More is not always better-comparison of three instruments measuring volume of drinking in a sample of young men and their association with consequences

OBJECTIVE: In general population survey instruments that measure volume of drinking, additional questions and shorter reference periods yield higher volumes. Comparison studies have focused on volume but not on associations between volume and consequences. METHOD: From a cohort study on substance use risk factors (Cohort Study on Substance Use Risk Factors [C-SURF]), baseline data were analyzed for 5,074 young (approximately 20-year-old) men who were drinkers in the past 12 months. Volume of drinking was measured by a generic quantity-frequency (QF) instrument, an extended QF (separately for weekends and weekdays) instrument with 12-months recall, and a retrospective past-week diary. Associations of consequences with and without attribution of alcohol as a cause, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for dependence, and DSM-5 alcohol use disorder in the past 12 months were analyzed. RESULTS: The generic QF measure resulted in lower volume compared with either the extended QF measure (more questions) or the retrospective diary (the most questions and the shortest recall period). For outcomes, however, the extended QF assessment performed the best and the diary the worst. CONCLUSIONS: Higher volume yields are not always better regarding associations with outcomes. The extended QF instrument better captures the variability of drinking. The retrospective diary performs poorly for associations because of the mismatch with the recall period for past-12-months consequences and the potential for misclassification of past-week abstainers and heavy drinkers because of an uncommon past week. Diaries are not recommended for research investigating individual associations between exposure and outcomes in young populations if consequences are measured with a sufficiently long interval to capture rare consequences. (J. Stud. Alcohol Drugs, 75, 880-888, 2014).

Cardiac rotation and relaxation after anterolateral myocardial infarction.

BACKGROUND: Both systolic and diastolic dysfunction have been observed in patients with anterolateral myocardial infarction. Diastolic dysfunction is related to disturbances in relaxation and diastolic filling. OBJECTIVE: To analyse cardiac rotation, regional shortening and diastolic relaxation in patients with anterolateral infarction. METHODS: Cardiac rotation and relaxation in controls and patients with chronic anterolateral infarction were assessed by myocardial tagging. Myocardial tagging is based on magnetic resonance imaging and allows us to label specific myocardial regions for imaging cardiac motion (rotation, translation and radial displacement). A rectangular grid was placed on the myocardium (basal, equatorial and apical short-axis plane) of each of 18 patients with chronic anterolateral infarction and 13 controls. Cardiac rotation, change in area and shortening of circumference were determined in each case. RESULTS: The left ventricle in controls performs a systolic wringing motion with a clockwise rotation at the base and a counterclockwise rotation at the apex when viewed from the apex. During relaxation a rotational motion in the opposite direction (namely untwisting) can be observed. In patients with anterolateral infarction, there is less systolic rotation at the apex and diastolic untwisting is delayed and prolonged in comparison with controls. In the presence of a left ventricular aneurysm (n = 4) apical rotation is completely lost. There is less shortening of circumference in infarcted and remote regions. CONCLUSIONS: The wringing motion of the myocardium might be an important mechanism involved in maintaining normal cardiac function with minimal expenditure of energy. This mechanism no longer operates in patients with left ventricular aneurysms and operates significantly less than normal in those with anterolateral hypokinaesia. Diastolic untwisting is significantly delayed and prolonged in patients with anterolateral infarction, which could explain the occurrence of diastolic dysfunction in these patients.

What is the most relevant standard of success in assisted reproduction?: The cumulated singleton/twin delivery rates per oocyte pick-up: the CUSIDERA and CUTWIDERA.

