie Rob A , Wolters Pieter MJC , Vlaeyen Johan WS , Leffers Pieter , Stelma Foekje , Bastiaanssen Janneke M , Essed Gerard GM , van den Brandt Piet A
Published: March 2006

Background

For the moment, scientific evaluation of programs on treatment of pregnancy-related pelvic girdle and/or low back pain after delivery is hardly available with only one study with a positive result, suggesting uncertainty about the optimal approach. Investigators draw particular attention to biomedical factors but there is growing evidence that biopsychosocial factors appear to be even more important as a basis of an intervention program.

Methods

We studied the effectiveness of a tailor-made program with respect to biopsychosocial factors (intervention group) in women with pregnancy-related pelvic girdle and/ or low back pain versus usual care based on a pain contingent basis (control group) shortly after delivery in a randomized controlled trial. Women with severe complaints shortly after delivery were selected from a longitudinal prospective cohort study (n = 7526), aimed at pregnancy-related pelvic girdle and/or low back pain in the Netherlands. A concealed block randomization was performed after collecting baseline data. Researchers were blinded to treatment assignment. Outcomes were evaluated within the domains of the biopsychosocial approach. Primary outcome concerned limitations in activities (RDQ). Follow-up measurements were performed 12 weeks after delivery.

Results

Since May 2001 until July 2003, 869 women out of the cohort made a request for treatment by a physiotherapist, 10 days after delivery. Because of a quick recovery in two weeks time, we included only 126 women three weeks after delivery. There was a statistically significant and clinically relevant difference in improvement on the primary outcome (RDQ) between the two groups in favor of the experimental intervention.

Conclusion

The results favored the hypotheses. Women's worries about their condition were major targets in the experimental intervention. The prognosis after delivery, especially in de first weeks, turned out to be favorable.
Efficient in vivoknock-down of estrogen receptor alpha: application of recombinant adenovirus vectors for delivery of short hairpin RNA
Authors: Krom Yvonne D , Fallaux Frits J , Que Ivo , Lowik Clemens , van Dijk Ko Willems
Published: March 2006

Background

Adenovirus (Ad) mediated gene transfer is a well-established tool to transiently express constructs in livers of mice in vivo. In the present study, we determined the specificity and efficiency of Ad vectors expressing short hairpin (sh) RNA constructs to knock-down the estrogen receptor α (ERα).

Results

Two different shRNA constructs derived from the murine ERα coding sequence were designed (shERα). In vitro, transfection of three mouse cell lines with pSUPER-shERα constructs resulted in up to 80% reduction of endogenous ERα activity. A single mismatch in the target sequence eliminated the reduction of ERα activity, demonstrating the specificity of shERα. The subsequently generated Ad.shERα vectors were equally effective in vitro. In vivo, intravenous administration of Ad.shERα resulted in 70% reduced hepatic mouse ERα mRNA levels. Co-injection of Ad.shERα with an Ad vector containing a luciferase (luc) gene driven by an estrogen responsive element (ERE) containing promoter resulted in a significant (90% on day five) down-regulation of hepatic luciferase activity, as determined by non-invasive optical imaging. Down-regulation was sustained up to day seven post-injection.

Conclusion

Ad mediated transfer of shERα expression constructs results in efficient and specific knockdown of endogenous ERα transcription both in vitro and in vivo.
Small-molecule and mutational analysis of allosteric Eg5 inhibition by monastrol
Authors: Maliga Zoltan , Mitchison Timothy J
Published: March 2006

Background

A recent crystal structure of monastrol in a ternary complex with the kinesin Eg5 motor domain highlights a novel, induced-fit drug binding site at atomic resolution. Mutational obliteration of the monastrol binding site results in a monastrol-resistant, but otherwise catalytically active Eg5 motor domain. However, considering the conformational changes at this site, it is unclear what specific interactions stabilize the interaction between monastrol and the Eg5 motor domain.

Results

To study the molecular complementarity of the monastrol-Eg5 interaction, we used a combination of synthetic chemistry and targeted mutations in Eg5 to measure the contribution of specific contacts to inhibition of Eg5 in vitro and in cultured cells. Structure-activity data on chemical derivatives, sequence analysis of Eg5 homologs from different species, and the effect of mutations near the drug binding site were consistent with the crystal structure.

