Allowing Physicians to Choose the Value of Compensation for Participation in a Web-Based Survey: Randomized Controlled Trial.

PubMed

Turnbull, Alison E; O'Connor, Cristi L; Lau, Bryan; Halpern, Scott D; Needham, Dale M

2015-07-29

Survey response rates among physicians are declining, and determining an appropriate level of compensation to motivate participation poses a major challenge. To estimate the effect of permitting intensive care physicians to select their preferred level of compensation for completing a short Web-based survey on physician (1) response rate, (2) survey completion rate, (3) time to response, and (4) time spent completing the survey. A total of 1850 US intensivists from an existing database were randomized to receive a survey invitation email with or without an Amazon.com incentive available to the first 100 respondents. The incentive could be instantly redeemed for an amount chosen by the respondent, up to a maximum of US $50. The overall response rate was 35.90% (630/1755). Among the 35.4% (111/314) of eligible participants choosing the incentive, 80.2% (89/111) selected the maximum value. Among intensivists offered an incentive, the response was 6.0% higher (95% CI 1.5-10.5, P=.01), survey completion was marginally greater (807/859, 94.0% vs 892/991, 90.0%; P=.06), and the median number of days to survey response was shorter (0.8, interquartile range [IQR] 0.2-14.4 vs 6.6, IQR 0.3-22.3; P=.001), with no difference in time spent completing the survey. Permitting intensive care physicians to determine compensation level for completing a short Web-based survey modestly increased response rate and substantially decreased response time without decreasing the time spent on survey completion.

Allowing Physicians to Choose the Value of Compensation for Participation in a Web-Based Survey: Randomized Controlled Trial

PubMed Central

O'Connor, Cristi L; Lau, Bryan; Halpern, Scott D; Needham, Dale M

2015-01-01

Background Survey response rates among physicians are declining, and determining an appropriate level of compensation to motivate participation poses a major challenge. Objective To estimate the effect of permitting intensive care physicians to select their preferred level of compensation for completing a short Web-based survey on physician (1) response rate, (2) survey completion rate, (3) time to response, and (4) time spent completing the survey. Methods A total of 1850 US intensivists from an existing database were randomized to receive a survey invitation email with or without an Amazon.com incentive available to the first 100 respondents. The incentive could be instantly redeemed for an amount chosen by the respondent, up to a maximum of US $50. Results The overall response rate was 35.90% (630/1755). Among the 35.4% (111/314) of eligible participants choosing the incentive, 80.2% (89/111) selected the maximum value. Among intensivists offered an incentive, the response was 6.0% higher (95% CI 1.5-10.5, P=.01), survey completion was marginally greater (807/859, 94.0% vs 892/991, 90.0%; P=.06), and the median number of days to survey response was shorter (0.8, interquartile range [IQR] 0.2-14.4 vs 6.6, IQR 0.3-22.3; P=.001), with no difference in time spent completing the survey. Conclusions Permitting intensive care physicians to determine compensation level for completing a short Web-based survey modestly increased response rate and substantially decreased response time without decreasing the time spent on survey completion. PMID:26223821

Self-Paced Exercise, Affective Response, and Exercise Adherence: A Preliminary Investigation Using Ecological Momentary Assessment.

PubMed

Williams, David M; Dunsiger, Shira; Emerson, Jessica A; Gwaltney, Chad J; Monti, Peter M; Miranda, Robert

2016-06-01

Affective response to exercise may mediate the effects of self-paced exercise on exercise adherence. Fiftynine low-active (exercise <60 min/week), overweight (body mass index: 25.0-39.9) adults (ages 18-65) were randomly assigned to self-paced (but not to exceed 76% maximum heart rate) or prescribed moderate intensity exercise (64-76% maximum heart rate) in the context of otherwise identical 6-month print-based exercise promotion programs. Frequency and duration of exercise sessions and affective responses (good/bad) to exercise were assessed via ecological momentary assessment throughout the 6-month program. A regression-based mediation model was used to estimate (a) effects of experimental condition on affective response to exercise (path a = 0.20, SE = 0.28, f 2 = 0.02); (b) effects of affective response on duration/latency of the next exercise session (path b = 0.47, SE = 0.25, f 2 = 0.04); and (c) indirect effects of experimental condition on exercise outcomes via affective response (path ab = 0.11, SE = 0.06, f 2 = 0.10). Results provide modest preliminary support for a mediational pathway linking self-paced exercise, affective response, and exercise adherence.

Medical students' subjective ratings of stress levels and awareness of student support services about mental health.

PubMed

Walter, Garry; Soh, Nerissa Li-Wey; Norgren Jaconelli, Sanna; Lampe, Lisa; Malhi, Gin S; Hunt, Glenn

2013-06-01

To descriptively assess medical students' concerns for their mental and emotional state, perceived need to conceal mental problems, perceived level of support at university, knowledge and use of student support services, and experience of stresses of daily life. From March to September 2011, medical students at an Australian university were invited to complete an anonymous online survey. 475 responses were received. Students rated study and examinations (48.9%), financial concerns (38.1%), isolation (19.4%) and relationship concerns (19.2%) as very or extremely stressful issues. Knowledge of available support services was high, with 90.8% indicating they were aware of the university's medical centre. Treatment rates were modest (31.7%). Students' concerns about their mental state were generally low, but one in five strongly felt they needed to conceal their emotional problems. Despite widespread awareness of appropriate support services, a large proportion of students felt they needed to conceal mental and emotional problems. Overall treatment rates for students who were greatly concerned about their mental and emotional state appeared modest, and, although comparable with those of similarly aged community populations, may reflect undertreatment. It would be appropriate for universities to address stressors identified by students. Strategies for encouraging distressed students to obtain appropriate assessment and treatment should also be explored. Those students who do seek healthcare are most likely to see a primary care physician, suggesting an important screening role for these health professionals.

Recovery and identification of human remains in post-conflict environments: A comparative study of the humanitarian forensic programs in Cyprus and Kosovo.

PubMed

Mikellide, Maria

2017-10-01

This study follows the humanitarian forensic programs in Cyprus and Kosovo over a ten-year period with an emphasis on the role of local capacity building. It begins by providing an in-depth historical account of forensic activities, followed by a comparison of the rate of excavations, exhumations and identifications. Through this analysis, a repeated pattern emerges whereby forensic activities in Kosovo start with a surge in values, which drop drastically in the first few years of operations, followed by a steadily declining productivity curve. By contrast, in Cyprus, activities begin modestly, with lower values allowing for some modest growth. Close observation of the two programs provides indications as to the factors that may influence the development of forensic programs as well as the elements that need to be set in place to create an environment conducive to greater sustainability through local ownership and responsibility. Copyright © 2017 Elsevier B.V. All rights reserved.

Omega-3 fatty acid monotherapy for pediatric bipolar disorder: a prospective open-label trial.

PubMed

Wozniak, Janet; Biederman, Joseph; Mick, Eric; Waxmonsky, James; Hantsoo, Liisa; Best, Catherine; Cluette-Brown, Joanne E; Laposata, Michael

2007-01-01

To test the effectiveness and safety of omega-3 fatty acids (Omegabrite(R) brand) in the treatment of pediatric bipolar disorder (BPD). Subjects (N=20) were outpatients of both sexes, 6 to 17 years of age, with a DSM-IV diagnosis of BPD and Young Mania Rating Scale (YMRS) score of >15 treated over an 8-week period in open-label trial with omega-3 fatty acids 1290 mg-4300 mg combined EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Subjects experienced a statistically significant but modest 8.9+/-2.9 point reduction in the YMRS scores (baseline YMRS=28.9+/-10.1; endpoint YMRS=19.1+/-2.6, p<0.001). Adverse events were few and mild. Red blood cell membrane levels of EPA and DHA increased in treated subjects. As only 35% of these subjects had a response by the usual accepted criteria of >50% decrease on the YMRS, omega-3 fatty acids treatment was associated with a very modest improvement in manic symptoms in children with BPD.

Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential

PubMed Central

Reissig, Chad J.; Harrison, Joseph A.; Carter, Lawrence P.; Griffiths, Roland R.

2014-01-01

Rationale Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects. Objectives This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route. Methods Placebo, inhaled alprazolam (0.5, 1, 2 mg), and oral alprazolam (1, 2, 4 mg) were administered under double-blind, double-dummy conditions using a cross-over design in 14 healthy participants with histories of drug abuse. Participant and observer ratings, and behavioral and cognitive performance measures were assessed repeatedly during 9 hour sessions. Results Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 minutes after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., “drug liking”) were similar across the two routes. On other measures (e.g., sedation and performance) the routes were equipotent. Conclusions The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low. PMID:25199955

Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential.

PubMed

Reissig, Chad J; Harrison, Joseph A; Carter, Lawrence P; Griffiths, Roland R

2015-03-01

Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects. This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route. Placebo, inhaled alprazolam (0.5, 1, and 2 mg), and oral alprazolam (1, 2, and 4 mg) were administered under double-blind, double-dummy conditions using a crossover design in 14 healthy participants with histories of drug abuse. Participant and observer ratings and behavioral and cognitive performance measures were assessed repeatedly during 9-h sessions. Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer-lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 min after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose-response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., "drug liking") were similar across the two routes. On other measures (e.g., sedation and performance), the routes were equipotent. The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low.

Hookworm Infection among School Age Children in Kintampo North Municipality, Ghana: Nutritional Risk Factors and Response to Albendazole Treatment

PubMed Central

Humphries, Debbie; Simms, Benjamin T.; Davey, Dylan; Otchere, Joseph; Quagraine, Josephine; Terryah, Shawn; Newton, Samuel; Berg, Elyssa; Harrison, Lisa M.; Boakye, Daniel; Wilson, Michael; Cappello, Michael

2013-01-01

Children (n = 812) 6–11 years of age attending 16 schools in the Kintampo North Municipality of Ghana were screened for participation in a study on hookworm infection, nutrition, and response to albendazole. The prevalence of Necator americanus hookworm infection (n = 286) was 39.1%, and significant predictors of infection included age, malaria parasitemia, lack of health care, school area, levels of antibodies against hookworm, and low consumption of animal foods. The cure rate after a single dose (400 mg) albendazole was 43%, and the mean fecal egg count reduction rate was 87.3%. Data for an in vitro egg hatch assay showed a trend toward reduced albendazole susceptibility in post-treatment hookworm isolates (P = 0.06). In summary, hookworm infection is prevalent among school age children in the Kintampo North Municipality and animal food intake inversely correlates with infection status. Modest cure rates and fecal egg count reduction rates reinforce the need for further investigation of potential benzimidazole resistance in Ghana. PMID:23836564

Updated estimates of the climate response to emissions and their policy implications (Invited)

NASA Astrophysics Data System (ADS)

Allen, M. R.; Otto, A.; Stocker, T. F.; Frame, D. J.

2013-12-01

We review the implications of observations of the global energy budget over recent decades, particularly the 'warming hiatus' period over the 2000s, for key climate system properties including equilibrium climate sensitivity (ECS), transient climate response (TCR) and transient climate response to cumulative carbon emissions (TCRE). We show how estimates of the upper bound of ECS remain, as ever, sensitive to prior assumptions and also how ECS, even if it were better constrained, would provide much less information about the social cost of carbon than TCR or TCRE. Hence the excitement over recent, apparently conflicting, estimates of ECS, is almost entirely misplaced. Of greater potential policy significance is the fact that recent observations imply a modest (of order 25%) downward revision in the upper bound and most likely values of TCR and TCRE, as compared to some, but not all, of the estimates published in the mid-2000s. This is partly due to the recent reduced rate of warming, and partly due to revisions in estimates of total anthropogenic forcing to date. Both of these developments may turn out to be short-lived, so the policy implications of this modest revision in TCR/TCRE should not be over-sold: nevertheless, it is interesting to explore what they are. The implications for climate change adaptation of a 25% downward revision in TCR and TCRE are minimal, being overshadowed by uncertainty due to internal variability and non-CO2 climate forcings over typical timescales for adaptation planning. We introduce a simple framework for assessing the implications for mitigation in terms of timing of peak emissions average rates of emission reduction required to avoid specific levels of peak warming. We show that, as long as emissions continue to increase approximately exponentially, the implications for mitigation of any revisions in the climate response are surprisingly small.

Incentive and Reminder Strategies to Improve Response Rate for Internet-Based Physician Surveys: A Randomized Experiment

PubMed Central

Wittich, Christopher M; Daniels, Wendlyn L; West, Colin P; Harris, Ann M; Beebe, Timothy J

2016-01-01

Background Most research on how to enhance response rates in physician surveys has been done using paper surveys. Uncertainties remain regarding how to enhance response rates in Internet-based surveys. Objective To evaluate the impact of a low-cost nonmonetary incentive and paper mail reminders (formal letter and postcard) on response rates in Internet-based physician surveys. Methods We executed a factorial-design randomized experiment while conducting a nationally representative Internet-based physician survey. We invited 3966 physicians (randomly selected from a commercial database of all licensed US physicians) via email to complete an Internet-based survey. We used 2 randomly assigned email messages: one message offered a book upon survey completion, whereas the other did not mention the book but was otherwise identical. All nonrespondents received several email reminders. Some physicians were further assigned at random to receive 1 reminder via paper mail (either a postcard or a letter) or no paper reminder. The primary outcome of this study was the survey response rate. Results Of the 3966 physicians who were invited, 451 (11.4%) responded to at least one survey question and 336 (8.5%) completed the entire survey. Of those who were offered a book, 345/2973 (11.6%) responded compared with 106/993 (10.7%) who were not offered a book (odds ratio 1.10, 95% CI 0.87-1.38, P=.42). Regarding the paper mail reminder, 168/1572 (10.7%) letter recipients, 148/1561 (9.5%) postcard recipients, and 69/767 (9.0%) email-only recipients responded (P=.35). The response rate for those receiving letters or postcards was similar (odds ratio 1.14, 95% CI 0.91-1.44, P=.26). Conclusions Offering a modest nonmonetary incentive and sending a paper reminder did not improve survey response rate. Further research on how to enhance response rates in Internet-based physician surveys is needed. PMID:27637296

Incentive and Reminder Strategies to Improve Response Rate for Internet-Based Physician Surveys: A Randomized Experiment.

PubMed

Cook, David A; Wittich, Christopher M; Daniels, Wendlyn L; West, Colin P; Harris, Ann M; Beebe, Timothy J

2016-09-16

Most research on how to enhance response rates in physician surveys has been done using paper surveys. Uncertainties remain regarding how to enhance response rates in Internet-based surveys. To evaluate the impact of a low-cost nonmonetary incentive and paper mail reminders (formal letter and postcard) on response rates in Internet-based physician surveys. We executed a factorial-design randomized experiment while conducting a nationally representative Internet-based physician survey. We invited 3966 physicians (randomly selected from a commercial database of all licensed US physicians) via email to complete an Internet-based survey. We used 2 randomly assigned email messages: one message offered a book upon survey completion, whereas the other did not mention the book but was otherwise identical. All nonrespondents received several email reminders. Some physicians were further assigned at random to receive 1 reminder via paper mail (either a postcard or a letter) or no paper reminder. The primary outcome of this study was the survey response rate. Of the 3966 physicians who were invited, 451 (11.4%) responded to at least one survey question and 336 (8.5%) completed the entire survey. Of those who were offered a book, 345/2973 (11.6%) responded compared with 106/993 (10.7%) who were not offered a book (odds ratio 1.10, 95% CI 0.87-1.38, P=.42). Regarding the paper mail reminder, 168/1572 (10.7%) letter recipients, 148/1561 (9.5%) postcard recipients, and 69/767 (9.0%) email-only recipients responded (P=.35). The response rate for those receiving letters or postcards was similar (odds ratio 1.14, 95% CI 0.91-1.44, P=.26). Offering a modest nonmonetary incentive and sending a paper reminder did not improve survey response rate. Further research on how to enhance response rates in Internet-based physician surveys is needed.

Case-mix adjustment of consumer reports about managed behavioral health care and health plans.

PubMed

Eselius, Laura L; Cleary, Paul D; Zaslavsky, Alan M; Huskamp, Haiden A; Busch, Susan H

2008-12-01

To develop a model for adjusting patients' reports of behavioral health care experiences on the Experience of Care and Health Outcomes (ECHO) survey to allow for fair comparisons across health plans. Survey responses from 4,068 individuals enrolled in 21 managed behavioral health plans who received behavioral health care within the previous year (response rate = 48 percent). Potential case-mix adjustors were evaluated by combining information about their predictive power and the amount of within- and between-plan variability. Changes in plan scores and rankings due to case-mix adjustment were quantified. The final case-mix adjustment model included self-reported mental health status, self-reported general health status, alcohol/drug treatment, age, education, and race/ethnicity. The impact of adjustment on plan report scores was modest, but large enough to change some plan rankings. Adjusting plan report scores on the ECHO survey for differences in patient characteristics had modest effects, but still may be important to maintain the credibility of patient reports as a quality metric. Differences between those with self-reported fair/poor health compared with those in excellent/very good health varied by plan, suggesting quality differences associated with health status and underscoring the importance of collecting quality information.

Strategic communication related to academic performance: Evidence from China.

PubMed

Zhao, Li; Chen, Lulu; He, Luwei; Heyman, Gail D

2017-09-01

We examined a range of forms of strategic communication relevant to academic performance among 151 seventh- and eleventh-grade adolescents in China. Participants were asked to rate the frequency of their engagement of strategic communication and to evaluate the possible motives for each strategy. The most commonly adopted strategy was to give a vague response about one's own performance, and the predominant motives for strategic communication were the desires to outcompete others, to be prosocial, and to be modest. Males were more likely than females to focus on gaining social approval, and eleventh graders were more likely than seventh graders to focus on being prosocial and modest when engaging in strategic communication. These findings provide insight into the development of strategic communication beyond Western culture. Statement of contribution What is already known on this subject? Adolescents in the West often hide their effort to appear more competent or to gain social acceptance. Little is known about other communication strategies related to academic performance. Little is known about the development of these strategies in non-Western samples. What does this study add? We show that in China, as in Western cultures, children often engage in strategic communication. We demonstrate links between different forms of strategic communication and specific motives. We demonstrate that strategic communication can be motivated by outcompeting others, by being prosocial, and by being modest. © 2017 The British Psychological Society.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolfe, R.R.; Peters, E.J.; Klein, S.

In this study the rate of lipolysis (fatty acid and glycerol release into blood) has been quantified in both normal weight and obese volunteers after both 15 and 87 h of fasting. In each study, the basal rate and subsequent response to epinephrine infusion were determined. The rate of appearance (R/sub a/) of free fatty acids (FFA) and glycerol were quantified by infusion of (1- TC)palmitate and D-5-glycerol, respectively. Substrate flux rates per unit of body fat mass and lean body mass were calculated from total body water measurements using H2 YO dilution. In normal volunteers, the basal R/sub a/more » FFA and R/sub a/ glycerol rose markedly with 87 h of fasting, whereas the increases were more modest in the obese subjects. However, the rate of mobilization of fat, in relation to the lean body mass, was higher in the obese subjects than in the normal subjects after 15 h of fasting, and the values were similar in both groups after 87 h of fasting. There was an increased lipolytic response to epinephrine after fasting in both groups. This increased sensitivity may have resulted from the enhancement of fatty acid-triglyceride substrate cycling that occurred after fasting.« less

Optical measurement of high-temperature melt flow rate.

PubMed

Bizjan, Benjamin; Širok, Brane; Chen, Jinpeng

2018-05-20

This paper presents an optical method and system for contactless measurement of the mass flow rate of melts by digital cameras. The proposed method is based on reconstruction of melt stream geometry and flow velocity calculation by cross correlation, and is very cost-effective due its modest hardware requirements. Using a laboratory test rig with a small inductive melting pot and reference mass flow rate measurement by weighing, the proposed method was demonstrated to have an excellent dynamic response (0.1 s order of magnitude) while producing deviations from the reference of about 5% in the steady-state flow regime. Similar results were obtained in an industrial stone wool production line for two repeated measurements. Our method was tested in a wide range of melt flow rates (0.05-1.2 kg/s) and did not require very fast cameras (120 frames per second would be sufficient for most industrial applications).

Comparison of Text Messages Versus E-mail When Communicating and Querying With Mothers About Safe Infant Sleep.

PubMed

Moon, Rachel Y; Hauck, Fern R; Kellams, Ann L; Colson, Eve R; Geller, Nicole L; Heeren, Timothy C; Kerr, Stephen M; Corwin, Michael J

To assess how mothers' choice of e-mail or text messages (SMS) to receive safe sleep communications is associated with educational video viewing and responses to care practice queries. Seven hundred ninety-two new mothers received safe sleep-related communications for 60 days after newborn hospital discharge as part of a trial of health education interventions on infant care practices. Mothers chose e-mail or SMS for study communications and were sent 22 short safe sleep videos and 41 queries regarding infant care practices. Study communications via e-mail were elected by 55.7% of participants. The SMS group had a modestly higher overall view rate of videos (59.1% vs 54.4%; adjusted odds ratio [aOR], 1.39; 95% confidence interval [CI], 1.07-1.81) and a substantially higher response rate to queries (70.0% vs 45.2%; aOR, 3.48; 95% CI, 2.74-4.43). Participants more commonly opted to receive infant care practice videos and queries via e-mail. SMS was associated with higher viewing and response rates, especially for query responses. These results highlight the importance of understanding how specific modalities of communication might vary in reach. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer

PubMed Central

Santa-Maria, Cesar August; Kato, Taigo; Park, Jae-Hyun; Kiyotani, Kazuma; Rademaker, Alfred; Shah, Ami N.; Gross, Leeaht; Blanco, Luis Z.; Jain, Sarika; Flaum, Lisa; Tellez, Claudia; Stein, Regina; Uthe, Regina; Gradishar, William J.; Cristofanilli, Massimo; Nakamura, Yusuke; Giles, Francis J.

2018-01-01

Immune checkpoint inhibitors produce modest responses in metastatic breast cancer, however, combination approaches may improve responses. A single arm pilot study was designed to determine the overall response rate (ORR) of durvalumab and tremelimumab, and evaluate immunogenomic dynamics in metastatic endocrine receptor (ER) positive or triple negative breast cancer (TNBC). Simon two-stage design indicated at least four responses from the first 18 patients were needed to proceed with the second stage. T-cell receptor (TCR) sequencing and immune-gene expression profiling were conducted at baseline and two months, whole exome sequencing was conducted at baseline. Eighteen evaluable patients were accrued (11 ER-positive; seven TNBC). Only three patients had a response (ORR = 17%), thus the study did not proceed to the second stage. Responses were only observed in patients with TNBC (ORR = 43%). Responders versus non-responders had upregulation of CD8, granzyme A, and perforin 1 gene expression, and higher mutational and neoantigen burden. Patients with TNBC had an oligoclonal shift of the most abundant TCR-beta clonotypes compared to those with ER-positive disease, p = 0.004. We conclude responses are low in unselected metastatic breast cancer, however, higher rates of clinical benefit were observed in TNBC. Immunogenomic dynamics may help identify phenotypes most likely to respond to immunotherapy. PMID:29721177

Some growth factors stimulate cultured adult rabbit ventricular myocyte hypertrophy in the absence of mechanical loading

NASA Technical Reports Server (NTRS)

Decker, R. S.; Cook, M. G.; Behnke-Barclay, M.; Decker, M. L.

1995-01-01

Cultured adult rabbit cardiac myocytes treated with recombinant growth factors display enhanced rates of protein accumulation (ie, growth) in response to insulin and insulin-like growth factors (IGFs), but epidermal growth factor, acidic or basic fibroblast growth factor, and platelet-derived growth factor failed to increase contractile protein synthesis or growth of the heart cells. Insulin and IGF-1 increased growth rates by stimulating anabolic while simultaneously inhibiting catabolic pathways, whereas IGF-2 elevated growth modestly by apparently inhibiting lysosomal proteolysis. Neutralizing antibodies directed against either IGF-1 or IGF-2 or IGF binding protein 3 blocked protein accumulation. A monoclonal antibody directed against the IGF-1 receptor also inhibited changes in protein turnover provoked by recombinant human IGF-1 but not IGF-2. Of the other growth factors tested, only transforming growth factor-beta 1 increased the fractional rate of myosin heavy chain (MHC) synthesis, with beta-MHC synthesis being elevated and alpha-MHC synthesis being suppressed. However, the other growth factors were able to modestly stimulate the rate of DNA synthesis in this preparation. Bromodeoxyuridine labeling revealed that these growth factors increased DNA synthesis in myocytes and nonmyocytes alike, but the heart cells displayed neither karyokinesis or cytokinesis. In contrast, cocultures of cardiac myocytes and nonmyocytes and nonmyocyte-conditioned culture medium failed to enhance the rate of cardiac MHC synthesis or its accumulation, implying that quiescent heart cells do not respond to "conditioning" by cardiac nonmyocytes. These findings demonstrated that insulin and the IGFs promote passively loaded cultured adult rabbit heart cells to hypertrophy but suggest that other growth factors tested may be limited in this regard.

Of nannies and nudges: the current state of U.S. obesity policymaking.

PubMed

Kersh, R

2015-08-01

In the sprawling American political debates over obesity, which date back a decade and a half, 'nanny state' has been a rhetorical cudgel used to oppose those seeking even modest state action to address rising obesity rates. This essay explores obesity policy through the prism of state involvement, focusing on four possible types of response to what virtually all those involved--physicians and nutritional scientists, public-health advocacy groups, even food industry executives--agree is a serious threat to individual and collective health. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

INDIVIDUAL DIFFERENCES IN IMPULSIVE CHOICE AND TIMING IN RATS

PubMed Central

Galtress, Tiffany; Garcia, Ana; Kirkpatrick, Kimberly

2012-01-01

Individual differences in impulsive choice behavior have been linked to a variety of behavioral problems including substance abuse, smoking, gambling, and poor financial decision-making. Given the potential importance of individual differences in impulsive choice as a predictor of behavioral problems, the present study sought to measure the extent of individual differences in a normal sample of hooded Lister rats. Three experiments utilized variations of a delay discounting task to measure the degree of variation in impulsive choice behavior across individual rats. The individual differences accounted for 22–55% of the variance in choice behavior across the three experiments. In Experiments 2 and 3, the individual differences were still apparent when behavior was measured across multiple choice points. Large individual differences in the rate of responding, and modest individual differences in timing of responding were also observed during occasional peak trials. The individual differences in timing and rate, however, did not correlate consistently with individual differences in choice behavior. This suggests that a variety of factors may affect choice behavior, response rate, and response timing. PMID:22851792

Impact of personal economic environment and personality factors on individual financial decision making.

PubMed

Prinz, Susanne; Gründer, Gerhard; Hilgers, Ralf D; Holtemöller, Oliver; Vernaleken, Ingo

2014-01-01

This study on healthy young male students aimed to enlighten the associations between an individual's financial decision making and surrogate makers for environmental factors covering long-term financial socialization, the current financial security/responsibility, and the personal affinity to financial affairs as represented by parental income, funding situation, and field of study. A group of 150 male young healthy students underwent two versions of the Holt and Laury (2002) lottery paradigm (matrix and random sequential version). Their financial decision was mainly driven by the factor "source of funding": students with strict performance control (grants, scholarships) had much higher rates of relative risk aversion (RRA) than subjects with support from family (ΔRRA = 0.22; p = 0.018). Personality scores only modestly affected the outcome. In an ANOVA, however, also the intelligence quotient significantly and relevantly contributed to the explanation of variance; the effects of parental income and the personality factors "agreeableness" and "openness" showed moderate to modest - but significant - effects. These findings suggest that environmental factors more than personality factors affect risk aversion.

Impact of personal economic environment and personality factors on individual financial decision making

PubMed Central

Prinz, Susanne; Gründer, Gerhard; Hilgers, Ralf D.; Holtemöller, Oliver; Vernaleken, Ingo

2014-01-01

This study on healthy young male students aimed to enlighten the associations between an individual’s financial decision making and surrogate makers for environmental factors covering long-term financial socialization, the current financial security/responsibility, and the personal affinity to financial affairs as represented by parental income, funding situation, and field of study. A group of 150 male young healthy students underwent two versions of the Holt and Laury (2002) lottery paradigm (matrix and random sequential version). Their financial decision was mainly driven by the factor “source of funding”: students with strict performance control (grants, scholarships) had much higher rates of relative risk aversion (RRA) than subjects with support from family (ΔRRA = 0.22; p = 0.018). Personality scores only modestly affected the outcome. In an ANOVA, however, also the intelligence quotient significantly and relevantly contributed to the explanation of variance; the effects of parental income and the personality factors “agreeableness” and “openness” showed moderate to modest – but significant – effects. These findings suggest that environmental factors more than personality factors affect risk aversion. PMID:24624100

The safety and efficacy of single-agent pemetrexed in platinum-resistant advanced urothelial carcinoma: a large single-institution experience.

PubMed

Bambury, Richard M; Benjamin, David J; Chaim, Joshua L; Zabor, Emily C; Sullivan, John; Garcia-Grossman, Ilana R; Regazzi, Ashley M; Ostrovnaya, Irina; Apollo, Aryln; Xiao, Han; Voss, Martin H; Iyer, Gopa; Bajorin, Dean F; Rosenberg, Jonathan E

2015-05-01

Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance. Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded. One hundred and twenty-nine patients were treated with pemetrexed. The objective response rate was 5% (95% confidence interval: 1%-9%), and the median duration of response was 8 months. Median progression-free survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no significant difference in response rate by age, Eastern Cooperative Oncology Group (ECOG) performance status, or number of prior therapies. On multivariable analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR (p < .01) had independent prognostic significance for overall survival. This 129-patient series is the largest reported data set describing pemetrexed use in advanced UC. Activity was modest, although discovery of molecular biomarkers predictive of response would be valuable to identify the small subset of patients who do gain significant benefit. Overall, the data highlight the urgent need to develop novel therapies for these patients. ©AlphaMed Press.

The Safety and Efficacy of Single-Agent Pemetrexed in Platinum-Resistant Advanced Urothelial Carcinoma: A Large Single-Institution Experience

PubMed Central

Benjamin, David J.; Chaim, Joshua L.; Zabor, Emily C.; Sullivan, John; Garcia-Grossman, Ilana R.; Regazzi, Ashley M.; Ostrovnaya, Irina; Apollo, Aryln; Xiao, Han; Voss, Martin H.; Iyer, Gopa; Bajorin, Dean F.; Rosenberg, Jonathan E.

2015-01-01

Background. Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance. Patients and Methods. Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded. Results. One hundred and twenty-nine patients were treated with pemetrexed. The objective response rate was 5% (95% confidence interval: 1%–9%), and the median duration of response was 8 months. Median progression-free survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no significant difference in response rate by age, Eastern Cooperative Oncology Group (ECOG) performance status, or number of prior therapies. On multivariable analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR (p < .01) had independent prognostic significance for overall survival. Conclusion. This 129-patient series is the largest reported data set describing pemetrexed use in advanced UC. Activity was modest, although discovery of molecular biomarkers predictive of response would be valuable to identify the small subset of patients who do gain significant benefit. Overall, the data highlight the urgent need to develop novel therapies for these patients. PMID:25845990

Illusions and Ignorance about the Family-Responsive Workplace.

ERIC Educational Resources Information Center

Kingston, Paul W.

1990-01-01

Contends American businesses have made modest headway in instituting family-responsive practices and that it is illusory to expect that market solutions will deliver good or equitable family policy in foreseeable future. Predicts uneven realization of the responsive workplace. (Author/ABL)

Chronic central ghrelin infusion reduces blood pressure and heart rate despite increasing appetite and promoting weight gain in normotensive and hypertensive rats.

PubMed

Freeman, John N; do Carmo, Jussara M; Adi, Ahmad H; da Silva, Alexandre A

2013-04-01

Acute studies showed that ghrelin acts on the central nervous system (CNS) to reduce blood pressure (BP), heart rate (HR) and sympathetic activity. However, the long-term CNS cardiovascular actions of ghrelin are still unclear. We tested whether chronic intracerebroventricular (ICV) infusion of ghrelin causes sustained reductions in BP, HR and whether it alters baroreceptor sensitivity (BRS) and autonomic input to the heart. A cannula was placed in the lateral ventricle of male Sprague-Dawley (SD) rats for ICV infusions via osmotic minipump (0.5 μl/h). BP and HR were measured 24-h/day by telemetry. After 5 days of control measurements, ghrelin (0.21 nmol/h) or saline vehicle were infused ICV for 10 days followed by a 5-day post-treatment period. Chronic ICV ghrelin infusion increased food intake (22±3 to 26±1 g/day) leading to ~50 g body weight gain. BP fell slightly during ghrelin infusion while HR decreased by ~26 bpm. In control animals BP and HR increased modestly. ICV Ghrelin infusion caused a 50% reduction in sympathetic tone to the heart but did not alter BRS. We also tested if the depressor responses to ICV ghrelin infusion were enhanced in spontaneously hypertensive rats (SHR) due to their high basal sympathetic tone. However, we observed similar BP and HR responses compared to normotensive rats. These results indicate that ghrelin, acting via direct actions on the CNS, has a sustained effect to lower HR and a modest impact to reduce BP in normotensive and hypertensive animals despite increasing appetite and body weight. Copyright © 2013 Elsevier Inc. All rights reserved.

Phase II study of neoadjuvant treatment with doxorubicin, docetaxel, and capecitabine (ATX) in locally advanced or inflammatory breast cancer.

PubMed

Manga, Gumersindo Pérez; Shahi, Parham Khosravi; Ureña, Miguel Méndez; Pereira, Rosa Quiben; Plaza, María Isabel Palomero; Peron, Yann Izarzugaza; Val, Ricardo González Del; Carrión, Joaquín Belón; Cañón, Esperanza Pérez; Alfonso, Pilar García

2010-07-01

Pathologic complete response (pCR) after preoperative systemic chemotherapy (PSCh) is associated with better outcome in locally advanced breast cancer (LABC). PSCh included: doxorubicin (A) 50 mg/m(2) i.v. on day 1; docetaxel (T) 30 mg/m(2) i.v. on days 1, 8 and 15; and capecitabine (X) 1,500 mg/m(2)/day p.o. on days 1-14, in a 4-week course repeated for up to four cycles (ATX), followed by surgery. The primary end point of this study was to evaluate the pCR rate. Secondary endpoints included clinical response rate, disease-free survival (DFS), overall survival (OS), and the toxicity profile. A total of 60 patients were included in the analysis. Median age was 49 years, and 63.3% of patients were hormone receptor positive. The median number of cycles of PSCh was four (95% CI: 3-4). Five patients (8.3%) achieved pCR in both breast and nodes, and 16.7% reached pCR only in nodes. The clinical response rate was 77% (27% complete response), but only 18% of the patients underwent conservative surgery. With a median follow-up of 20 months, 3-year DFS and OS were 76 and 90%, respectively. Grade III/IV toxicity included neutropenia (74%), febrile neutropenia (9%), mucositis (12%), and diarrhea (12%). ATX every 28 days for four cycles is associated with a modest activity (low pCR rate) in the neoadjuvant setting of LABC.

The Impact of Single-Container Malt Liquor Sales Restrictions on Urban Crime.

PubMed

McKee, Patricia; Erickson, Darin J; Toomey, Traci; Nelson, Toben; Less, Elyse Levine; Joshi, Spruha; Jones-Webb, Rhonda

2017-04-01

Many US cities have adopted legal restrictions on high-alcohol malt liquor sales in response to reports of crime and nuisance behaviors around retail alcohol outlets. We assessed whether these policies are effective in reducing crime in urban areas. We used a rigorous interrupted time-series design with comparison groups to examine monthly crime rates in areas surrounding alcohol outlets in the 3 years before and after adoption of malt liquor sales restrictions in two US cities. Crime rates in matched comparison areas not subject to restrictions served as covariates. Novel methods for matching target and comparison areas using virtual neighborhood audits conducted in Google Street View are described. In Minneapolis, Minnesota, sales of single containers of 16 oz or less were prohibited in individual liquor stores (n = 6). In Washington, D.C., the sale of single containers of any size were prohibited in all retail alcohol outlets within full or partial wards (n = 6). Policy adoption was associated with modest reductions in crime, particularly assaults and vandalism, in both cities. All significant outcomes were in the hypothesized direction. Our results provide evidence that retail malt liquor sales restrictions, even relatively weak ones, can have modest effects on a range of crimes. Policy success may depend on community support and concurrent restrictions on malt liquor substitutes.

A group sequential adaptive treatment assignment design for proof of concept and dose selection in headache trials.

PubMed

Hall, David B; Meier, Ulrich; Diener, Hans-Cristoph

2005-06-01

The trial objective was to test whether a new mechanism of action would effectively treat migraine headaches and to select a dose range for further investigation. The motivation for a group sequential, adaptive, placebo-controlled trial design was (1) limited information about where across the range of seven doses to focus attention, (2) a need to limit sample size for a complicated inpatient treatment and (3) a desire to reduce exposure of patients to ineffective treatment. A design based on group sequential and up and down designs was developed and operational characteristics were explored by trial simulation. The primary outcome was headache response at 2 h after treatment. Groups of four treated and two placebo patients were assigned to one dose. Adaptive dose selection was based on response rates of 60% seen with other migraine treatments. If more than 60% of treated patients responded, then the next dose was the next lower dose; otherwise, the dose was increased. A stopping rule of at least five groups at the target dose and at least four groups at that dose with more than 60% response was developed to ensure that a selected dose would be statistically significantly (p=0.05) superior to placebo. Simulations indicated good characteristics in terms of control of type 1 error, sufficient power, modest expected sample size and modest bias in estimation. The trial design is attractive for phase 2 clinical trials when response is acute and simple, ideally binary, placebo comparator is required, and patient accrual is relatively slow allowing for the collection and processing of results as a basis for the adaptive assignment of patients to dose groups. The acute migraine trial based on this design was successful in both proof of concept and dose range selection.

The demand for health insurance coverage by low-income workers: can reduced premiums achieve full coverage?

PubMed

Chernew, M; Frick, K; McLaughlin, C G

1997-10-01

To assess the degree to which premium reductions will increase the participation in employer-sponsored health plans by low-income workers who are employed in small businesses. Sample of workers in small business (25 or fewer employees) in seven metropolitan areas. The data were gathered as part of the Small Business Benefits Survey, a telephone survey of small business conducted between October 1992 and February 1993. Probit regressions were used to estimate the demand for health insurance coverage by low-income workers. Predictions based on these findings were made to assess the extent to which premium reductions might increase coverage rates. Workers included in the sample were selected, at random, from a randomly generated set of firms drawn from Dun and Bradstreet's DMI (Dun's Market Inclusion). The response rate was 81 percent. Participation in employer-sponsored plans is high when coverage is offered. However, even when coverage is offered to employees who have no other source of insurance, participation is not universal. Although premium reductions will increase participation in employer-sponsored plans, even large subsidies will not induce all workers to participate in employer-sponsored plans. For workers eligible to participate, subsidies as high as 75 percent of premiums are estimated to increase participation rates from 89.0 percent to 92.6 percent. For workers in firms that do not sponsor plans, similar subsidies are projected to achieve only modest increases in coverage above that which would be observed if the workers had access to plans at unsubsidized, group market rates. Policies that rely on voluntary purchase of coverage to reduce the number of uninsured will have only modest success.

The Impact of a Social Marketing Campaign on HIV and Sexually Transmissible Infection Testing Among Men Who Have Sex With Men in Australia.

PubMed

Wilkinson, Anna L; Pedrana, Alisa E; El-Hayek, Carol; Vella, Alyce M; Asselin, Jason; Batrouney, Colin; Fairley, Christopher K; Read, Tim R H; Hellard, Margaret; Stoové, Mark

2016-01-01

In response to increasing HIV and other sexually transmissible infection (HIV/STI) notifications in Australia, a social marketing campaign Drama Downunder (DDU) was launched in 2008 to promote HIV/STI testing among men who have sex with men (MSM). We analyzed prospective data from (1) an online cohort of MSM and (2) clinic-level HIV/STI testing to evaluate the impact of DDU on HIV, syphilis, gonorrhea, and chlamydia testing. (1) Cohort participants who completed 3 surveys (2010-2014) contributed to a Poisson regression model examining predictors of recent HIV testing.(2) HIV, syphilis, gonorrhea, and chlamydia tests among MSM attending high caseload primary care clinics (2007-2013) were included in an interrupted time series analysis. (1) Although campaign awareness was high among 242 MSM completing 726 prospective surveys, campaign recall was not associated with self-reported HIV testing. Reporting previous regular HIV testing (adjusted incidence rate ratio, 2.4; 95% confidence interval, 1.3-4.4) and more than 10 partners in the previous 6 months (adjusted incidence rate ratio, 1.2; 95% confidence interval, 1.1-1.4) was associated with recent HIV testing. (2) Analysis of 257,023 tests showed increasing monthly HIV, syphilis, gonorrhea, and chlamydia tests pre-DDU. Post-DDU, gonorrhea test rates increased significantly among HIV-negative MSM, with modest and nonsignificant increasing rates of HIV, syphilis, and chlamydia testing. Among HIV-positive MSM, no change in gonorrhea or chlamydia testing occurred and syphilis testing declined significantly. Increasing HIV/STI testing trends among MSM occurred pre- and post-DDU, coinciding with other plausible drivers of testing. Modest changes in HIV testing post-DDU suggest that structural changes to improve testing access may need to occur alongside health promotion to increase testing frequency.

The epidemiology of firearm suicide in the United States.

PubMed

Romero, Michael P; Wintemute, Garen J

2002-03-01

Little attention has been given to the role of firearms in suicide. In 1998, firearms were the leading method of committing suicide for both men and women, responsible for three times the number of suicides compared to the next leading method. Understanding the epidemiology of firearm suicide will increase awareness of firearm suicide as a major public health problem. Rates of firearm suicide have changed little over the past two decades and have consistently exceeded rates of firearm homicide. The firearm suicide rate among men is approximately six times that of women. While firearm suicide rates are highest among the elderly, the majority (66%) of firearm suicides are among persons under 55 years of age. Firearm suicide rates among women of all ages have dropped modestly, while rates among elderly men have risen considerably. Whites have roughly twice the rate of firearm suicide as do blacks and other race/ethnicity groups. Individual-level empirical studies have consistently indicated that keeping firearms in the home is associated with an increased risk of suicide. For suicide prevention to be effective, the availability and use of firearms in suicides must be addressed.

Phase 2 trial of neoadjuvant chemotherapy and transoral endoscopic surgery with risk-adapted adjuvant therapy for squamous cell carcinoma of the head and neck.

PubMed

Weiss, Jared M; Grilley-Olson, Juneko E; Deal, Allison Mary; Zevallos, Jose P; Chera, Bhishamjit S; Paul, Jennifer; Knowles, Mary Fleming; Usenko, Dmitriy; Weissler, Mark C; Patel, Samip; Hayes, David N; Hackman, Trevor

2018-05-09

The objective of this study was to demonstrate the feasibility and efficacy of induction chemotherapy, surgery, and pathology-guided adjuvant therapy to treat transorally resectable squamous head and neck cancer. Patients had squamous head and neck cancer that was resectable by the transoral route and advanced-stage disease (American Joint Committee on Cancer stage III-IV, T3-T4 tumors, and/or positive lymph nodes). They received treatment with weekly carboplatin at an area under the curve of 2, plus paclitaxel 135 mg/m 2 , and daily lapatinib 1000mg for 6 weeks followed by surgical resection. Pathology that revealed margins <5 mm, extracapsular extension, N2a of N2b lymph node status, perineural invasion, or lymphovascular space invasion resulted in adjuvant radiotherapy concurrent with weekly cisplatin. Pathology with N2c/N3 lymph node status or positive margins resulted in radiation with bolus cisplatin. The primary endpoint was the clinical response rate to induction chemotherapy, and a key secondary endpoint was feasibility. Toxicity was modest, and 37 of 40 patients completed study procedures as planned. The clinical response rate was 93%, the pathologic complete response rate was 36%, and the clinical response did not predict for a pathologic complete response. No patient on study follow-up has recurred or died. Twenty-nine of 39 patients who underwent surgery avoided radiation. Speech and swallowing function were well preserved. The study met both its primary efficacy endpoint and the secondary feasibility endpoint. Neoadjuvant, systemic therapy and surgical resection followed by risk-adapted adjuvant therapy resulted in high response rates and excellent long-term outcomes and should be further studied. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Targeted drug induces responses in aggressive lymphomas

Cancer.gov

Preliminary results from clinical trials in a subtype of lymphoma show that for a number of patients whose disease was not cured by other treatments, the drug ibrutinib can provide significant anti-cancer responses with modest side effects.

Pyrogenic renal hyperemia: the role of prostaglandins.

PubMed

Gagnon, J A; Ramwell, P W; Flamenbaum, W

1978-01-01

The intravenous administration of triple typhoid vaccine to anesthetized dogs resulted in a significant increase in renal blood flow accompanied by a modest decline in systemic blood pressure. This renal hyperemia was associated with elevated renal secretory rates of renin and prostaglandin E and F. Measurements of the intracortical distribution of radiolabeled microspheres revealed a progressive decrease in outer cortical blood flow rates and a progressive increase in inner cortical flow rates. When meclofenamate, an inhibitor of prostaglandin synthetase, was administered concomitantly with triple typhoid vaccine renal hyperemia did not develop. The renal renin secretory rate increased modestly and intracortical renal blood flow was not redistributed. The increased renal blood flow after triple typhoid vaccine administration to unanesthetized dogs was also reversed by meclofenamate. The marked increase in prostaglandin secretion by the kidney during renal hyperemia following triple typhoid vaccine administration (pyrogen), and the effect of meclofenamate, is consonant with a role for increased renal synthesis and release of prostaglandins.

A phase II study of flavopiridol in patients with advanced renal cell carcinoma: results of Southwest Oncology Group Trial 0109.

PubMed

Van Veldhuizen, Peter J; Faulkner, James R; Lara, Primo N; Gumerlock, Paul H; Goodwin, J Wendall; Dakhil, Shaker R; Gross, Howard M; Flanigan, Robert C; Crawford, E David

2005-07-01

Flavopiridol is a cyclin-dependent kinase inhibitor that prevents cell cycle progression and tumor growth. In initial phase I studies, encouraging responses were seen in advanced renal cell cancer (RCC). In a phase II study of flavopiridol given as a 72-h continuous infusion every 2 weeks in RCC, a response rate of 6% was seen but with considerable grade 3 or 4 asthenia, diarrhea, and thrombosis. Subsequently, an alternative 1-h bolus schedule was reported to have enhanced tolerability in a phase I trial. We therefore conducted a phase II study of this bolus regimen. A total of 38 patients with advanced RCC were entered into this multi-institutional phase II study. Flavopiridol (50 mg/m(2) per day) was administered by bolus intravenous injection daily for three consecutive days, repeated every 3 weeks. Out of 34 eligible patients, one complete response and three partial responses were observed, for an overall response rate of 12% (95% CI 3-27%). Of the 34 patients, 14 (41%) had stable disease (SD). The probability of not failing treatment by 6 months was 21% (95% CI 9-35%). Median overall survival time was 9 months (95% CI 8-18 months). The most common grade 3 or 4 toxicities were diarrhea (35%) and tumor pain (12%) along with anemia, dyspnea, and fatigue (9% each). Flavopiridol at this dose and schedule is feasible with an acceptable toxicity profile. Flavopiridol has some modest biologic activity against advanced RCC, as evidenced by its single-agent objective response and SD rates.

IL-2 infusion abrogates humoral immune responses in humans.

PubMed Central

Gottlieb, D J; Prentice, H G; Heslop, H E; Bello, C; Brenner, M K

1992-01-01

Although IL-2 infusion enhances cell-mediated cytotoxicity in patients with neoplastic disease, administration is paradoxically associated with a modest fall in total serum IgG and an increased risk of infection. We now show that the adverse effects of IL-2 infusion on the humoral immune system are substantial. Although IL-2 induces the B cell growth and differentiating factors IL-4 and IL-6, infusion abrogates primary antibody responses entirely and reduces secondary antibody responses 50-fold following antigen challenge. There is no evidence of the generation of cells with suppressive activity on B cells but IL-2 increases the ratio of circulating virgin:memory cells. These results may help to explain the increased rate of bacterial infection in patients receiving IL-2. As IL-2 plays a central role in the generation of an immune response, the finding that it is also sufficiently immunosuppressive to inhibit primary- and secondary-type antibody responses suggests that exploration of the underlying mechanisms may provide insights into immune system homeostasis and may offer new approaches to therapeutic immunosuppression. Images Fig. 1 PMID:1544235

Treatment of osteomyelitis and repair of bone defect by degradable bioactive borate glass releasing vancomycin.

PubMed

Xie, Zongping; Liu, Xin; Jia, Weitao; Zhang, Changqing; Huang, Wenhai; Wang, Jianqiang

2009-10-15

The effectiveness of a degradable and bioactive borate glass has been compared with the clinically used calcium sulfate in the treatment of osteomyelitis of rabbits, as a carrier for vancomycin. The bone infections were induced in the tibias of 65 rabbits by injecting methicillin-resistant Staphylococcus aureus (MRSA). After 3 weeks, these rabbits were distributed into 4 groups and treated by debridement. Pure borate glass (BG), vancomycin-loaded calcium sulfate (VCS) and vancomycin-loaded borate glass (VBG) were implanted into the infection sites of groups 2 to 4 respectively. After 8 weeks, the effectiveness of treatment was assessed radiographically, bacteriologically, and histopathologically. The results showed that the negative rates of MRSA examination for rabbits were 36.36%, 18.18%, 73.33% and 81.25% respectively for groups 1 to 4. Significant differences were observed radiographically, bacteriologically, and histopathologically between groups 1 and 4, groups 2 and 3, and between groups 2 and 4. The best result of treatment was observed in group 4. Radiographically, VBG was found to be mostly reabsorbed and replaced by lots of new bones, whereas, VCS was completely reabsorbed and replaced by modest new bones. Histopathologically, there were lots of newly formed bones around VBG without any foreign body response, and only modest new bones around VCS with obvious foreign body response. VBG proved to have excellent biocompatibility and to be very effective in eradicating osteomyelitis and simultaneously stimulating bone regeneration, avoiding the disadvantages of VCS.

Customer response to day-ahead wholesale market electricity prices: Case study of RTP program experience in New York

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldman, C.; Hopper, N.; Sezgen, O.

2004-07-01

There is growing interest in policies, programs and tariffs that encourage customer loads to provide demand response (DR) to help discipline wholesale electricity markets. Proposals at the retail level range from eliminating fixed rate tariffs as the default service for some or all customer groups to reinstituting utility-sponsored load management programs with market-based inducements to curtail. Alternative rate designs include time-of-use (TOU), day-ahead real-time pricing (RTP), critical peak pricing, and even pricing usage at real-time market balancing prices. Some Independent System Operators (ISOs) have implemented their own DR programs whereby load curtailment capabilities are treated as a system resource andmore » are paid an equivalent value. The resulting load reductions from these tariffs and programs provide a variety of benefits, including limiting the ability of suppliers to increase spot and long-term market-clearing prices above competitive levels (Neenan et al., 2002; Boren stein, 2002; Ruff, 2002). Unfortunately, there is little information in the public domain to characterize and quantify how customers actually respond to these alternative dynamic pricing schemes. A few empirical studies of large customer RTP response have shown modest results for most customers, with a few very price-responsive customers providing most of the aggregate response (Herriges et al., 1993; Schwarz et al., 2002). However, these studies examined response to voluntary, two-part RTP programs implemented by utilities in states without retail competition.1 Furthermore, the researchers had limited information on customer characteristics so they were unable to identify the drivers to price response. In the absence of a compelling characterization of why customers join RTP programs and how they respond to prices, many initiatives to modernize retail electricity rates seem to be stymied.« less

Prolonged remissions of metastatic breast cancer achieved with a six-drug regimen of relatively low toxicity.

PubMed

Hirshaut, Y; Kesselheim, H

1983-06-01

A combination of six chemotherapeutic agents was used to treat 30 women with unresectable metastatic carcinoma of the breast. In the first year five drugs (Cytoxan, methotrexate, 5-fluorouracil, vincristine, and prednisolone [CMFVP]) were given using a weekly schedule for administration of intravenous drugs. During the next year, a seven-week treatment cycle was introduced, with CMFVP given for four weeks, followed by an Adriamycin combination (Adriamycin, cyclophosphamide, and prednisone [ACP]) for three weeks and then the cycle repeated. Treatment was continued for three years or to time of relapse. Overall response rate was 66.7% (20/30). The median duration of response was 40 months and the median survival 39 months. Premenopausal women fared better than postmenopausal women with comparable response rates, duration of response and survival being 81.5%, 41 months, 56 months versus 50%, 20 months and 27 months. Of 16 premenopausal patients treated 7 achieved a complete response (CR) and, of these, 5 remained free of disease at 3 years. For these five individuals all treatment was then stopped. Disease recurred in two patients by five months but three remain disease-free after 43, 40 and 34 months, respectively without therapy. Toxicity was generally limited to heartburn and modest hair loss. This regimen appears to be more effective than those previously employed for metastatic breast cancer. However, comparative trials will be necessary to confirm its advantages.

Nitrogen deposition and forest carbon sequestration: a quantitative synthesis from plot to global scales

NASA Astrophysics Data System (ADS)

Goodale, C. L.; Thomas, R. Q.; Dentener, F. J.; Adams, M.; Baron, J.; Emmett, B.; Evans, C. B.; Fernandez, I. J.; Gundersen, P.; Hagedorn, F.; Kulmatiski, A.; Lovett, G. M.; McNulty, S.; Melvin, A. M.; Moldan, F.; Ollinger, S. V.; Schleppi, P.; Weiss, M.

2009-12-01

Atmospheric nitrogen deposition has long been proposed as a driver of terrestrial carbon sequestration, but its quantitative effect remains poorly constrained. Global models, observations along N deposition gradients, and plot-level forest N-addition experiments provide a range of estimates of the amount of C sequestered in response to added N. Synthesis of results from 48 multi-year N-addition studies in temperate forests show responses ranging from +53 to -95 kg C of live tree production per unit of N addition. Negative effects on live tree C occurred in stands with low rates of biomass accumulation, and occurred more rapidly with higher N application rates. More positive effects occurred in younger stands, and with greater efficiency of C gain at lower N addition rates. Observations of tree growth along N deposition gradients in Europe and the eastern U.S. produced broadly similar tree growth responses (19-56 kg C/kg N) as the N addition experiments. Soil C response increased with N addition rate, and averaged 4 + 12 kg C/kg N. These surface soil responses suggest modest suppression of soil decomposition induced by added N in some but not all sites due to several possible mechanisms, none of which are yet considered in global models. Global-scale estimates of N deposition effects on forest C sequestration have ranged from 0.1 to 2.0 Pg C/y depending on assumptions on the rate of N deposition to forests, its fate, and the C:N ratios of recipient C pools. A new group of biogeochemistry models designed for coupling with global climate models all simulate relatively limited terrestrial C sinks from atmospheric N deposition alone (0.2 - 0.4 PgC/y), more in combination with rising atmospheric CO2. Future model projections should benefit from rigorous comparisons with the range of observed C responses reviewed here.

Reduced Innate Immune Response to a Staphylococcus aureus Small Colony Variant Compared to Its Wild-Type Parent Strain

PubMed Central

Ou, Judy J. J.; Drilling, Amanda J.; Cooksley, Clare; Bassiouni, Ahmed; Kidd, Stephen P.; Psaltis, Alkis J.; Wormald, Peter J.; Vreugde, Sarah

2016-01-01

Background: Staphylococcus aureus (S. aureus) small colony variants (SCVs) can survive within the host intracellular milieu and are associated with chronic relapsing infections. However, it is unknown whether host invasion rates and immune responses differ between SCVs and their wild-type counterparts. This study used a stable S. aureus SCV (WCH-SK2SCV) developed from a clinical isolate (WCH-SK2WT) in inflammation-relevant conditions. Intracellular infection rates as well as host immune responses to WCH-SK2WT and WCH-SK2SCV infections were investigated. Method: NuLi-1 cells were infected with either WCH-SK2WT or WCH-SK2SCV, and the intracellular infection rate was determined over time. mRNA expression of cells infected with each strain intra- and extra-cellularly was analyzed using a microfluidic qPCR array to generate an expression profile of thirty-nine genes involved in the host immune response. Results: No difference was found in the intracellular infection rate between WCH-SK2WT and WCH-SK2SCV. Whereas, extracellular infection induced a robust pro-inflammatory response, intracellular infection elicited a modest response. Intracellular WCH-SK2WT infection induced mRNA expression of TLR2, pro-inflammatory cytokines (IL1B, IL6, and IL12) and tissue remodeling factors (MMP9). In contrast, intracellular WCH-SK2SCV infection induced up regulation of only TLR2. Conclusions: Whereas, host intracellular infection rates of WCH-SK2SCV and WCH-SK2WT were similar, WCH-SK2SCV intracellular infection induced a less widespread up regulation of pro-inflammatory and tissue remodeling factors in comparison to intracellular WCH-SK2WT infection. These findings support the current view that SCVs are able to evade host immune detection to allow their own survival. PMID:28083514

Altitude matters: differences in cardiovascular and respiratory responses to hypoxia in bar-headed geese reared at high and low altitudes.

PubMed

Lague, Sabine L; Chua, Beverly; Farrell, Anthony P; Wang, Yuxiang; Milsom, William K

2016-07-01

Bar-headed geese (Anser indicus) fly at high altitudes during their migration across the Himalayas and Tibetan plateau. However, we know relatively little about whether rearing at high altitude (i.e. phenotypic plasticity) facilitates this impressive feat because most of what is known about their physiology comes from studies performed at sea level. To provide this information, a comprehensive analysis of metabolic, cardiovascular and ventilatory responses to progressive decreases in the equivalent fractional composition of inspired oxygen (FiO2 : 0.21, 0.12, 0.09, 0.07 and 0.05) was made on bar-headed geese reared at either high altitude (3200 m) or low altitude (0 m) and on barnacle geese (Branta leucopsis), a low-altitude migrating species, reared at low altitude (0 m). Bar-headed geese reared at high altitude exhibited lower metabolic rates and a modestly increased hypoxic ventilatory response compared with low-altitude-reared bar-headed geese. Although the in vivo oxygen equilibrium curves and blood-oxygen carrying capacity did not differ between the two bar-headed goose study groups, the blood-oxygen carrying capacity was higher than that of barnacle geese. Resting cardiac output also did not differ between groups and increased at least twofold during progressive hypoxia, initially as a result of increases in stroke volume. However, cardiac output increased at a higher FiO2  threshold in bar-headed geese raised at high altitude. Thus, bar-headed geese reared at high altitude exhibited a reduced oxygen demand at rest and a modest but significant increase in oxygen uptake and delivery during progressive hypoxia compared with bar-headed geese reared at low altitude. © 2016. Published by The Company of Biologists Ltd.

Council tax valuation bands and contacts with a GP out-of-hours service.

PubMed

Beale, Norman; Taylor, Gordon; Gwynne, Mark; Peart, Carole

2006-04-01

UK GPs are no longer responsible for the organisation of out-of-hours care for their patients, but resources remains capitation-based. This cross-sectional study tests whether council tax valuation bands can predict the demand for such services. All out-of-hours contacts made by patients in North Wiltshire over 4 months were classified by council tax band; frequencies compared with official population statistics. Council tax band predicts out-of-hours GP workload irrespective of age and sex: the more modest the home, the higher the GP contact rate. It may prove more difficult to sustain out-of-hours services in deprived parts of the UK.

The Complex Role of Sleep in Adolescent Depression

PubMed Central

Clarke, Greg; Harvey, Allison G.

2013-01-01

Psychological and pharmacological treatments for youth depression yield post-acute response and remission rates that are modest at best. Improving these outcomes is an important long-term goal. To that end, in this paper, the authors examine the possibility that a youth CBT insomnia intervention may be employed as an adjunct to traditional depression-focused treatment with the aim of improving depression outcomes. This “indirect route” to improving youth depression treatment outcomes is based on research indicating that the risk of depression is increased by primary insomnia, that sleep problems interfere with depression treatment success, and on emerging adult depression RCT results. The authors describe the protocol they developed for treating insomnia in depressed youth. PMID:22537732

The Cognitive Assessment Interview (CAI): development and validation of an empirically derived, brief interview-based measure of cognition.

PubMed

Ventura, Joseph; Reise, Steven P; Keefe, Richard S E; Baade, Lyle E; Gold, James M; Green, Michael F; Kern, Robert S; Mesholam-Gately, Raquelle; Nuechterlein, Keith H; Seidman, Larry J; Bilder, Robert M

2010-08-01

Practical, reliable "real world" measures of cognition are needed to supplement neurocognitive performance data to evaluate possible efficacy of new drugs targeting cognitive deficits associated with schizophrenia. Because interview-based measures of cognition offer one possible approach, data from the MATRICS initiative (n=176) were used to examine the psychometric properties of the Schizophrenia Cognition Rating Scale (SCoRS) and the Clinical Global Impression of Cognition in Schizophrenia (CGI-CogS). We used classical test theory methods and item response theory to derive the 10-item Cognitive Assessment Interview (CAI) from the SCoRS and CGI-CogS ("parent instruments"). Sources of information for CAI ratings included the patient and an informant. Validity analyses examined the relationship between the CAI and objective measures of cognitive functioning, intermediate measures of cognition, and functional outcome. The rater's score from the newly derived CAI (10 items) correlate highly (r=.87) with those from the combined set of the SCoRS and CGI-CogS (41 items). Both the patient (r=.82) and the informant (r=.95) data were highly correlated with the rater's score. The CAI was modestly correlated with objectively measured neurocognition (r=-.32), functional capacity (r=-.44), and functional outcome (r=-.32), which was comparable to the parent instruments. The CAI allows for expert judgment in evaluating a patient's cognitive functioning and was modestly correlated with neurocognitive functioning, functional capacity, and functional outcome. The CAI is a brief, repeatable, and potentially valuable tool for rating cognition in schizophrenia patients who are participating in clinical trials. Copyright 2010 Elsevier B.V. All rights reserved.

The Cognitive Assessment Interview (CAI): Development and Validation of an Empirically Derived, Brief Interview-Based Measure of Cognition

PubMed Central

Ventura, Joseph; Reise, Steven P.; Keefe, Richard S. E.; Baade, Lyle E.; Gold, James M.; Green, Michael F.; Kern, Robert S.; Mesholam-Gately, Raquelle; Nuechterlein, Keith H.; Seidman, Larry J.; Bilder, Robert M.

2011-01-01

Background Practical, reliable “real world” measures of cognition are needed to supplement neurocognitive performance data to evaluate possible efficacy of new drugs targeting cognitive deficits associated with schizophrenia. Because interview-based measures of cognition offer one possible approach, data from the MATRICS initiative (n=176) were used to examine the psychometric properties of the Schizophrenia Cognition Rating Scale (SCoRS) and the Clinical Global Impression of Cognition in Schizophrenia (CGI-CogS). Method We used classical test theory methods and item response theory to derive the 10 item Cognitive Assessment Interview (CAI) from the SCoRS and CGI-Cogs (“parent instruments”). Sources of information for CAI ratings included the patient and an informant. Validity analyses examined the relationship between the CAI and objective measures of cognitive functioning, intermediate measures of cognition, and functional outcome. Results The rater’s score from the newly derived CAI (10-items) correlate highly (r = .87) with those from the combined set of the SCoRS and CGI-CogS (41 items). Both the patient (r= .82) and the informant (r= .95) data were highly correlated with the rater’s score. The CAI was modestly correlated with objectively measured neurocognition (r = −.32), functional capacity (r = −.44), and functional outcome (r = −.32), which was comparable to the parent instruments. Conclusions The CAI allows for expert judgment in evaluating a patient’s cognitive functioning and was modestly correlated with neurocognitive functioning, functional capacity, and functional outcome. The CAI is a brief, repeatable, and potentially valuable tool for rating cognition in schizophrenia patients who are participating in clinical trials. PMID:20542412

Twenty years of workers' compensation costs due to falls from height among union carpenters, Washington state.

PubMed

Lipscomb, Hester J; Schoenfisch, Ashley L; Cameron, Wilfrid; Kucera, Kristen L; Adams, Darrin; Silverstein, Barbara A

2014-09-01

Falls from height (FFH) are a longstanding, serious problem in construction. We report workers' compensation (WC) payments associated with FFH among a cohort (n = 24,830; 1989-2008) of carpenters. Mean/median payments, cost rates, and adjusted rate ratios based on hours worked were calculated using negative-binomial regression. Over the 20-year period FFH accounted for $66.6 million in WC payments or $700 per year for each full-time equivalent (2,000 hr of work). FFH were responsible for 5.5% of injuries but 15.1% of costs. Cost declines were observed, but not monotonically. Reductions were more pronounced for indemnity than medical care. Mean costs were 2.3 times greater among carpenters over 50 than those under 30; cost rates were only modestly higher. Significant progress has been made in reducing WC payments associated with FFH in this cohort particularly through 1996; primary gains reflect reduction in frequency of falls. FFH that occur remain costly. © 2014 Wiley Periodicals, Inc.

The relations of mothers' negative expressivity to children's experience and expression of negative emotion.

PubMed

Valiente, Carlos; Eisenberg, Nancy; Shepard, Stephanie A; Fabes, Richard A; Cumberland, Amanda J; Losoya, Sandra H; Spinrad, Tracy L

2004-03-01

Guided by the heuristic model proposed by Eisenberg et al. [Psychol. Inq. 9 (1998) 241], we examined the relations of mothers' reported and observed negative expressivity to children's (N = 159; 74 girls; M age = 7.67 years) experience and expression of emotion. Children's experience and/or expression of emotion in response to a distressing film were measured with facial, heart rate, and self-report measures. Children's heart rate and facial distress were modestly positively related. Children's facial distress was significantly positively related to mothers' reports of negative (dominant and submissive) expressivity; the positive relation between children's facial distress and mothers' observed negative expressivity approached the conventional level of significance. Moreover, mothers' observed negative expressivity was significantly negatively related to children's heart rate reactivity during the conflict film. The positive relation between children's reported distress and mothers' observed negative expressivity approached the conventional level of significance. Several possible explanations for the pattern of findings are discussed.

The relations of mothers’ negative expressivity to children’s experience and expression of negative emotion

PubMed Central

Valiente, Carlos; Eisenberg, Nancy; Shepard, Stephanie A.; Fabes, Richard A.; Cumberland, Amanda J.; Losoya, Sandra H.; Spinrad, Tracy L.

2010-01-01

Guided by the heuristic model proposed by Eisenberg et al. [Psychol. Inq. 9 (1998) 241], we examined the relations of mothers’ reported and observed negative expressivity to children’s (N = 159; 74 girls; M age = 7.67 years) experience and expression of emotion. Children’s experience and/or expression of emotion in response to a distressing film were measured with facial, heart rate, and self-report measures. Children’s heart rate and facial distress were modestly positively related. Children’s facial distress was significantly positively related to mothers’ reports of negative (dominant and submissive) expressivity; the positive relation between children’s facial distress and mothers’ observed negative expressivity approached the conventional level of significance. Moreover, mothers’ observed negative expressivity was significantly negatively related to children’s heart rate reactivity during the conflict film. The positive relation between children’s reported distress and mothers’ observed negative expressivity approached the conventional level of significance. Several possible explanations for the pattern of findings are discussed. PMID:20617103

Cost sharing and HEDIS performance.

PubMed

Chernew, Michael; Gibson, Teresa B

2008-12-01

Physicians, health plans, and health systems are increasingly evaluated and rewarded based on Health Plan Effectiveness Data and Information Set (HEDIS) and HEDIS-like performance measures. Concurrently, employers and health plans continue to try to control expenditures by increasing out-of-pocket costs for patients. The authors use fixed-effect logit models to assess how rising copayment rates for physician office visits and prescription drugs affect performance on HEDIS measures. Findings suggest that the increase in copayment rates lowers performance scores, demonstrating the connection between financial aspects of plan design and quality performance, and highlighting the potential weakness of holding plans and providers responsible for performance when payers and benefit plan managers also influence performance. Yet the effects are not consistent across all domains and, in many cases, are relatively modest in magnitude. This may reflect the HEDIS definitions and suggests that more sensitive measures may capture the impact of benefit design changes on performance.

Thermo-mechanical pressurization of experimental faults in cohesive rocks during seismic slip

NASA Astrophysics Data System (ADS)

Violay, M.; Di Toro, G.; Nielsen, S.; Spagnuolo, E.; Burg, J. P.

