Association of socioeconomic status with inflammatory markers: a two cohort comparison.

OBJECTIVE: To assess the association between socioeconomic status (SES) and inflammatory markers using two different European population samples. METHODS: We used data from the CoLaus (N=6412, Lausanne, Switzerland) and EPIPorto (N=1205, Porto, Portugal) studies. Education and occupational position were used as indicators of socioeconomic status (SES). High-sensitivity C-reactive protein (hs-CRP) was available for both cohorts. Interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were available in CoLaus; leukocyte count and fibrinogen in EPIPorto. RESULTS: We showed that low SES was significantly associated with high inflammation in both studies. We also showed that behavioural factors contributed the most to SES differences in inflammation. In both studies the larger difference between the lowest and the highest SES was observed for hs-CRP. In the Swiss sample, a linear association between education and hs-CRP persisted after adjustment for all mediating factors and confounders considered (p for linear trend <0.001). CONCLUSION: Large social differences exist in inflammatory activity, in part independently from demographic and behavioural factors, chronic conditions and medication use. SES differences in inflammation are also similar in countries with different underlying socioeconomic conditions.

Studies of the association of the A, B and Lewis Blood group antigens with carcinoembryonic antigen (CEA).

Carcinoembryonic antigen (CEA) was purified from primary tumour or from hepatic metastases obtained from ten cases of carcinoma of the colon. In nine cases the blood group antigens A, B, Lea or Leb were detected in CEA preparations by the binding of 125I-labelled CEA by blood group antibodies. The extent of binding appeared to preclude simple contamination of CEA preparations by blood group glycoprotein. In all cases the blood group antigens detected were consistent with the patients' known blood groups. Blood group I and i activities were not detected. It is concluded that the determinants of A, B and Lewis antigens and of CEA share the same glycoprotein carrier molecules.

Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer.

INTRODUCTION: To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years. RESULTS: Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V(120) (urethral volume receiving &gt; or =120% of the prescribed HDR-B dose) was associated with acute (P=.047) and late &gt; or = grade 2 GU toxicities (P=.049). CONCLUSIONS: Late grades 3 and 4GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V(120) on GU toxicity should be validated in further studies.

Survival of zirconia- and metal-supported fixed dental prostheses: a systematic review

Purpose: The aim of this review was to systematically evaluate and compare the frequency of veneer chipping and core fracture of zirconia fixed dental prostheses (FOPS) and porcelain-fused-to-metal (PFM) FDPs and determine possible influencing factors. Materials and Methods: The SCOPUS database and International Association of Dental Research abstracts were searched for clinical studies involving zirconia and PFM FDPs. Furthermore, studies that were integrated into systematic reviews on PFM FDPs were also evaluated. The principle investigators of any clinical studies on zirconia FDPs were contacted to provide additional information. Based on the available information for each FOP, a data file was constructed. Veneer chipping was divided into three grades (grade 1 = polishing, grade 2 = repair, grade 3 = replacement). To assess the frequency of veneer chipping and possible influencing factors, a piecewise exponential model was used to adjust for a study effect. Results: None of the studies on PFM FDPs (reviews and additional searching) sufficiently satisfied the criteria of this review to be included. Thirteen clinical studies on zirconia FDPs and two studies that investigated both zirconia and PFM FDPs were identified. These studies involved 664 zirconia and 134 PFM FDPs at baseline. Follow-up data were available for 595 zirconia and 127 PFM FDPs. The mean observation period was approximately 3 years for both groups. The frequency of core fracture was less than 1% in the zirconia group and 0% in the PFM group. When all studies were included, 142 veneer chippings were recorded for zirconia FDPs (24%) and 43 for PFM FDPs (34%). However, the studies differed extensively with regard to veneer chipping of zirconia: 85% of all chippings occurred in 4 studies, and 43% of all chippings included zirconia FDPs. If only studies that evaluated both types of core materials were included, the frequency of chipping was 54% for the zirconia-supported FDPs and 34% for PFM FDPs. When adjusting the survival rate for the study effect, the difference between zirconia and PFM FDPs was statistically significant for all grades of chippings (P = .001), as well as for chipping grade 3 (P = .02). If all grades of veneer chippings were taken into account, the survival of PFM FDPs was 97%, while the survival rate of the zirconia FDPs was 90% after 3 years for a typical study. For both PFM and zirconia FDPs, the frequency of grades 1 and 2 veneer chippings was considerably higher than grade 3. Veneer chipping was significantly less frequent in pressed materials than in hand-layered materials, both for zirconia and PFM FDPs (P = .04). Conclusions: Since the frequency of veneer chipping was significantly higher in the zirconia FDPs than PFM FDPs, and as refined processing procedures have started to yield better results in the laboratory, new clinical studies with these new procedures must confirm whether the frequency of veneer chipping can be reduced to the level of PFM. Int J Prosthodont 2010;23:493-502

