Evaluation of the efficacy and toxicity profile associated with intraperitoneal chemotherapy use in older women.

OBJECTIVE: Intraperitoneal (IP) chemotherapy (CT) for treatment of epithelial ovarian cancer (EOC) has been shown to provide a substantial OS advantage. This study aims to compare the toxicity and benefits of IP CT in patients ≥70 with those <70. METHODS: We performed a single institution retrospective review of patients diagnosed with Stage IIA-IIIC EOC from 2000 to 2013 who received IP CT. Clinicopathologic characteristics were extracted, and survival was calculated. RESULTS: 133 patients were included with 100 pts. <70years old and 33 pts. ≥70years old. Clinical trial enrollment was similar despite age. In trial enrolled patients, older patients received statistically fewer cycles of therapy (6.4 vs 5.8, p=0.002) but had similar dose delays (0.9 vs 0.7, p=0.72), and modifications (0.9 vs 0.36, p=0.11). Median PFS (27 vs 31months) and OS (71 and 62months) were not statistically different. Grade 3/4 neutropenia was significantly worse in the older patients (82% vs 100%, p=0.04). Neuropathy grade ≥2 and other non-hematologic toxicities were not different between age groups. CONCLUSIONS: Despite completing fewer cycles of IP CT, older EOC patients had comparable survival to younger patients. The population of older patients receiving IP CT in this study were on clinical trial and likely to be heartier than the general older population. IP CT appears well tolerated and effective among select older patients and is likely under-utilized outside of clinical trials.

Can Coarse Woody Debris Be Used for Carbon Storage in Open Grazed Woodlands?

Carbon dioxide off-setting policy in the agricultural sector is focused on manipulating the terrestrial carbon cycle by reafforestation and increasing the retention of carbon within agricultural soils. We quantified the amount of carbon stored in the living and dead biomass and the surface soils of a previously grazed woodland ecosystem. We demonstrate that modification of coarse woody debris management could potentially store 8 to 15 t C ha. This large carbon pool raises the prospect that appropriate management of temperate woodlands to retain coarse woody debris and increase its volume into the future could achieve increased landscape carbon storage.

Validation of a Community-Based Approach Toward Personalized Dementia Risk Reduction: The Kimel Family Centre for Brain Health and Wellness.

BACKGROUND/OBJECTIVES: The Kimel Family Centre for Brain Health and Wellness is a research-driven community centre testing the efficacy of personalized dementia risk reduction programming on dementia risk and cognition. The objective of this protocol is to validate this approach by following people for two years. DESIGN/SETTING: Participants will receive a comprehensive dementia risk assessment, including nonmodifiable and modifiable risk factors, from which they will receive a Personalized Dementia Risk Report and Program Strategy, indicating their health conditions increasing and their risk level in five modifiable risk domains: physical activity, brain-healthy eating, cognitive engagement, social connections, and mental wellbeing. Equipped with this information, participants will enroll in programs within the Centre to address their risk factors. Changes to their dementia risk, cognition, and Personalized Program Strategy will be communicated through re-assessments of risk factors every six months (risk and cognition) and every year (comprehensive assessment). PARTICIPANTS: Participants (n = 450) will be 50 years of age or older, without a diagnosis of dementia, and sufficiently fluent in English to complete the assessments and understand program instructors. One goal is that our participant sample will include people of low income (with fundraising providing free community centre membership), and from various ethno-racial backgrounds. INTERVENTION: Participants will select programs to meet their Personalized Program Strategy. For physical activity, they will gradually work toward the Canadian Society for Exercise Physiology guidelines. For brain-healthy eating, they will learn about the Brain Health Food Guide and food label reading, and then take additional programs. For cognitive engagement and mental wellbeing, they will take at least one hour of relevant programming per week. Social connections will be reinforced throughout all programs. All participants will also have access to the Canadian Consortium on Neurodegeneration's CAN-THUMBS Up online, educational program on modifiable dementia risk factors, called Brain Health PRO. MEASUREMENTS: The comprehensive assessment includes numerous dementia risk factors, but the primary measures are risk in the five domains, health conditions proximal to those five risk domains, and cognition, and how these are affected by adherence and quality of goal-directed future simulation. We hypothesize a reduced risk in the five domains within six months, improvements in health biomarkers within a year, and maintenance of cognition within two years, with these benefits accruing with greater adherence, but only up to a point, at which benefits will plateau, and greater benefits among participants whose goal-directed simulations are more vivid, personally-relevant, achievable, and positive. CONCLUSIONS: This innovative approach overcomes a number of limitations present in prior multidomain dementia prevention trials. Adapting a preference clinical trial that is embedded in a community centre, where participants have autonomy to choose programs to address their modifiable dementia risk factors, has real-world applicability in the global effort to reduce dementia risk.