National and international registries are essential tools for establishing new standards and comparing success rates, but they do not take into account the total pregnancy/delivery rate per oocyte recovery. In Switzerland and Germany, because of legal constraints, a maximum of three two-pronuclear zygotes are allocated for transfer whereas all the supernumerary pronuclear zygotes are immediately cryopreserved, preventing selection of the transferred embryos. We report on a 10 years' experience (1993-2002) of our centre which performs transfers of unselected embryos and cryopreservation at the two-pronuclear zygote stage. As approximately 30% of all deliveries are from cryo cycles, it is essential to take into account the contribution of the cryo transfers, and we propose therefore to evaluate, as a measure of IVF performance, the cumulated delivery rate per oocyte pick-up. This delivery rate is broken down further into the cumulated singleton delivery rate (CUSIDERA) and the cumulated twin delivery rate (CUTWIDERA). The sum (S) of these two rates is a measure of efficacy while the ratio CUTWIDERA/S as a percentage is a measure of safety of IVF treatments. Using these new indexes, the average 10 year efficacy and safety of our IVF programme were 26 and 19%, respectively. Both CUSIDERA and CUTWIDERA can be calculated easily in any clinical situation and yield useful parameters for patient counselling and internal/external benchmarking purposes.

Fungal co-culture as a new source of antifungal metabolites

Background: Over the last two decades, mortality from coronary heart disease (CHD) and cerebrovascular disease (CVD) declined by about 30% in the European Union (EU). Design: We analyzed trends in CHD (X ICD codes: I20-I25) and CVD (X ICD codes: I60-I69) mortality in young adults (age 35-44 years) in the EU as a whole and in 12 selected European countries, over the period 1980-2007. Methods: Data were derived from the World Health Organization mortality database. With joinpoint regression analysis, we identified significant changes in trends and estimated average annual percent changes (AAPC). Results: CHD mortality rates at ages 35-44 years have decreased in both sexes since the 1980s for most countries, except for Russia (130/100,000 men and 24/100,000 women, in 2005-7). The lowest rates (around 9/100,000 men, 2/100,000 women) were in France, Italy and Sweden. In men, the steepest declines in mortality were in the Czech Republic (AAPC = -6.1%), the Netherlands (-5.2%), Poland (-4.5%), and England and Wales (-4.5%). Patterns were similar in women, though with appreciably lower rates. The AAPC in the EU was -3.3% for men (rate = 16.6/100,000 in 2005-7) and -2.1% for women (rate = 3.5/100,000). For CVD, Russian rates in 2005-7 were 40/100,000 men and 16/100,000 women, 5 to 10-fold higher than in most western European countries. The steepest declines were in the Czech Republic and Italy for men, in Sweden and the Czech Republic for women. The AAPC in the EU was -2.5% in both sexes, with steeper declines after the mid-late 1990s (rates = 6.4/100,000 men and 4.3/100,000 women in 2005-7). Conclusions: CHD and CVD mortality steadily declined in Europe, except in Russia, whose rates were 10 to 15-fold higher than those of France, Italy or Sweden. Hungary and Poland, and also Scotland, where CHD trends were less favourable than in other western European countries, also emerge as priorities for preventive interventions.

Comparison of three commercially available radio frequency coils for human brain imaging at 3 Tesla.

OBJECTIVE: To evaluate a transverse electromagnetic (TEM), a circularly polarized (CP) (birdcage), and a 12-channel phased array head coil at the clinical field strength of B0 = 3T in terms of signal-to-noise ratio (SNR), signal homogeneity, and maps of the effective flip angle alpha. MATERIALS AND METHODS: SNR measurements were performed on low flip angle gradient echo images. In addition, flip angle maps were generated for alpha(nominal) = 30 degrees using the double angle method. These evaluation steps were performed on phantom and human brain data acquired with each coil. Moreover, the signal intensity variation was computed for phantom data using five different regions of interest. RESULTS: In terms of SNR, the TEM coil performs slightly better than the CP coil, but is second to the smaller 12-channel coil for human data. As expected, both the TEM and the CP coils show superior image intensity homogeneity than the 12-channel coil, and achieve larger mean effective flip angles than the combination of body and 12-channel coil with reduced radio frequency power deposition. CONCLUSION: At 3T the benefits of TEM coil design over conventional lumped element(s) coil design start to emerge, though the phased array coil retains an advantage with respect to SNR performance.

Can oxidative damage be treated nutritionally?