2015-11-01

Earthquakes occur because fault friction weakens with increasing slip and slip rates. Since the slipping zones of faults are often fluid-saturated, thermo-mechanical pressurization of pore fluids has been invoked as a mechanism responsible for frictional dynamic weakening, but experimental evidence is lacking. We performed friction experiments (normal stress 25 MPa, maximal slip-rate ∼3 ms-1) on cohesive basalt and marble under (1) room-humidity and (2) immersed in liquid water (drained and undrained) conditions. In both rock types and independently of the presence of fluids, up to 80% of frictional weakening was measured in the first 5 cm of slip. Modest pressurization-related weakening appears only at later stages of slip. Thermo-mechanical pressurization weakening of cohesive rocks can be negligible during earthquakes due to the triggering of more efficient fault lubrication mechanisms (flash heating, frictional melting, etc.).

Foaming in stout beers

NASA Astrophysics Data System (ADS)

Lee, W. T.; Devereux, M. G.

2011-10-01

We review the differences between bubble formation in champagne and other carbonated drinks, and stout beers which contain a mixture of dissolved nitrogen and carbon dioxide. The presence of dissolved nitrogen in stout beers gives them several properties of interest to connoisseurs and physicists. These remarkable properties come at a price: stout beers do not foam spontaneously and special technology, such as the widgets used in cans, is needed to promote foaming. Nevertheless, the same mechanism, nucleation by gas pockets trapped in cellulose fibers, responsible for foaming in carbonated drinks is active in stout beers, but at an impractically slow rate. This gentle rate of bubble nucleation makes stout beers an excellent model system for investigating the nucleation of gas bubbles. The equipment needed is modest, putting such experiments within reach of undergraduate laboratories. We also consider the suggestion that a widget could be constructed by coating the inside of a beer can with cellulose fibers.

Phase II trial of irinotecan in patients with metastatic colorectal carcinoma.

PubMed

Pitot, H C; Wender, D B; O'Connell, M J; Schroeder, G; Goldberg, R M; Rubin, J; Mailliard, J A; Knost, J A; Ghosh, C; Kirschling, R J; Levitt, R; Windschitl, H E

1997-08-01

To evaluate the objective tumor response rate and toxicities of patients with metastatic colorectal carcinoma treated with irinotecan hydrochloride (CPT-11). A total of 121 patients with advanced colorectal carcinoma--90 with prior fluorouracil (5-FU) exposure and 31 chemotherapeutically naive patients--were enrolled between May 1993 and June 1994. Patients were treated with CPT-11 at 125 mg/m2 intravenously weekly for 4 weeks followed by a 2-week rest. Among 90 patients with prior 5-FU chemotherapy, 12 partial responses were observed (response rate, 13.3%; 95% confidence interval [CI], 7.1% to 22.1%). Among 31 chemotherapy-naive patients, eight had partial responses (response rate, 25.8%; 95% CI, 11.9% to 44.6%). The median response duration as measured from time of initial treatment for the two groups was 7.7 months and 7.6 months, respectively. The major adverse reactions were gastrointestinal and hematologic. The incidence of grade 3 or 4 diarrhea was 36.4%, while the overall incidence of grade 3 or 4 leukopenia was 21.5% of patients. Only four of 121 patients (3.3%) developed neutropenic fever (grade 4 neutropenia with > or = grade 2 fever). The incidence of grade 4 leukopenia was higher in patients with prior pelvic radiotherapy (chi2 test P = .04), while the incidence of grade 3 or 4 diarrhea demonstrated no association with previous pelvic irradiation. According to the study design, CPT-11 showed promising activity in chemotherapy-naive patients with advanced colorectal carcinoma and modest activity in patients with prior 5-FU exposure. The toxicity with this schedule appears manageable with appropriate dose modification for individual patient tolerance and an intensive loperamide regimen for the management of diarrhea. Care should be taken when treating patients with prior pelvic radiotherapy because of the increased risk of neutropenia.

Intermittent exercise in response to cigarette cravings in the context of an Internet-based smoking cessation program

PubMed Central

Linke, Sarah E.; Rutledge, Thomas; Myers, Mark G.

2013-01-01

Background Interventions using sustained aerobic exercise programs to aid smoking cessation have resulted in modest, short-term cessation rates comparable to conventional cessation methods. No smoking cessation trial to date has prescribed intermittent bouts of exercise in response to nicotine cravings. Objectives This pilot randomized controlled trial examined the feasibility and efficacy of an Internet-based smoking cessation program alone (CON) vs. the same Internet-based program + intermittent exercise in response to cigarette cravings (EX). Study population Participants (N = 38; mean age = 43.6 [SD = 11.5]; 60.5% women) were generally healthy, inactive adult smokers who desired to quit. Results The overall retention rate was 60.5% (n = 23), and no significant retention rate differences were found between groups (EX vs. CON). Although retained participants achieved a higher cessation rate (26.1%) than all enrolled participants (15.8%), adjusted intent-to-treat and per-protocol binary logistic regression analyses revealed no significant cessation rate differences between EX and CON groups. Linear regression results indicated that additional days of self-reported exercise on the study website during the intervention phase predicted significantly higher reduction rates among EX group participants, F(2, 16) = 31.08, p < .001. Conclusions Results were mixed with regard to the incremental benefit of exercise in the presence of the apparently valuable Internet-based smoking cessation program. The results support findings from related research and underscore the need for additional investigation into both the mechanisms underlying the effect of exercise on cigarette cravings and the challenges of poor adherence in the context of exercise-based smoking cessation interventions. PMID:23956792

Lottery ticket was more effective than a prize draw in increasing questionnaire response among cancer survivors.

PubMed

Drummond, Frances J; O'Leary, Eamonn; Sharp, Linda

2015-07-01

Compare the effect of financial incentives on response to a cancer survivors' postal questionnaire. Prostate cancer survivors in Ireland, 1.5-18 years after diagnosis, were randomized to the (1) "lottery" arm [a € 1 lottery scratch card sent with the questionnaire (n = 2,413)] or (2) "prize" arm [entry into a draw on return of a completed questionnaire (n = 2,407)]. Impact of interventions on response overall and by survival period ("short term": < 5 years after diagnosis; "long term": ≥ 5 years after diagnosis) was compared as was cost-effectiveness. Adjusted response rate was 54.4%. Response was higher among younger men (P < 0.001) and those with earlier stage disease (P = 0.002). A modest 2.6% higher response rate was observed in the lottery compared with the prize arm [multivariate relative risk (RR) = 1.06; 95% confidence interval (CI): 1.00, 1.11]. When stratified by survival period, higher response in the lottery arm was only observed among long-term survivors (multivariate RR = 1.10; 95% CI: 1.02, 1.19; short-term survivors: RR = 1.01; 95% CI: 0.94, 1.09). Costs per completed questionnaire were € 4.54 and € 3.57 for the lottery and prize arms, respectively. Compared with the prize arm, cost per additional questionnaire returned in the lottery arm was € 25.65. Although more expensive, to optimize response to postal questionnaires among cancer survivors, researchers might consider inclusion of a lottery scratch card. Copyright © 2015 Elsevier Inc. All rights reserved.

Changes in inequality and unemployment over the 1980s: comparative cross-national responses.

PubMed

Blank, R M

1995-01-01

The steep recession in the early 1980s was followed by a recovery in nations of the Organization for Economic Cooperation and Development (OECD), but in western European countries unemployment rates remained high. On the other hand, the United States economy after 1983 revived and unemployment dropped rapidly. However, a new problem arose in the late 1980s: rising inequality in the wage rates of more and less skilled workers. The widening wage inequality in the US is proven by the fact that among male high school dropouts real wages fell by 13% between 1979-1989, while among male college graduates real wages rose by 11%. The wage inequality was modest in the Netherlands, no noticeable change occurred in France, Germany, and Italy; there was a modest rise in Canada, Japan, and Sweden; and a large rise in the United Kingdom and US in the 1980s. One hypothesis suggests the growing international competition faced by US firms; another credits the changing demand for more skilled workers driven by the technological shift in computer-intensive industries. The consequences of this wage inequality in the US has been increasing poverty: from 15.6% of households in 1979 to 18.1% in 1986, especially in younger households. In contrast, the respective percentages for Germany were 5.5 in 1979 and 6.8 in 1986. It is likely that both in the US and Europe this rising inequality is caused by international shifts in trade, employment, and technology. Policy responses are utilized by OECD countries: 1) income transfer programs, unemployment benefits, and welfare payments, which have become means-tested because of tight public budgets; 2) public sector job creation programs, with the disadvantage of high cost; 3) job placement and training programs, which are also expensive to operate; 4) wage subsidies, as tried in 1993 in the US by expanding the Earned Income Tax Credit; and 5) hiring subsidies, which encourage the private sector to increase employment.

Aldosterone regulation of sodium and potassium transport in the cortical collecting duct.

PubMed

O'Neil, R G

1990-07-01

The aldosterone-induced up-regulation of Na absorption and K secretion in the CCD is complex and involves the regulation of numerous transport proteins. Some aspects of the response may be species dependent. For example, stimulation of Na and K transport in the rabbit CCD involves a marked up-regulation in the apical cell membrane Na and K conductances, the basolateral cell membrane K conductance, and the basolateral membrane NaK-ATPase activity. In the rat CCD, aldosterone causes a similar up-regulation in the NaK-ATPase and the apical membrane Na conductance, but supposedly has little influence on the apical and basolateral membrane K conductances as evaluated by indirect methods. Furthermore, the marked hyperpolarization of the basolateral membrane with long-term aldosterone treatment in the rabbit CCD is blunted or absent in the rat CCD. Other differences between the CCD of these two species have been outlined. Nonetheless, the basic responses of the CCDs from the two species show similar trends. The actions of aldosterone in the CCD principal cell are summarized in Figure 5. The initial steps have been described previously. Aldosterone (A) diffuse across the cell membrane and binds to a cytoplasmic receptor (R). The receptor complex moves into the nucleus and binds to an acceptor site on chromatin, initiating transcription and the subsequent synthesis of a myriad of new proteins referred to as aldosterone-induced proteins (AIP). The initial observed action of aldosterone is an upregulation of the apical membrane Na conductance during the early phase, which occurs within 1 to 2 hours. The increase in Na conductance likely reflects activation of preexisting latent Na channels and not synthesis of new channels, although activation does require protein synthesis. The increased Na influx during the early phase presents a larger Na load to the Na pump, which is likely reflected as a modest transient increase in intracellular Na activity. Based on kinetic considerations alone, this should cause an increased transport turnover of the pump with a greater Na extrusion rate and K uptake rate. The stimulated Na influx also causes a modest depolarization of the apical membrane during the early phase, which when combined with the increased K uptake via the pump and an apparent modest elevation in the intracellular K activity, results in a more favorable gradient for K secretion (increased driving force) into the tubule lumen.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of psycho-behavioral interventions on immune functioning in cancer patients: a systematic review.

PubMed

Tong, Guixian; Geng, Qingqing; Cheng, Jing; Chai, Jing; Xia, Yi; Feng, Rui; Zhang, Lu; Wang, Debin

2014-01-01

This study aimed at summarizing evidence about effects of psycho-behavioral interventions (PBIs) on immune responses among cancer patients and analyzing quality of published studies so as to inform future researches. Literature retrieval utilized both highly inclusive algorithms searching randomized controlled studies published in English and Chinese and manual searching of eligible studies from references of relevant review papers. Two researchers examined the articles selected separately and extracted the information using a pre-designed form for soliciting data about the trials (e.g., sample size, disease status, intervention, immune responses) and quality ratings of the studies. Both narrative descriptions and meta-analysis (via Review manager 5) were used synthesizing the effects of PBIs on immune responses among cancer patients and state of art of the researches in this area. Seventy-six RCTs met inclusion criteria. PBIs implemented were divided into three major categories including psychological state adjustment, physical activity and dietary modification. Immune indicators measured included CD4+ cells, CD8+ cells, CD4/CDC8+ ratio, CD3+ cells, NK cell activity, etc. Effects of PBIs on immune responses documented in individual papers were mixed and pooled analysis of CD4+ cells, CD4+/CD8+ ratio, CD3+ cells, NKCA, IgG, IgM and IL-2 showed modest effects. However, there were huge discrepancies in intervention effects between studies published in English and Chinese and the results should be interpreted with caution. Besides, most studies suffer from some quality flaws concerning blinding, randomization procedures, compliance, attrition and intention-to-treat analyses, etc. Although there are considerable evidences of PBI effects on some immune indicators, the effect sizes are modest and it is still premature to conclude whether PBIs have effects on immune functions among cancer patients. There is a clear need for much more rigorous efforts in this area and future researches should pay particular attention to intervention dose and focus, sample size and comparable immune measures.

Piloted Simulator Investigation of Techniques to Achieve Attitude Command Response with Limited Authority Servos

NASA Technical Reports Server (NTRS)

Key, David L.; Heffley, Robert K.

2002-01-01

The purpose of the study was to develop generic design principles for obtaining attitude command response in moderate to aggressive maneuvers without increasing SCAS series servo authority from the existing +/- 10%. In particular, to develop a scheme that would work on the UH-60 helicopter so that it can be considered for incorporation in future upgrades. The basic math model was a UH-60A version of GENHEL. The simulation facility was the NASA-Ames Vertical Motion Simulator (VMS). Evaluation tasks were Hover, Acceleration-Deceleration, and Sidestep, as defined in ADS-33D-PRF for Degraded Visual Environment (DVE). The DVE was adjusted to provide a Usable Cue Environment (UCE) equal to two. The basic concept investigated was the extent to which the limited attitude command authority achievable by the series servo could be supplemented by a 10%/sec trim servo. The architecture used provided angular rate feedback to only the series servo, shared the attitude feedback between the series and trim servos, and when the series servo approached saturation the attitude feedback was slowly phased out. Results show that modest use of the trim servo does improve pilot ratings, especially in and around hover. This improvement can be achieved with little degradation in response predictability during moderately aggressive maneuvers.

Endurance training in mild hypertension - effects on ambulatory blood pressure and neural circulatory control.

PubMed

Narkiewicz; Somers

1997-10-01

This review examines the effects of a single bout of exercise and of endurance training on blood pressure in patients with hypertension. Possible autonomic mechanisms that mediate these changes in blood pressure are reviewed briefly. Blood pressure rises during exercise. During the second half hour after exercise blood pressure is lower. This p;ost-exercise reduction in blood pressure is associated with a decrease in muscle sympathetic nerve activity, an increase in baroreflex gain and a reduction in the level of blood pressure (set point) at which baroreflex activation occurs. The post-exercise fall in blood pressure appears to be limited to several hours and is not likely to explain any chronic reduction in blood pressure from endurance training. Endurance training elicits modest (approximately 4-5 mmHg) reductions in blood pressure. Because of the intrinsic variability of blood pressure, the decreases in blood pressure after endurance training is evident, especially when multiple measurements of blood pressure are obtained. Studies using 24 h blood pressure measurements suggest that, although endurance training lowers daytime blood pressure, blood pressure during sleep remains unchanged. The mechanism underlying the reduction in blood pressure in endurance training is not known. Although physical fitness is known to attenuate the sympathetic response to acute exercise, whether resting sympathetic drive is decreased with endurance training remains controversial. The slowing of heart rate that accompanies endurance training is also associated with an increase in variability of heart rate. The slower heart rate, increased variability of heart rate and lower blood pressure after endurance training are accompanied by an increase in baroreflex sensitivity. Even though the antihypertensive effect of endurance training is modest, the favourable effects of physical fitness on other risk factors for cardiovascular disease make exercise training an important approach in the management of hypertensive patients, particularly for sedentary patients with borderline and mild hypertension.

Accreting transition discs with large cavities created by X-ray photoevaporation in C and O depleted discs

NASA Astrophysics Data System (ADS)

Ercolano, Barbara; Weber, Michael L.; Owen, James E.

2018-01-01

Circumstellar discs with large dust depleted cavities and vigorous accretion on to the central star are often considered signposts for (multiple) giant planet formation. In this Letter, we show that X-ray photoevaporation operating in discs with modest (factors 3-10) gas-phase depletion of carbon and oxygen at large radii ( > 15 au) yields the inner radius and accretion rates for most of the observed discs, without the need to invoke giant planet formation. We present one-dimensional viscous evolution models of discs affected by X-ray photoevaporation assuming moderate gas-phase depletion of carbon and oxygen, well within the range reported by recent observations. Our models use a simplified prescription for scaling the X-ray photoevaporation rates and profiles at different metallicity, and our quantitative result depends on this scaling. While more rigorous hydrodynamical modelling of mass-loss profiles at low metallicities is required to constrain the observational parameter space that can be explained by our models, the general conclusion that metal sequestering at large radii may be responsible for the observed diversity of transition discs is shown to be robust. Gap opening by giant planet formation may still be responsible for a number of observed transition discs with large cavities and very high accretion rate.

Alcohol and Atrial Fibrillation: A Sobering Review.

PubMed

Voskoboinik, Aleksandr; Prabhu, Sandeep; Ling, Liang-Han; Kalman, Jonathan M; Kistler, Peter M

2016-12-13

Alcohol is popular in Western culture, supported by a perception that modest intake is cardioprotective. However, excessive drinking has detrimental implications for cardiovascular disease. Atrial fibrillation (AF) following an alcohol binge or the "holiday heart syndrome" is well characterized. However, more modest levels of alcohol intake on a regular basis may also increase the risk of AF. The pathophysiological mechanisms responsible for the relationship between alcohol and AF may include direct toxicity and alcohol's contribution to obesity, sleep-disordered breathing, and hypertension. We aim to provide a comprehensive review of the epidemiology and pathophysiology by which alcohol may be responsible for AF and determine whether alcohol abstinence is required for patients with AF. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Soil microbial responses to nitrogen addition in arid ecosystems

DOE PAGES

Sinsabaugh, Robert L.; Belnap, Jayne; Rudgers, Jennifer; ...

2015-08-14

The N cycle of arid ecosystems is influenced by low soil organic matter, high soil pH, and extremes in water potential and temperature that lead to open canopies and development of biological soil crusts (biocrusts). We investigated the effects of N amendment on soil microbial dynamics in a Larrea tridentata-Ambrosia dumosa shrubland site in southern Nevada USA. Sites were fertilized with a NO 3-NH 4 mix at 0, 7, and 15 kg N ha -1 y -1 from March 2012 to March 2013. In March 2013, biocrust (0–0.5 cm) and bulk soils (0–10 cm) were collected beneath Ambrosia canopies andmore » in the interspaces between plants. Biomass responses were assessed as bacterial and fungal SSU rRNA gene copy number and chlorophyll a concentration. Metabolic responses were measured by five ecoenzyme activities and rates of N transformation. By most measures, nutrient availability, microbial biomass, and process rates were greater in soils beneath the shrub canopy compared to the interspace between plants, and greater in the surface biocrust horizon compared to the deeper 10 cm soil profile. Most measures responded positively to experimental N addition. Effect sizes were generally greater for bulk soil than biocrust. Results were incorporated into a meta-analysis of arid ecosystem responses to N amendment that included data from 14 other studies. Effect sizes were calculated for biomass and metabolic responses. Regressions of effect sizes, calculated for biomass, and metabolic responses, showed similar trends in relation to N application rate and N load (rate × duration). The critical points separating positive from negative treatment effects were 88 kg ha -1 y -1 and 159 kg ha -1, respectively, for biomass, and 70 kg ha -1 y -1 and 114 kg ha -1, respectively, for metabolism. These critical values are comparable to those for microbial biomass, decomposition rates and respiration reported in broader meta-analyses of N amendment effects in mesic ecosystems. As a result, large effect sizes at low N addition rates indicate that arid ecosystems are sensitive to modest increments in anthropogenic N deposition.« less

Sauti Za Wananchi "voice of the people": patient satisfaction on the medical wards at a Kenyan Referral Hospital.

PubMed

Stone, Geren Starr; Jerotich, Tecla Sum; Cheriro, Betsy Rono; Kiptoo, Robert Sitienei; Crowe, Susie Joanne; Koros, Elijah Kipkorir; Muthoni, Doreen Mutegi; Onalo, Paul Theodore

2014-01-01

Patient satisfaction is one indicator of healthcare quality. Few studies have examined the inpatient experiences in resource-scarce environments in sub-Saharan Africa. To examine patient satisfaction on the public medical wards at a Kenyan referral hospital, we performed a cross-sectional survey focused on patients' satisfaction with medical information and their relationship with staffing and hospital routine. Ratings of communication with providers, efforts to protect privacy, information about costs, food, and hospital environment were also elicited. Overall, the average patient satisfaction rating was 64.7, nearly midway between "average" and "good" Higher rated satisfaction was associated with higher self-rated general health scores and self-rated health gains during the hospitalization (p=0.023 and p=0.001). Women who shared a hospital bed found privacy to be "below average" to "poor" Most men (72.7%) felt information about costs was insufficient. Patients rated food and environmental quality favorably while also frequently suggesting these areas could be improved. Overall, patients expressed satisfaction with the care provided. These ratings may reflect modest patients' expectations as well as acceptable circumstances and performance. Women expressed concern about privacy while men expressed a desire for more information on costs. Inconsistencies were noted between patient ratings and free response answers.

Heat and extension at mid- and lower crustal levels of the Rio Grande rift

NASA Technical Reports Server (NTRS)

Olsen, K. H.; Baldridge, W. S.; Callender, J. F.

1985-01-01

The process by which large amounts (50 to 200 percent) of crustal extension are produced was concisely described by W. Hamilton in 1982 and 1983. More recently, England, Sawyer, P. Morgan and others have moved toward quantifying models of lithospheric thinning by incorporating laboratory and theoretical data on rock rheology as a function of composition, temperature, and strain rate. Hamilton's description identifies three main crustal layers, each with a distinctive mechanical behavior; brittle fracturing and rotation in the upper crust, discontinuous ductile flow in the middle crust and laminar ductile flow in the lower crust. The temperature and composition dependent brittle-ductile transition essentially defines the diffuse boundary between upper and middle crust. It was concluded that the heat responsible for the highly ductile nature of the lower crust and the lensoidal and magma body structures at mid-crustal depths in the rift was infused into the crust by relatively modest ( 10 percent by mass) magmatic upwelling (feeder dikes) from Moho levels. Seismic velocity-versus-depth data, supported by gravity modeling and the fact that volumes of rift related volcanics are relatively modest ( 6000 cubic km) for the Rio Grande system, all imply velocities and densities too small to be consistent with a massive, composite, mafic intrusion in the lower crust.

Costs and benefits of jasmonic acid induced responses in soybean.

PubMed

Accamando, A K; Cronin, J T

2012-06-01

In response to herbivory, plants have evolved defense strategies to reduce herbivore preference and performance. A strategy whereby defenses are induced only upon herbivory can mitigate costs of defense when herbivores are scarce. Although costs and benefits of induced responses are generally assumed, empirical evidence for many species is lacking. Soybean (Glycine max L. Merr.) has emerged as a model species with which to address questions about induced responses. To our knowledge, this is the first study to examine the fitness costs and benefits of jasmonic acid-induced responses by soybean in the absence and presence of soybean loopers (Chrysodeix includens Walker) (Lepidoptera: Noctuidae). In a greenhouse experiment we demonstrated that soybean induction was costly. Induced plants produced 10.1% fewer seeds that were 9.0% lighter, and had 19.2% lower germination rates than noninduced plants. However, induction provided only modest benefits to soybeans. In a choice experiment, soybean loopers significantly preferred leaves from noninduced plants, consuming 62% more tissue than from induced plants. Soybean loopers that fed on plants that were previously subjected to treatment with jasmonic acid matured at the same rate and to the same size as those that fed on control plants. However, at high conspecific density, soybean looper survivorship was reduced by 44% on previously induced relative to control plants. Reduced soybean looper preference and survivorship did not translate into fitness benefits for soybeans. Our findings support theoretical predictions of costly induced defenses and highlight the importance of considering the environmental context in studies of plant defense.

Targeting the Tumor Microenvironment with Immunotherapy for Genitourinary Malignancies.

PubMed

Marciscano, Ariel E; Madan, Ravi A

2018-03-08

Bacillus Calmette-Guérin in urothelial carcinoma, high-dose interleukin-2 in renal cell carcinoma, and sipuleucel-T in prostate cancer serve as enduring examples that the host immune response can be harnessed to promote effective anti-tumor immunity in genitourinary malignancies. Recently, cancer immunotherapy with immune checkpoint inhibitors has transformed the prognostic landscape leading to durable responses in a subset of urothelial carcinoma and renal cell carcinoma patients with traditionally poor prognosis. Despite this success, many patients fail to respond to immune checkpoint inhibitors and progression/relapse remains common. Furthermore, modest clinical activity has been observed with ICIs as a monotherapy in advanced PCa. As such, novel treatment approaches are warranted and improved biomarkers for patient selection and treatment response are desperately needed. Future efforts should focus on exploring synergistic and rational combinations that safely and effectively boost response rates and survival in genitourinary malignancies. Specific areas of interest include (1) evaluating the optimal sequencing, disease burden, and timing of immuno-oncology agents with other anti-cancer therapeutics and (2) validating novel biomarkers of response to immunotherapy to optimize patient selection and to identify individuals most likely to benefit from immunotherapy across the heterogenous spectrum of genitourinary malignancies.

Optical Observations of GEO Debris with Two Telescopes

NASA Technical Reports Server (NTRS)

Seitzer, P.; Abercromby, K.; Rodriguez, H.; Barker, E.

2007-01-01

For several years, the Michigan Orbital DEbris Survey Telescope (MODEST), the University of Michigan s 0.6/0.9-m Schmidt telescope on Cerro Tololo Inter-American Observatory in Chile has been used to survey the debris population at GEO in the visible regime. Magnitudes, positions, and angular rates are determined for GEO objects as they move across the telescope s field-of-view (FOV) during a 5-minute window. This short window of time is not long enough to determine a full six parameter orbit so usually a circular orbit is assumed. A longer arc of time is necessary to determine eccentricity and to look for changes in the orbit with time. MODEST can follow objects in real-time, but only at the price of stopping survey operations. A second telescope would allow for longer arcs of orbit to obtain the full six orbital parameters, as well as assess the changes over time. An additional benefit of having a second telescope is the capability of obtaining BVRI colors of the faint targets, aiding efforts to determine the material type of faint debris. For 14 nights in March 2007, two telescopes were used simultaneously to observe the GEO debris field. MODEST was used exclusively in survey mode. As objects were detected, they were handed off in near real-time to the Cerro Tololo 0.9-m telescope for follow-up observations. The goal was to determine orbits and colors for all objects fainter than R = 15th magnitude (corresponds to 1 meter in size assuming a 0.2 albedo) detected by MODEST. The hand-off process was completely functional during the final eight nights and follow-ups for objects from night-to-night were possible. The cutoff magnitude level of 15th was selected on the basis of an abrupt change in the observed angular rate distribution in the MODEST surveys. Objects brighter than 15th magnitude tend to lie on a well defined locus in the angular rate plane (and have orbits in the catalog), while fainter objects fill the plane almost uniformly. We need to determine full six-parameter orbits to investigate what causes this change in observed angular rates. Are these faint objects either the same population of high area-to-mass (A/M) objects on eccentric orbits as discovered by the ESA Space Debris Telescope (Schildknecht, et al. 2004), or are they just normal debris from breakups in GEO?

Modest net autotrophy in the oligotrophic ocean

NASA Astrophysics Data System (ADS)

Letscher, Robert T.; Moore, J. Keith

2017-04-01

The metabolic state of the oligotrophic subtropical ocean has long been debated. Net community production (NCP) represents the balance of autotrophic carbon fixation with heterotrophic respiration. Many in vitro NCP estimates based on oxygen incubation methods and the corresponding scaling relationships used to predict the ecosystem metabolic balance have suggested the ocean gyres to be net heterotrophic; however, all in situ NCP methods find net autotrophy. Reconciling net heterotrophy requires significant allochthonous inputs of organic carbon to the oligotrophic gyres to sustain a preponderance of respiration over in situ production. Here we use the first global ecosystem-ocean circulation model that contains representation of the three allochthonous carbon sources to the open ocean, to show that the five oligotrophic gyres exhibit modest net autotrophy throughout the seasonal cycle. Annually integrated rates of NCP vary in the range 1.5-2.2 mol O2 m-2 yr-1 across the five gyre systems; however, seasonal NCP rates are as low as 1 ± 0.5 mmol O2 m-2 d-1 for the North Atlantic. Volumetric NCP rates are heterotrophic below the 10% light level; however, they become net autotrophic when integrated over the euphotic zone. Observational uncertainties when measuring these modest autotrophic NCP rates as well as the metabolic diversity encountered across space and time complicate the scaling up of in vitro measurements to the ecosystem scale and may partially explain the previous reports of net heterotrophy. The oligotrophic ocean is autotrophic at present; however, it could shift toward seasonal heterotrophy in the future as rising temperatures stimulate respiration.

Efficacy and safety of bio-chemotherapy with dacarbazine plus interleukin-2 in patients with unresectable malignant melanoma.

PubMed

Wu, Chun-Feng; Wang, Hung-Ming; Huang, Wen-Kuan; Chang, John Wen-Cheng

2015-12-01

This study retrospectively evaluated the toxicity and efficacy of dacarbazine (DTIC) with low-dose subcutaneous interleukin-2 (IL-2) for patients with advanced melanoma. Patients with unresectable malignant melanoma received bio-chemotherapy DTIC (330 mg/m(2) , every 3 weeks ) and IL-2 18 MIU (million international units) in divided doses by subcutaneous injection three times a week for 4 weeks. Treatment was performed for six cycles or until disease progression or unbearable toxicity. From October 2006 to November 2013, up to 31 patients (17 men; 14 women) were enrolled. Their median age was 48 years (range, 22-81 years). Subtypes of melanoma included 11 (35.4%) acral lentiginous, nodular, 1 (3.2%) superficial spreading, 10 (32.2%) mucosal and 5 (16.1%) others. The response rate was 19.3%, including 3.2% with a complete response, 16.1% with a partial response and 6.3% with stable disease. The median progression-free survival time was 3.5 months (95% CI: 3.0-3.9 months). The median overall survival time was 8.6 months (95% CI: 4.1-10.9 months). The 1-year survival rate was 39% and the 5-year survival rate was 10%. Our data demonstrated that low-dose subcutaneous IL-2 plus DTIC has modest efficacy and may produce long-term survival in small proportion of patients. Furthermore, the treatment is well tolerated by patients. © 2015 Wiley Publishing Asia Pty Ltd.

Efficacy and Safety of Antiintegrin Antibody for Inflammatory Bowel Disease

PubMed Central

Lin, Lianjie; Liu, Xiang; Wang, Dongxu; Zheng, Changqing

2015-01-01

Abstract We sought to evaluate the safety and efficacy of available biologics that inhibit T-cell migration by blocking α4β7 integrins in inflammatory bowel diseases. The aim of this study is to evaluate whether Crohn disease (CD) patients receiving either vedolizumab or natalizumab have any different effect in CD Activity Index (CDAI). Using Medline, Excerpta Medica dataBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar until October 31, 2013, we identified 10 studies examining the safety and efficacy of specific integrin inhibitors—vedolizumab, which targets an epitope comprising the α4β7 heterodimer; natalizumab, which recognizes the α4 integrin subunit; etrolizumab, which is specific for the β7 subunit—in the treatment of CD and ulcerative colitis (UC). CD patients receiving either vedolizumab or natalizumab demonstrated a modest increase in remission rate, when compared with that of the placebo group. Further, although both treatments reduced the CDAI slightly, the observed clinical response was less robust than that of the remission rate. UC patients treated with vedolizumab and natalizumab were found to show more prominent increases in both remission and clinical response, compared with placebo, than patients with CD. Etrolizumab, however, was not found to significantly affect either response or remission rates in UC patients. Biologics targeting integrins show promise as therapeutics in the treatment of inflammatory bowel disease in patients who are either nonresponsive or intolerant to traditional approaches, though further research is necessary to optimize treatment efficacies. PMID:25761174

Whose "Storm and Stress" Is It? Parent and Child Reports of Personality Development in the Transition to Early Adolescence.

PubMed

Göllner, Richard; Roberts, Brent W; Damian, Rodica I; Lüdtke, Oliver; Jonkmann, Kathrin; Trautwein, Ulrich

2017-06-01

The present study investigated Big Five personality trait development in the transition to early adolescence (from the fifth to eighth grade). Personality traits were assessed in 2,761 (47% female) students over a 3-year period of time. Youths' self-reports and parent ratings were used to test for cross-informant agreement. Acquiescent responding and measurement invariance were established with latent variable modeling. Growth curve models revealed three main findings: (a) Normative mean-level changes occurred for youths' self-report data and parent ratings with modest effects in both cases. (b) Agreeableness and Openness decreased for self-reports and parent ratings, whereas data source differences were found for Conscientiousness (decreased for self-reports and remained stable for parent ratings), Extraversion (increased for self-reports and decreased for parent ratings), and Neuroticism (remained stable for self-reports and decreased for parent ratings). (c) Girls showed a more mature personality overall (self-reports and parent ratings revealed higher levels of Agreeableness, Conscientiousness, and Openness) and became more extraverted in the middle of adolescence (self-reports). Personality changes modestly during early adolescence whereby change does not occur in the direction of maturation, and substantial differences exist between parent ratings and self-reports. © 2016 Wiley Periodicals, Inc.

Energy Storage (II): Developing Advanced Technologies

ERIC Educational Resources Information Center

Robinson, Arthur L

1974-01-01

Energy storage, considered by some scientists to be the best technological and economic advancement after advanced nuclear power, still rates only modest funding for research concerning the development of advanced technologies. (PEB)

Randomized phase 2/3 trial of CpG oligodeoxynucleotide PF-3512676 alone or with dacarbazine for patients with unresectable stage III and IV melanoma.

PubMed

Weber, Jeffrey S; Zarour, Hassan; Redman, Bruce; Trefzer, Uwe; O'Day, Steven; van den Eertwegh, Alfons J M; Marshall, Ernest; Wagner, Stefan

2009-09-01

The primary objective of this phase 2 study was to assess the objective response rate (complete response [CR] + partial responses [PR]), by Response Evaluation Criteria in Solid Tumors, of PF-3512676, a CpG oligodeoxynucleotide, alone in 2 doses or in combination with dacarbazine (DTIC) in patients with unresectable stage IIIB/C or stage IV malignant melanoma, with the aim of selecting an arm to take forward to a phase 3 portion of the study. A total of 184 patients were randomized to 1 of 4 treatments: PF-3512676 10 mg (low dose), at 40 mg (high dose), 40 mg plus DTIC (850 mg/m(2)), or DTIC (850 mg/m(2)) alone. Patients received PF-3512676 subcutaneously weekly in a 3-week cycle and received DTIC intravenously on the first week of the cycle. The objective response rate (PR or CR, confirmed or unconfirmed) in the 40 mg + DTIC arm was 16% (7 patients) compared with 8% (3 patients) with DTIC alone. One (2%) patient in the 10-mg and 0 patients in the 40-mg arms achieved an objective response. Best response of CR or PR or stable disease (SD), with no minimum duration defined for SD, was achieved by 15 (33%) patients in the 40 mg + DTIC arm, 15 (38%) patients in the DTIC-only arm, 8 (17%) patients in the 10-mg arm, and 9 (20%) patients in the 40-mg arm. The most frequently reported adverse events were classified as local injection site reactions or systemic flu-like symptoms, specifically fatigue, rigors, and pyrexia. PF-3512676 at the doses used was generally well tolerated. The modest objective response rates observed in all arms did not warrant continuation to the phase 3 portion of the study.

Cocaine-induced microvascular vasoconstriction but differential systemic haemodynamic responses in Yucatan versus Yorkshire varieties of swine.

PubMed Central

Miao, L.; Núñez, B. D.; Susulic, V.; Wheeler, S.; Carrozza, J. P.; Ross, J. N.; Morgan, J. P.

1996-01-01

1. Systemic and coronary haemodynamics were measured in 6 Yorkshire swine and 6 Yucatan miniature swine under isoflurane anaesthesia to investigate the influence of cocaine following its intravenous administration at 1, 3 and 7 mg kg-1. 2. Cocaine in Yorkshire swine decreased mean arterial pressure and rate pressure product (systolic pressure x heart rate), suggesting a cardiac depressant effect, whereas cocaine in Yucatan miniature swine increased these parameters, consistent with a hyperadrenergic state. 3. Cocaine in both Yorkshire swine and Yucatan miniature swine decreased coronary blood flow and coronary flow reserve, and increased coronary vascular resistance. 4. A modest generalized epicardial coronary artery constriction was observed by angiography, without evidence of focal spasm. 5. Our results confirm a marked vasoconstrictor effect of cocaine on the coronary arterial circulation, predominantly distal to the epicardial coronary arteries, but also indicate important differences in the systemic cardiovascular responses to the drug between two closely related strains of animals within the same species. Due to the similarities between the swine and human coronary arterial vasculature, we suggest that vasoconstriction in the coronary microcirculation may produce cardiac toxicity in man. PMID:8821549

Phase II Trial of Induction Chemotherapy Followed by Surgery for Squamous Cell Carcinoma of the Oral Tongue in Young Adults

PubMed Central

Kies, Merrill S.; Boatright, Dowin H.; Li, Guojun; Blumenschein, George; El-Naggar, Adel K.; Lewin, Jan S.; Steinhaus, Ganene; Sturgis, Erich M.

2013-01-01

Background We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. Methods From September 2001 to October 2004, 23 patients aged 18–49 years with clinical T2-3N0-2M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. Results On final surgical pathology, 9 (39%) patients had a complete/major (2 complete) histologic response at the primary tumor site; 8 (35%) had no response or progression. Similarly, 9 (39%) patients had a complete response in the neck or remained node negative; 6 (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 (43%) patients developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (P = .029), poor histologic differentiation (P = .012), and multiple adverse features on final surgical pathology (P = .040). Conclusions Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. PMID:22009800

Phase II trial of induction chemotherapy followed by surgery for squamous cell carcinoma of the oral tongue in young adults.

PubMed

Kies, Merrill S; Boatright, Dowin H; Li, Guojun; Blumenschein, George; El-Naggar, Adel K; Brandon Gunn, G; Lewin, Jan S; Steinhaus, Ganene D; Sturgis, Erich M

2012-09-01

We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. From September 2001 to October 2004, 23 patients aged 18 to 49 years with clinical T2-3 N0-2 M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. On final surgical pathology, 9 patients (39%) had a complete/major (2 complete) histologic response at the primary tumor site; 8 patients (35%) had no response or progression. Similarly, 9 patients (39%) had a complete response in the neck or remained node negative; 6 patients (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 patients (43%) developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (p = .029), poor histologic differentiation (p = .012), and multiple adverse features on final surgical pathology (p = .040). Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. Copyright © 2011 Wiley Periodicals, Inc.

Tuition Reciprocity in the United States

ERIC Educational Resources Information Center

Stewart, Gregory; Wright, Dianne Brown; Kennedy, Angelica

2008-01-01

Reciprocity agreements are contracts between two or more parties whereby students pay reduced tuition rates. The rate of reduction is determined by the parameters set forth in each individual state's agreement but may range from a modest reduction in fees to a waiver of full non-resident tuition. In addition to providing tuition relief,…

Trends in Chicago's Schools across Three Eras of Reform

ERIC Educational Resources Information Center

Luppescu, Stuart; Allensworth, Elaine M.; Moore, Paul; de la Torre, Marisa; Murphy, James

2011-01-01

"Trends in Chicago's Schools Across Three Eras of Reform" finds that Chicago Public Schools has experienced tremendous growth in graduation rates over the past 20 years, but learning gains have been modest. The report tracks elementary and high school test scores and graduation rates in Chicago since 1988, when U.S. Secretary of…

Mapping and load response of overload strain fields: Synchrotron X-ray measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shukla, V; Jisrawi, N M; Sadangi, R K

High energy synchrotron X-ray diffraction measurements have been performed to provide quantitative microscopic guidance for modeling of fatigue crack growth. Specifically we report local strain mapping, along with in situ loading strain response, results on 4140 steel fatigue specimens exhibiting the crack growth retardation 'overload effect'. Detailed, 2D, {epsilon}{gamma}{gamma}-strain field mapping shows that a single overload (OL) cycle creates a compressive strain field extending millimeters above and below the crack plane. The OL strain field structures are shown to persist after the crack tip has grown well beyond the OL position. The specimen exhibiting the maximal crack growth rate retardationmore » following overload exhibits a tensile residual strain region at the crack tip. Strain field results, on in situ tensile loaded specimens, show a striking critical threshold load, F{sub c}, phenomenon in their strain response. At loads below F{sub c} the strain response is dominated by a rapid suppression of the compressive OL feature with modest response at the crack tip. At loads above F{sub c} the strain response at the OL position terminates and the response at the crack tip becomes large. This threshold load response behavior is shown to exhibit lower F{sub c} values, and dramatically enhanced rates of strain change with load as the crack tip propagates farther beyond the OL position. The OL strain feature behind the crack tip also is shown to be suppressed by removing the opposing crack faces via an electron discharge cut passing through the crack tip. Finally unique 2D strain field mapping (imaging) results, through the depth of the specimen, of the fatigue crack front and the OL feature in the wake are also presented.« less

Proliferative responses in the local lymph node assay associated with concomitant exposure to 1,4-phenylenediamine and methyldibromo glutaronitrile: evidence for synergy?

PubMed

Jowsey, Ian R; Basketter, David A; Irwin, Anita

2008-08-01

A key consideration when undertaking risk assessments should be the potential for synergy between contact allergens. Previously, this concept has only been investigated during elicitation in contact allergic individuals. To determine whether there exists evidence for synergy between contact allergens during the induction phase of skin sensitization using the mouse local lymph node assay (LLNA) as a model system. Proliferative responses in draining lymph nodes were assessed with increasing concentrations of 1,4-phenylenediamine (PPD), methyldibromo glutaronitrile (MDBGN), and a combination of PPD and MDBGN. Data from each of two independent experiments show that lymph node cell proliferation associated with combined exposure to PPD and MDBGN was, in general, only modestly increased relative to that predicted from a simple summation of their individual responses. Although the increase in response is very modest, it does imply a relationship between this combination of sensitizers that may not be simply additive in terms of their ability to stimulate proliferative responses in draining lymph nodes. The reproducibility of this observation should be confirmed in future studies with additional pairs of contact allergens to ascertain whether or not this represents evidence of synergy.

MODEST: a web-based design tool for oligonucleotide-mediated genome engineering and recombineering

PubMed Central

Bonde, Mads T.; Klausen, Michael S.; Anderson, Mads V.; Wallin, Annika I.N.; Wang, Harris H.; Sommer, Morten O.A.

2014-01-01

Recombineering and multiplex automated genome engineering (MAGE) offer the possibility to rapidly modify multiple genomic or plasmid sites at high efficiencies. This enables efficient creation of genetic variants including both single mutants with specifically targeted modifications as well as combinatorial cell libraries. Manual design of oligonucleotides for these approaches can be tedious, time-consuming, and may not be practical for larger projects targeting many genomic sites. At present, the change from a desired phenotype (e.g. altered expression of a specific protein) to a designed MAGE oligo, which confers the corresponding genetic change, is performed manually. To address these challenges, we have developed the MAGE Oligo Design Tool (MODEST). This web-based tool allows designing of MAGE oligos for (i) tuning translation rates by modifying the ribosomal binding site, (ii) generating translational gene knockouts and (iii) introducing other coding or non-coding mutations, including amino acid substitutions, insertions, deletions and point mutations. The tool automatically designs oligos based on desired genotypic or phenotypic changes defined by the user, which can be used for high efficiency recombineering and MAGE. MODEST is available for free and is open to all users at http://modest.biosustain.dtu.dk. PMID:24838561

Outlook for trucks and trailers

DOT National Transportation Integrated Search

2005-11-01

Demand for commercial trucks and trailers scored impressive gains last year as a vibrant : economy, strong customer markets, relatively modest levels of inflation and interest rates, : and the accelerated depreciation provisions of the Tax Stimulus p...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sinsabaugh, Robert L.; Belnap, Jayne; Rudgers, Jennifer

The N cycle of arid ecosystems is influenced by low soil organic matter, high soil pH, and extremes in water potential and temperature that lead to open canopies and development of biological soil crusts (biocrusts). We investigated the effects of N amendment on soil microbial dynamics in a Larrea tridentata-Ambrosia dumosa shrubland site in southern Nevada USA. Sites were fertilized with a NO 3-NH 4 mix at 0, 7, and 15 kg N ha -1 y -1 from March 2012 to March 2013. In March 2013, biocrust (0–0.5 cm) and bulk soils (0–10 cm) were collected beneath Ambrosia canopies andmore » in the interspaces between plants. Biomass responses were assessed as bacterial and fungal SSU rRNA gene copy number and chlorophyll a concentration. Metabolic responses were measured by five ecoenzyme activities and rates of N transformation. By most measures, nutrient availability, microbial biomass, and process rates were greater in soils beneath the shrub canopy compared to the interspace between plants, and greater in the surface biocrust horizon compared to the deeper 10 cm soil profile. Most measures responded positively to experimental N addition. Effect sizes were generally greater for bulk soil than biocrust. Results were incorporated into a meta-analysis of arid ecosystem responses to N amendment that included data from 14 other studies. Effect sizes were calculated for biomass and metabolic responses. Regressions of effect sizes, calculated for biomass, and metabolic responses, showed similar trends in relation to N application rate and N load (rate × duration). The critical points separating positive from negative treatment effects were 88 kg ha -1 y -1 and 159 kg ha -1, respectively, for biomass, and 70 kg ha -1 y -1 and 114 kg ha -1, respectively, for metabolism. These critical values are comparable to those for microbial biomass, decomposition rates and respiration reported in broader meta-analyses of N amendment effects in mesic ecosystems. As a result, large effect sizes at low N addition rates indicate that arid ecosystems are sensitive to modest increments in anthropogenic N deposition.« less

MODEST - JPL GEODETIC AND ASTROMETRIC VLBI MODELING AND PARAMETER ESTIMATION PROGRAM

NASA Technical Reports Server (NTRS)

Sovers, O. J.

1994-01-01

Observations of extragalactic radio sources in the gigahertz region of the radio frequency spectrum by two or more antennas, separated by a baseline as long as the diameter of the Earth, can be reduced, by radio interferometry techniques, to yield time delays and their rates of change. The Very Long Baseline Interferometric (VLBI) observables can be processed by the MODEST software to yield geodetic and astrometric parameters of interest in areas such as geophysical satellite and spacecraft tracking applications and geodynamics. As the accuracy of radio interferometry has improved, increasingly complete models of the delay and delay rate observables have been developed. MODEST is a delay model (MOD) and parameter estimation (EST) program that takes into account delay effects such as geometry, clock, troposphere, and the ionosphere. MODEST includes all known effects at the centimeter level in modeling. As the field evolves and new effects are discovered, these can be included in the model. In general, the model includes contributions to the observables from Earth orientation, antenna motion, clock behavior, atmospheric effects, and radio source structure. Within each of these categories, a number of unknown parameters may be estimated from the observations. Since all parts of the time delay model contain nearly linear parameter terms, a square-root-information filter (SRIF) linear least-squares algorithm is employed in parameter estimation. Flexibility (via dynamic memory allocation) in the MODEST code ensures that the same executable can process a wide array of problems. These range from a few hundred observations on a single baseline, yielding estimates of tens of parameters, to global solutions estimating tens of thousands of parameters from hundreds of thousands of observations at antennas widely distributed over the Earth's surface. Depending on memory and disk storage availability, large problems may be subdivided into more tractable pieces that are processed sequentially. MODEST is written in FORTRAN 77, C-language, and VAX ASSEMBLER for DEC VAX series computers running VMS. It requires 6Mb of RAM for execution. The standard distribution medium for this package is a 1600 BPI 9-track magnetic tape in DEC VAX BACKUP format. It is also available on a TK50 tape cartridge in DEC VAX BACKUP format. Instructions for use and sample input and output data are available on the distribution media. This program was released in 1993 and is a copyrighted work with all copyright vested in NASA.

Blue gum gaming machine: an evaluation of responsible gambling features.

PubMed

Blaszczynski, Alexander; Gainsbury, Sally; Karlov, Lisa

2014-09-01

Structural characteristics of gaming machines contribute to persistence in play and excessive losses. The purpose of this study was to evaluate the effectiveness of five proposed responsible gaming features: responsible gaming messages; a bank meter quarantining winnings until termination of play; alarm clock facilitating setting time-reminders; demo mode allowing play without money; and a charity donation feature where residual amounts can be donated rather than played to zero credits. A series of ten modified gaming machines were located in five Australian gambling venues. The sample comprised 300 patrons attending the venue and who played the gaming machines. Participants completed a structured interview eliciting gambling and socio-demographic data and information on their perceptions and experience of play on the index machines. Results showed that one-quarter of participants considered that these features would contribute to preventing recreational gamblers from developing problems. Just under half of the participants rated these effects to be at least moderate or significant. The promising results suggest that further refinements to several of these features could represent a modest but effective approach to minimising excessive gambling on gaming machines.

Efficacy of dacarbazine as a rescue agent for histiocytic sarcoma in dogs.

PubMed

Kezer, K A; Barber, L G; Jennings, S H

2018-03-01

Canine histiocytic sarcoma (HS) is an aggressive neoplasm that is generally associated with a poor prognosis. CCNU is considered first-line medical therapy, although the majority of dogs ultimately develop progressive disease. The objective of this study was to evaluate the efficacy of dacarbazine as a rescue agent for HS. Medical records of dogs diagnosed with HS that received at least one dose of dacarbazine were reviewed. Information collected and analyzed included signalment, disease distribution, treatment history, dacarbazine treatments (including dose, interval and total number of cycles), adverse events, and response to treatment. Seventeen dogs were included, all of which had disseminated or metastatic disease and had received prior treatment with CCNU. Three dogs achieved partial remission for an overall response rate of 17.6%. The overall median event-free survival (EFS) was 21 days. For dogs that experienced an objective response, the EFS was 70 days. Toxicity secondary to dacarbazine was generally mild and self-limiting. In the setting of advanced disease, dacarbazine appears to have modest activity against HS and warrants further investigation. © 2017 John Wiley & Sons Ltd.

Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma: Are we getting there?

PubMed Central

Shao, Yu-Yun; Hsu, Chih-Hung; Cheng, Ann-Lii

2015-01-01

Sorafenib is the current standard treatment for advanced hepatocellular carcinoma (HCC), but its efficacy is modest with low response rates and short response duration. Predictive biomarkers for sorafenib efficacy are necessary. However, efforts to determine biomarkers for sorafenib have led only to potential candidates rather than clinically useful predictors. Studies based on patient cohorts identified the potential of blood levels of angiopoietin-2, hepatocyte growth factor, insulin-like growth factor-1, and transforming growth factor-β1 for predicting sorafenib efficacy. Alpha-fetoprotein response, dynamic contrast-enhanced magnetic resonance imaging, and treatment-related side effects may serve as early surrogate markers. Novel approaches based on super-responders or experimental mouse models may provide new directions in biomarker research. These studies identified tumor amplification of FGF3/FGF4 or VEGFA and tumor expression of phospho-Mapk14 and phospho-Atf2 as possible predictive markers that await validation. A group effort that considers various prognostic factors and proper collection of tumor tissues before treatment is imperative for the success of future biomarker research in advanced HCC. PMID:26420960

Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma: Are we getting there?

PubMed

Shao, Yu-Yun; Hsu, Chih-Hung; Cheng, Ann-Lii

2015-09-28

Sorafenib is the current standard treatment for advanced hepatocellular carcinoma (HCC), but its efficacy is modest with low response rates and short response duration. Predictive biomarkers for sorafenib efficacy are necessary. However, efforts to determine biomarkers for sorafenib have led only to potential candidates rather than clinically useful predictors. Studies based on patient cohorts identified the potential of blood levels of angiopoietin-2, hepatocyte growth factor, insulin-like growth factor-1, and transforming growth factor-β1 for predicting sorafenib efficacy. Alpha-fetoprotein response, dynamic contrast-enhanced magnetic resonance imaging, and treatment-related side effects may serve as early surrogate markers. Novel approaches based on super-responders or experimental mouse models may provide new directions in biomarker research. These studies identified tumor amplification of FGF3/FGF4 or VEGFA and tumor expression of phospho-Mapk14 and phospho-Atf2 as possible predictive markers that await validation. A group effort that considers various prognostic factors and proper collection of tumor tissues before treatment is imperative for the success of future biomarker research in advanced HCC.

Atomoxetine in abstinent cocaine users: Cognitive, subjective and cardiovascular effects.

PubMed

DeVito, Elise E; Herman, Aryeh I; Konkus, Noah S; Zhang, Huiping; Sofuoglu, Mehmet

2017-08-01

No pharmacotherapies are approved for the treatment of cocaine use disorders (CUD). Behavioral treatments for CUD are efficacious for some individuals, but recovery rates from CUD remain low. Cognitive impairments in CUD have been linked with poorer clinical outcomes. Cognitive enhancing pharmacotherapies have been proposed as promising treatments for CUD. Atomoxetine, a norepinephrine transporter inhibitor, shows potential as a treatment for CUD based on its efficacy as a cognitive enhancer in other clinical populations and impact on addictive processes in preclinical and human laboratory studies. In this randomized, double-blind, crossover study, abstinent individuals with CUD (N=39) received placebo, 40 and 80mg atomoxetine, over three sessions. Measures of attention, response inhibition and working memory; subjective medication effects and mood; and cardiovascular effects were collected. Analyses assessed acute, dose-dependent effects of atomoxetine. In addition, preliminary analyses investigating the modulation of atomoxetine dose effects by sex were performed. Atomoxetine increased heart rate and blood pressure, was rated as having positive and negative subjective drug effects, and had only modest effects on mood and cognitive enhancement. Copyright © 2017. Published by Elsevier Inc.

Sex and Locus of Control as Determinants of Children's Responses to Peer versus Adult Praise.

ERIC Educational Resources Information Center

Henry, Susan E.; And Others

1979-01-01

Black first graders varying in internal-external control completed digit substitution problems during which performance was praised by a Black boy and girl or a Black man and woman. Boys were most responsive to peer feedback and girls to adult feedback. Predictions involving locus of control were modestly supported. (Author/RD)

A twin study of spatial and non-spatial delayed response performance in middle age.

PubMed

Kremen, William S; Mai, Tuan; Panizzon, Matthew S; Franz, Carol E; Blankfeld, Howard M; Xian, Hong; Eisen, Seth A; Tsuang, Ming T; Lyons, Michael J

2011-06-01

Delayed alternation and object alternation are classic spatial and non-spatial delayed response tasks. We tested 632 middle-aged male veteran twins on variants of these tasks in order to compare test difficulty, measure their inter-correlation, test order effects, and estimate heritabilities (proportion of observed variance due to genetic influences). Non-spatial alternation (NSA), which may involve greater reliance on processing of subgoals, was significantly more difficult than spatial alternation (SA). Despite their similarities, NSA and SA scores were uncorrelated. NSA performance was worse when administered second; there was no SA order effect. NSA scores were modestly heritable (h(2)=.25; 26); SA was not. There was shared genetic variance between NSA scores and general intellectual ability (r(g)=.55; .67), but this also suggests genetic influences specific to NSA. Compared with findings from small, selected control samples, high "failure" rates in this community-based sample raise concerns about interpretation of brain dysfunction in elderly or patient samples. Copyright © 2011 Elsevier Inc. All rights reserved.

Combined chemotherapy with cytotoxic and targeted compounds for the management of human malignant pleural mesothelioma.

PubMed

Favoni, Roberto E; Florio, Tullio

2011-08-01

Human malignant pleural mesothelioma (hMPM) is an aggressive asbestos-associated cancer, the incidence of which is increasing and which, despite progress in diagnosis and therapy, continues to have a poor prognosis. Asbestos fibers induce aberrant cell signaling, leading to proto-oncogene activation and chemoresistance. In this review, we discuss the evolution of pharmacological management of hMPM up to the most recent advances. Monotherapy with single cytotoxic drugs achieves modest objective response rates, seldom reaching 30%. However, combination regimens using novel drugs and standard molecules are showing gradually improving responses and clinical benefits. Phase II/III studies have identified pemetrexed, a multitarget folate pathway inhibitor in combination with platinum derivatives, and the cisplatin/gemcitabine association as front-line chemotherapy for hMPM. Detailed knowledge of molecular mechanisms of signal transduction and neoangiogenesis in hMPM should aid in the design and screening of other promising compounds such as more efficacious receptor tyrosine kinase inhibitors. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Twin Study of Spatial and Non-Spatial Delayed Response Performance in Middle Age

PubMed Central

Kremen, William S.; Mai, Tuan; Panizzon, Matthew S.; Franz, Carol E.; Blankfeld, Howard M.; Xian, Hong; Eisen, Seth A.; Tsuang, Ming T.; Lyons, Michael J.

2011-01-01

Delayed alternation and object alternation are classic spatial and non-spatial delayed response tasks. We tested 632 middle-aged male veteran twins on variants of these tasks in order to compare test difficulty, measure their inter-correlation, test order effects, and estimate heritabilities (proportion of observed variance due to genetic influences). Non-spatial alternation (NSA), which may involve greater reliance on processing of subgoals, was significantly more difficult than spatial alternation (SA). Despite their similarities, NSA and SA scores were uncorrelated. NSA performance was worse when administered second; there was no SA order effect. NSA scores were modestly heritable (h2=.25; 26); SA was not. There was shared genetic variance between NSA scores and general intellectual ability (rg=.55; .67), but this also suggests genetic influences specific to NSA. Compared with findings from small, selected control samples, high “failure” rates in this community-based sample raise concerns about interpretation of brain dysfunction in elderly or patient samples. PMID:21477911

Chaos-induced modulation of reliability boosts output firing rate in downstream cortical areas.

PubMed

Tiesinga, P H E

2004-03-01

The reproducibility of neural spike train responses to an identical stimulus across different presentations (trials) has been studied extensively. Reliability, the degree of reproducibility of spike trains, was found to depend in part on the amplitude and frequency content of the stimulus [J. Hunter and J. Milton, J. Neurophysiol. 90, 387 (2003)]. The responses across different trials can sometimes be interpreted as the response of an ensemble of similar neurons to a single stimulus presentation. How does the reliability of the activity of neural ensembles affect information transmission between different cortical areas? We studied a model neural system consisting of two ensembles of neurons with Hodgkin-Huxley-type channels. The first ensemble was driven by an injected sinusoidal current that oscillated in the gamma-frequency range (40 Hz) and its output spike trains in turn drove the second ensemble by fast excitatory synaptic potentials with short term depression. We determined the relationship between the reliability of the first ensemble and the response of the second ensemble. In our paradigm the neurons in the first ensemble were initially in a chaotic state with unreliable and imprecise spike trains. The neurons became entrained to the oscillation and responded reliably when the stimulus power was increased by less than 10%. The firing rate of the first ensemble increased by 30%, whereas that of the second ensemble could increase by an order of magnitude. We also determined the response of the second ensemble when its input spike trains, which had non-Poisson statistics, were replaced by an equivalent ensemble of Poisson spike trains. The resulting output spike trains were significantly different from the original response, as assessed by the metric introduced by Victor and Purpura [J. Neurophysiol. 76, 1310 (1996)]. These results are a proof of principle that weak temporal modulations in the power of gamma-frequency oscillations in a given cortical area can strongly affect firing rate responses downstream by way of reliability in spite of rather modest changes in firing rate in the originating area.

Hyperglycaemia does not affect antigen-specific activation and cytolytic killing by CD8+ T cells in vivo.

PubMed

Recino, Asha; Barkan, Kerry; Wong, F Susan; Ladds, Graham; Cooke, Anne; Wallberg, Maja

2017-08-31

Metabolism is of central importance for T cell survival and differentiation. It is well known that T cells cannot function in the absence of glucose, but it is less clear how they respond to excessive levels of glucose. In the present study, we investigated how increasing levels of glucose affect T-cell-mediated immune responses. We examined the effects of increased levels of glucose on CD8 + T-cell behaviour in vitro by assessing activation and cytokine production, as well as oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and intracellular signalling. In addition, we assessed in vivo proliferation, cytokine production and cytolytic activity of cells in chemically induced diabetic C57BL/6 mice. Elevated levels of glucose in in vitro cultures had modest effects on proliferation and cytokine production, while in vivo hyperglycaemia had no effect on CD8 + T-cell proliferation, interferon γ (IFNγ) production or cytolytic killing. © 2017 The Author(s).

Kidney Response to the Spectrum of Diet-Induced Acid Stress

PubMed Central

Goraya, Nimrit; Wesson, Donald E.

2018-01-01

Chronic ingestion of the acid (H+)-producing diets that are typical of developed societies appears to pose a long-term threat to kidney health. Mechanisms employed by kidneys to excrete this high dietary H+ load appear to cause long-term kidney injury when deployed over many years. In addition, cumulative urine H+ excretion is less than the cumulative increment in dietary H+, consistent with H+ retention. This H+ retention associated with the described high dietary H+ worsens as the glomerular filtration rate (GFR) declines which further exacerbates kidney injury. Modest H+ retention does not measurably change plasma acid–base parameters but, nevertheless, causes kidney injury and might contribute to progressive nephropathy. Current clinical methods do not detect H+ retention in its early stages but the condition manifests as metabolic acidosis as it worsens, with progressive decline of the glomerular filtration rate. We discuss this spectrum of H+ injury, which we characterize as “H+ stress”, and the emerging evidence that high dietary H+ constitutes a threat to long-term kidney health. PMID:29751620

Does uninsurance affect the health outcomes of the insured? Evidence from heart attack patients in California.

PubMed

Daysal, N Meltem

2012-07-01

In this paper, I examine the impact of uninsured patients on the in-hospital mortality rate of insured heart attack patients. I employ panel data models using patient discharge and hospital financial data from California (1999-2006). My results indicate that uninsured patients have an economically significant effect that increases the mortality rate of insured heart attack patients. I show that these results are not driven by alternative explanations, including reverse causality, patient composition effects, sample selection or unobserved trends and that they are robust to a host of specification checks. The primary channel for the observed spillover effects is increased hospital uncompensated care costs. Although data limitations constrain my capacity to check how hospitals change their provision of care to insured heart attack patients in response to reduced revenues, the evidence I have suggests a modest increase in the quantity of cardiac services without a corresponding increase in hospital staff. Copyright © 2012 Elsevier B.V. All rights reserved.

Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

PubMed

Thigpen, T; Brady, M F; Homesley, H D; Soper, J T; Bell, J

2001-01-15

In two large Gynecologic Oncology Group studies of patients with advanced or recurrent endometrial carcinoma and no previous systemic therapy, progestins have demonstrated activity against advanced or recurrent endometrial carcinoma with response rates between 15% and 25%. Tamoxifen has been reported as variously active or inactive with or without previous systemic therapy. The purpose of this study was to determine whether tamoxifen exhibits enough activity in patients with advanced or recurrent endometrial carcinoma, who have not received systemic therapy, to warrant a phase III trial. Sixty-eight eligible patients with advanced or recurrent endometrial carcinoma received oral tamoxifen 20 mg bid until toxicity was unacceptable or disease progressed. Three complete (4%) and four partial (6%) responses were observed for an overall response rate of 10% (90% confidence interval [CI], 5.7% to 17.9%). Patients with tumors that were more anaplastic tended to respond less frequently. The median progression-free survival for all 68 eligible patients was 1.9 months (90% CI, 1.7 to 3.2 months). The median survival was 8.8 months (90% CI, 7.0 to 10.1 months). Tamoxifen demonstrated modest activity at best against endometrial carcinoma and does not warrant further investigation as a single agent for this disease. Ongoing trials will assess the sequential use of tamoxifen and progestational agents.

Intraglomerular inhibition maintains mitral cell response contrast across input frequencies

PubMed Central

Shao, Zuoyi; Puche, Adam C.

2013-01-01

Odor signals are transmitted to the olfactory bulb by olfactory nerve (ON) synapses onto mitral/tufted cells (MTCs) and external tufted cells (ETCs); ETCs provide additional feed-forward excitation to MTCs. Both are strongly regulated by intraglomerular inhibition that can last up to 1 s and, when blocked, dramatically increases ON-evoked MC spiking. Intraglomerular inhibition thus limits the magnitude and duration of MC spike responses to sensory input. In vivo, sensory input is repetitive, dictated by sniffing rates from 1 to 8 Hz, potentially summing intraglomerular inhibition. To investigate this, we recorded MTC responses to 1- to 8-Hz ON stimulation in slices. Inhibitory postsynaptic current area (charge) following each ON stimulation was unchanged from 1 to 5 Hz and modestly paired-pulse attenuated at 8 Hz, suggesting there is no summation and only limited decrement at the highest input frequencies. Next, we investigated frequency independence of intraglomerular inhibition on MC spiking. MCs respond to single ON shocks with an initial spike burst followed by reduced spiking decaying to baseline. Upon repetitive ON stimulation peak spiking is identical across input frequencies but the ratio of peak-to-minimum rate before the stimulus (max-min) diminishes from 30:1 at 1 Hz to 15:1 at 8 Hz. When intraglomerular inhibition is selectively blocked, peak spike rate is unchanged but trough spiking increases markedly decreasing max-min firing ratios from 30:1 at 1 Hz to 2:1 at 8 Hz. Together, these results suggest intraglomerular inhibition is relatively frequency independent and can “sharpen” MC responses to input across the range of frequencies. This suggests that glomerular circuits can maintain “contrast” in MC encoding during sniff-sampled inputs. PMID:23926045

Intraglomerular inhibition maintains mitral cell response contrast across input frequencies.

PubMed

Shao, Zuoyi; Puche, Adam C; Shipley, Michael T

2013-11-01

Odor signals are transmitted to the olfactory bulb by olfactory nerve (ON) synapses onto mitral/tufted cells (MTCs) and external tufted cells (ETCs); ETCs provide additional feed-forward excitation to MTCs. Both are strongly regulated by intraglomerular inhibition that can last up to 1 s and, when blocked, dramatically increases ON-evoked MC spiking. Intraglomerular inhibition thus limits the magnitude and duration of MC spike responses to sensory input. In vivo, sensory input is repetitive, dictated by sniffing rates from 1 to 8 Hz, potentially summing intraglomerular inhibition. To investigate this, we recorded MTC responses to 1- to 8-Hz ON stimulation in slices. Inhibitory postsynaptic current area (charge) following each ON stimulation was unchanged from 1 to 5 Hz and modestly paired-pulse attenuated at 8 Hz, suggesting there is no summation and only limited decrement at the highest input frequencies. Next, we investigated frequency independence of intraglomerular inhibition on MC spiking. MCs respond to single ON shocks with an initial spike burst followed by reduced spiking decaying to baseline. Upon repetitive ON stimulation peak spiking is identical across input frequencies but the ratio of peak-to-minimum rate before the stimulus (max-min) diminishes from 30:1 at 1 Hz to 15:1 at 8 Hz. When intraglomerular inhibition is selectively blocked, peak spike rate is unchanged but trough spiking increases markedly decreasing max-min firing ratios from 30:1 at 1 Hz to 2:1 at 8 Hz. Together, these results suggest intraglomerular inhibition is relatively frequency independent and can "sharpen" MC responses to input across the range of frequencies. This suggests that glomerular circuits can maintain "contrast" in MC encoding during sniff-sampled inputs.

Tobacco use in popular movies during the past decade.

PubMed

Mekemson, C; Glik, D; Titus, K; Myerson, A; Shaivitz, A; Ang, A; Mitchell, S

2004-12-01

The top 50 commercially successful films released per year from 1991 to 2000 were content coded to assess trends in tobacco use over time and attributes of films predictive of higher smoking rates. This observational study used media content analysis methods to generate data about tobacco use depictions in films studied (n = 497). Films are the basic unit of analysis. Once films were coded and preliminary analysis completed, outcome data were transformed to approximate multivariate normality before being analysed with general linear models and longitudinal mixed method regression methods. Tobacco use per minute of film was the main outcome measure used. Predictor variables include attributes of films and actors. Tobacco use was defined as any cigarette, cigar, and chewing tobacco use as well as the display of smoke and cigarette paraphernalia such as ashtrays, brand names, or logos within frames of films reviewed. Smoking rates in the top films fluctuated yearly over the decade with an overall modest downward trend (p < 0.005), with the exception of R rated films where rates went up. The decrease in smoking rates found in films in the past decade is modest given extensive efforts to educate the entertainment industry on this issue over the past decade. Monitoring, education, advocacy, and policy change to bring tobacco depiction rates down further should continue.

Programs for the Principal: A Survey

ERIC Educational Resources Information Center

Martin, Evelyn B.

1972-01-01

A modest survey to determine the nature of existing programs to prepare school principals bears out the author's thesis that these programs should be more responsive to the needs of principals who are enmeshed in today's societal crises. (Editor)

AYURVEDA, AN APPROPRIATE STRATEGY FOR SOCIAL HEALTH: An overview of the Indian Panorama

PubMed Central

Bijoy, C. R.

