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Bronchiolitis obliterans syndrome (BOS), the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group), and 26 samples at or after BOS diagnosis (diagnosis group). An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group). We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1), T-cell leukemia/lymphoma protein 1A (TCL1A), and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p

Background: Forensic psychiatry is a particular subspecialty within psychiatry, dedicated in applying psychiatric knowledge and psychiatric training for particular legal purposes. Given that within the scope of forensic psychiatry, a third party usually intervenes in the patient-doctor relationship, an amendment of the traditional ethical principles seems justified., Results: Thus, 47 articles, two book chapters and the guidelines produced by the World Psychiatric Association, the American Association of Psychiatry and the Law, as well as by the Royal Australian and New Zealand College of psychiatrists, were analyzed. The review revealed that the ethics of correctional forensic psychiatry and those of legal forensic psychiatry do not markedly differ from each other, but they are incongruent in terms of implementation., Methods: In an effort to better understand which ethical principles apply to forensic psychiatry, a chronological review of the literature published from 1950 to 2015 was carried out., Conclusion: The ethics of correctional forensic psychiatry are primarily deontological. The principle of justice translates into the principle of health care equivalence, the principle of beneficence into providing the best possible care to patients, and the principle of respect of autonomy into ensuring confidentiality and informed consent. The ethics of legal forensic psychiatry are rather consequentialist. In this latter setting, the principle of justice is mainly characterized by professionalism, the principle of beneficence by objectivity and impartiality, and the principle of respect of autonomy by informed consent. However, these two distinct fields of forensic psychiatry share in common the principle of non maleficence, defined as the non collaboration of the psychiatrist in any activity leading to inhuman and degrading treatment or to the death penalty.

The growing awareness of sexually-abused children has led to a major shift: previously considered untrustworthy, children are now regarded as competent in providing medico-legal evidence. Professionals undertaking the challenging task of assessing the child's credibility need to rely upon approved evaluation methods. The Criteria-Based Content Analysis is a tool developed to assess the truthfulness of a child's verbal statement. This field-based study explores its validity and its limitations. Three independent experts rated the verbatim statements of 60 real-life alleged victims of sexual abuse. The CBCA scoring and final assessment of credibility were linked to the outcomes: confirmed or unconfirmed allegation of sexual abuse. Inter-rater reliability coefficient was 0.74. The average overall accuracy rate corresponding to confirmed and unconfirmed cases was 75%. Among the confirmed allegations, the accuracy rate reached 90%, whereas the probability of discriminating the true negative cases within the unconfirmed cases was lower than chance level. Of all the 19 criteria, items 6 "Reproduction of conversation" and 12 "Accounts of subjective mental state" were the strongest predictors of genuine accounts. A significant association between age and CBCA scores was noted, the effect of age on CBCA scores was strongest in the unconfirmed cases. Although some may argue that the validity of the CBCA is reasonably acceptable, results from this field study are less convincing. Increasing the diagnostic accuracy of the CBCA by adding new criteria, so as to raise the percentage of correct classifications in the confirmed accounts as well as in the unconfirmed accounts, would represent a major improvement., (Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Background: Despite universal health care coverage, disparities in colorectal cancer (CRC) screening by income in Switzerland have been reported. However, it is not known if these disparities have changed over time. This study examines the association between socioeconomic position and CRC screening in Switzerland between 2007 and 2012., Methods: Data from the 2007 (n = 5,946) and 2012 (n = 7,224) population-based Swiss Health Interview Survey data (SHIS) were used to evaluate the association between monthly household income, education, and employment with CRC screening, defined as endoscopy in the past 10 years or fecal occult blood test (FOBT) in the past 2 years. Multivariable Poisson regression was used to estimate prevalence ratios (PR) and 95% Confidence Intervals (CI) adjusting for demographics, health status, and health utilization., Results: CRC screening increased from 18.9% in 2007 to 22.2% in 2012 (padjusted: = 0.036). During the corresponding time period, endoscopy increased (8.2% vs. 15.0%, padjusted:<0.001) and FOBT decreased (13.0% vs. 9.8%, padjusted:0.002). CRC screening prevalence was greater in the highest income (>$6,000) vs. lowest income (≤$2,000) group in 2007 (24.5% vs. 10.5%, PR:1.37, 95%CI: 0.96-1.96) and in 2012 (28.6% vs. 16.0%, PR:1.45, 95%CI: 1.09-1.92); this disparity did not significantly change over time., Conclusions: While CRC screening prevalence in Switzerland increased from 2007 to 2012, CRC screening coverage remains low and disparities in CRC screening by income persisted over time. These findings highlight the need for increased access to CRC screening as well as enhanced awareness of the benefits of CRC screening in the Swiss population, particularly among low-income residents.

