Early prediction of response to sunitinib after imatinib failure by 18F-fluorodeoxyglucose positron emission tomography in patients with gastrointestinal stromal tumor.

PURPOSE: Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) was used to evaluate treatment response in patients with gastrointestinal stromal tumors (GIST) after administration of sunitinib, a multitargeted tyrosine kinase inhibitor, after imatinib failure. PATIENTS AND METHODS: Tumor metabolism was assessed with FDG-PET before and after the first 4 weeks of sunitinib therapy in 23 patients who received one to 12 cycles of sunitinib therapy (4 weeks of 50 mg/d, 2 weeks off). Treatment response was expressed as the percent change in maximal standardized uptake values (SUV). The primary end point of time to tumor progression was compared with early PET results on the basis of traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Progression-free survival (PFS) was correlated with early FDG-PET metabolic response (P < .0001). Using -25% and +25% thresholds for SUV variations from baseline, early FDG-PET response was stratified in metabolic partial response, metabolically stable disease, or metabolically progressive disease; median PFS rates were 29, 16, and 4 weeks, respectively. Similarly, when a single FDG-PET positive/negative was considered after 4 weeks of sunitinib, the median PFS was 29 weeks for SUVs less than 8 g/mL versus 4 weeks for SUVs of 8 g/mL or greater (P < .0001). None of the patients with metabolically progressive disease subsequently responded according to RECIST criteria. Multivariate analysis showed shorter PFS in patients who had higher residual SUVs (P < .0001), primary resistance to imatinib (P = .024), or nongastric GIST (P = .002), regardless of the mutational status of the KIT and PDGFRA genes. CONCLUSION: Week 4 FDG-PET is useful for early assessment of treatment response and for the prediction of clinical outcome. Thus, it offers opportunities to individualize and optimize patient therapy.

Prediction of plant species distributions across six millennia.

The usefulness of species distribution models (SDMs) in predicting impacts of climate change on biodiversity is difficult to assess because changes in species ranges may take decades or centuries to occur. One alternative way to evaluate the predictive ability of SDMs across time is to compare their predictions with data on past species distributions. We use data on plant distributions, fossil pollen and current and mid-Holocene climate to test the ability of SDMs to predict past climate-change impacts. We find that species showing little change in the estimated position of their realized niche, with resulting good model performance, tend to be dominant competitors for light. Different mechanisms appear to be responsible for among-species differences in model performance. Confidence in predictions of the impacts of climate change could be improved by selecting species with characteristics that suggest little change is expected in the relationships between species occurrence and climate patterns.

Prediction of hip fracture risk by quantitative ultrasound in more than 7000 Swiss women > or =70 years of age: comparison of three technologically different bone ultrasound devices in the SEMOF study.

To compare the prediction of hip fracture risk of several bone ultrasounds (QUS), 7062 Swiss women > or =70 years of age were measured with three QUSs (two of the heel, one of the phalanges). Heel QUSs were both predictive of hip fracture risk, whereas the phalanges QUS was not. INTRODUCTION: As the number of hip fracture is expected to increase during these next decades, it is important to develop strategies to detect subjects at risk. Quantitative bone ultrasound (QUS), an ionizing radiation-free method, which is transportable, could be interesting for this purpose. MATERIALS AND METHODS: The Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk (SEMOF) study is a multicenter cohort study, which compared three QUSs for the assessment of hip fracture risk in a sample of 7609 elderly ambulatory women > or =70 years of age. Two QUSs measured the heel (Achilles+; GE-Lunar and Sahara; Hologic), and one measured the heel (DBM Sonic 1200; IGEA). The Cox proportional hazards regression was used to estimate the hazard of the first hip fracture, adjusted for age, BMI, and center, and the area under the ROC curves were calculated to compare the devices and their parameters. RESULTS: From the 7609 women who were included in the study, 7062 women 75.2 +/- 3.1 (SD) years of age were prospectively followed for 2.9 +/- 0.8 years. Eighty women reported a hip fracture. A decrease by 1 SD of the QUS variables corresponded to an increase of the hip fracture risk from 2.3 (95% CI, 1.7, 3.1) to 2.6 (95% CI, 1.9, 3.4) for the three variables of Achilles+ and from 2.2 (95% CI, 1.7, 3.0) to 2.4 (95% CI, 1.8, 3.2) for the three variables of Sahara. Risk gradients did not differ significantly among the variables of the two heel QUS devices. On the other hand, the phalanges QUS (DBM Sonic 1200) was not predictive of hip fracture risk, with an adjusted hazard risk of 1.2 (95% CI, 0.9, 1.5), even after reanalysis of the digitalized data and using different cut-off levels (1700 or 1570 m/s). CONCLUSIONS: In this elderly women population, heel QUS devices were both predictive of hip fracture risk, whereas the phalanges QUS device was not.