1981-01-01

The rationale for the thought of an appropriate strategy for social health, issues from the failiure to provide health with social Justice. Too much has been said and done along a devious path by the dominant class, that, increasing marginal rate of disutility threatens the very existence of man. A modest attempt has been made here to expose the corrosion in values and priorities and as to what little should and could be done to safeguard the right to health of underprivileged mass, in the light of the lack of political will and the rise of ‘elitism’ among the responsible people, the social relevance and the natural direction of progress consistent with the values and priorities of Ayurveda as a holistic system of health. PMID:22556469

AYURVEDA, AN APPROPRIATE STRATEGY FOR SOCIAL HEALTH: An overview of the Indian Panorama.

PubMed

Bijoy, C R

1981-10-01

The rationale for the thought of an appropriate strategy for social health, issues from the failiure to provide health with social Justice. Too much has been said and done along a devious path by the dominant class, that, increasing marginal rate of disutility threatens the very existence of man. A modest attempt has been made here to expose the corrosion in values and priorities and as to what little should and could be done to safeguard the right to health of underprivileged mass, in the light of the lack of political will and the rise of 'elitism' among the responsible people, the social relevance and the natural direction of progress consistent with the values and priorities of Ayurveda as a holistic system of health.

A meta-analysis of the relationship between organizational citizenship behavior and counterproductive work behavior.

PubMed

Dalal, Reeshad S

2005-11-01

Job performance is increasingly being seen to encompass constructs such as organizational citizenship behavior (OCB) and counterproductive work behavior (CWB). To clarify the OCB-CWB relationship, a meta-analysis was conducted. Results indicate a modest negative relationship (p = -0.32). The relationship strength did not increase appreciably when the target of the behavior (the organization vs. other employees) was the same. Moreover, OCB and CWB exhibited somewhat distinct patterns of relationships with antecedents. The OCB-CWB relationship was moderated by the source of the ratings, the presence of antithetical items, and the type of response options. An employee-centric perspective is proposed whereby both OCB and CWB are perceived as adaptive behavior. Implications for organizations are discussed. ((c) 2005 APA, all rights reserved).

Seasonal water storage, stress modulation, and California seismicity.

PubMed

Johnson, Christopher W; Fu, Yuning; Bürgmann, Roland

2017-06-16

Establishing what controls the timing of earthquakes is fundamental to understanding the nature of the earthquake cycle and critical to determining time-dependent earthquake hazard. Seasonal loading provides a natural laboratory to explore the crustal response to a quantifiable transient force. In California, water storage deforms the crust as snow and water accumulates during the wet winter months. We used 9 years of global positioning system (GPS) vertical deformation time series to constrain models of monthly hydrospheric loading and the resulting stress changes on fault planes of small earthquakes. The seasonal loading analysis reveals earthquakes occurring more frequently during stress conditions that favor earthquake rupture. We infer that California seismicity rates are modestly modulated by natural hydrological loading cycles. Copyright © 2017, American Association for the Advancement of Science.

Apatinib for advanced nonsmall-cell lung cancer: A retrospective case series analysis.

PubMed

Yang, Chengxi; Feng, Wen; Wu, Di

2018-01-01

Apatinib, a tyrosine kinase inhibitor which selectively inhibits vascular endothelial growth factor receptor-2, has been shown to be beneficial to patients with a variety of cancers, including advanced nonsmall-cell lung cancer (NSCLC). Thus, this study was aimed to retrospectively assess the efficacy and safety of apatinib in patients with advanced/metastatic NSCLC who failed more than two lines of treatment. Twenty-three NSCLC patients were involved in this study, who received oral apatinib at a daily dose of 250/500/750 mg, with the progression after the failure of second-line therapy. Treatment was continued until disease progression. The tumor assessments were determined according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Safety was evaluated with adverse reactions and toxicities based on the Common Terminology Criteria for Adverse Events (version 4.0). Response and safety for the included patients were evaluated every 8 weeks. In this study, 23 NSCLC patients were followed from January 2015 to December 2016. Available image efficacy was obtained in 22 patients, including 4 identified as partial responses, 17 stable disease, and 1 progressive disease; no complete responses was observed. The objective response rate was 18.2%, and the disease control rate was 95.5%. Median progression free survival and overall survival for apatinib were 203 days (95% CI, 120-269) and 227 days (95% CI, 146-294), respectively. The most frequent treatment-related adverse events were hypertension, gastrointestinal reactions, and hand-foot skin reaction. Apatinib exhibited modest activity and acceptable toxicity for advanced NSCLC after the failure of chemotherapy or other targeted therapy.

The SOS response increases bacterial fitness, but not evolvability, under a sublethal dose of antibiotic.

PubMed

Torres-Barceló, Clara; Kojadinovic, Mila; Moxon, Richard; MacLean, R Craig

2015-10-07

Exposure to antibiotics induces the expression of mutagenic bacterial stress-response pathways, but the evolutionary benefits of these responses remain unclear. One possibility is that stress-response pathways provide a short-term advantage by protecting bacteria against the toxic effects of antibiotics. Second, it is possible that stress-induced mutagenesis provides a long-term advantage by accelerating the evolution of resistance. Here, we directly measure the contribution of the Pseudomonas aeruginosa SOS pathway to bacterial fitness and evolvability in the presence of sublethal doses of ciprofloxacin. Using short-term competition experiments, we demonstrate that the SOS pathway increases competitive fitness in the presence of ciprofloxacin. Continued exposure to ciprofloxacin results in the rapid evolution of increased fitness and antibiotic resistance, but we find no evidence that SOS-induced mutagenesis accelerates the rate of adaptation to ciprofloxacin during a 200 generation selection experiment. Intriguingly, we find that the expression of the SOS pathway decreases during adaptation to ciprofloxacin, and this helps to explain why this pathway does not increase long-term evolvability. Furthermore, we argue that the SOS pathway fails to accelerate adaptation to ciprofloxacin because the modest increase in the mutation rate associated with SOS mutagenesis is offset by a decrease in the effective strength of selection for increased resistance at a population level. Our findings suggest that the primary evolutionary benefit of the SOS response is to increase bacterial competitive ability, and that stress-induced mutagenesis is an unwanted side effect, and not a selected attribute, of this pathway. © 2015 The Authors.

The SOS response increases bacterial fitness, but not evolvability, under a sublethal dose of antibiotic

PubMed Central

Torres-Barceló, Clara; Kojadinovic, Mila; Moxon, Richard; MacLean, R. Craig

2015-01-01

Exposure to antibiotics induces the expression of mutagenic bacterial stress–response pathways, but the evolutionary benefits of these responses remain unclear. One possibility is that stress–response pathways provide a short-term advantage by protecting bacteria against the toxic effects of antibiotics. Second, it is possible that stress-induced mutagenesis provides a long-term advantage by accelerating the evolution of resistance. Here, we directly measure the contribution of the Pseudomonas aeruginosa SOS pathway to bacterial fitness and evolvability in the presence of sublethal doses of ciprofloxacin. Using short-term competition experiments, we demonstrate that the SOS pathway increases competitive fitness in the presence of ciprofloxacin. Continued exposure to ciprofloxacin results in the rapid evolution of increased fitness and antibiotic resistance, but we find no evidence that SOS-induced mutagenesis accelerates the rate of adaptation to ciprofloxacin during a 200 generation selection experiment. Intriguingly, we find that the expression of the SOS pathway decreases during adaptation to ciprofloxacin, and this helps to explain why this pathway does not increase long-term evolvability. Furthermore, we argue that the SOS pathway fails to accelerate adaptation to ciprofloxacin because the modest increase in the mutation rate associated with SOS mutagenesis is offset by a decrease in the effective strength of selection for increased resistance at a population level. Our findings suggest that the primary evolutionary benefit of the SOS response is to increase bacterial competitive ability, and that stress-induced mutagenesis is an unwanted side effect, and not a selected attribute, of this pathway. PMID:26446807

Divestiture summary report: Sale of Eklutna and Snettisham hydroelectric projects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-04-01

This report accompanies the legislative proposal to authorize sale of the two Alaskan Federal hydroelectric projects and close out the Alaska Power Administration (APA). The 78,210 kill Snettisham Project serving Juneau would be sold to the Alaska Energy Authority, a State corporation which owns six other hydroelectric projects. The 30,000 kill Eklutna Project serving the Anchorage and Matanuska Valley areas would be sold to the three electric utilities which now purchase power from that project. Terms and conditions for the sales are set out in negotiated Purchase Agreements. Key aspects include: (1) Development of Transition Plans within six months aftermore » Congress authorizes the divestiture. (2) Transaction Date to be set in the Transition Plans. (3) Description of assets to be transferred. (4) Price and payment terms. (5) Environmental Management Plans. (6) Protection of interests in several important non-power'' uses of project land and water. Under a separate agreement, the Purchasers assume responsibility for developing and implementing post-sale programs for protection, mitigation, and enhancement of fish and wildlife resources impacted by hydroelectric development in the Eldutna and Snettisham basins. The estimated sale proceeds to the United States Treasury are between $73.5 and $80.3 million, assuming the transactions are completed between October 1, 1992 and October 1, 1993. Eklutna and Snettisham are modest-sized, single-purpose hydroelectric projects involving small river basins entirely within Alaska. Locally, they are important long-term suppliers of economically-priced hydroelectric power. The sale terms and structure assure that the projects will continue to serve their intended purposes. Modest rate increases are expected over the short term, but long-term power rates are expected to be similar to those that would prevail under continued Federal ownership.« less

Divestiture summary report: Sale of Eklutna and Snettisham hydroelectric projects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-04-01

This report accompanies the legislative proposal to authorize sale of the two Alaskan Federal hydroelectric projects and close out the Alaska Power Administration (APA). The 78,210 kill Snettisham Project serving Juneau would be sold to the Alaska Energy Authority, a State corporation which owns six other hydroelectric projects. The 30,000 kill Eklutna Project serving the Anchorage and Matanuska Valley areas would be sold to the three electric utilities which now purchase power from that project. Terms and conditions for the sales are set out in negotiated Purchase Agreements. Key aspects include: (1) Development of Transition Plans within six months aftermore » Congress authorizes the divestiture. (2) Transaction Date to be set in the Transition Plans. (3) Description of assets to be transferred. (4) Price and payment terms. (5) Environmental Management Plans. (6) Protection of interests in several important ``non-power`` uses of project land and water. Under a separate agreement, the Purchasers assume responsibility for developing and implementing post-sale programs for protection, mitigation, and enhancement of fish and wildlife resources impacted by hydroelectric development in the Eldutna and Snettisham basins. The estimated sale proceeds to the United States Treasury are between $73.5 and $80.3 million, assuming the transactions are completed between October 1, 1992 and October 1, 1993. Eklutna and Snettisham are modest-sized, single-purpose hydroelectric projects involving small river basins entirely within Alaska. Locally, they are important long-term suppliers of economically-priced hydroelectric power. The sale terms and structure assure that the projects will continue to serve their intended purposes. Modest rate increases are expected over the short term, but long-term power rates are expected to be similar to those that would prevail under continued Federal ownership.« less

Plant responses to fertilization experiments in lowland, species-rich, tropical forests.

PubMed

Wright, S Joseph; Turner, Benjamin L; Yavitt, Joseph B; Harms, Kyle E; Kaspari, Michael; Tanner, Edmund V J; Bujan, Jelena; Griffin, Eric A; Mayor, Jordan R; Pasquini, Sarah C; Sheldrake, Merlin; Garcia, Milton N

2018-05-01

We present a meta-analysis of plant responses to fertilization experiments conducted in lowland, species-rich, tropical forests. We also update a key result and present the first species-level analyses of tree growth rates for a 15-yr factorial nitrogen (N), phosphorus (P), and potassium (K) experiment conducted in central Panama. The update concerns community-level tree growth rates, which responded significantly to the addition of N and K together after 10 yr of fertilization but not after 15 yr. Our experimental soils are infertile for the region, and species whose regional distributions are strongly associated with low soil P availability dominate the local tree flora. Under these circumstances, we expect muted responses to fertilization, and we predicted species associated with low-P soils would respond most slowly. The data did not support this prediction, species-level tree growth responses to P addition were unrelated to species-level soil P associations. The meta-analysis demonstrated that nutrient limitation is widespread in lowland tropical forests and evaluated two directional hypotheses concerning plant responses to N addition and to P addition. The meta-analysis supported the hypothesis that tree (or biomass) growth rate responses to fertilization are weaker in old growth forests and stronger in secondary forests, where rapid biomass accumulation provides a nutrient sink. The meta-analysis found no support for the long-standing hypothesis that plant responses are stronger for P addition and weaker for N addition. We do not advocate discarding the latter hypothesis. There are only 14 fertilization experiments from lowland, species-rich, tropical forests, 13 of the 14 experiments added nutrients for five or fewer years, and responses vary widely among experiments. Potential fertilization responses should be muted when the species present are well adapted to nutrient-poor soils, as is the case in our experiment, and when pest pressure increases with fertilization, as it does in our experiment. The statistical power and especially the duration of fertilization experiments conducted in old growth, tropical forests might be insufficient to detect the slow, modest growth responses that are to be expected. © 2018 by the Ecological Society of America.

Morphological and sedimentological responses of streams to human impact in the southern Blue Ridge Mountains, USA

Treesearch

Katie Price; David S. Leigh

2006-01-01

Morphological and sedimentological responses of streams to basin-scale impact have been well documented for intensively agricultural or urban areas. Sensitivity thresholds of streams to modest levels of disturbance, however, are not well understood. This study addresses the influence of forest conversion on streams of the southern Blue Ridge Mountains, a region that...

Citation Help in Databases: The More Things Change, the More They Stay the Same

ERIC Educational Resources Information Center

Van Ullen, Mary; Kessler, Jane

2012-01-01

In 2005, the authors reviewed citation help in databases and found an error rate of 4.4 errors per citation. This article describes a follow-up study that revealed a modest improvement in the error rate to 3.4 errors per citation, still unacceptably high. The most problematic area was retrieval statements. The authors conclude that librarians…

Phase shift method to estimate solids circulation rate in circulating fluidized beds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ludlow, James Christopher; Panday, Rupen; Shadle, Lawrence J.

2013-01-01

While solids circulation rate is a critical design and control parameter in circulating fluidized bed (CFB) reactor systems, there are no available techniques to measure it directly at conditions of industrial interest. Cold flow tests have been conducted at NETL in an industrial scale CFB unit where the solids flow has been the topic of research in order to develop an independent method which could be applied to CFBs operating under the erosive and corrosive high temperatures and pressures of a coal fired boiler or gasifier. The dynamic responses of the CFB loop to modest modulated aeration flows in themore » return leg or standpipe were imposed to establish a periodic response in the unit without causing upset in the process performance. The resulting periodic behavior could then be analyzed with a dynamic model and the average solids circulation rate could be established. This method was applied to the CFB unit operated under a wide range of operating conditions including fast fluidization, core annular flow, dilute and dense transport, and dense suspension upflow. In addition, the system was operated in both low and high total solids inventories to explore the influence of inventory limiting cases on the estimated results. The technique was able to estimate the solids circulation rate for all transport circulating fluidized beds when operating above upper transport velocity, U{sub tr2}. For CFB operating in the fast fluidized bed regime (i.e., U{sub g}< U{sub tr2}), the phase shift technique was not successful. The riser pressure drop becomes independent of the solids circulation rate and the mass flow rate out of the riser does not show modulated behavior even when the riser pressure drop does.« less

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

PubMed

Alsina, Maria; Rivera, Fernando; Ramos, Francisco Javier; Galán, Maica; López, Rafael; García-Alfonso, Pilar; Alés-Martinez, José Enrique; Queralt, Bernardo; Antón, Antonio; Carrato, Alfredo; Grávalos, Cristina; Méndez-Vidal, Maria José; López, Carlos; de Mena, Inmaculada Ruiz; Tabernero, Josep; Giralt, Jordi; Aranda, Enrique

2018-02-01

Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate. We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study. Between November 2006 and April 2009, 50 patients with stage II-IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles. Six weeks later, patients with response or stabilisation initiated 6 weeks of cisplatin/cetuximab/radiotherapy, followed by surgery. The primary objective was the clinical complete response (cCR) rate after induction therapy plus chemoradiotherapy in intent-to-treat patients. Thirty-eight patients were evaluable after chemoradiotherapy, 84% of whom showed disease control. Six patients (12%) achieved a cCR, with a 54% overall response rate. Twenty-seven patients underwent surgery, 11 of whom (22%; nine SCC, two adenocarcinoma) had a pathological CR (41%). Fifteen patients were alive after a median follow-up of 23.2 months. Median progression-free survival was 12.2 months (95% confidence interval [CI] 1.7-22.8). Median overall survival was 23.4 months (95% CI 12.2-36.6) and was significantly longer among the 22 patients with complete resection than in the five patients without (42.1 vs. 24.9 months; p = 0.02, hazard ratio: 3.6, 95% CI 1.1-11.6). The toxicity profile was acceptable. Neoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature. Registration: The study is registered at ClinicalTrials.gov (NCT00733889).

HUMAN INTERINDIVIDUAL VARIABILITY IN SUSCEPTIBILITY TO AIRBORNE PARTICLES

EPA Science Inventory

Part of the explanation for the persistent epidemiological findings of associations between mortality and morbidity with relatively modest ambient exposures to airborne particles may be that some people are much more susceptible to particle-induced responses than others. This stu...

A written language intervention for at-risk second grade students: a randomized controlled trial of the process assessment of the learner lesson plans in a tier 2 response-to-intervention (RtI) model.

PubMed

Hooper, Stephen R; Costa, Lara-Jeane C; McBee, Matthew; Anderson, Kathleen L; Yerby, Donna Carlson; Childress, Amy; Knuth, Sean B

2013-04-01

In a randomized controlled trial, 205 students were followed from grades 1 to 3 with a focus on changes in their writing trajectories following an evidence-based intervention during the spring of second grade. Students were identified as being at-risk (n=138), and then randomized into treatment (n=68) versus business-as-usual conditions (n=70). A typical group also was included (n=67). The writing intervention comprised Lesson Sets 4 and 7 from the Process Assessment of the Learner (PAL), and was conducted via small groups (three to six students) twice a week for 12 weeks in accordance with a response-to-intervention Tier 2 model. The primary outcome was the Wechsler Individual Achievement Test-II Written Expression Scale. Results indicated modest support for the PAL lesson plans, with an accelerated rate of growth in writing skills following treatment. There were no significant moderator effects, although there was evidence that the most globally impaired students demonstrated a more rapid rate of growth following treatment. These findings suggest the need for ongoing examination of evidence-based treatments in writing for young elementary students.

Effects of high flavanol dark chocolate on cardiovascular function and platelet aggregation.

PubMed

Rull, Gurvinder; Mohd-Zain, Zetty N; Shiel, Julian; Lundberg, Martina H; Collier, David J; Johnston, Atholl; Warner, Timothy D; Corder, Roger

2015-08-01

Regular consumption of chocolate and cocoa products has been linked to reduced cardiovascular mortality. This study compared the effects of high flavanol dark chocolate (HFDC; 1064mg flavanols/day for 6weeks) and low flavanol dark chocolate (LFDC; 88mg flavanols/day for 6weeks) on blood pressure, heart rate, vascular function and platelet aggregation in men with pre-hypertension or mild hypertension. Vascular function was assessed by pulse wave analysis using radial artery applanation tonometry in combination with inhaled salbutamol (0.4mg) to assess changes due to endothelium-dependent vasodilatation. HFDC did not significantly reduce blood pressure compared to baseline or LFDC. Heart rate was increased by LFDC compared to baseline, but not by HFDC. Vascular responses to salbutamol tended to be greater after HFDC. Platelet aggregation induced by collagen or the thromboxane analogue U46619 was unchanged after LFDC or HFDC, whereas both chocolates reduced responses to ADP and the thrombin receptor activator peptide, SFLLRNamide (TRAP6), relative to baseline. Pre-incubation of platelets with theobromine also attenuated platelet aggregation induced by ADP or TRAP6. We conclude that consumption of HFDC confers modest improvements in cardiovascular function. Platelet aggregation is modulated by a flavanol-independent mechanism that is likely due to theobromine. Copyright © 2015 Elsevier Inc. All rights reserved.

Electric stimulus duration alters network-mediated responses depending on retinal ganglion cell type

NASA Astrophysics Data System (ADS)

Im, Maesoon; Werginz, Paul; Fried, Shelley I.

2018-06-01

Objective. To improve the quality of artificial vision that arises from retinal prostheses, it is important to bring electrically-elicited neural activity more in line with the physiological signaling patterns that arise normally in the healthy retina. Our previous study reported that indirect activation produces a closer match to physiological responses in ON retinal ganglion cells (RGCs) than in OFF cells (Im and Fried 2015 J. Physiol. 593 3677-96). This suggests that a preferential activation of ON RGCs would shape the overall retinal response closer to natural signaling. Recently, we found that changes to the rate at which stimulation was delivered could bias responses towards a stronger ON component (Im and Fried 2016a J. Neural Eng. 13 025002), raising the possibility that changes to other stimulus parameters can similarly bias towards stronger ON responses. Here, we explore the effects of changing stimulus duration on the responses in ON and OFF types of brisk transient (BT) and brisk sustained (BS) RGCs. Approach. We used cell-attached patch clamp to record RGC spiking in the isolated rabbit retina. Targeted RGCs were first classified as ON or OFF type by their light responses, and further sub-classified as BT or BS types by their responses to both light and electric stimuli. Spiking in targeted RGCs was recorded in response to electric pulses with durations varying from 5 to100 ms. Stimulus amplitude was adjusted at each duration to hold total charge constant for all experiments. Main results. We found that varying stimulus durations modulated responses differentially for ON versus OFF cells: in ON cells, spike counts decreased significantly with increasing stimulus duration while in OFF cells the changes were more modest. The maximum ratio of ON versus OFF responses occurred at a duration of ~10 ms. The difference in response strength for BT versus BS cells was much larger in ON cells than in OFF cells. Significance. The stimulation rates preferred by subjects during clinical trials are similar to the rates that maximize the ON/OFF response ratio in in vitro testing (Im and Fried 2016a J. Neural Eng. 13 025002). Here, we determine the stimulus duration that produces the strongest bias towards ON responses and speculate that it will further enhance clinical effectiveness.

Tobacco use in popular movies during the past decade

PubMed Central

Mekemson, C; Glik, D; Titus, K; Myerson, A; Shaivitz, A; Ang, A; Mitchell, S

2004-01-01

Objective: The top 50 commercially successful films released per year from 1991 to 2000 were content coded to assess trends in tobacco use over time and attributes of films predictive of higher smoking rates. Design: This observational study used media content analysis methods to generate data about tobacco use depictions in films studied (n = 497). Films are the basic unit of analysis. Once films were coded and preliminary analysis completed, outcome data were transformed to approximate multivariate normality before being analysed with general linear models and longitudinal mixed method regression methods. Main outcome measures: Tobacco use per minute of film was the main outcome measure used. Predictor variables include attributes of films and actors. Tobacco use was defined as any cigarette, cigar, and chewing tobacco use as well as the display of smoke and cigarette paraphernalia such as ashtrays, brand names, or logos within frames of films reviewed. Results: Smoking rates in the top films fluctuated yearly over the decade with an overall modest downward trend (p < 0.005), with the exception of R rated films where rates went up. Conclusions: The decrease in smoking rates found in films in the past decade is modest given extensive efforts to educate the entertainment industry on this issue over the past decade. Monitoring, education, advocacy, and policy change to bring tobacco depiction rates down further should continue. PMID:15564625

The effects of body temperature and mass on the postprandial metabolic responses of the African egg-eating snakes Dasypeltis scabra and Dasypeltis inornata.

PubMed

Greene, Sara; McConnachie, Suzanne; Secor, Stephen; Perrin, Mike

2013-06-01

African egg-eating snakes (Dasypeltis) feed only on freshly laid bird eggs which they perforate within their esophagus before swallowing the liquid contents and regurgitating the empty shell. Compared to a snake's typical intact meal, the liquid diet of Dasypeltis would expectedly generate a more moderate postprandial metabolic response and specific dynamic action (SDA). Free-ranging Dasypeltis feed over a range of ambient temperatures and thereby experience predicted temperature-dependent shifts in the duration and magnitude of their postprandial metabolic response. Such shifts would undoubtedly be shared among different species and age classes of Dasypeltis. To examine these expectations, we measured pre- and postprandial metabolic rates of adult Dasypeltis inornata and adult and neonate Dasypeltis scabra in response to liquid egg meals weighing 20% of snake body mass at 20, 25, 27, 30, and 32 °C. With an increase in body temperature, postprandial metabolic profiles of neonate and adult snakes became narrower and shorter in duration. Specific dynamic action varied among temperature treatments, increasing from 20 to 32 °C. Standard metabolic rate, postprandial peak metabolic rate, and SDA scaled with mass exponents that typically did not differ from 1.0. As expected, Dasypeltis digesting a liquid egg diet experienced a more modest postprandial response and SDA, expending on average only 10.6% of the meal's energy on the breakdown, absorption, and assimilation of the egg meal, whereas other colubrids consuming intact rodent or fish meals expend on average 16.3% of the meal's energy on digestion and assimilation. Actively foraging and feeding throughout the avian egg laying season enable Dasypeltis to survive when eggs are not available. The adaptive suite of traits that enable Dasypeltis to consume eggs of large relative size and ingest only the liquid contents may also be joined by physiological adaptations specific to their liquid diet and extended bouts of fasting. Copyright © 2013 Elsevier Inc. All rights reserved.

The Nation's Colleges Show a Modest Improvement in African-American Graduation Rates, but a Huge Racial Gap Remains.

ERIC Educational Resources Information Center

Journal of Blacks in Higher Education, 2003

2003-01-01

Nationwide, fewer than two out of five entering black college students earn their degrees, while three out of five entering white students go on to graduate. Nearly 19 out of 20 black students at highly competitive universities earn their diplomas. Black women outpace black men in college completion. Examines trends in black graduation rates at…

Daily Interpersonal and Affective Dynamics in Personality Disorder

PubMed Central

Wright, Aidan G.C.; Hopwood, Christopher J.; Simms, Leonard J.

2015-01-01

In this naturalistic study we adopt the lens of interpersonal theory to examine between-and within-person differences in dynamic processes of daily affect and interpersonal behaviors among individuals (N = 101) previously diagnosed with personality disorders who completed daily diaries over the course of 100 days. Dispositional ratings of interpersonal problems and measures of daily stress were used as predictors of daily shifts in interpersonal behavior and affect in multilevel models. Results indicate that ~40%–50% of the variance in interpersonal behavior and affect is due to daily fluctuations, which are modestly related to dispositional measures of interpersonal problems but strongly related to daily stress. The findings support conceptions of personality disorders as a dynamic form of psychopathology involving the individuals interacting with and regulating in response to the contextual features of their environment. PMID:26200849

Proinflammatory Stem Cell Signaling in Cardiac Ischemia

PubMed Central

Herrmann, Jeremy L.; Markel, Troy A.; Abarbanell, Aaron M.; Weil, Brent R.; Wang, Meijing; Wang, Yue; Tan, Jiangning

2009-01-01

Abstract Cardiovascular disease remains a leading cause of mortality in developed nations, despite continued advancement in modern therapy. Progenitor and stem cell–based therapy is a novel treatment for cardiovascular disease, and modest benefits in cardiac recovery have been achieved in small clinical trials. This therapeutic modality remains challenged by limitations of low donor-cell survival rates, transient recovery of cardiac function, and the technical difficulty of applying directed cell therapy. Understanding the signaling mechanisms involved in the stem cell response to ischemia has revealed opportunities to modify directly aspects of these pathways to improve their cardioprotective abilities. This review highlights general considerations of stem cell therapy for cardiac disease, reviews the major proinflammatory signaling pathways of mesenchymal stem cells, and reviews ex vivo modifications of stem cells based on these pathways. Antioxid. Redox Signal. 11, 1883–1896. PMID:19187005

Mechanisms of breathing instability in patients with obstructive sleep apnea.

PubMed

Younes, Magdy; Ostrowski, Michele; Atkar, Raj; Laprairie, John; Siemens, Andrea; Hanly, Patrick

2007-12-01

The response to chemical stimuli (chemical responsiveness) and the increases in respiratory drive required for arousal (arousal threshold) and for opening the airway without arousal (effective recruitment threshold) are important determinants of ventilatory instability and, hence, severity of obstructive apnea. We measured these variables in 21 obstructive apnea patients (apnea-hypopnea index 91 +/- 24 h(-1)) while on continuous-positive-airway pressure. During sleep, pressure was intermittently reduced (dial down) to induce severe hypopneas. Dial downs were done on room air and following approximately 30 s of breathing hypercapneic and/or hypoxic mixtures, which induced a range of ventilatory stimulation before dial down. Ventilation just before dial down and flow during dial down were measured. Chemical responsiveness, estimated as the percent increase in ventilation during the 5(th) breath following administration of 6% CO(2) combined with approximately 4% desaturation, was large (187 +/- 117%). Arousal threshold, estimated as the percent increase in ventilation associated with a 50% probability of arousal, ranged from 40% to >268% and was <120% in 12/21 patients, indicating that in many patients arousal occurs with modest changes in chemical drive. Effective recruitment threshold, estimated as percent increase in pre-dial-down ventilation associated with a significant increase in dial-down flow, ranged from zero to >174% and was <110% in 12/21 patients, indicating that in many patients reflex dilatation occurs with modest increases in drive. The two thresholds were not correlated. In most OSA patients, airway patency may be maintained with only modest increases in chemical drive, but instability results because of a low arousal threshold and a brisk increase in drive following brief reduction in alveolar ventilation.

Does catatonic schizophrenia improve faster with electroconvulsive therapy than other subtypes of schizophrenia?

PubMed

Thirthalli, Jagadisha; Phutane, Vivek H; Muralidharan, Kesavan; Kumar, Channaveerachari Naveen; Munishwar, Bharat; Baspure, Prashant; Gangadhar, Bangalore N

2009-01-01

Electroconvulsive therapy (ECT) is generally recommended for treating catatonic schizophrenia. Non-catatonic schizophrenia patients also receive ECT. We compared the speed of response to ECT among patients with catatonic and other subtypes of schizophrenia. Consecutive schizophrenia patients referred for ECT within 3 months of starting antipsychotic treatment were studied (19 with catatonic and 34 with non-catatonic schizophrenia). Nurse's Observation Scale for Inpatient Evaluation (NOSIE-30) and Clinical Global Impression (CGI) were used to rate improvement. Referring psychiatrists stopped ECTs based on clinical impression of improvement. Total number of ECTs was taken as an indirect measure of speed of response. NOSIE-30 scores were compared using repeated measures analysis of variance. Catatonic schizophrenia patients required significantly fewer ECTs to achieve clinically significant improvement. There was a significant group x occasion effect in NOSIE scores, suggesting faster response to ECT in the catatonia group (F=41.6; P<0.001). Survival analysis suggested that patients with catatonic schizophrenia required significantly fewer ECTs (one less session on an average) to achieve clinical improvement (Log-rank statistic =5.31; P=0.02). Catatonic schizophrenia responds faster to ECT than non-catatonic schizophrenia. However, the magnitude of the difference is modest.

High mutation rates limit evolutionary adaptation in Escherichia coli

PubMed Central

Wagner, Andreas

2018-01-01

Mutation is fundamental to evolution, because it generates the genetic variation on which selection can act. In nature, genetic changes often increase the mutation rate in systems that range from viruses and bacteria to human tumors. Such an increase promotes the accumulation of frequent deleterious or neutral alleles, but it can also increase the chances that a population acquires rare beneficial alleles. Here, we study how up to 100-fold increases in Escherichia coli’s genomic mutation rate affect adaptive evolution. To do so, we evolved multiple replicate populations of asexual E. coli strains engineered to have four different mutation rates for 3000 generations in the laboratory. We measured the ability of evolved populations to grow in their original environment and in more than 90 novel chemical environments. In addition, we subjected the populations to whole genome population sequencing. Although populations with higher mutation rates accumulated greater genetic diversity, this diversity conveyed benefits only for modestly increased mutation rates, where populations adapted faster and also thrived better than their ancestors in some novel environments. In contrast, some populations at the highest mutation rates showed reduced adaptation during evolution, and failed to thrive in all of the 90 alternative environments. In addition, they experienced a dramatic decrease in mutation rate. Our work demonstrates that the mutation rate changes the global balance between deleterious and beneficial mutational effects on fitness. In contrast to most theoretical models, our experiments suggest that this tipping point already occurs at the modest mutation rates that are found in the wild. PMID:29702649

Cloud-to-Ground Lightning Characteristics of a Major Tropical Cyclone Tornado Outbreak

NASA Technical Reports Server (NTRS)

McCaul, Eugene W., Jr.; Buechler, Dennis; Goodman, Steven J.

1999-01-01

A comprehensive analysis has been conducted of the cloud-to-ground lightning activity occurring within a landfalling tropical cyclone that produced an outbreak of strong and damaging tornadoes. Radar data indicate that 12 convective cells were responsible for 29 tornadoes, several of which received an F3 intensity rating, in the southeastern United States on 16 August 1994 within the remnants of Tropical Storm Beryl. Of these 12 tornadic storms, the most active cell produced 315 flashes over a 5.5 hour period, while the other storms were less active. Three tornadic storms failed to produce any CG lightning at all. In general, the tornadic storms were more active electrically than other non-tornadic cells within Beryl's remnants, although the flash rates were rather modest by comparison with significant midlatitude severe storm events. Very few positive polarity flashes were found in the Beryl outbreak. During some of the stronger tornadoes, CG flash rates in the parent storms showed sharp transient decreases. Doppler radar data suggest the stronger tornadic storms were small supercells, and the lightning data indicate these storms exhibited lightning characteristics similar to those found in heavy-precipitation supercell storms.

Complimentary mechanisms of dual checkpoint blockade expand unique T-cell repertoires and activate adaptive anti-tumor immunity in triple-negative breast tumors

PubMed Central

Wei, Junping; Yang, Xiao Yi; Lei, Gangjun; Wang, Tao; Liu, Cong-Xiao; Morse, Michael A.; Gouin, Kenneth; Knott, Simon R. V.; Hartman, Zachary C.

2018-01-01

ABSTRACT Triple-negative breast cancer (TNBC) is an aggressive and molecularly diverse breast cancer subtype typified by the presence of p53 mutations (∼80%), elevated immune gene signatures and neoantigen expression, as well as the presence of tumor infiltrating lymphocytes (TILs). As these factors are hypothesized to be strong immunologic prerequisites for the use of immune checkpoint blockade (ICB) antibodies, multiple clinical trials testing single ICBs have advanced to Phase III, with early indications of heterogeneous response rates of <20% to anti-PD1 and anti-PDL1 ICB. While promising, these modest response rates highlight the need for mechanistic studies to understand how different ICBs function, how their combination impacts functionality and efficacy, as well as what immunologic parameters predict efficacy to different ICBs regimens in TNBC. To address these issues, we tested anti-PD1 and anti-CTLA4 in multiple models of TNBC and found that their combination profoundly enhanced the efficacy of either treatment alone. We demonstrate that this efficacy is due to anti-CTLA4-driven expansion of an individually unique T-cell receptor (TCR) repertoire whose functionality is enhanced by both intratumoral Treg suppression and anti-PD1 blockade of tumor expressed PDL1. Notably, the individuality of the TCR repertoire was observed regardless of whether the tumor cells expressed a nonself antigen (ovalbumin) or if tumor-specific transgenic T-cells were transferred prior to sequencing. However, responsiveness was strongly correlated with systemic measures of tumor-specific T-cell and B-cell responses, which along with systemic assessment of TCR expansion, may serve as the most useful predictors for clinical responsiveness in future clinical trials of TNBC utilizing anti-PD1/anti-CTLA4 ICB. PMID:29721371

Complimentary mechanisms of dual checkpoint blockade expand unique T-cell repertoires and activate adaptive anti-tumor immunity in triple-negative breast tumors.

PubMed

Crosby, Erika J; Wei, Junping; Yang, Xiao Yi; Lei, Gangjun; Wang, Tao; Liu, Cong-Xiao; Agarwal, Pankaj; Korman, Alan J; Morse, Michael A; Gouin, Kenneth; Knott, Simon R V; Lyerly, H Kim; Hartman, Zachary C

2018-01-01

Triple-negative breast cancer (TNBC) is an aggressive and molecularly diverse breast cancer subtype typified by the presence of p53 mutations (∼80%), elevated immune gene signatures and neoantigen expression, as well as the presence of tumor infiltrating lymphocytes (TILs). As these factors are hypothesized to be strong immunologic prerequisites for the use of immune checkpoint blockade (ICB) antibodies, multiple clinical trials testing single ICBs have advanced to Phase III, with early indications of heterogeneous response rates of <20% to anti-PD1 and anti-PDL1 ICB. While promising, these modest response rates highlight the need for mechanistic studies to understand how different ICBs function, how their combination impacts functionality and efficacy, as well as what immunologic parameters predict efficacy to different ICBs regimens in TNBC. To address these issues, we tested anti-PD1 and anti-CTLA4 in multiple models of TNBC and found that their combination profoundly enhanced the efficacy of either treatment alone. We demonstrate that this efficacy is due to anti-CTLA4-driven expansion of an individually unique T-cell receptor (TCR) repertoire whose functionality is enhanced by both intratumoral Treg suppression and anti-PD1 blockade of tumor expressed PDL1. Notably, the individuality of the TCR repertoire was observed regardless of whether the tumor cells expressed a nonself antigen (ovalbumin) or if tumor-specific transgenic T-cells were transferred prior to sequencing. However, responsiveness was strongly correlated with systemic measures of tumor-specific T-cell and B-cell responses, which along with systemic assessment of TCR expansion, may serve as the most useful predictors for clinical responsiveness in future clinical trials of TNBC utilizing anti-PD1/anti-CTLA4 ICB.

Metabolic consequences of resistive-type exercise

NASA Technical Reports Server (NTRS)

Dudley, G. A.

1988-01-01

This brief review concerns acute and chronic metabolic responses to resistive-type exercise (RTE) (i.e., Olympic/power weight lifting and bodybuilding). Performance of RTE presents power output substantially greater (10-15-fold) than that evident with endurance-type exercise. Accordingly, RTE relies heavily on the anaerobic enzyme machinery of skeletal muscle for energy supply, with alterations in the rate of aerobic metabolism being modest. Hydrolysis of high energy phosphate compounds (PC, ATP), glycogenolysis, and glycolysis are evident during an acute bout of RTE as indicated by metabolic markers in mixed fiber type skeletal muscle samples. The type of RTE probably influences the magnitude of these responses since the increase in blood lactate is much greater during a typical "bodybuilding" than "power lifting" session. The influence of RTE training on acute metabolic responses to RTE has received little attention. An individual's inherent metabolic characteristics are apparently sufficient to meet the energy demands of RTE as training of this type does not increase VO2max or substantially alter the content of marker enzymes in mixed fiber type skeletal muscle. Analyses of pools of fast- vs slow-twitch fibers, however, indicate that RTE-induced changes may be fiber type specific. Future studies should better delineate the metabolic responses to RTE and determine whether these are related to the enhanced performance associated with such training.

Impact of task-related changes in heart rate on estimation of hemodynamic response and model fit.

PubMed

Hillenbrand, Sarah F; Ivry, Richard B; Schlerf, John E

2016-05-15

The blood oxygen level dependent (BOLD) signal, as measured using functional magnetic resonance imaging (fMRI), is widely used as a proxy for changes in neural activity in the brain. Physiological variables such as heart rate (HR) and respiratory variation (RV) affect the BOLD signal in a way that may interfere with the estimation and detection of true task-related neural activity. This interference is of particular concern when these variables themselves show task-related modulations. We first establish that a simple movement task reliably induces a change in HR but not RV. In group data, the effect of HR on the BOLD response was larger and more widespread throughout the brain than were the effects of RV or phase regressors. The inclusion of HR regressors, but not RV or phase regressors, had a small but reliable effect on the estimated hemodynamic response function (HRF) in M1 and the cerebellum. We next asked whether the inclusion of a nested set of physiological regressors combining phase, RV, and HR significantly improved the model fit in individual participants' data sets. There was a significant improvement from HR correction in M1 for the greatest number of participants, followed by RV and phase correction. These improvements were more modest in the cerebellum. These results indicate that accounting for task-related modulation of physiological variables can improve the detection and estimation of true neural effects of interest. Copyright © 2016 Elsevier Inc. All rights reserved.

Does interview mode matter for food security measurement? Telephone versus in-person interviews in the Current Population Survey Food Security Supplement.

PubMed

Nord, Mark; Hopwood, Heather

2007-12-01

To assess whether interview mode (telephone vs. in-person) affects the results of surveys that measure food security. Responses given by households interviewed by telephone and in-person in recent US Current Population Survey Food Security Supplements (CPS-FSS) were compared. Statistical methods based on the Rasch measurement model were used to assess whether response patterns differed between the two interview modes. Multivariate logistic regression analysis was then used to gauge the effect of interview mode on the measured household prevalence rates of food insecurity and very low food security while controlling for income, employment, household structure, and other household characteristics that affect food security. Response patterns to the indicators that comprise the food security scale did not differ substantially between interview modes. Prevalence rates of food insecurity and very low food security estimated from the two interview modes differed by only small proportions after accounting for differences in the socio-economic characteristics of households. Findings suggest that effects of interview mode on food security measurement in the CPS-FSS are small, or at most modest. Prevalence estimates may be biased upwards somewhat for households interviewed in-person compared with those interviewed by telephone. The extent to which these results can be generalised may depend, to some extent, on survey characteristics other than interview mode, such as surveyor name recognition and respondents' trust and confidence in the surveyor.

Acquisition of Conditioning between Methamphetamine and Cues in Healthy Humans

PubMed Central

Mayo, Leah M.; de Wit, Harriet

2016-01-01

Environmental stimuli repeatedly paired with drugs of abuse can elicit conditioned responses that are thought to promote future drug seeking. We recently showed that healthy volunteers acquired conditioned responses to auditory and visual stimuli after just two pairings with methamphetamine (MA, 20 mg, oral). This study extended these findings by systematically varying the number of drug-stimuli pairings. We expected that more pairings would result in stronger conditioning. Three groups of healthy adults were randomly assigned to receive 1, 2 or 4 pairings (Groups P1, P2 and P4, Ns = 13, 16, 16, respectively) of an auditory-visual stimulus with MA, and another stimulus with placebo (PBO). Drug-cue pairings were administered in an alternating, counterbalanced order, under double-blind conditions, during 4 hr sessions. MA produced prototypic subjective effects (mood, ratings of drug effects) and alterations in physiology (heart rate, blood pressure). Although subjects did not exhibit increased behavioral preference for, or emotional reactivity to, the MA-paired cue after conditioning, they did exhibit an increase in attentional bias (initial gaze) toward the drug-paired stimulus. Further, subjects who had four pairings reported “liking” the MA-paired cue more than the PBO cue after conditioning. Thus, the number of drug-stimulus pairings, varying from one to four, had only modest effects on the strength of conditioned responses. Further studies investigating the parameters under which drug conditioning occurs will help to identify risk factors for developing drug abuse, and provide new treatment strategies. PMID:27548681

Auditory brainstem response latency in forward masking, a marker of sensory deficits in listeners with normal hearing thresholds

PubMed Central

Mehraei, Golbarg; Gallardo, Andreu Paredes; Shinn-Cunningham, Barbara G.; Dau, Torsten

2017-01-01

In rodent models, acoustic exposure too modest to elevate hearing thresholds can nonetheless cause auditory nerve fiber deafferentation, interfering with the coding of supra-threshold sound. Low-spontaneous rate nerve fibers, important for encoding acoustic information at supra-threshold levels and in noise, are more susceptible to degeneration than high-spontaneous rate fibers. The change in auditory brainstem response (ABR) wave-V latency with noise level has been shown to be associated with auditory nerve deafferentation. Here, we measured ABR in a forward masking paradigm and evaluated wave-V latency changes with increasing masker-to-probe intervals. In the same listeners, behavioral forward masking detection thresholds were measured. We hypothesized that 1) auditory nerve fiber deafferentation increases forward masking thresholds and increases wave-V latency and 2) a preferential loss of low-SR fibers results in a faster recovery of wave-V latency as the slow contribution of these fibers is reduced. Results showed that in young audiometrically normal listeners, a larger change in wave-V latency with increasing masker-to-probe interval was related to a greater effect of a preceding masker behaviorally. Further, the amount of wave-V latency change with masker-to-probe interval was positively correlated with the rate of change in forward masking detection thresholds. Although we cannot rule out central contributions, these findings are consistent with the hypothesis that auditory nerve fiber deafferentation occurs in humans and may predict how well individuals can hear in noisy environments. PMID:28159652

Cochlea-scaled spectral entropy predicts rate-invariant intelligibility of temporally distorted sentences.

PubMed

Stilp, Christian E; Kiefte, Michael; Alexander, Joshua M; Kluender, Keith R

2010-10-01

Some evidence, mostly drawn from experiments using only a single moderate rate of speech, suggests that low-frequency amplitude modulations may be particularly important for intelligibility. Here, two experiments investigated intelligibility of temporally distorted sentences across a wide range of simulated speaking rates, and two metrics were used to predict results. Sentence intelligibility was assessed when successive segments of fixed duration were temporally reversed (exp. 1), and when sentences were processed through four third-octave-band filters, the outputs of which were desynchronized (exp. 2). For both experiments, intelligibility decreased with increasing distortion. However, in exp. 2, intelligibility recovered modestly with longer desynchronization. Across conditions, performances measured as a function of proportion of utterance distorted converged to a common function. Estimates of intelligibility derived from modulation transfer functions predict a substantial proportion of the variance in listeners' responses in exp. 1, but fail to predict performance in exp. 2. By contrast, a metric of potential information, quantified as relative dissimilarity (change) between successive cochlear-scaled spectra, is introduced. This metric reliably predicts listeners' intelligibility across the full range of speaking rates in both experiments. Results support an information-theoretic approach to speech perception and the significance of spectral change rather than physical units of time.

Demonstration of a high repetition rate capillary discharge waveguide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonsalves, A. J., E-mail: ajgonsalves@lbl.gov; Pieronek, C.; Daniels, J.

2016-01-21

A hydrogen-filled capillary discharge waveguide operating at kHz repetition rates is presented for parameters relevant to laser plasma acceleration (LPA). The discharge current pulse was optimized for erosion mitigation with laser guiding experiments and MHD simulation. Heat flow simulations and measurements showed modest temperature rise at the capillary wall due to the average heat load at kHz repetition rates with water-cooled capillaries, which is promising for applications of LPAs such as high average power radiation sources.

Phenotypic clines, energy balances and ecological responses to climate change.

PubMed

Buckley, Lauren B; Nufio, César R; Kingsolver, Joel G

2014-01-01

The Metabolic Theory of Ecology has renewed interest in using energetics to scale across levels of ecological organization. Can scaling from individual phenotypes to population dynamics provides insight into why species have shifted their phenologies, abundances and distributions idiosyncratically in response to recent climate change? We consider how the energetic implications of phenotypes may scale to understand population and species level responses to climate change using four focal grasshopper species along an elevation gradient in Colorado. We use a biophysical model to translate phenotypes and environmental conditions into estimates of body temperatures. We measure thermal tolerances and preferences and metabolic rates to assess rates of energy use and acquisition. Body mass declines along the elevation gradient for all species, but mass-specific metabolic rates increases only modestly. We find interspecific differences in both overall thermal tolerances and preferences and in the variation of these metrics along the elevation gradient. The more dispersive species exhibit significantly higher thermal tolerance and preference consistent with much of their range spanning hot, low elevation areas. When integrating these metrics to consider metabolic constraints, we find that energetic costs decrease along the elevation gradient due to decreasing body size and temperature. Opportunities for energy acquisition, as reflected by the proportion of time that falls within a grasshopper's thermal tolerance range, peak at mid elevations. We discuss methods for translating these energetic metrics into population dynamics. Quantifying energy balances and allocation offers a viable approach for predicting how populations will respond to climate change and the consequences for species composed of populations that may be locally adapted. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

Managing the downturn

Treesearch

Urs Buehlmann; Matt Bumgardner; Al Schuler; Jeff Crissey

2008-01-01

After years of seemingly unrestricted growth, the housing market has turned and is deteriorating fast. Housing construction and sales have slowed dramatically, foreclosures have skyrocketed and mortgage rates have increased modestly despite the Federal Reserve's easing of monetary policy. Given the increasingly high dependency of the wood products industry on...

Smoking cessation after 12 months with multi-component therapy.

PubMed

Raich, Antònia; Martínez-Sánchez, Jose Maria; Marquilles, Emili; Rubio, Lídia; Fu, Marcela; Fernández, Esteve

2015-03-01

Smoking is one of the most important causes of morbidity and mortality in developed countries. One of the priorities of public health programmes is the reduction of its prevalence, which would involve millions of people quitting smoking, but cessation programs often have modest results, especially within certain population groups. The aim of this study was to analyze the variables determining the success of a multicomponent therapy programme for smoking cessation. We conducted the study in the Smoking Addiction Unit at the Hospital of Manresa, with 314 patients (91.4% of whom had medium or high-level dependency). We observed that higher educational level, not living with a smoker, following a multimodal programme or smoking cessation with psychological therapy, and pharmacological treatment are relevant factors for quitting smoking. Abstinence rates are not associated with other factors, such as sex, age, smoking behaviour characteristics or psychiatric history. The combination of pharmacological and psychological treatment increased success rates in multicomponent therapy. Psychological therapy only also obtained positive results, though somewhat more modest.

Understanding the demographic drivers of realized population growth rates.

PubMed

Koons, David N; Arnold, Todd W; Schaub, Michael

2017-10-01

Identifying the demographic parameters (e.g., reproduction, survival, dispersal) that most influence population dynamics can increase conservation effectiveness and enhance ecological understanding. Life table response experiments (LTRE) aim to decompose the effects of change in parameters on past demographic outcomes (e.g., population growth rates). But the vast majority of LTREs and other retrospective population analyses have focused on decomposing asymptotic population growth rates, which do not account for the dynamic interplay between population structure and vital rates that shape realized population growth rates (λt=Nt+1/Nt) in time-varying environments. We provide an empirical means to overcome these shortcomings by merging recently developed "transient life-table response experiments" with integrated population models (IPMs). IPMs allow for the estimation of latent population structure and other demographic parameters that are required for transient LTRE analysis, and Bayesian versions additionally allow for complete error propagation from the estimation of demographic parameters to derivations of realized population growth rates and perturbation analyses of growth rates. By integrating available monitoring data for Lesser Scaup over 60 yr, and conducting transient LTREs on IPM estimates, we found that the contribution of juvenile female survival to long-term variation in realized population growth rates was 1.6 and 3.7 times larger than that of adult female survival and fecundity, respectively. But a persistent long-term decline in fecundity explained 92% of the decline in abundance between 1983 and 2006. In contrast, an improvement in adult female survival drove the modest recovery in Lesser Scaup abundance since 2006, indicating that the most important demographic drivers of Lesser Scaup population dynamics are temporally dynamic. In addition to resolving uncertainty about Lesser Scaup population dynamics, the merger of IPMs with transient LTREs will strengthen our understanding of demography for many species as we aim to conserve biodiversity during an era of non-stationary global change. © 2017 by the Ecological Society of America.

An Investigation of the Generalizability and Dependability of Direct Behavior Rating Single Item Scales (DBR-SIS) to Measure Academic Engagement and Disruptive Behavior of Middle School Students

ERIC Educational Resources Information Center

Chafouleas, Sandra M.; Briesch, Amy M.; Riley-Tillman, T. Chris; Christ, Theodore J.; Black, Anne C.; Kilgus, Stephen P.

2010-01-01

A total of 4 raters, including 2 teachers and 2 research assistants, used Direct Behavior Rating Single Item Scales (DBR-SIS) to measure the academic engagement and disruptive behavior of 7 middle school students across multiple occasions. Generalizability study results for the full model revealed modest to large magnitudes of variance associated…

Single-joint outcome measures: preliminary validation of patient-reported outcomes and physical examination.

PubMed

Heald, Alison E; Fudman, Edward J; Anklesaria, Pervin; Mease, Philip J

2010-05-01

To assess the validity, responsiveness, and reliability of single-joint outcome measures for determining target joint (TJ) response in patients with inflammatory arthritis. Patient-reported outcomes (PRO), consisting of responses to single questions about TJ global status on a 100-mm visual analog scale (VAS; TJ global score), function on a 100-mm VAS (TJ function score), and pain on a 5-point Likert scale (TJ pain score) were piloted in 66 inflammatory arthritis subjects in a phase 1/2 clinical study of an intraarticular gene transfer agent and compared to physical examination measures (TJ swelling, TJ tenderness) and validated function questionnaires (Disabilities of the Arm, Shoulder and Hand scale, Rheumatoid Arthritis Outcome Score, and the Health Assessment Questionnaire). Construct validity was assessed by evaluating the correlation between the single-joint outcome measures and validated function questionnaires using Spearman's rank correlation. Responsiveness or sensitivity to change was assessed through calculating effect size and standardized response means (SRM). Reliability of physical examination measures was assessed by determining interobserver agreement. The single-joint PRO were highly correlated with each other and correlated well with validated functional measures. The TJ global score exhibited modest effect size and modest SRM that correlated well with the patient's assessment of response on a 100-mm VAS. Physical examination measures exhibited high interrater reliability, but correlated less well with validated functional measures and the patient's assessment of response. Single-joint PRO, particularly the TJ global score, are simple to administer and demonstrate construct validity and responsiveness in patients with inflammatory arthritis. (ClinicalTrials.gov identifier NCT00126724).

Activation of coagulation by a thalidomide-based regimen.

PubMed

Hoshi, Asuka; Matsumoto, Aya; Chung, Jihwa; Isozumi, Yu; Koyama, Takatoshi

2011-09-01

Combining thalidomide (Thal) with chemotherapeutic agents or steroid preparations led to improved response rates in the treatment of multiple myeloma. However, deep vein thrombosis (DVT) is one of the most serious side-effects noted with this regimen, and how a Thal-based regimen causes DVT is unclear. We investigated the procoagulant effects of Thal when combined with chemotherapeutic agents in vitro, focusing on tissue factor (TF) and phosphatidylserine. We examined the effects of the chemotherapeutic doxorubicin hydrochloride (Dox) and the steroid dexamethasone (Dex), with or without Thal. Our study used the human vascular endothelial, monocytic, and myeloma cell lines, EAhy926, THP-1, and RPMI8226, respectively. In EAhy926 and THP-1, Dex treatment increased expression of TF, which may induce procoagulant activity (PCA). Upregulation of TF mRNA correlated with activation of the Egr-1 pathway. In Thal and Dex treatments, the increase of PCA induction from phosphatidylserine exposure was modest. In contrast, Dox and Thal-Dox increased phosphatidylserine exposure in both cell types. In THP-1 cells, cell surface phosphatidylserine exposure correlated with increased PCA by Dox. Thal alone showed a modest increase in phosphatidylserine exposure in endothelial cells and monocytes. When Thal is given in combination with chemotherapies or Dex, endothelial cell and monocyte PCA may be induced through phosphatidylserine exposure, or TF expression. Induction may be protracted by Thal, which has an antiangiogenic activity. Therefore, prophylactic anticoagulant strategies should be considered in Thal-based combination regimens.

Fiber-type differences in muscle mitochondrial profiles.

PubMed

Leary, S C; Lyons, C N; Rosenberger, A G; Ballantyne, J S; Stillman, J; Moyes, C D

2003-10-01

Although striated muscles differ in mitochondrial content, the extent of fiber-type specific mitochondrial specializations is not well known. To address this issue, we compared mitochondrial structural and functional properties in red muscle (RM), white muscle (WM), and cardiac muscle of rainbow trout. Overall preservation of the basic relationships between oxidative phosphorylation complexes among fiber types was confirmed by kinetic analyses, immunoblotting of native holoproteins, and spectroscopic measurements of cytochrome content. Fiber-type differences in mitochondrial properties were apparent when parameters were expressed per milligram mitochondrial protein. However, the differences diminished when expressed relative to cytochrome oxidase (COX), possibly a more meaningful denominator than mitochondrial protein. Expressed relative to COX, there were no differences in oxidative phosphorylation enzyme activities, pyruvate-based respiratory rates, H2O2 production, or state 4 proton leak respiration. These data suggest most mitochondrial qualitative properties are conserved across fiber types. However, there remained modest differences ( approximately 50%) in stoichiometries of selected enzymes of the Krebs cycle, beta-oxidation, and antioxidant enzymes. There were clear differences in membrane fluidity (RM > cardiac, WM) and proton conductance (H+/min/mV/U COX: WM > RM > cardiac). The pronounced differences in mitochondrial content between fiber types could be attributed to a combination of differences in myonuclear domain and modest effects on the expression of nuclear- and mitochondrially encoded respiratory genes. Collectively, these studies suggest constitutive pathways that transcend fiber types are primarily responsible for determining most quantitative and qualitative properties of mitochondria.

Activation of PI3K/AKT and MAPK Pathway through a PDGFRβ-Dependent Feedback Loop Is Involved in Rapamycin Resistance in Hepatocellular Carcinoma

PubMed Central

Yao, Li-Qing; Tan, Chang-Jun; Huang, Xiao-Yong; Ke, Ai-Wu; Dai, Zhi; Fan, Jia; Zhou, Jian

2012-01-01

Background Rapamycin is an attractive approach for the treatment and prevention of HCC recurrence after liver transplantation. However, the objective response rates of rapamycin achieved with single-agent therapy were modest, supporting that rapamycin resistance is a frequently observed characteristic of many cancers. Some studies have been devoted to understanding the mechanisms of rapamycin resistance, however, the mechanisms are cell-type-dependent and studies on rapamycin resistance in HCC are extremely limited. Methodology/Principal Findings The anti-tumor sensitivity of rapamycin was modest in vitro and in vivo. In both human and rat HCC cells, rapamycin up-regulated the expression and phosphorylation of PDGFRβ in a time and dose-dependent manner as assessed by RT-PCR and western blot analysis. Using siRNA mediated knockdown of PDGFRβ, we confirmed that subsequent activation of AKT and ERK was PDGFRβ-dependent and compromised the anti-tumor activity of rapamycin. Then, blockade of this PDGFRβ-dependent feedback loop by sorafenib enhanced the anti-tumor sensitivity of rapamycin in vitro and in an immunocompetent orthotopic rat model of HCC. Conclusions Activation of PI3K/AKT and MAPK pathway through a PDGFRβ-dependent feedback loop compromises the anti-tumor activity of rapamycin in HCC, and blockade of this feedback loop by sorafenib is an attractive approach to improve the anti-tumor effect of rapamycin, particularly in preventing or treating HCC recurrence after liver transplantation. PMID:22428038

Differences Between US and UK Adults in Stroke Preparedness

PubMed Central

Ford, Gary A.; Morgenstern, Lewis B.; White, Martin; Sniehotta, Falko F.; Mackintosh, Joan E.; Gellert, Paul; Skolarus, Lesli E.

2015-01-01

Background and Purpose— Although time-dependent treatment is available, most people delay contacting emergency medical services for stroke. Given differences in the healthcare system and public health campaigns, exploring between-country differences in stroke preparedness may identify novel ways to increase acute stroke treatment. Methods— A survey was mailed to population-based samples in Ingham County, Michigan, US (n=2500), and Newcastle upon Tyne, UK (n=2500). Surveys included stroke perceptions and stroke/nonstroke scenarios to assess recognition and response to stroke. Between-country differences and associations with stroke preparedness were examined using t tests and linear mixed models. Results— Overall response rate was 27.4%. The mean age of participants was 55 years, and 58% were female. US participants were better in recognizing stroke (70% versus 63%, d=0.27) and were more likely to call emergency medical services (55% versus 52%, d=0.11). After controlling for demographics and comorbidities, US participants remained more likely to recognize stroke but were not more likely to respond appropriately. A greater belief that medical treatment can help with stroke and understanding of stroke was associated with improved stroke recognition and response. Conclusions— Overall, stroke recognition and response were moderate. US participants were modestly better at recognizing stroke, although there was little difference in response to stroke. Future stroke awareness interventions could focus more on stroke outcome expectations and developing a greater understanding of stroke among the public. PMID:26419968

Application of environmental sensitivity theories in personalized prevention for youth substance abuse: a transdisciplinary translational perspective.

PubMed

Thibodeau, Eric L; August, Gerald J; Cicchetti, Dante; Symons, Frank J

2016-03-01

Preventive interventions that target high-risk youth, via one-size-fits-all approaches, have demonstrated modest effects in reducing rates of substance use. Recently, substance use researchers have recommended personalized intervention strategies. Central to these approaches is matching preventatives to characteristics of an individual that have been shown to predict outcomes. One compelling body of literature on person × environment interactions is that of environmental sensitivity theories, including differential susceptibility theory and vantage sensitivity. Recent experimental evidence has demonstrated that environmental sensitivity (ES) factors moderate substance abuse outcomes. We propose that ES factors may augment current personalization strategies such as matching based on risk factors/severity of problem behaviors (risk severity (RS)). Specifically, individuals most sensitive to environmental influence may be those most responsive to intervention in general and thus need only a brief-type or lower-intensity program to show gains, while those least sensitive may require more comprehensive or intensive programming for optimal responsiveness. We provide an example from ongoing research to illustrate how ES factors can be incorporated into prevention trials aimed at high-risk adolescents.

Hearing conservation in the primary aluminium industry

PubMed Central

Frisch, N.; Dixon-Ernst, C.; Chesson, B. J.; Cullen, M. R.

2016-01-01

Background Noise-induced hearing loss has been an intractable problem for heavy industry. Aims To report our experience in reducing the incidence of age-corrected confirmed 10 dB hearing shifts (averaged over 2, 3 and 4kHz) in employees in the primary aluminium industry in Australia over the period 2006–13. Methods We analysed annual audiometric data to determine the number of permanent hearing shifts that occurred in employees in two bauxite mines, three alumina refineries and two aluminium smelters. Annual hearing shift rates were calculated based on the number of employees tested per year. Hearing conservation initiatives undertaken during the study period are described. An assessment of similar exposure group noise exposures was also undertaken to determine the magnitude of noise exposure reduction during the study period. Results Across all operations, hearing shift rates declined from 5.5% per year in 2006 to 1.3% per year in 2013 (P < 0.001). The decline in shift rates was greater in mines and refineries, where baseline shift rates were higher, than in smelter workers. Modest reductions in noise exposure occurred during the study period. Conclusions We observed a substantial decline in hearing shift rates during the study period. We describe the hearing conservation initiatives that were collectively associated with this decline. We suspect these initiatives could be deployed relatively easily and at modest cost in other industries with noise-exposed employees. PMID:26470945

Utility of the Conners' Adult ADHD Rating Scale validity scales in identifying simulated attention-deficit hyperactivity disorder and random responding.

PubMed

Walls, Brittany D; Wallace, Elizabeth R; Brothers, Stacey L; Berry, David T R

2017-12-01

Recent concern about malingered self-report of symptoms of attention-deficit hyperactivity disorder (ADHD) in college students has resulted in an urgent need for scales that can detect feigning of this disorder. The present study provided further validation data for a recently developed validity scale for the Conners' Adult ADHD Rating Scale (CAARS), the CAARS Infrequency Index (CII), as well as for the Inconsistency Index (INC). The sample included 139 undergraduate students: 21 individuals with diagnoses of ADHD, 29 individuals responding honestly, 54 individuals responding randomly (full or half), and 35 individuals instructed to feign. Overall, the INC showed moderate sensitivity to random responding (.44-.63) and fairly high specificity to ADHD (.86-.91). The CII demonstrated modest sensitivity to feigning (.31-.46) and excellent specificity to ADHD (.91-.95). Sequential application of validity scales had correct classification rates of honest (93.1%), ADHD (81.0%), feigning (57.1%), half random (42.3%), and full random (92.9%). The present study suggests that the CII is modestly sensitive (true positive rate) to feigned ADHD symptoms, and highly specific (true negative rate) to ADHD. Additionally, this study highlights the utility of applying the CAARS validity scales in a sequential manner for identifying feigning. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Relation between stress and cytokine responses in inner-city mothers.

PubMed

Gruenberg, David A; Wright, Rosalind J; Visness, Cynthia M; Jaffee, Katy F; Bloomberg, Gordon R; Cruikshank, William W; Kattan, Meyer; Sandel, Megan T; Wood, Robert A; Gern, James E

2015-11-01

Women in poor urban neighborhoods have high rates of stress and allergic diseases, but whether stress or stress correlates such as depression promote inflammatory and type 2 cytokine responses is unknown. To examine associations among external stressors, perceived stress, depression, and peripheral blood mononuclear cell cytokine responses of mothers enrolled in the Urban Environment and Childhood Asthma Study and test the hypothesis that stress would be positively associated with type 2 and selected proinflammatory (tumor necrosis factor-α and interleukin-8) responses. Questionnaire data from mothers living in 4 inner cities included information about external stress, stress perception, and depression. The external stress domains (interpersonal problems, housing, and neighborhood stress) were combined into a Composite Stressor score. Peripheral blood mononuclear cells were stimulated ex vivo and cytokine responses to innate, adaptive, and polyclonal immune stimuli were compared with stress and depression scores for 469 of the 606 study participants. There were no significant positive associations between Composite Stressor scores, perceived stress, or depression scores and proinflammatory or type 2 cytokine responses, and these findings were not modified by allergy or asthma status. There were some modest associations with individual stressors and cytokine responses, but no consistent relations were noted. Depression was associated with decreased responses to some stimuli, particularly dust mite. Composite measurements of stressors, perceived stress, or depression were not positively related to proinflammatory or type 2 cytokine responses in these young urban women. These data do not support the hypothesis that these factors promote cytokine responses associated with allergy. ClinicalTrials.gov, identifier NCT00114881. Copyright © 2015. Published by Elsevier Inc.

The effect of the rate of hydrostatic pressure depressurization on cells in culture.

PubMed

Tworkoski, Ellen; Glucksberg, Matthew R; Johnson, Mark

2018-01-01

Changes in hydrostatic pressure, at levels as low as 10 mm Hg, have been reported in some studies to alter cell function in vitro; however, other studies have found no detectable changes using similar methodologies. We here investigate the hypothesis that the rate of depressurization, rather than elevated hydrostatic pressure itself, may be responsible for these reported changes. Hydrostatic pressure (100 mm Hg above atmospheric pressure) was applied to bovine aortic endothelial cells (BAECs) and PC12 neuronal cells using pressurized gas for periods ranging from 3 hours to 9 days, and then the system was either slowly (~30 minutes) or rapidly (~5 seconds) depressurized. Cell viability, apoptosis, proliferation, and F-actin distribution were then assayed. Our results did not show significant differences between rapidly and slowly depressurized cells that would explain differences previously reported in the literature. Moreover, we found no detectable effect of elevated hydrostatic pressure (with slow depressurization) on any measured variables. Our results do not confirm the findings of other groups that modest increases in hydrostatic pressure affect cell function, but we are not able to explain their findings.

Kidney Response to the Spectrum of Diet-Induced Acid Stress.

PubMed

Goraya, Nimrit; Wesson, Donald E

2018-05-11

Chronic ingestion of the acid (H⁺)-producing diets that are typical of developed societies appears to pose a long-term threat to kidney health. Mechanisms employed by kidneys to excrete this high dietary H⁺ load appear to cause long-term kidney injury when deployed over many years. In addition, cumulative urine H⁺ excretion is less than the cumulative increment in dietary H⁺, consistent with H⁺ retention. This H⁺ retention associated with the described high dietary H⁺ worsens as the glomerular filtration rate (GFR) declines which further exacerbates kidney injury. Modest H⁺ retention does not measurably change plasma acid⁻base parameters but, nevertheless, causes kidney injury and might contribute to progressive nephropathy. Current clinical methods do not detect H⁺ retention in its early stages but the condition manifests as metabolic acidosis as it worsens, with progressive decline of the glomerular filtration rate. We discuss this spectrum of H⁺ injury, which we characterize as “H⁺ stress”, and the emerging evidence that high dietary H⁺ constitutes a threat to long-term kidney health.

The effect of the rate of hydrostatic pressure depressurization on cells in culture

PubMed Central

Tworkoski, Ellen; Glucksberg, Matthew R.

