Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593.

PURPOSE: Patients with primary cutaneous melanoma > or = 1.5 mm in thickness are at high risk of having regional micrometastases at the time of initial surgical treatment. A phase III international study was designed to evaluate whether prophylactic isolated limb perfusion (ILP) could prevent regional recurrence and influence survival. PATIENTS AND METHODS: A total of 832 assessable patients from 16 centers entered the study; 412 were randomized to wide excision (WE) only and 420 to WE plus ILP with melphalan and mild hyperthermia. Median age was 50 years, 68% of patients were female, 79% of melanomas were located on a lower limb, and 47% had a thickness > or = 3 mm. RESULTS: Median follow-up duration is 6.4 years. There was a trend for a longer disease-free interval (DFI) after ILP. The difference was significant for patients who did not undergo elective lymph node dissection (ELND). The impact of ILP was clearly on the occurrence-as first site of progression - of in-transit metastases (ITM), which were reduced from 6.6% to 3.3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6%. There was no benefit from ILP in terms of time to distant metastasis or survival. Side effects were higher after ILP, but transient in most patients. There were two amputations for limb toxicity after ILP. CONCLUSION: Prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma.

Comparing Bone Microarchitecture by Trabecular Bone Score (TBS) in Caucasian American Women with and Without Osteoporotic Fractures.

Several cross-sectional studies have shown the ability of the TBS to discriminate between those with and without fractures in European populations. The aim of this study was to assess the ability of TBS to discriminate between those with and without fractures in a large female Caucasian population in the USA. This was a case-control study of 2,165 Caucasian American women aged 40 and older. Patients with illness or taking medications known to affect bone metabolism were excluded. Those in the fracture group (n = 289) had at least one low-energy fracture. BMD was measured at L1-L4, TBS calculated directly from the same DXA image. Descriptive statistics and inferential tests for difference were used. Univariate and multivariate logistic regression models were created to investigate possible association between independent variables and the status of fracture. Odds ratios per standard deviation decrease (OR) and areas under the ROC curve were calculated for discriminating parameters. Weak correlations were observed between TBS and BMD and between TBS and BMI (r = 0.33 and -0.17, respectively, p < 0.01). Mean age, weight, BMD and TBS were significantly different between control and fracture groups (all p ≤ 0.05), whereas no difference was noted for BMI or height. After adjusting for age, weight, BMD, smoking, and maternal and family history of fracture, TBS (but not BMD) remained a significant predictor of fracture: OR 1.28[1.13-1.46] even after adjustment. In a US female population, TBS again was able to discriminate between those with and those without fractures, even after adjusting for other clinical risk factors.

Linking life-history traits, ecology, and niche breadth evolution in north american eriogonoids (polygonaceae).

Abstract Macroevolutionary and microevolutionary studies provide complementary explanations of the processes shaping the evolution of niche breadth. Macroevolutionary approaches scrutinize factors such as the temporal and spatial environmental heterogeneities that drive differentiation among species. Microevolutionary studies, in contrast, focus on the processes that affect intraspecific variability. We combine these perspectives by using macroevolutionary models in a comparative study of intraspecific variability. We address potential differences in rates of evolution of niche breadth and position in annual and perennial plants of the Eriogonoideae subfamily of the Polygonaceae. We anticipated higher rates of evolution in annuals than in perennials owing to differences in generation time that are paralleled by rates of molecular evolution. Instead, we found that perennial eriogonoid species present greater environmental tolerance (wider climate niche) than annual species. Niche breadth of perennial species has evolved two to four times faster than in annuals, while niche optimum has diversified more rapidly among annual species than among perennials. Niche breadth and average elevation of species are correlated. Moreover, niche breadth increases more rapidly with mean species elevation in perennials than in annuals. Our results suggest that both environmental gradients and life-history strategy influence rates and patterns of niche breadth evolution.

Structural characterization of rockfall sources in Yosemite Valley from remote sensing data and field surveys

Yosemite Valley poses significant rockfall hazard and related risk due to its glacially steepened walls and approximately 4 million visitors annually. To assess rockfall hazard, it is necessary to evaluate the geologic structure that contributes to the destabilization of rockfall sources and locate the most probable future source areas. Coupling new remote sensing techniques (Terrestrial Laser Scanning, Aerial Laser Scanning) and traditional field surveys, we investigated the regional geologic and structural setting, the orientation of the primary discontinuity sets for large areas of Yosemite Valley, and the specific discontinuity sets present at active rockfall sources. This information, combined with better understanding of the geologic processes that contribute to the progressive destabilization and triggering of granitic rock slabs, contributes to a more accurate rockfall susceptibility assessment for Yosemite Valley and elsewhere.

Glover's rule in North American barn owls

Studying the geographic variation of phenotypic traits can provide key information about the potential adaptive function of alternative phenotypes. Gloger's rule posits that animals should be dark-vs. light-colored in warm and humid vs. cold and dry habitats, respectively. The rule is based on the assumption that melanin pigments and/or dark coloration confer selective advantages in warm and humid regions. This rule may not apply, however, if genes for color are acting on other traits conferring fitness benefits in specific climes. Covariation between coloration and climate will therefore depend on the relative importance of coloration or melanin pigments and the genetically correlated physiological and behavioral processes that enable an animal to deal with climatic factors. The Barn Owl (Tyto alba) displays three melanin-based plumage traits, and we tested whether geographic variation in these traits at the scale of the North American continent supported Gloger's rule. An analysis of variation of pheomelanin-based reddish coloration and of the number and size of black feather spots in 1,369 museum skin specimens showed that geographic variation was correlated with ambient temperature and precipitation. Owls were darker red in color and displayed larger but fewer black feather spots in colder regions. Owls also exhibited more and larger black spots in regions where the climate was dry in winter. We propose that the associations between pigmentation and ambient temperature are of opposite sign for reddish coloration and spot size vs. the number of spots because selection exerted by climate (or a correlated variable) is plumage trait-specific or because plumage traits are genetically correlated with different adaptations.