Results of An International Study of Quantitative BCR/ABL Assays Using Defined RNA Samples

Molecular monitoring of BCR/ABL transcripts by real time quantitative reverse transcription PCR (qRT-PCR) is an essential technique for clinical management of patients with BCR/ABL-positive CML and ALL. Though quantitative BCR/ABL assays are performed in hundreds of laboratories worldwide, results among these laboratories cannot be reliably compared due to heterogeneity in test methods, data analysis, reporting, and lack of quantitative standards. Recent efforts towards standardization have been limited in scope. Aliquots of RNA were sent to clinical test centers worldwide in order to evaluate methods and reporting for e1a2, b2a2, and b3a2 transcript levels using their own qRT-PCR assays. Total RNA was isolated from tissue culture cells that expressed each of the different BCR/ABL transcripts. Serial log dilutions were prepared, ranging from 100 to 10-5, in RNA isolated from HL60 cells. Laboratories performed 5 independent qRT-PCR reactions for each sample type at each dilution. In addition, 15 qRT-PCR reactions of the 10-3 b3a2 RNA dilution were run to assess reproducibility within and between laboratories. Participants were asked to run the samples following their standard protocols and to report cycle threshold (Ct), quantitative values for BCR/ABL and housekeeping genes, and ratios of BCR/ABL to housekeeping genes for each sample RNA. Thirty-seven (n=37) participants have submitted qRT-PCR results for analysis (36, 37, and 34 labs generated data for b2a2, b3a2, and e1a2, respectively). The limit of detection for this study was defined as the lowest dilution that a Ct value could be detected for all 5 replicates. For b2a2, 15, 16, 4, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. For b3a2, 20, 13, and 4 labs showed a limit of detection at the 10-5, 10-4, and 10-3 dilutions, respectively. For e1a2, 10, 21, 2, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. Log %BCR/ABL ratio values provided a method for comparing results between the different laboratories for each BCR/ABL dilution series. Linear regression analysis revealed concordance among the majority of participant data over the 10-1 to 10-4 dilutions. The overall slope values showed comparable results among the majority of b2a2 (mean=0.939; median=0.9627; range (0.399 - 1.1872)), b3a2 (mean=0.925; median=0.922; range (0.625 - 1.140)), and e1a2 (mean=0.897; median=0.909; range (0.5174 - 1.138)) laboratory results (Fig. 1-3)). Thirty-four (n=34) out of the 37 laboratories reported Ct values for all 15 replicates and only those with a complete data set were included in the inter-lab calculations. Eleven laboratories either did not report their copy number data or used other reporting units such as nanograms or cell numbers; therefore, only 26 laboratories were included in the overall analysis of copy numbers. The median copy number was 348.4, with a range from 15.6 to 547,000 copies (approximately a 4.5 log difference); the median intra-lab %CV was 19.2% with a range from 4.2% to 82.6%. While our international performance evaluation using serially diluted RNA samples has reinforced the fact that heterogeneity exists among clinical laboratories, it has also demonstrated that performance within a laboratory is overall very consistent. Accordingly, the availability of defined BCR/ABL RNAs may facilitate the validation of all phases of quantitative BCR/ABL analysis and may be extremely useful as a tool for monitoring assay performance. Ongoing analyses of these materials, along with the development of additional control materials, may solidify consensus around their application in routine laboratory testing and possible integration in worldwide efforts to standardize quantitative BCR/ABL testing.

