Ultra-high pressure liquid chromatography-mass spectrometry for plant metabolomics: a systematic comparison of high-resolution quadrupole-time-of-flight and single stage Orbitrap mass spectrometers.

The response of Arabidopsis to stress caused by mechanical wounding was chosen as a model to compare the performances of high resolution quadrupole-time-of-flight (Q-TOF) and single stage Orbitrap (Exactive Plus) mass spectrometers in untargeted metabolomics. Both instruments were coupled to ultra-high pressure liquid chromatography (UHPLC) systems set under identical conditions. The experiment was divided in two steps: the first analyses involved sixteen unwounded plants, half of which were spiked with pure standards that are not present in Arabidopsis. The second analyses compared the metabolomes of mechanically wounded plants to unwounded plants. Data from both systems were extracted using the same feature detection software and submitted to unsupervised and supervised multivariate analysis methods. Both mass spectrometers were compared in terms of number and identity of detected features, capacity to discriminate between samples, repeatability and sensitivity. Although analytical variability was lower for the UHPLC-Q-TOF, generally the results for the two detectors were quite similar, both of them proving to be highly efficient at detecting even subtle differences between plant groups. Overall, sensitivity was found to be comparable, although the Exactive Plus Orbitrap provided slightly lower detection limits for specific compounds. Finally, to evaluate the potential of the two mass spectrometers for the identification of unknown markers, mass and spectral accuracies were calculated on selected identified compounds. While both instruments showed excellent mass accuracy (<2.5ppm for all measured compounds), better spectral accuracy was recorded on the Q-TOF. Taken together, our results demonstrate that comparable performances can be obtained at acquisition frequencies compatible with UHPLC on Q-TOF and Exactive Plus MS, which may thus be equivalently used for plant metabolomics.

Could moderate alcohol consumption help prevent the metabolic syndrome and diabetes mellitus ?

Aim and purpose: Moderate alcohol consumption has been associated with lower risk of diabetes mellitus, but few data exist on the metabolic syndrome and on the metabolic impact of heavy drinking. The aim of our study was to investigate the complex relationship between alcohol and the metabolic syndrome and diabetes mellitus in a population-based study in Switzerland with high mean alcohol consumption. Design and methods: In 6188 adults aged 35 to 75, alcohol consumption was categorized as 0, 1-6, 7-13, 14-20, 21-27, 28-34 and >= 35 drinks/week or as nondrinkers, moderate (1-13 drinks), high (14-34 drinks) and very high (>= 35 drinks) alcohol consumption. The metabolic syndrome was defined according to the ATP-III criteria and diabetes mellitus as fasting glycemia >= 7 mmol/l or self-reported medication.We used multivariate analysis adjusted for age, gender, smoking status, physical activity and education level to determine the prevalence of the conditions according to drinking categories. Results: 73% (n = 4502) of the participants consumed alcohol, 16% (n = 993) were high drinkers and 2% (n = 126) very high drinkers. In multivariate analysis, alcohol consumption had a U-shaped relationship with the metabolic syndrome and diabetes mellitus. The prevalence of the metabolic syndrome significantly differed between nondrinkers (24%), moderate (19%), high (20%) and very high drinkers (29%) (P<= 0.005). The prevalence of diabetes mellitus also significantly differed between nondrinkers (6.0%), moderate (3.6%), high (3.8%) and very high drinkers (6.7%) (P<= 0.05). These relationships did not differ according to beverage types. Conclusions: The prevalence of the metabolic syndrome and diabetes mellitus decrease with moderate alcohol consumption and increase with heavy drinking, without differences according to beverage types. Recommending to limit alcohol consumption to 1-2 drinks/day might help prevent these conditions in primary care Metabolic Syndrome and Diabetes Mellitus.

Validation of an adapted falls efficacy scale in older rehabilitation patients.