Conclusion

The mechanism of monastrol revealed by our data rationalizes its specificity for Eg5 over other kinesins and highlights a potential mechanism of drug resistance for anti-cancer therapy targeting this site in Eg5.
Echocardiographic assessment of subclinical left ventricular eccentric hypertrophy in adult-onset GHD patients by geometric remodeling: an observational case-control study
Authors: de Gregorio Cesare , Curtò Lorenzo , Recupero Antonino , Grimaldi Patrizia , Almoto Barbara , Venturino Marilena , Cento Domenico , Narbone Maria Carola , Trimarchi Francesco , Coglitore Sebastiano , Cannavò Salvatore
Published: March 2006

Background

Most patients with growth hormone deficiency (GHD) show high body mass index. Overweight subjects, but GHD patients, were demonstrated to have high left ventricular mass index (LVMi) and abnormal LV geometric remodeling. We sought to study these characteristics in a group of GHD patients, in an attempt to establish the BMI-independent role of GHD.

Methods

Fifty-four patients, 28 F and 26 M, aged 45.9 ± 13.1, with adult-onset GHD (pituitary adenomas 48.2%, empty sella 27.8%, pituitary inflammation 5.5%, cranio-pharyngioma 3.7%, not identified pathogenesis 14.8%) were enrolled. To minimize any possible interferences of BMI on the aim of this study, the control group included 20 age- and weight-matched healthy subjects. The LV geometry was identified by the relationship between LVMi (cut-off 125 g/m2) and relative wall thickness (cut-off 0.45) at echocardiography.

Results

There was no significant between-group difference in resting cardiac morphology and function, nor when considering age-related discrepancy. The majority of patients had normal-low LVM/LVMi, but about one fourth of them showed higher values. These findings correlated to relatively high circulating IGF-1 and systolic blood pressure at rest. The main LV geometric pattern was eccentric hypertrophy in 22% of GHD population (26% of with severe GHD) and in 15% of controls (p = NS).

Conclusion

Though the lack of significant differences in resting LV morphology and function, about 25% of GHD patients showed high LVMi (consisting of eccentric hypertrophy), not dissimilarly to overweight controls. This finding, which prognostic role is well known in obese and hypertensive patients, is worthy to be investigated in GHD patients through wider controlled trials.
Can standardized patients replace physicians as OSCE examiners?
Authors: McLaughlin Kevin , Gregor Laura , Jones Allan , Coderre Sylvain
Published: March 2006

Background

To reduce inter-rater variability in evaluations and the demand on physician time, standardized patients (SP) are being used as examiners in OSCEs. There is concern that SP have insufficient training to provide valid evaluation of student competence and/or provide feedback on clinical skills. It is also unknown if SP ratings predict student competence in other areas. The objectives of this study were: to examine student attitudes towards SP examiners; to compare SP and physician evaluations of competence; and to compare predictive validity of these scores, using performance on the multiple choice questions examination (MCQE) as the outcome variable.

Methods

This was a cross-sectional study of third-year medical students undergoing an OSCE during the Internal Medicine clerkship rotation. Fifty-two students rotated through 8 stations (6 physician, 2 SP examiners). Statistical tests used were Pearson's correlation coefficient, two-sample t-test, effect size calculation, and multiple linear regression.

Results

Most students reported that SP stations were less stressful, that SP were as good as physicians in giving feedback, and that SP were sufficiently trained to judge clinical skills. SP scored students higher than physicians (mean 90.4% +/- 8.9 vs. 82.2% +/- 3.7, d = 1.5, p < 0.001) and there was a weak correlation between the SP and physician scores (coefficient 0.4, p = 0.003). Physician scores were predictive of summative MCQE scores (regression coefficient = 0.88 [0.15, 1.61], P = 0.019) but there was no relationship between SP scores and summative MCQE scores (regression coefficient = -0.23, P = 0.133).

Conclusion

These results suggest that SP examiners are acceptable to medical students, SP rate students higher than physicians and, unlike physician scores, SP scores are not related to other measures of competence.
Consumer e-health education in HIV/AIDS: a pilot study of a web-based video workshop
Authors: O'Grady Laura A
Published: March 2006

Background

Members of the HIV/AIDS community are known to use web-based tools to support learning about treatment issues. Initial research indicated components such as message forums or web-based documentation were effectively used by persons with HIV/AIDS. Video has also shown promise as a technology to aid consumer health education. However, no research has been published thus far investigating the impact of web-based environments combining these components in an educational workshop format.