BACKGROUND & AIMS: Nutrition and dietary patterns have been shown to have direct impact on health of the population and of selected patient groups. The beneficial effects have been attributed to the reduction of oxidative damage caused by the normal or excessive free radical production. The papers aims at collecting evidence of successful supplementation strategies. METHODS: Review of the literature reporting on antioxidant supplementation trials in the general population and critically ill patients. RESULTS: Antioxidant vitamin and trace element intakes have been shown to be particularly important in the prevention of cancer, cardiovascular diseases, age related ocular diseases and in aging. In animal models, targeted interventions have been associated with reduction of tissue destruction is brain and myocardium ischemia-reperfusion models. In the critically ill antioxidant supplements have resulted in reduction of organ failure and of infectious complications. CONCLUSIONS: Antioxidant micronutrients have beneficial effects in defined models and pathologies, in the general population and in critical illness: ongoing research encourages this supportive therapeutic approach. Further research is required to determined the optimal micronutrient combinations and the doses required according to timing of intervention.

Predicting current and future biological invasions: both native and invaded ranges matter.

The classical approach to predicting the geographical extent of species invasions consists of training models in the native range and projecting them in distinct, potentially invasible areas. However, recent studies have demonstrated that this approach could be hampered by a change of the realized climatic niche, allowing invasive species to spread into habitats in the invaded ranges that are climatically distinct from those occupied in the native range. We propose an alternative approach that involves fitting models with pooled data from all ranges. We show that this pooled approach improves prediction of the extent of invasion of spotted knapweed (Centaurea maculosa) in North America on models based solely on the European native range. Furthermore, it performs equally well on models based on the invaded range, while ensuring the inclusion of areas with similar climate to the European niche, where the species is likely to spread further. We then compare projections from these models for 2080 under a severe climate warming scenario. Projections from the pooled models show fewer areas of intermediate climatic suitability than projections from the native or invaded range models, suggesting a better consensus among modelling techniques and reduced uncertainty.

Development, optimization, and validation of novel anti-TEM1/CD248 affinity agent for optical imaging in cancer.

Tumor Endothelial Marker-1 (TEM1/CD248) is a tumor vascular marker with high therapeutic and diagnostic potentials. Immuno-imaging with TEM1-specific antibodies can help to detect cancerous lesions, monitor tumor responses, and select patients that are most likely to benefit from TEM1-targeted therapies. In particular, near infrared(NIR) optical imaging with biomarker-specific antibodies can provide real-time, tomographic information without exposing the subjects to radioactivity. To maximize the theranostic potential of TEM1, we developed a panel of all human, multivalent Fc-fusion proteins based on a previously identified single chain antibody (scFv78) that recognizes both human and mouse TEM1. By characterizing avidity, stability, and pharmacokinectics, we identified one fusion protein, 78Fc, with desirable characteristics for immuno-imaging applications. The biodistribution of radiolabeled 78Fc showed that this antibody had minimal binding to normal organs, which have low expression of TEM1. Next, we developed a 78Fc-based tracer and tested its performance in different TEM1-expressing mouse models. The NIR imaging and tomography results suggest that the 78Fc-NIR tracer performs well in distinguishing mouse- or human-TEM1 expressing tumor grafts from normal organs and control grafts in vivo. From these results we conclude that further development and optimization of 78Fc as a TEM1-targeted imaging agent for use in clinical settings is warranted.