OBJECTIVE: To determine the psychometric properties of an adapted version of the Falls Efficacy Scale (FES) in older rehabilitation patients. DESIGN: Cross-sectional survey. SETTING: Postacute rehabilitation facility in Switzerland. PARTICIPANTS: Seventy elderly persons aged 65 years and older receiving postacute, inpatient rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: FES questions asked about subject's confidence (range, 0 [none]-10 [full]) in performing 12 activities of daily living (ADLs) without falling. Construct validity was assessed using correlation with measures of physical (basic ADLs [BADLs]), cognitive (Mini-Mental State Examination [MMSE]), affective (15-item Geriatric Depression Scale [GDS]), and mobility (Performance Oriented Mobility Assessment [POMA]) performance. Predictive validity was assessed using the length of rehabilitation stay as the outcome. To determine test-retest reliability, FES administration was repeated in a random subsample (n=20) within 72 hours. RESULTS: FES scores ranged from 10 to 120 (mean, 88.7+/-26.5). Internal consistency was optimal (Cronbach alpha=.90), and item-to-total correlations were all significant, ranging from .56 (toilet use) to .82 (reaching into closets). Test-retest reliability was high (intraclass correlation coefficient, .97; 95% confidence interval, .95-.99; P<.001). Subjects reporting a fall in the previous year had lower FES scores than nonfallers (85.0+/-25.2 vs 94.4+/-27.9, P=.054). The FES correlated with POMA (Spearman rho=.40, P<.001), MMSE (rho=.37, P=.001), BADL (rho=.43, P<.001), and GDS (rho=-.53, P<.001) scores. These relationships remained significant in multivariable analysis for BADLs and GDS, confirming FES construct validity. There was a significant inverse relationship between FES score and the length of rehabilitation stay, independent of sociodemographic, functional, cognitive, and fall status. CONCLUSIONS: This adapted FES is reliable and valid in older patients undergoing postacute rehabilitation. The independent association between poor falls efficacy and increased length of stay has not been previously described and needs further investigations.

Leukemic cluster growth in culture is an independent risk factor for acute myeloid leukemia and short survival in patients with myelodysplastic syndrome

In patients with myelodysplastic syndrome (MDS) precursor cell cultures (colony-forming unit cells, CFU-C) can provide an insight into the growth potential of malignant myeloid cells. In a retrospective single-center study of 73 untreated MDS patients we assessed whether CFU-C growth patterns were of prognostic value in addition to established criteria. Abnormalities were classified as qualitative (i.e. leukemic cluster growth) or quantitative (i.e. strongly reduced/absent growth). Thirty-nine patients (53%) showed leukemic growth, 26 patients (36%) had strongly reduced/absent colony growth, and 12 patients showed both. In a univariate analysis the presence of leukemic growth was associated with strongly reduced survival (at 10 years 4 vs. 34%, p = 0.004), and a high incidence of transformation to AML (76 vs. 32%, p = 0.01). Multivariate analysis identified leukemic growth as a strong and independent predictor of early death (relative risk 2.12, p = 0.03) and transformation to AML (relative risk 2.63, p = 0.04). Quantitative abnormalities had no significant impact on the disease course. CFU- C assays have significant predictive value in addition to established prognostic factors in MDS. Leukemic growth identifies a subpopulation of MDS patients with poor prognosis.

Trends in self-reported prevalence and management of hypertension, dyslipidaemia and diabetes in adults in Switzerland, 1992-2007

Purpose: to assess the trends of self-reported prevalence of cardiovascular risk factors (CV RFs: hypertension, dyslipidaemia, diabetes) and their management for period 1992 to 2007 in the Swiss population. Methods: four National health interview surveys conducted between 1992 and 2007 in representative samples of the Swiss population (63,782 subjects overall). Self-reported CV RFs prevalence, treatment and controllevels were computed after weighting. Weights were calculated by raking ratio such that the marginal distribution of the weighted totals conforms to the marginal distribution of the targeted population. Multivariate analysis adjusted on age, sex, education, nationality and SMI was conducted using logistic regression. Results: prevalence of ail CV RFs increased between 1992 and 2007, see table. Although the self-reported prevalence of treatment among subjects with CV RFs increased, and this was confirmed by multivariate analysis: OR for hypocholesterolaemic treatment relative to 1992: 0.64 [0.52-0.78]; 1.39 [1.18-1.65] and 2.00 [1.69-2.36] for 1997, 2002 and 2007, respectively. Still, in 2007, circa 40% of hypertensive, 60% of dyslipidaemic and 50% of diabetic subjects weren't treated. Conversely, an adequate control of CV RFs was reported by treated subjects, with an increase during the study period. This increase was confirmed by multivariate analysis (not shown). Conclusion: the self-reported prevalence of hypertension, dyslipidaemia and diabetes increased between 1992 and 2007 in the Swiss population. Despite a good control of treated subjects, still a significant percentage of subjects with CV RFs are not treated.