Methods

In this qualitative study HIV/AIDS community members provided feedback on an integrated web-based consumer health education environment. Participants were recruited through organizations that serve the HIV/AIDS community located in Toronto, Canada. Demographics, data on Internet use, including messages exchanged in the study environment were collected. A group interview provided feedback on usability of the study environment, preferences for information formats, use of the message forum, and other sources for learning about treatment information.

Results

In this pilot study analysis of the posted messages did not demonstrate use for learning of the workshop content. Participants did not generally find the environment of value for learning about treatment information. However, participants did share how they were meeting these needs. It was indicated that a combination of resources are being used to find and discuss treatment information, including in-person sources.

Conclusion

More research on the ways in which treatment information needs are being met by HIV/AIDS community members and how technology fits in this process is necessary before investing large amounts of money into web-based interventions. Although this study had a limited number of participants, the findings were unexpected and, therefore, of interest to those who intend to implement online consumer health education initiatives or interventions.
Episodic homelessness and health care utilization in a prospective cohort of HIV-infected persons with alcohol problems
Authors: Kim Theresa W , Kertesz Stefan G , Horton Nicholas J , Tibbetts Nicole , Samet Jeffrey H
Published: March 2006

Background

Because individuals with HIV/AIDS often have complex medical and social needs, the impact of housing status on medical service utilization is difficult to isolate from the impact of conditions that may worsen during periods of homelessness such as depression and substance abuse. We examine whether episodes of homelessness are independently associated with suboptimal medical utilization even when accounting for concurrent addiction severity and depression.

Methods

We used data from a 30-month cohort of patients with HIV/AIDS and alcohol problems. Housing status, utilization (ambulatory visits, emergency department (ED) visits, and hospitalizations) and other features were assessed with standardized research interviews at 6-month intervals. Multivariable longitudinal regression models calculated incidence rate ratios (IRR) comparing utilization rates during 6-month intervals (homeless versus housed). Additional models assessed whether addiction severity and depressive symptoms could account for utilization differences.

Results

Of the 349 subjects, 139 (39%) reported homelessness at least once during the study period; among these subjects, the median number of nights homeless per 6-month interview period was 30. Homelessness was associated with higher ED utilization (IRR = 2.17; 95% CI = 1.72–2.74) and hospitalizations (IRR = 2.30; 1.70–3.12), despite no difference in ambulatory care utilization (IRR = 1.09; 0.89–1.33). These associations were attenuated but remained significant when adjusting for addiction severity and depressive symptoms.

Conclusion

In patients with HIV/AIDS and alcohol problems, efforts to improve housing stability may help to mitigate intensive medical utilization patterns.
Concepts for risk-based surveillance in the field of veterinary medicine and veterinary public health: Review of current approaches
Authors: Stärk Katharina DC , Regula Gertraud , Hernandez Jorge , Knopf Lea , Fuchs Klemens , Morris Roger S , Davies Peter
Published: March 2006

Background

Emerging animal and zoonotic diseases and increasing international trade have resulted in an increased demand for veterinary surveillance systems. However, human and financial resources available to support government veterinary services are becoming more and more limited in many countries world-wide. Intuitively, issues that present higher risks merit higher priority for surveillance resources as investments will yield higher benefit-cost ratios. The rapid rate of acceptance of this core concept of risk-based surveillance has outpaced the development of its theoretical and practical bases.

Discussion

The principal objectives of risk-based veterinary surveillance are to identify surveillance needs to protect the health of livestock and consumers, to set priorities, and to allocate resources effectively and efficiently. An important goal is to achieve a higher benefit-cost ratio with existing or reduced resources. We propose to define risk-based surveillance systems as those that apply risk assessment methods in different steps of traditional surveillance design for early detection and management of diseases or hazards. In risk-based designs, public health, economic and trade consequences of diseases play an important role in selection of diseases or hazards. Furthermore, certain strata of the population of interest have a higher probability to be sampled for detection of diseases or hazards. Evaluation of risk-based surveillance systems shall prove that the efficacy of risk-based systems is equal or higher than traditional systems; however, the efficiency (benefit-cost ratio) shall be higher in risk-based surveillance systems.

Risk-based surveillance considerations are useful to support both strategic and operational decision making. This article highlights applications of risk-based surveillance systems in the veterinary field including food safety. Examples are provided for risk-based hazard selection, risk-based selection of sampling strata as well as sample size calculation based on risk considerations.
Antenna design for microwave hepatic ablation using an axisymmetric electromagnetic model
Authors: Bertram John M , Yang Deshan , Converse Mark C , Webster John G , Mahvi David M
Published: March 2006

Background

An axisymmetric finite element method (FEM) model was employed to demonstrate important techniques used in the design of antennas for hepatic microwave ablation (MWA). To effectively treat deep-seated hepatic tumors, these antennas should produce a highly localized specific absorption rate (SAR) pattern and be efficient radiators at approved generator frequencies.