Source wavelet estimation for waveform inversion of crosshole georadar data

AbstractFor a wide range of environmental, hydrological, and engineering applications there is a fast growing need for high-resolution imaging. In this context, waveform tomographic imaging of crosshole georadar data is a powerful method able to provide images of pertinent electrical properties in near-surface environments with unprecedented spatial resolution. In contrast, conventional ray-based tomographic methods, which consider only a very limited part of the recorded signal (first-arrival traveltimes and maximum first-cycle amplitudes), suffer from inherent limitations in resolution and may prove to be inadequate in complex environments. For a typical crosshole georadar survey the potential improvement in resolution when using waveform-based approaches instead of ray-based approaches is in the range of one order-of- magnitude. Moreover, the spatial resolution of waveform-based inversions is comparable to that of common logging methods. While in exploration seismology waveform tomographic imaging has become well established over the past two decades, it is comparably still underdeveloped in the georadar domain despite corresponding needs. Recently, different groups have presented finite-difference time-domain waveform inversion schemes for crosshole georadar data, which are adaptations and extensions of Tarantola's seminal nonlinear generalized least-squares approach developed for the seismic case. First applications of these new crosshole georadar waveform inversion schemes on synthetic and field data have shown promising results. However, there is little known about the limits and performance of such schemes in complex environments. To this end, the general motivation of my thesis is the evaluation of the robustness and limitations of waveform inversion algorithms for crosshole georadar data in order to apply such schemes to a wide range of real world problems.One crucial issue to making applicable and effective any waveform scheme to real-world crosshole georadar problems is the accurate estimation of the source wavelet, which is unknown in reality. Waveform inversion schemes for crosshole georadar data require forward simulations of the wavefield in order to iteratively solve the inverse problem. Therefore, accurate knowledge of the source wavelet is critically important for successful application of such schemes. Relatively small differences in the estimated source wavelet shape can lead to large differences in the resulting tomograms. In the first part of my thesis, I explore the viability and robustness of a relatively simple iterative deconvolution technique that incorporates the estimation of the source wavelet into the waveform inversion procedure rather than adding additional model parameters into the inversion problem. Extensive tests indicate that this source wavelet estimation technique is simple yet effective, and is able to provide remarkably accurate and robust estimates of the source wavelet in the presence of strong heterogeneity in both the dielectric permittivity and electrical conductivity as well as significant ambient noise in the recorded data. Furthermore, our tests also indicate that the approach is insensitive to the phase characteristics of the starting wavelet, which is not the case when directly incorporating the wavelet estimation into the inverse problem.Another critical issue with crosshole georadar waveform inversion schemes which clearly needs to be investigated is the consequence of the common assumption of frequency- independent electromagnetic constitutive parameters. This is crucial since in reality, these parameters are known to be frequency-dependent and complex and thus recorded georadar data may show significant dispersive behaviour. In particular, in the presence of water, there is a wide body of evidence showing that the dielectric permittivity can be significantly frequency dependent over the GPR frequency range, due to a variety of relaxation processes. The second part of my thesis is therefore dedicated to the evaluation of the reconstruction limits of a non-dispersive crosshole georadar waveform inversion scheme in the presence of varying degrees of dielectric dispersion. I show that the inversion algorithm, combined with the iterative deconvolution-based source wavelet estimation procedure that is partially able to account for the frequency-dependent effects through an "effective" wavelet, performs remarkably well in weakly to moderately dispersive environments and has the ability to provide adequate tomographic reconstructions.

High incidence of childhood hemolytic uremic syndrome in Switzerland is associated with indicators of livestock farming intensity

Background: Hemolytic-uremic syndrome (HUS) is a multisystem disorder associated with significant morbidity and mortality. Typically, HUS is preceded by an episode of (bloody) diarrhea mostly due to Shiga-toxin (Stx) producing Escherichia coli (STEC). The main reservoir for STEC is the intestine of healthy ruminants, mostly cattle, and recent studies have revealed an association between indicators of livestock density and human STEC infection or HUS, respectively. Nationwide data on HUS in Switzerland have been established through the Swiss Pediatric Surveillance Unit (SPSU) [Schifferli et al. Eur J Pediatr. 2010; 169:591-8]. Aims: Analysis of age-specific incidence rate of childhood HUS and possible association of Shiga-toxin associated HUS (Stx-HUS) with indicators of livestock farming intensity. Methods: Epidemiological and ecological analysis based on the SPSU data (1997-2003) and the database of the Swiss Federal Statistical Office (data on population and agriculture). Results: One hundred-fourteen cases were registered, 88% were ≤5 years old. The overall annual incidence rate was 1.42 (0.60-1.91) and 4.23 (1.76-6.19) per 100000 children ≤5 and ≤16 years, respectively (P = 0.005). Stx-HUS was more frequent compared to cases not associated with STEC (P = 0.002). The incidence rate for Stx-HUS was 3.85 (1.76-5.65) in children ≤5, compared to 0.27 (0.00-0.54) per 100'000 children 5-16 years (P = 0.002), respectively. The incidence rate of cases not associated with STEC infection did not significantly vary with age (P = 0.107). Compared to data from Scotland, Canada, Ireland, Germany, England, Australia, Italy, and Austria the annual incidence rate of HUS in young children is highest in Switzerland. Ecological analysis revealed strong association between the incidence rate of Stx-HUS and indicators of rural occupation (agricultural labourer / population, P = 0.030), farming intensity (livestock breeding farms / population, P = 0.027) and cattle density (cattle / cultivated area, P = 0.013). Conclusions: Alike in other countries, HUS in Switzerland is mostly associated with STEC infection and affects predominantly young children. However, the incidence rate is higher compared to countries abroad and is significantly correlated with indicators of livestock farming intensity. The present data support the impact of direct and indirect contact with animals or fecal contaminants in transmission of STEC to humans.