Socio-economic status (SES) is related to increased risk of airway disease in terms of forced expiratory volume in one second (FEV1) and forced vital capacity. No data are available as to what extent SES predicts alveolar function in a general population. In this cross-sectional study, 1,275 subjects aged 18-73 yrs underwent pulmonary testing, including the single-breath carbon monoxide transfer capacity of the lungs (TL,CO). Educational level was used as an index for SES. Mean +/- SD TL,CO % predicted was 97% among those with primary school education, 99% among those with secondary school education and 104% among those with a university degree. In a multiple linear regression analysis, adjusting for age, height, haemoglobin, carboxyhaemoglobin, smoking habits, occupational exposure, FEV1 and body mass index, TL,CO was significantly related to educational level in males but not in females. Occupational exposure was not significant. In this study, socio-economic status was found to be an independent determinant of TL,CO. Even in an affluent country such as Norway, socio-environmental risk factors may differ based on individuals' SES. Such risk factors may, for instance, be higher exposure to airborne pollutants, poorer housing conditions, or lower consumption of fruit and vegetables. Further exploration is called for.

The burdens of chronic obstructive airway diseases among the elderly in Europe, and worldwide, are increasing. Although asthma is common in all ages, the main airway disease affecting the elderly is chronic obstructive pulmonary disease (COPD). The aim of this paper is to review the prevalence and incidence of COPD on the basis of population studies. As the prevalence estimates of asthma are probably well known, only the incidence and remission of asthma will be discussed. The underdiagnosis of obstructive airway diseases is huge. A Dutch programme for early detection of obstructive airway disease among the elderly has, thus, been included in the presentation. A prerequisite for fighting COPD is to acquire data on illnesses and death. COPD has only recently been defined by cut-off points of spirometric outcomes, which is why measures of the prevalence of COPD have been distorted by use of a large number of different diagnostic terms and lung function criteria. The prevalence of clinically-relevant COPD has been estimated in several community studies to 4-6% in adult population samples, with a considerable increase by age, particularly among smokers. The incidence of COPD not only increases heavily with age and smoking, but also occupational exposure to dust, gas and damp. Precise estimates of the incidence of COPD or spirometric airflow limitation are not available. Demographic changes will result in a further substantial increase of chronic obstructive airway disorders, mainly chronic obstructive pulmonary disease, among the elderly. The increasing burden of chronic obstructive pulmonary disease has to come to the awareness of the public, governments, health authorities, and industry.

The aim was to examine the relationship of serum inflammatory markers to the level of single-breath diffusing capacity of carbon monoxide (TL,CO). A stratified sample (n = 1,121) of a Norwegian general population aged 18-73 yrs was examined. The inflammatory markers measured were calprotectin, a prominent protein in the cytosol fraction of neutrophil granulocytes, and alpha1-antitrypsin (alpha1-AT), the major inhibitor of neutrophil elastase in the lower respiratory system. Both markers have increased circulating levels in the course of an acute inflammatory reaction. Subjects with a TL,CO < 80% of predicted value had a higher level of both alpha1-AT (p = 0.003) and calprotectin (p < 0.03) than those with a TL,CO > 100%. In multiple linear regression analyses, alpha1-AT was still significantly associated with TL,CO after adjusting for sex, age, smoking habits, haemoglobin, carboxyhaemoglobin, forced expiratory volume in one second and alveolar volume. In a similar analysis, no significant overall association was found between calprotectin and TL,CO, but in a stratified analysis, calprotectin was significantly related to TL,CO in females. However, no significant sex interaction in the relationship between the inflammatory markers and TL,COo was found. The findings suggest that increased levels of alpha1-antitrypsin and of calprotectin are risk factors for decreased diffusing capacity of carbon monoxide.

