Background: Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, ...prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer receiving conventional cancer management. Methods: A total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40 : 60 to dietary intervention (n = 975) or control (n = 1462) groups. An interim analysis was performed after a median follow-up of 60 months when funding for the intervention ceased. Mean differences between dietary intervention and control groups in nutrient intakes and anthropometric variables were compared with t tests. Relapse-free survival was examined using Kaplan–Meier analysis, stratified log-rank tests, and Cox proportional hazards models. Statistical tests were two-sided. Results: Dietary fat intake was lower in the intervention than in the control group (fat grams/day at 12 months, 33.3 95% confidence interval {CI} = 32.2 to 34.5 versus 51.3 95% CI = 50.0 to 52.7, respectively; P<.001), corresponding to a statistically significant (P = .005), 6-pound lower mean body weight in the intervention group. A total of 277 relapse events (local, regional, distant, or ipsilateral breast cancer recurrence or new contralateral breast cancer) have been reported in 96 of 975 (9.8%) women in the dietary group and 181 of 1462 (12.4%) women in the control group. The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 (95% CI = 0.60 to 0.98, P = .077 for stratified log rank and P = .034 for adjusted Cox model analysis). Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status. Conclusions: A lifestyle intervention reducing dietary fat intake, with modest influence on body weight, may improve relapse-free survival of breast cancer patients receiving conventional cancer management. Longer, ongoing nonintervention follow-up will address original protocol design plans, which called for 3 years of follow-up after completion of recruitment.
The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal ...obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (∼16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle peroxisome proliferator-activated receptor gamma coactivator (PGC1)α, PGC1β, and estrogen-related receptor (ERR)α, consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life.
Background Because of the failure of numerous clinical trials, various recommendations have been made to improve the usefulness of preclinical studies. Specifically, the STAIR (Stroke Therapy ...Academic Industry Roundtable) recommendations highlighted functional outcome as a critical measure. Recent reviews of experimental subarachnoid hemorrhage ( SAH ) studies have brought to light the numerous neurobehavioral scoring systems that are used in preclinical SAH studies. To gain insight into the utility of these scoring systems, as well as to identify a scoring system that best captures the deficits caused by SAH in mice, we designed the current study. Methods and Results Adult male C57 BL /6J mice were used. One cohort of mice was randomly allocated to either sham or SAH and had functional testing performed on days 1 to 3 post- SAH using the modified Bederson Score, Katz Score, Garcia Neuroscore, and Parra Neuroscore, as well as 21 individual subtests. A new composite neuroscore was developed using the 8 most diagnostically accurate subtests. To validate the use of the developed composite neuroscore, another cohort of mice was randomly assigned to either the sham or SAH group and neurobehavior was evaluated on days 1 to 3, 5, and 7 after injury. Receiver operating characteristic curves were used to analyze the diagnostic accuracy of each scoring system, as well as the subtests. Of the 4 published scoring systems, the Parra Neuroscore was diagnostically accurate for SAH injury in mice versus the modified Bederson and Katz Scores, but not the Garcia Neuroscore. However, the newly developed composite neuroscore was found to be statistically more diagnostically accurate than even the Parra Neuroscore. Conclusions The findings of this study promote use of the newly developed composite neuroscore for experimental SAH studies in mice.
Recent studies show that acute neuromodulation of the prefrontal cortex with transcranial direct current stimulation (tDCS) can decrease food craving, attentional bias to food, and actual food ...intake. These data suggest potential clinical applications for tDCS in the field of obesity. However, optimal stimulation parameters in obese individuals are uncertain. One fundamental concern is whether a thick, low-conductivity layer of subcutaneous fat around the head can affect current density distribution and require dose adjustments during tDCS administration. The aim of this study was to investigate the role of head fat on the distribution of current during tDCS and evaluate whether dosing standards for tDCS developed for adult individuals in general are adequate for the obese population. We used MRI-derived high-resolution computational models that delineated fat layers in five human heads from subjects with body mass index (BMI) ranging from "normal-lean" to "super-obese" (20.9 to 53.5 kg/m(2)). Data derived from these simulations suggest that head fat influences tDCS current density across the brain, but its relative contribution is small when other components of head anatomy are added. Current density variability between subjects does not appear to have a direct and/or simple link to BMI. These results indicate that guidelines for the use of tDCS can be extrapolated to obese subjects without sacrificing efficacy and/or treatment safety; the recommended standard parameters can lead to the delivery of adequate current flow to induce neuromodulation of brain activity in the obese population.
Purpose
Pituitary apoplexy can be a life threatening and vision compromising event. Antiplatelet and anticoagulation use has been reported as a contributing factor in pituitary apoplexy (PA). ...Utilizing one of the largest cohorts in the literature, this study aims to determine the risk of PA in patients on antiplatelet/anticoagulation (AP/AC) therapy.
Methods
A single center, retrospective study was conducted on 342 pituitary adenoma patients, of which 77 patients presented with PA (23%). Several potential risk factors for PA were assessed, including: patient demographics, tumor characteristics, pre-operative hormone replacement, neurologic deficits, coagulation studies, platelet count, and AP/AC therapy.
Results
Comparing patients with and without apoplexy, there was no significant difference in the proportion of patients taking aspirin (45 no apoplexy vs. 10 apoplexy; p = 0.5), clopidogrel (10 no apoplexy vs. 4 apoplexy; p = 0.5), and anticoagulation (7 no apoplexy vs. 3 apoplexy; p = 0.7). However, male sex (p-value < 0.001) was a predictor for apoplexy while pre-operative hormone treatment was a protective factor from apoplexy (p-value < 0.001). A non-clinical difference in INR was also noted as a predictor for apoplexy (no apoplexy: 1.01 ± 0.09, apoplexy: 1.07 ± 0.15; p < 0.001).