Methods and results

As an example, a double slot choked antenna for hepatic MWA was designed and implemented using FEMLAB™ 3.0.

Discussion

This paper emphasizes the importance of factors that can affect simulation accuracy, which include boundary conditions, the dielectric properties of liver tissue, and mesh resolution.
Genetic variation in the myeloperoxidase gene and cognitive impairment in Multiple Sclerosis
Authors: Manna I , Valentino P , La Russa A , Condino F , Nisticò R , Liguori M , Clodomiro A , Andreoli V , Pirritano D , Cittadella R , Quattrone A
Published: March 2006

There is evidence that multiple sclerosis (MS) may associated with cognitive impairment in 25 to 40% of cases. The gene encoding myeloperoxidase (MPO) is involved in molecular pathways leading to β-amyloid deposition. We investigated a functional biallelic (G/A) polymorphism in the promoter region (-463) of the MPO gene in 465 patients affected by MS, divided into 204 cognitively normal and 261 impaired. We did not find significant differences in allele or genotype distributions between impaired and preserved MS patients. Our findings suggest that MPO polymorphism is not a risk factor for cognitive impairment in MS.
The use of digit ratios as markers for perinatal androgen action
Authors: McIntyre Matthew H
Published: March 2006

Since the ratio of the second-to-fourth finger length was first proposed as a marker for prenatal androgen action in 1998, over 100 studies have been published that have either further tested the association between the digit ratio and prenatal androgens, or employed digit ratios as a marker to investigate the association between prenatal androgens and a variety of outcomes, including behavior, fertility, and disease risks. Despite the clear demand for an adult marker of prenatal androgen action and increased use of digit ratios as such a marker, its validity remains controversial. This review (1) evaluates current evidence for the relationship between digit ratios and prenatal androgens (using experimentation with animal models, amniotic testosterone, and congenital adrenal hyperplasia case-control studies), (2) describes opportunities for future validation tests, and (3) compares the potential advantages and disadvantages of digit ratio measures with more established methods for studying the effects of prenatal androgens.
The effects of powered ankle-foot orthoses on joint kinematics and muscle activation during walking in individuals with incomplete spinal cord injury
Authors: Sawicki Gregory S , Domingo Antoinette , Ferris Daniel P
Published: March 2006

Background

Powered lower limb orthoses could reduce therapist labor during gait rehabilitation after neurological injury. However, it is not clear how patients respond to powered assistance during stepping. Patients might allow the orthoses to drive the movement pattern and reduce their muscle activation. The goal of this study was to test the effects of robotic assistance in subjects with incomplete spinal cord injury using pneumatically powered ankle-foot orthoses.

Methods

Five individuals with chronic incomplete spinal cord injury (ASIA C-D) participated in the study. Each subject was fitted with bilateral ankle-foot orthoses equipped with artificial pneumatic muscles to power ankle plantar flexion. Subjects walked on a treadmill with partial bodyweight support at four speeds (0.36, 0.54, 0.72 and 0.89 m/s) under three conditions: without wearing orthoses, wearing orthoses unpowered (passively), and wearing orthoses activated under pushbutton control by a physical therapist. Subjects also attempted a fourth condition wearing orthoses activated under pushbutton control by them. We measured joint angles, electromyography, and orthoses torque assistance.

Results

A therapist quickly learned to activate the artificial pneumatic muscles using the pushbuttons with the appropriate amplitude and timing. The powered orthoses provided ~50% of peak ankle torque. Ankle angle at stance push-off increased when subjects walked with powered orthoses versus when they walked with passive-orthoses (ANOVA, p < 0.05). Ankle muscle activation amplitudes were similar for powered and passive-orthoses conditions except for the soleus (~13% lower for powered condition; p < 0.05).

Two of the five subjects were able to control the orthoses themselves using the pushbuttons. The other three subjects found it too difficult to coordinate pushbutton timing. Orthoses assistance and maximum ankle angle at push-off were smaller when the subject controlled the orthoses compared to when the therapist-controlled the orthoses (p < 0.05). Muscle activation amplitudes were similar between the two powered conditions except for tibialis anterior (~31% lower for therapist-controlled; p < 0.05).