Reduced single-breath transfer factors of the lung for carbon monoxide are seen in a number of conditions. The hypothesis of the present study was that self-reported respiratory symptoms differ in their prediction of TL,CO level in a general population in Norway. A cross-sectional survey of a general population sample in Norway, made up of 1,275 subjects aged 18-73 yrs, was conducted in 1987-1988. The attendees (84% response rate) filled in a questionnaire on respiratory symptoms and underwent standardized spirometric and TL,CO measurements and clinical examination. Associations between TL,CO and respiratory symptoms were assessed using multiple regression models. Tests for interaction were used to examine whether these associations varied with sex, age and smoking habits. Data from 1,221 subjects were analysed. Both males and females who reported respiratory symptoms had significantly lower TL,CO after adjusting for age and height. In a multiple linear regression analysis of TL,CO, adjusting for sex, age, height and smoking habits, the symptoms for which statistical significance was attained, were morning cough, chronic cough and breathlessness. However, only the breathlessness score was independently associated with the TL,CO (-0.42 mmol x min(-1) x kPa(-1) per breathlessness score unit) after adjusting for other respiratory symptoms, and the relationship was stronger in males than in females. In this study, the strongest predictor for a decreased single-breath transfer factor of the lung for carbon monoxide was the presence of self-reported breathlessness, regardless of age, smoking habits and height.

The river Meuse, located in western Europe, is contaminated by different pollutants, of both organic and inorganic nature. The predominant sources of Meuse contamination in The Netherlands are agricultural activities and pollution derived from urban areas. Crayfish, water, and sediment samples were collected at four different locations of the river Meuse, in order to cover a large part of the catchment area of this river in The Netherlands. Crayfish may be very useful in biomonitoring studies, since they can integrate body load by pollutants over time in an area-bound manner. In these crayfish, levels of aromatic DNA adducts, heavy metal residues, polychlorinated biphenyls (PCBs), and organochlorine pesticides were determined in hepatopancreatic tissue. Also analyzed were water and sediment samples derived from the same locations, for polycyclic aromatic hydrocarbons (PAHs), heavy metals, and organochlorine compounds. In sediments from the four different sampling sites, no clear differences were observed in PCB levels. Organochlorine pesticide concentrations were highest at location A, the most upstream sampling site, whereas a general decrease was observed following the river Meuse downstream. A similar pattern was observed for the metal compounds. For PAH sediment levels no consistent tendency could be observed. Highest values were detected at site B, followed by, respectively, locations A, D, and C. In water samples, a different pattern was observed. The highest metal concentration was observed at location D, whereas the total organochlorine level was higher at sites B and D, compared to the two other sampling sites. Differences in pollution levels in crayfish between sampling sites were evident. Site D, the most downstream-situated site examined, appeared to be the most polluted site with respect to PCBs, DDT, DDE, and Cu in crayfish. Moreover, DNA adduct levels, which may serve as a dosimeter for the internal dose of aromatic compounds such as PAHs and PCBs, were also significantly higher in hepatopancreatic tissue of crayfish captured at site D, compared to the three other sampling sites. Moreover, significant correlations were observed between DNA adduct levels and the lower chlorinated PCB congeners (PCB 28-PCB 101). By correlating the different pollutants in water and/or sediment with xenobiotic levels in crayfish, no consistency could be observed, indicating that monitoring aquatic species may provide specific information on the presence of surface water pollutants. These results indicate that crayfish can be used as biological indicators of exposure to both organic and inorganic pollution in aquatic systems., (Copyright 1999 Academic Press.)

The test of single-breath diffusing capacity for carbon monoxide (DLCO) has been widely used in population surveys. However, little is known about the effect of meeting or failing to meet the criteria for acceptability of this test. The American Thoracic Society (ATS) recommends a breathholding time of 9 to 11 s, two measurements within +/- 10% or 3 ml CO(STPD)/min/mm Hg of the average DLCO, and an inspiratory vital capacity (IVC) of at least 90% of the largest previously measured forced vital capacity (FVC) as criteria for this test. The objective of the present study was to examine the extent to which these criteria were met in a community study. To do this, a random sample of 3,740 persons, aged 15 to 70 yr, of the general population of the city of Bergen and 11 surrounding municipalities on the southwest coast of Norway were enrolled in a two-phase cross-sectional study. In the second phase, a stratified sample (n = 1,512) of the respondents to the postal questionnaire used for recruitment for the study (n = 3,370) were invited to a clinical and respiratory physiologic examination that included the DLCO test. The attendance rate was 84% (1,275 of 1,512). In the examination, all subjects were able to maintain a breathholding time of 9 to 11 s, and 98% had two DLCO values within +/- 10% or 3 ml CO(STPD)/min/mm Hg of the average DLCO. The criterion of an IVC of at least 90% of FVC in the two tests was met by 68% of the subjects. Younger age was an independent predictor of failure to meet the required criteria. Thus, only two-thirds of the participants fulfilled all of the ATS criteria for the DLCO test, the main reason for failure being an IVC of less than 90% FVC. This should not necessarily lead to the exclusion from further analysis of those failing to meet this criterion.