Association of electrocardiogram abnormalities and incident heart failure events.

Unless effective preventive strategies are implemented, aging of the population will result in a significant worsening of the heart failure (HF) epidemic. Few data exist on whether baseline electrocardiographic (ECG) abnormalities can refine risk prediction for HF. METHODS: We examined a prospective cohort of 2,915 participants aged 70 to 79 years without preexisting HF, enrolled between April 1997 and June 1998 in the Health, Aging, and Body Composition (Health ABC) study. Minnesota Code was used to define major and minor ECG abnormalities at baseline and at year 4 follow-up. Using Cox models, we assessed (1) the association between ECG abnormalities and incident HF and (2) the incremental value of adding ECG to the Health ABC HF Risk Score using the net reclassification index. RESULTS: At baseline, 380 participants (13.0%) had minor, and 620 (21.3%) had major ECG abnormalities. During a median follow-up of 11.4 years, 485 participants (16.6%) developed incident HF. After adjusting for the Health ABC HF Risk Score variables, the hazard ratio (HR) was 1.27 (95% CI 0.96-1.68) for minor and 1.99 (95% CI 1.61-2.44) for major ECG abnormalities. At year 4, 263 participants developed new and 549 had persistent abnormalities; both were associated with increased subsequent HF risk (HR 1.94, 95% CI 1.38-2.72 for new and HR 2.35, 95% CI 1.82-3.02 for persistent ECG abnormalities). Baseline ECG correctly reclassified 10.5% of patients with HF events, 0.8% of those without HF events, and 1.4% of the overall population. The net reclassification index across the Health ABC HF risk categories was 0.11 (95% CI 0.03-0.19). CONCLUSIONS: Among older adults, baseline and new ECG abnormalities are independently associated with increased risk of HF. The contribution of ECG screening for targeted prevention of HF should be evaluated in clinical trials.

Meta-analysis and imputation refines the association of 15q25 with smoking quantity.

Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

Long synthetic peptides as biologically active proteins: the example of the chemokines.

Chemokines constitute an expanding protein family of over 40 members which exhibit a wide variety of biological activities and are involved in many normal physiological processes, such as cellular migration, differentiation and activation, but also in pathological situations, such as inflammation and metastasis. Over the last few years, we have developed methods to manufacture long synthetic peptides of up to 130 residues, and to achieve the formation of native-like cysteine pairings. This ability prompted us to undertake the total chemical synthesis of chemokines. So far, we have successfully produced over 30 chemokine species, which exhibit biological activities similar to, or greater than, those reported by others. Chemical synthesis offers a clear advantage over recombinant technologies for the introduction of fluorochromes and haptens at molecularly defined positions. In addition, approval of chemically synthesized products for use in humans is straightforward compared with material produced by biological methods.

International comparison of Russian food processing industry -Finnish perspective