2018-01-01

Changes in hydrostatic pressure, at levels as low as 10 mm Hg, have been reported in some studies to alter cell function in vitro; however, other studies have found no detectable changes using similar methodologies. We here investigate the hypothesis that the rate of depressurization, rather than elevated hydrostatic pressure itself, may be responsible for these reported changes. Hydrostatic pressure (100 mm Hg above atmospheric pressure) was applied to bovine aortic endothelial cells (BAECs) and PC12 neuronal cells using pressurized gas for periods ranging from 3 hours to 9 days, and then the system was either slowly (~30 minutes) or rapidly (~5 seconds) depressurized. Cell viability, apoptosis, proliferation, and F-actin distribution were then assayed. Our results did not show significant differences between rapidly and slowly depressurized cells that would explain differences previously reported in the literature. Moreover, we found no detectable effect of elevated hydrostatic pressure (with slow depressurization) on any measured variables. Our results do not confirm the findings of other groups that modest increases in hydrostatic pressure affect cell function, but we are not able to explain their findings. PMID:29315329

Circuitry Linking the Csr and Stringent Response Global Regulatory Systems

PubMed Central

Edwards, Adrianne N.; Patterson-Fortin, Laura M.; Vakulskas, Christopher A.; Mercante, Jeffrey W.; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I.; Fields, Joshua A.; Thompson, Stuart A.; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

2011-01-01

Summary CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR, and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. PMID:21488981

Affording shared responsibility for universal coverage: insights from California.

PubMed

Curtis, Rick; Neuschler, Ed

2009-01-01

This paper presents key insights from California's recent experience in developing a plan for universal health coverage with "shared responsibility" among individuals, employers, and governments. A major challenge was finding an acceptable balance among the goals of affordability, equity, and cost to the state. Although reform did not pass, the state's approach-particularly differences from Massachusetts regarding modest-income workers and related employer and public roles-provides important insights for federal reform.

Ontogeny of vestibular compound action potentials in the domestic chicken

NASA Technical Reports Server (NTRS)

Jones, S. M.; Jones, T. A.

2000-01-01

Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of -0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately -25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6-P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 microV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ.

Dam Breach Release of Non-Cohesive Sediments: Channel Response and Recovery Rates

NASA Astrophysics Data System (ADS)

Collins, M. J.; Boardman, G.; Banks, W.; Andrews, M.; Conlon, M.; Dillow, J. J. A.; Gellis, A.; Lowe, S.; McClain, S.; Miller, A. J.; Snyder, N. P.; Wilcock, P. R.

2014-12-01

Dam removals featuring unchecked releases of non-cohesive sediments are excellent opportunities to learn more about stream channel response to abrupt increases in bed material supply that can occur deliberately or by natural processes like landslides and volcanic eruptions. Understanding channel response to sediment pulses, including response rates, is essential because human uses of river channels and floodplains are impacted by these events as are aquatic habitats. We had the opportunity to study a dam removal site at the Simkins Dam in Maryland, USA, that shares many important geophysical attributes of another well-studied dam removal in the humid northeast United States [Merrimack Village Dam, New Hampshire; Pearson et al., 2011]. The watershed sizes are the same order of magnitude (102 km2), and at both sites relatively low head dams were removed (~ 3-4 m) and ~60,000 m3 of dominantly sand-sized sediments discharged to low-gradient reaches immediately downstream. Analyzing four years of repeat morphometry and bed sediment grain size surveys at the Simkins site on the Patapsco River, as well as continuous discharge and suspended sediment gaging data, we clearly document a two-phase response in the upstream reach as described by Pearson et al. [2011] for their New Hampshire site and noted at other dam removals [e.g., Major et al., 2012]. In the early phase, approximately 50% of the impounded sediment mass was eroded rapidly over a period of about three months when flows were very modest (Figure 1). After incision to base level and channel widening in the former impoundment, a second phase began when further erosion depended on floods large enough to access impounded sediments more distant from the newly-formed channel. We also found important differences in the upstream responses at the Maryland and New Hampshire sites that appear to be related to valley type (non-glaciated versus glaciated, respectively). Response variances immediately downstream between the respective sites are potentially related to local gradient and hydraulics.

Ontogeny of Vestibular Compound Action Potentials in the Domestic Chicken

PubMed Central

M. Jones, Sherri

2000-01-01

Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of –0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately –25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6–P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 μV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ. PMID:11545229

Automobile fuel; Economy and CO2 emissions in industrialized countries : troubling trends through 2005/6

DOT National Transportation Integrated Search

2005-01-01

A review of recently available data on both on-road fuel economy and new car test fuel economy : shows that while US on-road fuel economy has been flat for almost 15 years, major European countries and Japan have shown modest improvements in response...

Report of the National Heart, Lung, and Blood Institute Working Group on epigenetics and hypertension

USDA-ARS?s Scientific Manuscript database

Hypertension affects greater than 1 billion people worldwide and in 2009 it cost the US healthcare system more than $73 billion. Despite the availability of many antihypertensive therapies, individual responses vary, and efficacy remains a concern. Current treatments have yielded only modest reduct...

Boosting serotonin in the brain: is it time to revamp the treatment of depression?

PubMed

Torrente, Mariana P; Gelenberg, Alan J; Vrana, Kent E

2012-05-01

Abnormalities in serotonin systems are presumably linked to various psychiatric disorders including schizophrenia and depression. Medications intended for these disorders aim to either block the reuptake or the degradation of this neurotransmitter. In an alternative approach, efforts have been made to enhance serotonin levels through dietary manipulation of precursor levels with modest clinical success. In the last 30 years, there has been little improvement in the pharmaceutical management of depression, and now is the time to revisit therapeutic strategies for the treatment of this disease. Tryptophan hydroxylase (TPH) catalyzes the first and rate-limiting step in the biosynthesis of serotonin. A recently discovered isoform, TPH2, is responsible for serotonin biosynthesis in the brain. Learning how to activate this enzyme (and its polymorphic versions) may lead to a new, more selective generation of antidepressants, able to regulate the levels of serotonin in the brain with fewer side effects.

Irradiation response of commercial, high-Tc superconducting tapes: Electromagnetic transport properties

DOE PAGES

Gapud, A. A.; Greenwood, N. T.; Alexander, J. A.; ...

2015-07-01

Effects of low dose irradiation on the electrical transport current properties of commercially available high-temperature superconducting, coated-conductor tapes were investigated, in view of potential applications in the irradiative environment of fusion reactors. Three different tapes, each with unique as-grown flux-pinning structures, were irradiated with Au and Ni ions at energies that provide a range of damage effects, with accumulated damage levels near that expected for conductors in a fusion reactor environment. Measurements using transport current determined the pre- and post-irradiation resistivity, critical current density, and pinning force density, yielding critical temperatures, irreversibility lines, and inferred vortex creep rates. Results showmore » that at the irradiation damage levels tested, any detriment to as-grown pre-irradiation properties is modest; indeed in one case already-superior pinning forces are enhanced, leading to higher critical currents.« less

Food Prices and Obesity: A Review1234

PubMed Central

Finkelstein, Eric A.; Strombotne, Kiersten L.; Zhen, Chen; Epstein, Leonard H.

2014-01-01

In response to rising rates of obesity in the United States due in part to excess food consumption, researchers and policy makers have argued that levying food taxes on obesity-promoting foods, perhaps combined with subsidies on healthier options, would be an effective tool to stem the obesity epidemic. The extent to which overall energy intake or weight outcomes will improve as a result of these policies is ultimately an empirical question. This review examines the link between food or beverage price changes and energy intake or weight outcomes among U.S. consumers. Current evidence indicates that, by themselves, targeted food taxes and subsidies as considered to date are unlikely to have a major effect on individual weight or obesity prevalence. While research suggests that the effects are modest, food taxes and subsidies may play an important role in a multifaceted approach to reducing obesity incidence. PMID:25398747

The collapse of pelagic fishes in the upper San Francisco estuary

USGS Publications Warehouse

Sommer, T.; Armor, C.; Baxter, R.; Breuer, R.; Brown, L.; Chotkowski, M.; Culberson, S.; Feyrer, F.; Gingras, M.; Herbold, B.; Kimmerer, W.; Mueller-Solger, A.; Nobriga, M.; Souza, K.

2007-01-01

Although the pelagic fish community of the upper San Francisco Estuary historically has shown substantial variability, a recent collapse has captured the attention of resource managers, scientists, legislators, and the general public. The ecological and management consequences of the decline are most serious for delta smelt (Hypomesus transpacificus), a threatened species whose narrow range overlaps with large water diversions that supply water to over 25 million people. The decline occurred despite recent moderate hydrology, which typically results in at least modest recruitment, and investments of hundreds of millions of dollars in habitat restoration and environmental water allocations to support native fishes. In response to the pelagic fish collapse, an ambitious multi-agency research team has been working since 2005 to evaluate the causes of the decline, which likely include a combination of factors: stock-recruitment effects, a decline in habitat quality, increased mortality rates, and reduced food availability due to invasive species.

Outcomes in the management of esophageal cancer.

PubMed

Paul, Subroto; Altorki, Nasser

2014-10-01

Esophageal cancer rates have continued to rise in the Western World. Esophageal cancer will be responsible for an estimated 15,450 deaths in the United States in 2014 alone. Esophageal resection with or without preoperative therapy remains the mainstay of treatment. Advances in surgical technique and perioperative care have improved short-term outcomes considerably by decreasing operative mortality. Despite these advances though, esophagectomy remains a procedure associated with considerable morbidity from a wide range of complications. Prompt recognition and treatment of complications can lower overall morbidity and mortality. Unfortunately, long-term outcomes remain poor as the vast majority of patients present with loco-regionally advanced or metastatic disease. Surgery by itself provides poor loco-regional control and fails to address micrometastatic disease. Neoadjuvant chemotherapy or chemoradiation provides a modest survival advantage compared to surgical resection alone. Future gains in understanding the molecular biology of esophageal cancer will hopefully lead to improved therapeutics and resultant outcomes. © 2014 Wiley Periodicals, Inc.

Food prices and obesity: a review.

PubMed

Finkelstein, Eric A; Strombotne, Kiersten L; Zhen, Chen; Epstein, Leonard H

2014-11-01

In response to rising rates of obesity in the United States due in part to excess food consumption, researchers and policy makers have argued that levying food taxes on obesity-promoting foods, perhaps combined with subsidies on healthier options, would be an effective tool to stem the obesity epidemic. The extent to which overall energy intake or weight outcomes will improve as a result of these policies is ultimately an empirical question. This review examines the link between food or beverage price changes and energy intake or weight outcomes among U.S. consumers. Current evidence indicates that, by themselves, targeted food taxes and subsidies as considered to date are unlikely to have a major effect on individual weight or obesity prevalence. While research suggests that the effects are modest, food taxes and subsidies may play an important role in a multifaceted approach to reducing obesity incidence. © 2014 American Society for Nutrition.

Impact of a transition to more restrictive drug formulary on therapy discontinuation and medication adherence.

PubMed

Shirneshan, E; Kyrychenko, P; Matlin, O S; Avila, J P; Brennan, T A; Shrank, W H

2016-02-01

There is conclusive evidence demonstrating that formulary restrictions are associated with reduced utilization and pharmacy spending of the restricted drugs. However, prior efforts to implement restrictive formularies have been associated with inconsistent rates of therapy discontinuation and mixed impacts on adherence to therapy. Also, the impact of transferring patients from an already restrictive formulary to a more aggressive model has not been previously examined. This study evaluated the impact of implementation of a more restrictive formulary on therapy disruption, adherence rates, pharmacy costs and generic utilization among patients with common chronic conditions. In 2014, CVS Health implemented Value Formulary (VF), a restrictive benefit design with the aim of reducing spending while preserving access to and adherence to essential therapy, was used. A retrospective cohort study was conducted to assess changes in therapy disruption rates, pharmacy costs and generic dispensing rate (GDR) (for continuers) and medication adherence (for initiators) following the implementation of VF. The study group was selected from members of three existing employer clients transitioned from standard formulary (SF) to VF on January 2014. The control population was a matched group of six employers with the same preperiod formulary structure, business unit, adherence programmes and patient out-of-pocket cost as the study group. The control group retained SF in 2014. To assess therapy disruption after VF implementation, we categorized patients by their subsequent medication use into three groups: (i) therapy stopped, (ii) therapy continued and (iii) therapy switched. Medication adherence was measured as monthly proportion of days covered (PDC). Pharmacy cost and GDR were measured per utilizer per month (PUPM). Rates of therapy disruption in study and control groups were compared using the chi-square test. Differences in monthly PDC between matched groups were evaluated using multivariate linear regression. Impact of VF on pharmacy cost and GDR was measured through segmented regression of interrupted time series data with generalized estimating equations. A transition from SF to VF influenced drug coverage for approximately 13% of members (as their medications were either no longer covered, or covered restrictively under VF). Compared to patients whose plan sponsors retained SF, the patients that transitioned to VF had a modest (1·3%) but statistically significant increase in therapy discontinuation rates. This was offset by similarly modest improvements in adherence; patients who initiated therapy under VF demonstrated a 1·5% higher adherence to medications as compared to SF patients (P < 0·001). Medication costs in the VF group were lower by $20 PUPM (P < 0·001), and GDR was greater by 4·2% (P < 0·001). Transition of patients to a more restrictive drug formulary led to modest therapy discontinuation, similarly modest improvements in medication adherence and substantial prescription drug cost savings. As healthcare payors search for ways to control the rapid rise in spending for medications without compromising quality, the Value Formulary can serve as a useful tool. © 2016 John Wiley & Sons Ltd.

A PHASE II STUDY OF GEMCITABINE AND CAPECITABINE IN PATIENTS WITH ADVANCED RENAL CELL CANCER (RCC): SOUTHWEST ONCOLOGY GROUP STUDY S0312

PubMed Central

Van Veldhuizen, Peter J.; Hussey, Michael; Lara, Primo N.; Mack, Philip C.; Gandour-Edwards, Regina; Clark, Joseph I.; Lange, Marianne K.; Crawford, E. David

2010-01-01

Background Gemcitabine plus capecitabine has modest efficacy in patients with advanced RCC but has considerable toxicity. We evaluated the efficacy and toxicity of a modified dose-schedule of this doublet in patients with advanced unresectable or metastatic RCC. Methods Chemotherapy-naïve patients were treated with gemcitabine at 900mg/m2 on days 1,8,15 and capecitabine at 625mg/m2 twice daily on days 1 through 21, every 28 days. Eligible patients must have adequate performance status and end-organ function. The primary endpoint was tumor response rate (RR). No further evaluation of this regimen would be pursued if the RR was ≤ 5%. In an exploratory manner using archival specimens, we also evaluated potential markers of prognosis and treatment response including thymidylate synthase (TS) gene polymorphisms and tumor expression of p53, PTEN, pAKT, pmTOR, and ERCC1. Results Of 43 patients registered, 1 was ineligible and 2 were not analyzable. There was 1 confirmed complete response (CR) and three unconfirmed partial responses (PR), for an overall response rate of 10% (95% CI: 3, 24). Nineteen patients (48%) had stable disease (SD). The six-month freedom-from-treatment-failure and overall survival rates were 20% (95% CI: 8, 32) and 75% (95% CI: 62, 88), respectively. Median survival time was 23 months (95% CI: 10, 37). One patient each experienced Grade 4 neutropenia, fatigue, thrombocytopenia and hemolysis with renal failure. The most common Grade 3 toxicities were neutropenia (12 patients), fatigue (5), and leucopenia (4). Patients with a best response of stable disease or better were more likely to have a decrease in expression of PTEN and an increased expression of pmTOR. Conclusions Gemcitabine plus capecitabine at this reduced dose-schedule benefits a small percentage of patients with RCC with an acceptable toxicity profile. The combination of gemcitabine and capecitabine may serve as a base regimen for combination therapy with targeted agents in select RCC patients. PMID:19487915

Design and Field Procedures in the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A)

PubMed Central

Kessler, Ronald C.; Avenevoli, Shelli; Costello, E. Jane; Green, Jennifer Greif; Gruber, Michael J.; Heeringa, Steven; Merikangas, Kathleen R.; Pennell, Beth-Ellen; Sampson, Nancy A.; Zaslavsky, Alan M.

2009-01-01

An overview is presented of the design and field procedures of the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A), a US face-to-face household survey of the prevalence and correlates of DSM-IV mental disorders. The survey was based on a dual-frame design that included 904 adolescent residents of the households that participated in the US National Comorbidity Survey Replication (85.9% response rate) and 9,244 adolescent students selected from a nationally representative sample of 320 schools (74.7% response rate). After expositing the logic of dual-frame designs, comparisons are presented of sample and population distributions on Census socio-demographic variables and, in the school sample, school characteristics. These document only minor differences between the samples and the population. The results of statistical analysis of the bias-efficiency trade-off in weight trimming are then presented. These show that modest trimming meaningfully reduces mean squared error. Analysis of comparative sample efficiency shows that the household sample is more efficient than the school sample, leading to the household sample getting a higher weight relative to its size in the consolidated sample relative to the school sample. Taken together, these results show that the NCS-A is an efficient sample of the target population with good representativeness on a range of socio-demographic and geographic variables. PMID:19507169

Costs of immune responses are related to host body size and lifespan

DOE PAGES

Brace, Amber J.; Lajeunesse, Marc J.; Ardia, Daniel R.; ...

2017-06-01

A central assumption in ecological immunology is that immune responses are costly, with costs manifesting directly (e.g., increases in metabolic rate and increased amino acid usage) or as tradeoffs with other life processes (e.g., reduced growth and reproductive success). Across taxa, host longevity, timing of maturity, and reproductive effort affect the organization of immune systems. It is reasonable, therefore, to expect that these and related factors should also affect immune activation costs. Specifically, species that spread their breeding efforts over a long lifetime should experience lower immune costs than those that mature and breed quickly and die comparatively early. Likewise,more » body mass should affect immune costs, as body size affects the extent to which hosts are exposed to parasites as well as how hosts can combat infections (via its effects on metabolic rates and other factors). Here in this paper, we used phylogenetic meta-regression to reveal that, in general, animals incur costs of immune activation, but small species that are relatively long-lived incur the largest costs. These patterns probably arise because of the relative need for defense when infection risk is comparatively high and fitness can only be realized over a comparatively long period. However, given the diversity of species considered here and the overall modest effects of body mass and life history on immune costs, much more research is necessary before generalizations are appropriate.« less

Outcomes with single agent LIPO-DOX in platinum-resistant ovarian and fallopian tube cancers and primary peritoneal adenocarcinoma - Chiang Mai University Hospital experience.

PubMed

Suprasert, Prapaporn; Manopunya, Manatsawee; Cheewakriangkrai, Chalong

2014-01-01

Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 mg/m2 every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

Physiological and Microfluorometric Studies of Reduction and Clearance of Retinal in Bleached Rod Photoreceptors

PubMed Central

Tsina, Efthymia; Chen, Chunhe; Koutalos, Yiannis; Ala-Laurila, Petri; Tsacopoulos, Marco; Wiggert, Barbara; Crouch, Rosalie K.; Cornwall, M. Carter

2004-01-01

The visual cycle comprises a sequence of reactions that regenerate the visual pigment in photoreceptors during dark adaptation, starting with the reduction of all-trans retinal to all-trans retinol and its clearance from photoreceptors. We have followed the reduction of retinal and clearance of retinol within bleached outer segments of red rods isolated from salamander retina by measuring its intrinsic fluorescence. Following exposure to a bright light (bleach), increasing fluorescence intensity was observed to propagate along the outer segments in a direction from the proximal region adjacent to the inner segment toward the distal tip. Peak retinol fluorescence was achieved after ∼30 min, after which it declined very slowly. Clearance of retinol fluorescence is considerably accelerated by the presence of the exogenous lipophilic substances IRBP (interphotoreceptor retinoid binding protein) and serum albumin. We have used simultaneous fluorometric and electrophysiological measurements to compare the rate of reduction of all-trans retinal to all-trans retinol to the rate of recovery of flash response amplitude in these cells in the presence and absence of IRBP. We find that flash response recovery in rods is modestly accelerated in the presence of extracellular IRBP. These results suggest such substances may participate in the clearance of retinoids from rod photoreceptors, and that this clearance, at least in rods, may facilitate dark adaptation by accelerating the clearance of photoproducts of bleaching. PMID:15452202

Costs of immune responses are related to host body size and lifespan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brace, Amber J.; Lajeunesse, Marc J.; Ardia, Daniel R.

A central assumption in ecological immunology is that immune responses are costly, with costs manifesting directly (e.g., increases in metabolic rate and increased amino acid usage) or as tradeoffs with other life processes (e.g., reduced growth and reproductive success). Across taxa, host longevity, timing of maturity, and reproductive effort affect the organization of immune systems. It is reasonable, therefore, to expect that these and related factors should also affect immune activation costs. Specifically, species that spread their breeding efforts over a long lifetime should experience lower immune costs than those that mature and breed quickly and die comparatively early. Likewise,more » body mass should affect immune costs, as body size affects the extent to which hosts are exposed to parasites as well as how hosts can combat infections (via its effects on metabolic rates and other factors). Here in this paper, we used phylogenetic meta-regression to reveal that, in general, animals incur costs of immune activation, but small species that are relatively long-lived incur the largest costs. These patterns probably arise because of the relative need for defense when infection risk is comparatively high and fitness can only be realized over a comparatively long period. However, given the diversity of species considered here and the overall modest effects of body mass and life history on immune costs, much more research is necessary before generalizations are appropriate.« less

The Genetic Covariation between Fear Conditioning and Self-Report Fears

PubMed Central

Hettema, John M.; Annas, Peter; Neale, Michael C.; Fredrikson, Mats; Sci, Dr Med; Kendler, Kenneth S.

2008-01-01

Background Fear conditioning is a traditional model for the acquisition of phobias, while behavioral therapies utilize processes underlying extinction to treat phobic and other anxiety disorders. Furthermore, fear conditioning has been proposed as an endophenotype for genetic studies of anxiety disorders. While prior studies have demonstrated that fear conditioning and self-report fears are heritable, no studies have determined whether they share a common genetic basis. Methods We obtained fear conditioning data from 173 twin pairs from the Swedish Twin Registry who also provided self-report ratings of 16 common fears. Using multivariate structural equation modeling, we analyzed factor-derived scores for the subjective fear ratings together with the electrophysiologic skin conductance responses during habituation, acquisition, and extinction to determine the extent of their genetic covariation. Results Phenotypic correlations between experimental and self-report fear measures were modest and, and counter-intuitively, negative; that is, subjects who reported themselves as more fearful had smaller electrophysiologic responses. Best-fit models estimated a significant (negative) genetic correlation between them, although genetic factors underlying fear conditioning accounted for only 9% of individual differences in self-report fears. Conclusions Experimentally-derived fear conditioning measures share only a small portion of the genetic factors underlying individual differences in subjective fears, cautioning against relying too heavily on the former as an endophenotype for genetic studies of phobic disorders. PMID:17698042

Circadian rhythms in myocardial metabolism and contractile function: influence of workload and oleate.

PubMed

Durgan, David J; Moore, Michael W S; Ha, Ngan P; Egbejimi, Oluwaseun; Fields, Anna; Mbawuike, Uchenna; Egbejimi, Anu; Shaw, Chad A; Bray, Molly S; Nannegari, Vijayalakshmi; Hickson-Bick, Diane L; Heird, William C; Dyck, Jason R B; Chandler, Margaret P; Young, Martin E

2007-10-01

Multiple extracardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its responsiveness to changes in workload and/or fatty acid (oleate) availability. Thus, hearts were isolated from male Wistar rats (housed during a 12:12-h light-dark cycle: lights on at 9 AM) at 9 AM, 3 PM, 9 PM, and 3 AM and perfused in the working mode ex vivo with 5 mM glucose plus either 0.4 or 0.8 mM oleate. Following 20-min perfusion at normal workload (i.e., 100 cm H(2)O afterload), hearts were challenged with increased workload (140 cm H(2)O afterload plus 1 microM epinephrine). In the presence of 0.4 mM oleate, myocardial metabolism exhibited a marked circadian rhythm, with decreased rates of glucose oxidation, increased rates of lactate release, decreased glycogenolysis capacity, and increased channeling of oleate into nonoxidative pathways during the light phase. Rat hearts also exhibited a modest circadian rhythm in responsiveness to the workload challenge when perfused in the presence of 0.4 mM oleate, with increased myocardial oxygen consumption at the dark-to-light phase transition. However, rat hearts perfused in the presence of 0.8 mM oleate exhibited a markedly blunted contractile function response to the workload challenge during the light phase. In conclusion, these studies expose marked circadian rhythmicities in myocardial oxidative and nonoxidative metabolism as well as responsiveness of the rat heart to changes in workload and fatty acid availability.

The Association of State Rate Review Authority with Health Insurance Premiums.

PubMed

Ticse, Caroline

2015-10-01

Key findings. (1) Adjusted premiums in the individual market in states with prior approval authority combined with loss ratio requirements were lower in 2010-2013 than premiums in states with no rate review authority or file-and-use regulations only. (2) Adjusted premiums declined modestly in prior approval states while premiums increased in states with no rate review authority or with file-and-use regulations only. (3) The findings suggest that states with prior approval authority and loss ratio requirements constrained increases in health insurance premiums.

Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Yan-Jie; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Juan, Chi-Chang

Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET{sub A}R during insulin resistance,more » ET{sub A}R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET{sub A}R expression, but not ET{sub B}R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET{sub A}R pathway suppressed insulin-induced AKT activation, whereas remained insulin-induced ERK activation. ET-1 and insulin synergistically potentiated migration and proliferation mainly through ET{sub A}R/ERK dependent pathway, which is dominant in VSMCs during modest insulin resistance syndrome. Therefore, ET-1 and ET{sub A}R are potential targets responsible for the observed synergism effect in the hypertensive atherosclerotic process through enhancement of ET-1 binding, ET-1 binding, ET{sub A}R expression, and ET-1-induced mitogenic actions in aortic VSMCs. - Highlights: • ET-1/ET{sub A}R signaling and insulin-induced pERK were high in modest insulin resistance. • ET-1 via ET{sub A}R suppressed insulin-induced pAKT but remained intact pERK in VSMCs. • Insulin potentiated ET-1-induced VSMC mitogenic action was ET{sub A}R/ERK dependent.« less

The hepatitis C cascade of care: identifying priorities to improve clinical outcomes.

PubMed

Linas, Benjamin P; Barter, Devra M; Leff, Jared A; Assoumou, Sabrina A; Salomon, Joshua A; Weinstein, Milton C; Kim, Arthur Y; Schackman, Bruce R

2014-01-01

As highly effective hepatitis C virus (HCV) therapies emerge, data are needed to inform the development of interventions to improve HCV treatment rates. We used simulation modeling to estimate the impact of loss to follow-up on HCV treatment outcomes and to identify intervention strategies likely to provide good value for the resources invested in them. We used a Monte Carlo state-transition model to simulate a hypothetical cohort of chronically HCV-infected individuals recently screened positive for serum HCV antibody. We simulated four hypothetical intervention strategies (linkage to care; treatment initiation; integrated case management; peer navigator) to improve HCV treatment rates, varying efficacies and costs, and identified strategies that would most likely result in the best value for the resources required for implementation. Sustained virologic responses (SVRs), life expectancy, quality-adjusted life expectancy (QALE), costs from health system and program implementation perspectives, and incremental cost-effectiveness ratios (ICERs). We estimate that imperfect follow-up reduces the real-world effectiveness of HCV therapies by approximately 75%. In the base case, a modestly effective hypothetical peer navigator program maximized the number of SVRs and QALE, with an ICER compared to the next best intervention of $48,700/quality-adjusted life year. Hypothetical interventions that simultaneously addressed multiple points along the cascade provided better outcomes and more value for money than less costly interventions targeting single steps. The 5-year program cost of the hypothetical peer navigator intervention was $14.5 million per 10,000 newly diagnosed individuals. We estimate that imperfect follow-up during the HCV cascade of care greatly reduces the real-world effectiveness of HCV therapy. Our mathematical model shows that modestly effective interventions to improve follow-up would likely be cost-effective. Priority should be given to developing and evaluating interventions addressing multiple points along the cascade rather than options focusing solely on single points.

The Hepatitis C Cascade of Care: Identifying Priorities to Improve Clinical Outcomes

PubMed Central

Linas, Benjamin P.; Barter, Devra M.; Leff, Jared A.; Assoumou, Sabrina A.; Salomon, Joshua A.; Weinstein, Milton C.; Kim, Arthur Y.; Schackman, Bruce R.

2014-01-01

Background As highly effective hepatitis C virus (HCV) therapies emerge, data are needed to inform the development of interventions to improve HCV treatment rates. We used simulation modeling to estimate the impact of loss to follow-up on HCV treatment outcomes and to identify intervention strategies likely to provide good value for the resources invested in them. Methods We used a Monte Carlo state-transition model to simulate a hypothetical cohort of chronically HCV-infected individuals recently screened positive for serum HCV antibody. We simulated four hypothetical intervention strategies (linkage to care; treatment initiation; integrated case management; peer navigator) to improve HCV treatment rates, varying efficacies and costs, and identified strategies that would most likely result in the best value for the resources required for implementation. Main measures Sustained virologic responses (SVRs), life expectancy, quality-adjusted life expectancy (QALE), costs from health system and program implementation perspectives, and incremental cost-effectiveness ratios (ICERs). Results We estimate that imperfect follow-up reduces the real-world effectiveness of HCV therapies by approximately 75%. In the base case, a modestly effective hypothetical peer navigator program maximized the number of SVRs and QALE, with an ICER compared to the next best intervention of $48,700/quality-adjusted life year. Hypothetical interventions that simultaneously addressed multiple points along the cascade provided better outcomes and more value for money than less costly interventions targeting single steps. The 5-year program cost of the hypothetical peer navigator intervention was $14.5 million per 10,000 newly diagnosed individuals. Conclusions We estimate that imperfect follow-up during the HCV cascade of care greatly reduces the real-world effectiveness of HCV therapy. Our mathematical model shows that modestly effective interventions to improve follow-up would likely be cost-effective. Priority should be given to developing and evaluating interventions addressing multiple points along the cascade rather than options focusing solely on single points. PMID:24842841

Ultrasonic vocalizations in golden hamsters (Mesocricetus auratus) reveal modest sex differences and nonlinear signals of sexual motivation.

PubMed

Fernández-Vargas, Marcela; Johnston, Robert E

2015-01-01

Vocal signaling is one of many behaviors that animals perform during social interactions. Vocalizations produced by both sexes before mating can communicate sex, identity and condition of the caller. Adult golden hamsters produce ultrasonic vocalizations (USV) after intersexual contact. To determine whether these vocalizations are sexually dimorphic, we analyzed the vocal repertoire for sex differences in: 1) calling rates, 2) composition (structural complexity, call types and nonlinear phenomena) and 3) acoustic structure. In addition, we examined it for individual variation in the calls. The vocal repertoire was mainly composed of 1-note simple calls and at least half of them presented some degree of deterministic chaos. The prevalence of this nonlinear phenomenon was confirmed by low values of harmonic-to-noise ratio for most calls. We found modest sexual differences between repertoires. Males were more likely than females to produce tonal and less chaotic calls, as well as call types with frequency jumps. Multivariate analysis of the acoustic features of 1-note simple calls revealed significant sex differences in the second axis represented mostly by entropy and bandwidth parameters. Male calls showed lower entropy and inter-quartile bandwidth than female calls. Because the variation of acoustic structure within individuals was higher than among individuals, USV could not be reliably assigned to the correct individual. Interestingly, however, this high variability, augmented by the prevalence of chaos and frequency jumps, could be the result of increased vocal effort. Hamsters motivated to produce high calling rates also produced longer calls of broader bandwidth. Thus, the sex differences found could be the result of different sex preferences but also of a sex difference in calling motivation or condition. We suggest that variable and complex USV may have been selected to increase responsiveness of a potential mate by communicating sexual arousal and preventing habituation to the caller.

Differences in Early Cytokine Production Are Associated With Development of a Greater Number of Symptoms Following West Nile Virus Infection.

PubMed

Hoffman, Kevin W; Sachs, David; Bardina, Susana V; Michlmayr, Daniela; Rodriguez, Carlos A; Sum, Janet; Foster, Gregory A; Krysztof, David; Stramer, Susan L; Lim, Jean K

2016-08-15

West Nile virus (WNV) is an emerging cause of meningitis and encephalitis in the United States. Although severe neuroinvasive disease and death can occur in rare instances, the majority of infected individuals remain asymptomatic or present with a range of clinical manifestations associated with West Nile fever. To better understand the interindividual variability associated with the majority of WNV infections, we evaluated the association of cytokine/chemokine production and outcome of infection among 115 WNV-positive US blood donors identified in 2008-2011. All subjects self-reported symptoms as having occurred during the 2 weeks following blood donation, using a standardized questionnaire. We discovered that, prior to seroconversion, an early potent, largely type I interferon-mediated response correlated with development of a greater number of symptoms in WNV-infected individuals. Interestingly, individuals who developed fewer symptoms had not only a more modest type I interferon response initially, but also a protracted cytokine response after seroconversion, marked by the production of monocyte and T-cell-associated chemokines. Collectively, our data suggest that, although an early type I interferon response appears to be crucial to control WNV infection, successful immunity may require a modest early response that is maintained during the course of infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Evolutionary Diagnosis of non-synonymous variants involved in differential drug response

PubMed Central

2015-01-01

Background Many pharmaceutical drugs are known to be ineffective or have negative side effects in a substantial proportion of patients. Genomic advances are revealing that some non-synonymous single nucleotide variants (nsSNVs) may cause differences in drug efficacy and side effects. Therefore, it is desirable to evaluate nsSNVs of interest in their ability to modulate the drug response. Results We found that the available data on the link between drug response and nsSNV is rather modest. There were only 31 distinct drug response-altering (DR-altering) and 43 distinct drug response-neutral (DR-neutral) nsSNVs in the whole Pharmacogenomics Knowledge Base (PharmGKB). However, even with this modest dataset, it was clear that existing bioinformatics tools have difficulties in correctly predicting the known DR-altering and DR-neutral nsSNVs. They exhibited an overall accuracy of less than 50%, which was not better than random diagnosis. We found that the underlying problem is the markedly different evolutionary properties between positions harboring nsSNVs linked to drug responses and those observed for inherited diseases. To solve this problem, we developed a new diagnosis method, Drug-EvoD, which was trained on the evolutionary properties of nsSNVs associated with drug responses in a sparse learning framework. Drug-EvoD achieves a TPR of 84% and a TNR of 53%, with a balanced accuracy of 69%, which improves upon other methods significantly. Conclusions The new tool will enable researchers to computationally identify nsSNVs that may affect drug responses. However, much larger training and testing datasets are needed to develop more reliable and accurate tools. PMID:25952014

Allergic Sensitization through the Airway Primes Th17-dependent Neutrophilia and Airway Hyperresponsiveness

PubMed Central

Wilson, Rhonda H.; Whitehead, Gregory S.; Nakano, Hideki; Free, Meghan E.; Kolls, Jay K.; Cook, Donald N.

2009-01-01

Rationale: In humans, immune responses to inhaled aeroallergens develop in the lung and draining lymph nodes. Many animal models of asthma bypass this route and instead use intraperitoneal injections of allergen using aluminum hydroxide as an adjuvant. Objectives: We investigated whether allergic sensitization through the airway elicits immune responses qualitatively different than those arising in the peritoneum. Methods: Mice were sensitized to allergen through the airway using low-dose LPS as an adjuvant, or through the peritoneum using aluminum hydroxide as an adjuvant. After a single allergen challenge, ELISA and flow cytometry were used to measure cytokines and leukocyte subsets. Invasive measurements of airway resistance were used to measure allergen-induced airway hyperreactivity (AHR). Measurements and Main Results: Sensitization through the peritoneum primed strong Th2 responses and eosinophilia, but not AHR, after a single allergen challenge. By contrast, allergic sensitization through the airway primed only modest Th2 responses, but strong Th17 responses. Th17 cells homed to the lung and released IL-17 into the airway on subsequent encounter with inhaled allergen. As a result, these mice developed IL-17–dependent airway neutrophilia and AHR. This AHR was neutrophil-dependent because it was abrogated in CXCR2-deficient mice and also in wild-type mice receiving a neutrophil-depleting antibody. Individually, neither IL-17 nor ongoing Th2 responses were sufficient to confer AHR, but together they acted synergistically to promote neutrophil recruitment, eosinophil recruitment and AHR. Conclusions: Allergic sensitization through the airway primes modest Th2 responses but strong Th17 responses that promote airway neutrophilia and acute AHR. These findings support a causal role for neutrophils in severe asthma. PMID:19661246

Study on effectiveness of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related non-Hodgkin's lymphoma.

PubMed

Zhong, Dong Ta; Shi, Chun Mei; Chen, Qiang; Huang, Jing Ze; Liang, Jian Gang

2012-11-01

Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. Even though NHL is commonly chemosensitive to primary treatment, failure or relapse still occurs in a large number of patients. We conducted this retrospective study to evaluate the efficacy and safety of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related NHL (AIDS-NHL). Forty-eight patients with relapsed or refractory AIDS-NHL were treated with intravenous combination chemotherapy with GDP. The overall objective response rate was 54.1% (95% confidence interval, CI, 40.1-68.3%), with 10 complete responses and 16 partial responses. The 2-year overall survival rate (OS) was 70.8% (95% CI 58.0-83.7%), and the 5-year OS was 41.7% (95% CI 27.7-55.6%). The 2-year progression-free survival rate (PFS) was 37.5% (95% CI 23.8-51.2%), and the 5-year PFS was 25.0% (95% CI 12.8-37.3%). The median progression-free survival was 8.8 months (95% CI 0-20.3 months), and the median overall survival was 40.6 months (95% CI 22.6-58.6 months). Patients with B cell tumors who relapsed but had no B symptoms were clinical stage I/II, had infiltration fewer than two extranodal sites, had CD4⁺ counts >200 cells/μL, and had lactate dehydrogenase (LDH) less than the upper limit of normal benefited from GDP. The level of LDH had a significant impact on the response rate to chemotherapy with GDP (P = 0.015). Myelosuppression was the main side effect; the incidence of grade 3-4 anemia was 8.3%; leukopenia, 37.5%; and thrombocytopenia, 48.3%. Univariate and multivariate analyses were performed to determine variables for OS and PFS. This study confirms that GDP is an effective and safe salvage regimen in relapsed or refractory AIDS-NHL, was associated with modest declines in CD4⁺ lymphocyte counts, and did not promote HIV-1 viral replication.

Rheologic effects of crystal preferred orientation in upper mantle flow near plate boundaries

NASA Astrophysics Data System (ADS)

Blackman, Donna; Castelnau, Olivier; Dawson, Paul; Boyce, Donald

2016-04-01

Observations of anisotropy provide insight into upper mantle processes. Flow-induced mineral alignment provides a link between mantle deformation patterns and seismic anisotropy. Our study focuses on the rheologic effects of crystal preferred orientation (CPO), which develops during mantle flow, in order to assess whether corresponding anisotropic viscosity could significantly impact the pattern of flow. We employ a coupled nonlinear numerical method to link CPO and the flow model via a local viscosity tensor field that quantifies the stress/strain-rate response of a textured mineral aggregate. For a given flow field, the CPO is computed along streamlines using a self-consistent texture model and is then used to update the viscosity tensor field. The new viscosity tensor field defines the local properties for the next flow computation. This iteration produces a coupled nonlinear model for which seismic signatures can be predicted. Results thus far confirm that CPO can impact flow pattern by altering rheology in directionally-dependent ways, particularly in regions of high flow gradient. Multiple iterations run for an initial, linear stress/strain-rate case (power law exponent n=1) converge to a flow field and CPO distribution that are modestly different from the reference, scalar viscosity case. Upwelling rates directly below the spreading axis are slightly reduced and flow is focused somewhat toward the axis. Predicted seismic anisotropy differences are modest. P-wave anisotropy is a few percent greater in the flow 'corner', near the spreading axis, below the lithosphere and extending 40-100 km off axis. Predicted S-wave splitting differences would be below seafloor measurement limits. Calculations with non-linear stress/strain-rate relation, which is more realistic for olivine, indicate that effects are stronger than for the linear case. For n=2-3, the distribution and strength of CPO for the first iteration are greater than for n=1, although the fast seismic axis directions are similar. The greatest difference in CPO for the nonlinear cases develop at the flow 'corner' at depths of 10-30 km and 20-100 km off-axis. J index values up to 10% greater than the linear case are predicted near the lithosphere base in that region. Viscosity tensor components are notably altered in the nonlinear cases. Iterations between the texture and flow calculations for the non-linear cases are underway this winter; results will be reported in the presentation.

Sildenafil effects on sexual and cardiovascular responses in women with spinal cord injury.

PubMed

Sipski, M L; Rosen, R C; Alexander, C J; Hamer, R M

2000-06-01

Sexual dysfunction is common in women with spinal cord injuries (SCIs) and other neurologic conditions. Sildenafil has previously been shown to be safe and effective in the treatment of erectile dysfunction due to SCI. This study is the first to evaluate the sexual and cardiovascular effects of sildenafil in women with SCIs in a controlled, laboratory setting. Nineteen premenopausal women with SCIs were randomly assigned to receive either sildenafil (50 mg) or placebo in a double-blind, crossover design study. Physiologic and subjective measures of sexual response, heart rate, and blood pressure were recorded during baseline and sexual stimulation conditions. Adverse events were also recorded. Significant increases in subjective arousal (SA) were observed with both drug (P <0.01) and sexual stimulation conditions (P <0.001), and a borderline significant (P <0.07) effect of drug administration on vaginal pulse amplitude (VPA) was noted. Maximal responses occurred when sildenafil was combined with visual and manual sexual stimulation. Cardiovascular data showed modest increases in heart rate (+/-5 bpm) and mild decreases in blood pressure (+/-4 mm Hg) across all stimulation conditions, consistent with the peripheral vasodilatory mechanism of the drug. Sildenafil was well tolerated with no evidence of significant adverse events. Findings suggest that sildenafil may partially reverse the sexual dysfunction commonly associated with SCI in women. Consistent with previous findings in men, the sexual effects of the drug were most evident under conditions of optimal stimulation. Mild, clinically insignificant cardiovascular effects were also noted. Further large-scale studies of sildenafil's effects in women with neurogenic sexual dysfunction are strongly indicated.

Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer.

PubMed

Rugo, Hope S; Delord, Jean-Pierre; Im, Seock-Ah; Ott, Patrick A; Piha-Paul, Sarina A; Bedard, Philippe L; Sachdev, Jasgit; Tourneau, Christophe Le; van Brummelen, Emilie M J; Varga, Andrea; Salgado, Roberto; Loi, Sherene; Saraf, Sanatan; Pietrangelo, Dina; Karantza, Vassiliki; Tan, Antoinette R

2018-03-20

Purpose: We investigated the safety and antitumor activity of the anti-programmed death 1 monoclonal antibody pembrolizumab in patients with estrogen receptor-positive (ER + )/human epidermal growth factor receptor 2-negative (HER2 - ) advanced breast cancer with programmed death ligand 1-positive (PD-L1-positive) tumors in the phase Ib open-label, multicohort KEYNOTE-028 (NCT02054806) study. Experimental Design: Patients with ER + /HER2 - advanced breast cancer with PD-L1-positive tumors (combined positive score ≥1) received pembrolizumab (10 mg/kg every 2 weeks) up to 2 years or until confirmed progression/intolerable toxicity. Primary endpoints were safety and overall response rate (ORR), based on Response Evaluation Criteria in Solid Tumors, version 1 (RECIST v1.1) as assessed by investigator review. Results: Between April 2014 and January 2015, 25 patients were enrolled. Median number of prior therapies for breast cancer, including endocrine agents, was 9 (range, 3-15). Median follow-up was 9.7 months (range, 0.7-31.8 months). Three patients experienced partial response (PR) and none experienced complete response (CR), resulting in an ORR of 12.0% (95% CI, 2.5%-31.2%); 16% of patients had stable disease (SD) and clinical benefit rate (CR + PR + [SD for ≥24 weeks]) was 20% (95% CI, 7-41). Median duration of response was 12.0 months (range, 7.4-15.9 months). The incidence of treatment-related adverse events was 64%; nausea (20%) and fatigue (12%) were most common and were predominantly grade 1/2. No treatment-related discontinuations or deaths occurred. Conclusions: Pembrolizumab was well tolerated with modest but durable overall response in certain patients with previously treated, advanced, PD-L1-positive, ER + /HER2 - breast cancer. Clin Cancer Res; 1-8. ©2018 AACR. ©2018 American Association for Cancer Research.

Design and validity of a clinic-based case-control study on the molecular epidemiology of lymphoma

PubMed Central

Cerhan, James R; Fredericksen, Zachary S; Wang, Alice H; Habermann, Thomas M; Kay, Neil E; Macon, William R; Cunningham, Julie M; Shanafelt, Tait D; Ansell, Stephen M; Call, Timothy G; Witzig, Thomas E; Slager, Susan L; Liebow, Mark

2011-01-01

We present the design features and implementation of a clinic-based case-control study on the molecular epidemiology of lymphoma conducted at the Mayo Clinic (Rochester, Minnesota, USA), and then assess the internal and external validity of the study. Cases were newly diagnosed lymphoma patients from Minnesota, Iowa and Wisconsin seen at Mayo and controls were patients from the same region without lymphoma who had a pre-scheduled general medical examination, frequency matched on age, sex and residence. Overall response rates were 67% for cases and 70% for controls; response rates were lower for cases and controls over age 70 years, cases with more aggressive disease, and controls from the local area, although absolute differences were modest. Cases and controls were well-balanced on age, sex, and residence characteristics. Demographic and disease characteristics of NHL cases were similar to population-based cancer registry data. Control distributions were similar to population-based data on lifestyle factors and minor allele frequencies of over 500 SNPs, although smoking rates were slightly lower. Associations with NHL in the Mayo study for smoking, alcohol use, family history of lymphoma, autoimmune disease, asthma, eczema, body mass index, and single nucleotide polymorphisms in TNF (rs1800629), LTA (rs909253), and IL10 (rs1800896) were at a magnitude consistent with estimates from pooled studies in InterLymph, with history of any allergy the only directly discordant result in the Mayo study. These data suggest that this study should have strong internal and external validity. This framework may be useful to others who are designing a similar study. PMID:21686124

Community Colleges in the Spotlight and under the Microscope

ERIC Educational Resources Information Center

Boggs, George R.

2011-01-01

Never before have community colleges received so much attention and recognition. From modest beginnings at the start of the twentieth century, community colleges have become the largest, most affordable, and most responsive sector of American higher education. Policy makers, media, and the public in general seem to have only now discovered…

The Effects of Maternal Social Phobia on Mother-Infant Interactions and Infant Social Responsiveness

ERIC Educational Resources Information Center

Murray, Lynne; Cooper, Peter; Creswell, Cathy; Schofield, Elizabeth; Sack, Caroline

2007-01-01

Background: Social phobia aggregates in families. The genetic contribution to intergenerational transmission is modest, and parenting is considered important. Research on the effects of social phobia on parenting has been subject to problems of small sample size, heterogeneity of samples and lack of specificity of observational frameworks. We…

Bullying and Stress in Early Adolescence: The Role of Coping and Social Support

ERIC Educational Resources Information Center

Konishi, Chiaki; Hymel, Shelley

2009-01-01

Prior research from Norway and Japan has demonstrated positive relationships between stress and bullying--The more stress students experience, the more they engage in bullying. The modest correlations, however, suggest that other variables may moderate the stress-bullying link, serving as protective factors that make such negative responses to…

Unlocking Potential: How Political Skill Can Maximize Superintendent Effectiveness

ERIC Educational Resources Information Center

Hill, Paul; Jochim, Ashley

2018-01-01

Local superintendents must do an important job while equipped with, at best, modest authority. Superintendents are ultimately responsible for all the schools in their district, and they at least nominally supervise everything that happens in those schools. Yet superintendents cannot count on obedience or even support from the people who work for…

Introduction: Community College Leadership: Perspectives of Women as Presidents.

ERIC Educational Resources Information Center

Gillett-Karam, Rosemary

2001-01-01

Asserts that women are making a modest gain in the community college leadership roles. Discusses university research on women leaders in higher education, most notably that of Gilligan, who stated that women arrive at their responsibilities through care and concern, a different way from the path of justice men emphasized. Presents author's…

Selected regulation of gastrointestinal acid-base secretion and tissue metabolism for the diamondback water snake and Burmese python.

PubMed

Secor, Stephen M; Taylor, Josi R; Grosell, Martin

2012-01-01

Snakes exhibit an apparent dichotomy in the regulation of gastrointestinal (GI) performance with feeding and fasting; frequently feeding species modestly regulate intestinal function whereas infrequently feeding species rapidly upregulate and downregulate intestinal function with the start and completion of each meal, respectively. The downregulatory response with fasting for infrequently feeding snakes is hypothesized to be a selective attribute that reduces energy expenditure between meals. To ascertain the links between feeding habit, whole-animal metabolism, and GI function and metabolism, we measured preprandial and postprandial metabolic rates and gastric and intestinal acid-base secretion, epithelial conductance and oxygen consumption for the frequently feeding diamondback water snake (Nerodia rhombifer) and the infrequently feeding Burmese python (Python molurus). Independent of body mass, Burmese pythons possess a significantly lower standard metabolic rate and respond to feeding with a much larger metabolic response compared with water snakes. While fasting, pythons cease gastric acid and intestinal base secretion, both of which are stimulated with feeding. In contrast, fasted water snakes secreted gastric acid and intestinal base at rates similar to those of digesting snakes. We observed no difference between fasted and fed individuals for either species in gastric or intestinal transepithelial potential and conductance, with the exception of a significantly greater gastric transepithelial potential for fed pythons at the start of titration. Water snakes experienced no significant change in gastric or intestinal metabolism with feeding. Fed pythons, in contrast, experienced a near-doubling of gastric metabolism and a tripling of intestinal metabolic rate. For fasted individuals, the metabolic rate of the stomach and small intestine was significantly lower for pythons than for water snakes. The fasting downregulation of digestive function for pythons is manifested in a depressed gastric and intestinal metabolism, which selectively serves to reduce basal metabolism and hence promote survival between infrequent meals. By maintaining elevated GI performance between meals, fasted water snakes incur the additional cost of tissue activity, which is expressed in a higher standard metabolic rate.

A phase II study of sunitinib in patients with recurrent epithelial ovarian and primary peritoneal carcinoma: an NCIC Clinical Trials Group Study.

PubMed

Biagi, J J; Oza, A M; Chalchal, H I; Grimshaw, R; Ellard, S L; Lee, U; Hirte, H; Sederias, J; Ivy, S P; Eisenhauer, E A

2011-02-01

Sunitinib is a multitargeted receptor tyrosine kinase inhibitor. We conducted a two-stage phase II study to evaluate the objective response rate of oral sunitinib in recurrent epithelial ovarian cancer. Eligibility required measurable disease and one or two prior chemotherapies, at least one platinum based. Platinum-sensitive or -resistant disease was allowed. Initial dose schedule was sunitinib 50 mg daily, 4 of 6 weeks. Observation of fluid accumulations during off-treatment periods resulted in adoption of continuous 37.5 mg daily dosing in the second stage of accrual. Of 30 eligible patients, most had serous histology (67%), were platinum sensitive (73%) and had two prior chemotherapies (60%). One partial response (3.3%) and three CA125 responses (10%) were observed, all in platinum-sensitive patients using intermittent dosing. Sixteen (53%) had stable disease. Five had >30% decrease in measurable disease. Overall median progression-free survival was 4.1 months. Common adverse events included fatigue, gastrointestinal symptoms, hand-foot syndrome and hypertension. No gastrointestinal perforation occurred. Single-agent sunitinib has modest activity in recurrent platinum-sensitive ovarian cancer, but only at the 50 mg intermittent dose schedule, suggesting that dose and schedule may be vital considerations in further evaluation of sunitinib in this cancer setting.

Emotional and physiological reactivity in Complicated Grief.

PubMed

LeBlanc, Nicole J; Unger, Leslie D; McNally, Richard J

2016-04-01

Grief is a psychobiological response to the loss of a loved one. Some grief theorists suggest that this predictable response may arise from withdrawal of psychobiological regulation previously provided by the deceased (e.g. assistance with emotion regulation). Accordingly, recovery from loss may require bereaved individuals to re-establish self-regulatory control to avoid developing Complicated Grief (CG). This model implies that adults with CG may exhibit aberrant emotional responding to environmental stimuli. The present study was designed to test this hypothesis. We recruited a sample of 23 bereaved adults with CG and 26 healthy bereaved adults to complete an emotional reactivity paradigm. Participants watched a series of emotional film clips and provided measures of their self-reported emotional response. We also assessed their heart rate, respiratory sinus arrhythmia (RSA), and skin conductance level in response to these clips. Though emotional and physiological differences between the groups were rare, the CG group exhibited attenuated RSA reactivity to some emotional film clips, suggesting blunted parasympathetic nervous system reactivity in those with the disorder. Limitations include the modest sample size and unequal group sizes. Individuals with CG do not exhibit pervasive differences in emotional and physiological reactivity compared to healthy bereaved individuals. However, we did observe evidence of blunted parasympathetic nervous system reactivity in individuals with CG, which may mediate emotional inflexibility among those who develop the disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

Cardiorespiratory responses in an Antarctic fish suggest limited capacity for thermal acclimation.

PubMed

Egginton, Stuart; Campbell, Hamish A

2016-05-01

Polar fishes are at high risk from increasing seawater temperatures. Characterising the physiological responses to such changes may both clarify mechanisms that permit life under extreme conditions and identify limitations in the response to continued global warming. We hypothesised that Notothenia coriiceps would show physiological compensation after an acute exposure to 5°C, and following 6 weeks warm acclimation, compared with ambient temperature (0°C). However, initial tachycardia (22.4±2.8 versus 12.8±1.1 min(-1); P<0.01) was not reversed by acclimation (21.0±1.9 min(-1)). Hyperventilation (45.5±3.1 versus 21.4±2.4 breaths min(-1); P<0.001) showed a modest reduction following acclimation (38.0±2.9 min(-1); P<0.05), while resting oxygen consumption (0.52±0.08 mmol kg(-1) h(-1)) was acutely increased at 5°C (1.07±0.10 mmol kg(-1) h(-1); P<0.001) but unchanged with acclimation. Autonomic blockade showed initial responses were mainly of vagal origin, with little subsequent withdrawal or recovery in long-term heart rate variability after 6 weeks. Given the limited cardiorespiratory capacity to withstand sustained warming, effective physiological compensation probably requires a more prolonged acclimation period. © 2016. Published by The Company of Biologists Ltd.

Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib

PubMed Central

Furman, Richard R.; Coutre, Steven E.; Burger, Jan A.; Blum, Kristie A.; Coleman, Morton; Wierda, William G.; Jones, Jeffrey A.; Zhao, Weiqiang; Heerema, Nyla A.; Johnson, Amy J.; Shaw, Yun; Bilotti, Elizabeth; Zhou, Cathy; James, Danelle F.; O'Brien, Susan

2015-01-01

Ibrutinib is an orally administered inhibitor of Bruton tyrosine kinase that antagonizes B-cell receptor, chemokine, and integrin-mediated signaling. In early-phase studies, ibrutinib demonstrated high response rates and prolonged progression-free survival (PFS) in chronic lymphocytic leukemia (CLL). The durable responses observed with ibrutinib relate in part to a modest toxicity profile that allows the majority of patients to receive continuous therapy for an extended period. We report on median 3-year follow-up of 132 patients with symptomatic treatment-naïve and relapsed/refractory CLL or small lymphocytic lymphoma. Longer treatment with ibrutinib was associated with improvement in response quality over time and durable remissions. Toxicity with longer follow-up diminished with respect to occurrence of grade 3 or greater cytopenias, fatigue, and infections. Progression remains uncommon, occurring primarily in some patients with relapsed del(17)(p13.1) and/or del(11)(q22.3) disease. Treatment-related lymphocytosis remains largely asymptomatic even when persisting >1 year and does not appear to alter longer-term PFS and overall survival compared with patients with partial response or better. Collectively, these data provide evidence that ibrutinib controls CLL disease manifestations and is well tolerated for an extended period; this information can help direct potential treatment options for different subgroups to diminish the long-term risk of relapse. PMID:25700432

Hearing conservation in the primary aluminium industry.

PubMed

Donoghue, A M; Frisch, N; Dixon-Ernst, C; Chesson, B J; Cullen, M R

2016-04-01

Noise-induced hearing loss has been an intractable problem for heavy industry. To report our experience in reducing the incidence of age-corrected confirmed 10 dB hearing shifts (averaged over 2, 3 and 4 kHz) in employees in the primary aluminium industry in Australia over the period 2006-13. We analysed annual audiometric data to determine the number of permanent hearing shifts that occurred in employees in two bauxite mines, three alumina refineries and two aluminium smelters. Annual hearing shift rates were calculated based on the number of employees tested per year. Hearing conservation initiatives undertaken during the study period are described. An assessment of similar exposure group noise exposures was also undertaken to determine the magnitude of noise exposure reduction during the study period. Across all operations, hearing shift rates declined from 5.5% per year in 2006 to 1.3% per year in 2013 (P < 0.001). The decline in shift rates was greater in mines and refineries, where baseline shift rates were higher, than in smelter workers. Modest reductions in noise exposure occurred during the study period. We observed a substantial decline in hearing shift rates during the study period. We describe the hearing conservation initiatives that were collectively associated with this decline. We suspect these initiatives could be deployed relatively easily and at modest cost in other industries with noise-exposed employees. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine.

Circuitry linking the Csr and stringent response global regulatory systems.

PubMed

Edwards, Adrianne N; Patterson-Fortin, Laura M; Vakulskas, Christopher A; Mercante, Jeffrey W; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I; Fields, Joshua A; Thompson, Stuart A; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

2011-06-01

CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. © Published 2011. This article is a US Government work and is in the public domain in the USA.

Serum levels of cytokines in water buffaloes experimentally infected with Fasciola gigantica.

PubMed

Zhang, Fu-Kai; Guo, Ai-Jiang; Hou, Jun-Ling; Sun, Miao-Miao; Sheng, Zhao-An; Zhang, Xiao-Xuan; Huang, Wei-Yi; Elsheikha, Hany M; Zhu, Xing-Quan

2017-09-15

Fasciola gigantica infection in water buffaloes causes significant economic losses especially in developing countries. Although modulation of the host immune response by cytokine neutralization or vaccination is a promising approach to control infection with this parasite, our understanding of cytokine's dynamic during F. gigantica infection is limited. To address this, we quantified the levels of serum cytokines produced in water buffaloes following experimental infection with F. gigantica. Five buffaloes were infected via oral gavage with 500 viable F. gigantica metacercariae and blood samples were collected from buffaloes one week before infection and for 13 consecutive weeks thereafter. The levels of 10 cytokines in serum samples were simultaneously determined using ELISA. F. gigantica failed to elicit the production of various pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-2, IL-6, IL-12, and IFN-γ. On the other hand, evidence of a Th2 type response was detected, but only early in the course of parasite colonization and included modest increase in the levels of IL-10 and IL-13. The results also revealed suppression of the immune responses as a feature of chronic F. gigantica infection in buffaloes. Taken together, F. gigantica seems to elicit a modest Th2 response at early stage of infection in order to downregulate harmful Th1- and Th17-type inflammatory responses in experimentally infected buffaloes. The full extent of anti-F. gigantica immune response and its relation to pathogenesis requires further study. Copyright © 2017 Elsevier B.V. All rights reserved.

Scholarly contributions of required senior research projects in a doctor of pharmacy curriculum.

PubMed

Assemi, Mitra; Ibarra, Francisco; Mallios, Ronna; Corelli, Robin L

2015-03-25

To determine dissemination outcomes and faculty perceptions of senior research projects conducted from 2008 to 2011 by PharmD students in a curricular pathway focused on direct patient care. Preceptors' reported dissemination outcomes of research projects were surveyed and their perceptions of the precepting experience were rated using a web-based survey. Results were compared to those from an earlier pharmaceutical care cohort (2002-2007) and a combined cohort of 2, more research-intensive curricular pathways at the school. The overall response rate was 90.2%. Project dissemination included 61.3% at an institutional forum, 42.3% as a submitted publication, 37.8% as a poster, and 4.5% as an oral presentation. Projects completed from 2008-2011 were significantly more likely than those from 2002-2007 to be submitted for publication (42.3% vs 10.7%, p<0.001) and published (28.8% vs 5.3%, p<0.001). Most preceptors found their research projects valuable to them professionally (88.3%) and to their own or another institution (83.5% and 78.5%, respectively). Ninety-five percent of preceptors would precept again. Dissemination rates for pharmaceutical care projects increased over time. Despite modest dissemination levels, the majority of preceptors agreed that required student research projects provide a valuable learning experience for students.

A CW Gunn Diode Switching Element.

ERIC Educational Resources Information Center

Hurtado, Marco; Rosenbaum, Fred J.

As part of a study of the application of communication satellites to educational development, certain technical aspects of such a system were examined. A current controlled bistable switching element using a CW Gunn diode is reported on here. With modest circuits switching rates of the order of 10 MHz have been obtained. Switching is initiated by…

It's Who I Am: Student Identity Centrality and College Student Success

ERIC Educational Resources Information Center

Bowman, Nicholas A.; Felix, Vivienne

2017-01-01

Despite considerable research on student retention and persistence, college graduation rates remain modest. This article proposes the concept of student identity centrality, which is defined as the extent to which being a student is important to one's self-image or identity. This study found student identity centrality was positively related to…

Are We Talking about the Same Child? Parent-Teacher Ratings of Preschoolers' Social-Emotional Behaviors

ERIC Educational Resources Information Center

Major, Sofia O.; Seabra-Santos, Maria J.; Martin, Roy P.

2015-01-01

The parent-teacher agreement has become an important issue of children's psychological assessment. However, the amount of research available for preschool children is small and mainly based on one index of agreement with samples of modest size/representativeness. This study examined parent-teacher agreement (correlations) and discrepancies (t…

How Reading Is Being Reimagined

ERIC Educational Resources Information Center

Kirschenbaum, Matthew

2007-01-01

Google, in cooperation with several dozen research libraries worldwide, is digitizing books at the rate of 3,000 a day. The noncommercial Open Content Alliance is scanning at a more modest pace but gaining ground, especially among institutions who chafe at some of the restrictions imposed by Google and its competitors. LibraryThing, an online book…

Genetic variance partitioning and genome-wide prediction with allele dosage information in autotetraploid potato

USDA-ARS?s Scientific Manuscript database

Potato breeding cycles typically last 6-7 years because of the modest seed multiplication rate and large number of traits required of new varieties. Genomic selection has the potential to increase genetic gain per unit of time, through higher accuracy and/or a shorter cycle. Both possibilities were ...

Simulations of the modified gap experiment

NASA Astrophysics Data System (ADS)

Sutherland, Gerrit T.; Benjamin, Richard; Kooker, Douglas

2017-01-01

Modified gap experiment (test) hydrocode simulations predict the trends seen in experimental excess free surface velocity versus input pressure curves for explosives with both large and modest failure diameters. Simulations were conducted for explosive "A", an explosive with a large failure diameter, and for cast TNT, which has a modest failure diameter. Using the best available reactive rate models, the simulations predicted sustained ignition thresholds similar to experiment. This is a threshold where detonation is likely given a long enough run distance. For input pressures greater than the sustained ignition threshold pressure, the simulations predicted too little velocity for explosive "A" and too much velocity for TNT. It was found that a better comparison of experiment and simulation requires additional experimental data for both explosives. It was observed that the choice of reactive rate model for cast TNT can lead to large differences in the predicted modified gap experiment result. The cause of the difference is that the same data was not used to parameterize both models; one set of data was more shock reactive than the other.

Sci-Thur PM – Brachytherapy 04: Commissioning and Implementation of a Cobalt-60 High Dose Rate Brachytherapy Source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dysart, Jonathan

An Eckert & Ziegler Bebig Co0.A86 cobalt 60 high dose rate (HDR) brachytherapy source was commissioned for clinical use. Long-lived Co-60 HDR sources offer potential logistical and economic advantages over Ir-192 sources, and should be considered for low to medium workload brachytherapy departments where modest increases in treatment times are not a factor. In optimized plans, the Co-60 source provides a similar dose distribution to Ir-192 despite the difference in radiation energy. By switching to Co-60, source exchange frequency can be reduced by a factor of 20, resulting in overall financial savings of more than 50% compared to Ir-192 sources.more » In addition, a reduction in Physicist QA workload of roughly 200 hours over the 5 year life of the Co-60 source is also expected. These benefits should be considered against the modest increases in average treatment time compared to those of Ir-192 sources, as well as the centre-specific needs for operating room shielding modification.« less

In vivo growth rates are poorly correlated with phage therapy success in a mouse infection model.

PubMed

Bull, J J; Otto, G; Molineux, I J

2012-02-01

Two classes of phages yield profoundly different levels of recovery in mice experimentally infected with an Escherichia coli O18:K1:H7 strain. Phages requiring the K1 capsule for infection (K1-dep) rescue virtually all infected mice, whereas phages not requiring the capsule (K1-ind) rescue modest numbers (∼30%). To rescue infected mice, K1-ind phages require at least a 10(6)-fold-higher inoculum than K1-dep phages. Yet their in vivo growth dynamics are only modestly inferior to those of K1-dep phages, and competition between the two phage types in the same mouse reveals only a slight growth advantage for the K1-dep phage. The in vivo growth rate seems unlikely to be the primary determinant of phage therapy success. An alternative explanation is that the success of K1-dep phages is due substantially to their proteomic composition. They encode an enzyme that degrades the K1 capsule, which has been shown in other work to be sufficient to cure infection in the complete absence of phages.

Trends of Thyroid Cancer in Israel: 1980–2012

PubMed Central

Keinan-Boker, Lital; Silverman, Barbara G.

2016-01-01

Objectives: Thyroid cancer incidence is increasing worldwide, while mortality from thyroid cancer is stable or decreasing. Consequently, survival rates are rising. We describe time trends in the incidence, mortality, and 5-year survival of thyroid cancer in Israel in 1980–2012, in light of the global trends. Methods: Israel National Cancer Registry database provided information regarding thyroid cancer incidence and vital status, which enabled computation of survival rates. The Central Bureau of Statistics database provided information on thyroid cancer mortality. Incidence and mortality rates were age-adjusted and presented by population group (Jews/Arabs) and gender. Relative 5-year survival rates which account for the general population survival in the corresponding time period were presented by population group and gender. Joinpoint analyses were used to assess incidence trends over time. Results: In 1980–2012 significant increases in the incidence of thyroid cancer were observed, with an annual percent change (APC) range of 3.98–6.93, driven almost entirely by papillary carcinoma (APCs 5.75–8.86), while rates of other types of thyroid cancer remained stable or decreased. Furthermore, higher rates of early detection were noted. In 1980–2012, a modest reduction in thyroid cancer mortality was observed in Jewish women (APC −1.07) with no substantial change in Jewish men. The 5-year relative survival after thyroid cancer diagnosis has increased to ≥90% in both population groups and both genders. Conclusions: The Israeli secular trends of thyroid cancer incidence (increasing), mortality (mostly stable), and survival (modestly increasing) closely follow reported global trends. PMID:26886958

Effects of concurrent physical and cognitive demands on muscle activity and heart rate variability in a repetitive upper-extremity precision task.

PubMed

Srinivasan, Divya; Mathiassen, Svend Erik; Hallman, David M; Samani, Afshin; Madeleine, Pascal; Lyskov, Eugene

2016-01-01

Most previous studies of concurrent physical and cognitive demands have addressed tasks of limited relevance to occupational work, and with dissociated physical and cognitive task components. This study investigated effects on muscle activity and heart rate variability of executing a repetitive occupational task with an added cognitive demand integral to correct task performance. Thirty-five healthy females performed 7.5 min of standardized repetitive pipetting work in a baseline condition and a concurrent cognitive condition involving a complex instruction for correct performance. Average levels and variabilities of electromyographic activities in the upper trapezius and extensor carpi radialis (ECR) muscles were compared between these two conditions. Heart rate and heart rate variability were also assessed to measure autonomic nervous system activation. Subjects also rated perceived fatigue in the neck-shoulder region, as well as exertion. Concurrent cognitive demands increased trapezius muscle activity from 8.2% of maximum voluntary exertion (MVE) in baseline to 9.0% MVE (p = 0.0005), but did not significantly affect ECR muscle activity, heart rate, heart rate variability, perceived fatigue or exertion. Trapezius muscle activity increased by about 10%, without any accompanying cardiovascular response to indicate increased sympathetic activation. We suggest this slight increase in trapezius muscle activity to be due to changed muscle activation patterns within or among shoulder muscles. The results suggest that it may be possible to introduce modest cognitive demands necessary for correct performance in repetitive precision work without any major physiological effects, at least in the short term.

Diversity and Homogeneity in Responses of Midbrain Dopamine Neurons

PubMed Central

Fiorillo, Christopher D.; Yun, Sora R.; Song, Minryung R.