The Strength of Promissory Representation : What Makes MPs Change their Positions ?

The paper analyses the positional congruence between pre-election statements in the Swiss voting assistance application "smartvote" and post-election behaviour in the Swiss lower house between 2003 and 2009. For this purpose, we selected 34 smartvote questions which subsequently came up in parliament. Unlike previous studies which assessed the program-to-policy linkage of governments or party groups the paper examines the question at the level of individual MPs which seems appropriate for political systems which follow the idea of power dispersion. While the average rate of political congruence is at some 85 percent, a multivariate analysis detects the underlying factors which push or curb a candidate's propensity to change his or her mind once elections are over. The results show that positional changes are more likely if (1) MPs are freshmen, (2) individual voting behaviour is invisible to the public, (3) the vote is not about a party's core issue, (4) the MP belongs to a party which is located in the political centre, and (5) if the pre-election statement is in disagreement with the majority position of the legislative party group. The last-mentioned factor is paramount: the farer away a candidate's pre-election profile from his or her party is located, the weaker turns out to be the electoral link of promissory representation.

Risk factors of latent tuberculosis infection among asylum-seekers recently arrived in Switzerland : A pilot study in Vaud county

Background: Asylum seekers may have a higher rate of latenttuberculosis infection (LTBI) than resident populations in Westerncountries. LTBI can be detected by an Interferon Gamma ReleaseAssay (IGRA). Screening asylum seekers at highest risk for LTBI orfuture tuberculosis by IGRA could be considered. The aims of this pilotstudy were to assess the prevalence and the risk factors of LTBI amonga group of asylum seekers recently arrived in Switzerland.Methods: A prospective cross-sectional study was performed amongadult asylum seekers, staying in two migrant centers of the Vaud county,Switzerland, after a first screening for active tuberculosis at the border.The participants were offered IGRA screening using T-SPOT.TB andwere questioned about risk factors associated with LTBI. Migrants with apositive test had a chest radiograph and a medical examination. Thosewith active tuberculosis were excluded and were treated. The migrantswith LTBI received a preventive treatment, if indicated. The risk factorswere analyzed by univariate and multivariate logistical regression.Results: Among 788 migrants recently arrived, 639 were adults, 393agreed to be screened (61.50%) and 98 of them had a positive T-SPOT.TB (24.93%) of which 5 (5.1%) had an active tuberculosis (previouslynot detected at the border), and 2 had already been treated for activetuberculosis. In univariate analysis, the major risk factors associatedwith LTBI were country of origin and travel conditions. Compared withmigrants from Balkanic countries, migrants from Africa had an OR forLTBI of 3.68, migrants from Asia an OR of 4.3 and migrants fromFormer Soviet Union an OR of 4.5. Migrants who crossed severalborders before arriving in Switzerland had an OR of LTBI of 2.49compared with migrants who came directly from the home country.Age, cough and prior exposure to tuberculosis had a non-significantinfluence on the rate of test positivity. In multivariate analysis, thecombination of country of origin, travel conditions, age, cough andexposure to tuberculosis resulted in a score with optimal predictivevalue (Roc = 81%).Conclusions: Asylum seekers recently arrived in Vaud county had ahigh prevalence of LTBI and active tuberculosis. The major risk factorswere country of origin and travel conditions. Selecting for screening byIGRA the asylum seekers with the highest risk factors seems possible.

Decreased local control following radiation therapy alone in early-stage glottic carcinoma with anterior commissure extension.

