Associations of Weight Change With Changes in Calf Muscle Characteristics and Functional Decline in Peripheral Artery Disease.

Background Among people with lower extremity peripheral artery disease, obesity is associated with faster functional decline than normal weight. The association of weight loss with functional decline in peripheral artery disease is unknown. Methods and Results Adults with an ankle-brachial index <0.90 were identified from Chicago-area hospitals in 2002-2004. Weight and 6-minute walk distance were measured annually. Weight change categories were weight loss or gain (≥5 pounds/year at ≥1 visit) or stable (weight change <5 pounds at each visit). Participants reported whether weight loss was "intentional" or "unintentional." Calf muscle area was measured with computed tomography every 2 years. Associations of weight change with changes in calf muscle area and 6-minute walk distance were analyzed using mixed-effects models and adjusted for age, body mass index, ankle-brachial index, physical activity, and other confounders. Among 389 participants, mean ankle-brachial index was 0.63±0.16, mean age was 74.5±7.8, and mean body mass index was 28.1±5.1 kg/m2. Over 3.23±1.37 years, muscle area declined more in adults with intentional weight loss versus stable or gain (pair-wise comparisons, P<0.001). Intentional weight loss was associated with less annual decline in 6-minute walk distance than weight gain (intentional loss, 3.7 m; stable, -14.0 m; gain, -28.5 m; unintentional loss, -20.8 m; pair-wise comparison intentional loss versus gain, P=0.003). Conclusions Despite a greater loss of calf muscle area, adults with peripheral artery disease who intentionally lost ≥5 pounds experienced less functional decline than those who gained weight. A randomized trial is needed to establish whether benefits of weight loss in peripheral artery disease outweigh potential adverse effects

A theoretical look at ensemble-based optimization in reservoir management

Ensemble-based optimization has recently received great attention as a potentially powerful technique for life-cycle production optimization, which is a crucial element of reservoir management. Recent publications have increased both the number of applications and the theoretical understanding of the algorithm. However, there is still ample room for further development since most of the theory is based on strong assumptions. Here, the mathematics (or statistics) of Ensemble Optimization is studied, and it is shown that the algorithm is a special case of an already well defined natural evolution strategy known as Gaussian Mutation. A natural description of uncer-tainty in reservoir management arises from the use of an ensemble of history-matched geological realizations. A logical step is therefore to incorporate this uncertainty description in robust life-cycle production optimization through the expected objective function value. The expected value is approximated with the mean over all geological realizations. It is shown that the frequently advocated strategy of applying a different control sample to each reservoir realization delivers an unbiased estimate of the gradi-ent of the expected objective function. However, this procedure is more variance prone than the deterministic strategy of applying the entire ensemble of perturbed control samples to each reservoir model realization. In order to reduce the variance of the gradient estimate, an importance sampling algorithm is proposed and tested on a toy problem with increasing dimensionality.acceptedVersio

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Ischemia and reperfusion of the soleus muscle of rats with pentoxifylline