2013-01-01

Dopamine neurons of the ventral midbrain have been found to signal a reward prediction error that can mediate positive reinforcement. Despite the demonstration of modest diversity at the cellular and molecular levels, there has been little analysis of response diversity in behaving animals. Here we examine response diversity in rhesus macaques to appetitive, aversive, and neutral stimuli having relative motivational values that were measured and controlled through a choice task. First, consistent with previous studies, we observed a continuum of response variability and an apparent absence of distinct clusters in scatter plots, suggesting a lack of statistically discrete subpopulations of neurons. Second, we found that a group of “sensitive” neurons tend to be more strongly suppressed by a variety of stimuli and to be more strongly activated by juice. Third, neurons in the “ventral tier” of substantia nigra were found to have greater suppression, and a subset of these had higher baseline firing rates and late “rebound” activation after suppression. These neurons could belong to a previously identified subgroup of dopamine neurons that express high levels of H-type cation channels but lack calbindin. Fourth, neurons further rostral exhibited greater suppression. Fifth, although we observed weak activation of some neurons by aversive stimuli, this was not associated with their aversiveness. In conclusion, we find a diversity of response properties, distributed along a continuum, within what may be a single functional population of neurons signaling reward prediction error. PMID:23486943

The Use of Fast Neutron Detection for Materials Accountability

NASA Astrophysics Data System (ADS)

Nakae, L. F.; Chapline, G. F.; Glenn, A. M.; Kerr, P. L.; Kim, K. S.; Ouedraogo, S. A.; Prasad, M. K.; Sheets, S. A.; Snyderman, N. J.; Verbeke, J. M.; Wurtz, R. E.

2014-02-01

For many years at LLNL, we have been developing time-correlated neutron detection techniques and algorithms for applications such as Arms Control, Threat Detection and Nuclear Material Assay. Many of our techniques have been developed specifically for the relatively low efficiency (a few percent) inherent in man-portable systems. Historically, thermal neutron detectors (mainly 3He) were used, taking advantage of the high thermal neutron interaction cross-sections, but more recently we have been investigating the use of fast neutron detection with liquid scintillators, inorganic crystals, and in the near future, pulse-shape discriminating plastics that respond over 1000 times faster (nanoseconds versus tens of microseconds) than thermal neutron detectors. Fast neutron detection offers considerable advantages, since the inherent nanosecond production timescales of fission and neutron-induced fission are preserved and measured instead of being lost in the thermalization of thermal neutron detectors. We are now applying fast neutron technology to the safeguards regime in the form of high efficiency counters. Faster detector response times and sensitivity to neutron momentum show promise in measuring, differentiating, and assaying samples that have modest to very high count rates, as well as mixed neutron sources (e.g., Pu oxide or Mixed Cm and Pu). Here we report on measured results with our existing liquid scintillator array and promote the design of a nuclear material assay system that incorporates fast neutron detection, including the surprising result that fast liquid scintillator becomes competitive and even surpasses the precision of 3He counters measuring correlated pairs in modest (kg) samples of plutonium.

Novel MCP-Based Electron Source Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haughey, M.; Shiltsev V., Shiltsev V.; Stancari, G.

Microchannel plates (MCPs) were recently proposed as novel type of cathodes for electron guns [1], suitable for applications in design of electron lenses. We report results of the first systematic study of microchannel plate based photomultiplier time response and maximum cur-rent density tests using different sources of light pulses. The Burle 85011-501 MCP-PMT is found to have good time response properties being capable of producing na-nosecond long pulses with modest maximum current density and performance strongly dependent on magnetic field strength.

Kinome rewiring reveals AURKA is a molecular barrier to the efficacy of PI3K/mTOR-pathway inhibitors in breast cancer | Office of Cancer Genomics

Cancer.gov

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest. We hypothesized that dynamic changes in signaling, including adaptation and feedback, limit drug efficacy. Using a quantitative chemoproteomics approach we mapped dynamic changes in the kinome in response to various agents and identified signaling changes that correlate with drug sensitivity.

Single-Event Upsets Caused by High-Energy Protons

NASA Technical Reports Server (NTRS)

Price, W. E.; Nichols, D. K.; Smith, L. S.; Soli, G. A.

1986-01-01

Heavy secondary ions do not significantly alter device responses. Conclusion that external reaction products cause no significant alteration of single-event-upset response based on comparison of data obtained from both lidded and unlidded devices and for proton beams impinging at angles ranging from 0 degrees to 180 degrees with respect to chip face. Study also found single-event-upset cross section increases only modestly as proton energy increased to 590 MeV, characteristic of maximum energies expected in belts of trapped protons surrounding Earth and Jupiter.

Early Preterm Birth Across Generations Among Whites and African-Americans: A Population-Based Study.

PubMed

Dorner, Rebecca A; Rankin, Kristin M; Collins, James W

2017-11-01

Objectives To determine the extent to which non-Latina White and African-American mother's gestational age is associated with extremely early (<30 weeks), modestly early (30-33 weeks), and late (34-36 weeks) infant preterm birth (PTB) rates. Methods Race-specific stratified and multivariable logistic regression analyses were performed on the Illinois Transgenerational Birth File of non-Latino White and African-American infants (born 1989-1991) and their mothers (born 1956-1976). Results White mothers (n = 184) born at <30 weeks had a greater extremely early infant PTB rate than White mothers (n = 131,980) born at term: 1.6 versus 0.5%, respectively; RR = 3.6 (1.2, 11.0). African-American mothers (n = 269) born at <30 weeks had a greater extremely early infant PTB rate than African-American mothers (n = 34,885) born at term: 4.1 versus 2.1%, respectively; RR = 2.0 (1.1, 3.6). In logistic regression models the adjusted (controlling for maternal age, education, parity, prenatal care, marital status, and cigarette smoking) OR of extremely early PTB for White and African-American mothers born <30 (compared to ≥37) weeks equaled 4.0 (1.2, 12.6) and 2.3 (1.2, 4.3), respectively. The adjusted OR of modestly early PTB for White and African-American mothers born 30-33 (compared to ≥37) weeks equaled 1.6 (1.0, 2.5) and 1.3 (0.9, 1.7), respectively. The adjusted OR of late PTB for White and African-American mothers born 34-36 (compared to ≥37) weeks equaled 1.2 (1.0, 1.3) and 1.1 (1.0, 1.2), respectively. Conclusions A generational association of extremely early, but not modestly early or late, PTB exists among non-Latino Whites and African-Americans.

Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents.

PubMed

Papakostas, George I; Thase, Michael E; Fava, Maurizio; Nelson, J Craig; Shelton, Richard C

2007-12-01

Recent studies suggest that the treatment of major depressive disorder (MDD) with newer antidepressant drugs that simultaneously enhance norepinephrine and serotonin neurotransmission might result in higher response and remission rates than the selective serotonin reuptake inhibitors (SSRIs). The goal of our work was to compare response rates among patients with MDD treated with either of these two broad categories of antidepressant drugs. Medline/Pubmed, EMBase, clinical trial registries, program syllabi from major psychiatric meetings held since 1995, and documents from relevant pharmaceutical companies were searched for double-blind, randomized trials comparing a newer serotonergic-noradrenergic antidepressant drug (venlafaxine, duloxetine, milnacipran, mirtazapine, mianserin, or moclobemide) with an SSRI for MDD. Ninety-three trials (n = 17,036) were combined using a random-effects model. Treatment with serotonergic + noradrenergic antidepressant drugs was more likely to result in clinical response than the SSRIs (risk ratio [RR] = 1.059; response rates 63.6% versus 59.3%; p = .003). There was no evidence for heterogeneity among studies combined (p = 1.0). Excluding each individual agent did not significantly alter the pooled RR. With the exception of duloxetine (.985), RRs for response for each individual serotonergic + noradrenergic antidepressant drug were within the 95% confidence interval of the pooled RR (1.019-1.101). Serotonergic-noradrenergic antidepressant drugs seem to have a modest efficacy advantage compared with SSRIs in MDD. With the Number Needed to Treat (NNT) statistic as one indicator of clinical significance, nearly 24 patients would need to be treated with dual-action antidepressant drugs instead of SSRIs in order to obtain one additional responder. This difference falls well below the mark of NNT = 10 suggested by the United Kingdom's National Institute of Clinical Excellence but nonetheless might be of public health relevance given the large number of depressed patients treated with SSRI /serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant drugs. Further research is needed to examine whether larger differences between classes of antidepressant drugs might exist in specific MDD sub-populations or for specific MDD symptoms.

Falls among union carpenters.

PubMed

Lipscomb, Hester J; Li, Leiming; Dement, John M

2003-08-01

Falls are a leading cause of morbidity and mortality in the construction trades. We identified a cohort of 16,215 active union carpenters, hours worked, and their workers' compensation claims for a 10-year period. The data on this well-defined cohort were used to describe their work-related falls; to define rates of injury and the associated costs; and to identify high-risk groups. Same level falls occurred at a rate of 1.8/200,000 hours worked; falls from elevations at a rate of 2.3/200,000 hours worked. These injuries resulted in direct payments of 0.30 dollars per hour of work or 2.40 dollars per 8-hr day. Mean costs per fall increased with increasing age. Age was not associated with risk of falls from elevations; younger carpenters had modestly reduced rates of falls from the same level. Rates of falls decreased with increasing time in the union. Carpenters whose usual work involved drywall installation or residential work were at highest risk. Falls are a significant public health risk for carpenters and they are responsible for a significant burden of work-related injury costs. While there is a need for prevention of falls from elevations--through training, enforcement of fall protection regulations, improved safety climate, or engineering changes--there is also the need to prevent falls from lower elevations. Differences in risk likely reflect varying exposures and safety practices in different areas of carpentry, as well as training, experience, and job assignments based on longevity in the union. Copyright 2003 Wiley-Liss, Inc.

A massive early atmosphere on Triton

NASA Technical Reports Server (NTRS)

Lunine, Jonathan I.; Nolan, Michael C.

1992-01-01

The idea of an early greenhouse atmosphere for Triton is presented and the conditions under which it may have been sustained are quantified. The volatile content of primordial Triton is modeled, and tidal heating rates are assessed to set bounds on the available energy. The atmospheric model formalism is presented, and it is shown how a massive atmosphere could have been raised by modest tidal heating fluxes. The implications of the model atmospheres for the atmospheric escape rates, the chemical evolution, and the cratering record are addressed.

How might immunization rates change if cost sharing is eliminated?

PubMed

Shen, Angela K; O'Grady, Michael J; McDevitt, Roland D; Pickreign, Jeremy D; Laudenberger, Laura K; Esber, Allahna; Shortridge, Emily F

2014-01-01

There is a debate regarding the effect of cost sharing on immunization, particularly as the Affordable Care Act will eliminate cost sharing for recommended vaccines. This study estimates changes in immunization rates and spending associated with extending first-dollar coverage to privately insured children for four childhood vaccines. We used the 2008 National Immunization Survey and peer-reviewed literature to generate estimates of immunization status for each vaccine by age group and insurance type. We used the Truven Health Analytics 2006 MarketScan Commercial Claims and Encounters Database of line-item medical claims to estimate changes in immunization rates that would result from eliminating cost sharing, and we used the Kaiser Family Foundation/Health Research and Educational Trust Employer Health Benefits Survey to determine the prevalence of coverage for patients with first-dollar coverage, patients who face office visit cost sharing, and patients who face cost sharing for all vaccine cost components. We assumed that once cost sharing is removed, coverage rates in plans that impose cost sharing will rise to the level of plans that do not. We estimate that immunization rates would increase modestly and result in additional direct spending of $26.0 million to insurers/employers. Further, these payers would have an additional $11.0 million in spending associated with eliminating cost sharing for children already receiving immunizations. The effects of eliminating cost sharing for vaccines vary by vaccine. Overall, immunization rates will rise modestly given high insurance coverage for vaccinations, and these increases would be more substantial for those currently facing cost sharing. However, in addition to the removal of cost sharing for immunizations, these findings suggest other strategies to consider to further increase immunization rates.

Propensity to Work Among Chronically Unemployed Adult Drug Users

PubMed Central

Sigurdsson, Sigurdur Oli; DeFulio, Anthony; Long, Lauren; Silverman, Kenneth

2014-01-01

Analyses were conducted to compare rates of employment before, during, and after employment at the therapeutic workplace, which is a novel employment-based treatment for drug misuse. Participants in two clinical trials attended the therapeutic workplace at higher rates than they worked before intake and six months after discharge. These data suggest that unemployed chronic drug misusers will attend work at higher rates at the therapeutic workplace than in the community when paid modest wages, and that the failure of chronic drug misusers to obtain employment in the community may not result from lack of interest in work. PMID:20964531

Hypothyroidism and obesity: An intriguing link.

PubMed

Sanyal, Debmalya; Raychaudhuri, Moutusi

2016-01-01

According to common perception, hypothyroidism is held responsible for obesity. However, linking them causally is controversial. Overt hypothyroidism is associated with modest weight gain, but there is a lack of clarity regarding subclinical hypothyroidism. Novel view indicates that changes in thyroid-stimulating hormone (TSH) could well be secondary to obesity. The increasing prevalence of obesity further confounds definition of normal TSH range in population studies. Thyroid autoantibody status may help in establishing the diagnosis of subclinical hypothyroidism in obesity. High leptin levels may play a role in the hyperthyrotropinemia of obesity and also increase susceptibility to thyroid autoimmunity and subsequent hypothyroidism. There is at most a modest effect of L-T4 treatment in overt hypothyroidism in inducing weight loss; benefit in subclinical hypothyroidism is not established with no data supporting thyroid hormone use in euthyroid obese patients.

The Efficacy of Equine-Assisted Activities and Therapies on Improving Physical Function.

PubMed

Rigby, B Rhett; Grandjean, Peter W

2016-01-01

To summarize the physical benefits of therapeutic horseback riding and hippotherapy and suggest directions for future research. Review of databases for peer-reviewed articles related to equine-assisted activities and therapies. Databases included MEDLINE via EBSCO, Web of Science, PubMed, Google Scholar, and Academic Search Complete. Articles were limited to those with full-text access published in English since 1987. Acute and residual improvements in physical benefits, such as gross motor function (e.g., walking, running, jumping), spasticity, muscle symmetry, posture, balance, and gait occur in adults and children with varying disabilities. The benefits appear to be greatest following multiweek interventions with one or more sessions per week. Modest acute cardiovascular responses are observed during equine-assisted activities and therapies with little or no evidence for training improvements in heart rate or blood pressure at rest or during riding. The present body of literature provides evidence that equine-assisted activities and therapies are an effective means of improving many measures of physical health. However, more controlled trials are urgently needed to strengthen the current knowledge base, establish dose-response characteristics of equine-assisted activities and therapies, and explore the physiologic basis for the promising results suggested from the literature.

Management strategies in pancreatic cancer.

PubMed

Campen, Christopher J; Dragovich, Tomislav; Baker, Amanda F

2011-04-01

Current first-line and adjuvant chemotherapeutic strategies for management of patients with pancreatic cancer are reviewed. Pancreatic adenocarcinoma is the 10th most prevalent cancer and the fourth most common cause of cancer deaths in the United States. More than 80% of patients with pancreatic cancer are diagnosed with locally advanced or metastatic disease and are not candidates for surgery; these patients often require multimodal treatment. The most widely used chemotherapy for such patients, as well as patients requiring adjuvant therapy after surgery, is gemcitabine or gemcitabine-based chemotherapy. All current chemotherapies for pancreatic cancer are associated with dose-limiting hematologic toxicity and other adverse effects that require ongoing monitoring and dosage adjustment to balance the benefits and risks of treatment. Pharmacists can play an important role in monitoring and providing drug information and guidance to patients and oncologists. Current investigational strategies include efforts to improve chemotherapy response rates and outcomes through modulation of cell signaling pathways and use of nanotechnology to improve drug delivery. Current management of pancreatic cancer is multifaceted, involving anticancer therapy, supportive care, and toxicity management. Standard systemic therapy with gemcitabine as a single agent or in combination with other cytotoxic agents provides modest benefits in terms of response and symptom control.

Alterations in bioenergetic function induced by Parkinson's disease mimetic compounds: Lack of correlation with superoxide generation

PubMed Central

Dranka, Brian P.; Zielonka, Jacek; Kanthasamy, Anumantha G.; Kalyanaraman, Balaraman

2012-01-01

In vitro and in vivo models of Parkinson's disease (PD) suggest that increased oxidant production leads to mitochondrial dysfunction in dopaminergic neurons and subsequent cell death. However, it remains unclear if cell death in these models is caused by inhibition of mitochondrial function or oxidant production. The objective of the present study was to determine the relationship between mitochondrial dysfunction and oxidant production in response to multiple PD neurotoxicant mimetics. MPP+ caused a dose-dependent decrease in the basal oxygen consumption rate (OCR) in dopaminergic N27 cells, indicating a loss of mitochondrial function. In parallel, we found that MPP+ only modestly increased oxidation of hydroethidine as a diagnostic marker of superoxide production in these cells. Similar results were found using rotenone as a mitochondrial inhibitor, or 6-hydroxydopamine as a mechanistically distinct PD neurotoxicant, but not with exposure to paraquat. Additionally, the Extracellular Acidification Rate, used as a marker of glycolysis, was stimulated to compensate for OCR inhibition after exposure to MPP+, rotenone, or 6-hydroxydopamine, but not paraquat. Together these data indicate that MPP+, rotenone and 6-hydroxydopamine dramatically shift bioenergetic function away from the mitochondria and towards glycolysis in N27 cells. PMID:22708893

24 CFR 891.670 - Cost containment and modest design standards.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Cost containment and modest design... Handicapped Families and Individuals-Section 162 Assistance § 891.670 Cost containment and modest design standards. (a) Restrictions on amenities. Projects must be modest in design. Except as provided in paragraph...

24 CFR 891.670 - Cost containment and modest design standards.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Cost containment and modest design... Handicapped Families and Individuals-Section 162 Assistance § 891.670 Cost containment and modest design standards. (a) Restrictions on amenities. Projects must be modest in design. Except as provided in paragraph...

24 CFR 891.670 - Cost containment and modest design standards.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Cost containment and modest design... Handicapped Families and Individuals-Section 162 Assistance § 891.670 Cost containment and modest design standards. (a) Restrictions on amenities. Projects must be modest in design. Except as provided in paragraph...

24 CFR 891.670 - Cost containment and modest design standards.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Cost containment and modest design... Handicapped Families and Individuals-Section 162 Assistance § 891.670 Cost containment and modest design standards. (a) Restrictions on amenities. Projects must be modest in design. Except as provided in paragraph...

24 CFR 891.670 - Cost containment and modest design standards.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Cost containment and modest design... Handicapped Families and Individuals-Section 162 Assistance § 891.670 Cost containment and modest design standards. (a) Restrictions on amenities. Projects must be modest in design. Except as provided in paragraph...

Capture of sandhill cranes using alpha-chloralose: a 10-year follow-up.

PubMed

Hartup, Barry K; Schneider, Lauren; Engels, J Michael; Hayes, Matthew A; Barzen, Jeb A

2014-01-01

Seasonal adjustment of alpha-chloralose captures of sandhill cranes was associated with a modest increase in capture efficacy (+13%), decreased morbidity from exertional myopathy (-1.4%), and overall mortality (-1.7%) rates despite little change in sedation scores. Postcapture fluid administration also decreased confinement times by several hours over most sedation scores.

Workforce: North Dakota

ERIC Educational Resources Information Center

Western Interstate Commission for Higher Education, 2006

2006-01-01

Between 2002 and 2012, the rate of job growth in North Dakota will be modest: under 1 percent annually. However, a large number of positions-close to a quarter of all jobs in the state-will open up for hiring due to retirements and separations. In addition, the demand for well-educated employees will only increase over the next several years. In…

An Investigation of the Raudenbush (1988) Test for Studying Variance Heterogeneity.

ERIC Educational Resources Information Center

Harwell, Michael

1997-01-01

The meta-analytic method proposed by S. W. Raudenbush (1988) for studying variance heterogeneity was studied. Results of a Monte Carlo study indicate that the Type I error rate of the test is sensitive to even modestly platykurtic score distributions and to the ratio of study sample size to the number of studies. (SLD)

Three-dimension imaging lidar

NASA Technical Reports Server (NTRS)

Degnan, John J. (Inventor)

2007-01-01

This invention is directed to a 3-dimensional imaging lidar, which utilizes modest power kHz rate lasers, array detectors, photon-counting multi-channel timing receivers, and dual wedge optical scanners with transmitter point-ahead correction to provide contiguous high spatial resolution mapping of surface features including ground, water, man-made objects, vegetation and submerged surfaces from an aircraft or a spacecraft.

"But I Thought I Knew That!" Student Confidence Judgments on Course Examinations in Introductory Psychology

ERIC Educational Resources Information Center

Nevid, Jeffrey S.; Cheney, Brianna; Thompson, Clarissa

2015-01-01

Students in an introductory psychology class rated their level of confidence in their answers to exam questions on four multiple-choice exams through the course of a semester. Correlations between confidence judgments and accuracy (correct vs. incorrect) at the individual item level showed modest but significant relationships for item sets scaled…

Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS.

PubMed

Gower, Barbara A; Chandler-Laney, Paula C; Ovalle, Fernando; Goree, Laura Lee; Azziz, Ricardo; Desmond, Renee A; Granger, Wesley M; Goss, Amy M; Bates, G Wright

2013-10-01

Diet-induced reduction in circulating insulin may be an attractive nonpharmacological treatment for women with polycystic ovary syndrome (PCOS) among whom elevated insulin may exacerbate symptoms by stimulating testosterone synthesis. This study was designed to determine whether a modest reduction in dietary carbohydrate (CHO) content affects β-cell responsiveness, serum testosterone concentration and insulin sensitivity in women with PCOS. In a crossover design, two diets ('Standard,' STD, 55:18:27% energy from carbohydrate/protein/fat; lower-carbohydrate, 41:19:40) were provided for 8 weeks in random order with a 4-week washout between. Thirty women with PCOS. β-cell responsiveness assessed as the C-peptide response to glucose during a liquid meal test; insulin sensitivity from insulin and glucose values throughout the test; insulin resistance (HOMA-IR); and total testosterone by immunoassay. Paired t-test indicated that the lower-CHO diet induced significant decreases in basal β-cell response (PhiB), fasting insulin, fasting glucose, HOMA-IR, total testosterone and all cholesterol measures, and significant increases in insulin sensitivity and dynamic ('first-phase') β-cell response. The STD diet induced a decrease in HDL-C and an increase in the total cholesterol-to-HDL-C ratio. Across all data combined, the change in testosterone was positively associated with the changes in fasting insulin, PhiB and insulin AUC (P < 0·05). In women with PCOS, modest reduction in dietary CHO in the context of a weight-maintaining diet has numerous beneficial effects on the metabolic profile that may lead to a decrease in circulating testosterone. © 2013 John Wiley & Sons Ltd.

Climate response of the South Asian monsoon system to anthropogenic aerosols

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganguly, Dilip; Rasch, Philip J.; Wang, Hailong

2012-07-13

The equilibrium climate response to the total effects (direct, indirect and semi-direct effects) of aerosols arising from anthropogenic and biomass burning emissions on the South Asian summer monsoon system is studied using a coupled atmosphere-slab ocean model. Our results suggest that anthropogenic and biomass burning aerosols generally induce a reduction in mean summer monsoon precipitation over most parts of the Indian subcontinent, strongest along the western coastline of the Indian peninsula and eastern Nepal region, but modest increases also occur over the north western part of the subcontinent. While most of the noted reduction in precipitation is triggered by increasedmore » emissions of aerosols from anthropogenic activities, modest increases in the north west are mostly associated with decreases in local emissions of aerosols from forest fire and grass fire sources. Anthropogenic aerosols from outside Asia also contribute to the overall reduction in precipitation but the dominant contribution comes from aerosol sources within Asia. Local emissions play a more important role in the total rainfall response to anthropogenic aerosol sources during the early monsoon period, whereas both local as well as remote emissions of aerosols play almost equally important roles during the later part of the monsoon period. While precipitation responses are primarily driven by local aerosol forcing, regional surface temperature changes over the region are strongly influenced by anthropogenic aerosols from sources further away (non-local changes). Changes in local anthropogenic organic and black carbon emissions by as much as a factor of two (preserving their ratio) produce the same basic signatures in the model's summer monsoon temperature and precipitation responses.« less

Chronic heart failure does not attenuate the total activity of sympathetic outflow to skin during whole-body heating.

PubMed

Cui, Jian; Boehmer, John P; Blaha, Cheryl; Lucking, Robert; Kunselman, Allen R; Sinoway, Lawrence I

2013-03-01

Previous studies show that the rise in skin blood flow and cutaneous vascular conductance during heat stress is substantially attenuated in chronic heart failure (CHF) patients. The mechanisms responsible for this finding are not clear. In particular, little is known regarding the responses of skin sympathetic nerve activity (SSNA) that control the skin blood flow during heat stress in CHF patients. We examined the effects of a modest heat stress to test the hypothesis that SSNA responses could be attenuated in CHF. We assessed SSNA (microneurography) from the peroneal nerve and skin blood flow (forearm laser Doppler) in 9 patients with stable class II-III CHF and in matched healthy subjects during passive whole-body heating with a water-perfused suit. Whole-body heating induced similar increases in internal temperature (≈0.6 °C) in both groups. Whole-body heat stress evoked similar SSNA activation in CHF patients (Δ891±110 U/min) and the control subjects (Δ787±84 U/min; P=0.66), whereas the elevation in forearm cutaneous vascular conductance in patients with CHF was significantly lower than that in healthy control subjects (Δ131±29% vs. Δ623±131%; P=0.001). The present data show that SSNA activation during a modest whole-body heat stress is not attenuated in CHF. Thus, the attenuated skin vasodilator response in CHF patients is not attributable to a reduction in total activity of sympathetic outflow to skin.

Genome-Wide Association Study of d-Amphetamine Response in Healthy Volunteers Identifies Putative Associations, Including Cadherin 13 (CDH13)

PubMed Central

Wardle, Margaret C.; Sokoloff, Greta; Stephens, Matthew; de Wit, Harriet; Palmer, Abraham A.

2012-01-01

Both the subjective response to d-amphetamine and the risk for amphetamine addiction are known to be heritable traits. Because subjective responses to drugs may predict drug addiction, identifying alleles that influence acute response may also provide insight into the genetic risk factors for drug abuse. We performed a Genome Wide Association Study (GWAS) for the subjective responses to amphetamine in 381 non-drug abusing healthy volunteers. Responses to amphetamine were measured using a double-blind, placebo-controlled, within-subjects design. We used sparse factor analysis to reduce the dimensionality of the data to ten factors. We identified several putative associations; the strongest was between a positive subjective drug-response factor and a SNP (rs3784943) in the 8th intron of cadherin 13 (CDH13; P = 4.58×10−8), a gene previously associated with a number of psychiatric traits including methamphetamine dependence. Additionally, we observed a putative association between a factor representing the degree of positive affect at baseline and a SNP (rs472402) in the 1st intron of steroid-5-alpha-reductase-α-polypeptide-1 (SRD5A1; P = 2.53×10−7), a gene whose protein product catalyzes the rate-limiting step in synthesis of the neurosteroid allopregnanolone. This SNP belongs to an LD-block that has been previously associated with the expression of SRD5A1 and differences in SRD5A1 enzymatic activity. The purpose of this study was to begin to explore the genetic basis of subjective responses to stimulant drugs using a GWAS approach in a modestly sized sample. Our approach provides a case study for analysis of high-dimensional intermediate pharmacogenomic phenotypes, which may be more tractable than clinical diagnoses. PMID:22952603

Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13).

PubMed

Hart, Amy B; Engelhardt, Barbara E; Wardle, Margaret C; Sokoloff, Greta; Stephens, Matthew; de Wit, Harriet; Palmer, Abraham A

2012-01-01

Both the subjective response to d-amphetamine and the risk for amphetamine addiction are known to be heritable traits. Because subjective responses to drugs may predict drug addiction, identifying alleles that influence acute response may also provide insight into the genetic risk factors for drug abuse. We performed a Genome Wide Association Study (GWAS) for the subjective responses to amphetamine in 381 non-drug abusing healthy volunteers. Responses to amphetamine were measured using a double-blind, placebo-controlled, within-subjects design. We used sparse factor analysis to reduce the dimensionality of the data to ten factors. We identified several putative associations; the strongest was between a positive subjective drug-response factor and a SNP (rs3784943) in the 8(th) intron of cadherin 13 (CDH13; P = 4.58×10(-8)), a gene previously associated with a number of psychiatric traits including methamphetamine dependence. Additionally, we observed a putative association between a factor representing the degree of positive affect at baseline and a SNP (rs472402) in the 1(st) intron of steroid-5-alpha-reductase-α-polypeptide-1 (SRD5A1; P = 2.53×10(-7)), a gene whose protein product catalyzes the rate-limiting step in synthesis of the neurosteroid allopregnanolone. This SNP belongs to an LD-block that has been previously associated with the expression of SRD5A1 and differences in SRD5A1 enzymatic activity. The purpose of this study was to begin to explore the genetic basis of subjective responses to stimulant drugs using a GWAS approach in a modestly sized sample. Our approach provides a case study for analysis of high-dimensional intermediate pharmacogenomic phenotypes, which may be more tractable than clinical diagnoses.

Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens

PubMed Central

Asbach, Benedikt; Kliche, Alexander; Köstler, Josef; Perdiguero, Beatriz; Esteban, Mariano; Jacobs, Bertram L.; Montefiori, David C.; LaBranche, Celia C.; Yates, Nicole L.; Tomaras, Georgia D.; Ferrari, Guido; Foulds, Kathryn E.; Roederer, Mario; Landucci, Gary; Forthal, Donald N.; Seaman, Michael S.; Hawkins, Natalie; Self, Steven G.; Sato, Alicia; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, James; Barnett, Susan W.; Burke, Brian; Cristillo, Anthony D.; Weiss, Deborah E.; Francis, Jesse; Galmin, Lindsey; Ding, Song; Heeney, Jonathan L.; Pantaleo, Giuseppe

2016-01-01

ABSTRACT In a follow-up to the modest efficacy observed in the RV144 trial, researchers in the HIV vaccine field seek to substantiate and extend the results by evaluating other poxvirus vectors and combinations with DNA and protein vaccines. Earlier clinical trials (EuroVacc trials 01 to 03) evaluated the immunogenicity of HIV-1 clade C GagPolNef and gp120 antigens delivered via the poxviral vector NYVAC. These showed that a vaccination regimen including DNA-C priming prior to a NYVAC-C boost considerably enhanced vaccine-elicited immune responses compared to those with NYVAC-C alone. Moreover, responses were improved by using three as opposed to two DNA-C primes. In the present study, we assessed in nonhuman primates whether such vaccination regimens can be streamlined further by using fewer and accelerated immunizations and employing a novel generation of improved DNA-C and NYVAC-C vaccine candidates designed for higher expression levels and more balanced immune responses. Three different DNA-C prime/NYVAC-C+ protein boost vaccination regimens were tested in rhesus macaques. All regimens elicited vigorous and well-balanced CD8+ and CD4+ T cell responses that were broad and polyfunctional. Very high IgG binding titers, substantial antibody-dependent cellular cytotoxicity (ADCC), and modest antibody-dependent cell-mediated virus inhibition (ADCVI), but very low neutralization activity, were measured after the final immunizations. Overall, immune responses elicited in all three groups were very similar and of greater magnitude, breadth, and quality than those of earlier EuroVacc vaccines. In conclusion, these findings indicate that vaccination schemes can be simplified by using improved antigens and regimens. This may offer a more practical and affordable means to elicit potentially protective immune responses upon vaccination, especially in resource-constrained settings. IMPORTANCE Within the EuroVacc clinical trials, we previously assessed the immunogenicity of HIV clade C antigens delivered in a DNA prime/NYVAC boost regimen. The trials showed that the DNA prime crucially improved the responses, and three DNA primes with a NYVAC boost appeared to be optimal. Nevertheless, T cell responses were primarily directed toward Env, and humoral responses were modest. The aim of this study was to assess improved antigens for the capacity to elicit more potent and balanced responses in rhesus macaques, even with various simpler immunization regimens. Our results showed that the novel antigens in fact elicited larger numbers of T cells with a polyfunctional profile and a good Env-GagPolNef balance, as well as high-titer and Fc-functional antibody responses. Finally, comparison of the different schedules indicates that a simpler regimen of only two DNA primes and one NYVAC boost in combination with protein may be very efficient, thus showing that the novel antigens allow for easier immunization protocols. PMID:26865719

Performance of three glomerular filtration rate estimation equations in a population of sub-Saharan Africans with Type 2 diabetes.

PubMed

Agoons, D D; Balti, E V; Kaze, F F; Azabji-Kenfack, M; Ashuntantang, G; Kengne, A P; Sobngwi, E; Mbanya, J C

2016-09-01

We evaluated the performance of the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault (CG) equations against creatinine clearance (CrCl) to estimate glomerular filtration rate (GFR) in 51 patients with Type 2 diabetes. The CrCl value was obtained from the average of two consecutive 24-h urine samples. Results were adjusted for body surface area using the Dubois formula. Serum creatinine was measured using the kinetic Jaffe method and was calibrated to standardized levels. Bland-Altman analysis and kappa statistic were used to examine agreement between measured and estimated GFR. Estimates of GFR from the CrCl, MDRD, CKD-EPI and CG equations were similar (overall P = 0.298), and MDRD (r = 0.58; 95% CI: 0.36-0.74), CKD-EPI (r = 0.55; 95% CI: 0.33-0.72) and CG (r = 0.61; 95% CI: 0.39-0.75) showed modest correlation with CrCl (all P < 0.001). Bias was -0.3 for MDRD, 1.7 for CKD-EPI and -5.4 for CG. All three equations showed fair-to-moderate agreement with CrCl (kappa: 0.38-0.51). The c-statistic for all three equations ranged between 0.75 and 0.77 with no significant difference (P = 0.639 for c-statistic comparison). The MDRD equation seems to have a modest advantage over CKD-EPI and CG in estimating GFR and detecting impaired renal function in sub-Saharan African patients with Type 2 diabetes. The overall relatively modest correlation with CrCl, however, suggests the need for context-specific estimators of GFR or context adaptation of existing estimators. © 2015 Diabetes UK.

Trends and Issues in California's Low Carbon Fuel Standard - Learning from Response to Existing Climate Policy

NASA Astrophysics Data System (ADS)

Witcover, J.

2015-12-01

Debate over lower greenhouse gas (GHG) emissions from transportation has included heated discussion about appropriate policies and their cost and feasibility. One prominent policy mechanism, a carbon intensity standard, rates transport fuels based on analysis of lifecycle GHG emissions, and targets lower fuel pool carbon intensity through a market mechanism that uses a system of tradable, bankable credits and deficits. California instituted such a policy -- the Low Carbon Fuel Standard (LCFS) - in 2010, which targets a 10% carbon intensity (CI) reduction by 2020. The program rolled out amid concerns over slow development of new fuels expected to be very low carbon (such as cellulosic) and has faced court challenges that added considerable policy uncertainty. Since the program's start, state transport energy mix has shifted modestly but noticeably. Looking ahead, emerging issues for the program include amendments and re-adoption in response to a court ruling, potential interaction with California's multi-sector cap on carbon emissions (which started covering transport fuels in 2015), and impacts from similar CI standards in other jurisdictions. This study provides an analysis of fuel mix changes since the LCFS was implemented in 2011, and a discussion of emerging issues focusing on policy interaction. Descriptive statistics on alternative fuel use, available fuel pathways, and CI ratings are presented based on data from the California Air Resources Board (which runs the program). They document a shift towards more alternative fuels in a more diverse mix, with lower average CI ratings for most alternative fuel types. Financial incentives for various fuels are compared under the LCFS and the US federal Renewable Fuel Standard; disincentives from conceptually different carbon pricing schemes under the LCFS and the Cap-and-Trade are also outlined. The results provide important information on response to an existing market-based policy mechanism for addressing GHG emissions in transportation, as other jurisdictions weigh similar climate policies and debate mechanisms and costs and California announced an ambitious target of halving petroleum use by 2030.

African-American women's Upward Economic Mobility and Small for Gestational Age Births: A Population-Based Study.

PubMed

Collins, James W; Mariani, Allison; Rankin, Kristin

2018-03-01

Background The relationship between African-American women's upward economic mobility and small for gestational age (weight for gestational < 10th percentile, SGA) rates is incompletely understood. Objective To ascertain the extent to which African-American women's upward economic mobility from early-life impoverishment is coupled with reduced SGA rates. Methods Stratified and multilevel logistic regression analyses were completed on the Illinois transgenerational dataset of African-American infants (1989-1991) and their Chicago-born mothers (1956-1976) with linked U.S. census income information. Results Impoverished-born (defined as lowest quartile of neighborhood income distribution) African-American women (n = 4891) who remained impoverished by the time of delivery had a SGA rate of 19.7%. Individuals who achieved low (n = 5827), modest (n = 2254), or high (n = 732) upward economic mobility by adulthood had lower SGA rates of 17.2, 14.8, and 13.7%, respectively; RR = 0.9 (0.8-0.9), 0.8 (0.7-0.8), and 0.7 (0.6-0.8), respectively. In adjusted (controlling for traditional individual-level risk factors) multilevel regression models, there was a decreasing linear trend in SGA rates with increasing levels of upward economic mobility; the adjusted RR of SGA birth for impoverished-born African-American women who experienced low, modest, of high (compared to no) upward mobility equaled 0.95 (0.91, 0.99), 0.90 (0.83, 0.98), and 0.86 (0.75, 0.98), respectively, p < 0.05. Conclusions African-American women's upward economic mobility from early-life residence in poor urban communities is associated with lower SGA rates independent of adulthood risk status.

Epigenetic modifiers in immunotherapy: a focus on checkpoint inhibitors.

PubMed

Terranova-Barberio, Manuela; Thomas, Scott; Munster, Pamela N

2016-06-01

Immune surveillance should be directed to suppress tumor development and progression, involving a balance of coinhibitory and costimulatory signals that amplify immune response without overwhelming the host. Immunotherapy confers durable clinical benefit in 'immunogenic tumors', whereas in other tumors the responses are modest. Thus, immune checkpoint inhibitors may need to be combined with strategies to boost immune response or increase the tumor immune profile. Epigenetic aberrations contribute significantly to carcinogenesis. Recent findings suggest that epigenetic drugs prime the immune response by increasing expression of tumor-associated antigens and immune-related genes, as well as modulating chemokines and cytokines involved in immune system activation. This review describes our current understanding regarding epigenetic and immunotherapy combination, focusing on immune response priming to checkpoint blockade.

Re-evaluating the 1940s CO2 plateau

NASA Astrophysics Data System (ADS)

Bastos, A.; Ciais, P.; Barichivitch, J.; Brovkin, V.; Gasser, T.; Pongratz, J.; Trudinger, C. M.

2016-12-01

The ice-core record reveals a stabilisation of atmospheric CO2 in the 1940s (the so called "plateau"), in spite of continued emissions from fossil fuel burning (FF) and land-use change (LUC). This stabilisation has been previously attributed to very strong oceanic CO2 uptake, perhaps in response to the El-Niño event in 1940. However, this explanation is questionable, since recent atmospheric CO2 data indicate that El Niño events generally lead to higher atmospheric CO2 growth-rates because of the terrestrial response, and oceanic CO2 measurements indicate the range of variability in the ocean sink has been rather modest in recent decades. We use up-to-date reconstructions of the CO2 sources (FF and LUC), ocean uptake from two different reconstructions and the terrestrial sink (from TRENDY models) over the 20th century to evaluate whether these allow capturing the CO2 plateau and provide further insight about its drivers. While these datasets provide a plausible explanation for most of the 20th century carbon budget, especially since 1970, they overestimate atmospheric CO2 growth rate during the plateau period by 0.9-2.0PgC.yr-1. We test the possible explanations for this mismatch, namely i) the role of natural variability in the ocean sink; ii) the representation of the terrestrial sink response to the climate anomalies during the 1940s by land-surface models; iii) the contribution of land-use processes possibly not represented in the current datasets. We conclude that a strong terrestrial sink concurrent with enhanced oceanic uptake is required to explain the CO2 stabilisation. Tests performed using the OSCAR carbon-cycle model suggest that changes in land-use coinciding with drastic socioeconomic changes during WW2 could plausibly contribute to the additional sink required.

Specific dynamic action: a review of the postprandial metabolic response.

PubMed

Secor, Stephen M

2009-01-01

For more than 200 years, the metabolic response that accompanies meal digestion has been characterized, theorized, and experimentally studied. Historically labeled "specific dynamic action" or "SDA", this physiological phenomenon represents the energy expended on all activities of the body incidental to the ingestion, digestion, absorption, and assimilation of a meal. Specific dynamic action or a component of postprandial metabolism has been quantified for more than 250 invertebrate and vertebrate species. Characteristic among all of these species is a rapid postprandial increase in metabolic rate that upon peaking returns more slowly to prefeeding levels. The average maximum increase in metabolic rate stemming from digestion ranges from a modest 25% for humans to 136% for fishes, and to an impressive 687% for snakes. The type, size, composition, and temperature of the meal, as well as body size, body composition, and several environmental factors (e.g., ambient temperature and gas concentration) can each significantly impact the magnitude and duration of the SDA response. Meals that are large, intact or possess a tough exoskeleton require more digestive effort and thus generate a larger SDA than small, fragmented, or soft-bodied meals. Differences in the individual effort of preabsorptive (e.g., swallowing, gastric breakdown, and intestinal transport) and postabsorptive (e.g., catabolism and synthesis) events underlie much of the variation in SDA. Specific dynamic action is an integral part of an organism's energy budget, exemplified by accounting for 19-43% of the daily energy expenditure of free-ranging snakes. There are innumerable opportunities for research in SDA including coverage of unexplored taxa, investigating the underlying sources, determinants, and the central control of postprandial metabolism, and examining the integration of SDA across other physiological systems.

Blood pressure response to CPAP treatment in subjects with obstructive sleep apnoea: the predictive value of 24-h ambulatory blood pressure monitoring.

PubMed

Castro-Grattoni, Anabel L; Torres, Gerard; Martínez-Alonso, Montserrat; Barbé, Ferran; Turino, Cecilia; Sánchez-de-la-Torre, Alicia; Cortijo, Anunciacion; Duran-Cantolla, Joaquin; Egea, Carlos; Cao, Gonzalo; Sánchez-de-la-Torre, Manuel

2017-10-01

The reduction in blood pressure (BP) with continuous positive airway pressure (CPAP) is modest and highly variable. In this study, we identified the variables that predict BP response to CPAP.24-h ambulatory BP monitoring (ABPM), C-reactive protein (CRP), leptin, adiponectin and 24-h urinary catecholamine were measured before and after 6 months of CPAP in obstructive sleep apnoea (OSA) patients.Overall, 88 middle-aged, obese male patients with severe OSA (median apnoea-hypopnoea index 42 events·h -1 ) were included; 28.4% had hypertension. 62 patients finished the study, and 60 were analysed. The daytime diastolic BP (-2 mmHg) and norepinephrine (-109.5 nmol·day -1 ) were reduced after CPAP, but no changes in the 24-h BP, night-time BP, dopamine, epinephrine, CRP, leptin or adiponectin were detected. The nocturnal normotension was associated with an increased night-time-BP (+4 mmHg) after CPAP, whereas nocturnal hypertension was associated with a reduction of 24-h BP (-3 mmHg). A multivariate linear regression model showed differential night-time BP changes after CPAP. Specifically, low night-time heart rate (<68 bpm) and BP dipper profile were associated with increased night-time BP and new diagnosis of nocturnal hypertension.Our results suggest that nocturnal hypertension, circadian BP pattern and night-time heart rate could be clinical predictors of BP response to CPAP and support the usefulness of 24-h ABPM for OSA patients before treatment initiation. These results need to be confirmed in further studies. Copyright ©ERS 2017.

Phase II study of sunitinib in recurrent or metastatic squamous cell carcinoma of the head and neck: GORTEC 2006-01.

PubMed

Machiels, Jean-Pascal H; Henry, Stéphanie; Zanetta, Sylvie; Kaminsky, Marie-Christine; Michoux, Nicolas; Rommel, Denis; Schmitz, Sandra; Bompas, Emmanuelle; Dillies, Anne-Françoise; Faivre, Sandrine; Moxhon, Anne; Duprez, Thierry; Guigay, Joel

2010-01-01

PURPOSE To assess the efficacy and toxicity of sunitinib monotherapy in palliative squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Thirty-eight patients with SCCHN having evidence of progressive disease (PD) were treated with sunitinib 37.5 mg/d given continuously until PD or unacceptable toxicity. The primary end point was the rate of disease control, defined as stable disease (SD) or partial response (PR) at 6 to 8 weeks after treatment initiation (two-stage design, Simon). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed in a subset of patients before and 6 to 8 weeks after treatment. The volume transfer constant of the contrast agent (K(trans)) was used to measure changes in the microcirculation blood flow and endothelial permeability of the tumor. Results A PR was observed in one patient, SD in 18, and PD in 19 (Response Evaluation Criteria in Solid Tumors [RECIST]), resulting in a disease control rate of 50%. Among the 18 patients with SD, there were five unconfirmed PRs and six additional minor responses. A significant decrease in K(trans) was seen in three of the four patients who received DCE-MRI monitoring. Grade 5 head and neck bleeds occurred in four patients. Local complications, including the appearance or worsening of tumor skin ulceration or tumor fistula, were recorded in 15 patients. CONCLUSION Sunitinib demonstrated modest activity in palliative SSCHN. The severity of some of the complications highlights the importance of improved patient selection for future studies with sunitinib in head and neck cancer. Sunitinib should not be used outside clinical trials in SSCHN.

Assessing the difference of tolerance and phytoremediation potential in mercury contaminated soil of a non-food energy crop, Helianthus tuberosus L. (Jerusalem artichoke).

PubMed

Lv, Shiqi; Yang, Bin; Kou, Yixuan; Zeng, Jun; Wang, Ruixiong; Xiao, Yumeng; Li, Fencan; Lu, Ying; Mu, Yuwen; Zhao, Changming

2018-01-01

This study was conducted to evaluate the effects of mercury stress on growth, photosynthesis and mercury accumulation in different cultivars of a non-food energy crop, Jerusalem artichoke, and to screen appropriate cultivars for their efficacy in the phytoremediation of mercury (Hg 2+ ) contaminated soil. Cultivars LZJ033 (high above-ground biomass and nutrient content, and strongly sexual reproduction) and LZJ119 (a long period of vegetative growth) exhibited more tolerance to mercury stress than LZJ047 (the highest tuber yield and total sugar content). The lines LZJ119 and LZJ047 showed delays in emergence time of about four weeks, and LZJ047 exhibited the highest mortality rate, 85.19%, under treatment with 10 mg kg -1 mercury. The MDA (malondialdehyde) content increased whereas and the P n (net photosynthetic rate), F v ∕ F m (the maximum quantum yield of PSII photochemistry) and chlorophyll content decreased in response to mercury stress. The stem diameter, stem biomass and photosynthetic rate of Jerusalem artichoke showed some modest increases in response to mercury stress and exhibited hormesis at least 1 mg kg -1 mercury treatment. Overall, LZJ119 produced more biomass under mercury stress, whereas LZJ033 exhibited a greater capacity for mercury bioaccumulation. Accordingly, LZJ119 may be a good candidate cultivar for use in cases of moderate-low mercury contamination, whereas LZJ033 may be a better candidate under conditions of high mercury contamination. When Jerusalem artichoke was cultivated in mercury contaminated soil, it not only removed the mercury from soil but also produced large amounts of tubers and shoots which could be used as feedstock for the production of bioethanol.

Attentional Control and Subjective Executive Function in Treatment-Naive Adults with Attention Deficit Hyperactivity Disorder

PubMed Central

Grane, Venke Arntsberg; Endestad, Tor; Pinto, Arnfrid Farbu; Solbakk, Anne-Kristin

2014-01-01

We investigated performance-derived measures of executive control, and their relationship with self- and informant reported executive functions in everyday life, in treatment-naive adults with newly diagnosed Attention Deficit Hyperactivity Disorder (ADHD; n = 36) and in healthy controls (n = 35). Sustained attentional control and response inhibition were examined with the Test of Variables of Attention (T.O.V.A.). Delayed responses, increased reaction time variability, and higher omission error rate to Go signals in ADHD patients relative to controls indicated fluctuating levels of attention in the patients. Furthermore, an increment in NoGo commission errors when Go stimuli increased relative to NoGo stimuli suggests reduced inhibition of task-irrelevant stimuli in conditions demanding frequent responding. The ADHD group reported significantly more cognitive and behavioral executive problems than the control group on the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). There were overall not strong associations between task performance and ratings of everyday executive function. However, for the ADHD group, T.O.V.A. omission errors predicted self-reported difficulties on the Organization of Materials scale, and commission errors predicted informant reported difficulties on the same scale. Although ADHD patients endorsed more symptoms of depression and anxiety on the Achenbach System of Empirically Based Assessment (ASEBA) than controls, ASEBA scores were not significantly associated with T.O.V.A. performance scores. Altogether, the results indicate multifaceted alteration of attentional control in adult ADHD, and accompanying subjective difficulties with several aspects of executive function in everyday living. The relationships between the two sets of data were modest, indicating that the measures represent non-redundant features of adult ADHD. PMID:25545156

Attentional control and subjective executive function in treatment-naive adults with Attention Deficit Hyperactivity Disorder.

PubMed

Grane, Venke Arntsberg; Endestad, Tor; Pinto, Arnfrid Farbu; Solbakk, Anne-Kristin

2014-01-01

We investigated performance-derived measures of executive control, and their relationship with self- and informant reported executive functions in everyday life, in treatment-naive adults with newly diagnosed Attention Deficit Hyperactivity Disorder (ADHD; n = 36) and in healthy controls (n = 35). Sustained attentional control and response inhibition were examined with the Test of Variables of Attention (T.O.V.A.). Delayed responses, increased reaction time variability, and higher omission error rate to Go signals in ADHD patients relative to controls indicated fluctuating levels of attention in the patients. Furthermore, an increment in NoGo commission errors when Go stimuli increased relative to NoGo stimuli suggests reduced inhibition of task-irrelevant stimuli in conditions demanding frequent responding. The ADHD group reported significantly more cognitive and behavioral executive problems than the control group on the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). There were overall not strong associations between task performance and ratings of everyday executive function. However, for the ADHD group, T.O.V.A. omission errors predicted self-reported difficulties on the Organization of Materials scale, and commission errors predicted informant reported difficulties on the same scale. Although ADHD patients endorsed more symptoms of depression and anxiety on the Achenbach System of Empirically Based Assessment (ASEBA) than controls, ASEBA scores were not significantly associated with T.O.V.A. performance scores. Altogether, the results indicate multifaceted alteration of attentional control in adult ADHD, and accompanying subjective difficulties with several aspects of executive function in everyday living. The relationships between the two sets of data were modest, indicating that the measures represent non-redundant features of adult ADHD.

Assessing the difference of tolerance and phytoremediation potential in mercury contaminated soil of a non-food energy crop, Helianthus tuberosus L. (Jerusalem artichoke)

PubMed Central

Lv, Shiqi; Yang, Bin; Kou, Yixuan; Zeng, Jun; Wang, Ruixiong; Xiao, Yumeng; Li, Fencan; Lu, Ying; Mu, Yuwen

2018-01-01

This study was conducted to evaluate the effects of mercury stress on growth, photosynthesis and mercury accumulation in different cultivars of a non-food energy crop, Jerusalem artichoke, and to screen appropriate cultivars for their efficacy in the phytoremediation of mercury (Hg2+) contaminated soil. Cultivars LZJ033 (high above-ground biomass and nutrient content, and strongly sexual reproduction) and LZJ119 (a long period of vegetative growth) exhibited more tolerance to mercury stress than LZJ047 (the highest tuber yield and total sugar content). The lines LZJ119 and LZJ047 showed delays in emergence time of about four weeks, and LZJ047 exhibited the highest mortality rate, 85.19%, under treatment with 10 mg kg-1 mercury. The MDA (malondialdehyde) content increased whereas and the Pn (net photosynthetic rate), Fv∕Fm (the maximum quantum yield of PSII photochemistry) and chlorophyll content decreased in response to mercury stress. The stem diameter, stem biomass and photosynthetic rate of Jerusalem artichoke showed some modest increases in response to mercury stress and exhibited hormesis at least 1 mg kg-1 mercury treatment. Overall, LZJ119 produced more biomass under mercury stress, whereas LZJ033 exhibited a greater capacity for mercury bioaccumulation. Accordingly, LZJ119 may be a good candidate cultivar for use in cases of moderate—low mercury contamination, whereas LZJ033 may be a better candidate under conditions of high mercury contamination. When Jerusalem artichoke was cultivated in mercury contaminated soil, it not only removed the mercury from soil but also produced large amounts of tubers and shoots which could be used as feedstock for the production of bioethanol. PMID:29404218

Free Compulsory Education: A Natural Next Step after "Two Exceptions and One Subsidy" (TEOS)

ERIC Educational Resources Information Center

Brock, Andy; Wenbin, Hu; Wong, Christine

2008-01-01

Since 2001, the Chinese central government has begun to take on more financial responsibility for basic education beginning with a modest RMB100 million to provide free textbooks to poor students in western rural areas. This practice has been gradually expanded with the central government providing free textbooks to a widening pool of poor rural…

Stress Management-Augmented Behavioral Weight Loss Intervention for African American Women: A Pilot, Randomized Controlled Trial

ERIC Educational Resources Information Center

Cox, Tiffany L.; Krukowski, Rebecca; Love, ShaRhonda J.; Eddings, Kenya; DiCarlo, Marisha; Chang, Jason Y.; Prewitt, T. Elaine; West, Delia Smith

2013-01-01

The relationship between chronic stress and weight management efforts may be a concern for African American (AA) women, who have a high prevalence of obesity, high stress levels, and modest response to obesity treatment. This pilot study randomly assigned 44 overweight/obese AA women with moderate to high stress levels to either a 12-week…

Buses, Cars, Bicycles and Walkers: The Influence of the Type of Human Transport on the Flight Responses of Waterbirds

PubMed Central

McLeod, Emily M.; Guay, Patrick-Jean; Taysom, Alice J.; Robinson, Randall W.; Weston, Michael A.

2013-01-01

One way to manage disturbance to waterbirds in natural areas where humans require access is to promote the occurrence of stimuli for which birds tolerate closer approaches, and so cause fewer responses. We conducted 730 experimental approaches to 39 species of waterbird, using five stimulus types (single walker, three walkers, bicycle, car and bus) selected to mimic different human management options available for a controlled access, Ramsar-listed wetland. Across species, where differences existed (56% of 25 cases), motor vehicles always evoked shorter flight-initiation distances (FID) than humans on foot. The influence of stimulus type on FID varied across four species for which enough data were available for complete cross-stimulus analysis. All four varied FID in relation to stimuli, differing in 4 to 7 of 10 possible comparisons. Where differences occurred, the effect size was generally modest, suggesting that managing stimulus type (e.g. by requiring people to use vehicles) may have species-specific, modest benefits, at least for the waterbirds we studied. However, different stimulus types have different capacities to reduce the frequency of disturbance (i.e. by carrying more people) and vary in their capacity to travel around important habitat. PMID:24367498

Attitudes and behaviour towards waste management in the Dublin, Ireland region.

PubMed

Purcell, M; Magette, W L

2010-10-01

The hypothesis of this research was that attitudes about the management of biodegradable municipal waste (BMW) are spatially variable, even within a city of modest (1.2 million) population. For a select number of representative electoral districts in the Dublin, Ireland region, residents were surveyed regarding attitudes towards waste management in general, and BMW management in particular. A total of 850 survey responses were collected. Door-to-door interviews produced 688 responses in the residential sector; these were supplemented by 162 responses to a web-based survey. The surveys revealed that the majority of households use local authority, rather than private, waste collection services (both are available). The majority of residents, regardless of the local authority in which they live, were satisfied with their waste management service. "Reducing the quantity of waste generated" was regarded the most important future issue for 28% of residential respondents. Statistical analyses of the survey responses showed that the local authority in which respondents resided significantly influenced most responses (including waste collection service used, waste service satisfaction and backyard composting activity). Many responses (including waste service satisfaction, waste management influences) were also significantly related to the respondents' personal characteristics (e.g., education level, type of accommodation, age, etc.). These statistical results proved the hypothesis of the research and demonstrated that waste management initiatives designed for one area of the city (or, indeed, for uniform application to the city as a whole) could ignore the needs of other areas. The survey responses suggest that targeted intervention strategies would lead to improved diversion rates of BMW from landfill, a requirement of the Landfill Directive 1999/31/EC. (c) 2010 Elsevier Ltd. All rights reserved.

Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib.

PubMed

Byrd, John C; Furman, Richard R; Coutre, Steven E; Burger, Jan A; Blum, Kristie A; Coleman, Morton; Wierda, William G; Jones, Jeffrey A; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Shaw, Yun; Bilotti, Elizabeth; Zhou, Cathy; James, Danelle F; O'Brien, Susan

2015-04-16

Ibrutinib is an orally administered inhibitor of Bruton tyrosine kinase that antagonizes B-cell receptor, chemokine, and integrin-mediated signaling. In early-phase studies, ibrutinib demonstrated high response rates and prolonged progression-free survival (PFS) in chronic lymphocytic leukemia (CLL). The durable responses observed with ibrutinib relate in part to a modest toxicity profile that allows the majority of patients to receive continuous therapy for an extended period. We report on median 3-year follow-up of 132 patients with symptomatic treatment-naïve and relapsed/refractory CLL or small lymphocytic lymphoma. Longer treatment with ibrutinib was associated with improvement in response quality over time and durable remissions. Toxicity with longer follow-up diminished with respect to occurrence of grade 3 or greater cytopenias, fatigue, and infections. Progression remains uncommon, occurring primarily in some patients with relapsed del(17)(p13.1) and/or del(11)(q22.3) disease. Treatment-related lymphocytosis remains largely asymptomatic even when persisting >1 year and does not appear to alter longer-term PFS and overall survival compared with patients with partial response or better. Collectively, these data provide evidence that ibrutinib controls CLL disease manifestations and is well tolerated for an extended period; this information can help direct potential treatment options for different subgroups to diminish the long-term risk of relapse. © 2015 by The American Society of Hematology.

Industry Responsibilities in Tackling Direct-to-Consumer Marketing of Unproven Stem Cell Treatments.

PubMed

Master, Z; Fu, W; Paciulli, D; Sipp, D

2017-08-01

The direct-to-consumer marketing of unproven stem cell interventions (SCIs) is a serious public health concern. Regulations and education have had modest impact, indicating that different actors must play a role to stop this unfettered market. We consider the role of the biotech industry in tackling unproven SCIs. Grounded in the concept of corporate social responsibility, we argue that biotech companies should screen consumers to ensure that products and services are being used appropriately and educate employees about unproven SCIs. © 2017 ASCPT.

Pin1 as a Biomarker of ER+ Breast Cancers to Predict the Response to Tamoxifen and mTOR Inhibitors

DTIC Science & Technology

2009-04-01

for Pin1 in modulating S6K and Akt activity. We did, however, find a modest but reproducible defect in global protein synthesis and G0 exit. To...MEFs led to a small but reproducible defect in global protein synthesis and G0 exit. The immune system is comprised of multiple cell types that...and Franchi , L. STAT3 tyrosine phosphorylation is critical for interleukin 1 beta and interleukin-6 production in response to lipopolysaccharide and

Reduced Platelet Serotonergic Responsivity as Assessed by Dense Granule Secretion in First-Episode Psychosis

PubMed Central

Reddy, Ravinder D.; Keshavan, Matcheri S.; Yao, Jeffrey. K.

2007-01-01

SUMMARY Objectives To determine whether blunted serotonergic responsivity, indicated by decreased platelet dense granule secretion (DGS), occurs in neuroleptic-naive patients with schizophrenia, as observed previously in chronic schizophrenia. Design and Methods Serotonin (5-HT)-amplified DGS was examined in 40 first-episode neuroleptic-naive patients (24 with schizophrenia and 16 with mood disorders) and 24 healthy subjects. Results Healthy controls showed robustly increased DGS. Schizophrenic patients showed very modest DGS increases; mood disorder patients showed intermediate response. Conclusions Blunted DGS appears to a characteristic of schizophrenia that is observed in the treatment-naïve condition. PMID:17601524

Rising College Costs and an Illinois Effort to Control Them: A Preliminary Review

ERIC Educational Resources Information Center

North, Teresa Lynn

2013-01-01

Rising college costs are of increasing concern. At the 12 public universities in Illinois, average increases in tuition were modest, generally in the 4% range, until 1999 when individual campuses begin to increase tuition at double digit rates. In 2002-2003, the overall average increase in tuition/fees more than doubled at 13.79%. In an effort to…

Maternal depression, stress and feeding styles: towards a framework for theory and research in child obesity

USDA-ARS?s Scientific Manuscript database

Against the background of rising rates of obesity in children and adults in the USA, and modest effect sizes for obesity interventions, the aim of the present narrative review paper is to extend the UNICEF care model to focus on childhood obesity and its associated risks with an emphasis on the emot...

Student Ratings and Evaluation in Undergraduate Business Law Courses: A Modest Correlative Study

ERIC Educational Resources Information Center

Dhooge, Lucien J.; Eakin, Cynthia F.

2007-01-01

There are few topics more controversial in higher education than the evaluation of teaching effectiveness. The continuing relevancy of issues relating to what constitutes an effective teacher and methods by which to measure such effectiveness is evidenced by the more than 2,000 articles devoted to this topic by researchers in a wide variety of…

The Move to Mass Higher Education in the UK: Many Questions and Some Answers

ERIC Educational Resources Information Center

Mayhew, Ken; Deer, Cecile; Dua, Mehak

2004-01-01

This article describes the course and causes of the expansion of higher education in the UK since the 1960s. The number of university students from modest social backgrounds has increased, but they comprise much the same proportion of the university population as they did 40 years ago. Though personal rates of return from higher education are…

Acceptance and Commitment Therapy as a Novel Treatment for Eating Disorders: An Initial Test of Efficacy and Mediation

ERIC Educational Resources Information Center

Juarascio, Adrienne; Shaw, Jena; Forman, Evan; Timko, C. Alix; Herbert, James; Butryn, Meghan; Bunnell, Douglas; Matteucci, Alyssa; Lowe, Michael

2013-01-01

Eating disorders are among the most challenging disorders to treat, with even state-of-the-art cognitive-behavioral treatments achieving only modest success. One possible reason for the high rate of treatment failure for eating disorders is that existing treatments do not attend sufficiently to critical aspects of the disorder such as high…

The Draw-a-Person Test: An Indicator of Children's Cognitive and Socioemotional Adaptation?

ERIC Educational Resources Information Center

Ter Laak, J.; De Goede, M.; Aleva, A.; Van Rijswijk, P.

2005-01-01

The authors examined aspects of reliability and validity of the Goode-nough-Harris Draw-A-Person Test (DAP; D. B. Harris, 1963). The participants were 115 seven- to nine-year-old students attending regular or special education schools. Three judges, with a modest degree of training similar to that found among practicing clinicians, rated the…

Next Generation sequencing of the Trichinella murrelli mitochondrial genome allows comprehensive comparison of its divergence from the principal agent of human trichinellosis, Trichinella spiralis

USDA-ARS?s Scientific Manuscript database

The mitochondrial genome’s non-recombinant mode of inheritance and relatively rapid rate of evolution has promoted its use as a marker for studying the biogeographic history and evolutionary interrelationships among many metazoan species. A modest portion of the mitochondrial genome has been define...

The feasibility and effectiveness of Catch It, an innovative CBT smartphone app.

PubMed

Kinderman, Peter; Hagan, Paul; King, Sophie; Bowman, James; Chahal, Jasprit; Gan, Li; McKnight, Rebecca; Waldon, Charlotte; Smith, Matthew; Gilbertson, John; Tai, Sara

2016-05-01

The widespread use of smartphones makes effective therapies such as cognitive-behavioural therapy (CBT) potentially accessible to large numbers of people. This paper reports the usage data of the first trial of Catch It, a new CBT smartphone app. Uptake and usage rates, fidelity of user responses to CBT principles, and impact on reported negative and positive moods were assessed. A relatively modest proportion of people chose to download the app. Once used, the app tended to be used more than once, and 84% of the user-generated content was consistent with the basic concepts of CBT. There were statistically significant reductions in negative mood intensity and increases in positive mood intensity. Smartphone apps have potential beneficial effects in mental health through the application of basic CBT principles. More research with randomised controlled trial designs should be conducted. None. © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Hemodynamic Effects of Midodrine After Space Flight in Astronauts Without Orthostatic Hypotension

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Ziegler, Michael G.; Waters, Wendy W.; Meck, Janice V.

2006-01-01

Orthostatic hypotension and presyncope are common and potentially serious risks for astronauts returning from space. Susceptible subjects fail to generate an adequate adrenergic response to upright posture. The -1 adrenergic agonist, midodrine, may be an effective countermeasure. We tested the hypothesis that midodrine would have no negative hemodynamic effect on healthy astronauts returning from space. Five male astronauts participated in preflight and postflight tilt testing on a control flight as well as on the test flights, where midodrine (10 mg, orally) was administered after landing, approximately 1 hour before testing. None of these astronauts exhibited orthostatic hypotension or presyncope before or after either flight. Midodrine did not cause any untoward reactions in these subjects before or after flight, in fact a modest beneficial effect was seen on postflight tachycardia (p=0.036). These data show that midodrine protected against post-spaceflight increases in heart rate, without having any adverse hemodynamic effects on non-presyncopal, male astronauts. Among these subjects, midodrine was a safe cardiovascular countermeasure.

The effects of sustained manual pressure stimulation according to Vojta Therapy on heart rate variability.

PubMed

Opavsky, Jaroslav; Slachtova, Martina; Kutin, Miroslav; Hok, Pavel; Uhlir, Petr; Opavska, Hana; Hlustik, Petr

2018-05-23

The physiotherapeutic technique of Vojta reflex locomotion is often accompanied by various autonomic activity changes and unpleasant sensations. It is unknown whether these effects are specific to Vojta Therapy. Therefore, the aim of this study was to compare changes in cardiac autonomic control after Vojta reflex locomotion stimulation and after an appropriate sham stimulation. A total of 28 young healthy adults (20.4 - 25.7 years) were enrolled in this single-blind randomized cross-over study. Participants underwent two modes of 20-minute sustained manual pressure stimulation on the surface of the foot on two separate visits. One mode used manual pressure on the lateral heel, i.e., in a zone employed in the Vojta Therapy (active stimulation). The other mode used pressure on the lateral ankle (control), in an area not included among the active zones used by Vojta Therapy and whose activation does not evoke manifestations of reflex locomotion. Autonomic nervous system activity was evaluated using spectral analysis of heart rate variability before and after the intervention. The active stimulation was perceived as more unpleasant than the control stimulation. Heart rate variability parameters demonstrated almost identical autonomic responses after both stimulation types, showing either modest increase in parasympathetic activity, or increased heart rate variability with similar contribution of parasympathetic and sympathetic activity. The results demonstrate changes of cardiac autonomic control in both active and control stimulation, without evidence for a significant difference between the two.

Emotional reasoning and parent-based reasoning in non-clinical children, and their prospective relationships with anxiety symptoms.

PubMed

Morren, Mattijn; Muris, Peter; Kindt, Merel; Schouten, Erik; van den Hout, Marcel

2008-12-01

Emotional and parent-based reasoning refer to the tendency to rely on personal or parental anxiety response information rather than on objective danger information when estimating the dangerousness of a situation. This study investigated the prospective relationships of emotional and parent-based reasoning with anxiety symptoms in a sample of non-clinical children aged 8-14 years (n = 122). Children completed the anxiety subscales of the Revised Children's Anxiety and Depression Scale (Muris et al. Clin Psychol Psychother 9:430-442, 2002) and provided danger ratings of scenarios that systematically combined objective danger and objective safety information with anxiety-response and positive-response information. These measurements were repeated 10 months later (range 8-11 months). Emotional and parent-based reasoning effects emerged on both occasions. In addition, both effects were modestly stable, but only in case of objective safety. Evidence was found that initial anxiety levels were positively related to emotional reasoning 10 months later. In addition, initial levels of emotional reasoning were positively related to anxiety at a later time, but only when age was taken into account. That is, this relationship changed with increasing age from positive to negative. No significant prospective relationships emerged between anxiety and parent-based reasoning. As yet the clinical implications of these findings are limited, although preliminary evidence indicates that interpretation bias can be modified to decrease anxiety.

In vitro fatty acid enrichment of macrophages alters inflammatory response and net cholesterol accumulation

PubMed Central

Wang, Shu; Wu, Dayong; Lamon-Fava, Stefania; Matthan, Nirupa R.; Honda, Kaori L.; Lichtenstein, Alice H.