Genome-wide prediction of matrix attachment regions that increase gene expression in mammalian cells.

Gene transfer in eukaryotic cells and organisms suffers from epigenetic effects that result in low or unstable transgene expression and high clonal variability. Use of epigenetic regulators such as matrix attachment regions (MARs) is a promising approach to alleviate such unwanted effects. Dissection of a known MAR allowed the identification of sequence motifs that mediate elevated transgene expression. Bioinformatics analysis implied that these motifs adopt a curved DNA structure that positions nucleosomes and binds specific transcription factors. From these observations, we computed putative MARs from the human genome. Cloning of several predicted MARs indicated that they are much more potent than the previously known element, boosting the expression of recombinant proteins from cultured cells as well as mediating high and sustained expression in mice. Thus we computationally identified potent epigenetic regulators, opening new strategies toward high and stable transgene expression for research, therapeutic production or gene-based therapies.

A genetic risk score combining 32 SNPs is associated with body mass index and improves obesity prediction in people with major depressive disorder.

BACKGROUND: Obesity is strongly associated with major depressive disorder (MDD) and various other diseases. Genome-wide association studies have identified multiple risk loci robustly associated with body mass index (BMI). In this study, we aimed to investigate whether a genetic risk score (GRS) combining multiple BMI risk loci might have utility in prediction of obesity in patients with MDD. METHODS: Linear and logistic regression models were conducted to predict BMI and obesity, respectively, in three independent large case-control studies of major depression (Radiant, GSK-Munich, PsyCoLaus). The analyses were first performed in the whole sample and then separately in depressed cases and controls. An unweighted GRS was calculated by summation of the number of risk alleles. A weighted GRS was calculated as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver operating characteristic (ROC) analysis was used to compare the discriminatory ability of predictors of obesity. RESULTS: In the discovery phase, a total of 2,521 participants (1,895 depressed patients and 626 controls) were included from the Radiant study. Both unweighted and weighted GRS were highly associated with BMI (P <0.001) but explained only a modest amount of variance. Adding 'traditional' risk factors to GRS significantly improved the predictive ability with the area under the curve (AUC) in the ROC analysis, increasing from 0.58 to 0.66 (95% CI, 0.62-0.68; χ(2) = 27.68; P <0.0001). Although there was no formal evidence of interaction between depression status and GRS, there was further improvement in AUC in the ROC analysis when depression status was added to the model (AUC = 0.71; 95% CI, 0.68-0.73; χ(2) = 28.64; P <0.0001). We further found that the GRS accounted for more variance of BMI in depressed patients than in healthy controls. Again, GRS discriminated obesity better in depressed patients compared to healthy controls. We later replicated these analyses in two independent samples (GSK-Munich and PsyCoLaus) and found similar results. CONCLUSIONS: A GRS proved to be a highly significant predictor of obesity in people with MDD but accounted for only modest amount of variance. Nevertheless, as more risk loci are identified, combining a GRS approach with information on non-genetic risk factors could become a useful strategy in identifying MDD patients at higher risk of developing obesity.

Bond strength tests of dental adhesive systems and their correlation with clinical results : a meta-analysis

OBJECTIVE: To evaluate the variability of bond strength test results of adhesive systems (AS) and to correlate the results with clinical parameters of clinical studies investigating cervical restorations. MATERIALS AND METHODS: Regarding the clinical studies, the internal database which had previously been used for a meta-analysis on cervical restorations was updated with clinical studies published between 2008 and 2012 by searching the PubMed and SCOPUS databases. PubMed and the International Association for Dental Research abstracts online were searched for laboratory studies on microtensile, macrotensile and macroshear bond strength tests. The inclusion criteria were (1) dentin, (2) testing of at least four adhesive systems, (3) same diameter of composite and (4) 24h of water storage prior to testing. The clinical outcome variables were retention loss, marginal discoloration, detectable margins, and a clinical index comprising the three parameters by weighing them. Linear mixed models which included a random study effect were calculated for both, the laboratory and the clinical studies. The variability was assessed by calculating a ratio of variances, dividing the variance among the estimated bonding effects obtained in the linear mixed models by the sum of all variance components estimated in these models. RESULTS: Thirty-two laboratory studies fulfilled the inclusion criteria comprising 183 experiments. Of those, 86 used the microtensile test evaluating 22 adhesive systems (AS). Twenty-seven used the macrotensile test with 17 AS, and 70 used the macroshear test with 24 AS. For 28 AS the results from clinical studies were available. Microtensile and macrotensile (Spearman rho=0.66, p=0.007) were moderately correlated and also microtensile and macroshear (Spearman rho=0.51, p=0.03) but not macroshear and macrotensile (Spearman rho=0.34, p=0.22). The effect of the adhesive system was significant for microtensile and macroshear (p<0.001) but not for macrotensile. The effect of the adhesive system could explain 36% of the variability of the microtensile test, 27% of the macrotensile and 33% of the macroshear test. For the clinical trials, about 49% of the variability of retained restorations could be explained by the adhesive system. With respect to the correlation between bond strength tests and clinical parameters, only a moderate correlation between micro- and macrotensile test results and marginal discoloration was demonstrated. However, no correlation between these tests and a retention loss or marginal integrity was shown. The correlation improved when more studies were included compared to assessing only one study. SIGNIFICANCE: The high variability of bond strength test results highlights the need to establish individual acceptance levels for a given test institute. The weak correlation of bond-strength test results with clinical parameters leads to the conclusion that one should not rely solely on bond strength tests to predict the clinical performance of an adhesive system but one should conduct other laboratory tests like tests on the marginal adaptation of fillings in extracted teeth and the retention loss of restorations in non-retentive cavities after artificial aging.