Time Series Input Selection using Multiple Kernel Learning

In this paper we study the relevance of multiple kernel learning (MKL) for the automatic selection of time series inputs. Recently, MKL has gained great attention in the machine learning community due to its flexibility in modelling complex patterns and performing feature selection. In general, MKL constructs the kernel as a weighted linear combination of basis kernels, exploiting different sources of information. An efficient algorithm wrapping a Support Vector Regression model for optimizing the MKL weights, named SimpleMKL, is used for the analysis. In this sense, MKL performs feature selection by discarding inputs/kernels with low or null weights. The approach proposed is tested with simulated linear and nonlinear time series (AutoRegressive, Henon and Lorenz series).

BME-based uncertainty assessment of the Chernobyl fallout

The vast territories that have been radioactively contaminated during the 1986 Chernobyl accident provide a substantial data set of radioactive monitoring data, which can be used for the verification and testing of the different spatial estimation (prediction) methods involved in risk assessment studies. Using the Chernobyl data set for such a purpose is motivated by its heterogeneous spatial structure (the data are characterized by large-scale correlations, short-scale variability, spotty features, etc.). The present work is concerned with the application of the Bayesian Maximum Entropy (BME) method to estimate the extent and the magnitude of the radioactive soil contamination by 137Cs due to the Chernobyl fallout. The powerful BME method allows rigorous incorporation of a wide variety of knowledge bases into the spatial estimation procedure leading to informative contamination maps. Exact measurements (?hard? data) are combined with secondary information on local uncertainties (treated as ?soft? data) to generate science-based uncertainty assessment of soil contamination estimates at unsampled locations. BME describes uncertainty in terms of the posterior probability distributions generated across space, whereas no assumption about the underlying distribution is made and non-linear estimators are automatically incorporated. Traditional estimation variances based on the assumption of an underlying Gaussian distribution (analogous, e.g., to the kriging variance) can be derived as a special case of the BME uncertainty analysis. The BME estimates obtained using hard and soft data are compared with the BME estimates obtained using only hard data. The comparison involves both the accuracy of the estimation maps using the exact data and the assessment of the associated uncertainty using repeated measurements. Furthermore, a comparison of the spatial estimation accuracy obtained by the two methods was carried out using a validation data set of hard data. Finally, a separate uncertainty analysis was conducted that evaluated the ability of the posterior probabilities to reproduce the distribution of the raw repeated measurements available in certain populated sites. The analysis provides an illustration of the improvement in mapping accuracy obtained by adding soft data to the existing hard data and, in general, demonstrates that the BME method performs well both in terms of estimation accuracy as well as in terms estimation error assessment, which are both useful features for the Chernobyl fallout study.

Disegni come documento e disegni come monumento : Giovanni Ciampini, Sebastiano Resta e la fortuna del Medioevo artistico nella Roma di Bellori