2010-01-01

Dietary long-chain PUFA, both n-3 and n-6, have unique benefits with respect to CVD risk. The aim of the present study was to determine the mechanisms by which n-3 PUFA (EPA, DHA) and n-6 PUFA (linoleic acid (LA), arachidonic acid (AA)) relative to SFA (myristic acid (MA), palmitic acid (PA)) alter markers of inflammation and cholesterol accumulation in macrophages (MΦ). Cells treated with AA and EPA elicited significantly less inflammatory response than control cells or those treated with MA, PA and LA, with intermediate effects for DHA, as indicated by lower levels of mRNA and secretion of TNFα, IL-6 and monocyte chemoattractant protein-1. Differences in cholesterol accumulation after exposure to minimally modified LDL were modest. AA and EPA resulted in significantly lower MΦ scavenger receptor 1 mRNA levels relative to control or MA-, PA-, LA- and DHA-treated cells, and ATP-binding cassette A1 mRNA levels relative to control or MA-, PA- and LA-treated cells. These data suggest changes in the rate of bidirectional cellular cholesterol flux. In summary, individual long-chain PUFA have differential effects on inflammatory response and markers of cholesterol flux in MΦ which are not related to the n position of the first double bond, chain length or degree of saturation. PMID:19660150

Pump-probe spectroscopy and imaging of heme proteins: temperature effects and data analysis

NASA Astrophysics Data System (ADS)

Wang, Erkang; Domingue, Scott R.; Bartels, Randy A.; Wilson, Jesse W.

2017-08-01

Ultrafast pump-probe microscopy enables visualization of non-fluorescent materials in biological tissue, such as melanin and hemoglobin. Whereas transient absorption has been primarily a physical chemistry technique, used to gain insight into molecular and electronic structure, pump-probe microscopy represents a paradigm shift in translating transient absorption into an analytical technique, which can clearly resolve pigments with nearly indistinguishable linear absorption spectra. Extending this technique to other important targets, such as mitochondrial respiratory chain hemes, will require new laser sources and new data processing techniques to estimate heme content from the pump-probe response. We will present recent developments on both of these fronts. The laser system we have developed to elicit a pump probe response of respiratory chain hemes is based on an amplified Yb:fiber ultrafast laser that uses modest spectral broadening followed by sum frequency generation to produce a tunable pulse pair in the visible region. Wavelength tuning is accomplished by changing quasi-phase matching conditions. We will present preliminary imaging data in addition to discussing management of sample heating problems that arise from performing transient absorption measurements at the high repetition rates needed for imaging microscopy. In the second part of the talk, we will present the use of regularized and non-negative least squares fitting, along with feature-preserving noise removal to estimate composition of a pixel from its pump-probe response.

The etiology of behavior problems in 7-year-old twins: substantial genetic influence and negligible shared environmental influence for parent ratings and ratings by same and different teachers.

PubMed

Saudino, Kimberly J; Ronald, Angelica; Plomin, Robert

2005-02-01

Parent ratings of behavior problems in childhood show substantial genetic influence and modest shared environmental influence. However, few studies have compared these results to teacher ratings and no previous studies have compared same-teacher ratings to different-teacher ratings. 3,714 7-year-old twin pairs in the Twins Early Development Study were rated by parents and teachers on the Strengths and Difficulties Questionnaire. Substantial heritability and negligible shared environmental influence were found for data from all three raters for total behavior problems, hyperactivity, prosocial behavior, peer problems, conduct problems, and emotional symptoms. Sex-limitation models revealed similar results for males and females, although there was some evidence for greater heritability for boys, especially when twins were rated by the same teacher.

Automating concept identification in the electronic medical record: an experiment in extracting dosage information.

PubMed Central

Evans, D. A.; Brownlow, N. D.; Hersh, W. R.; Campbell, E. M.

1996-01-01

We discuss the development and evaluation of an automated procedure for extracting drug-dosage information from clinical narratives. The process was developed rapidly using existing technology and resources, including categories of terms from UMLS96. Evaluations over a large training and smaller test set of medical records demonstrate an approximately 80% rate of exact and partial matches' on target phrases, with few false positives and a modest rate of false negatives. The results suggest a strategy for automating general concept identification in electronic medical records. PMID:8947694

Scholarly Contributions of Required Senior Research Projects in a Doctor of Pharmacy Curriculum

PubMed Central

Ibarra, Francisco; Mallios, Ronna; Corelli, Robin L.

2015-01-01

Objective. To determine dissemination outcomes and faculty perceptions of senior research projects conducted from 2008 to 2011 by PharmD students in a curricular pathway focused on direct patient care. Methods. Preceptors’ reported dissemination outcomes of research projects were surveyed and their perceptions of the precepting experience were rated using a web-based survey. Results were compared to those from an earlier pharmaceutical care cohort (2002-2007) and a combined cohort of 2, more research-intensive curricular pathways at the school. Results. The overall response rate was 90.2%. Project dissemination included 61.3% at an institutional forum, 42.3% as a submitted publication, 37.8% as a poster, and 4.5% as an oral presentation. Projects completed from 2008-2011 were significantly more likely than those from 2002-2007 to be submitted for publication (42.3% vs 10.7%, p<0.001) and published (28.8% vs 5.3%, p<0.001). Most preceptors found their research projects valuable to them professionally (88.3%) and to their own or another institution (83.5% and 78.5%, respectively). Ninety-five percent of preceptors would precept again. Conclusion. Dissemination rates for pharmaceutical care projects increased over time. Despite modest dissemination levels, the majority of preceptors agreed that required student research projects provide a valuable learning experience for students. PMID:25861104

Riparian Meadow Response to Modern Conservation Grazing Management

NASA Astrophysics Data System (ADS)

Oles, Kristin M.; Weixelman, Dave A.; Lile, David F.; Tate, Kenneth W.; Snell, Laura K.; Roche, Leslie M.

2017-09-01

Riparian meadows occupy a small proportion of the public lands in the western United States but they provide numerous ecosystem services, including the production of high-quality forage for livestock grazing. Modern conservation management strategies (e.g., reductions in livestock stocking rates and adoption of new riparian grazing standards) have been implemented to better balance riparian conservation and livestock production objectives on publicly managed lands. We examined potential relationships between long-term changes in plant community, livestock grazing pressure and environmental conditions at two spatial scales in meadows grazed under conservation management strategies. Changes in plant community were not associated with either livestock stocking rate or precipitation at the grazing allotment (i.e., administrative) scale. Alternatively, both grazing pressure and precipitation had significant, albeit modest, associations with changes in plant community at the meadow (i.e., ecological site) scale. These results suggest that reductions in stocking rate have improved the balance between riparian conservation and livestock production goals. However, associations between elevation, site wetness, precipitation, and changes in plant community suggest that changing climate conditions (e.g., reduced snowpack and changes in timing of snowmelt) could trigger shifts in plant communities, potentially impacting both conservation and agricultural services (e.g., livestock and forage production). Therefore, adaptive, site-specific management strategies are required to meet grazing pressure limits and safeguard ecosystem services within individual meadows, especially under more variable climate conditions.

Riparian Meadow Response to Modern Conservation Grazing Management.

PubMed

Oles, Kristin M; Weixelman, Dave A; Lile, David F; Tate, Kenneth W; Snell, Laura K; Roche, Leslie M

2017-09-01

Riparian meadows occupy a small proportion of the public lands in the western United States but they provide numerous ecosystem services, including the production of high-quality forage for livestock grazing. Modern conservation management strategies (e.g., reductions in livestock stocking rates and adoption of new riparian grazing standards) have been implemented to better balance riparian conservation and livestock production objectives on publicly managed lands. We examined potential relationships between long-term changes in plant community, livestock grazing pressure and environmental conditions at two spatial scales in meadows grazed under conservation management strategies. Changes in plant community were not associated with either livestock stocking rate or precipitation at the grazing allotment (i.e., administrative) scale. Alternatively, both grazing pressure and precipitation had significant, albeit modest, associations with changes in plant community at the meadow (i.e., ecological site) scale. These results suggest that reductions in stocking rate have improved the balance between riparian conservation and livestock production goals. However, associations between elevation, site wetness, precipitation, and changes in plant community suggest that changing climate conditions (e.g., reduced snowpack and changes in timing of snowmelt) could trigger shifts in plant communities, potentially impacting both conservation and agricultural services (e.g., livestock and forage production). Therefore, adaptive, site-specific management strategies are required to meet grazing pressure limits and safeguard ecosystem services within individual meadows, especially under more variable climate conditions.

How do stimulant treatments for ADHD work? Evidence for mediation by improved cognition.

PubMed

Hawk, Larry W; Fosco, Whitney D; Colder, Craig R; Waxmonsky, James G; Pelham, William E; Rosch, Keri S

2018-05-07

Stimulant medications such as methylphenidate (MPH) are the frontline treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). Despite their well-documented efficacy, the mechanisms by which stimulants improve clinical outcomes are not clear. The current study evaluated whether MPH effects on classroom behavior were mediated by improved cognitive functioning. Children with ADHD (n = 82; 9-12 years old) participated in a week-long summer research camp, consisting of cognitive testing, classroom periods, and recreational activities. After a baseline day, participants completed a 3-day randomized, double-blind, placebo-controlled trial of MPH (at doses approximating 0.3 and 0.6 mg/kg of immediate-release MPH dosed TID). Cognitive domains included inhibitory control (Stop Signal Task and prepulse inhibition of startle), attention (Continuous Performance Task and reaction time variability), and working memory (forward and backward spatial span). Clinical outcomes included math seatwork productivity and teacher-rated classroom behavior. A within-subjects path-analytic approach was used to test mediation. MPH-placebo and dose-response contrasts were used to evaluate drug effects. Methylphenidate improved seatwork productivity and teacher ratings (ds = 1.4 and 1.1) and all domains of cognition (ds = 0.3-1.1). Inhibitory control (Stop Signal Task, SST) and working memory backward uniquely mediated the effect of MPH (vs. placebo) on productivity. Only working memory backward mediated the impact of MPH on teacher-rated behavior. The dose-response (0.6 vs. 0.3 mg/kg) effects were more modest for clinical outcomes (ds = 0.4 and 0.2) and cognition (ds = 0-0.3); there was no evidence of cognitive mediation of the clinical dose-response effects. These findings are novel in demonstrating that specific cognitive processes mediate clinical improvement with stimulant treatment for ADHD. They converge with work on ADHD theory, neurobiology, and treatment development in suggesting that inhibitory control and working memory may be mechanisms of stimulant treatment response in ADHD. More work is necessary to evaluate the degree to which these findings generalize to chronic treatment, a broader array of clinical outcomes, and nonstimulant treatments. © 2018 Association for Child and Adolescent Mental Health.

Ineffectiveness of commercial weight-loss programs for achieving modest but meaningful weight loss: Systematic review and meta-analysis.

PubMed

McEvedy, Samantha M; Sullivan-Mort, Gillian; McLean, Siân A; Pascoe, Michaela C; Paxton, Susan J

2017-10-01

This study collates existing evidence regarding weight loss among overweight but otherwise healthy adults who use commercial weight-loss programs. Systematic search of 3 databases identified 11 randomized controlled trials and 14 observational studies of commercial meal-replacement, calorie-counting, or pre-packaged meal programs which met inclusion criteria. In meta-analysis using intention-to-treat data, 57 percent of individuals who commenced a commercial weight program lost less than 5 percent of their initial body weight. One in two (49%) studies reported attrition ≥30 percent. A second meta-analysis found that 37 percent of program completers lost less than 5 percent of initial body weight. We conclude that commercial weight-loss programs frequently fail to produce modest but clinically meaningful weight loss with high rates of attrition suggesting that many consumers find dietary changes required by these programs unsustainable.

Pricing and Welfare in Health Plan Choice.

PubMed

Bundorf, M Kate; Levin, Jonathan; Mahoney, Neale

2012-12-01

Premiums in health insurance markets frequently do not reflect individual differences in costs, either because consumers have private information or because prices are not risk rated. This creates inefficiencies when consumers self-select into plans. We develop a simple econometric model to study this problem and estimate it using data on small employers. We find a welfare loss of 2-11 percent of coverage costs compared to what is feasible with risk rating. Only about one-quarter of this is due to inefficiently chosen uniform contribution levels. We also investigate the reclassification risk created by risk rating individual incremental premiums, finding only a modest welfare cost.

Rain rate range profiling from a spaceborne radar

NASA Technical Reports Server (NTRS)

Meneghini, R.

1980-01-01

At certain frequencies and incidence angles the relative invariance of the surface scattering properites over land can be used to estimate the total attenuation and the integrated rain from a spaceborne attenuation-wavelength radar. The technique is generalized so that rain rate profiles along the radar beam can be estimated, i.e., rain rate determination at each range bin. This is done by modifying the standard algorithm for an attenuating-wavelength radar to include in it the measurement of the total attenuation. Simple error analyses of the estimates show that this type of profiling is possible if the total attenuation can be measured with a modest degree of accuracy.

Both cladribine and alemtuzumab may effect MS via B-cell depletion.

PubMed

Baker, David; Herrod, Samuel S; Alvarez-Gonzalez, Cesar; Zalewski, Lukasz; Albor, Christo; Schmierer, Klaus

2017-07-01

To understand the efficacy of cladribine (CLAD) treatment in MS through analysis of lymphocyte subsets collected, but not reported, in the pivotal phase III trials of cladribine and alemtuzumab induction therapies. The regulatory submissions of the CLAD Tablets Treating Multiple Sclerosis Orally (CLARITY) (NCT00213135) cladribine and Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, study one (CARE-MS I) (NCT00530348) alemtuzumab trials were obtained from the European Medicine Agency through Freedom of Information requests. Data were extracted and statistically analyzed. Either dose of cladribine (3.5 mg/kg; 5.25 mg/kg) tested in CLARITY reduced the annualized relapse rate to 0.16-0.18 over 96 weeks, and both doses were similarly effective in reducing the risk of MRI lesions and disability. Surprisingly, however, T-cell depletion was rather modest. Cladribine 3.5 mg/kg depleted CD4 + cells by 40%-45% and CD8 + cells by 15%-30%, whereas alemtuzumab suppressed CD4 + cells by 70%-95% and CD8 + cells by 47%-55%. However, either dose of cladribine induced 70%-90% CD19 + B-cell depletion, similar to alemtuzumab (90%). CD19 + cells slowly repopulated to 15%-25% of baseline before cladribine redosing. However, alemtuzumab induced hyperrepopulation of CD19 + B cells 6-12 months after infusion, which probably forms the substrate for B-cell autoimmunities associated with alemtuzumab. Cladribine induced only modest depletion of T cells, which may not be consistent with a marked influence on MS, based on previous CD4 + T-cell depletion studies. The therapeutic drug-response relationship with cladribine is more consistent with lasting B-cell depletion and, coupled with the success seen with monoclonal CD20 + depletion, suggests that B-cell suppression could be the major direct mechanism of action.

Differential Lymphocyte and Antibody Responses in Deer Mice Infected with Sin Nombre Hantavirus or Andes Hantavirus

PubMed Central

Quackenbush, Sandra; Rovnak, Joel; Haddock, Elaine; Black, William C.; Feldmann, Heinz; Prescott, Joseph

2014-01-01

ABSTRACT Hantavirus cardiopulmonary syndrome (HCPS) is a rodent-borne disease with a high case-fatality rate that is caused by several New World hantaviruses. Each pathogenic hantavirus is naturally hosted by a principal rodent species without conspicuous disease and infection is persistent, perhaps for life. Deer mice (Peromyscus maniculatus) are the natural reservoirs of Sin Nombre virus (SNV), the etiologic agent of most HCPS cases in North America. Deer mice remain infected despite a helper T cell response that leads to high-titer neutralizing antibodies. Deer mice are also susceptible to Andes hantavirus (ANDV), which causes most HCPS cases in South America; however, deer mice clear ANDV. We infected deer mice with SNV or ANDV to identify differences in host responses that might account for this differential outcome. SNV RNA levels were higher in the lungs but not different in the heart, spleen, or kidneys. Most ANDV-infected deer mice had seroconverted 14 days after inoculation, but none of the SNV-infected deer mice had. Examination of lymph node cell antigen recall responses identified elevated immune gene expression in deer mice infected with ANDV and suggested maturation toward a Th2 or T follicular helper phenotype in some ANDV-infected deer mice, including activation of the interleukin 4 (IL-4) pathway in T cells and B cells. These data suggest that the rate of maturation of the immune response is substantially higher and of greater magnitude during ANDV infection, and these differences may account for clearance of ANDV and persistence of SNV. IMPORTANCE Hantaviruses persistently infect their reservoir rodent hosts without pathology. It is unknown how these viruses evade sterilizing immune responses in the reservoirs. We have determined that infection of the deer mouse with its homologous hantavirus, Sin Nombre virus, results in low levels of immune gene expression in antigen-stimulated lymph node cells and a poor antibody response. However, infection of deer mice with a heterologous hantavirus, Andes virus, results in a robust lymph node cell response, signatures of T and B cell maturation, and production of antibodies. These findings suggest that an early and aggressive immune response to hantaviruses may lead to clearance in a reservoir host and suggest that a modest immune response may be a component of hantavirus ecology. PMID:24829335

Differential lymphocyte and antibody responses in deer mice infected with Sin Nombre hantavirus or Andes hantavirus.

PubMed

Schountz, Tony; Quackenbush, Sandra; Rovnak, Joel; Haddock, Elaine; Black, William C; Feldmann, Heinz; Prescott, Joseph

2014-08-01

Hantavirus cardiopulmonary syndrome (HCPS) is a rodent-borne disease with a high case-fatality rate that is caused by several New World hantaviruses. Each pathogenic hantavirus is naturally hosted by a principal rodent species without conspicuous disease and infection is persistent, perhaps for life. Deer mice (Peromyscus maniculatus) are the natural reservoirs of Sin Nombre virus (SNV), the etiologic agent of most HCPS cases in North America. Deer mice remain infected despite a helper T cell response that leads to high-titer neutralizing antibodies. Deer mice are also susceptible to Andes hantavirus (ANDV), which causes most HCPS cases in South America; however, deer mice clear ANDV. We infected deer mice with SNV or ANDV to identify differences in host responses that might account for this differential outcome. SNV RNA levels were higher in the lungs but not different in the heart, spleen, or kidneys. Most ANDV-infected deer mice had seroconverted 14 days after inoculation, but none of the SNV-infected deer mice had. Examination of lymph node cell antigen recall responses identified elevated immune gene expression in deer mice infected with ANDV and suggested maturation toward a Th2 or T follicular helper phenotype in some ANDV-infected deer mice, including activation of the interleukin 4 (IL-4) pathway in T cells and B cells. These data suggest that the rate of maturation of the immune response is substantially higher and of greater magnitude during ANDV infection, and these differences may account for clearance of ANDV and persistence of SNV. Hantaviruses persistently infect their reservoir rodent hosts without pathology. It is unknown how these viruses evade sterilizing immune responses in the reservoirs. We have determined that infection of the deer mouse with its homologous hantavirus, Sin Nombre virus, results in low levels of immune gene expression in antigen-stimulated lymph node cells and a poor antibody response. However, infection of deer mice with a heterologous hantavirus, Andes virus, results in a robust lymph node cell response, signatures of T and B cell maturation, and production of antibodies. These findings suggest that an early and aggressive immune response to hantaviruses may lead to clearance in a reservoir host and suggest that a modest immune response may be a component of hantavirus ecology. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Lessons from the Past: Three Modest Suggestions toward School Reform for Poor Students

ERIC Educational Resources Information Center

Davis, Matthew D.

2007-01-01

At the end of August 2005, Hurricane Katrina laid bare a wide swath of the U.S. Gulf Coast. The devastation left in the wake of this natural disaster and the all-too-slow governmental response to it shocked the nation. Hidden even deeper in the media aftermath of Katrina were the stories of the particularly harsh fury that the hurricane had…

Aim High or Go Low? Pricing Strategies and Enrollment Effects when the Net Price Elasticity Varies with Need and Ability

ERIC Educational Resources Information Center

Curs, Bradley R.; Singell, Larry D., Jr.

2010-01-01

Detailed data on individual applicants to a large public university are used to demonstrate that net price responsiveness decreases with need and ability. Enrollment effects are simulated and show a movement towards a high tuition/high aid (low tuition/low aid) policy significantly lowers (raises) tuition revenue with a modest increase (decrease)…

The effects of age on inflammatory and coagulation-fibrinolysis response in patients hospitalized for pneumonia.

PubMed

Kale, Sachin; Yende, Sachin; Kong, Lan; Perkins, Amy; Kellum, John A; Newman, Anne B; Vallejo, Abbe N; Angus, Derek C

2010-11-04

To determine whether inflammatory and hemostasis response in patients hospitalized for pneumonia varies by age and whether these differences explain higher mortality in the elderly. In an observational cohort of subjects with community-acquired pneumonia (CAP) recruited from emergency departments (ED) in 28 hospitals, we divided subjects into 5 age groups (<50, 51-64, 65-74, 75-84, and ≥85). We measured circulating levels of inflammatory (TNF, IL-6, and IL-10), hemostasis (D-dimer, Factor IX, thrombin-antithrombin complex, antithrombin and plasminogen-activator inhibitor-1), and cell-surface markers (TLR-2, TLR-4, and HLA-DR) during the first week of hospitalization and at discharge and compared 90-day mortality. We used logistic regression to compare odds ratios (OR) for 90-day mortality between age groups, adjusting for differences in pre-infection factors alone and then additionally adjusting for immune markers. Of 2,183 subjects, 495, 444, 403, 583, and 258 subjects were <50, 51-64, 65-74, 75-84, and ≥85 years of age, respectively. Large age-related differences were observed in 90-day mortality (0.82% vs. 3.2% vs. 6.4% vs. 12.8% vs. 13.6%, p<0.01). No age-related differences in inflammatory and cell surface markers occurred during the first week. Older subjects had higher pro-coagulant markers on ED presentation and over first week (p ≤ 0.03), but these differences were modest (1.0-1.7-fold differences). Odds of death for older adults changed minimally in models incorporating differences in hemostasis and inflammatory markers (for subjects ≥ 85 compared to those <50, OR = 4.36, when adjusted for pre-infection factors and OR = 3.49 when additionally adjusted for hemostasis markers). At discharge, despite clinical recovery as evidenced by normal vital signs in >85% subjects, older subjects had modestly increased hemostasis markers and IL-6 levels (p<0.01). Modest age-related increases in coagulation response occur during hospitalization for CAP; however these differences do not explain the large differences in mortality. Despite clinical recovery, immune resolution may be delayed in older adults at discharge.

Response surface modeling of remifentanil-propofol interaction on cardiorespiratory control and bispectral index.

PubMed

Nieuwenhuijs, Diederik J F; Olofsen, Erik; Romberg, Raymonda R; Sarton, Elise; Ward, Denham; Engbers, Frank; Vuyk, Jaap; Mooren, Rene; Teppema, Luc J; Dahan, Albert

2003-02-01

Since propofol and remifentanil are frequently combined for monitored anesthesia care, we examined the influence of the separate and combined administration of these agents on cardiorespiratory control and bispectral index in humans. The effect of steady-state concentrations of remifentanil and propofol was assessed in 22 healthy male volunteer subjects. For each subject, measurements were obtained from experiments using remifentanil alone, propofol alone, and remifentanil plus propofol (measured arterial blood concentration range: propofol studies, 0-2.6 microg/ml; remifentanil studies, 0-2.0 ng/ml). Respiratory experiments consisted of ventilatory responses to three to eight increases in end-tidal Pco2 (Petco2). Invasive blood pressure, heart rate, and bispectral index were monitored concurrently. The nature of interaction was assessed by response surface modeling using a population approach with NONMEM. Values are population estimate plus or minus standard error. A total of 94 responses were obtained at various drug combinations. When given separately, remifentanil and propofol depressed cardiorespiratory variables in a dose-dependent fashion (resting V(i) : 12.6 +/- 3.3% and 27.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; V(i) at fixed Petco of 55 mmHg: 44.3 +/- 3.9% and 57.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; blood pressure: 9.9 +/- 1.8% and 3.7 +/- 1.1% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively). When given in combination, their effect on respiration was synergistic (greatest synergy observed for resting V(i)). The effects of both drugs on heart rate and blood pressure were modest, with additive interactions when combined. Over the dose range studied, remifentanil had no effect on bispectral index even when combined with propofol (inert interaction). These data show dose-dependent effects on respiration at relatively low concentrations of propofol and remifentanil. When combined, their effect on respiration is strikingly synergistic, resulting in severe respiratory depression.

Tumor mutational analysis of GOG248, a phase II study of temsirolimus or temsirolimus and alternating megestrol acetate and tamoxifen for advanced endometrial cancer (EC): An NRG Oncology/Gynecologic Oncology Group study

PubMed Central

Myers, Andrea P.; Filiaci, Virginia L.; Zhang, Yuping; Pearl, Michael; Behbakht, Kian; Makker, Vicky; Hanjani, Parviz; Zweizig, Susan; Burke, James J.; Downey, Gordon; Leslie, Kimberly K.; Van Hummelen, Paul; Birrer, Michael J.; Fleming, Gini F.

2016-01-01

Objective Rapamycin analogs have reproducible but modest efficacy in endometrial cancer (EC). Identification of molecular biomarkers that predict benefit could guide clinical development. Methods Fixed primary tissue and whole blood were collected prospectively from patients enrolled on GOG 248. DNA was isolated from macro-dissected tumors and blood; next–generation sequence analysis was performed on a panel of cancer related genes. Associations between clinical outcomes [response rate (RR) 20%; progression-free survival (PFS) median 4.9 months] and mutations (PTEN, PIK3CA, PIK3R1, KRAS, CTNNB1, AKT1, TSC1, TSC2, NF1, FBXW7) were explored. Results Sequencing data was obtained from tumors of 55 of the 73 enrolled pts. Mutation rates were consistent with published reports: mutations in PTEN (45%), PIK3CA (29%), PIK3R1 (24%), K-RAS (16%), CTNNB1 (18%) were common and mutations in AKT1 (4%), TSC1 (2%), TSC2 (2%), NF1 (9%) and FBXW7 (4%) were less common. Increased PFS (HR 0.16; 95% CI 0.01–0.78) and RR (response difference 0.83; 95% CI 0.03–0.99) were noted for AKT1 mutation. An increase in PFS (HR 0.46; 95% CI 0.20–0.97) but not RR (response difference 0.00, 95% CI −0.34–0.34) was identified for CTNNB1 mutation. Both patients with TSC mutations had an objective response. There were no statistically significant associations between mutations in PIK3CA, PTEN, PIK3R1, or KRAS and PFS or RR. Conclusions Mutations in AKT1, TSC1 and TSC2 are rare, but may predict clinical benefit from temsirolimus. CTNNB1 mutations were associated with longer PFS on temsirolimus. PMID:27016228

A Randomized Trial of the Effect of Centralized Reminder/Recall on Immunizations and Preventive Care Visits for Adolescents

PubMed Central

Szilagyi, Peter G.; Albertin, Christina; Humiston, Sharon G.; Rand, Cynthia M.; Schaffer, Stanley; Brill, Howard; Stankaitis, Joseph; Yo, Byung-Kwang; Blumkin, Aaron; Stokley, Shannon

2015-01-01

Objective To assess the impact of a managed care-based patient reminder/recall system on immunization rates and preventive care visits among low-income adolescents. Methods We conducted a randomized controlled trial between December 2009 and December 2010 that assigned adolescents aged 11–17 years to one of three groups: mailed letter, telephone reminders, or control. Publicly insured youths (n = 4, 115) were identified in 37 participating primary care practices. The main outcome measures were immunization rates for routine vaccines (meningococcus, pertussis, HPV) and preventive visit rates at study end. Results Intervention and control groups were similar at baseline for demographics, immunization rates, and preventive visits. Among adolescents who were behind at the start, immunization rates at study end increased by 21% for mailed (P < .01 vs control), 17% for telephone (P < .05), and 13% for control groups. The proportion of adolescents with a preventive visit (within 12 months) was: mailed (65%; P <.01), telephone (63%; P <.05), and controls (59%). The number needed to treat for an additional fully vaccinated adolescent was 14 for mailed and 25 for telephone reminders; for an additional preventive visit, it was 17 and 29. The intervention cost $18.78 (mailed) or $16.68 (phone) per adolescent per year to deliver. The cost per additional adolescent fully vaccinated was $463.99 for mailed and $714.98 for telephone; the cost per additional adolescent receiving a preventive visit was $324.75 and $487.03. Conclusions Managed care-based mail or telephone reminder/recall improved adolescent immunizations and preventive visits, with modest costs and modest impact. PMID:23510607

Hospital Use of Observation Stays: Cross-sectional Study of the Impact on Readmission Rates.

PubMed

Venkatesh, Arjun K; Wang, Changqin; Ross, Joseph S; Altaf, Faseeha K; Suter, Lisa G; Vellanky, Smitha; Grady, Jacqueline N; Bernheim, Susannah M

2016-12-01

The Centers for Medicare and Medicaid Services publicly reports hospital risk-standardized readmission rates (RSRRs) as a measure of quality and performance; mischaracterizations may occur because observation stays are not captured by current measures. To describe variation in hospital use of observation stays, the relationship between hospitals observation stay use and RSRRs. Cross-sectional analysis of Medicare fee-for-service beneficiaries discharged after acute myocardial infarction (AMI), heart failure, or pneumonia between July 2011 and June 2012. We calculated 3 hospital-specific 30-day outcomes: (1) observation rate, the proportion of all discharges followed by an observation stay without a readmission; (2) observation proportion, the proportion of observation stays among all patients with an observation stay or readmission; and (3) RSRR. For all 3 conditions, hospitals' observation rates were <2.5% and observation proportions were <12%, although there was variation across hospitals, including 28% of hospital with no observation stay use for AMI, 31% for heart failure, and 43% for pneumonia. There were statistically significant, but minimal, correlations between hospital observation rates and RSRRs: AMI (r=-0.02), heart failure (r=-0.11), and pneumonia (r=-0.02) (P<0.001). There were modest inverse correlations between hospital observation proportion and RSRR: AMI (r=-0.34), heart failure (r=-0.26), and pneumonia (r=-0.21) (P<0.001). If observation stays were included in readmission measures, <4% of top performing hospitals would be recategorized as having average performance. Hospitals' observation stay use in the postdischarge period is low, but varies widely. Despite modest correlation between the observation proportion and RSRR, counting observation stays in readmission measures would minimally impact public reporting of performance.

A randomized trial of the effect of centralized reminder/recall on immunizations and preventive care visits for adolescents.

PubMed

Szilagyi, Peter G; Albertin, Christina; Humiston, Sharon G; Rand, Cynthia M; Schaffer, Stanley; Brill, Howard; Stankaitis, Joseph; Yoo, Byung-Kwang; Blumkin, Aaron; Stokley, Shannon

2013-01-01

To assess the impact of a managed care-based patient reminder/recall system on immunization rates and preventive care visits among low-income adolescents. We conducted a randomized controlled trial between December 2009 and December 2010 that assigned adolescents aged 11-17 years to one of three groups: mailed letter, telephone reminders, or control. Publicly insured youths (n = 4115) were identified in 37 participating primary care practices. The main outcome measures were immunization rates for routine vaccines (meningococcus, pertussis, HPV) and preventive visit rates at study end. Intervention and control groups were similar at baseline for demographics, immunization rates, and preventive visits. Among adolescents who were behind at the start, immunization rates at study end increased by 21% for mailed (P < .01 vs control), 17% for telephone (P < .05), and 13% for control groups. The proportion of adolescents with a preventive visit (within 12 months) was: mailed (65%; P < .01), telephone (63%; P < .05), and controls (59%). The number needed to treat for an additional fully vaccinated adolescent was 14 for mailed and 25 for telephone reminders; for an additional preventive visit, it was 17 and 29. The intervention cost $18.78 (mailed) or $16.68 (phone) per adolescent per year to deliver. The cost per additional adolescent fully vaccinated was $463.99 for mailed and $714.98 for telephone; the cost per additional adolescent receiving a preventive visit was $324.75 and $487.03. Managed care-based mail or telephone reminder/recall improved adolescent immunizations and preventive visits, with modest costs and modest impact. Copyright © 2013 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Biphasic dose responses in biology, toxicology and medicine: accounting for their generalizability and quantitative features.

PubMed

Calabrese, Edward J

2013-11-01

The most common quantitative feature of the hormetic-biphasic dose response is its modest stimulatory response which at maximum is only 30-60% greater than control values, an observation that is consistently independent of biological model, level of organization (i.e., cell, organ or individual), endpoint measured, chemical/physical agent studied, or mechanism. This quantitative feature suggests an underlying "upstream" mechanism common across biological systems, therefore basic and general. Hormetic dose response relationships represent an estimate of the peak performance of integrative biological processes that are allometrically based. Hormetic responses reflect both direct stimulatory or overcompensation responses to damage induced by relatively low doses of chemical or physical agents. The integration of the hormetic dose response within an allometric framework provides, for the first time, an explanation for both the generality and the quantitative features of the hormetic dose response. Copyright © 2013 Elsevier Ltd. All rights reserved.

Efficacy of bupropion and the selective serotonin reuptake inhibitors in the treatment of major depressive disorder with high levels of anxiety (anxious depression): a pooled analysis of 10 studies.

PubMed

Papakostas, George I; Stahl, Stephen M; Krishen, Alok; Seifert, Cheryl A; Tucker, Vivian L; Goodale, Elizabeth P; Fava, Maurizio

2008-08-01

The goal of this work was to compare the efficacy of the norepinephrine and dopamine reuptake inhibitor bupropion with the selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder with high levels of anxiety (anxious depression). Ten double-blind, randomized studies from 1991 through 2006 were combined (N = 2122). Anxious depression was defined as a 17-item Hamilton Rating Scale for Depression (HAM-D-17) anxiety-somatization factor score >or= 7. Among patients with anxious depression (N = 1275), response rates were greater following SSRI than bupropion treatment according to the HAM-D-17 (65.4% vs. 59.4%, p = .03) and the Hamilton Rating Scale for Anxiety (61.5% vs. 54.5%, p = .03). There was also a greater reduction in HAM-D-17 mean +/- SD scores (-14.1 +/- 7.6 vs. -13.2 +/- 7.9, p = .03) and a trend toward statistical significance for a greater reduction in HAM-A mean +/- SD scores (-10.5 +/- 7.4 vs. -9.6 +/- 7.6, p = .05) in favor of SSRI treatment among patients with anxious depression. There was no statistically significant difference in efficacy between bupropion and the SSRIs among patients with moderate/low levels of anxiety. There appears to be a modest advantage for the SSRIs compared to bupropion in the treatment of anxious depression (6% difference in response rates). Using the number-needed-to-treat (NNT) statistic as 1 indicator of clinical significance, nearly 17 patients would need to be treated with an SSRI than with bupropion in order to obtain 1 additional responder. This difference falls well above the limit of NNT = 10, which was suggested by the United Kingdom's National Institute of Clinical Excellence. Nevertheless, the present work is of theoretical interest because it provides preliminary evidence suggesting a central role for serotonin in the regulation of symptoms of negative affect such as anxiety.

Prioritizing blood flow: cardiovascular performance in response to the competing demands of locomotion and digestion for the Burmese python, Python molurus.

PubMed

Secor, Stephen M; White, Scott E

2010-01-01

Individually, the metabolic demands of digestion or movement can be fully supported by elevations in cardiovascular performance, but when occurring simultaneously, vascular perfusion may have to be prioritized to either the gut or skeletal muscles. Burmese pythons (Python molurus) experience similar increases in metabolic rate during the digestion of a meal as they do while crawling, hence each would have an equal demand for vascular supply when these two actions are combined. To determine, for the Burmese python, whether blood flow is prioritized when snakes are digesting and moving, we examined changes in cardiac performance and blood flow in response to digestion, movement, and the combination of digestion and movement. We used perivascular blood flow probes to measure blood flow through the left carotid artery, dorsal aorta, superior mesenteric artery and hepatic portal vein, and to calculate cardiac output, heart rate and stroke volume. Fasted pythons while crawling experienced a 2.7- and 3.3-fold increase, respectively, in heart rate and cardiac output, and a 66% decrease in superior mesenteric flow. During the digestion of a rodent meal equaling in mass to 24.7% of the snake's body mass, heart rate and cardiac output increased by 3.3- and 4.4-fold, respectively. Digestion also resulted in respective 11.6- and 14.1-fold increases in superior mesenteric and hepatic portal flow. When crawling while digesting, cardiac output and dorsal aorta flow increased by only 21% and 9%, respectively, a modest increase compared with that when they start to crawl on an empty stomach. Crawling did triggered a significant reduction in blood flow to the digesting gut, decreasing superior mesenteric and hepatic portal flow by 81% and 47%, respectively. When faced with the dual demands of digestion and crawling, Burmese pythons prioritize blood flow, apparently diverting visceral supply to the axial muscles.

Subthalamic nucleus activity optimizes maximal effort motor responses in Parkinson's disease.

PubMed

Anzak, Anam; Tan, Huiling; Pogosyan, Alek; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Ashkan, Keyoumars; Bogdanovic, Marko; Green, Alexander L; Aziz, Tipu; Brown, Peter

2012-09-01

The neural substrates that enable individuals to achieve their fastest and strongest motor responses have long been enigmatic. Importantly, characterization of such activities may inform novel therapeutic strategies for patients with hypokinetic disorders, such as Parkinson's disease. Here, we ask whether the basal ganglia may play an important role, not only in the attainment of maximal motor responses under standard conditions but also in the setting of the performance enhancements known to be engendered by delivery of intense stimuli. To this end, we recorded local field potentials from deep brain stimulation electrodes implanted bilaterally in the subthalamic nuclei of 10 patients with Parkinson's disease, as they executed their fastest and strongest handgrips in response to a visual cue, which was accompanied by a brief 96-dB auditory tone on random trials. We identified a striking correlation between both theta/alpha (5-12 Hz) and high-gamma/high-frequency (55-375 Hz) subthalamic nucleus activity and force measures, which explained close to 70% of interindividual variance in maximal motor responses to the visual cue alone, when patients were ON their usual dopaminergic medication. Loud auditory stimuli were found to enhance reaction time and peak rate of development of force still further, independent of whether patients were ON or OFF l-DOPA, and were associated with increases in subthalamic nucleus power over a broad gamma range. However, the contribution of this broad gamma activity to the performance enhancements observed was only modest (≤13%). The results implicate frequency-specific subthalamic nucleus activities as substantial factors in optimizing an individual's peak motor responses at maximal effort of will, but much less so in the performance increments engendered by intense auditory stimuli.

Effect of exercise on postprandial lipemia following a higher calorie meal in Yucatan miniature swine.

PubMed

Rector, R Scott; Thomas, Tom R; Liu, Ying; Henderson, Kyle K; Holiman, Denise A; Sun, Grace Y; Sturek, Michael

2004-08-01

Exercise has been shown to attenuate the postprandial lipemic (PPL) response to a modest kcal high-fat meal in numerous human studies, but has not been fully examined in swine. In addition, the effects of exercise on a high-fat meal of larger magnitude have not been examined in humans or in swine. Thus, the purpose of this study was to examine the PPL response to a single, high-fat/cholesterol (HFC) meal (approximately 3,000 kcal, 1,300 kcal from fat) and determine if exercise attenuates the PPL response. Sedentary, female Yucatan miniature swine (n = 10) completed 3 PPL trials: (1) pre diet (PRE); (2) post HFC diet (POST); and (3) post HFC diet plus exercise (EX, 45 minutes at 75% heart rate maximum). Blood samples were collected before (0 hour) and at 2, 4, 6, and 8 hours after the single HFC meal for PPL analysis. Postheparin lipoprotein lipase (LPL) activity was assessed at 8 hours. While fasting LPL activity was significantly increased with the HFC diet, the PPL response to the HFC meal did not differ depending on diet. Furthermore, the PPL response was not significantly altered with a single session of exercise, perhaps because of the severity of the HFC meal, the sedentary nature of the swine, or because LPL activity was not elevated after exercise. These findings suggest that administration of a HFC meal of this magnitude (approximately 3,000 kcal, 1,300 kcal from fat) will promote significant elevations in postprandial triglyceride (TG) concentrations, overwhelm the adaptive response to a HFC diet (elevated LPL activity), and attenuate the beneficial effects of a single exercise session on this system. Copyright 2004 Elsevier Inc.

Dengue Virus Selectively Annexes Endoplasmic Reticulum-Associated Translation Machinery as a Strategy for Co-opting Host Cell Protein Synthesis.

PubMed

Reid, David W; Campos, Rafael K; Child, Jessica R; Zheng, Tianli; Chan, Kitti Wing Ki; Bradrick, Shelton S; Vasudevan, Subhash G; Garcia-Blanco, Mariano A; Nicchitta, Christopher V

2018-04-01

A primary question in dengue virus (DENV) biology is the molecular strategy for recruitment of host cell protein synthesis machinery. Here, we combined cell fractionation, ribosome profiling, and transcriptome sequencing (RNA-seq) to investigate the subcellular organization of viral genome translation and replication as well as host cell translation and its response to DENV infection. We report that throughout the viral life cycle, DENV plus- and minus-strand RNAs were highly partitioned to the endoplasmic reticulum (ER), identifying the ER as the primary site of DENV translation. DENV infection was accompanied by an ER compartment-specific remodeling of translation, where ER translation capacity was subverted from host transcripts to DENV plus-strand RNA, particularly at late stages of infection. Remarkably, translation levels and patterns in the cytosol compartment were only modestly affected throughout the experimental time course of infection. Comparisons of ribosome footprinting densities of the DENV plus-strand RNA and host mRNAs indicated that DENV plus-strand RNA was only sparsely loaded with ribosomes. Combined, these observations suggest a mechanism where ER-localized translation and translational control mechanisms, likely cis encoded, are used to repurpose the ER for DENV virion production. Consistent with this view, we found ER-linked cellular stress response pathways commonly associated with viral infection, namely, the interferon response and unfolded protein response, to be only modestly activated during DENV infection. These data support a model where DENV reprograms the ER protein synthesis and processing environment to promote viral survival and replication while minimizing the activation of antiviral and proteostatic stress response pathways. IMPORTANCE DENV, a prominent human health threat with no broadly effective or specific treatment, depends on host cell translation machinery for viral replication, immune evasion, and virion biogenesis. The molecular mechanism by which DENV commandeers the host cell protein synthesis machinery and the subcellular organization of DENV replication and viral protein synthesis is poorly understood. Here, we report that DENV has an almost exclusively ER-localized life cycle, with viral replication and translation largely restricted to the ER. Surprisingly, DENV infection largely affects only ER-associated translation, with relatively modest effects on host cell translation in the cytosol. DENV RNA translation is very inefficient, likely representing a strategy to minimize disruption of ER proteostasis. Overall these findings demonstrate that DENV has evolved an ER-compartmentalized life cycle; thus, targeting the molecular signatures and regulation of the DENV-ER interaction landscape may reveal strategies for therapeutic intervention. Copyright © 2018 American Society for Microbiology.

Evaluation of Optogenetic Electrophysiology Tools in Human Stem Cell-Derived Cardiomyocytes.

PubMed

Björk, Susann; Ojala, Elina A; Nordström, Tommy; Ahola, Antti; Liljeström, Mikko; Hyttinen, Jari; Kankuri, Esko; Mervaala, Eero

2017-01-01

Current cardiac drug safety assessments focus on hERG channel block and QT prolongation for evaluating arrhythmic risks, whereas the optogenetic approach focuses on the action potential (AP) waveform generated by a monolayer of human cardiomyocytes beating synchronously, thus assessing the contribution of several ion channels on the overall drug effect. This novel tool provides arrhythmogenic sensitizing by light-induced pacing in combination with non-invasive, all-optical measurements of cardiomyocyte APs and will improve assessment of drug-induced electrophysiological aberrancies. With the help of patch clamp electrophysiology measurements, we aimed to investigate whether the optogenetic modifications alter human cardiomyocytes' electrophysiology and how well the optogenetic analyses perform against this gold standard. Patch clamp electrophysiology measurements of non-transduced stem cell-derived cardiomyocytes compared to cells expressing the commercially available optogenetic constructs Optopatch and CaViar revealed no significant changes in action potential duration (APD) parameters. Thus, inserting the optogenetic constructs into cardiomyocytes does not significantly affect the cardiomyocyte's electrophysiological properties. When comparing the two methods against each other (patch clamp vs. optogenetic imaging) we found no significant differences in APD parameters for the Optopatch transduced cells, whereas the CaViar transduced cells exhibited modest increases in APD-values measured with optogenetic imaging. Thus, to broaden the screen, we combined optogenetic measurements of membrane potential and calcium transients with contractile motion measured by video motion tracking. Furthermore, to assess how optogenetic measurements can predict changes in membrane potential, or early afterdepolarizations (EADs), cells were exposed to cumulating doses of E-4031, a hERG potassium channel blocker, and drug effects were measured at both spontaneous and paced beating rates (1, 2 Hz). Cumulating doses of E-4031 produced prolonged APDs, followed by EADs and drug-induced quiescence. These observations were corroborated by patch clamp and contractility measurements. Similar responses, although more modest were seen with the I Ks potassium channel blocker JNJ-303. In conclusion, optogenetic measurements of AP waveforms combined with optical pacing compare well with the patch clamp gold standard. Combined with video motion contractile measurements, optogenetic imaging provides an appealing alternative for electrophysiological screening of human cardiomyocyte responses in pharmacological efficacy and safety testings.

Evaluation of Optogenetic Electrophysiology Tools in Human Stem Cell-Derived Cardiomyocytes

PubMed Central

Björk, Susann; Ojala, Elina A.; Nordström, Tommy; Ahola, Antti; Liljeström, Mikko; Hyttinen, Jari; Kankuri, Esko; Mervaala, Eero

2017-01-01

Current cardiac drug safety assessments focus on hERG channel block and QT prolongation for evaluating arrhythmic risks, whereas the optogenetic approach focuses on the action potential (AP) waveform generated by a monolayer of human cardiomyocytes beating synchronously, thus assessing the contribution of several ion channels on the overall drug effect. This novel tool provides arrhythmogenic sensitizing by light-induced pacing in combination with non-invasive, all-optical measurements of cardiomyocyte APs and will improve assessment of drug-induced electrophysiological aberrancies. With the help of patch clamp electrophysiology measurements, we aimed to investigate whether the optogenetic modifications alter human cardiomyocytes' electrophysiology and how well the optogenetic analyses perform against this gold standard. Patch clamp electrophysiology measurements of non-transduced stem cell-derived cardiomyocytes compared to cells expressing the commercially available optogenetic constructs Optopatch and CaViar revealed no significant changes in action potential duration (APD) parameters. Thus, inserting the optogenetic constructs into cardiomyocytes does not significantly affect the cardiomyocyte's electrophysiological properties. When comparing the two methods against each other (patch clamp vs. optogenetic imaging) we found no significant differences in APD parameters for the Optopatch transduced cells, whereas the CaViar transduced cells exhibited modest increases in APD-values measured with optogenetic imaging. Thus, to broaden the screen, we combined optogenetic measurements of membrane potential and calcium transients with contractile motion measured by video motion tracking. Furthermore, to assess how optogenetic measurements can predict changes in membrane potential, or early afterdepolarizations (EADs), cells were exposed to cumulating doses of E-4031, a hERG potassium channel blocker, and drug effects were measured at both spontaneous and paced beating rates (1, 2 Hz). Cumulating doses of E-4031 produced prolonged APDs, followed by EADs and drug-induced quiescence. These observations were corroborated by patch clamp and contractility measurements. Similar responses, although more modest were seen with the IKs potassium channel blocker JNJ-303. In conclusion, optogenetic measurements of AP waveforms combined with optical pacing compare well with the patch clamp gold standard. Combined with video motion contractile measurements, optogenetic imaging provides an appealing alternative for electrophysiological screening of human cardiomyocyte responses in pharmacological efficacy and safety testings. PMID:29163220

Customizing Therapies for Lung Cancer | Center for Cancer Research

Cancer.gov

Lung cancer is the leading cause of cancer-related death in both men and women. Although there have been modest improvements in short-term survival over the last few decades, five-year survival rates for lung cancer remain low at only 16 percent. Treatment for lung cancer depends on the stage of the disease at diagnosis, but generally consists of some combination of surgery,

Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms for HIV-1 Prevention: A Randomized Trial.

PubMed

Baden, Lindsey R; Karita, Etienne; Mutua, Gaudensia; Bekker, Linda-Gail; Gray, Glenda; Page-Shipp, Liesl; Walsh, Stephen R; Nyombayire, Julien; Anzala, Omu; Roux, Surita; Laher, Fatima; Innes, Craig; Seaman, Michael S; Cohen, Yehuda Z; Peter, Lauren; Frahm, Nicole; McElrath, M Juliana; Hayes, Peter; Swann, Edith; Grunenberg, Nicole; Grazia-Pau, Maria; Weijtens, Mo; Sadoff, Jerry; Dally, Len; Lombardo, Angela; Gilmour, Jill; Cox, Josephine; Dolin, Raphael; Fast, Patricia; Barouch, Dan H; Laufer, Dagna S

2016-03-01

A prophylactic HIV-1 vaccine is a global health priority. To assess a novel vaccine platform as a prophylactic HIV-1 regimen. Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149). United States, East Africa, and South Africa. Healthy adults without HIV infection. 2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26.EnvA] and adenovirus serotype 35 with an HIV-1 envelope A insert [Ad35.Env], both administered at a dose of 5 × 1010 viral particles) in homologous and heterologous combinations. Safety and immunogenicity and the effect of baseline vector immunity. 217 participants received at least 1 vaccination, and 210 (>96%) completed follow-up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30-300 to 3000). The heterologous regimen of Ad26-Ad35 elicited significantly higher EnvA antibody titers than Ad35-Ad26. T-cell responses were modest and lower in East Africa than in South Africa and the United States. Because the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown. Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response. International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland.

Influence of adenovirus and MVA vaccines on the breadth and hierarchy of T cell responses.

PubMed

Rollier, Christine S; Hill, Adrian V S; Reyes-Sandoval, Arturo

2016-08-31

Viral-vectored vaccines are in clinical development for several infectious diseases where T-cell responses can mediate protection, and responses to sub-dominant epitopes is needed. Little is known about the influence of MVA or adenoviral vectors on the hierarchy of the dominant and sub-dominant T-cell epitopes. We investigated this aspect in mice using a malaria immunogen. Our results demonstrate that the T-cell hierarchy is influenced by the timing of analysis, rather than by the vector after a single immunization, with hierarchy changing over time. Repeated homologous immunization reduced the breadth of responses, while heterologous prime-boost induced the strongest response to the dominant epitope, albeit with only modest response to the sub-dominant epitopes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of IV Acetaminophen on Core Body Temperature and Hemodynamic Responses in Febrile Critically Ill Adults: A Randomized Controlled Trial.

PubMed

Schell-Chaple, Hildy M; Liu, Kathleen D; Matthay, Michael A; Sessler, Daniel I; Puntillo, Kathleen A

2017-07-01

To determine the effects of IV acetaminophen on core body temperature, blood pressure, and heart rate in febrile critically ill patients. Randomized, double-blind, placebo-controlled clinical trial. Three adult ICUs at a large, urban, academic medical center. Forty critically ill adults with fever (core temperature, ≥ 38.3°C). An infusion of acetaminophen 1 g or saline placebo over 15 minutes. Core temperature and vital signs were measured at baseline and at 5-15-minute intervals for 4 hours after infusion of study drug. The primary outcome was time-weighted average core temperature adjusted for baseline temperature. Secondary outcomes included adjusted time-weighted average heart rate, blood pressure, and respiratory rate, along with changes-over-time for each. Baseline patient characteristics were similar in those given acetaminophen and placebo. Patients given acetaminophen had an adjusted time-weighted average temperature that was 0.47°C less than those given placebo (95% CI, -0.76 to -0.18; p = 0.002). The acetaminophen group had significantly lower adjusted time-weighted average systolic blood pressure (-17 mm Hg; 95% CI, -25 to -8; p < 0.001), mean arterial pressure (-7 mm Hg; 95% CI, -12 to -1; p = 0.02), and heart rate (-6 beats/min; 95% CI, -10 to -1; p = 0.03). Changes-over-time temperature, blood pressure, and heart rate outcomes were also significantly lower at 2 hours, but not at 4 hours. Among febrile critically ill adults, treatment with acetaminophen decreased temperature, blood pressure, and heart rate. IV acetaminophen thus produces modest fever reduction in critical care patients, along with clinically important reductions in blood pressure.

Heart rate, rate-pressure product, and oxygen uptake during four sexual activities.

PubMed

Bohlen, J G; Held, J P; Sanderson, M O; Patterson, R P

1984-09-01

Heart rate, rate-pressure product, and VO2 were measured in ten healthy men during four specified sexual activities: coitus with husband on top, coitus with wife on top, noncoital stimulation of husband by wife, and self-stimulation by husband. Foreplay generated slight, but statistically significant, increases above resting baseline in cardiac and metabolic variables. From stimulation through orgasm, average effort was modest for relatively short spans. Maximum exercise values occurred during the brief spans of orgasm, then returned quickly to near baseline levels. The two noncoital activities required lower expenditures than the two coital positions, with man-on-top coitus rating the highest. Large variations among subjects and among activities discourage use of a general equivalent activity for comparison, such as "two flights of stairs," to represent "sexual activity."

High-dose interleukin2 - a 10-year single-site experience in the treatment of metastatic renal cell carcinoma: careful selection of patients gives an excellent outcome.

PubMed

Chow, S; Galvis, V; Pillai, M; Leach, R; Keene, E; Spencer-Shaw, A; Shablak, A; Shanks, J; Liptrot, T; Thistlethwaite, F; Hawkins, R E

2016-01-01

VEGF-targeted therapy has become the mainstay of treatment for majority of mRCC patients. For most patients, benefit is short-lived and therefore treatment remains palliative in intent. HD IL2 is an effective immunotherapy treatment capable of durable remission in some patients but its unselected use has been difficult due to its modest response rate and considerable adverse effects. Using set pathology criteria as a selection tool in clinical practice, we have been able to show improved outcomes in our previous report. Here, we present an updated and extended report of this treatment and seek to explore any pathological, clinical and treatment variables likely to predict better outcomes. This is an extension of a previously reported clinical audit, which includes mRCC cases treated with HD IL2 between 2003 and 2013. Since 2006, tumour specimens of potential candidates were routinely reviewed prospectively and stratified into Favourable or Other categories based on constitution of histological growth pattern, namely alveolar or solid versus papillary and/or sarcomatoid architecture; clear cell versus granular cell cytoplasmic morphology. HD IL2 was preferentially offered to patients with Favourable pathology. Outcome evaluation includes response rates, survival, and treatment tolerance. Multivariate analysis was performed to explore potential prognostic and predictive factors. Among prospectively selected patients with Favourable pathology ( n  = 106), overall response rate was 48.1 % (51/106) with CR rate of 21.6 % (23/106). Median OS was 58.1 months. Factors associated with significantly better response and/or survival includes favourable pathology pattern, higher cycle 1 tolerance and lower number of metastatic organ sites (<3). CAIX (Carbonic anhydrase 9) has prognostic value but is not predictive of response. Toxicities were those expected of IL2 but were manageable on general medical wards, with no treatment-related death. Importantly most complete responses were durable with 76 % (23/30) cases remained relapse-free (median 39 months follow up) and 2 of the seven who relapsed had had long-term disease free survival after resection of oligometastatic relapse. Our experience shows that HD IL2 remains an effective and safe treatment in well-selected cases of mRCC. The result in this single-institution patient series confirms similar outcomes to our previously reported retrospective series. Given the prospect of long-term remission, fit patients with Favourable histology and low disease burden should be considered for HD IL2 in an experienced centre. Better understanding has been gained from this in-depth analysis especially the examination of possible response predictors and strategies that can improve treatment outcome.

Influence of Modest Endotoxemia on Postoperative Antithrombin Deficiency and Circulating Secretory Immunoglobulin A Levels

PubMed Central

Fujita, Tetsuji; Imai, Takashi; Anazawa, Sadao

2003-01-01

Objective: To evaluate the influence of modest endotoxemia on postoperative antithrombin deficiency and cholestasis. Summary Background Data: It has not been determined whether endotoxin translocation in small amounts is a physiological phenomenon or whether it is a potential health hazard. Methods: Blood endotoxin, antithrombin III (ATIII), secretory immunoglobulin A (sIgA), which was selected as a marker of cholestasis, C-reactive protein (CRP), and α-1-antitrypsin (AAT) concentrations were measured from the 20 patients undergoing curative gastrectomy for gastric cancer preoperatively and postoperatively. Portal and systemic blood samples were taken for the analysis of endotoxin and interleukin-6 (IL-6) concentrations during surgery in these patients. Results: Although plasma endotoxin levels showed a significant increase during surgery, we did not find a correlation with ATIII, sIgA, CRP, and IL-6 levels. Systemic blood endotoxin levels during surgery correlated with a postoperative rise of serum AAT levels. Plasma ATIII levels transiently decreased on the first and third postoperative day, and sIgA levels were shown to increase on the seventh postoperative day. There was a weak relationship between the extent of postoperative endotoxemia and a reduction in ATIII concentrations. Conclusions: The influence of modest endotoxemia on postoperative antithrombin deficiency and cholestasis was limited, and increased translocational endotoxemia during abdominal surgery may be a physiological phenomenon to trigger off an acute-phase protein response. PMID:12894020

Circulating basal anti-Müllerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization.

PubMed

Nardo, Luciano G; Gelbaya, Tarek A; Wilkinson, Hannah; Roberts, Stephen A; Yates, Allen; Pemberton, Phil; Laing, Ian

2009-11-01

To evaluate the clinical value of basal anti-Müllerian hormone (AMH) measurements compared with other available determinants, apart from chronologic age, in the prediction of ovarian response to gonadotrophin stimulation. Prospective cohort study. Tertiary referral center for reproductive medicine and an IVF unit. Women undergoing their first cycle of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Basal levels of FSH and AMH as well as antral follicle count (AFC) were measured in 165 subjects. All patients were followed prospectively and their cycle outcomes recorded. Predictive value of FSH, AMH, and AFC for extremes of ovarian response to stimulation. Out of the 165 women, 134 were defined as normal responders, 15 as poor responders, and 16 as high responders. Subjects in the poor response group were significantly older then those in the other two groups. Anti-Müllerian hormone levels and AFC were markedly raised in the high responders and decreased in the poor responders. Compared with FSH and AFC, AMH performed better in the prediction of excessive response to ovarian stimulation-AMH area under receiver operating characteristic curve (ROC(AUC)) 0.81, FSH ROC(AUC) 0.66, AFC ROC(AUC) 0.69. For poor response, AMH (ROC(AUC) 0.88) was a significantly better predictor than FSH (ROC(AUC) 0.63) but not AFC (ROC(AUC) 0.81). AMH prediction of ovarian response was independent of age and PCOS. Anti-Müllerian hormone cutoffs of >3.75 ng/mL and <1.0 ng/mL would have modest sensitivity and specificity in predicting the extremes of response. Circulating AMH has the ability to predict excessive and poor response to stimulation with exogenous gonadotrophins. Overall, this biomarker is superior to basal FSH and AFC, and has the potential to be incorporated in to work-up protocols to predict patient's ovarian response to treatment and to individualize strategies aiming at reducing the cancellation rate and the iatrogenic complications of COH.

Treatment response to the RENEW weight loss intervention in schizophrenia: Impact of intervention setting

PubMed Central

Brown, Catana; Goetz, Jeannine; Hamera, Edna; Gajewski, Byron

2014-01-01

Background Individuals with serious mental illness have high rates of obesity and a need for specialized weight loss intervention programs. This study examines the efficacy of the RENEW weight loss intervention and examines the impact of the intervention setting on outcomes. Method 136 individuals with serious mental illness from 4 different settings were randomly assigned to receive the RENEW weight loss intervention or a control condition of treatment as usual. The RENEW intervention is a one year program that includes an intensive, maintenance and intermittent supports phase. Results The intervention group experienced a modest weight loss of 4.8 lbs at 3 months, 4.1 lbs at 6 months and a slight weight gain of 1.5 lbs at 12 months. The control group gained a total of 6.2 lbs at 12 months. However when settings were examined separately the responder sites had a weight loss of 9.4 lbs at 3 months, 10.9 lbs at 6 months and 7 lbs at 12 months. Discussion These results suggest that the settings in which individuals receive services may act as a support or hindrance toward response to weight loss interventions. The concept of the obesogenic environment deserves further examination as a factor in the success of weight loss programs. PMID:25261884

Treatment response to the RENEW weight loss intervention in schizophrenia: impact of intervention setting.

PubMed

Brown, Catana; Goetz, Jeannine; Hamera, Edna; Gajewski, Byron

2014-11-01

Individuals with serious mental illness have high rates of obesity and a need for specialized weight loss intervention programs. This study examines the efficacy of the RENEW weight loss intervention and examines the impact of the intervention setting on outcomes. 136 individuals with serious mental illness from 4 different settings were randomly assigned to receive the RENEW weight loss intervention or a control condition of treatment as usual. The RENEW intervention is a one year program that includes an intensive, maintenance and intermittent supports phase. The intervention group experienced a modest weight loss of 4.8 lbs at 3 months, 4.1 lbs at 6 months and a slight weight gain of 1.5 lbs at 12 months. The control group gained a total of 6.2 lbs at 12 months. However when settings were examined separately the responder sites had a weight loss of 9.4 lbs at 3 months, 10.9 lbs at 6 months and 7 lbs at 12 months. These results suggest that the settings in which individuals receive services may act as a support or hindrance toward response to weight loss interventions. The concept of the obesogenic environment deserves further examination as a factor in the success of weight loss programs. Copyright © 2014 Elsevier B.V. All rights reserved.

Changes in snowmelt runoff timing in western North America under a 'business as usual' climate change scenario

USGS Publications Warehouse

Stewart, I.T.; Cayan, D.R.; Dettinger, M.D.

2004-01-01

Spring snowmelt is the most important contribution of many rivers in western North America. If climate changes, this contribution may change. A shift in the timing of springtime snowmelt towards earlier in the year already is observed during 1948-2000 in many western rivers. Streamflow timing changes for the 1995-2099 period are projected using regression relations between observed streamflow-timing responses in each river, measured by the temporal centroid of streamflow (CT) each year, and local temperature (TI) and precipitation (PI) indices. Under 21st century warming trends predicted by the Parallel Climate Model (PCM) under business-as-usual greenhouse-gas emissions, streamflow timing trends across much of western North America suggest even earlier springtime snowmelt than observed to date. Projected CT changes are consistent with observed rates and directions of change during the past five decades, and are strongest in the Pacific Northwest, Sierra Nevada, and Rocky Mountains, where many rivers eventually run 30-40 days earlier. The modest PI changes projected by PCM yield minimal CT changes. The responses of CT to the simultaneous effects of projected TI and PI trends are dominated by the TI changes. Regression-based CT projections agree with those from physically-based simulations of rivers in the Pacific Northwest and Sierra Nevada.

Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma.

PubMed

Reardon, David A; Norden, Andrew D; Desjardins, Annick; Vredenburgh, James J; Herndon, James E; Coan, April; Sampson, John H; Gururangan, Sridharan; Peters, Katherine B; McLendon, Roger E; Norfleet, Julie A; Lipp, Eric S; Drappatz, Jan; Wen, Patrick Y; Friedman, Henry S

2012-01-01

We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea in patients with progressive/recurrent meningioma. A total of 21 patients with progressive/recurrent meningioma were enrolled in this dual center, single-arm, phase II trial. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg/day for patients not on CYP3A enzyme inducing anti-epileptic drugs (EIAEDs) and at 500 mg twice a day for patients on EIAEDs. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary endpoints were safety, radiographic response rate, and overall survival (OS). Best radiographic response was stable disease and was observed in 14 patients (67%). PFS-6 for all patients, those with grade I tumors (n = 8) and those with grade II or III tumors (n = 13) was 61.9, 87.5 and 46.2%, respectively. Patients with grade II or III tumors had poorer PFS and OS than those with grade I tumors, (P = 0.025 and P = 0.018) respectively. The only grade 3 or greater adverse event occurring in ≥ 10% of patients was anemia (10%). Imatinib plus hydroxyurea is well tolerated among patients with meningioma but has modest anti-tumor activity for this indication.

Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma

PubMed Central

Norden, Andrew D.; Desjardins, Annick; Vredenburgh, James J.; Herndon, James E.; Coan, April; Sampson, John H.; Gururangan, Sridharan; Peters, Katherine B.; McLendon, Roger E.; Norfleet, Julie A.; Lipp, Eric S.; Drappatz, Jan; Wen, Patrick Y.; Friedman, Henry S.

2011-01-01

We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea in patients with progressive/recurrent meningioma. A total of 21 patients with progressive/recurrent meningioma were enrolled in this dual center, single-arm, phase II trial. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg/day for patients not on CYP3A enzyme inducing anti-epileptic drugs (EIAEDs) and at 500 mg twice a day for patients on EIAEDs. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary endpoints were safety, radiographic response rate, and overall survival (OS). Best radiographic response was stable disease and was observed in 14 patients (67%). PFS-6 for all patients, those with grade I tumors (n = 8) and those with grade II or III tumors (n = 13) was 61.9, 87.5 and 46.2%, respectively. Patients with grade II or III tumors had poorer PFS and OS than those with grade I tumors, (P = 0.025 and P = 0.018) respectively. The only grade 3 or greater adverse event occurring in ≥10% of patients was anemia (10%). Imatinib plus hydroxyurea is well tolerated among patients with meningioma but has modest anti-tumor activity for this indication. PMID:21938530

The evolving landscape of therapeutic drug development for hepatocellular carcinoma.

PubMed

Chong, Dawn Qingqing; Tan, Iain Beehuat; Choo, Su-Pin; Toh, Han Chong

2013-11-01

Currently, only one drug, sorafenib, is FDA approved for the treatment of advanced hepatocellular carcinoma (HCC), achieving modest objective response rates while still conferring an overall survival benefit. Unlike other solid tumors, no oncogenic addiction loops have been validated as clinically actionable targets in HCC. Outcomes of HCC could potentially be improved if critical molecular subclasses with distinct therapeutic vulnerabilities can be identified, biomarkers that predict recurrence or progression early can be determined and key epigenetic, genetic or microenvironment drivers that determine best response to a specific targeting treatment can be uncovered. Our group and others have examined the molecular heterogeneity of hepatocellular carcinoma. We have developed a panel of patient derived xenograft models to enable focused pre-clinical drug development of rationally designed therapies in specific molecular subgroups. We observed unique patterns, including synergies, of drug activity across our molecularly diverse HCC xenografts, pointing to specific therapeutic vulnerabilities for individual tumors. These efforts inform clinical trial designs and catalyze therapeutic development. It also argues for efficient strategic allocation of patients into appropriate enriched clinical trials. Here, we will discuss some of the recent important therapeutic studies in advanced HCC and also some of the potential strategies to optimize clinical therapeutic development moving forward. Copyright © 2013 Elsevier Inc. All rights reserved.

Infliximab therapy in pediatric patients 7 years of age and younger.

PubMed

Kelsen, Judith R; Grossman, Andrew B; Pauly-Hubbard, Helen; Gupta, Kernika; Baldassano, Robert N; Mamula, Petar

2014-12-01

Infliximab (IFX) is efficacious for induction and maintenance of remission in pediatric patients with moderate-to-severe inflammatory bowel disease (IBD). It has, however, not been studied in patients 7 years old and younger. Our aim was to characterize efficacy and safety of IFX therapy in this cohort. This was a retrospective study of patients with IBD ages 7 years and younger, treated with IFX between 1999 and 2011. Medical records were reviewed for age of diagnosis, disease phenotype, therapy, surgery, IFX infusion dates, dose, and intervals. Outcome measures included physician global assessment, corticosteroid requirement, and adverse events. Thirty-three children (ages 2.4-7 years) were included. Twenty patients had Crohn disease, 4 had ulcerative colitis, and 9 had indeterminate colitis. Maintenance of IFX therapy at 1, 2, and 3 years was 36%, 18%, and 12%, respectively. Patients of age 5 years and younger had the lowest rates of maintenance of therapy at 25% at year 1, and 10% at years 2 and 3 combined. Nine percent of all of the patients demonstrated response measured by the physician global assessment and were steroid free at 1 year. There were 8 infusion reactions. There were no malignancies, serious infections, or deaths. IFX demonstrated a modest response rate and a low steroid-sparing effect in patients with IBD 7 years old and younger. Although this is a limited study, there appears to be a trend for decreased sustained efficacy with IFX in this age group, particularly in children 5 years old and younger, when compared with the previously published literature in older children.