Työn päätavoitteena on kartoittaa Venäjän elintarviketeollisuutta ulkomaisen investoijan näkökulmasta. Tutkimus arvioi liiketoimintamahdollisuuksia ja kilpailutilannetta Venäjän elintarviketeollisuudessa ja auttaa ulkomaisia yrityksiä toteuttamaan liiketoimintastrategioitaan Venäjällä. Venäjän ja muiden siirtymätalousmaiden markkinatilannevertailujen lisäksi Venäjän alueita verrataan keskenään. Myös mahdollisen WTO jäsenyyden vaikutuksia arvioidaan. Kommunismin perintö vaikuttaa edelleen Venäjän elintarviketeollisuuteen ja maatalouteen. Maatalouden tuottavuus on kaukana länsimaisesta tasosta ja maatiloilta puuttuu rahoitusta. Etenkin maidon- ja lihanjalostajat kärsivät raaka-ainepulasta. Venäjän kriisi vuonna 1998 vahvisti paikallista teollisuustuotantoa mutta aiheutti ongelmia ulkomaisille investoijille ja yrityksille, jotka vievät tuotteitaan Venäjälle. Edut, joita mahdollinen maailmankauppajärjestö WTO:n jäsenyys tuo, ovat merkittävämpiä Venäjälle kuin sen kauppakumppaneille. Venäjän alueet eivät ole yhtäläisesti kehittyneitä ja kuluttajien ostovoima vaihtelee paljon. Itsestään selvin ja houkuttelevin vaihtoehto menestyvien elintarvikeyritysten laajentumiselle löytyy alueilta, joilla ostovoima on suurin. Tähän asti kansainväliset elintarvikeyritykset ovat olleet enemmän kiinnostuneita Itä- ja Keski-Euroopan maista. Käytettävissä olevat tulot ovat Itä- ja Keski-Euroopan maissa suurempia kuin Venäjällä, joten tuottajat pystyvät myymään myös kalliimpia tuotteita. Työvoimakustannukset Venäjällä tulevat olemaan suotuisia vielä muutaman vuosikymmenen ja markkinoiden koko on merkittävä. Siksi kansainvälisillä elintarvikeyrityksillä riittää kiinnostusta tulevaisuudessa investoida myös Venäjälle.

Association of MMP-2 polymorphisms with severe and very severe COPD: a case control study of MMPs-1, 9 and 12 in a European population.

BACKGROUND: Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis of the pathogenesis of COPD. These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease--antiprotease imbalance theory for the cause of COPD. Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies. METHODS: To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations. We used logistic regression to adjust for age, gender, centre and smoking history. RESULTS: Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV. CONCLUSIONS: Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94). The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129). This implicates haplotypes of MMP-12 as modifiers of disease severity.

Association of socioeconomic status with sleep disturbances in the Swiss population-based CoLaus study.

OBJECTIVE: To examine the association of socioeconomic status (SES) with subjective and objective sleep disturbances and the role of socio-demographic, behavioural and psychological factors in explaining this association. METHODS: Analyses are based on 3391 participants (53% female, aged 40-81 years) of the follow-up of the CoLaus study (2009-2012), a population-based sample of the city of Lausanne, Switzerland. All participants completed a sleep questionnaire and a sub-sample (N = 1569) underwent polysomnography. RESULTS: Compared with men with a high SES, men with a low SES were more likely to suffer from poor sleep quality [prevalence ratio (PR) for occupational position = 1.68, 95% Confidence Interval (CI): 1.30-2.17], and to have long sleep latency (PR = 4.90, 95%CI: 2.14-11.17), insomnia (PR = 1.47, 95% CI: 1.12-1.93) and short sleep duration (PR = 3.03, 95% CI: 1.78-5.18). The same pattern was observed among women (PR = 1.29 for sleep quality, 2.34 for sleep latency, 2.01 for daytime sleepiness, 3.16 for sleep duration, 95%CIs ranging from 1.00 to 7.51). Use of sleep medications was not patterned by SES. SES differences in sleep disturbances were only marginally attenuated by adjustment for other socio-demographic, behavioural and psychological factors. Results from polysomnography confirmed poorer sleep patterns among participants with low SES (p <0.05 for sleep efficiency/stage shifts), but no SES differences were found for sleep duration. CONCLUSIONS: In this population-based sample, low SES was strongly associated with sleep disturbances, independently of socio-demographic, behavioural, and psychological factors. Further research should establish the extent to which social differences in sleep contribute to socioeconomic differences in health outcomes.

Adjuvant cisplatin-based combined chemotherapy for lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC): a retrospective international study of >1500 patients.