Bandlike transport in strongly coupled and doped quantum dot solids: a route to high-performance thin-film electronics.

We report bandlike transport in solution-deposited, CdSe QD thin-films with room temperature field-effect mobilities for electrons of 27 cm(2)/(V s). A concomitant shift and broadening in the QD solid optical absorption compared to that of dispersed samples is consistent with electron delocalization and measured electron mobilities. Annealing indium contacts allows for thermal diffusion and doping of the QD thin-films, shifting the Fermi energy, filling traps, and providing access to the bands. Temperature-dependent measurements show bandlike transport to 220 K on a SiO(2) gate insulator that is extended to 140 K by reducing the interface trap density using an Al(2)O(3)/SiO(2) gate insulator. The use of compact ligands and doping provides a pathway to high performance, solution-deposited QD electronics and optoelectronics.

Acute high-intensity interval exercise reduces the postprandial glucose response and prevalence of hyperglycaemia in patients with type 2 diabetes.

High-volume endurance exercise (END) improves glycaemic control in type 2 diabetes (T2D) but many individuals cite 'lack of time' as a barrier to regular participation. High-intensity interval training (HIT) is a time-efficient method to induce physiological adaptations similar to END, but little is known regarding the effect of HIT in T2D. Using continuous glucose monitoring (CGM), we examined the 24-h blood glucose response to one session of HIT consisting of 10 × 60 s cycling efforts at ~90% maximal heart rate, interspersed with 60 s rest. Seven adults with T2D underwent CGM for 24-h on two occasions under standard dietary conditions: following acute HIT and on a non-exercise control day (CTL). HIT reduced hyperglycaemia measured as proportion of time spent above 10 mmol/l (HIT: 4.5 ± 4.4 vs. CTL: 15.2 ± 12.3%, p = 0.04). Postprandial hyperglycaemia, measured as the sum of post-meal areas under the glucose curve, was also lower after HIT vs. CTL (728 ± 331 vs. 1142 ± 556 mmol/l·9 h, p = 0.01). These findings highlight the potential for HIT to improve glycaemic control in T2D.

Oxidative stress, inflammation, and muscle soreness in an 894-km relay trail run.

We describe the effects of multi-day relay trail running on muscle soreness and damage, and systemic immune, inflammatory, and oxidative responses. 16 male and 4 female athletes ran 894 km in 47 stages over 95 h, with mean (SD) 6.4 (1.0) stages per athlete and 19.0 (1.7) km per stage. We observed post-pre run increases in serum creatine kinase (qualified effect size extremely large, p = 0.002), IL-6 (extremely large, p < 0.001), urinary 8-isoprostane/creatinine (extremely large, p = 0.04), TNF-α (large, p = 0.002), leukocyte count (very large, p < 0.0001) and neutrophil fraction (very large, p < 0.001); and reductions in hemoglobin (moderate, p < 0.001), hematocrit (moderate, p < 0.001), and lymphocyte fraction (trivial, p < 0.001). An increase in ORAC total antioxidant capacity (TAC, small, p = 0.3) and decrease in urinary 8-OHdG/creatinine (small, p = 0.1) were not statistically significant. During the run, muscle soreness was most frequent in the quadriceps. The threshold for muscle pain (pain-pressure algometry) in the vastus lateralis and gastrocnemius was lower post-run (small, p = 0.04 and 0.03). Average running speed was correlated with algometer pain and leukocyte count (large, r = 0.52), and TAC was correlated with IL-6 (very large, r = 0.76) and 8-isoprostane/creatinine (very large, r = -0.72). Multi-day stage-racing increases inflammation, lipid peroxidation, muscle damage and soreness without oxidative DNA damage. High TAC is associated with reduced exercise-induced lipid peroxidation, but is not related to immune response or muscle damage.