Commentary: deconstructing gender difference.

PubMed

Carnes, Molly

2010-04-01

In Japan, as in the United States, a growing proportion of physicians are women. Hence, the different social roles that men and women occupy and the gendered norms for behavior are increasingly relevant in ensuring that male and female physicians have equal opportunity to participate and advance in all aspects of medicine. Elsewhere in this issue, Nomura and colleagues report on a large survey of primary care residents in Japan. They found that on average women's self-rated confidence on many clinical tasks was lower than men's. This is not surprising given similar gender differences in self-assessed competence in other research and the socialization of women in virtually all cultures to be modest. The actual differences in average scores were small suggesting considerable overlap in the distributions of responses from male and female residents. In addition, research from other countries finds no association between physicians' self-reported confidence in clinical tasks and objective measures of competence on which female physicians rate at or above the level of their male counterparts. Congruent with different social roles for men and women, Nomura and colleagues also found gender differences in the average responses about work-family priorities and aspirations toward leadership, but some women indicated a desire for research careers and some men were "life-oriented." The author of this commentary argues that to draw conclusions about all male or all female physicians from average differences of a large group of residents may reinforce gender stereotypes that continue to impede each individual female physician's career advancement and each individual male physician's struggle for work-life balance.

Effects of pesticide applications and cultural controls on efficacy of control for adult Japanese beetles (Coleoptera: Scarabaeidae) on roses.

PubMed

Vitullo, Justin M; Sadof, Clifford S

2007-02-01

Cultural and chemical controls were evaluated to determine their ability to deter feeding by Japanese beetles, Popillia japonica Newman (Coleoptera: Scarabaeidae), on floribunda type roses, Rosa 'Acadia Sunrise'. Roses were arranged in field plots and exposed to resident adult beetle populations. Cultural controls were designed to block the feeding-induced aggregation response by manually removing beetles and/ or damaged blooms from rose plants. Azadirachtin, carbaryl, and imidacloprid were evaluated in field and laboratory trials. In no-choice laboratory assays, foliar applications of azadirachtin caused low rates of morbidity to adult beetles and were unable to deter feeding. Foliar-applied carbaryl and soil-applied imidacloprid caused high rates of morbidity and reduced feeding injury. In the field, foliar sprays of azadirachtin and carbaryl, deterred feeding on foliage under low beetle pressure (maximum of 29% defoliation in untreated controls), when applied weekly after first beetle flight or every 2 wk after 5% injury was reached. A single foliar application of these materials at the 5% injury level did not significantly reduce peak defoliation. Soil applications of imidacloprid also deterred foliar feeding in the field. Blooms were more difficult to protect with both foliar- and soil-applied insecticides with only weekly application of foliar insecticides providing significant reductions in bloom injury. Removing beetles and/or blooms provided marginally greater reductions in leaf and flower injury. This suggests that blocking the feeding-induced aggregation response of Japanese beetles can provide only modest levels of control in roses where both flowers and feeding-induced volatiles recruit beetles to plants.

MDMA: a social drug in a social context.

PubMed

Kirkpatrick, Matthew G; de Wit, Harriet

2015-03-01

The drug ±3,4-methylenedioxymethamphetamine (MDMA, "ecstasy," "molly") is thought to produce prosocial effects and enhance social interaction. However, in most laboratory studies to date, the participants have been tested under nonsocial conditions, which may not simulate the effects the drug produces in more naturalistic social settings. Healthy experienced MDMA users participated in three laboratory sessions in which they received MDMA (0.5 or 1.0 mg/kg or placebo, double blind). They were randomly assigned to one of three social conditions, in which they were tested alone (solitary (SOL); N = 10), in the presence of a research assistant (research assistant present (RAP); N = 11) or in the presence of another participant who also received the drug (other participant present (OPP); N = 11). As expected, MDMA increased heart rate and blood pressure and produced positive subjective effects in all the three groups. It also increased ratings of attractiveness of another person and increased social interaction in RAP and OPP. The social context affected certain responses to the drug. The effects of MDMA were greater in the OPP condition, compared to the SOL or RAP conditions, on measures of "feel drug," "dizzy," and on cardiovascular. But responses to the drug on other measures, including social behavior, did not differ across the conditions. These findings provide some support for the idea that drugs produce greater effects when they are used in the presence of other drug users. However, the influence of the social context was modest, and it remains to be determined whether other variables related to social context would substantially alter the effects of MDMA or other drugs.

Comparison of acalabrutinib, a selective Bruton tyrosine kinase inhibitor, with ibrutinib in chronic lymphocytic leukemia cells

PubMed Central

Patel, Viralkumar; Balakrishnan, Kumudha; Bibikova, Elena; Ayres, Mary; Keating, Michael J.; Wierda, William G.; Gandhi, Varsha

2017-01-01

Purpose Ibrutinib inhibits Bruton tyrosine kinase (BTK) by irreversibly binding to the Cys-481 residue in the enzyme. However, ibrutinib also inhibits several other enzymes that contain cysteine residues homologous to Cys-481 in BTK. Patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL) demonstrate a high overall response rate to ibrutinib with prolonged survival. Acalabrutinib, a selective BTK inhibitor developed to minimize off-target activity, has shown promising overall response rates in patients with relapsed/refractory CLL. A head-to-head comparison of ibrutinib and acalabrutinib in CLL cell cultures and healthy T cells is needed to understand preclinical biologic and molecular effects. Experimental Design Using samples from patients with CLL, we compared the effects of both BTK inhibitors on biologic activity, chemokine production, cell migration, BTK phosphorylation, and downstream signaling in primary CLL lymphocytes and on normal T-cell signaling to determine effects on other kinases. Results Both BTK inhibitors induced modest cell death accompanied by cleavage of PARP and caspase 3. Production of CCL3 and CCL4 chemokines and pseudoemperipolesis were inhibited by both drugs to a similar degree. These drugs also showed similar inhibitory effects on phosphorylation of BTK and downstream S6 and ERK kinases. By contrast, off-target effects on SRC-family kinases were more pronounced with ibrutinib than acalabrutinib in healthy T lymphocytes. Conclusion Both BTK inhibitors show similar biological and molecular profile in primary CLL cells but appear different on their effect on normal T-cells. PMID:28034907

Adult Blood Lead Levels in Minnesota: Rates and Trends, 2005-2012.

PubMed

Landsteiner, Adrienne; Yendell, Stephanie; Lindgren, Paula; Olson, Larry; Williams, Allan

2016-01-01

Lead exposure is associated with a number of adverse health events including peripheral neuropathy, anemia, renal damage and cognitive impairment. The vast majority of adult lead exposures occur in the workplace. By statute, all results from blood lead level (BLL) tests performed in Minnesota are submitted to the Minnesota Department of Health for surveillance purposes. We analyzed that data to examine lead exposure trends from 2005 through 2012. We found that an average of 548 persons 16 years of age and older had a BLL greater than 10 μg/dL each year during that period. Analysis of the prevalence rate of elevated BLLs among adults for the years 2005-2012 showed a modest, nonsignificant decline among those with BLLs greater than 1O μg/dL. Much has been done to reduce exposures and BLLs among young children. However, the policies and standards that protect workers have not been similarly adjusted, and many workers remain at risk of exposure. Although OSHA is responsible for developing and implementing policies and standards to protect workers, health care providers can play a critical role in identifying cases of lead exposure by asking patients about their occupation and industry. Those working in high-risk industries should be tested to determine whether they have been exposed and intervention is warranted.

Differences in Patient Experience Between Hispanic and Non-Hispanic White Patients Across U.S. Hospitals.

PubMed

Figueroa, Jose F; Reimold, Kimberly E; Zheng, Jie; Orav, Endel John

2017-12-15

Despite the increased emphasis on patient experience, little is known about whether there are meaningful differences in hospital satisfaction between Hispanic and non-Hispanic whites. To determine if satisfaction differs, we used Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey data (2009-2010) reported by hospitals to compare responses between Hispanic and non-Hispanic white patients. Clustered logistic regression models identified within-hospital and between-hospital differences in satisfaction. Of the 3,864,938 respondents, 6.2% were Hispanics, who were more often younger and females and less likely to have graduated from high school. Hispanics were overall more likely to recommend their hospital (74.1% vs. 70.9%, p < .001) and to rate it 9 or 10 (72.5% vs. 65.9%, p < .001) than whites. Increased satisfaction among Hispanics was more pronounced when compared with whites within the same hospitals, with significantly higher ratings on all HCAHPS measures. However, hospitals serving a higher percentage of Hispanics had lower satisfaction scores for both Hispanic and white patients than other hospitals. There were significant but only modest-sized differences in patient experience between Hispanic and white patients across U.S. hospitals. Hispanics tended to be more satisfied with their care but received care at lower-performing hospitals.

A mutli-omic systems approach to elucidating Yersinia virulence mechanisms

PubMed Central

Ansong, Charles; Schrimpe-Rutledge, Alexandra C.; Mitchell, Hugh; Chauhan, Sadhana; Jones, Marcus B.; Kim, Young-Mo; McAteer, Kathleen; Deatherage Kaiser, Brooke L.; Dubois, Jennifer L.; Brewer, Heather M.; Frank, Bryan C.; McDermott, Jason E.; Metz, Thomas O.; Peterson, Scott N.; Smith, Richard D.; Motin, Vladimir L.; Adkins, Joshua N.

2012-01-01

The underlying mechanisms that lead to dramatic differences between closely related pathogens are not always readily apparent. For example, the genomes of Yersinia pestis (YP) the causative agent of plague with a high mortality rate and Yersinia pseudotuberculosis (YPT) an enteric pathogen with a modest mortality rate are highly similar with some species specific differences; however the molecular causes of their distinct clinical outcomes remain poorly understood. In this study, a temporal multi-omic analysis of YP and YPT at physiologically relevant temperatures was performed to gain insights into how an acute and highly lethal bacterial pathogen, YP, differs from its less virulent progenitor, YPT. This analysis revealed higher gene and protein expression levels of conserved major virulence factors in YP relative to YPT, including the Yop virulon and the pH6 antigen. This suggests that adaptation in the regulatory architecture, in addition to the presence of unique genetic material, may contribute to the increased pathogenenicity of YP relative to YPT. Additionally, global transcriptome and proteome responses of YP and YPT revealed conserved post-transcriptional control of metabolism and the translational machinery including the modulation of glutamate levels in Yersiniae. Finally, the omics data was coupled with a computational network analysis, allowing an efficient prediction of novel Yersinia virulence factors based on gene and protein expression patterns. PMID:23147219

Shape Optimization of Cylindrical Shell for Interior Noise

NASA Technical Reports Server (NTRS)

Robinson, Jay H.

1999-01-01

In this paper an analytic method is used to solve for the cross spectral density of the interior acoustic response of a cylinder with nonuniform thickness subjected to turbulent boundary layer excitation. The cylinder is of honeycomb core construction with the thickness of the core material expressed as a cosine series in the circumferential direction. The coefficients of this series are used as the design variable in the optimization study. The objective function is the space and frequency averaged acoustic response. Results confirm the presence of multiple local minima as previously reported and demonstrate the potential for modest noise reduction.

Predicting the effects of climate change on ecosystems and wildlife habitat in northwest Alaska: results from the WildCast project

Treesearch

Anthony R. DeGange; Bruce G. Marcot; James Lawler; Torre Jorgenson; Robert Winfree

2013-01-01

We used a modeling framework and a recent ecological land classification and land cover map to predict how ecosystems and wildlife habitat in northwest Alaska might change in response to increasing temperature. Our results suggest modest increases in forest and tall shrub ecotypes in Northwest Alaska by the end of this century thereby increasing habitat for forest-...

The impact of skin colour on human photobiological responses.

PubMed

Fajuyigbe, Damilola; Young, Antony R

2016-11-01

Terrestrial solar ultraviolet radiation (UVR) exerts both beneficial and adverse effects on human skin. Epidemiological studies show a lower incidence of skin cancer in people with pigmented skins compared to fair skins. This is attributed to photoprotection by epidermal melanin, as is the poorer vitamin D status of those with darker skins. We summarize a wide range of photobiological responses across different skin colours including DNA damage and immunosuppression. Some studies show the generally modest photoprotective properties of melanin, but others show little or no effect. DNA photodamage initiates non-melanoma skin cancer and is reduced by a factor of about 3 in pigmented skin compared with white skin. This suggests that if such a modest reduction in DNA damage can result in the significantly lower skin cancer incidence in black skin, the use of sunscreen protection might be extremely beneficial for susceptible population. Many contradictory results may be explained by protocol differences, including differences in UVR spectra and exposure protocols. We recommend that skin type comparisons be done with solar-simulated radiation and standard erythema doses or physical doses (J/m 2 ) rather than those based solely on clinical endpoints such as minimal erythema dose (MED). © 2016 The Authors. Pigment Cell & Melanoma Research Published by John Wiley & Sons Ltd.

Generation of insulin-producing cells from human bone marrow-derived mesenchymal stem cells: comparison of three differentiation protocols.

PubMed

Gabr, Mahmoud M; Zakaria, Mahmoud M; Refaie, Ayman F; Khater, Sherry M; Ashamallah, Sylvia A; Ismail, Amani M; El-Badri, Nagwa; Ghoneim, Mohamed A

2014-01-01

Many protocols were utilized for directed differentiation of mesenchymal stem cells (MSCs) to form insulin-producing cells (IPCs). We compared the relative efficiency of three differentiation protocols. Human bone marrow-derived MSCs (HBM-MSCs) were obtained from three insulin-dependent type 2 diabetic patients. Differentiation into IPCs was carried out by three protocols: conophylline-based (one-step protocol), trichostatin-A-based (two-step protocol), and β -mercaptoethanol-based (three-step protocol). At the end of differentiation, cells were evaluated by immunolabeling for insulin production, expression of pancreatic endocrine genes, and release of insulin and c-peptide in response to increasing glucose concentrations. By immunolabeling, the proportion of generated IPCs was modest ( ≃ 3%) in all the three protocols. All relevant pancreatic endocrine genes, insulin, glucagon, and somatostatin, were expressed. There was a stepwise increase in insulin and c-peptide release in response to glucose challenge, but the released amounts were low when compared with those of pancreatic islets. The yield of functional IPCs following directed differentiation of HBM-MSCs was modest and was comparable among the three tested protocols. Protocols for directed differentiation of MSCs need further optimization in order to be clinically meaningful. To this end, addition of an extracellular matrix and/or a suitable template should be attempted.

Does adding clinical data to administrative data improve agreement among hospital quality measures?

PubMed

Hanchate, Amresh D; Stolzmann, Kelly L; Rosen, Amy K; Fink, Aaron S; Shwartz, Michael; Ash, Arlene S; Abdulkerim, Hassen; Pugh, Mary Jo V; Shokeen, Priti; Borzecki, Ann

2017-09-01

Hospital performance measures based on patient mortality and readmission have indicated modest rates of agreement. We examined if combining clinical data on laboratory tests and vital signs with administrative data leads to improved agreement with each other, and with other measures of hospital performance in the nation's largest integrated health care system. We used patient-level administrative and clinical data, and hospital-level data on quality indicators, for 2007-2010 from the Veterans Health Administration (VA). For patients admitted for acute myocardial infarction (AMI), heart failure (HF) and pneumonia we examined changes in hospital performance on 30-d mortality and 30-d readmission rates as a result of adding clinical data to administrative data. We evaluated whether this enhancement yielded improved measures of hospital quality, based on concordance with other hospital quality indicators. For 30-d mortality, data enhancement improved model performance, and significantly changed hospital performance profiles; for 30-d readmission, the impact was modest. Concordance between enhanced measures of both outcomes, and with other hospital quality measures - including Joint Commission process measures, VA Surgical Quality Improvement Program (VASQIP) mortality and morbidity, and case volume - remained poor. Adding laboratory tests and vital signs to measure hospital performance on mortality and readmission did not improve the poor rates of agreement across hospital quality indicators in the VA. Efforts to improve risk adjustment models should continue; however, evidence of validation should precede their use as reliable measures of quality. Published by Elsevier Inc.

The potential impact of integrated malaria transmission control on entomologic inoculation rate in highly endemic areas.

PubMed

Killeen, G F; McKenzie, F E; Foy, B D; Schieffelin, C; Billingsley, P F; Beier, J C

2000-05-01

We have used a relatively simple but accurate model for predicting the impact of integrated transmission control on the malaria entomologic inoculation rate (EIR) at four endemic sites from across sub-Saharan Africa and the southwest Pacific. The simulated campaign incorporated modestly effective vaccine coverage, bed net use, and larval control. The results indicate that such campaigns would reduce EIRs at all four sites by 30- to 50-fold. Even without the vaccine, 15- to 25-fold reductions of EIR were predicted, implying that integrated control with a few modestly effective tools can meaningfully reduce malaria transmission in a range of endemic settings. The model accurately predicts the effects of bed nets and indoor spraying and demonstrates that they are the most effective tools available for reducing EIR. However, the impact of domestic adult vector control is amplified by measures for reducing the rate of emergence of vectors or the level of infectiousness of the human reservoir. We conclude that available tools, including currently neglected methods for larval control, can reduce malaria transmission intensity enough to alleviate mortality. Integrated control programs should be implemented to the fullest extent possible, even in areas of intense transmission, using simple models as decision-making tools. However, we also conclude that to eliminate malaria in many areas of intense transmission is beyond the scope of methods which developing nations can currently afford. New, cost-effective, practical tools are needed if malaria is ever to be eliminated from highly endemic areas.

Reports of severe physical punishment and exposure to animal cruelty by inmates convicted of felonies and by university students.

PubMed

Miller, K S; Knutson, J F

1997-01-01

A self-report questionnaire designed to assess abusive childhood environments and exposure to animal cruelty was administered to 314 inmates in a prisoner classification center. Although high rates of physical punishment characterized the entire sample, persons charged with violent, but nonhomicidal crimes reported more severely punitive childhood histories than those charged with homicidal crimes, sex offenses, and nonviolent offenses. Some exposure to animal cruelty was widespread in the sample, but there was no association between experiencing animal cruelty and the type of crime committed. Moreover, there were only modest associations between animal cruelty experiences and the aversive childhood histories of the subjects, as well as the subjects' reported use of physical and sexual coercion in dating and intimate relationships. To determine whether the high base rate of exposure to animal cruelty was unique to the incarcerated sample, a follow-up study was completed with university undergraduates. Widespread exposure to some animal cruelty was reported by undergraduates; there were modest associations between reporting animal cruelty and reporting punitive and acrimonious childhood histories. In general, the findings were consistent with the hypothesis that there is an association between punitive childhood histories and antisocial behavior but not consistent with the hypothesis that exposure to animal cruelty is importantly related to antisocial behavior or child maltreatment.

Gas-fired power in the UK: Bridging supply gaps and implications of domestic shale gas exploitation for UK climate change targets.

PubMed

Turk, Jeremy K; Reay, David S; Haszeldine, R Stuart

2018-03-01

There is a projected shortcoming in the fourth carbon budget of 7.5%. This shortfall may be increased if the UK pursues a domestic shale gas industry to offset projected decreases in traditional gas supply. Here we estimate that, if the project domestic gas supply gap for power generation were to be met by UK shale gas with low fugitive emissions (0.08%), an additional 20.4MtCO 2 e 1 would need to be accommodated during carbon budget periods 3-6. We find that a modest fugitive emissions rate (1%) for UK shale gas would increase global emissions compared to importing an equal quantity of Qatari liquefied natural gas. Additionally, we estimate that natural gas electricity generation would emit 420-466MtCO 2 e (460 central estimate) during the same time period within the traded EU emissions cap. We conclude that domestic shale gas production with even a modest 1% fugitive emissions rate would risk exceedance of UK carbon budgets. We also highlight that, under the current production-based greenhouse gas accounting system, the UK is incentivized to import natural gas rather than produce it domestically. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparing Individual Differences in Inconsistency and Plasticity as Predictors of Cognitive Function in Older Adults

PubMed Central

Grand, Jacob H.G.; Stawski, Robert S.; MacDonald, Stuart W.S.

2016-01-01

Introduction Recent theorizing differentiates key constraints on cognition, including one’s current range of processing efficiency (i.e., flexibility or inconsistency) as well as the capacity to expand flexibility over time (i.e., plasticity). The present study uses intensive assessment of response time data to examine the interplay between markers of intraindividual variability (inconsistency) and gains across biweekly retest sessions (plasticity) in relation to age-related cognitive function. Method Participants included 304 adults (aged 64 to 92 years: M=74.02, SD=5.95) from Project MIND, a longitudinal burst design study assessing performance across micro and macro intervals (response latency trials, weekly bursts, annual retests). For two reaction time measures (choice RT and one-back choice RT), baseline measures of response time (RT) inconsistency (intraindividual standard deviation (ISD) across-trials at the first testing session) and plasticity (within-person performance gains in average RT across the 5 biweekly burst sessions) were computed, and then employed in linear mixed models as predictors of individual differences in cognitive function and longitudinal (6 year) rates of cognitive change. Results Independent of chronological age and years of education, higher RT inconsistency was associated uniformly with poorer cognitive function at baseline and with increased cognitive decline for measures of episodic memory and crystallized verbal ability. In contrast, predictive associations for plasticity were more modest for baseline cognitive function and were absent for 6-year cognitive change. Conclusions These findings underscore the potential utility of response times for articulating inconsistency and plasticity as dynamic predictors of cognitive function in older adults. PMID:26898536

Oxygen consumption of the chicken embryo: interaction between temperature and oxygenation.

PubMed

Mortola, Jacopo P; Labbè, Katherine

2005-03-01

We measured the effects of hypoxia and changes in ambient temperature (T) on the oxygen consumption (VO2) of chicken embryos at embryonic days 11, 16 and 20 (E11, E16 and E20, respectively), and post-hatching day 1 (H1). Between 30 and 39 degrees C, at E11 and E16, VO2 changed linearly with T, as in ectothermic animals, with a Q10 of about 2.1. At E20, VO2 did not significantly change with T, indicating the onset of endothermy. At H1, a drop in T increased VO2, a clear thermogenic response. Hypoxia (11% O2 for 30 min) decreased VO2, by an amount that varied with T and age. At H1, hypoxia lowered VO2 especially at low T. At E20, hypoxic hypometabolism was similar at all T. At E11 and E16, hypoxia lowered VO2 only at the higher T. In fact, at E11, with T=39 degrees C even a modest hypoxia (15-18% O2) decreased VO2. Upon return to normoxia after 40 min of 11% O2, VO2 did not rise above the pre-hypoxic level, indicating that the hypometabolism during hypoxia did not generate an O2 debt. At E11, during modest hypoxia (16% O2) at 36 degrees C, the drop in VO2 was lifted by raising the T to 39 degrees C, suggesting that the hypoxic hypometabolism at 36 degrees C was not due to O2-supply limitation. In conclusion, the hypometabolic effects of hypoxia on the chicken embryo's VO2 depend on the development of the thermogenic ability, occurring predominantly at high T during the early (ectothermic phase) and at low T during the late (endothermic) phase. At E11, both low T and low oxygen force VO2 to drop. However, at a near-normal T, modest hypoxia promotes a hypometabolic response with the characteristics of regulated O2 conformism.

What is the truth? An application of the Extended Parallel Process Model to televised truth® ads.

PubMed

Lavoie, Nicole R; Quick, Brian L

2013-01-01

The purpose of this study was to analyze television ads in the truth® campaign using the Extended Parallel Process Model (EPPM) as a framework. Among the ads (n = 86) analyzed, results revealed a heavy reliance on severity messages, modest attention to susceptibility messages, and no inclusion of recommended response messages in the form of self-efficacy and response efficacy. The reliance on emphasizing the health threat, without incorporating recommended response messages, is discussed with respect to the likelihood of galvanizing maladaptive responses such as psychological reactance, denial, and defensive avoidance resulting from exposure to these ads. Additionally, the unintended outcomes for secondary audiences including but not limited to stigma are considered. Implications and suggestions for practitioners and theorists are explored.

Seventeen years of statin pharmacogenetics: a systematic review.

PubMed

Leusink, Maarten; Onland-Moret, N Charlotte; de Bakker, Paul I W; de Boer, Anthonius; Maitland-van der Zee, Anke H

2016-01-01

We evaluated the evidence of pharmacogenetic associations with statins in a systematic review. Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events. In candidate gene studies, 141 loci were claimed to be associated with LDL-C response. Only 5% of these associations were positively replicated. In addition, six genome-wide association studies of LDL-C response identified common SNPs in APOE, LPA, SLCO1B1, SORT1 and ABCG2 at genome-wide significance. None of the investigated SNPs consistently affected the risk reduction for cardiovascular events. Only five genetic loci were consistently associated with LDL-C response. However, as effect sizes are modest, there is no evidence for the value of genetic testing in clinical practice.

α4-Containing nicotinic receptors contribute to the effects of perinatal nicotine on ventilatory and metabolic responses of neonatal mice to ambient cooling.

PubMed

Avraam, Joanne; Cummings, Kevin J; Frappell, Peter B

2016-10-01

Among numerous studies, perinatal nicotine exposure (PN) has had variable effects on respiratory control in the neonatal period. The effects of acute nicotine exposure on breathing are largely mediated by α4-containing nicotine acetylcholine receptors (nAChRs). These receptors are also involved in thermoregulatory responses induced by both acetylcholine and nicotine. We therefore hypothesized that α4-containing nAChRs would mediate the effects of PN on the metabolic and ventilatory responses of neonates to modest cold exposure. Wild-type (WT) and α4 knockout (KO) mice were exposed to 6 mg·kg -1 ·day -1 nicotine or vehicle from embryonic day 14 At postnatal day (P) 7 mice were cooled from an ambient temperature (T A ) of 32 to 20°C. Body temperature (T B ), rate of O 2 consumption (V̇o 2 ), ventilation (V̇e), respiratory frequency (F B ), and tidal volume (V T ) were continually monitored. An absence of α4 had no effect on the metabolic response to ambient cooling. Surprisingly, PN selectively increased the metabolic response of KO pups to cooling. Regardless, KO pups became hypothermic to the same degree as WT pups, and for both genotypes the drop in T B was exacerbated by PN. PN led to hyperventilation in WT pups caused by an increase in V T , an effect that was absent in α4 KO littermates. We show that PN interacts with α4-containing nAChRs in unique ways to modulate the control of breathing and thermoregulation in the early postnatal period. Copyright © 2016 the American Physiological Society.

Socioeconomic and urban-rural differentials in exposure to air pollution and mortality burden in England.

PubMed

Milojevic, Ai; Niedzwiedz, Claire L; Pearce, Jamie; Milner, James; MacKenzie, Ian A; Doherty, Ruth M; Wilkinson, Paul

2017-10-06

Socioeconomically disadvantaged populations often have higher exposures to particulate air pollution, which can be expected to contribute to differentials in life expectancy. We examined socioeconomic differentials in exposure and air pollution-related mortality relating to larger scale (5 km resolution) variations in background concentrations of selected pollutants across England. Ozone and particulate matter (sub-divided into PM 10 , PM 2.5 , PM 2.5-10 , primary, nitrate and sulphate PM 2.5 ) were simulated at 5 km horizontal resolution using an atmospheric chemistry transport model (EMEP4UK). Annual mean concentrations of these pollutants were assigned to all 1,202,578 residential postcodes in England, which were classified by urban-rural status and socioeconomic deprivation based on the income and employment domains of the 2010 English Index of Multiple Deprivation for the Lower-level Super Output Area of residence. We used life table methods to estimate PM 2.5 -attributable life years (LYs) lost in both relative and absolute terms. Concentrations of the most particulate fractions, but not of nitrate PM 2.5 or ozone, were modestly higher in areas of greater socioeconomic deprivation. Relationships between pollution level and socioeconomic deprivation were non-linear and varied by urban-rural status. The pattern of PM 2.5 concentrations made only a small contribution to the steep socioeconomic gradient in LYs lost due to PM 2.5 per 10 3 population, which primarily was driven by the steep socioeconomic gradient in underlying mortality rates. In rural areas, the absolute burden of air pollution-related LYs lost was lowest in the most deprived deciles. Air pollution shows modest socioeconomic patterning at 5 km resolution in England, but absolute attributable mortality burdens are strongly related to area-level deprivation because of underlying mortality rates. Measures that cause a general reduction in background concentrations of air pollution may modestly help narrow socioeconomic differences in health.

Heart Disease Death Rates Among Blacks and Whites Aged ≥35 Years - United States, 1968-2015.

PubMed

Van Dyke, Miriam; Greer, Sophia; Odom, Erika; Schieb, Linda; Vaughan, Adam; Kramer, Michael; Casper, Michele

2018-03-30

Heart disease is the leading cause of death in the United States. In 2015, heart disease accounted for approximately 630,000 deaths, representing one in four deaths in the United States. Although heart disease death rates decreased 68% for the total population from 1968 to 2015, marked disparities in decreases exist by race and state. 1968-2015. The National Vital Statistics System (NVSS) data on deaths in the United States were abstracted for heart disease using diagnosis codes from the eighth, ninth, and tenth revisions of the International Classification of Diseases (ICD-8, ICD-9, and ICD-10) for 1968-2015. Population estimates were obtained from NVSS files. National and state-specific heart disease death rates for the total population and by race for adults aged ≥35 years were calculated for 1968-2015. National and state-specific black-white heart disease mortality ratios also were calculated. Death rates were age standardized to the 2000 U.S. standard population. Joinpoint regression was used to perform time trend analyses. From 1968 to 2015, heart disease death rates decreased for the total U.S. population among adults aged ≥35 years, from 1,034.5 to 327.2 per 100,000 population, respectively, with variations in the magnitude of decreases by race and state. Rates decreased for the total population an average of 2.4% per year, with greater average decreases among whites (2.4% per year) than blacks (2.2% per year). At the national level, heart disease death rates for blacks and whites were similar at the start of the study period (1968) but began to diverge in the late 1970s, when rates for blacks plateaued while rates for whites continued to decrease. Heart disease death rates among blacks remained higher than among whites for the remainder of the study period. Nationwide, the black-white ratio of heart disease death rates increased from 1.04 in 1968 to 1.21 in 2015, with large increases occurring during the 1970s and 1980s followed by small but steady increases until approximately 2005. Since 2005, modest decreases have occurred in the black-white ratio of heart disease death rates at the national level. The majority of states had increases in black-white mortality ratios from 1968 to 2015. The number of states with black-white mortality ratios >1 increased from 16 (40%) to 27 (67.5%). Although heart disease death rates decreased both for blacks and whites from 1968 to 2015, substantial differences in decreases were found by race and state. At the national level and in most states, blacks experienced smaller decreases in heart disease death rates than whites for the majority of the period. Overall, the black-white disparity in heart disease death rates increased from 1968 to 2005, with a modest decrease from 2005 to 2015. Since 1968, substantial increases have occurred in black-white disparities of heart disease death rates in the United States at the national level and in many states. These increases appear to be due to faster decreases in heart disease death rates for whites than blacks, particularly from the late 1970s until the mid-2000s. Despite modest decreases in black-white disparities at the national level since 2005, in 2015, heart disease death rates were 21% higher among blacks than among whites. This study demonstrates the use of NVSS data to conduct surveillance of heart disease death rates by race and of black-white disparities in heart disease death rates. Continued surveillance of temporal trends in heart disease death rates by race can provide valuable information to policy makers and public health practitioners working to reduce heart disease death rates both for blacks and whites and disparities between blacks and whites.

Heart Disease Death Rates Among Blacks and Whites Aged ≥35 Years — United States, 1968–2015

PubMed Central

Van Dyke, Miriam; Greer, Sophia; Odom, Erika; Schieb, Linda; Vaughan, Adam; Kramer, Michael; Casper, Michele

2018-01-01

Problem/Condition Heart disease is the leading cause of death in the United States. In 2015, heart disease accounted for approximately 630,000 deaths, representing one in four deaths in the United States. Although heart disease death rates decreased 68% for the total population from 1968 to 2015, marked disparities in decreases exist by race and state. Period Covered 1968–2015. Description of System The National Vital Statistics System (NVSS) data on deaths in the United States were abstracted for heart disease using diagnosis codes from the eighth, ninth, and tenth revisions of the International Classification of Diseases (ICD-8, ICD-9, and ICD-10) for 1968–2015. Population estimates were obtained from NVSS files. National and state-specific heart disease death rates for the total population and by race for adults aged ≥35 years were calculated for 1968–2015. National and state-specific black-white heart disease mortality ratios also were calculated. Death rates were age standardized to the 2000 U.S. standard population. Joinpoint regression was used to perform time trend analyses. Results From 1968 to 2015, heart disease death rates decreased for the total U.S. population among adults aged ≥35 years, from 1,034.5 to 327.2 per 100,000 population, respectively, with variations in the magnitude of decreases by race and state. Rates decreased for the total population an average of 2.4% per year, with greater average decreases among whites (2.4% per year) than blacks (2.2% per year). At the national level, heart disease death rates for blacks and whites were similar at the start of the study period (1968) but began to diverge in the late 1970s, when rates for blacks plateaued while rates for whites continued to decrease. Heart disease death rates among blacks remained higher than among whites for the remainder of the study period. Nationwide, the black-white ratio of heart disease death rates increased from 1.04 in 1968 to 1.21 in 2015, with large increases occurring during the 1970s and 1980s followed by small but steady increases until approximately 2005. Since 2005, modest decreases have occurred in the black-white ratio of heart disease death rates at the national level. The majority of states had increases in black-white mortality ratios from 1968 to 2015. The number of states with black-white mortality ratios >1 increased from 16 (40%) to 27 (67.5%). Interpretation Although heart disease death rates decreased both for blacks and whites from 1968 to 2015, substantial differences in decreases were found by race and state. At the national level and in most states, blacks experienced smaller decreases in heart disease death rates than whites for the majority of the period. Overall, the black-white disparity in heart disease death rates increased from 1968 to 2005, with a modest decrease from 2005 to 2015. Public Health Action Since 1968, substantial increases have occurred in black-white disparities of heart disease death rates in the United States at the national level and in many states. These increases appear to be due to faster decreases in heart disease death rates for whites than blacks, particularly from the late 1970s until the mid-2000s. Despite modest decreases in black-white disparities at the national level since 2005, in 2015, heart disease death rates were 21% higher among blacks than among whites. This study demonstrates the use of NVSS data to conduct surveillance of heart disease death rates by race and of black-white disparities in heart disease death rates. Continued surveillance of temporal trends in heart disease death rates by race can provide valuable information to policy makers and public health practitioners working to reduce heart disease death rates both for blacks and whites and disparities between blacks and whites. PMID:29596406

Production of lunar fragmental material by meteoroid impact.

NASA Technical Reports Server (NTRS)

Marcus, A. H.

1973-01-01

The rate of production of new fragmental lunar surface material is derived theoretically on the hypothesis that such material is excavated from a bedrock layer by meteoroid impacts. An overlaying regolith effectively shields the bedrock layer from small impacts, reducing the production rate of centimeter-sized and smaller blocks by a large factor. Logarithmic production rate curves for centimeter to motor-sized blocks are nonlinear for any regolith from centimeters to tens of meters in thickness, with small blocks relatively much less frequent for thicker (older) regoliths, suggesting the possibility of a statistical reverse bedding. Modest variations in the exponents of scaling laws for crater depth-diameter ratio and maximum block-diameter to crater diameter ratio are shown to have significant effects on the production rates. The production rate increases slowly with increasing size of the largest crater affecting the region.

Personality Stability from Childhood to Midlife: Relating Teachers' Assessments in Elementary School to Observer- and Self-Ratings 40 Years Later.

PubMed

Edmonds, Grant W; Goldberg, Lewis R; Hampson, Sarah E; Barckley, Maureen

2013-10-01

We report on the longitudinal stability of personality traits across an average 40 years in the Hawaii Personality and Health Cohort relating childhood teacher assessments of personality to adult self- and observer- reports. Stabilities based on self-ratings in adulthood were compared to those measured by the Structured Interview for the Five-Factor Model (SIFFM; Trull & Widiger, 1997), and trait ratings completed by interviewers. Although convergence between self-reports and observer-ratings was modest, childhood traits demonstrated similar levels of stability across methods in adulthood. Extraversion and Conscientiousness generally showed higher stabilities, whereas Neuroticism showed none. For Agreeableness and Intellect/Openness, stability was highest when assessed with observer-ratings. These findings are discussed in terms of differences in trait evaluativeness and observability across measurement methods.

Personality Stability from Childhood to Midlife: Relating Teachers’ Assessments in Elementary School to Observer- and Self-Ratings 40 Years Later

PubMed Central

Edmonds, Grant W.; Goldberg, Lewis R.; Hampson, Sarah E.; Barckley, Maureen

2013-01-01

We report on the longitudinal stability of personality traits across an average 40 years in the Hawaii Personality and Health Cohort relating childhood teacher assessments of personality to adult self- and observer- reports. Stabilities based on self-ratings in adulthood were compared to those measured by the Structured Interview for the Five-Factor Model (SIFFM; Trull & Widiger, 1997), and trait ratings completed by interviewers. Although convergence between self-reports and observer-ratings was modest, childhood traits demonstrated similar levels of stability across methods in adulthood. Extraversion and Conscientiousness generally showed higher stabilities, whereas Neuroticism showed none. For Agreeableness and Intellect/Openness, stability was highest when assessed with observer-ratings. These findings are discussed in terms of differences in trait evaluativeness and observability across measurement methods. PMID:24039315

Results of a Phase II Study to Evaluate the Efficacy of Docetaxel and Carboplatin in Metastatic Malignant Melanoma Patients Who Failed First-Line Therapy Containing Dacarbazine.

PubMed

Lee, Choong-kun; Jung, Minkyu; Choi, Hye Jin; Kim, Hye Ryun; Kim, Hyo Song; Roh, Mi Ryung; Ahn, Joong Bae; Chung, Hyun Cheol; Heo, Su Jin; Rha, Sun Young; Shin, Sang Joon

2015-10-01

There is no standard second-line regimen for malignant melanoma patients with disease progression after first-line chemotherapy, and platinum-alkylating agents combined with paclitaxel have shown modest efficacy. We conducted a phase II, open-label, single-arm study to test the efficacy of docetaxel combined with carboplatin for malignant melanoma patients who failed previous treatment with dacarbazine. Intravenous docetaxel (35 mg/m(2) on days 1 and 8 of each cycle) and carboplatin (area under the curve 3 on days 1 and 8 of each cycle) was administered every 21 days. Primary end point was objective response rate (ORR). Thirty patients were enrolled in the study, and the median follow-up duration was 19.8 months. Among 25 per-protocol patients, there were three responders (1 with complete response and 2 with partial response) and 17 stable disease patients (ORR, 12.0%). Among the per-protocol population, the median progression-free survival (PFS) was 4.3 months and the median overall survival (OS) was 9.6 months. Uveal melanoma patients (n=9) showed the best prognosis compared to other subtypes (median PFS, 7.6 months; OS, 9.9 months). The most common grade 3 or 4 adverse event was neutropenia (n=15, 50.0%). Docetaxel combined with carboplatin showed association with an acceptable safety profile and overall efficacy for patients with malignant melanoma who had progressed on chemotherapy containing dacarbazine.

An EGFR autocrine loop encodes a slow-reacting but dominant mode of mechanotransduction in a polarized epithelium

PubMed Central

Kojic, Nikola; Chung, Euiheon; Kho, Alvin T.; Park, Jin-Ah; Huang, Austin; So, Peter T. C.; Tschumperlin, Daniel J.

2010-01-01

The mechanical landscape in biological systems can be complex and dynamic, with contrasting sustained and fluctuating loads regularly superposed within the same tissue. How resident cells discriminate between these scenarios to respond accordingly remains largely unknown. Here, we show that a step increase in compressive stress of physiological magnitude shrinks the lateral intercellular space between bronchial epithelial cells, but does so with strikingly slow exponential kinetics (time constant ∼110 s). We confirm that epidermal growth factor (EGF)-family ligands are constitutively shed into the intercellular space and demonstrate that a step increase in compressive stress enhances EGF receptor (EGFR) phosphorylation with magnitude and onset kinetics closely matching those predicted by constant-rate ligand shedding in a slowly shrinking intercellular geometry. Despite the modest degree and slow nature of EGFR activation evoked by compressive stress, we find that the majority of transcriptomic responses to sustained mechanical loading require ongoing activity of this autocrine loop, indicating a dominant role for mechanotransduction through autocrine EGFR signaling in this context. A slow deformation response to a step increase in loading, accompanied by synchronous increases in ligand concentration and EGFR activation, provides one means for cells to mount a selective and context-appropriate response to a sustained change in mechanical environment.—Kojic, N., Chung, E., Kho, A. T., Park, J.-A., Huang, A., So, P. T. C., Tschumperlin, D. J. An EGFR autocrine loop encodes a slow-reacting but dominant mode of mechanotransduction in a polarized epithelium. PMID:20056713

Examination of the Triarchic Assessment Procedure for Inconsistent Responding in six non-English language samples.

PubMed

Kelley, Shannon E; van Dongen, Josanne D M; Donnellan, M Brent; Edens, John F; Eisenbarth, Hedwig; Fossati, Andrea; Howner, Katarina; Somma, Antonella; Sörman, Karolina

2018-05-01

The Triarchic Assessment Procedure for Inconsistent Responding (TAPIR; Mowle et al., 2016) was recently developed to identify inattentiveness or comprehension difficulties that may compromise the validity of responses on the Triarchic Psychopathy Measure (TriPM; Patrick, 2010). The TAPIR initially was constructed and cross-validated using exclusively English-speaking participants from the United States; however, research using the TriPM has been increasingly conducted internationally, with numerous foreign language translations of the measure emerging. The present study examined the cross-language utility of the TAPIR in German, Dutch, Swedish, and Italian translations of the TriPM using 6 archival samples of community members, university students, forensic psychiatric inpatients, forensic detainees, and adolescents residing outside the United States (combined N = 5,404). Findings suggest that the TAPIR effectively detects careless responding across these 4 translated versions of the TriPM without the need for language-specific modifications. The TAPIR total score meaningfully discriminated genuine participant responses from both fully and partially randomly generated data in every sample, and demonstrated further utility in detecting fixed "all true" or "all false" response patterns. In addition, TAPIR scores were reliably associated with inconsistent responding scores from another psychopathy inventory. Specificity for a range of tentative cut scores for assessing profile validity was modestly reduced among our samples relative to rates previously obtained with the English version of the TriPM; however, overall the TAPIR appears to demonstrate satisfactory cross-language generalizability. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Recent ecological and biogeochemical changes in alpine lakes of Rocky Mountain National Park (Colorado, USA): A response to anthropogenic nitrogen deposition

USGS Publications Warehouse

Wolfe, A.P.; Van Gorp, A.C.; Baron, Jill S.

2003-01-01

Dated sediment cores from five alpine lakes (>3200 m asl) in Rocky Mountain National Park (Colorado Front Range, USA) record near-synchronous stratigraphic changes that are believed to reflect ecological and biogeochemical responses to enhanced nitrogen deposition from anthropogenic sources. Changes in sediment proxies include progressive increases in the frequencies of mesotrophic planktonic diatom taxa and diatom concentrations, coupled with depletions of sediment δ15N and C : N values. These trends are especially pronounced since approximately 1950. The most conspicuous diatoms to expand in recent decades are Asterionella formosa and Fragilaria crotonensis. Down-core species changes are corroborated by a year-long sediment trap experiment from one of the lakes, which reveals high frequencies of these two taxa during autumn and winter months, the interval of peak annual limnetic [NO3-]. Although all lakes record recent changes, the amplitude of stratigraphic shifts is greater in lakes east of the Continental Divide relative to those on the western slope, implying that most nitrogen enrichment originates from urban, industrial and agricultural sources east of the Rocky Mountains. Deviations from natural trajectories of lake ontogeny are illustrated by canonical correspondence analysis, which constrains the diatom record as a response to changes in nitrogen biogeochemistry. These results indicate that modest rates of anthropogenic nitrogen deposition are fully capable of inducing directional biological and biogeochemical shifts in relatively pristine ecosystems.

Trends and burden of firearm-related hospitalizations in the United States across 2001-2011.

PubMed

Agarwal, Shikhar

2015-05-01

Firearm-related hospitalizations are a major burden to the current health care infrastructure. We examined the trends in the incidence and case-fatality rates of firearm-related hospitalizations over the past decade. We also hypothesized that major national economic perturbations would be partly responsible and correlate temporally with national firearm-related hospitalization trends. We used the 2001-2011 Nationwide Inpatient Sample for analysis. Firearm-related hospitalizations were identified using International Classification of Diseases, 9(th) Revision codes. In addition, we examined the relationship between the US stock market performance (Dow Jones Industrial Average) and the annual firearm-related hospitalization incidence rates. In the last decade, there has been a modest decline in firearm-related hospitalizations, interrupted by spikes in the annual incidence that closely corresponded to periods of national economic instability. In addition, the overall case-fatality rate following firearm-related hospitalization has been stable at ∼8%; the highest rates being present among those who attempted suicide using firearms. Also, there has been an increase in the prevalence of mental health disorders among individuals admitted with firearm-related injuries. Moreover, there was an increase in the length of stay and the cost/charges associated with hospitalization over the last decade. Over 2001-2011, the national incidence of firearm-related hospitalizations has closely tracked the national stock market performance, suggesting that economic perturbations and resultant insecurities might underlie the perpetuation of firearm-related injuries. Although the case-fatality rates have remained stable, the length of stay and hospitalization costs have increased, imposing additional burden on existing health care resources. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of ethanol on cerebral blood flow (CBF) and metabolism (CMRO2) in conscious sheep

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krasney, J.A.; Zubkov, B.; Iwamoto, J.

1991-03-11

A moderate dose of ethanol severely depresses CBF and CMRO2 in the awake sheep fetus. However, the effects of ethanol on CBF and CMRO2 in the adult are unclear. The same dose of ethanol was infused for 2 hr in 5 ewes instrumented with aortic, left ventricular and sagittal sinus catheters. Ethanol caused ataxia accompanied by early modest and variable increases of total and regional CBF and CMRO2, followed by later modest and variable decreases of total and regional CBF (cerebellum) and CMRO2. Ethanol caused a cerebral transcapillary fluid shift as indicated by significant increases of the arterial-cerebral venous differencesmore » for hematocrit and hemoglobin. Brain wet-dry ratios increased by 10% above control levels. However, cerebral venous pressures were unchanged. The authors conclude that the adult cerebral response to ethanol differs quantitatively from that of the fetus. The functional significance of the cerebral fluid shift is unclear.« less

Suicide, gender, and age variations in India. Are women in indian society protected from suicide?

PubMed

Mayer, Peter; Ziaian, Tahereh

2002-01-01

A new set of data concerning the pattern of suicide in India between 1991-1997 are presented. Suicide rates rose over this period despite a small decline in the Indian suicide rate in 1995 and 1996. It was found that between 1995 and 1997 there was a modest fall in the suicide rates among under 29-year-olds of both sexes, and an increase among those 30 years and older. The pattern of suicides in India is bimodal: the incidence of suicides is highest for those in the 30-44-year-old category of both sexes and tends to decline in higher age categories. Suicide rates were nearly equal for young women and men, a contrast with the pattern of suicide sex ratios in eight developed countries.

On the density and field sensitivities of dielectronic recombination. [rates in coronal plasmas of late stars and sun

NASA Technical Reports Server (NTRS)

Reisenfeld, Daniel B.; Raymond, John C.; Young, Albert R.; Kohl, John L.

1992-01-01

Dielectronic recombination dominates the recombination rates of most ions in coronal plasmas at their temperatures of peak concentration. Because dielectronic recombination goes by way of high nl doubly excited levels, it is susceptible to collisional excitation and ionization, leading to a decreased rate. On the other hand, theoretical studies show that Stark mixing of the nl levels by a modest electric field enhances the dielectronic recombination rate severalfold. The ionization balance is computed here as as function of density, and it is found that the new results require increased emission measures to match the C IV emission line intensities observed in the sun and in late-type stars. They also make it more difficult to interpret the overall EUV emission line spectrum of the sun.

Channel response to sediment release: insights from a paired analysis of dam removal

USGS Publications Warehouse

Collins, Mathias J.; Snyder, Noah P.; Boardman, Graham; Banks, William S.; Andrews, Mary; Baker, Matthew E.; Conlon, Maricate; Gellis, Allen; McClain, Serena; Miller, Andrew; Wilcock, Peter

2017-01-01

Dam removals with unmanaged sediment releases are good opportunities to learn about channel response to abruptly increased bed material supply. Understanding these events is important because they affect aquatic habitats and human uses of floodplains. A longstanding paradigm in geomorphology holds that response rates to landscape disturbance exponentially decay through time. However, a previous study of the Merrimack Village Dam (MVD) removal on the Souhegan River in New Hampshire, USA, showed that an exponential function poorly described the early geomorphic response. Erosion of impounded sediments there was two-phased. We had an opportunity to quantitatively test the two-phase response model proposed for MVD by extending the record there and comparing it with data from the Simkins Dam removal on the Patapsco River in Maryland, USA. The watershed sizes are the same order of magnitude (102 km2), and at both sites low-head dams were removed (~3–4 m) and ~65 000 m3 of sand-sized sediments were discharged to low-gradient reaches. Analyzing four years of repeat morphometry and sediment surveys at the Simkins site, as well as continuous discharge and turbidity data, we observed the two-phase erosion response described for MVD. In the early phase, approximately 50% of the impounded sediment at Simkins was eroded rapidly during modest flows. After incision to base level and widening, a second phase began when further erosion depended on floods large enough to go over bank and access impounded sediments more distant from the newly-formed channel. Fitting functional forms to the data for both sites, we found that two-phase exponential models with changing decay constants fit the erosion data better than single-phase models. Valley width influences the two-phase erosion responses upstream, but downstream responses appear more closely related to local gradient, sediment re-supply from the upstream impoundments, and base flows.

How Will Higher Minimum Wages Affect Family Life and Children's Well-Being?

PubMed

Hill, Heather D; Romich, Jennifer

2018-06-01

In recent years, new national and regional minimum wage laws have been passed in the United States and other countries. The laws assume that benefits flow not only to workers but also to their children. Adolescent workers will most likely be affected directly given their concentration in low-paying jobs, but younger children may be affected indirectly by changes in parents' work conditions, family income, and the quality of nonparental child care. Research on minimum wages suggests modest and mixed economic effects: Decreases in employment can offset, partly or fully, wage increases, and modest reductions in poverty rates may fade over time. Few studies have examined the effects of minimum wage increases on the well-being of families, adults, and children. In this article, we use theoretical frameworks and empirical evidence concerning the effects on children of parental work and family income to suggest hypotheses about the effects of minimum wage increases on family life and children's well-being.

Strategies to enhance the therapeutic efficacy of antidepressants: targeting residual symptoms

PubMed Central

Kurian, Benji T; Greer, Tracy L; Trivedi, Madhukar H

2009-01-01

Major depressive disorder (MDD) is an illness of great morbidity that affects many people across the world. The current goal for treatment of MDD is to achieve remission (i.e., no depressive symptoms). However, despite scientific advances in the treatment for MDD, antidepressants as first-line agents yield only modest remission rates. In fact, a recent study indicated that only one out of three subjects who received a standard, first-line antidepressant attained remission. Not achieving remission from depressive symptoms increases the risk of a more chronic and debilitating course of illness with frequent recurrences. Although a number of reasons contribute to these modest outcomes, the presence of residual symptoms is a major problem. Residual symptoms are defined as symptoms that linger despite an adequate dose and duration of an antidepressant medication. This article reviews the prevalence and clinical impact of common residual symptoms and discusses the utility of aggressively addressing residual symptoms to enhance the efficacy of antidepressant medications. PMID:19589048

Sustained inflation during neonatal resuscitation.

PubMed

Keszler, Martin

2015-04-01

Sustained inflation performed shortly after birth to help clear lung fluid and establish functional residual capacity in preterm infants is gaining popularity, but definitive evidence for its effectiveness is lacking. Although there is a sound physiologic basis for this approach, and much preclinical experimental evidence of effectiveness, the results of recent animal studies and clinical trials have been inconsistent. The most recent data from a multicenter randomized trial suggest a modest benefit of sustained inflation in reducing the need for mechanical ventilation in extremely-low-birth-weight infants. However, the impact may be more modest than earlier retrospective cohort comparisons suggested. The trend toward more airleak and a higher rate of intraventricular hemorrhage is worrisome. Sustained inflation may be ineffective unless some spontaneous respiratory effort is present. Several on-going trials should further clarify the putative benefits of sustained inflation. Delivery room sustained inflation is an attractive concept that holds much promise, but widespread clinical application should await definitive evidence from on-going clinical trials.

Natural Firing Patterns Imply Low Sensitivity of Synaptic Plasticity to Spike Timing Compared with Firing Rate

PubMed Central

Wallisch, Pascal; Ostojic, Srdjan

2016-01-01

Synaptic plasticity is sensitive to the rate and the timing of presynaptic and postsynaptic action potentials. In experimental protocols inducing plasticity, the imposed spike trains are typically regular and the relative timing between every presynaptic and postsynaptic spike is fixed. This is at odds with firing patterns observed in the cortex of intact animals, where cells fire irregularly and the timing between presynaptic and postsynaptic spikes varies. To investigate synaptic changes elicited by in vivo-like firing, we used numerical simulations and mathematical analysis of synaptic plasticity models. We found that the influence of spike timing on plasticity is weaker than expected from regular stimulation protocols. Moreover, when neurons fire irregularly, synaptic changes induced by precise spike timing can be equivalently induced by a modest firing rate variation. Our findings bridge the gap between existing results on synaptic plasticity and plasticity occurring in vivo, and challenge the dominant role of spike timing in plasticity. SIGNIFICANCE STATEMENT Synaptic plasticity, the change in efficacy of connections between neurons, is thought to underlie learning and memory. The dominant paradigm posits that the precise timing of neural action potentials (APs) is central for plasticity induction. This concept is based on experiments using highly regular and stereotyped patterns of APs, in stark contrast with natural neuronal activity. Using synaptic plasticity models, we investigated how irregular, in vivo-like activity shapes synaptic plasticity. We found that synaptic changes induced by precise timing of APs are much weaker than suggested by regular stimulation protocols, and can be equivalently induced by modest variations of the AP rate alone. Our results call into question the dominant role of precise AP timing for plasticity in natural conditions. PMID:27807166

A priming effect of benthic gastropod mucus on sedimentary organic matter remineralization

NASA Astrophysics Data System (ADS)

Hannides, A. K.; Aller, R. C.

2016-02-01

Mucous gels are produced by benthic animals rapidly and in copious amounts, and have previously been shown to significantly affect diffusion rates of redox-sensitive ions and organic compounds in sediment pore waters. They are also a highly likely priming substrate whose addition in modest amounts affects sedimentary organic matter remineralization. We tested the priming effect of benthic infaunal mucus using secretions of the common gastropod Neverita duplicata as model substrate. Their composition is typical of marine molluscan mucus, consisting primarily of water (>96% by weight), which is in relative equilibrium with seawater. Salt-free dry weight constitutes 0.7% and 0.6% of total pedal and hypobranchial mucus, respectively. The C:N ratios of pedal and hypobranchial mucus indicate that the organic component consists of a mucopolysaccharide-glycoprotein complex that varies depending on its function, while low C:S ratios of the insoluble component and positive staining with Alcian Blue dye are indicative of S-ester and alkyl-SO42- groups bridging mucopolysaccharide and glycoprotein components. Anoxic incubations of pedal mucus of N. duplicata, sediment, and mucus-sediment mixture, resulted in the anaerobic generation of ΣCO2 and NH4+ at ratios lower than initial C:N ratios, indicating the preferential decomposition of N-rich moieties. Production rates of SCO2 and NH4+ in mucus-sediment incubations are higher, by 9±16% and 29±11%, respectively, than those predicted from linear addition of mucus-only and sediment-only rates. The statistically significant accelerated remineralization rate of N in the presence of modest mucus contribution (0.2% of total N), suggests that benthic mucus addition affects sedimentary organic matter remineralization processes through a "priming" effect.

Intellectual Issues in the History of Artificial Intelligence

DTIC Science & Technology

1982-10-28

the history of science is in terms of important scientific events and discoveries, linked to and by the scientists who were responsible for them...knowledge (coupled, sometimes, with modest search). However, as is usual in the history of science , work on powerful Al programs never stopped; it only...for AL, perhaps, because the nature of mind seems i,* .othe quick. But the history of science reminds us easily 0enough that at various stages

Approximations for Quantitative Feedback Theory Designs

NASA Technical Reports Server (NTRS)

Henderson, D. K.; Hess, R. A.

1997-01-01

The computational requirements for obtaining the results summarized in the preceding section were very modest and were easily accomplished using computer-aided control system design software. Of special significance is the ability of the PDT to indicate a loop closure sequence for MIMO QFT designs that employ sequential loop closure. Although discussed as part of a 2 x 2 design, the PDT is obviously applicable to designs with a greater number of inputs and system responses.

Intracerebral Mycobacterium bovis bacilli Calmette-Guerin infection-induced immune responses in the CNS 1

PubMed Central

Lee, JangEun; Ling, Changying; Kosmalski, Michelle M.; Hulseberg, Paul; Schreiber, Heidi A.; Sandor, Matyas; Fabry, Zsuzsanna

2010-01-01

To study whether cerebral mycobacterial infection induces granuloma and protective immunity similar to systemic infection, we intracerebrally infected mice with Mycobacterium bovis bacilli Calmette-Guerin. Granuloma and IFN-γ+CD4+ T cell responses are induced in the central nervous system (CNS) similar to periphery, but the presence of IFN-γIL-17 double-positive CD4+ T cells is unique to the CNS. The major CNS source of TNF-α is microglia, with modest production by CD4+ T cells and macrophage. Protective immunity is accompanied by accumulation of Foxp3+CD4+ T cells and PD-L2+ dendritic cells, suggesting that both inflammatory and anti-inflammatory responses develop in the CNS following mycobacterial infection. PMID:19535154

Enhancement of antibody response by one-trial conditioning: contrasting results using different antigens.

PubMed

Espinosa, Enrique; Calderas, Tania; Flores-Muciño, Oscar; Pérez-García, Georgina; Vázquez-Camacho, Ana C; Bermúdez-Rattoni, Federico

2004-01-01

New research in conditioned enhancement of antibody response requires a general paradigm effective with different antigens. In this experiment series we applied a one-trial protocol using keyhole limpet hemocyanin immunization as an unconditioned stimulus. Several different conditions were tested. Two different times between conditioning and test trial, two relevant antigen doses and the use of an antigen booster during test trial were investigated. We did not find a conditioned effect in any of the conditions used. In contrast, we found a reliable albeit modest conditioned effect using hen egg lysozyme as unconditioned stimulus. By comparing these and other findings we conclude that the number of conditioning trials is a possible requirement for a more reliable conditioning of antibody response.

Biosurveillance in a Highly Mobile Population - Year 3

DTIC Science & Technology

2012-04-01

airline transportation of the illness found that the rate of increased air transportation surrounding the Thanksgiving holiday serves as a modest...begins in early December, then drops slightly during the holidays and begins to show rapid acceleration at about week 3 of the at the beginning of...31/1/17.full>. Cowgill, K., Lucas, C., Benson, R., et al. (2005). “Recurrence of legionnaire’s disease at a hotel in the United States Virgin

The Separate and Cumulative Effects of TBI and PTSD on Cognitive Function and Emotional Control

DTIC Science & Technology

2011-04-01

participants has been successful. Finally, subjects completed three standardized questionnaires: the Barratt Impulsiveness Scale (BIS), the PTSD Checklist...function tasks. Self-rated impulsivity on the Barratt Impulsiveness Scale (BIS) showed a modest correlation with performance in the 90% Go...Normative data and a short form of the Barratt Impulsiveness Scale. (2007). Int J Neurosci. 117(3):359-68. Swick D, Ashley V, Turken AU. (2008). Left

Clean fuels from biomass. [cellulose fermentation to methane

NASA Technical Reports Server (NTRS)

Hsu, Y. Y.

1974-01-01

The potential of growing crops as a source of fuels is examined, and it is shown that enough arable land is available in the U.S. so that, even with a modest rate of crop yield, the nation could be supplied by fuel crops. The technologies for fuel conversion are available; however, some R&D efforts are needed for scaling up design. Fuel crop economics are discussed and shown to be nonprohibitive.

Runaway Costs in Medi-Cal—A Myth

PubMed Central

Heckman, John R.; Jones, Michael W.

1980-01-01

An analysis of increases in Medi-Cal expenditures to their present level, more than $4 billion a year, shows them to be attributable largely to changes in eligibility and scope of benefits. The actual costs of providing care have risen at a relatively modest rate. If in fact costs are to be lowered from present levels, public policy makers must make important decisions concerning program changes which transcend merely altering payment and delivery methods. PMID:6996335

Modern Outcomes of Inflammatory Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rehman, Sana; Northeast Ohio Medical University, Rootstown, Ohio; Reddy, Chandana A.

2012-11-01

Purpose: To report contemporary outcomes for inflammatory breast cancer (IBC) patients treated in the modern era of trastuzumab and taxane-based chemotherapy. Methods and Materials: We retrospectively reviewed the charts of 104 patients with nonmetastatic IBC treated between January 2000 and December 2009. Patients who received chemotherapy, surgery, and radiation therapy were considered to have completed the intended therapy. Kaplan-Meier curves estimated locoregional control (LRC), distant metastases-free survival (DMFS), and overall survival. Results: The median follow-up time was 34 months; 57 (55%) patients were estrogen receptor progesterone receptor (ER/PR) negative, 34 (33%) patients were human epidermal growth factor receptor 2 (her2)/neumore » amplified, and 78 (75%) received definitive postoperative radiation. Seventy-five (72%) patients completed all of the intended therapy, of whom 67 (89%) received a taxane and 18/28 (64%) of her2/neu-amplified patients received trastuzumab. For the entire cohort, the 5-year rates of overall survival, LRC, and DMFS were 46%, 83%, and 44%, respectively. The ER/PR-negative patients had a 5-year DMFS of 39% vs. 52% for ER/PR-positive patients (p = 0.03). The 5-year DMFS for patients who achieved a pathologic complete response compared with those who did not was 83% vs. 44% (p < 0.01). Those patients who received >60.4 Gy (n = 15) to the chest wall had a 5-year LRC rate of 100% vs. 83% for those who received 45 to 60.4 Gy (n = 49; p = 0.048). On univariate analysis, significant predictors of DMFS included achieving a complete response to neoadjuvant chemotherapy (hazard ratio [HR] = 5.8; 95% confidence interval [CI] = 1.4-24.4; p = 0.02) and pathologically negative lymph nodes (HR = 4.1; 95% CI = 1.4-11.9; p < 0.01), but no factor was significant on multivariate analysis. Conclusions: For IBC patients, the rate of distant metastases is still high despite excellent local control, particularly for patients who received >60.4 Gy to the chest wall. Despite the use of taxanes and trastuzumab, outcomes remain modest, particularly for those with ER/PR-negative disease and those without a pathologic complete response.« less

Mice expressing a “hyper-sensitive” form of the CB1 cannabinoid receptor (CB1) show modestly enhanced alcohol preference and consumption

PubMed Central

Gonek, Maciej; Zee, Michael L.; Farnsworth, Jill C.; Amin, Randa A.; Andrews, Mary-Jeanette; Davis, Brian J.; Mackie, Ken; Morgan, Daniel J.

2017-01-01

We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a “hyper-sensitive” form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6%) but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg), morphine (10 mg/kg), and cocaine (10 mg/kg), demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model. PMID:28426670

Poverty eradication in a carbon constrained world.

PubMed

Hubacek, Klaus; Baiocchi, Giovanni; Feng, Kuishuang; Patwardhan, Anand

2017-10-24

The UN Framework Convention on Climate Change aims to keep warming below 2 °C while recognizing developing countries' right to eradicate extreme poverty. Poverty eradication is also the first of the Sustainable Development Goals. This paper investigates potential consequences for climate targets of achieving poverty eradication. We find that eradicating extreme poverty, i.e., moving people to an income above $1.9 purchasing power parity (PPP) a day, does not jeopardize the climate target even in the absence of climate policies and with current technologies. On the other hand, bringing everybody to a still modest expenditure level of at least $2.97 PPP would have long-term consequences on achieving emission targets. Compared to the reference mitigation pathway, eradicating extreme poverty increases the effort by 2.8% whereas bringing everybody to at least $2.97 PPP would increase the required mitigation rate by 27%. Given that the top 10% global income earners are responsible for 36% of the current carbon footprint of households; the discourse should address income distribution and the carbon intensity of lifestyles.

The feasibility and effectiveness of Catch It, an innovative CBT smartphone app

PubMed Central

Hagan, Paul; King, Sophie; Bowman, James; Chahal, Jasprit; Gan, Li; McKnight, Rebecca; Waldon, Charlotte; Smith, Matthew; Gilbertson, John; Tai, Sara

2016-01-01

Background The widespread use of smartphones makes effective therapies such as cognitive–behavioural therapy (CBT) potentially accessible to large numbers of people. Aims This paper reports the usage data of the first trial of Catch It, a new CBT smartphone app. Method Uptake and usage rates, fidelity of user responses to CBT principles, and impact on reported negative and positive moods were assessed. Results A relatively modest proportion of people chose to download the app. Once used, the app tended to be used more than once, and 84% of the user-generated content was consistent with the basic concepts of CBT. There were statistically significant reductions in negative mood intensity and increases in positive mood intensity. Conclusions Smartphone apps have potential beneficial effects in mental health through the application of basic CBT principles. More research with randomised controlled trial designs should be conducted. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703777

In Vivo Regulation of Hepatitis B Virus Replication by Peroxisome Proliferators†

PubMed Central

Guidotti, Luca G.; Eggers, Carrie M.; Raney, Anneke K.; Chi, Susan Y.; Peters, Jeffrey M.; Gonzalez, Frank J.; McLachlan, Alan

1999-01-01

The role of the peroxisome proliferator-activated receptor α (PPARα) in regulating hepatitis B virus (HBV) transcription and replication in vivo was investigated in an HBV transgenic mouse model. Treatment of HBV transgenic mice with the peroxisome proliferators Wy-14,643 and clofibric acid resulted in a less than twofold increase in HBV transcription rates and steady-state levels of HBV RNAs in the livers of these mice. In male mice, this increase in transcription was associated with a 2- to 3-fold increase in replication intermediates, whereas in female mice it was associated with a 7- to 14-fold increase in replication intermediates. The observed increases in transcription and replication were dependent on PPARα. HBV transgenic mice lacking this nuclear hormone receptor showed similar levels of HBV transcripts and replication intermediates as untreated HBV transgenic mice expressing PPARα but failed to demonstrate alterations in either RNA or DNA synthesis in response to peroxisome proliferators. Therefore, it appears that very modest alterations in transcription can, under certain circumstances, result in relatively large increases in HBV replication in HBV transgenic mice. PMID:10559356

Fifty years of advances in sarcoma treatment: moving the needle from conventional chemotherapy to targeted therapy.

PubMed

Patel, Shreyaskumar R

2014-01-01

Much of the progress in systemic therapy for sarcomas was accomplished in the first half of the last 5 decades. Various chemotherapeutic agents were tested in the 70s through the 80s and became part of the standard of care for this patient population. During the decade of the 90s, dose intensification became feasible as a result of improved supportive care and the availability of growth factors, thus maximizing the therapeutic potential of this class of agents. However, response rates and survival plateaued and it became obvious that newer and mechanistically different agents were needed to improve the therapeutic index and gain further enhancement of outcomes. Since early 2000, primarily inspired by the experience with imatinib in gastrointestinal stromal tumors (GISTs), several targeted therapies have been tested in sarcomas with modest success. The major limitations encountered include the lack of drivers and actionable targets for bone and soft tissue sarcomas with complex genomic profiles. Continued investigations and sequencing of larger numbers of these rare and heterogeneous malignancies could shed some light on a path toward improved outcomes.

Role of chemotherapy and molecularly targeted agents in the treatment of adenoid cystic carcinoma of the lacrimal gland.

PubMed

Le Tourneau, Christophe; Razak, Albiruni R A; Levy, Christine; Calugaru, Valentin; Galatoire, Olivier; Dendale, Rémi; Desjardins, Laurence; Gan, Hui K

2011-11-01

Adenoid cystic carcinoma (ACC) is the most common malignant epithelial cancer of the lacrimal gland. Despite a slow rate of growth, ACCs are ultimately associated with poor clinical outcome. Given the rarity of this disease, most recommendations regarding therapy are guided by expert opinion and retrospective data rather than level 1 evidence. Surgery and postoperative radiation therapy are commonly used as initial local treatment. In patients at high risk of recurrence, concomitant platinum-based chemotherapy may be added to postoperative radiotherapy in an attempt to enhance radio-sensitivity. While encouraging responses have been reported with intra-arterial neoadjuvant chemotherapy, this strategy is associated with substantial toxicity and should be considered investigational. For patients with metastatic disease not amenable to surgery or radiotherapy, chemotherapy may have a role based on its modest efficacy in non-lacrimal ACC. Similarly, molecular targeted agents may have a role, although the agents tested to date in non-lacrimal ACC have been disappointing. A better understanding of the biology of ACC will be crucial to the future success of developing targeted agents for this disease.