PURPOSE: To assess the patterns of failure in the treatment of early-stage squamous cell carcinoma of the glottic larynx. PATIENTS AND METHODS: Between 1983-2000, 122 consecutive patients treated for early laryngeal cancer (UICC T1N0 and T2N0) by radical radiation therapy (RT) were retrospectively studied. Male-to-female ratio was 106 : 16, and median age 62 years (35-92 years). There were 68 patients with T1a, 18 with T1b, and 36 with T2 tumors. Diagnosis was made by biopsy in 104 patients, and by laser vaporization or stripping in 18. Treatment planning consisted of three-dimensional (3-D) conformal RT in 49 (40%) patients including nine patients irradiated using arytenoid protection. A median dose of 70 Gy (60-74 Gy) was given (2 Gy/fraction) over a median period of 46 days (21-79 days). Median follow-up period was 85 months. RESULTS: The 5-year overall, cancer-specific, and disease-free survival amounted to 80%, 94%, and 70%, respectively. 5-year local control was 83%. Median time to local recurrence in 19 patients was 13 months (5-58 months). Salvage treatment consisted of surgery in 17 patients (one patient refused salvage and one was inoperable; total laryngectomy in eleven, and partial laryngectomy or cordectomy in six patients). Six patients died because of laryngeal cancer. Univariate analyses revealed that prognostic factors negatively influencing local control were anterior commissure extension, arytenoid protection, and total RT dose < 66 Gy. Among the factors analyzed, multivariate analysis (Cox model) demonstrated that anterior commissure extension, arytenoid protection, and male gender were the worst independent prognostic factors in terms of local control. CONCLUSION: For early-stage laryngeal cancer, outcome after RT is excellent. In case of anterior commissure extension, surgery or higher RT doses are warranted. Because of a high relapse risk, arytenoid protection should not be attempted.

CD4+ T cell count recovery in HIV type 1-infected patients is independent of class of antiretroviral therapy.

BACKGROUND: In recent years, treatment options for human immunodeficiency virus type 1 (HIV-1) infection have changed from nonboosted protease inhibitors (PIs) to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) and boosted PI-based antiretroviral drug regimens, but the impact on immunological recovery remains uncertain. METHODS: During January 1996 through December 2004 [corrected] all patients in the Swiss HIV Cohort were included if they received the first combination antiretroviral therapy (cART) and had known baseline CD4(+) T cell counts and HIV-1 RNA values (n = 3293). For follow-up, we used the Swiss HIV Cohort Study database update of May 2007 [corrected] The mean (+/-SD) duration of follow-up was 26.8 +/- 20.5 months. The follow-up time was limited to the duration of the first cART. CD4(+) T cell recovery was analyzed in 3 different treatment groups: nonboosted PI, NNRTI, or boosted PI. The end point was the absolute increase of CD4(+) T cell count in the 3 treatment groups after the initiation of cART. RESULTS: Two thousand five hundred ninety individuals (78.7%) initiated a nonboosted-PI regimen, 452 (13.7%) initiated an NNRTI regimen, and 251 (7.6%) initiated a boosted-PI regimen. Absolute CD4(+) T cell count increases at 48 months were as follows: in the nonboosted-PI group, from 210 to 520 cells/muL; in the NNRTI group, from 220 to 475 cells/muL; and in the boosted-PI group, from 168 to 511 cells/muL. In a multivariate analysis, the treatment group did not affect the response of CD4(+) T cells; however, increased age, pretreatment with nucleoside reverse-transcriptase inhibitors, serological tests positive for hepatitis C virus, Centers for Disease Control and Prevention stage C infection, lower baseline CD4(+) T cell count, and lower baseline HIV-1 RNA level were risk factors for smaller increases in CD4(+) T cell count. CONCLUSION: CD4(+) T cell recovery was similar in patients receiving nonboosted PI-, NNRTI-, and boosted PI-based cART.

The effect of thrombolysis on short-term improvement depends on initial stroke severity.