Inducing vortices in a Bose-Einstein condensate using holographically produced light beams.

In this paper we demonstrate a technique that can create non-equilibrium vortex configurations with almost arbitrary charge and geometry in a Bose-Einstein condensate. We coherently transfer orbital angular momentum from a holographically generated light beam to a 87Rb condensate using a two-photon stimulated Raman process. Using matter wave interferometry, we verify the phase pattern imprinted onto the atomic wave function for a single vortex and a vortex-antivortex pair. In addition to their phase winding, the vortices created with this technique have an associated hyperfine spin texture.

Inflammation and metabolism gene sets in subcutaneous abdominal adipose tissue are altered 1 hour after exercise in adults with obesity.

Although the health benefits of exercise in adults with obesity are well described, the direct effects of exercise on adipose tissue that may lead to improved metabolic health are poorly understood. The primary aims of this study were to perform an unbiased analysis of the subcutaneous abdominal adipose tissue transcriptomic response to acute exercise in adults with obesity, and to compare the effects of moderate-intensity continuous exercise versus high-intensity interval exercise on this response. Twenty-nine adults with obesity performed a session of either high-intensity interval exercise (HI; 10 × 1 min at 90%HRpeak, 1 min recovery between intervals; n = 14) or moderate-intensity continuous exercise (MI; 45 min at 70%HRpeak; n = 15). Groups were well matched for BMI (HI 33 ± 3 vs. MI 33 ± 4 kg/m2), sex (HI: 9 women vs. MI: 10 women), and age (HI: 32 ± 6 vs. MI: 29 ± 5). Subcutaneous adipose tissue was collected before and 1 h after the session of HI or MI, and samples were processed for RNA sequencing. Gene set enrichment analysis revealed 7 of 21 gene sets enriched postexercise overlapped between HI and MI. Interestingly, both HI and MI upregulated gene sets involved in inflammation (IL6-JAK-STAT3 signaling, allograft rejection, TNFα signaling via NFκB, and inflammatory response; FDR q value < 0.25). Exercise also downregulated adipogenic and oxidative metabolism gene sets in both groups. Overall, these data suggest genes involved in subcutaneous adipose tissue metabolism and inflammation may be an important part of the initial response after a session of exercise.NEW & NOTEWORTHY This study compared the effects of a single session of high-intensity interval exercise versus moderate-intensity continuous exercise on transcriptional changes in subcutaneous abdominal adipose tissue collected from adults with obesity. Our novel findings indicate exercise upregulated inflammation-related gene sets, while it downregulated metabolism-related gene sets - after both high-intensity and moderate-intensity exercise. These data suggest exercise can alter the adipose tissue transcriptome 1 h after exercise in ways that may impact inflammation and metabolism.

Imaging biomarkers of adiposity and sarcopenia as potential predictors for overall survival among patients with endometrial cancer treated with bevacizumab.