Conclusion

Mechanical assistance from powered ankle-foot orthoses improved ankle push-off kinematics without substantially reducing muscle activation during walking in subjects with incomplete spinal cord injury. These results suggest that robotic plantar flexion assistance could be used during gait rehabilitation without promoting patient passivity.
Mutational analysis of the potential catalytic residues of the VV G1L metalloproteinase
Authors: Honeychurch Kady M , Byrd Chelsea M , Hruby Dennis E
Published: March 2006

The vaccinia virus G1L open-reading frame is predicted to be a metalloproteinase based upon the presence of a conserved zinc-binding motif. Western blot analysis demonstrates G1L undergoes proteolytic processing during the course of infection, although the significance of this event is unknown. In order to determine which amino acid residues are important for G1L activity, a plasmid-borne library of G1L constructs containing mutations in and about the active site was created. Transient expression analysis coupled with a trans complementation assay of a conditionally-lethal mutant virus suggest that, of the mutants, only glutamic acid 120 is non-essential for G1L processing to occur.
The C(-1019)G 5-HT1A promoter polymorphism and personality traits: no evidence for significant association in alcoholic patients
Authors: Koller G , Bondy B , Preuss UW , Zill P , Soyka M
Published: March 2006

The 5HT1A receptor is one of at least 14 different receptors for serotonin which has a role in moderating several brain functions and may be involved in the aetiology of several psychiatric disorders. The C(-1019)G 5-HT1A promoter polymorphism was reported to be associated with major depression, depression-related personality traits and suicidal behavior in various samples. The G(-1019) allele carriers are prone to depressive personality traits and suicidal behavior, because serotonergic neurotransmission is reduced.

The aim of this study is to replicate previous findings in a sample of 185 Alcohol-dependent individuals. Personality traits were evaluated using the NEO FFI and TCI. History of suicidal behavior was assessed by a standardized semistructured interview (SSAGA). No significant differences across C(-1019)G 5-HT1A genotype groups were found for TCI temperament and character traits and for NEO FFI personality scales. No association was detected between this genetic variant and history of suicide attempts. These results neither support a role of C(-1019)G 5-HT1A promoter polymorphism in the disposition of personality traits like harm avoidance or neuroticism, nor confirm previous research reporting an involvement of the G allele in suicidal behavior in alcoholics. Significant associations, however, were detected between Babor's Type B with number of suicide attempts in history, high neuroticism and harm avoidance scores in alcoholics.
Multifactorial day hospital intervention to reduce falls in high risk older people in primary care: a multi-centre randomised controlled trial [ISRCTN46584556]
Authors: Masud Tahir , Coupland Carol , Drummond Avril , Gladman John , Kendrick Denise , Sach Tracey , Harwood Rowan , Kumar Pradeep , Morris Rob , Taylor Rachael , Youde Jane , Conroy Simon
Published: March 2006

Falls in older people are a major public health concern in terms of morbidity, mortality and cost. Previous studies suggest that multifactorial interventions can reduce falls, and many geriatric day hospitals are now offering falls intervention programmes. However, no studies have investigated whether these programmes, based in the day hospital are effective, nor whether they can be successfully applied to high-risk older people screened in primary care.

The hypothesis is that a multidisciplinary falls assessment and intervention at Day hospitals can reduce the incidence of falls in older people identified within primary care as being at high risk of falling. This will be tested by a pragmatic parallel-group randomised controlled trial in which the participants, identified as at high risk of falling, will be randomised into either the intervention Day hospital arm or to a control (current practice) arm. Those participants preferring not to enter the full randomised study will be offered the opportunity to complete brief diaries only at monthly intervals. This data will be used to validate the screening questionnaire. Three day hospitals (2 Nottingham, 1 Derby) will provide the interventions, and the University of Nottingham's Departments of Primary Care, the Division of Rehabilitation and Ageing Unit, and the Trent Institute for Health Service Research will provide the methodological and statistical expertise. Four hundred subjects will be randomised into the two arms. The primary outcome measure will be the rate of falls over one year. Secondary outcome measures will include the proportion of people experiencing at least one fall, the proportion of people experiencing recurrent falls (>1), injuries, fear of falling, quality of life, institutionalisation rates, and use of health services. Cost-effectiveness analyses will be performed to inform health commissioners about resource allocation issues. The importance of this trial is that the results may be applicable to any UK day hospital setting.

Sites

General practices across Nottinghamshire and Derbyshire.