The present study was undertaken to evaluate the contribution of various individual characteristics and lifestyle factors on sister chromatid exchange (SCE) frequencies in human peripheral blood lymphocytes (PBLs). These also included associations between plasma retinol and alpha-tocopherol and SCE frequencies. The study population consisted of 50 healthy, smoking and nonsmoking, male and female volunteers, ages 22-49. SCE frequencies in PBLs were significantly higher in smokers than in nonsmokers. SCE frequencies correlated with variables of smoking habits and history, with the number of pack-years smoked correlating most strongly (r = 0.501; P < 0.001). Inverse but nonsignificant correlations were observed between plasma retinol and alpha-tocopherol levels and SCE frequencies in PBLs. In addition, with the use of multiple regression analysis, significant associations were found with age and possible occupational exposure after adjustment for smoking habits (r2 = 0.428; P = 0.0001). For males (n = 20), SCE frequencies were found to be associated significantly with the number of cigarettes smoked per day and possible occupational exposure (r2 = 0.485; P < 0.01). SCE frequencies in PBLs of females (n = 30) were associated positively with the number of pack-years smoked and age, and significantly inversely correlated with plasma alpha-tocopherol concentrations (r2 = 0.586; P = 0.0001). After exclusion of possible occupationally exposed persons (n = 8) from the study population and adjustment for the effects of age and smoking behavior, a weak inverse correlation was found between plasma alpha-tocopherol and SCE frequencies (r = -0.286; P = 0.0732).(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of frequencies of 6-thioguanine-resistant (TGr) human peripheral lymphocytes may contribute to quantitative genetic risk assessment in occupationally or environmentally exposed human populations. A simple procedure for the detection of TGr human peripheral blood lymphocytes was developed in our laboratory, using whole blood culturing and 5-bromodeoxyuridine (BrdU) labeling in combination with immunocytochemical staining. Modifications of the procedure designed to reduce the false positive effects of spontaneously cycling lymphocytes (phenocopies), and to optimize duration of BrdU labeling and the culturing period, were evaluated. A standard procedure was developed which applied 24 h cold storage of the diluted heparinized blood (1:10, v:v in RPMI 1640 medium) at 4 degrees C to reduce the effect of spontaneously cycling lymphocytes, and whole blood culturing in RPMI 1640 complete medium with stimulation of T lymphocytes using phytohemagglutinin (PHA), selection of TGr lymphocytes by adding TG to a final concentration of 2 x 10(-4) M and, after 24 h of incubation, labeling of TGr lymphocytes with 2.5 x 10(-5) M BrdU during 16 h. Using this standard procedure, frequencies of TGr cells in 45 healthy individuals (aged 21-64) were observed to range from 0.3 to 229.8 x 10(-6), with a mean variant frequency (VF) (+/- SD) of 136 x 10(-6) (+/- 35.8). After exclusion of the one extremely high value of 229.8 x 10(-6), mean VF was 8.7 x 10(-6) (+/- 14.1). A significant inverse correlation was found between logVF and the labeling index of control cultures (LIc), indicating that cultures with low LIc tend to yield higher VF.(ABSTRACT TRUNCATED AT 250 WORDS)

A murine IgG3 mAb, clone 6-19, derived from non-manipulated autoimmune MRL/MpJ-lpr/lpr mice is a rheumatoid factor specific for IgG2a and is able to generate cryoglobulins via nonspecific IgG3 Fc-Fc interaction. Intraperitoneal passive transfer of ascites containing the 6-19 mAb into BALB/c mice induces, within 18 h, remarkable pathology characterized by skin vasculitis and acute glomerulonephritis associated with cryoglobulinemia. In order to evaluate the possibility of modulating the development of tissue lesions by an anti-Id antibody, we have raised an IgG2b anti-Id mAb specific to the 6-19 mAb. The cryoprecipitation of 6-19 mAb was completely inhibited in the presence of excess amounts of anti-Id mAb in vitro. In vivo, pretreatment of BALB/c mice with anti-6-19 anti-Id mAb inhibited development of skin vasculitis and glomerulonephritis induced by the 6-19 mAb. The cryoglobulin formation was markedly diminished due to enhanced elimination of the 6-19 mAb from the circulation. In contrast, pretreatment with an IgM anti-IgG3 rheumatoid factor mAb neither protected nor aggravated the development of tissue lesions. These results suggest possible implications in the anti-Id treatment of similar vascular diseases in man.