La tesi di Dottorato, condotta in accordo di colutela tra l'Università di Roma Tor Vergata e l'UNIL di Losanna, ha affrontato l'analisi di un gruppo di undici disegni custodia presso la National Gallery of Scotland di Edimburgo, copie di alcuni dei più significativi mosaici medioevali delle chiese di Roma, ricostruendone la genesi, quindi le vicende legate alla committenza, e il percorso collezionistico. I disegni scozzesi, oggetto di un importante articolo di Julian Gardner pubblicato sul Burlington Magatine nel 1973, furono commissionati intorno agli anni Settanta del XVII secolo dall'antiquario romano Giovanni Giustino Ciampini (1633-1698) in connessione alla stesura della sua opera di erudizione più avvertita e famosa: i Vetera Mommenta in' quibus praecipue Musiva Opera, sacrarum, profanan,mque, Aedìum structura, ac nonnulli antiqui ritus dissertationibus iconìbusque illustrantur. La composizione dei Vetera Mommenta - un'opera riccamente illustrata che nasce per rispondere alle esigenze della ideologia della Chiesa di Roma in un momento di rinnovata crisi del sistema - impone a Ciampini di porsi da un lato nella prospettiva della più alta tradizione antiquaria cinque e seicentesca, di cui recupera i metodi di lettura e di analisi applicati allo studio delle monete e dei monumenti antichi interpretati quali prove per la ricostruzione storica, e dall'altra, come è emerso dalle mie ricerche, lo pone immediatamente in contatto con gli avamposti del più moderno metodo di indagine storica e filologica applicato alle fonti e ai documenti della storia ecclesiastica, inaugurato dall'ambiente bollandista e inaurino. I monumenti paleocristiani e medioevali assumono in quest'ottica lo status di 'fatti incontestabili', le fonti primarie attraverso le quali Ciampini ricuce le tappe salienti della storia della Chiesa, da Costantino fino al XV secolo. Nel 1700 le copie di Edimburgo arrivano nelle mani del mercante e connoisseur milanese il padre oratoriano Sebastiano Resta (1635-1714), di stanza a Roma presso la Chiesa Nuova della Vallicella dal 1660, che decide di rilegarle tutte insieme in un volume da donare al suo maggiore acquirente e patrono, il vescovo di Arezzo Giovanni Matteo Marchetti. Come spiega Resta in alcune sue lettere, il presente avrebbe dovuto costituire insieme una curiosità ed offrire un confronto: infatti «le copie delli mosaici di Roma che erano di Monsignor Ciampini» - afferma Resta - avrebbero mostrato al Marchetti «le maniere di que' tempi gottici, barbari e divoti de cristiani e [fatto] spiccare i secoli seguenti». Questa indagine infatti ha fatto riemergere aspetti della precoce attenzione di Sebastiano Resta per l'arte dei "secoli bassi", mai debitamente affrontata dagli studi. E' infatti sulla scorta di una profonda conoscenza dei testi della letteratura artistica, e in connessione alla esplosione vivacissima della controversia Malvasia/Baldinucci sul primato del risorgere delle arti in Toscana, che Sebastiano a partire dagli anni Ottanta del Seicento comincia a meditare sul Medioevo artistico con il fine di spiegare l'evoluzione del linguaggio tecnico e formale che ha condotto alla perfezione dell'atte moderna. In questa prospettiva ι disegni del XIV e XV secolo che egli riuscì ad intercettare sul mercato valgono quali testimonianze delle maniere degli artefici più antichi e sono imbastiti nei molteplici album che Resta compone nel rispetto della successione cronologica dei presunti autori, e ordinati in base alle scuole pittoriche di pertinenza. La tesi permette perciò di descrivere nelle loro diverse specificità: da un lato il modo dei conoscitori come Resta, interessati nell'opera al dato stilistico, con immediate e sensibili ricadute sul mercato, e disposti anche con passione a ricercare i documenti relativi all'opera in quanto pressati dall'urgenza di collocarla nella sequenza cronologica dello sviluppo del linguaggio formale e tecnico; dall'altro gli antiquari come Ciampini e come Bianchini, per i quali le opere del passato valgono come prove irrefutabili della ricostruzione storica, e divengono quindi esse stesse, anche nel loro statuto di copia, documento della stona. Sono due approcci che si manifestano nel Seicento, e talvolta in una medesima persona, come mostra il caso anche per questo cruciale di Giovati Pietro Bellori, ma che hanno radici cinquecentesche, di cui i protagonisti di queste vicende sono ben consapevoli: e se dietro Resta c'è palesemente Vasari, dietro Ciampini e soprattutto Bianchini c'è la più alta tradizione antiquaria del XVI secolo, da Antonio Augustin a Fulvio Orsini.