BACKGROUND: Reperfusion of the skeletal muscle worsens existing lesions during ischemia, since the production of reactive oxygen species, associated with intense participation of neutrophils, increases the inflammatory reaction that induces tissue changes. OBJECTIVE: To evaluate the morphological and immunohistochemical changes of the skeletal (soleus) muscle of rats submitted to ischemia and reperfusion with pentoxifylline. METHODS: Sixty rats were submitted to ischemia of the pelvic limb for 6 hours induced by clamping the left common iliac artery. After ischemia, group A animals (n = 30) were observed for 4 hours and group B animals (n = 30) for 24 hours. Six animals constituted the sham group. Pentoxifylline was applied only in the reperfusion period A2 (n = 10) and B2 (n = 10), and in ischemia and reperfusion periods in A3 (n = 10) and B3 (n = 10). The soleus muscle was evaluated by histological (fiber disruption, leukocyte infiltrate, necrosis) and immunohistochemical (apoptosis through caspase-3 expression) analysis. The non-parametric tests Kruskal-Wallis and Mann-Whitney (p < 0.05) were applied. RESULTS: The changes were more intense in group B1, with fiber disruption mean scores of 2.16±0.14; neutrophilic infiltrate of 2.05±0.10; and caspase-3 expression in the perivascular area of 4.30±0.79; and less intense in group A3, with means of 0.76±0.16; 0.92±0.10; 0.67±0,15, respectively (p < 0.05). Caspase-3 was more expressive in group B1 in the perivascular area, with mean of 4.30±0.79 when compared with group B1 in the perinuclear area, with mean of 0.91±0.32 (p < 0.05) CONCLUSIONS: The lesions were more intense when observation time was longer after reperfusion, and pentoxifylline attenuated these lesions, above all when used in the beginning of ischemia and reperfusion phases.CONTEXTO: A reperfusão de músculo esquelético piora as lesões já presentes no período de isquemia, pois a produção de espécies reativas de oxigênio, associadas à intensa participação de neutrófilos, amplia a reação inflamatória que induz alterações teciduais. OBJETIVO: Avaliar as alterações morfológicas e imuno-histoquímicas de músculo esquelético (sóleo) de ratos submetidos a isquemia e reperfusão com pentoxifilina. MÉTODOS: Sessenta ratos foram submetidos a isquemia do membro pélvico, por 6 horas, pelo clampeamento da artéria ilíaca comum esquerda. Após isquemia, os animais do grupo A (n = 30) foram observados por 4 horas, e os do grupo B (n = 30), por 24 horas. Seis animais constituíram o grupo simulado. Administrou-se pentoxifilina apenas no período de reperfusão em A2 (n = 10) e B2 (n = 10) e nos períodos de isquemia e reperfusão em A3 (n = 10) e B3 (n = 10). O músculo sóleo foi avaliado por análise histológica (dissociação de fibras, infiltrado leucocitário, necrose) e imuno-histoquímica (apoptose pela expressão da caspase-3). Foram aplicados os testes não-paramétricos de Kruskal-Wallis e Mann-Whitney (p < 0,05). RESULTADOS: As alterações foram mais intensas no grupo B1, com médias de escore da dissociação de fibras musculares de 2,16 ± 0,14, infiltrado neutrofílico de 2,05 ± 0,10 e expressão da caspase-3 na área perivascular de 4,30 ± 0,79; e menos intensas no grupo A3, com respectivas médias de 0,76 ± 0,16, 0,92 ± 0,10 e 0,67 ± 0,15 (p < 0,05). A caspase-3 mostrou-se mais expressiva no grupo B1 na área perivascular, com média de 4,30 ± 0,79, em comparação com o grupo B1 na área perinuclear, com média de 0,91 ± 0,32 (p < 0,05). CONCLUSÕES: As lesões são mais intensas quando o tempo de observação é maior após a reperfusão, e a pentoxifilina atenua essas lesões, sobretudo quando usada no início das fases de isquemia e de reperfusão.SBACVUniversidade Federal de Mato Grosso do Sul Hospital UniversitárioUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUFMSUNIFESP-EPM Departamento de PatologiaUFMS Departamento de Clínica CirúrgicaUFMS Hospital Universitário Comissão de Residência MédicaUNIFESP, EPM, Depto. de PatologiaSciEL

Wear behavior of a microhybrid composite vs. a nanocomposite in the treatment of severe tooth wear patients:A 5-year clinical study

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Robust metabolic transcriptional components in 34,494 patient-derived cancer-related samples and cell lines

BACKGROUND: Patient-derived bulk expression profiles of cancers can provide insight into the transcriptional changes that underlie reprogrammed metabolism in cancer. These profiles represent the average expression pattern of all heterogeneous tumor and non-tumor cells present in biopsies of tumor lesions. Hence, subtle transcriptional footprints of metabolic processes can be concealed by other biological processes and experimental artifacts. However, consensus independent component analyses (c-ICA) can capture statistically independent transcriptional footprints of both subtle and more pronounced metabolic processes. METHODS: We performed c-ICA with 34,494 bulk expression profiles of patient-derived tumor biopsies, non-cancer tissues, and cell lines. Gene set enrichment analysis with 608 gene sets that describe metabolic processes was performed to identify the transcriptional components enriched for metabolic processes (mTCs). The activity of these mTCs was determined in all samples to create a metabolic transcriptional landscape. RESULTS: A set of 555 mTCs was identified of which many were robust across different datasets, platforms, and patient-derived tissues and cell lines. We demonstrate how the metabolic transcriptional landscape defined by the activity of these mTCs in samples can be used to explore the associations between the metabolic transcriptome and drug sensitivities, patient outcomes, and the composition of the immune tumor microenvironment. CONCLUSIONS: To facilitate the use of our transcriptional metabolic landscape, we have provided access to all data via a web portal (www.themetaboliclandscapeofcancer.com). We believe this resource will contribute to the formulation of new hypotheses on how to metabolically engage the tumor or its (immune) microenvironment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40170-021-00272-7