Power spectral changes of the superimposed M wave during isometric voluntary contractions of increasing strength.

INTRODUCTION: We examined the power spectral changes of the compound muscle action potential (M wave) evoked during isometric contractions of increasing strength. METHODS: Surface electromyography (sEMG) of the vastus lateralis and medialis was recorded from 20 volunteers who performed 4-s step-wise isometric contractions of different intensities. A maximal M wave was elicited by a single stimulus to the femoral nerve and superimposed on the voluntary contractions. The spectral characteristics (Fmean and Fmedian) of sEMG and M-wave signals were calculated. RESULTS: M-wave spectral indicators increased systematically with contraction intensity up to 60% MVC and then leveled off at higher forces. Over the 10-60% MVC range, the increase in spectral indicators was 3 times higher for M waves (36%) than for sEMG (12%). CONCLUSIONS: The consistent increase in M-wave spectral characteristics with force is due to the fact that the number of motor units recruited by the superimposed supramaximal stimulus is approximately stable.

The Atherosclerosis Burden Score (ABS): a Convenient Ultrasound-Based Score of Peripheral Atherosclerosis for Coronary Artery Disease Prediction.

Ultrasonographic detection of subclinical atherosclerosis improves cardiovascular risk stratification, but uncertainty persists about the most discriminative method to apply. In this study, we found that the "atherosclerosis burden score (ABS)", a novel straightforward ultrasonographic score that sums the number of carotid and femoral arterial bifurcations with plaques, significantly outperformed common carotid intima-media thickness, carotid mean/maximal thickness, and carotid/femoral plaque scores for the detection of coronary artery disease (CAD) (receiver operating characteristic (ROC) curve area under the curve (AUC) = 0.79; P = 0.027 to <0.001 with the other five US endpoints) in 203 patients undergoing coronary angiography. ABS was also more correlated with CAD extension (R = 0.55; P < 0.001). Furthermore, in a second group of 1128 patients without cardiovascular disease, ABS was weakly correlated with the European Society of Cardiology chart risk categories (R (2) = 0.21), indicating that ABS provided information beyond usual cardiovascular risk factor-based risk stratification. Pending prospective studies on hard cardiovascular endpoints, ABS appears as a promising tool in primary prevention.

Prediction in forensic science: a critical examination of common understandings

In this commentary, we argue that the term 'prediction' is overly used when in fact, referring to foundational writings of de Finetti, the correspondent term should be inference. In particular, we intend (i) to summarize and clarify relevant subject matter on prediction from established statistical theory, and (ii) point out the logic of this understanding with respect practical uses of the term prediction. Written from an interdisciplinary perspective, associating statistics and forensic science as an example, this discussion also connects to related fields such as medical diagnosis and other areas of application where reasoning based on scientific results is practiced in societal relevant contexts. This includes forensic psychology that uses prediction as part of its vocabulary when dealing with matters that arise in the course of legal proceedings.

Prediction of Post-Weaning Fibrinogen Status during Cardiopulmonary Bypass: An Observational Study in 110 Patients.