A large number of parameters have been identified as predictors of early outcome in patients with acute ischemic stroke. In the present work we analyzed a wide range of demographic, metabolic, physiological, clinical, laboratory and neuroimaging parameters in a large population of consecutive patients with acute ischemic stroke with the aim of identifying independent predictors of the early clinical course. We used prospectively collected data from the Acute Stroke Registry and Analysis of Lausanne. All consecutive patients with ischemic stroke admitted to our stroke unit and/or intensive care unit between 1 January 2003 and 12 December 2008 within 24 h after last-well time were analyzed. Univariate and multivariate analyses were performed to identify significant associations with the National Institute of Health Stroke Scale (NIHSS) score at admission and 24 h later. We also sought any interactions between the identified predictors. Of the 1,730 consecutive patients with acute ischemic stroke who were included in the analysis, 260 (15.0%) were thrombolyzed (mostly intravenously) within the recommended time window. In multivariate analysis, the NIHSS score at 24 h after admission was associated with the NIHSS score at admission (β = 1, p < 0.001), initial glucose level (β = 0.05, p < 0.002) and thrombolytic intervention (β = -2.91, p < 0.001). There was a significant interaction between thrombolysis and the NIHSS score at admission (p < 0.001), indicating that the short-term effect of thrombolysis decreases with increasing initial stroke severity. Thrombolytic treatment, lower initial glucose level and lower initial stroke severity predict a favorable early clinical course. The short-term effect of thrombolysis appears mainly in minor and moderate strokes, and decreases with increasing initial stroke severity.

Liver Transplantation for Neuroendocrine Tumors in Europe-Results and Trends in Patient Selection: A 213-Case European Liver Transplant Registry Study.

OBJECTIVE:: The purpose of this study was to assess outcomes and indications in a large cohort of patients who underwent liver transplantation (LT) for liver metastases (LM) from neuroendocrine tumors (NET) over a 27-year period. BACKGROUND:: LT for NET remains controversial due to the absence of clear selection criteria and the scarcity and heterogeneity of reported cases. METHODS:: This retrospective multicentric study included 213 patients who underwent LT for NET performed in 35 centers in 11 European countries between 1982 and 2009. One hundred seven patients underwent transplantation before 2000 and 106 after 2000. Mean age at the time of LT was 46 years. Half of the patients presented hormone secretion and 55% had hepatomegaly. Before LT, 83% of patients had undergone surgical treatment of the primary tumor and/or LM and 76% had received chemotherapy. The median interval between diagnosis of LM and LT was 25 months (range, 1-149 months). In addition to LT, 24 patients underwent major resection procedures and 30 patients underwent minor resection procedures. RESULTS:: Three-month postoperative mortality was 10%. At 5 years after LT, overall survival (OS) was 52% and disease-free survival was 30%. At 5 years from diagnosis of LM, OS was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to LT, poor tumor differentiation, and hepatomegaly. Since 2000, 5-year OS has increased to 59% in relation with fewer patients presenting poor prognostic factors. Multivariate analysis of the 106 cases treated since 2000 identified the following predictors of poor outcome: hepatomegaly, age more than 45 years, and any amount of resection concurrent with LT. CONCLUSIONS:: LT is an effective treatment of unresectable LM from NET. Patient selection based on the aforementioned predictors can achieve a 5-year OS between 60% and 80%. However, use of overly restrictive criteria may deny LT to some patients who could benefit. Optimal timing for LT in patients with stable versus progressive disease remains unclear.

High expectation in non-evidence-based smoking cessation interventions among smokers--the CoLaus study.

To assess the preferred methods to quit smoking among current smokers. Cross-sectional, population-based study conducted in Lausanne between 2003 and 2006 including 988 current smokers. Preference was assessed by questionnaire. Evidence-based (EB) methods were nicotine replacement, bupropion, physician or group consultations; non-EB-based methods were acupuncture, hypnosis and autogenic training. EB methods were frequently (physician consultation: 48%, 95% confidence interval (45-51); nicotine replacement therapy: 35% (32-38)) or rarely (bupropion and group consultations: 13% (11-15)) preferred by the participants. Non-EB methods were preferred by a third (acupuncture: 33% (30-36)), a quarter (hypnosis: 26% (23-29)) or a seventh (autogenic training: 13% (11-15)) of responders. On multivariate analysis, women preferred both EB and non-EB methods more frequently than men (odds ratio and 95% confidence interval: 1.46 (1.10-1.93) and 2.26 (1.72-2.96) for any EB and non-EB method, respectively). Preference for non-EB methods was higher among highly educated participants, while no such relationship was found for EB methods. Many smokers are unaware of the full variety of methods to quit smoking. Better information regarding these methods is necessary.