OBJECTIVE: To compare outcomes of patients with lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) treated with or without cisplatin-based combined adjuvant chemotherapy (AC) after radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analysed 1523 patients with LN-positive UCB, who underwent RC with bilateral pelvic LN dissection. All patients had no evidence of disease after RC. AC was administered within 3 months. Competing-risks models were applied to compare UCB-related mortality. RESULTS: Of the 1523 patients, 874 (57.4%) received AC. The cumulative 1-, 2- and 5-year UCB-related mortality rates for all patients were 16%, 36% and 56%, respectively. Administration of AC was associated with an 18% relative reduction in the risk of UCB-related death (subhazard ratio 0.82, P = 0.005). The absolute reduction in mortality was 3.5% at 5 years. The positive effect of AC was detectable in patients aged ≤70 years, in women, in pT3-4 disease, and in those with a higher LN density and lymphovascular invasion. This study is limited by its retrospective and non-randomised design, selection bias, the absence of central pathological review and lack in standardisation of LN dissection and cisplatin-based protocols. CONCLUSION: AC seems to reduce UCB-related mortality in patients with LN-positive UCB after RC. Younger patients, women and those with high-risk features such as pT3-4 disease, a higher LN density and lymphovascular invasion appear to benefit most. Appropriately powered prospective randomised trials are necessary to confirm these findings.

The international epidemiology of child sexual abuse: a continuation of Finkelhor

Objective: The purpose of this paper was to compare the prevalence rates of child sexual abuse reported by [Finkelhor, D. (1994). The international epidemiology of child sexual abuse. Child Abuse & Neglect, 18 (5), 409-417] with those found in recent publications in order to confirm the widespread prevalence of child sexual abuse. Methods: Relevant articles about prevalence of child sexual abuse were identified through searches of computerized databases and a handsearch of Child Abuse & Neglect and the Journal of Child Sexual Abuse. Results: Thirty-eight independent articles were identified, corresponding to 39 prevalence studies; these articles report the prevalence of childhood sexual abuse in 21 different countries, ranging from 0 to 53% for women and 0 to 60% for men. Conclusions: Comparison of the present study with that of [Finkelhor, D. (1994). The international epidemiology of child sexual abuse. Child Abuse & Neglect, 18 (5), 409-417] shows a similarity between prevalence distributions; there appears to be a general pattern that remains more or less constant over the years, especially in women. Practice implications: Twelve years after the first revision study about the international prevalence of child sexual abuse, there is still a need for new data about this topic. The present study shows child sexual abuse is still a widespread problem in the society. In this research, carried out on 38 independent studies, there is new data for 21 countries over the world, being especially relevant the results obtained from other countries different from those pertaining toNorth America or Europe. It is important to point out the high prevalence found in most of the countries, so this information could be a new warning to make society and governments aware of this problem and undertake actions to prevent sexual abuse in childhood.

The international epidemiology of child sexual abuse: a continuation of Finkelhor

Objective: The purpose of this paper was to compare the prevalence rates of child sexual abuse reported by [Finkelhor, D. (1994). The international epidemiology of child sexual abuse. Child Abuse & Neglect, 18 (5), 409-417] with those found in recent publications in order to confirm the widespread prevalence of child sexual abuse. Methods: Relevant articles about prevalence of child sexual abuse were identified through searches of computerized databases and a handsearch of Child Abuse & Neglect and the Journal of Child Sexual Abuse. Results: Thirty-eight independent articles were identified, corresponding to 39 prevalence studies; these articles report the prevalence of childhood sexual abuse in 21 different countries, ranging from 0 to 53% for women and 0 to 60% for men. Conclusions: Comparison of the present study with that of [Finkelhor, D. (1994). The international epidemiology of child sexual abuse. Child Abuse & Neglect, 18 (5), 409-417] shows a similarity between prevalence distributions; there appears to be a general pattern that remains more or less constant over the years, especially in women. Practice implications: Twelve years after the first revision study about the international prevalence of child sexual abuse, there is still a need for new data about this topic. The present study shows child sexual abuse is still a widespread problem in the society. In this research, carried out on 38 independent studies, there is new data for 21 countries over the world, being especially relevant the results obtained from other countries different from those pertaining toNorth America or Europe. It is important to point out the high prevalence found in most of the countries, so this information could be a new warning to make society and governments aware of this problem and undertake actions to prevent sexual abuse in childhood.