BACKGROUND: After cardiac surgery with cardiopulmonary bypass (CPB), acquired coagulopathy often leads to post-CPB bleeding. Though multifactorial in origin, this coagulopathy is often aggravated by deficient fibrinogen levels. OBJECTIVE: To assess whether laboratory and thrombelastometric testing on CPB can predict plasma fibrinogen immediately after CPB weaning. PATIENTS / METHODS: This prospective study in 110 patients undergoing major cardiovascular surgery at risk of post-CPB bleeding compares fibrinogen level (Clauss method) and function (fibrin-specific thrombelastometry) in order to study the predictability of their course early after termination of CPB. Linear regression analysis and receiver operating characteristics were used to determine correlations and predictive accuracy. RESULTS: Quantitative estimation of post-CPB Clauss fibrinogen from on-CPB fibrinogen was feasible with small bias (+0.19 g/l), but with poor precision and a percentage of error >30%. A clinically useful alternative approach was developed by using on-CPB A10 to predict a Clauss fibrinogen range of interest instead of a discrete level. An on-CPB A10 ≤10 mm identified patients with a post-CPB Clauss fibrinogen of ≤1.5 g/l with a sensitivity of 0.99 and a positive predictive value of 0.60; it also identified those without a post-CPB Clauss fibrinogen <2.0 g/l with a specificity of 0.83. CONCLUSIONS: When measured on CPB prior to weaning, a FIBTEM A10 ≤10 mm is an early alert for post-CPB fibrinogen levels below or within the substitution range (1.5-2.0 g/l) recommended in case of post-CPB coagulopathic bleeding. This helps to minimize the delay to data-based hemostatic management after weaning from CPB.

Tie Strength and Family Formation : which Personal Relationships are Influential ?

Based on the analysis of qualitative interviews in western Germany, we argue that personal relationships have a strong impact on individuals' family formation processes and fertility intentions. We identify persons who influence individuals' fertility choices. Strong ties, such as those among core family members (i.e., parents and siblings), are an important contributing factor, but we are also able to show that weak ties, such as those among colleagues, and acquaintances need to be considered when examining social influence on family formation processes. Apart from single network partners, we have identified influential groups of persons. Such groups serve as a comparative standard regarding the timing of having one's first child and subsequent children.

Prédiction des complications après duodénopancréatectomie céphalique: validation d'un score de complications postopératoires = Prediction of complications after pancreaticoduodenectomy: validation of a postoperative complication score

Objectifs La chirurgie pancréatique reste associée à une morbidité postopératoire importante. Les efforts sont concentrés la plupart du temps sur la diminution de cette morbidité, mais la détection précoce de patients à risque de complications pourrait être une autre stratégie valable. Un score simple de prédiction des complications après duodénopancréatectomie céphalique a récemment été publié par Braga et al. La présente étude a pour but de valider ce score et de discuter de ses possibles implications cliniques. Méthodes De 2000 à 2015, 245 patients ont bénéficié d'une duodénopancréatectomie céphalique dans notre service. Les complications postopératoires ont été recensées selon la classification de Dindo et Clavien. Le score de Braga se base sur quatre paramètres : le score ASA (American Society of Anesthesiologists), la texture du pancréas, le diamètre du canal de Wirsung (canal pancréatique principal) et les pertes sanguines intra-opératoires. Un score de risque global de 0 à 15 peut être calculé pour chaque patient. La puissance de discrimination du score a été calculée en utilisant une courbe ROC (receiver operating characteristic). Résultats Des complications majeures sont apparues chez 31% des patients, alors que 17% des patients ont eu des complications majeures dans l'article de Braga. La texture du pancréas et les pertes sanguines étaient statistiquement significativement corrélées à une morbidité accrue. Les aires sous la courbe étaient respectivement de 0.95 et 0.99 pour les scores classés en quatre catégories de risques (de 0 à 3, 4 à 7, 8 à 11 et 12 à 15) et pour les scores individuels (de 0 à 15). Conclusions Le score de Braga permet donc une bonne discrimination entre les complications mineures et majeures. Notre étude de validation suggère que ce score peut être utilisé comme un outil pronostique de complications majeures après duodénopancréatectomie céphalique. Les implications cliniques, c'est-à-dire si les stratégies de prise en charge postopératoire doivent être adaptées en fonction du risque individuel du patient, restent cependant à élucider. -- Objectives Pancreatic surgery remains associated with important morbidity. Efforts are most commonly concentrated on decreasing postoperative morbidity, but early detection of patients at risk could be another valuable strategy. A simple prognostic score has recently been published. This study aimed to validate this score and discuss possible clinical implications. Methods From 2000 to 2012, 245 patients underwent pancreaticoduodenectomy. Complications were graded according to the Dindo-Clavien classification. The Braga score is based on American Society of Anesthesiologists score, pancreatic texture, Wirsung duct diameter, and blood loss. An overall risk score (from 0 to 15) can be calculated for each patient. Score discriminant power was calculated using a receiver operating characteristic curve. Results Major complications occurred in 31% of patients compared to 17% in Braga's data. Pancreatic texture and blood loss were independently statistically significant for increased morbidity. The areas under curve were 0.95 and 0.99 for 4-risk categories and for individual scores, respectively. Conclusions The Braga score discriminates well between minor and major complications. Our validation suggests that it can be used as prognostic tool for major complications after pancreaticoduodenectomy. The clinical implications, i.e., whether postoperative treatment strategies should be adapted according to the patient's individual risk, remain to be elucidated.