IEF pattern classification-derived criteria for the identification of epoetin-delta in urine.

Epoetin-delta (Dynepo Shire Pharmaceuticals, Basing stoke, UK) is a synthetic form of erythropoietin (EPO) whose resemblance with endogenous EPO makes it hard to identify using the classical identification criteria. Urine samples collected from six healthy volunteers treated with epoetin-delta injections and from a control population were immuno-purified and analyzed with the usual IEF method. On the basis of the EPO profiles integration, a linear multivariate model was computed for discriminant analysis. For each sample, a pattern classification algorithm returned a bands distribution and intensity score (bands intensity score) saying how representative this sample is of one of the two classes, positive or negative. Effort profiles were also integrated in the model. The method yielded a good sensitivity versus specificity relation and was used to determine the detection window of the molecule following multiple injections. The bands intensity score, which can be generalized to epoetin-alpha and epoetin-beta, is proposed as an alternative criterion and a supplementary evidence for the identification of EPO abuse.

Prognostic Factors Influencing Progression-Free Survival Determined From a Series of Sporadic Desmoid Tumors: A Wait-and-See Policy According to Tumor Presentation.

PURPOSE Desmoid tumors are mesenchymal fibroblastic/myofibroblastic proliferations with locoregional aggressiveness and high ability to recur after initial treatment. We present the results of the largest series of sporadic desmoid tumors ever published to determine the prognostic factors of these rare tumors. PATIENTS AND METHODS Four hundred twenty-six patients with a desmoid tumor at diagnosis were included, and the following parameters were studied: age, sex, delay between first symptoms and diagnosis, tumor size, tumor site, previous history of surgery or trauma in the area of the primary tumor, surgical margins, and context of abdominal wall desmoids in women of child-bearing age during or shortly after pregnancy. We performed univariate and multivariate analysis for progression-free survival (PFS). Results In univariate analysis, age, tumor size, tumor site, and surgical margins (R2 v R0/R1) had a significant impact on PFS. PFS curves were not significantly different for microscopic assessment of surgical resection quality (R0 v R1). In multivariate analysis, age, tumor size, and tumor site had independent values. Three prognostic groups for PFS were defined on the basis of the number of independent unfavorable prognostic factors (0 or 1, 2, and 3). CONCLUSION This study clearly demonstrates that there are different prognostic subgroups of desmoid tumors that could benefit from different therapeutic strategies, including a wait-and-see policy.

The promise of advanced imaging techniques for the detection of hepatitis C virus antigens in the infected liver.

Injection drug use before and after liver transplantation: a retrospective multicenter analysis on incidence and outcome. Clin Transplant 2009 DOI: 10.1111/j.1399-0012.2009.01121.x. Background and aims: Injecting drug use (IDU) before and after liver transplantation (LT) is poorly described. The aim of this study was to quantify relapse and survival in this population and to describe the causes of mortality after LT. Methods: Past injection drug users were identified from the LT listing protocols from four centers in Switzerland and France. Data on survival and relapse were collected and used for uni- and multivariate analysis. Results: Between 1988 and 2006, we identified 59 patients with a past history of IDU. The mean age at transplantation was 42.4 yr and the majority of patients were men (84.7%). The indication for LT was for the vast majority viral cirrhosis accounting for 91.5% of cases, while alcoholic cirrhosis was 5.1%. There were 16.9% of patients who had a substitution therapy before and 6.8% who continued after LT. Two patients (3.4%) relapsed into IDU after LT and died at 18 and 41 months. The mean follow-up was 51 months. Overall survival was 84%, 66%, and 61% at 1, 5, and 10 yr after transplantation. Conclusions: Documented IDU was rare in liver transplanted patients. Past IDU was not associated with poorer survival after LT, and relapse after LT occurred in 3.4%.