Conclusions
Although pituitary tumors have a high risk for spontaneous hemorrhage, the use of aspirin is not a risk for hemorrhage. Our study did not find an increased risk of apoplexy with clopidogrel or anticoagulation, but further investigation is needed with a larger cohort. Confirming other reports, male sex is associated with an increased risk for PA.
Networks made of single‐walled carbon nanotubes (SWNTs) and metallic nanowire networks, graphene, and ultra‐thin metal films have all been proposed as replacements for transparent conducting oxides ...(TCOs) in photovoltaic and other applications. However, only limited comparisons of nanostructured networks and TCOs are available. Several common figures of merit that are often used to compare the electrical and optical performance of the transparent contacts are evaluated here, and the merits of each method of comparison are discussed. Calculating the current loss due to absorption in the TCO is the most useful metric for evaluating new materials for use in solar cells with well‐defined sheet resistance requirements and known quantum efficiencies. The ‘Haacke’ figure of merit, ΦH, correlates fairly well with current loss and is a good metric for evaluating electro‐optical performance for more general applications. The analyses presented here demonstrate that silver nanowire networks are much closer to achieving optimal electrical and optical properties than carbon‐based networks.
The optoelectronic performance and physics of carbon nanotubes, metallic nanowires, and graphene networks are compared with traditional transparent conducting oxides (TCOs). The state‐of‐the art performance of these networks has not yet matched that of TCOs due to a number of factors, including fundamental physical differences between the materials; however, silver nanowire networks are more promising candidates than carbon‐based networks.
The Agency for Healthcare Research and Quality patient safety indicators (PSIs) and the Centers for Medicare and Medicaid Services hospital-acquired conditions (HACs) are publicly reported quality ...metrics linked directly to reimbursement. The occurrence of PSIs and HACs is associated with increased mortality and hospital costs after stroke. The relationship between insurance status and PSI and HAC rates in hospitalized patients treated for acute ischemic stroke was determined using the Nationwide Inpatient Sample (NIS) database.
The NIS was queried for all hospitalizations involving acute ischemic stroke between 2002 and 2011. The rate of each PSI and HAC was determined by searching the hospital records for ICD-9 codes. The SAS statistical software package was used to calculate rates and perform multivariable analyses to determine the effects of patient variables on the probability of developing each indicator.
The NIS query revealed 1,507,336 separate patient admissions that had information on both primary payer and hospital teaching status. There were 227,676 PSIs (15.1% of admissions) and 42,841 HACs reported (2.8%). Patient safety indicators occurred more frequently in Medicaid/self-pay/no-charge patients (19.1%) and Medicare patients (15.0%) than in those with private insurance (13.6%; p < 0.0001). In a multivariable analysis, Medicaid, self-pay, or nocharge patients had significantly longer hospital stays, higher mortality, and worse outcomes than those with private insurance (p < 0.0001).
Insurance status is an independent predictor of patient safety events after stroke. Private insurance is associated with lower mortality, shorter lengths of stay, and improved clinical outcomes.
We present a comprehensive study of the effects of doping and temperature on the conductivity of single-walled carbon nanotube (SWNT) networks. We investigated nearly type-pure networks as well as ...networks comprising precisely tuned mixtures of metallic and semiconducting tubes. Networks were studied in their as-produced state and after treatments with nitric acid, thionyl chloride, and hydrazine to explore the effects of both intentional and adventitious doping. For intentionally and adventitiously doped networks, the sheet resistance (R(s)) exhibits an irreversible increase with temperature above approximately 350 K. Dopant desorption is shown to be the main cause of this increase and the observed hysteresis in the temperature-dependent resistivity. Both thermal and chemical dedoping produced networks free of hysteresis. Temperature-programmed desorption data showed that dopants are most strongly bound to the metallic tubes and that networks consisting of metallic tubes exhibit the best thermal stability. At temperatures below the dopant desorption threshold, conductivity in the networks is primarily controlled by thermally assisted tunneling through barriers at the intertube or interbundle junctions.
The Fermi Gamma-ray Burst Monitor (GBM) is currently the most prolific detector of gamma-ray bursts (GRBs). Recently the detection rate of short GRBs (SGRBs) has been dramatically increased through ...the use of ground-based searches that analyze GBM continuous time-tagged event (CTTE) data. Here, we examine the efficiency of a method developed to search CTTE data for sub-threshold transient events in temporal coincidence with LIGO/Virgo compact binary coalescence triggers. This targeted search operates by coherently combining data from all 14 GBM detectors by taking into account the complex spatial and energy dependent response of each detector. We use the method to examine a sample of SGRBs that were independently detected by the Burst Alert Telescope on board the Neil Gehrels Swift Observatory, but which were too intrinsically weak or viewed with unfavorable instrument geometry to initiate an onboard trigger of GBM. We find that the search can successfully recover a majority of the BAT detected sample in the CTTE data. We show that the targeted search of CTTE data will be crucial in increasing the GBM sensitivity, and hence the gamma-ray horizon, to weak events such as GRB 170817A. We also examine the properties of the GBM signal possibly associated with the LIGO detection of GW150914 and show that it is consistent with the observed properties of other sub-threshold SGRBs in our sample. We find that the targeted search is capable of recovering true astrophysical signals as weak as the signal associated with GW150914 in the untriggered data.
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