Factor analysis of the North American Spine Society outcome assessment instrument: a study based on a spine registry of patients treated with lumbar and cervical disc arthroplasty.

BACKGROUND CONTEXT: Studies involving factor analysis (FA) of the items in the North American Spine Society (NASS) outcome assessment instrument have revealed inconsistent factor structures for the individual items. PURPOSE: This study examined whether the factor structure of the NASS varied in relation to the severity of the back/neck problem and differed from that originally recommended by the developers of the questionnaire, by analyzing data before and after surgery in a large series of patients undergoing lumbar or cervical disc arthroplasty. STUDY DESIGN/SETTING: Prospective multicenter observational case series. PATIENT SAMPLE: Three hundred ninety-one patients with low back pain and 553 patients with neck pain completed questionnaires preoperatively and again at 3 to 6 and 12 months follow-ups (FUs), in connection with the SWISSspine disc arthroplasty registry. OUTCOME MEASURES: North American Spine Society outcome assessment instrument. METHODS: First, an exploratory FA without a priori assumptions and subsequently a confirmatory FA were performed on the 17 items of the NASS-lumbar and 19 items of the NASS-cervical collected at each assessment time point. The item-loading invariance was tested in the German version of the questionnaire for baseline and FU. RESULTS: Both NASS-lumbar and NASS-cervical factor structures differed between baseline and postoperative data sets. The confirmatory analysis and item-loading invariance showed better fit for a three-factor (3F) structure for NASS-lumbar, containing items on "disability," "back pain," and "radiating pain, numbness, and weakness (leg/foot)" and for a 5F structure for NASS-cervical including disability, "neck pain," "radiating pain and numbness (arm/hand)," "weakness (arm/hand)," and "motor deficit (legs)." CONCLUSIONS: The best-fitting factor structure at both baseline and FU was selected for both the lumbar- and cervical-NASS questionnaires. It differed from that proposed by the originators of the NASS instruments. Although the NASS questionnaire represents a valid outcome measure for degenerative spine diseases, it is able to distinguish among all major symptom domains (factors) in patients undergoing lumbar and cervical disc arthroplasty; overall, the item structure could be improved. Any potential revision of the NASS should consider its factorial structure; factorial invariance over time should be aimed for, to allow for more precise interpretations of treatment success.

Trabecular bone score is associated with volumetric bone density and microarchitecture as assessed by central QCT and HRpQCT in Chinese American and white women.

Although high-resolution peripheral quantitative computed tomography (HRpQCT) and central quantitative computed tomography (QCT) studies have shown bone structural differences between Chinese American (CH) and white (WH) women, these techniques are not readily available in the clinical setting. The trabecular bone score (TBS) estimates trabecular microarchitecture from dual-energy X-ray absorptiometry spine images. We assessed TBS in CH and WH women and investigated whether TBS is associated with QCT and HRpQCT indices. Areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry, lumbar spine (LS) TBS, QCT of the LS and hip, and HRpQCT of the radius and tibia were performed in 71 pre- (37 WH and 34 CH) and 44 postmenopausal (21 WH and 23 CH) women. TBS did not differ by race in either pre- or postmenopausal women. In the entire cohort, TBS positively correlated with LS trabecular volumetric bone mineral density (vBMD) (r = 0.664), femoral neck integral (r = 0.651), trabecular (r = 0.641) and cortical vBMD (r = 0.346), and cortical thickness (C/I; r = 0.540) by QCT (p < 0.001 for all). TBS also correlated with integral (r = 0.643), trabecular (r = 0.574) and cortical vBMD (r = 0.491), and C/I (r = 0.541) at the total hip (p < 0.001 for all). The combination of TBS and LS aBMD predicted more of the variance in QCT measures than aBMD alone. TBS was associated with all HRpQCT indices (r = 0.20-0.52) except radial cortical thickness and tibial trabecular thickness. Significant associations between TBS and measures of HRpQCT and QCT in WH and CH pre- and postmenopausal women demonstrated here suggest that TBS may be a useful adjunct to aBMD for assessing bone quality.

25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients.

BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients.METHODS: We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and =15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type.RESULTS: Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04).CONCLUSIONS: Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor.

Estime et respect de soi, justice, reconnaissance. De quelques défis actuels en éthique

L'éthique est aujourd'hui en pleine mutation (l'éthique théologique en subissant le contre-coup). Effervescence réjouissante ou valse des éthiques, progrès de la conscience morale ou fuite en avant dans ses sub-stitutions juridiques -le biodroit remplaçant la bioéthique?- relativisme moral ou quête d'une éthique commune, morale planétaire ou éthique des vertus, comment s'y retrouver dans ce carrousel tournoyant, sans perdre la tête, mais sans se laisser non plus séduire par des simplifications abusives? Mon propos sera de suggérer une ligne de crête nous permettant d'avancer au-dessus des précipices ou des abîmes et de baliser une marche plus assurée malgré les équilibres instables et fragiles qui sont de plus en plus les nôtres.