OBJECTIVE: To examine associations of body mass index (BMI), subcutaneous fat area (SFA) and density (SFD), visceral fat area (VFA) and density (VFD) and total psoas area (TPA) to outcomes among patients receiving chemotherapy with or without bevacizumab for advanced or recurrent endometrial cancer (EC). METHODS: This was a multi-institutional, retrospective study of patients with EC treated with and without bevacizumab as part of front-line, platinum based chemotherapy. Demographics and clinical characteristics were collected. SFA, VFA, SFD, VFD, and TPA were determined from pre-treatment CT scans using a deep learning algorithm. Data was compared with overall survival (OS) and progression free survival (PFS). RESULTS: Seventy-eight patients were analyzed. The majority were Caucasian (87.2%) with a mean BMI of 34.7 kg/m2. PFS and OS did not differ between patients with BMI, SFA, VFA, SFD, VFD, or TPA ≥ the 50th percentile compared to <50th percentile (p = 0.91, 0.45, 0.71, 0.74, 0.60, and 0.74 respectively) and (p = 0.99, 0.59, 0.14, 0.77, and 0.85 respectively). When adjusting for prognostic factors, elevated VFA trended towards shorter OS (25.1 vs 59.5 months, HR = 1.68 [0.92-3.05]).Patients receiving bevacizumab had similar OS compared to those who did not (37.6 vs 44.5 months, p = 0.409). When stratified by adiposity markers, no subset demonstrated benefit from bevacizumab. CONCLUSION: Obesity has been associated with increased levels of vascular endothelial growth factor (VEGF), the main target for bevacizumab therapy. Imaging measurements of VFA may provide prognostic information for patients with EC but no adiposity marker was predictive of improved response to bevacizumab.

Determination of oxygen extraction ratios by magnetic resonance imaging.

The oxygen extraction ratio (OER) of a tissue describes the interplay between oxygen delivery and consumption and, as such, directly reflects the viability and activity of any organ. It is shown that OER can be quantified using a single magnetic resonance imaging observable, namely the relaxation time T2 of venous blood draining from the tissue. This principle is applied to study local OER changes in the brain on visual stimulation in humans, unambiguously demonstrating a mismatch between changes in blood flow and oxygen metabolism on activation.

Indicator dilution time-activity curves demonstrated by rapid magnetic resonance imaging techniques and paramagnetic contrast agent.

Indicator dilution time-activity curves are demonstrated using magnetic resonance imaging (MRI) as the detector and a paramagnetic contrast agent as the indicator. Manganese chloride was injected into a flow phantom. The nuclear magnetic resonance (MR) intensity was measured downstream. Several flow rates were used. The observed MR intensity decreased as the paramagnetic indicator passed through the imaging plane. The qualitative changes of the MR intensity decrease varied in accordance with indicator dilution theory. The equations for gradient refocused echoes, paramagnetic compound relaxation changes, and the indicator dilution analysis were combined and evaluated. Quantitative analysis demonstrates several problems in its implementation.

Interactions of paramagnetic contrast agents and the spin echo pulse sequence.

The theoretical equations for paramagnetic contrast agent effects and the spin echo pulse sequence are combined to graph magnetic resonance (MR) intensity as a function of paramagnetic contrast agent concentration for various tissues. Analysis of the graphs and equations demonstrate several technical and clinical implications. These include: (1) positive enhancement is most likely to occur with short TEs and TRs; (2) changes in machine parameters TE and TR will change the concentration of agent at which the peak enhancing MR intensity will occur; (3) there is an absolute maximum MR intensity that can be reached with contrast enhancement; (4) the maximum MR intensity reached with enhancement is dependent on the tissues' T2 and, to a lesser degree, T1 relaxation times; (5) certain TE and TR combinations will cause no enhancement; (6) if positive enhancement does occur, it will usually occur only over a limited range of agent concentration; and (7) the tissues' T1 relaxation time but not its T2 time determines whether positive enhancement will occur and the relative amount of enhancement.

Comparison of the rates of adverse drug reactions. Ionic contrast agents, ionic agents combined with steroids, and nonionic agents.