Day hospitals:

Derbyshire Royal Infirmary (Southern Derbyshire Acute Hospitals NHS Trust)

Sherwood Day Service (Nottingham City Hospital Trust)

Leengate Day Hospital (Queen's Medical Centre Nottingham University Hospital NHS Trust)
Trunk and hip muscle recruitment patterns during the prone leg extension following a lateral ankle sprain: A prospective case study pre and post injury
Authors: Lehman Gregory J
Published: March 2006

Background and case presentation

The prone leg extension (PLE) is commonly used to identify dysfunction of muscle recruitment patterns. The prone leg extension is theorized to identify proximal muscle disturbances which are a result of distal injury or dysfunction (i.e. an ankle sprain). This case study compares the trunk and hip muscle (bilateral lower erector spine, ipsilateral hamstring and ipsilateral gluteus maximus) timing during a PLE of a 27 year old female runner during a healthy state (pre ankle sprain) and 2 and 8 weeks post ankle sprain.

Results and discussion

The gluteus maximus muscle onsets at 8 weeks post injury appeared to occur earlier compared with 2 weeks post injury. The Right Erector Spinae at 8 weeks post injury was also active earlier compared with the participant's non-injured state. A large degree of variability can be noted within trials on the same day for all muscle groups.

Conclusion

An acute ankle injury did not result in a delay in gluteus maximus muscle activation. The utility of the prone leg extension as a clinical and functional test is questionable due to the normal variability seen during the test and our current inability to determine what is normal and what is dysfunctional.
Variable hydrology and salinity of salt ponds in the British Virgin Islands
Authors: Jarecki Lianna , Walkey Mike
Published: March 2006

Caribbean salt ponds are unique wetlands that have received little scientific attention. They are common features of dry Caribbean coastlines, but they are threatened by rapid coastal development. We compared hydrology and salinity of 17 salt ponds in the British Virgin Islands. Ponds were mostly hypersaline (>50 ppt), and they exhibited dramatic salinity fluctuations in response to rainfall and evaporation. Individual ponds varied in their mean salinities and thus experienced different ranges of salinity. Differences in mean salinity appeared to be linked with hydrological characteristics. Hydrological variation ranged from permanently inundated ponds with direct sea connection to those fully isolated from the sea and retaining water only after rainfall. We characterized groups of ponds by their major hydrological characteristics, particularly their period of inundation and their degree of connection with the sea. The resulting classification appeared to reflect a continuum of increasing isolation from the sea, concurring with published geological records from salt pond sediments elsewhere. The patterns of variability and succession described here are applicable to salt pond management interests throughout the Caribbean.
Coat colour in dogs: identification of the Merlelocus in the Australian shepherd breed
Authors: Hédan Benoit , Corre Sébastien , Hitte Christophe , Dréano Stéphane , Vilboux Thierry , Derrien Thomas , Denis Bernard , Galibert Francis , Galibert Marie-Dominique , André Catherine
Published: March 2006

Background

Coat colours in canines have many natural phenotypic variants. Some of the genes and alleles involved also cause genetic developmental defects, which are also observed in humans and mice. We studied the genetic bases of the merle phenotype in dogs to shed light on the pigmentation mechanisms and to identify genes involved in these complex pathways. The merle phenotype includes a lack of eumelanic pigmentation and developmental defects, hearing impairments and microphthalmia. It is similar to that observed in microphthalmia mouse mutants.

Results

Taking advantage of the dog as a powerful genetic model and using recently available genomic resources, we investigated the segregation of the merle phenotype in a five-generation pedigree, comprising 96 sampled Australian shepherd dogs. Genetic linkage analysis allowed us to identify a locus for the merle phenotype, spanning 5.5 megabases, at the centromeric tip of canine chromosome 10 (CFA10). This locus was supported by a Lod score of 15.65 at a recombination fraction θ = 0. Linkage analysis in three other breeds revealed that the same region is linked to the merle phenotype. This region, which is orthologous to human chromosome 12 (HSA12 q13-q14), belongs to a conserved ordered segment in the human and mouse genome and comprises several genes potentially involved in pigmentation and development.

Conclusion

This study has identified the locus for the merle coat colour in dogs to be at the centromeric end of CFA10. Genetic studies on other breeds segregating the merle phenotype should allow the locus to be defined more accurately with the aim of identifying the gene. This work shows the power of the canine system to search for the genetic bases of mammalian pigmentation and developmental pathways.