The influence of ionic agents alone, of diatrizoate plus two oral doses of methylprednisolone premedication, and of a nonionic agent (iohexol) upon the frequency and severity of adverse drug reactions (ADRs) was compared in ten hospitals during three separate time periods from 1985 to 1989. Nonionic agents were found to reduce significantly total ADRs; 52 of 8857 patients receiving nonionic agents experienced reactions, versus 263 of 6006 patients for ionics (P less than .0001). The frequency of reactions classed as mild (2.9% for ionic agents versus 0.476 for nonionic agents: P less than .001), moderate (1.2% versus 0.1%; P less than .001), or severe (0.37% versus 0.01%; P less than .001), also favored nonionic agents. Steroid premedication provided some protection, but iohexol was significantly better with respect to mild reactions (2.9% versus 0.4%, P less than .001), moderate reactions (0.9% versus 0.1%, P less than .01), and severe reactions (0.25% versus 0.01%, P less than .01). The contrast medium was the greatest risk factor for adverse reaction (odds ratio 7.3), while prior contrast reaction (odds ratio 6.25), and hay fever (odds ratio 2.3) were found to be significant independent risks. We conclude that nonionic agents are safer for intravenous use than ionic agents given alone or with corticosteroid premedication.

Description and validation of an ECG removal procedure for EMGdi power spectrum analysis.

We describe a cross-correlation procedure for removing contaminating electrocardiogram (ECG) complexes from the diaphragmatic electromyogram (EMGdi). First, the operator selects ECG templates from the EMGdi signal during expiratory intervals. Second, these templates are used to locate ECG complexes occurring during inspiratory EMGdi activity. Third, at the point of maximum correlation between the template and these ECG complexes, the template is adjusted in size and offset to "match" the ECG complex, and adjustments are determined by the linear regression coefficients. Finally, the modified template is subtracted from the EMGdi signal. To evaluate our method, we compared the power spectral density (PSD) obtained from processing EMGdi signals by our method with those obtained from the EMGdi signal in which ECG complexes had been removed by gating. Our results indicate that PSD obtained by these two different methods shows no statistically significant differences with respect to the following features: centroid frequency, median frequency, total power, standard deviation, skewness, and kurtosis.

Magnetic resonance imaging of children without sedation: preparation with simulation.

OBJECTIVE: It was hypothesized that a scanner simulator that replicates the magnetic resonance imaging (MRI) environment could be used to prepare pediatric subjects for successful completion of a diagnostic-quality MRI examination without pharmacological sedation. METHOD: Sixteen healthy children, 6 to 17 years of age, were matched for age and sex with 16 psychotropic medication-naive children with obsessive-compulsive disorder. Distress was measured throughout simulation and scanning procedures using heart rate and a self-report distress scale. Ten healthy children, 6 to 17 years of age, also underwent the same actual MRI scanning procedure but did not undergo the simulation scanning procedure. RESULTS: Significant decreases in heart rate and self-reported distress level were observed in all subjects during the simulator session that were maintained to the end of the actual scanner experience. All subjects successfully completed MRI examinations without chemical restraint. Subjects who were not trained in the simulator had higher heart rates and self-reported distress levels in the actual scanner than did simulation-trained subjects. CONCLUSIONS: Simulation without pharmacological sedation successfully prepared pediatric subjects in this pilot study for high-quality MRI studies. Subject preparation may be an alternative procedure to sedation for routine MRI examination in healthy and anxious children 6 years of age and older.

Potential influences of residencies' health risk policies on their rankings by Ohio applicants.

Residents' health risks constitute an area of increasing concern for hospitals and residencies. This study examined the importance of health risk policies in the context of students' selection of residencies. In 1991, all 836 fourth-year students in six Ohio medical schools were surveyed about their attitudes regarding residencies' policies on drug screening, HIV (human immunodeficiency virus) testing, and smoke-free workplaces. Of 763 surveys able to be delivered, 341 (45%) were returned. Substantial subsets of the students indicated that they would rank lower or not at all a program that required pre-residency drug screening (22%) or HIV testing (31%). Conversely, almost half the students (48%) responded that they would rank a program higher whose institution has a smoke-free policy. A discussion of potential factors affecting these findings is presented, with recommendations for hospitals, residencies, and residency applicants.

Post-ECT increases in MRI regional T2 relaxation times and their relationship to cognitive side effects: a pilot study.

This pilot study examined the hypothesis that magnetic resonance imaging T2 relaxation times of specific brain regions increase after electroconvulsive therapy (ECT) and that these increases are related to the cognitive side effects of ECT. Six depressed patients undergoing unilateral ECT were studied. The results demonstrate significant post-ECT T2 increases in the right and left thalamus, and suggest a correlation between regional T2 increase and anterograde memory impairment following ECT. These findings are consistent with a post-ECT increase in brain water content (perhaps secondary to a breakdown of the blood-brain barrier) and suggest that this process may be related to the memory impairment following ECT.

Functional brain MR imaging based on bolus tracking with a fast T2*-sensitized gradient-echo method.

Dynamic physiological scanning, based on temporary changes in local field homogeneity during the passage of a contrast agent bolus, has been performed hitherto with echo-planar imaging (EPI) or conventional gradient-recalled techniques (FLASH). Here, it is shown that the T2* sensitivity of conventional FLASH techniques can be improved drastically on a conventional whole body instrument by delaying the gradient-echo until the subsequent TR-period without increasing total imaging time. Examples are given for a full k-space matrix (128 x 256) obtained within 2 s with a TE of 25 ms, resulting in images free of artifacts. The method is applied to bolus tracking through the brain of healthy volunteers during visual stimulation and in the dark. An average increase of regional cerebral blood volume (rCBV) in the visual cortex of 10.9% (n = 9, p = .001) was found.

Structured emergency medicine board review and resident in-service examination scores.

OBJECTIVE: To determine whether the institution of a structured board review program is associated with improved in-service examination scores by residents at an emergency medicine (EM) residency program. METHODS: A retrospective, historical control analysis of the association of a board review program and in-service examination scores at one EM residency program was performed. A structured board review consisting of monthly reading assignments in "classic" EM textbooks followed by a graded multiple-choice written examination was instituted in 1987. Percentile scores on the American Board of Emergency Medicine (ABEM) in-service examination before (1985-1986) and after (1987-1994) initiation of the board review process were compared by resident level (EM-1, 2, or 3). RESULTS: The EM-1 mean percentile score before review was 50.7 and rose to 68.9 after the institution of the board review program (p = 0.039). Mean EM-2 scores (66.8 vs 65.4) and EM-3 scores (74.4 vs 67.4) decreased slightly; these decreases were not statistically significant. Due to the large increase in EM-1 scores, the mean scores for the total program increased slightly (63.4 vs 67.4; p = NS). CONCLUSION: In this study, EM-1 in-service scores improved in association with the institution of a structured board review program. This formalized didactic program may increase the knowledge base and test performance of EM-1 residents. A favorable effect on EM-2 and EM-3 resident scores was not seen.

Factors associated with recurrence and voice quality following radiation therapy for T1 and T2 glottic carcinomas.

Evaluation of 63 patients undergoing primary radiation therapy for treatment of T1 and T2 glottic carcinomas was undertaken to evaluate the success of primary treatment and to identify factors which might influence recurrence or voice quality. Twelve patients (19%) recurred following radiation therapy, with ultimate salvage in 11, for a 3-year survival rate of 98%. Voice preservation was achieved in 83%. Continued smoking after radiation therapy was associated with significantly greater risk of recurrence. Stage of tumor and anterior commissure involvement were not associated with increased recurrences. Sixty-seven percent of patients who did not recur had good voice quality after treatment. Vocal fold stripping or excisional biopsy rather than limited biopsy for initial diagnosis, complications of treatment, and continued smoking after treatment were all significantly associated with an increased risk of poorer voice quality after treatment while bilateral vocal fold tumors were associated with risks that approached significance. Voice analysis of five patients revealed that objective changes in voice can be detected after radiation therapy in those with associated risk factors but may be normal in those without these risk factors.