Cognitive switching processes in young people with attention-deficit/hyperactivity disorder.

PubMed

Oades, Robert D; Christiansen, Hanna

2008-01-01

Patients with attention-deficit/hyperactivity disorder (ADHD) can be slow at switching between stimuli, or between sets of stimuli to control behaviour appropriate to changing situations. We examined clinical and experimental parameters that may influence the speed of such processes measured in the trail-making (TMT) and switch-tasks in cases with ADHD combined type, their non-affected siblings and unrelated healthy controls. The latency for completion of the trail-making task controlling for psychomotor processing (TMT-B-A) was longer for ADHD cases, and correlated with Conners' ratings of symptom severity across all subjects. The effect decreased with age. Switch-task responses to questions of "Which number?" and "How many?" between sets of 1/111 or 3/333 elicited differential increases in latency with condition that affected all groups. But there was evidence for increased symptom-related intra-individual variability among the ADHD cases, and across all subjects. Young siblings showed familiality for some measures of TMT and switch-task performance but these were modest. The potential influences of moderator variables on the efficiency of processing stimulus change rather than the speed of processing are discussed.

Motivation for compliance with environmental regulations related to forest health.

PubMed

Peterson, Kim; Diss-Torrance, Andrea

2012-12-15

This study extends previous research on motivations for compliance with environmental regulations. It addresses contexts where regulatees have primarily sporadic short term interests, where costs of compliance are modest, and where costs of non-compliance are low. The behavior studied is the movement of firewood for camping, a principal cause for the spread of the emerald ash borer (Agrilus planipennis), one of several invasive species plaguing the eastern United States. Based on a three-wave mail survey that produced 495 usable returns (64% response rate), findings suggest that motivations are influential in these contexts. Calculated motivations exert the greatest influence-especially when related to firewood price and convenience, while normative motivations (civic duty based) exert less influence, as does ability to comply. These findings have important implications, not only for controlling the spread of forest diseases and invasive pests, but also for regulating natural resources in general. They suggest that national, state, and local governments can manage natural resources to encourage user compliance with environmental rules, and develop communication strategies that leverage pro-environment norms. Copyright © 2012 Elsevier Ltd. All rights reserved.

Edge-Induced Shear Banding in Entangled Polymeric Fluids

NASA Astrophysics Data System (ADS)

Hemingway, Ewan J.; Fielding, Suzanne M.

2018-03-01

Despite decades of research, the question of whether solutions and melts of highly entangled polymers exhibit shear banding as their steady state response to a steadily imposed shear flow remains controversial. From a theoretical viewpoint, an important unanswered question is whether the underlying constitutive curve of shear stress σ as a function of shear rate γ ˙ (for states of homogeneous shear) is monotonic, or has a region of negative slope, d σ /d γ ˙ <0 , which would trigger banding. Attempts to settle the question experimentally via velocimetry of the flow field inside the fluid are often confounded by an instability of the free surface where the sample meets the outside air, known as "edge fracture." Here we show by numerical simulation that in fact even only very modest edge disturbances—which are the precursor of full edge fracture but might well, in themselves, go unnoticed experimentally—can cause strong secondary flows in the form of shear bands that invade deep into the fluid bulk. Crucially, this is true even when the underlying constitutive curve is monotonically increasing, precluding true bulk shear banding in the absence of edge effects.

The influence of stimulants, sedatives, and fatigue on tunnel vision: risk factors for driving and piloting.

PubMed

Mills, K C; Spruill, S E; Kanne, R W; Parkman, K M; Zhang, Y

2001-01-01

A computerized task was used in two studies to examine the influence of stimulants, sedatives, and fatigue on single-target and divided-attention responses in different parts of the visual field. The drug effects were evaluated over time with repeated behavioral and subjective measures against ascending and descending drug levels. In the first study, 18 fully rested participants received placebo, alprazolam (0.5 mg), and dextroamphetamine (10 mg). Alprazolam impairs performance, whereas dextroamphetamine induces enhancement and tunnel vision. Study 2 exposed 32 participants to fatigue and no fatigue with a repeated-measures crossover design. Four independent groups subsequently received placebo, dextroamphetamine (10 mg), caffeine (250 mg), or alcohol (.07%). Under fatigue, stimulants have no performance-enhancing effects, whereas impairment from alcohol is severe. Under no fatigue, alcohol has a modest effect, caffeine has no effect, and dextroamphetamine significantly enhances divided-attention performance coincident with tunnel vision. Participants rate all drug effects more stimulating and less sedating while fatigued. Implications for transportation safety are discussed. Actual or potential applications of this research include driver and pilot training.

Using a higher criticism statistic to detect modest effects in a genome-wide study of rheumatoid arthritis

PubMed Central

2009-01-01

In high-dimensional studies such as genome-wide association studies, the correction for multiple testing in order to control total type I error results in decreased power to detect modest effects. We present a new analytical approach based on the higher criticism statistic that allows identification of the presence of modest effects. We apply our method to the genome-wide study of rheumatoid arthritis provided in the Genetic Analysis Workshop 16 Problem 1 data set. There is evidence for unknown bias in this study that could be explained by the presence of undetected modest effects. We compared the asymptotic and empirical thresholds for the higher criticism statistic. Using the asymptotic threshold we detected the presence of modest effects genome-wide. We also detected modest effects using 90th percentile of the empirical null distribution as a threshold; however, there is no such evidence when the 95th and 99th percentiles were used. While the higher criticism method suggests that there is some evidence for modest effects, interpreting individual single-nucleotide polymorphisms with significant higher criticism statistics is of undermined value. The goal of higher criticism is to alert the researcher that genetic effects remain to be discovered and to promote the use of more targeted and powerful studies to detect the remaining effects. PMID:20018032

Live-Attenuated Lentivirus Immunization Modulates Innate Immunity and Inflammation while Protecting Rhesus Macaques from Vaginal Simian Immunodeficiency Virus Challenge

PubMed Central

Genescà, Meritxell; Ma, Zhong-Min; Wang, Yichuan; Assaf, Basel; Qureshi, Huma; Fritts, Linda; Huang, Ying; McChesney, Michael B.

2012-01-01

Immunization with attenuated lentiviruses is the only reliable method of protecting rhesus macaques (RM) from vaginal challenge with pathogenic simian immunodeficiency virus (SIV). CD8+ lymphocyte depletion prior to SIVmac239 vaginal challenge demonstrated that a modest, Gag-specific CD8+ T cell response induced by immunization with simian-human immunodeficiency virus 89.6 (SHIV89.6) protects RM. Although CD8+ T cells are required for protection, there is no anamnestic expansion of SIV-specific CD8+ T cells in any tissues except the vagina after challenge. Further, SHIV immunization increased the number of viral target cells in the vagina and cervix, suggesting that the ratio of target cells to antiviral CD8+ T cells was not a determinant of protection. We hypothesized that persistent replication of the attenuated vaccine virus modulates inflammatory responses and limits T cell activation and expansion by inducing immunoregulatory T cell populations. We found that attenuated SHIV infection decreased the number of circulating plasmacytoid dendritic cells, suppressed T cell activation, decreased mRNA levels of proinflammatory mediators, and increased mRNA levels of immunoregulatory molecules. Three days after SIV vaginal challenge, SHIV-immunized RM had significantly more T regulatory cells in the vagina than the unimmunized RM. By day 14 postchallenge, immune activation and inflammation were characteristic of unimmunized RM but were minimal in SHIV-immunized RM. Thus, a modest vaccine-induced CD8+ T cell response in the context of immunoregulatory suppression of T cell activation may protect against vaginal HIV transmission. PMID:22696662

A Modest Critical Pedagogy for English as a Foreign Language Education

ERIC Educational Resources Information Center

Kim, Mi Kyong; Pollard, Vikki Ann

2017-01-01

This paper uses the introduction of critical pedagogy to an English as a Foreign Language class in the Republic of Korea as a case study for a "modest critical pedagogy" (Tinning 2002). Focusing on the stress and resistances experienced during the introduction, we suggest a modest critical pedagogy that 1) makes the paradigm itself an…

Does legalized gambling elevate the risk of suicide? An analysis of U.S. counties and metropolitan areas.

PubMed

McCleary, Richard; Chew, Kenneth S Y; Merrill, Vincent; Napolitano, Carol

2002-01-01

This study addresses a possible link between suicide and casino gambling. Resident suicide rates are analyzed for (a) a 1990 cross-section of 148 U.S. metropolitan areas and (b) before and after the advent of legalized casinos in five U.S. counties. Data are drawn from government and gaming industry sources. In cross-section, metro area suicide is strongly correlated with region, accidental death and homicide rates, age and race composition, and economic vitality, followed by a modest net positive correlation with casino presence. By contrast, the time series analysis yields no evidence of a gambling effect.

Growth in HMO share of the Medicare market, 1989-1994.

PubMed

Welch, W P

1996-01-01

Between 1989 and 1994 the health maintenance organization (HMO) share of the Medicare market grew rapidly. It is still heavily concentrated geographically, however. The most influential factor in this growth is HMO penetration into an area's general health care market. Medicare payment rates and prior Medicare HMO penetration also have an impact, but their effects are much weaker. Thus, payment rate reform is likely to have only a modest impact on Medicare HMO growth in the short term. In the longer term, the HMO share of the Medicare market will continue to grow, because HMO penetration in the general health care market is growing rapidly.

Effect of probiotic on innate inflammatory response and viral shedding in experimental rhinovirus infection - a randomised controlled trial.

PubMed

Turner, R B; Woodfolk, J A; Borish, L; Steinke, J W; Patrie, J T; Muehling, L M; Lahtinen, S; Lehtinen, M J

2017-04-26

Ingestion of probiotics appears to have modest effects on the incidence of viral respiratory infection. The mechanism of these effects is not clear; however, there is evidence from animal models that the probiotic may have an effect on innate immune responses to pathogens. The purpose of this randomised, placebo-controlled study was to determine the effect of administration of Bifidobacterium animalis subspecies lactis Bl-04 on innate and adaptive host responses to experimental rhinovirus challenge. The effect on the response of chemokine (C-X-C motif) ligand 8 (CXCL8) to rhinovirus infection was defined as the primary endpoint for the study. 152 seronegative volunteers who had been supplemented for 28 days, 73 with probiotic and 79 with placebo, were challenged with RV-A39. Supplement or placebo administration was then continued for five days during collection of specimens for assessment of host response, infection, and symptoms. 58 probiotic and 57 placebo-supplemented volunteers met protocol-defined criteria for analysis. Probiotic resulted in higher nasal lavage CXCL8 on day 0 prior to virus challenge (90 vs 58 pg/ml, respectively, P=0.04, ANCOVA). The CXCL8 response to rhinovirus infection in nasal lavage was significantly reduced in the probiotic treated group (P=0.03, ANCOVA). Probiotic was also associated with a reduction in nasal lavage virus titre and the proportion of subjects shedding virus in nasal secretions (76% in the probiotic group, 91% in the placebo group, P=0.04, Fisher Exact test). The administration of probiotic did not influence lower respiratory inflammation (assessed by exhaled nitric oxide), subjective symptom scores, or infection rate. This study demonstrates that ingestion of Bl-04 may have an effect on the baseline state of innate immunity in the nose and on the subsequent response of the human host to rhinovirus infection. Clinicaltrials.gov registry number: NCT01669603.

Characterization of Kentucky dairy producer decision-making behavior.

PubMed

Russell, R A; Bewley, J M

2013-07-01

To address dairy clientele needs, industry professionals need to understand how dairy producers make decisions. A survey was distributed to all licensed Kentucky milk producers (n=1,074) to better understand factors that influence dairy producer decisions. A total of 236 surveys were returned; 7 were omitted because they were incomplete, leaving 229 for subsequent analyses (21% response rate). The survey consisted of questions about dairy operational success criteria, decision evaluation criteria, information sources, and technology adoption. The mean response to each survey question was calculated after assigning the following numeric values to producer response categories: 1 = not important, 3 = important, 5 = very important. The most important source of influence or information in decision making was advice from consultants, nutritionists, and veterinarians (3.70±1.23), followed by consultation with business partners and family members (3.68±1.29), and intuition and gut feeling (3.10±1.45). Producers with large herds (≥200 cows) relied more heavily on information from consultants, nutritionists, and veterinarians and on employee input than did producers with small herds (1 to 49 cows). Producers with small herds did not use effect on employee morale as a criterion to evaluate decisions as much as those with larger herds did. In regard to adoption of automated monitoring technologies, producers indicated that modest adoption rates were a result of (1) not being familiar with technologies that are available (55%), (2) undesirable cost to benefit ratios (42%), and (3) too much information provided without knowing what to do with it (36%). As herd size increased, the percentage of producers selecting poor technical support and training and compatibility issues as reasons for slow adoption of automated technologies increased. This insight into dairy producer decision making should help industry professionals address dairy producer issues and concerns. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Specificity Elicits Higher Maximal and Submaximal Cardiorespiratory Responses During a New Taekwondo Aerobic Test.

PubMed

Hausen, Matheus; Soares, Pedro Paulo; Araujo, Marcus Paulo; Esteves, Débora; Julio, Hilbert; Tauil, Roberto; Junca, Marcus; Porto, Flávia; Franchini, Emerson; Bridge, Craig Alan; Gurgel, Jonas

2018-05-10

The purpose of the present study was to propose and validate new taekwondo-specific cardiopulmonary exercise tests. Twelve male national-level taekwondo athletes (age 20 ± 2 yrs; body mass 67.5 ± 5.7 kg; height 175 ± 8 cm; training experience 7 ± 3 yrs) performed three separate exercise tests in a randomized counterbalanced order: 1) a Treadmill Running Cardiopulmonary Exercise Test (CPET); 2) Continuous and 3) Interval Taekwondo Cardiopulmonary Exercise Tests (cTKDet and iTKDet, respectively). The CPET was administered using an individualized ramp protocol. Taekwondo tests comprised sequences of turning kicks performed upon a stationary target. The impacts were recorded via an electronic scoring sensor used in official competition. Stages on the cTKDet and iTKDet lasted 1-min and progressively reduced the kick interval duration. These were guided by a sound signal, starting with 4.6s between kicks and reducing by 0.4s every minute until the test ended. Oxygen uptake (V̇O 2 ), heart rate (HR), capillary blood lactate and ratings of perceived exertion were measured. Modest differences were identified in V̇O 2MAX between the tests (F 2,22 =3.54; p=0.046; ES=0.16). HR MAX was higher during both taekwondo tests (F 2,22 =14.3; p=0.001; ES=1.14) compared with CPET. Specific tests also yielded higher responses in the 1 st ventilatory threshold V̇O 2 (F 2,22 =6.5; p=0.04; ES=0.27) and HR (F 2,22 =12.3; p<0.001; ES=1.06), and HR at the 2 nd ventilatory threshold (F 2,22 =5.7; p=0.02; ES=0.72). Taekwondo-specific cardiopulmonary tests enhance the validity of some cardiopulmonary responses, and might therefore be considered to optimise routine diagnostic testing and training prescription for this athletic group.

Wall extensibility and cell hydraulic conductivity decrease in enlarging stem tissues at low water potentials.

PubMed

Nonami, H; Boyer, J S

1990-08-01

Measurements with a guillotine psychrometer (H Nonami, JS Boyer [1990] Plant Physiol 94: 1601-1609) indicate that the inhibition of stem growth at low water potentials (low psi(w)) is accompanied by decreases in cell wall extensibility and tissue hydraulic conductance to water that eventually limit growth rate in soybean (Glycine max L. Merr.). To check this conclusion, we measured cell wall properties and cell hydraulic conductivities with independent techniques in soybean seedlings grown and treated the same way, i.e. grown in the dark and exposed to low psi(w) by transplanting dark grown seedlings to vermiculite of low water content. Wall properties were measured with an extensiometer modified for intact plants, and conductances were measured with a cell pressure probe in intact plants. Theory was developed to relate the wall measurements to those with the psychrometer. In the elongation zone, the plastic deformability of the walls decreased when measured with the extensiometer while growth was inhibited at low psi(w). It increased during a modest growth recovery. This behavior was the same as that for the wall extensibility observed previously with the psychrometer. Tissue that was killed before measurement with the extensiometer also showed a similar response, indicating that changes in wall extensibility represented changes in wall physical properties and not rates of wall biosynthesis. The elastic compliance (reciprocal of bulk elastic modulus) did not change in the elongating or mature tissue. The hydraulic conductivity of cortical cells decreased in the elongating tissue and increased slightly during growth recovery in a response similar to that observed with the psychrometer. We conclude that the plastic properties of the cell walls and the conductance of the cells to water were decreased at low psi(w) but that the elastic properties of the walls were of little consequence in this response.

Wall Extensibility and Cell Hydraulic Conductivity Decrease in Enlarging Stem Tissues at Low Water Potentials 1

PubMed Central

Nonami, Hiroshi; Boyer, John S.

1990-01-01

Measurements with a guillotine psychrometer (H Nonami, JS Boyer [1990] Plant Physiol 94: 1601-1609) indicate that the inhibition of stem growth at low water potentials (low ψw) is accompanied by decreases in cell wall extensibility and tissue hydraulic conductance to water that eventually limit growth rate in soybean (Glycine max L. Merr.). To check this conclusion, we measured cell wall properties and cell hydraulic conductivities with independent techniques in soybean seedlings grown and treated the same way, i.e. grown in the dark and exposed to low ψw by transplanting dark grown seedlings to vermiculite of low water content. Wall properties were measured with an extensiometer modified for intact plants, and conductances were measured with a cell pressure probe in intact plants. Theory was developed to relate the wall measurements to those with the psychrometer. In the elongation zone, the plastic deformability of the walls decreased when measured with the extensiometer while growth was inhibited at low ψw. It increased during a modest growth recovery. This behavior was the same as that for the wall extensibility observed previously with the psychrometer. Tissue that was killed before measurement with the extensiometer also showed a similar response, indicating that changes in wall extensibility represented changes in wall physical properties and not rates of wall biosynthesis. The elastic compliance (reciprocal of bulk elastic modulus) did not change in the elongating or mature tissue. The hydraulic conductivity of cortical cells decreased in the elongating tissue and increased slightly during growth recovery in a response similar to that observed with the psychrometer. We conclude that the plastic properties of the cell walls and the conductance of the cells to water were decreased at low ψw but that the elastic properties of the walls were of little consequence in this response. PMID:16667664

Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease.

PubMed

Karimi, M; Golchin, N; Tabbal, S D; Hershey, T; Videen, T O; Wu, J; Usche, J W M; Revilla, F J; Hartlein, J M; Wernle, A R; Mink, J W; Perlmutter, J S

2008-10-01

Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (r(s) = -0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (r(s) = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (r(s) = -0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease.

Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease

PubMed Central

Karimi, M.; Golchin, N.; Tabbal, S. D.; Hershey, T.; Videen, T. O.; Wu, J.; Usche, J. W. M.; Revilla, F. J.; Hartlein, J. M.; Wernle, A. R.; Mink, J. W.

2008-01-01

Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (rs = –0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (rs = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (rs = –0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease. PMID:18697909

Assessing children's perceptions of academic interventions: The Kids Intervention Profile.

PubMed

Eckert, Tanya L; Hier, Bridget O; Hamsho, Narmene F; Malandrino, Rigby D

2017-06-01

The psychometric properties of the Kids Intervention Profile (KIP), a rating scale designed to measure academic intervention acceptability from the perspective of students, were examined as well as the influence of background factors on students' acceptability ratings. Data were extracted from 4 randomized controlled trials investigating the effects of a performance feedback intervention on third-grade students' writing fluency (n = 228). Results indicated that the KIP contains 2 factors (General Intervention Acceptability, Skill Improvement) and has adequate internal consistency and stability across a 3-week period. There were gender differences in students' acceptability ratings, with female students rating the intervention as significantly more acceptable than males. In addition, results suggested a modest, positive relationship between students' intervention acceptability ratings and their intervention outcomes. Considerations regarding the use of the KIP, as well as limitations of the study, are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Incorporating lower grade toxicity information into dose finding designs

PubMed Central

Iasonos, Alexia; Zohar, Sarah; O’Quigley, John

2012-01-01

Background Toxicity grades underlie the definition of a dose limiting toxicity (DLT) but in the majority of phase I designs, the information contained in the individual grades is not used. Some authors have argued that it may be more appropriate to consider a polytomous rather than dichotomous response. Purpose We investigate whether the added information on individual grades can improve the operating characteristics of the Continual Reassessment Method (CRM). Methods We compare the original CRM design for a binary response with two stage CRM designs which make di erent use of lower-grade toxicity information via simulations. Specifically we study; a two-stage design that utilizes lower-grade toxicities in the first stage only, during the initial non model-based escalation, and two-stage designs where lower grades are used throughout the trial via explicit models. We postulate a model relating the rates of lower grade toxicities to the rate of DLTs, or assume the relative rates of low to high grade toxicities is unknown. The designs were compared in terms of accuracy, patient allocation and precision. Results Significant gains can be achieved when using grades in the first stage of a two-stage design. Otherwise, only modest improvements are seen when the information on grades is exploited via the use of explicit models, where the parameters are known precisely. CRM with some use of grade information, increases the number of patients treated at the MTD by approximately 5%. The additional information from lower grades can lead to a small increase in the precision of our estimate of the MTD. Limitations Our comparisons are not exhaustive and it would be worth studying other models and situations. Conclusions Although, the gains in performance were not as great as we had hoped, we observed no cases where the performance of CRM was poorer. Our recommendation is that investigators might consider using graded toxicities at the design stage. PMID:21835856

Geiger-mode avalanche photodiode focal plane arrays for three-dimensional imaging LADAR

NASA Astrophysics Data System (ADS)

Itzler, Mark A.; Entwistle, Mark; Owens, Mark; Patel, Ketan; Jiang, Xudong; Slomkowski, Krystyna; Rangwala, Sabbir; Zalud, Peter F.; Senko, Tom; Tower, John; Ferraro, Joseph

2010-09-01

We report on the development of focal plane arrays (FPAs) employing two-dimensional arrays of InGaAsP-based Geiger-mode avalanche photodiodes (GmAPDs). These FPAs incorporate InP/InGaAs(P) Geiger-mode avalanche photodiodes (GmAPDs) to create pixels that detect single photons at shortwave infrared wavelengths with high efficiency and low dark count rates. GmAPD arrays are hybridized to CMOS read-out integrated circuits (ROICs) that enable independent laser radar (LADAR) time-of-flight measurements for each pixel, providing three-dimensional image data at frame rates approaching 200 kHz. Microlens arrays are used to maintain high fill factor of greater than 70%. We present full-array performance maps for two different types of sensors optimized for operation at 1.06 μm and 1.55 μm, respectively. For the 1.06 μm FPAs, overall photon detection efficiency of >40% is achieved at <20 kHz dark count rates with modest cooling to ~250 K using integrated thermoelectric coolers. We also describe the first evalution of these FPAs when multi-photon pulses are incident on single pixels. The effective detection efficiency for multi-photon pulses shows excellent agreement with predictions based on Poisson statistics. We also characterize the crosstalk as a function of pulse mean photon number. Relative to the intrinsic crosstalk contribution from hot carrier luminescence that occurs during avalanche current flows resulting from single incident photons, we find a modest rise in crosstalk for multi-photon incident pulses that can be accurately explained by direct optical scattering.

Patient and Family Experience: A Comparison of Intensive Care and Overall Hospitalization.

PubMed

Lah, Soowhan; Wilson, Emily L; Rozenblum, Ronen; Hirshberg, Eliotte L; Hopkins, Ramona O; Orme, James; Brown, Samuel M

2017-05-01

The Hospital Consumer Assessment of Healthcare Providers and Systems survey is the most commonly used instrument for measuring patients' perceptions of the quality of inpatient care. To determine if the hospital survey can also be used to measure patients' experience of intensive care as indicated by scores on a parallel questionnaire, the Patient Perception of Quality. Scores on both instruments of all adult patients admitted to an intensive care unit from 2007 through 2012 were analyzed. A total of 1766 matching pairs of hospital and critical care surveys were identified. Patients' ratings of the overall hospital and critical care experiences had low correlation: r = 0.32 (95% CI, 0.28-0.37). Using the standard reporting convention, 77% of the participants rated the hospital as 9 or 10 on a 10-point scale, and 65% rated the intensive care unit as 5 on a 5-point scale. Although the hospital survey was always completed by the patient, the critical care survey was completed by a patient's family member or friend in 76% of cases and by the patient in 24%. Patient-completed critical care surveys had more correlation with hospital surveys ( r = 0.45) than did critical care surveys completed by family members ( r = 0.30), but the overall correlation remained modest. Scores on the hospital survey were at best modestly associated with scores on the critical care survey and did not reflect the specific experiences of patients and patients' families in the intensive care unit. ©2017 American Association of Critical-Care Nurses.

Flood pattern and weather determine Populus leaf litter breakdown and nitrogen dynamics on a cold desert floodplain

USGS Publications Warehouse

Andersen, D.C.; Nelson, S.M.

2006-01-01

Patterns and processes involved in litter breakdown on desert river floodplains are not well understood. We used leafpacks containing Fremont cottonwood (Populus deltoides subsp. wislizenii) leaf litter to investigate the roles of weather and microclimate, flooding (immersion), and macroinvertebrates on litter organic matter (OM) and nitrogen (N) loss on a floodplain in a cool-temperate semi-arid environment (Yampa River, northwestern Colorado, USA). Total mass of N in fresh autumn litter fell by ∼20% over winter and spring, but in most cases there was no further N loss prior to termination of the study after 653 days exposure, including up to 20 days immersion during the spring flood pulse. Final OM mass was 10–40% of initial values. The pattern of OM and N losses suggested most N would be released outside the flood season, when retention within the floodplain would be likely. The exclusion of macroinvertebrates modestly reduced the rate of OM loss (by about 10%) but had no effect on N dynamics over nine months. Immersion in floodwater accelerated OM loss, but modest variation in litter quality did not affect the breakdown rate. These results are consistent with the concept that decomposition on desert floodplains progresses much as does litter processing in desert uplands, but with periodic bouts of processing typical of aquatic environments when litter is inundated by floodwaters. The strong dependence of litter breakdown rate on weather and floods means that climate change or river flow management can easily disrupt floodplain nutrient dynamics.

THE POTENTIAL IMPACT OF INTEGRATED MALARIA TRANSMISSION CONTROL ON ENTOMOLOGIC INOCULATION RATE IN HIGHLY ENDEMIC AREAS

PubMed Central

KILLEEN, GERRY F.; McKENZIE, F. ELLIS; FOY, BRIAN D.; SCHIEFFELIN, CATHERINE; BILLINGSLEY, PETER F.; BEIER, JOHN C.

2008-01-01

We have used a relatively simple but accurate model for predicting the impact of integrated transmission control on the malaria entomologic inoculation rate (EIR) at four endemic sites from across sub-Saharan Africa and the southwest Pacific. The simulated campaign incorporated modestly effective vaccine coverage, bed net use, and larval control. The results indicate that such campaigns would reduce EIRs at all four sites by 30- to 50-fold. Even without the vaccine, 15- to 25-fold reductions of EIR were predicted, implying that integrated control with a few modestly effective tools can meaningfully reduce malaria transmission in a range of endemic settings. The model accurately predicts the effects of bed nets and indoor spraying and demonstrates that they are the most effective tools available for reducing EIR. However, the impact of domestic adult vector control is amplified by measures for reducing the rate of emergence of vectors or the level of infectiousness of the human reservoir. We conclude that available tools, including currently neglected methods for larval control, can reduce malaria transmission intensity enough to alleviate mortality. Integrated control programs should be implemented to the fullest extent possible, even in areas of intense transmission, using simple models as decision-making tools. However, we also conclude that to eliminate malaria in many areas of intense transmission is beyond the scope of methods which developing nations can currently afford. New, cost-effective, practical tools are needed if malaria is ever to be eliminated from highly endemic areas. PMID:11289662

Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

PubMed Central

Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

2013-01-01

Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (p<0.05) among groups in both phases; the 200 mg group received the least amount in Phase 1, and the 600 mg group received the most in both phases. In Phase 1, tramadol 200 mg produced significantly lower peak ratings than placebo on ratings of insomnia, lacrimation, muscular tension, and sneezing. Only tramadol 600 mg produced miosis in Phase 1. In Phase 2, tramadol 600 mg produced higher peak ratings of rhinorrhea, irritable, depressed, heavy/sluggish, and hot/cold flashes than placebo. There were no serious adverse events and no signal of abuse liability for tramadol. Conclusions ER tramadol 200 mg modestly attenuated opioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

Site-Specific Bluff Recession Rates Measured on the Alaskan Beaufort Sea Coast

NASA Astrophysics Data System (ADS)

Richmond, B.; Gadd, P.; Crowell, W.

2017-12-01

OverviewThe effects of climate change are being studied globally with coastal erosion in Arctic regions of particular concern. In support of Hilcorp Alaska's Northstar Development, short- and long-term bluff recession rates have been documented at a pipeline shore crossing located in Gwydyr Bay on the Alaskan Beaufort Sea coast. These data are presented, along with the predominant forcing mechanisms, and compared to local and regional recession rates recently published by the U.S. Geological Survey (USGS). Arctic Bluff RecessionCoastal retreat along the northern coast of Alaska occurs at two different rates: infrequent, but rapid erosion induced by strong westerly storms, and seasonal retreat related to thawing and sediment removal under more moderate wave conditions. Variability in the rate of bluff retreat is related to a number of factors, including bluff composition (ice content and sediment type), existence of a fronting beach, and wave exposure. Measured Bluff Recession at the Northstar Pipeline Shore CrossingThe location of the Northstar Development pipeline shore crossing was chosen based on analysis of historical aerial photos acquired between 1949 and 1996. Over this 47-year period, the average annualized rate of bluff retreat in the study area ranged from 1.6 to 3.0 ft/yr. Beginning in 1996, ground-based shoreline monitoring surveys have been conducted along the bluff and ten shore-perpendicular transects at the site. The rates of bluff retreat derived from the survey data have been modest, ranging from no change to 5.8 ft/yr. The monitoring surveys indicate that waves and currents erode the bluffs by direct impact only during infrequent, but strong westerly storms that promote a short-term rise in sea level (storm surge). The more prevalent easterly storms can cause set-down, or reduction in the sea level which limits direct wave impact on the bluff, thereby decreasing the potential for wave induced erosion. Comparative StudiesRecent studies conducted by the USGS utilizing remote sensing data indicate that bluff recession rates can be as high as 61.0 ft/yr in selected areas, with much more modest regional rates, typically in the 1.0 to 6.5 ft/yr range. The average recession rate noted along the Beaufort Sea coast was 5.6 ft/yr, which is similar to the rates observed at the Northstar Pipeline

Impact of regulated secretion on anti-parasitic CD8 T cell responses

PubMed Central

Grover, Harshita Satija; Chu, H. Hamlet; Kelly, Felice D.; Yang, Soo Jung; Reese, Michael L.; Blanchard, Nicolas; Gonzalez, Federico; Chan, Shiao Wei; Boothroyd, John C.; Shastri, Nilabh; Robey, Ellen A.

2014-01-01

Summary CD8 T cells play a key role in defense against the intracellular parasite Toxoplasma but why certain CD8 responses are more potent than others is not well understood. Here, we describe a parasite antigen ROP5 that elicits a modest CD8 T cell response in genetically susceptible mice. ROP5 is secreted via parasite organelles termed rhoptries that are injected directly into host cells during invasion, whereas the protective, dense granule antigen, GRA6, is constitutively secreted into the parasitophorous vacuole. Transgenic parasites in which the ROP5 antigenic epitope was targeted for secretion through dense granules led to enhanced CD8 T cell responses, whereas targeting the GRA6 epitope to rhoptries led to reduced CD8 responses. CD8 T cell responses to the dense granule-targeted ROP5 epitope resulted in reduced parasite load in the brain. These data suggest that the mode of secretion impacts the efficacy of parasite-specific CD8 T cell responses. PMID:24857659

Role of Botulinum Toxin in Depression.

PubMed

Parsaik, Ajay K; Mascarenhas, Sonia S; Hashmi, Aqeel; Prokop, Larry J; John, Vineeth; Okusaga, Olaoluwa; Singh, Balwinder

2016-03-01

The goal of this review was to consolidate the evidence concerning the efficacy of botulinum toxin type A (onabotulinumtoxinA) in depression. We searched MEDLINE, EMBASE, Cochrane, and Scopus through May 5, 2014, for studies evaluating the efficacy of botulinum toxin A in depression. Only randomized controlled trials were included in the meta-analysis. A pooled mean difference in primary depression score, and pooled odds ratio for response and remission rate with 95% confidence interval (CI) were estimated using the random-effects model. Heterogeneity was assessed using Cochran Q test and χ statistic. Of the 639 articles that were initially retrieved, 5 studies enrolling 194 subjects (age 49±9.6 y) were included in the systematic review, and 3 randomized controlled trials enrolling 134 subjects were included in the meta-analysis. The meta-analysis showed a significant decrease in mean primary depression scores among patients who received botulinum toxin A compared with placebo (-9.80; 95% CI, -12.90 to -6.69) with modest heterogeneity between the studies (Cochran Q test, χ=70). Response and remission rates were 8.3 and 4.6 times higher, respectively, among patients receiving botulinum toxin A compared with placebo, with no heterogeneity between the studies. The 2 studies excluded from the meta-analysis also found a significant decrease in primary depression scores in patients after receiving botulinum toxin A. A few subjects had minor side effects, which were similar between the groups receiving botulinum toxin and those receiving placebo. This study suggests that botulinum toxin A can produce significant improvement in depressive symptoms and is a safe adjunctive treatment for patients receiving pharmacotherapy for depression. Future trials are needed to evaluate the antidepressant effect per se of botulinum toxin A and to further elucidate the underlying antidepressant mechanism of botulinum toxin A.

Sorafenib in advanced melanoma: a critical role for pharmacokinetics?

PubMed Central

Pécuchet, N; Lebbe, C; Mir, O; Billemont, B; Blanchet, B; Franck, N; Viguier, M; Coriat, R; Tod, M; Avril, M-F; Goldwasser, F

2012-01-01

Background: Inter-patient pharmacokinetic variability can lead to suboptimal drug exposure, and therefore might impact the efficacy of sorafenib. This study reports long-term pharmacokinetic monitoring of patients treated with sorafenib and a retrospective pharmacodynamic/pharmacokinetic analysis in melanoma patients. Patients and methods: Heavily pretreated patients with stage IV melanoma were started on sorafenib 400 mg twice daily (bid). In the absence of limiting toxicity, dose escalation of 200 mg bid levels was done every 2 weeks. Plasma sorafenib measurement was performed at each visit, allowing a retrospective pharmacodynamic/pharmacokinetic analysis for safety and efficacy. Results: In all, 19 of 30 patients underwent dose escalation over 400 mg bid, and 28 were evaluable for response. The overall disease control rate was 61% (95% confidence interval (CI): 42.6–78.8), including three confirmed responses (12%). Disease control rate and progression-free survival (PFS) were improved in patients with high vs low exposure (80% vs 32%, P=0.02, and 5.25 vs 2.5 months, P=0.005, hazard ratio (HR)=0.28 (95% CI: 0.11–0.73)). In contrast, drug dosing had no effect on PFS. In multivariate analysis, drug exposure was the only factor associated with PFS (HR=0.36 (95% CI: 0.13–0.99)). Diarrhoea and anorexia were correlated with drug dosing, while hypertension and hand–foot skin reaction were correlated with drug exposure. Conclusions: Although sorafenib had modest efficacy in melanoma, these results suggest a correlation between exposure and efficacy of sorafenib. Therefore, dose optimisation in patients with low exposure at standard doses should be evaluated in validated indications. PMID:22767146

Efficacy and safety of sorafenib in combination with gemcitabine in patients with advanced hepatocellular carcinoma: a multicenter, open-label, single-arm phase II study.

PubMed

Srimuninnimit, Vichien; Sriuranpong, Virote; Suwanvecho, Suthida

2014-09-01

Currently, the only standard systemic treatment for advanced hepatocellular carcinoma is sorafenib monotherapy. The study was conducted to assess the efficacy and safety of the novel combination of sorafenib and gemcitabine in the treatment of advanced hepatocellular carcinoma. Between March 2008 and October 2010, patients with advanced pathologically proven hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A or B received sorafenib plus gemcitabine. Treatment included 4-week cycle of gemcitabine (1000 mg/m(2) days 1, 8, 15) to the maximum of six cycles together with sorafenib (400 mg twice daily). Patient continued sorafenib until disease progression or withdrawal from other reasons. The primary end point is progression-free survival. Forty-five patients were enrolled in this study. The median progression-free survival was 3.7 months (95% CI 3.5-3.8). The overall response rate was 4% with no complete responses and the disease control rate was 66%. The median overall survival (OS) was 11.6 months (95% CI 7.4-15.9). The median time to progression was 3.6 months (95% CI 3.4-3.7). The most frequently reported grade 3/4 treatment-related adverse events included thrombocytopenia 33%, neutropenia 16% and hand-foot skin reaction 13%. The study regimen was well tolerated. The combination of sorafenib and gemcitabine in advanced hepatocellular carcinoma is generally well tolerated and has modest clinical efficacy. The median OS is up to 1 year. However, well-designed randomized controlled trials with a sorafenib alone comparator arm are needed to confirm this finding. © 2014 Wiley Publishing Asia Pty Ltd.

Modeling Acute Health Effects of Astronauts from Exposure to Large Solar Particle Events

NASA Technical Reports Server (NTRS)

Hu, Shaowen; Kim, Myung-Hee Y.; Cucinotta, Francis A.

2011-01-01

In space exploration outside the Earth s geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possible failure of the mission. Acute risks are of special concern during extra-vehicular activities because of the rapid onset of SPE. However, most SPEs will not lead to acute risks but can lead to mission disruption if accurate projection methods are not available. Acute Radiation Sickness (ARS) is a group of clinical syndromes developing acutely (within several seconds to 3 days) after high dose whole-body or significant partial-body ionizing radiation exposures. The manifestation of these syndromes reflects the disturbance of physiological processes of various cellular groups damaged by radiation. Hematopoietic cells, skin, epithelium, intestine, and vascular endothelium are among the most sensitive tissues of human body to ionizing radiation. Most ARS symptoms are directly related to these tissues and other systems (nervous, endocrine, and cardiovascular, etc.) with coupled regulations. Here we report the progress in bio-mathematical models to describe the dose and time-dependent early human responses to ionizing radiation. The responses include lymphocyte depression, granulocyte modulation, fatigue and weakness syndrome, and upper gastrointestinal distress. The modest dose and dose-rates of SPEs are predicted to lead to large sparing of ARS, however detailed experimental data on a range of proton dose-rates for organ doses from 0.5 to 2 Gy is needed to validate the models. We also report on the ARRBOD code that integrates the BRYNTRN and SUMDOSE codes, which are used to estimate the SPE organ doses for astronauts under various space travel scenarios, with our models of ARS. The more recent effort is to provide easy web access to space radiation risk assessment using the ARRBOD code.

A randomized study to compare sequential chemoradiotherapy with concurrent chemoradiotherapy for unresectable locally advanced esophageal cancer.

PubMed

Gupta, Arunima; Roy, Somnath; Majumdar, Anup; Hazra, Avijit; Mallik, Chandrani

2014-01-01

Chemotherapy combined with radiotherapy can improve outcome in locally advanced esophageal cancer. This study aimed to compare efficacy and toxicity between concurrent chemoradiotherapy (CCRT) and sequential chemoradiotherapy (SCRT) in unresectable, locally advanced, esophageal squamous cell carcinoma (ESSC). Forty-one patients with unresectable, locally advanced ESCC were randomized into two arms. In the CCRT arm (Arm A), 17 patients received 50.4 Gy at 1.8 Gy per fraction over 5.6 weeks along with concurrent cisplatin (75 mg m(-2) intravenously on day 1 and 5-fluorouracil (1000 mg m(-2) continuous intravenous infusion on days 1-4 starting on the first day of irradiation and given after 28 days. In the SCRT arm (Arm B), 20 patients received two cycles of chemotherapy, using the same schedule, followed by radiotherapy fractionated in a similar manner. The endpoints were tumor response, acute and late toxicities, and disease-free survival. With a median follow up of 12.5 months, the complete response rate was 82.4% in Arm A and 35% in Arm B (P = 0.003). Statistically significant differences in frequencies of acute skin toxicity (P = 0.016), gastrointestinal toxicity (P = 0.005) and late radiation pneumonitis (P = 0.002) were found, with greater in the CCRT arm. A modest but non-significant difference was observed in median time to recurrence among complete responders in the two arms (Arm A 13 months and Arm B 15.5 months, P = 0.167) and there was also no significant difference between the Kaplan Meier survival plots (P = 0.641) of disease-free survival. Compared to sequential chemoradiotherapy, concurrent chemoradiotherapy can significantly improve local control rate but with greater risk of adverse reactions.

Does physiological acclimation to climate warming stabilize the ratio of canopy respiration to photosynthesis?

PubMed

Drake, John E; Tjoelker, Mark G; Aspinwall, Michael J; Reich, Peter B; Barton, Craig V M; Medlyn, Belinda E; Duursma, Remko A

2016-08-01

Given the contrasting short-term temperature dependences of gross primary production (GPP) and autotrophic respiration, the fraction of GPP respired by trees is predicted to increase with warming, providing a positive feedback to climate change. However, physiological acclimation may dampen or eliminate this response. We measured the fluxes of aboveground respiration (Ra ), GPP and their ratio (Ra /GPP) in large, field-grown Eucalyptus tereticornis trees exposed to ambient or warmed air temperatures (+3°C). We report continuous measurements of whole-canopy CO2 exchange, direct temperature response curves of leaf and canopy respiration, leaf and branch wood respiration, and diurnal photosynthetic measurements. Warming reduced photosynthesis, whereas physiological acclimation prevented a coincident increase in Ra . Ambient and warmed trees had a common nonlinear relationship between the fraction of GPP that was respired above ground (Ra /GPP) and the mean daily temperature. Thus, warming significantly increased Ra /GPP by moving plants to higher positions on the shared Ra /GPP vs daily temperature relationship, but this effect was modest and only notable during hot conditions. Despite the physiological acclimation of autotrophic respiration to warming, increases in temperature and the frequency of heat waves may modestly increase tree Ra /GPP, contributing to a positive feedback between climate warming and atmospheric CO2 accumulation. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Assessing fidelity in individual and family therapy for adolescent substance abuse.

PubMed

Hogue, Aaron; Dauber, Sarah; Chinchilla, Priscilla; Fried, Adam; Henderson, Craig; Inclan, Jaime; Reiner, Robert H; Liddle, Howard A

2008-09-01

This study introduces an observational measure of fidelity in evidence-based practices for adolescent substance abuse treatment. The Therapist Behavior Rating Scale-Competence (TBRS-C) measures adherence and competence in individual cognitive-behavioral therapy and multidimensional family therapy for adolescent substance abuse. The TBRS-C assesses fidelity to the core therapeutic goals of each approach and also contains global ratings of therapist competence. Study participants were 136 clinically referred adolescents and their families observed in 437 treatment sessions. The TBRS-C demonstrated strong interrater reliability for goal-specific ratings of treatment adherence, and modest reliability for goal-specific and global ratings of therapist competence, evidence of construct validity, and discriminant validity with an observational measure of therapeutic alliance. The utility of the TBRS-C for evaluating treatment fidelity in field settings is discussed.

A diagnostic-ratio approach to measuring beliefs about the leadership abilities of male and female managers.

PubMed

Martell, R F; Desmet, A L

2001-12-01

This study departed from previous research on gender stereotyping in the leadership domain by adopting a more comprehensive view of leadership and using a diagnostic-ratio measurement strategy. One hundred and fifty-one managers (95 men and 56 women) judged the leadership effectiveness of male and female middle managers by providing likelihood ratings for 14 categories of leader behavior. As expected, the likelihood ratings for some leader behaviors were greater for male managers, whereas for other leader behaviors, the likelihood ratings were greater for female managers or were no different. Leadership ratings revealed some evidence of a same-gender bias. Providing explicit verification of managerial success had only a modest effect on gender stereotyping. The merits of adopting a probabilistic approach in examining the perception and treatment of stigmatized groups are discussed.

Alignment of dust grains in ionized regions

NASA Technical Reports Server (NTRS)

Anderson, Nels; Watson, William D.

1993-01-01

The rate at which charged dust grains in a plasma are torqued by passing ions and electrons is calculated. When photo-emission of electrons is not important, attraction of ions by the grain monopole potential increases the rate at which the grains' spins are dealigned by nearly an order of magnitude. Consequently, the energy density of the magnetic field required to align grains in an H II region may be increased by about an order of magnitude. In contrast, electric dipole and quadrupole moments are unlikely to produce large dealignment rates for grains of modest length-to-width ratio. Nonetheless, for positively charged grains these higher-order moments likely prevent monopole repulsion of ions from reducing the dealignment rate far below that for neutral grains. The presence of positive grain charge therefore does not greatly facilitate grain alignment in an H II region.

Increased West Antarctic and unchanged East Antarctic ice discharge over the last 7 years

NASA Astrophysics Data System (ADS)

Gardner, Alex S.; Moholdt, Geir; Scambos, Ted; Fahnstock, Mark; Ligtenberg, Stefan; van den Broeke, Michiel; Nilsson, Johan

2018-02-01

Ice discharge from large ice sheets plays a direct role in determining rates of sea-level rise. We map present-day Antarctic-wide surface velocities using Landsat 7 and 8 imagery spanning 2013-2015 and compare to earlier estimates derived from synthetic aperture radar, revealing heterogeneous changes in ice flow since ˜ 2008. The new mapping provides complete coastal and inland coverage of ice velocity north of 82.4° S with a mean error of < 10 m yr-1, resulting from multiple overlapping image pairs acquired during the daylight period. Using an optimized flux gate, ice discharge from Antarctica is 1929 ± 40 Gigatons per year (Gt yr-1) in 2015, an increase of 36 ± 15 Gt yr-1 from the time of the radar mapping. Flow accelerations across the grounding lines of West Antarctica's Amundsen Sea Embayment, Getz Ice Shelf and Marguerite Bay on the western Antarctic Peninsula, account for 88 % of this increase. In contrast, glaciers draining the East Antarctic Ice Sheet have been remarkably constant over the period of observation. Including modeled rates of snow accumulation and basal melt, the Antarctic ice sheet lost ice at an average rate of 183 ± 94 Gt yr-1 between 2008 and 2015. The modest increase in ice discharge over the past 7 years is contrasted by high rates of ice sheet mass loss and distinct spatial patters of elevation lowering. The West Antarctic Ice Sheet is experiencing high rates of mass loss and displays distinct patterns of elevation lowering that point to a dynamic imbalance. We find modest increase in ice discharge over the past 7 years, which suggests that the recent pattern of mass loss in Antarctica is part of a longer-term phase of enhanced glacier flow initiated in the decades leading up to the first continent-wide radar mapping of ice flow.

Elucidating dynamic responses of North Pacific fish populations to climatic forcing: Influence of life-history strategy

NASA Astrophysics Data System (ADS)

Yatsu, A.; Aydin, K. Y.; King, J. R.; McFarlane, G. A.; Chiba, S.; Tadokoro, K.; Kaeriyama, M.; Watanabe, Y.

2008-05-01

In order to explore mechanistic linkages between low-frequency ocean/climate variability, and fish population responses, we undertook comparative studies of time-series of recruitment-related productivity and the biomass levels of fish stocks representing five life-history strategies in the northern North Pacific between the 1950s and the present. We selected seven species: Japanese sardine ( Sardinopus melanostictus) and California sardine ( Sardinopus sagax) (opportunistic strategists), walleye pollock ( Theragra chalcogramma, intermediate strategist), pink salmon ( Oncorhynchus gorbuscha, salmonic strategist), sablefish ( Anoplopoma fimbria) and Pacific halibut ( Hippoglossus stenolepis) (periodic strategists) and spiny dogfish ( Squalus acanthias, equilibrium strategist). The responses in terms of productivity of sardine, pink salmon, sablefish and halibut to climatic regime shifts were generally immediate, delayed, or no substantial responses depending on the particular regime shift year and fish stock (population). In walleye pollock, there were some periods of high productivity and low productivity, but not coincidental to climatic regime shifts, likely due to indirect climate forcing impacts on both bottom-up and top-down processes. Biomass of zooplankton and all fish stocks examined, except for spiny dogfish whose data were limited, indicated a decadal pattern with the most gradual changes in periodic strategists and most intensive and rapid changes in opportunistic strategists. Responses of sardine productivity to regime shifts were the most intense, probably due to the absence of density-dependent effects and the availability of refuges from predators when sardine biomass was extremely low. Spiny dogfish were least affected by environmental variability. Conversely, spiny dogfish are likely to withstand only modest harvest rates due to their very low intrinsic rate of increase. Thus, each life-history strategy type had a unique response to climatic forcing, owing to their inherent biological traits such as mode, frequency and intensity of reproduction, early life style, age of maturity and longevity. On the other hand, responses of different stocks within a species to climatic regime shifts were unique to each local region, because large-scale climatic forcings are modulated by local physical, chemical and biological processes. The observed response time or absence of response in recruitment-related fish productivity to climatic regime shifts may be influenced by (1) local environmental conditions (immediate, with a delay or no effects), (2) phenological shifts in zooplankton life-history (immediate or with a delay), and (3) stochastic episodic events in both top-down and bottom-up processes (immediate, with a delay or no effects).

Projections of the Size and Composition of the U.S. Population: 2014 to 2060. Population Estimates and Projections. Current Population Reports. P25-1143

ERIC Educational Resources Information Center

Colby, Sandra L.; Ortman, Jennifer M.

2015-01-01

Between 2014 and 2060, the U.S. population is projected to increase from 319 million to 417 million, reaching 400 million in 2051. The U.S. population is projected to grow more slowly in future decades than in the recent past, as these projections assume that fertility rates will continue to decline and that there will be a modest decline in the…

Engineering Robust Nanocomposite Networks

DTIC Science & Technology

2014-12-16

Krieger –Dougherty  type  constitutive  relationship  and  steady-­‐state  viscosity   measurements  to  estimate  the...state  thixotropic   behavior  of  the  rod  suspensions  at  modest  concentrations,  using  a  fit  to  the   Krieger ...fits   reveal  an  aggregate  density  that  increases  with  shear  rate  (B).   Krieger -­‐Dougherty

Survival benefit of surgery in recurrent glioblastoma multiforme.

PubMed

Choudry, Usama Khalid; Khan, Saad Akhtar; Shamim, Muhammad Shahzad

2017-12-01

There is an ongoing debate regarding role of surgery for recurrent glioblastoma multiforme (GBM). Older literature hinted at only modest survival benefits with surgery and a high rate of morbidity. However, more recent literature suggests better survival that may be attributed to better surgical techniques and better options in adjuvant treatment. Herein the authors review recent literature with regards to the possible role of surgery in recurrent GBM and also look into the key factors impacting second surgery. .

Wire-packed heat exchangers for dilution refrigerators.

PubMed

Polturak, E; Rappaport, M; Rosenbaum, R

1978-03-01

Very simple wire-packed step heat exchangers for dilution refrigerators are described. No sintering is used in fabrication. Flow impedances and thermal resistance between the liquid and the copper wires are low. A refrigerator with five wire-packed heat exchangers in addition to a countercurrent heat exchanger attains a temperature of 11.4 mK with a single mixing chamber and 6.1 mK with two mixing chambers. High cooling power is achieved at modest (3)He circulation rates.

High Rate Lithium-Thionyl Chloride Battery Development for Undersea Weapon Propulsion Applications. Revised.

DTIC Science & Technology

1978-08-23

dislodged only a fraction of the SAB. According to FMI, thinner, more open grades of vitreous carbon paper would permit higher loading of SAB...bonded carbon fiber, porous silver and porous nickel cathodes were dis- charged in test cells. All polarized immediately below 2. 7 volts at 52 mA/cm2...Increased electrolyte molarity delivered a modest increase in run time but resulted -_ in somewhat lower load voltage plateaus. - As before, carbon fiber

Psychotic experiences are linked to cannabis use in adolescents in the community because of common underlying environmental risk factors.

PubMed

Shakoor, Sania; Zavos, Helena M S; McGuire, Philip; Cardno, Alastair G; Freeman, Daniel; Ronald, Angelica

2015-06-30

Cannabis users are more likely to have psychotic experiences (PEs). The degree to which these associations are driven by genetic or environmental influences in adolescence is unknown. This study estimated the genetic and environmental contributions to the relationship between cannabis use and PEs. Specific PEs were measured in a community-based twin sample (4830 16-year-old pairs) using self-reports and parent-reports. Adolescents reported on ever using cannabis. Multivariate liability threshold structural equation model-fitting was conducted. Cannabis use was significantly correlated with PEs. Modest heritability (37%), common environmental influences (55%) and unique environment (8%) were found for cannabis use. For PEs, modest heritability (27-54%), unique environmental influences (E=12-50%) and little common environmental influences (11-20%), with the exception of parent-rated Negative Symptoms (42%), were reported. Environmental influences explained all of the covariation between cannabis use and paranoia, cognitive disorganization and parent-rated negative symptoms (bivariate common environment=69-100%, bivariate unique environment=28-31%), whilst the relationship between cannabis use and hallucinations indicated familial influences. Cannabis use explains 2-5% of variance in positive, cognitive, and negative PEs. Cannabis use and psychotic experience co-occur due to environmental factors. Focus on specific environments may reveal why adolescent cannabis use and psychotic experiences tend to 'travel together'. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Psychotic experiences are linked to cannabis use in adolescents in the community because of common underlying environmental risk factors

PubMed Central

Shakoor, Sania; Zavos, Helena M.S.; McGuire, Philip; Cardno, Alastair G.; Freeman, Daniel; Ronald, Angelica

2015-01-01

Cannabis users are more likely to have psychotic experiences (PEs). The degree to which these associations are driven by genetic or environmental influences in adolescence is unknown. This study estimated the genetic and environmental contributions to the relationship between cannabis use and PEs. Specific PEs were measured in a community-based twin sample (4830 16-year-old pairs) using self-reports and parent-reports. Adolescents reported on ever using cannabis. Multivariate liability threshold structural equation model-fitting was conducted. Cannabis use was significantly correlated with PEs. Modest heritability (37%), common environmental influences (55%) and unique environment (8%) were found for cannabis use. For PEs, modest heritability (27–54%), unique environmental influences (E=12–50%) and little common environmental influences (11–20%), with the exception of parent-rated Negative Symptoms (42%), were reported. Environmental influences explained all of the covariation between cannabis use and paranoia, cognitive disorganization and parent-rated negative symptoms (bivariate common environment=69–100%, bivariate unique environment=28–31%), whilst the relationship between cannabis use and hallucinations indicated familial influences. Cannabis use explains 2–5% of variance in positive, cognitive, and negative PEs. Cannabis use and psychotic experience co-occur due to environmental factors. Focus on specific environments may reveal why adolescent cannabis use and psychotic experiences tend to ‘travel together’. PMID:25912376

Comparisons of Fluticasone to Budesonide in the Treatment of Eosinophilic Esophagitis.

PubMed

Albert, Dustin; Heifert, Theresa A; Min, Steve B; Maydonovitch, Corinne L; Baker, Thomas P; Chen, Yen-Ju; Moawad, Fouad J

2016-07-01

Topical steroids are first-line treatment agents for eosinophilic esophagitis; however, some studies have demonstrated modest efficacy in inducing histologic remission. The aim of this study was to determine response to two topical steroids (fluticasone and budesonide), compare their efficacy, and examine patient characteristics which could predict non-response to topical steroids. We performed a retrospective review of an established EoE registry. Inclusion criteria were patients >1 year of age who were diagnosed with EoE as defined by the most recent consensus guidelines. All patients were treated with an 8-week course of either swallowed fluticasone or viscous budesonide. Responders were defined as achieving <15 eosinophils per high-power field (eos/hpf) in both proximal and distal esophageal biopsies. Demographic, clinical, endoscopic, and histologic features were examined. The study cohort included 75 EoE patients with a median age of 33 years (range 2-64 years), 71 % adults, 84 % male, and 76 % Caucasian. Overall histologic response rate to topical steroids was 51 %, while clinical response was 71 %. There was no significant differences in histologic response to treatment between children and adults (68 vs. 44 %, p = 0.111). There was no significant difference in response between males and females (47 vs. 73 %, p = 0.191) and between the two types of steroids (48 vs. 56 %, p = 0.632). Responders and non-responders were similar in clinical presentation and baseline endoscopic findings. Following treatment, responders had significantly less peak proximal (4.0 ± 4.4 vs. 46 ± 53, p < 0.001) and distal eosinophil counts (3.5 ± 3.8 vs. 60 ± 47, p < 0.001) compared to non-responders. There were no predictors of response to steroids identified. Histologic response to treatment was observed in approximately half the cohort, while more than two-thirds experienced clinical response to topical steroids. Response was similar between fluticasone and budesonide. Given the lack of differences in clinical presentation or endoscopic features, predictors of non-response were not seen.

The social perception of emotional abilities: expanding what we know about observer ratings of emotional intelligence.

PubMed

Elfenbein, Hillary Anger; Barsade, Sigal G; Eisenkraft, Noah

2015-02-01

We examine the social perception of emotional intelligence (EI) through the use of observer ratings. Individuals frequently judge others' emotional abilities in real-world settings, yet we know little about the properties of such ratings. This article examines the social perception of EI and expands the evidence to evaluate its reliability and cross-judge agreement, as well as its convergent, divergent, and predictive validity. Three studies use real-world colleagues as observers and data from 2,521 participants. Results indicate significant consensus across observers about targets' EI, moderate but significant self-observer agreement, and modest but relatively consistent discriminant validity across the components of EI. Observer ratings significantly predicted interdependent task performance, even after controlling for numerous factors. Notably, predictive validity was greater for observer-rated than for self-rated or ability-tested EI. We discuss the minimal associations of observer ratings with ability-tested EI, study limitations, future directions, and practical implications. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Multi-Method Assessment of ADHD Characteristics in Preschool Children: Relations between Measures

PubMed Central

Sims, Darcey M.; Lonigan, Christopher J.

2011-01-01

Several forms of assessment tools, including behavioral rating scales and objective tests such as the Continuous Performance Test (CPT), can be used to measure inattentive and hyperactive/impulsive behaviors associated with Attention-Deficit/Hyperactivity Disorder (ADHD). However, research with school-age children has shown that the correlations between parent ratings, teacher ratings, and scores on objective measures of ADHD-characteristic behaviors are modest at best. In this study, we examined the relations between parent and teacher ratings of ADHD and CPT scores in a sample of 65 preschoolers ranging from 50 to 72 months of age. No significant associations between teacher and parent ratings of ADHD were found. Parent-ratings of both inattention and hyperactivity/impulsivity accounted for variance in CPT omission errors but not CPT commission errors. Teacher ratings showed evidence of convergent and discriminant validity when entered simultaneously in a hierarchical regression. These tools may be measuring different aspects of inattention and hyperactivity/impulsivity. PMID:22518069

Anti-müllerian hormone levels are associated with live birth rates in ART, but the predictive ability of anti-müllerian hormone is modest.

PubMed

Alson, Sara S E; Bungum, Leif J; Giwercman, Aleksander; Henic, Emir

2018-06-01

The aim was to evaluate the association between serum Anti-Müllerian Hormone (AMH) level and cumulative live birth rates (LBR) in patients undergoing their first in vitro fertilization (IVF) treatment cycle, and to compare serum AMH levels with Antral Follicle Count (AFC) and Ovarian Sensitivity Index (OSI) as predictors of live birth. A prospective cohort study of 454 patients under the age of 40 and with a regular menstrual cycle of 21-35 days, undergoing their first IVF treatment cycles between September 2010 and June 2015. Participants were divided into three groups based on their AMH level, (AMH ≤10, AMH 10-<30 and AMH ≥30 pmol/l). Any difference in AMH-distribution between patients with or without live birth was analyzed using a Mann-Whitney-test, and live birth rates were compared between groups by a chi-squared test for linear trend. The ability of AMH, OSI and AFC as predictors of live birth was assessed by a receiver operating characteristics-analysis and the area under the curve (AUC) was calculated. Patients with live birth had a higher AMH, median (range) 26 [0-137] pmol/l, compared with patients without live birth, AMH 22 [0-154] pmol/l, p = 0.035. Mean live birth rate (SD) was 0.36 (0.48) in the total cohort, 0.26 (0.44) in AMH-group <10, 0.34 (0.48) in AMH-group 10-<30, and 0.41(0.49) in AMH-group ≥30. Thus live birth rates increased with 8% per AMH-group (95% CI: 0.02 -0.14, p = 0.015). The AUC for AFC was 0.56, for AMH 0.57 and for OSI 0.63, respectively. AMH concentration in serum is associated with live birth rates after IVF. Our results suggest that both AMH, AFC and OSI have an equal but modest predictive ability in relation to live birth rate. Copyright © 2018 Elsevier B.V. All rights reserved.

Steady, modest slip over multiple earthquake cycles on the Owens Valley and Little Lake fault zones

NASA Astrophysics Data System (ADS)

Amos, C. B.; Haddon, E. K.; Burgmann, R.; Zielke, O.; Jayko, A. S.

2015-12-01

A comprehensive picture of current plate-boundary deformation requires integration of short-term geodetic records with longer-term geologic strain. Comparing rates of deformation across these time intervals highlights potential time-dependencies in both geodetic and geologic records and yields critical insight into the earthquake deformation process. The southern Walker Lane Belt in eastern California represents one location where short-term strain recorded by geodesy apparently outpaces longer-term geologic fault slip measured from displaced rocks and landforms. This discrepancy persists both for individual structures and across the width of the deforming zone, where ~1 cm/yr of current dextral shear exceeds Quaternary slip rates summed across individual faults. The Owens Valley and Little Lake fault systems form the western boundary of the southern Walker Lane and host a range of published slip rate estimates from ~1 - 7 mm/yr over varying time intervals based on both geodetic and geologic measurements. New analysis of offset geomorphic piercing lines from airborne lidar and field measurements along the Owens Valley fault provides a snapshot of deformation during individual earthquakes and over many seismic cycles. Viewed in context of previously reported ages from pluvial and other landforms in Owens Valley, these offsets suggest slip rates of ~0.6 - 1.6 mm/yr over the past 103 - 105 years. Such rates agree with similar estimates immediately to the south on the Little Lake fault, where lidar measurements indicate dextral slip averaging ~0.6 - 1.3 mm/yr over comparable time intervals. Taken together, these results suggest steady, modest slip in the absence of significant variations over the Mid-to-Late Quaternary for a ~200 km span of the southwestern Walker Lane. Our findings argue against the presence of long-range fault interactions and slip-rate variations for this portion of the larger, regional fault network. This result also suggests that faster slip-rate estimates from geodetic measurements reflect transients over much shorter time scales. Additionally, the persistence of relatively faster geodetic shear in comparison with time-averaged fault slip leaves open the possibility of significant off-fault deformation or slip on subsidiary structures across the Owens Valley.

Effects of a Diet High in Salt, Fat, and Sugar on Telemetric Blood Pressure Measurements in Conscious, Unrestrained Adult Yucatan Miniature Swine (Sus scrofa)

PubMed Central

Myrie, Semone B; McKnight, Leslie L; King, J Christopher; McGuire, John J; Vliet, Bruce N Van; Bertolo, Robert F

2012-01-01

Radiotelemetry was used to evaluate diet-related elevation of blood pressure in adult Yucatan miniature swine. Systolic arterial blood pressure (SAP), diastolic atrial blood pressure (DAP), heart rate, and locomotor activity were assessed in 9- or 11-mo-old Yucatan miniature pigs fed a standard diet or a North American-type diet high in salt, fat, and sugar (HSFS). Compared with pigs fed standard diet, pigs fed HSFS diet showed markedly elevated SAP (132 ± 3 compared with 156 ± 6 mm Hg), whereas DAP was unchanged (92 ± 2 compared with 99 ± 5 mm Hg). In addition, all pigs were modestly sensitive to short-term changes in dietary salt, as indicated by a 6% to 7% response in blood pressure parameters. According to these data, the increase in SAP for pigs on the HSFS diet was too large to be explained by the NaCl content of the diet alone. We found no evidence of endothelial dysfunction, and the relaxation responses of isolated coronary arteries actually were enhanced in the HSFS group. In conclusion, in a Yucatan miniature pigs model chronically fed a HSFS diet, DAP did not increase, but SAP and pulse pressure appeared to be affected by high dietary levels of fat or sugar (or both). PMID:23043781

Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment

PubMed Central

Martin, Petra; Biniecka, Monika; Ó'Meachair, Shane; Maguire, Aoife; Tosetto, Miriam; Nolan, Blathnaid; Hyland, John; Sheahan, Kieran; O'Donoghue, Diarmuid; Mulcahy, Hugh; Fennelly, David; O'Sullivan, Jacintha

2018-01-01

Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC. PMID:29535825

Association between violent behaviour and impaired prepulse inhibition of the startle response in antisocial personality disorder and schizophrenia.

PubMed

Kumari, Veena; Das, Mrigen; Hodgins, Sheilagh; Zachariah, Elizabeth; Barkataki, Ian; Howlett, Michael; Sharma, Tonmoy

2005-03-07

Violent behaviour has a strong association with antisocial personality disorder (APD) and schizophrenia. Although developments in the understanding of socio-environmental factors associated with violence should not be ignored, advances in prevention and treatment of violent behaviour would benefit by improved understanding of its neurobiological and cognitive basis. The authors, therefore, investigated prepulse inhibition (PPI) of the startle response in APD and schizophrenia in relation to a history of serious violence. The neural substrates of PPI, especially the hippocampus, amygdala, thalamus and basal ganglia, are implicated in violence as well as in APD and schizophrenia. The study included four groups: (i) patients with APD and a history of violence, (ii) patients with schizophrenia and a history of violence, (iii) patients with schizophrenia without a history of violence, and (iv) healthy subjects with no history of violence or a mental disorder. All subjects were assessed identically on acoustic PPI. Compared to healthy subjects, significantly reduced PPI occurred in APD, violent schizophrenia and non-violent schizophrenia patients. Although PPI did not significantly differentiate the three clinical groups, high ratings of violence were modestly associated with reduced PPI across the entire study sample. Violent patients with impulsive and premeditated violence showed comparable PPI. The association between violent behaviour and impaired PPI suggests that neural structures and functions underlying PPI are implicated in (inhibition of) violence.

InSAR Remote Sensing of Localized Surface Layer Subsidence in New Orleans, LA

NASA Astrophysics Data System (ADS)

An, K.; Jones, C. E.; Blom, R. G.; Kent, J. D.; Ivins, E. R.

2015-12-01

More than half of Louisiana's drinking water is dependent on groundwater, and extraction of these resources along with high oil and gas production has contributed to localized subsidence in many parts of New Orleans. This increases the vulnerability of levee failure during intense storms such as Hurricane Katrina in 2005, before which rapid subsidence had already been identified and contributed to the failing levees and catastrophic flooding. An interferogram containing airborne radar data from NASA's UAVSAR was combined with local geographic information systems (GIS) data for 2009-12 to help identify the sources of subsidence and mask out unrelated features such as surface water. We have observed the highest vertical velocity rates at the NASA Michoud Assembly Facility (high water use) and Norco (high oil/gas production). Many other notable features such as the: Bonnet-Carre Spillway, MRGO canal, levee lines along the Lower 9th Ward and power plants, are also showing concerning rates of subsidence. Even new housing loads, soil type differences, and buried beach sands seem to have modest correlations with patterns seen in UAVSAR. Current hurricane protection and coastal restoration efforts still have not incorporated late 20th century water level and geodetic data into their projections. Using SAR interferometry and local GIS datasets, areas of subsidence can be identified in a more efficient and economical manner, especially for emergency response.

Comparison of gamma-gamma Phase Coarsening Responses of Three Powder Metal Disk Superalloys

NASA Technical Reports Server (NTRS)

Gabb, T. P.; Gayda, J.; Johnson, D. F.; MacKay, R. A.; Rogers, R. B.; Sudbrack, C. K.; Garg, A.; Locci, I. E.; Semiatin, S. L.; Kang, E.

2016-01-01

The phase microstructures of several powder metal (PM) disk superalloys were quantitatively evaluated. Contents, chemistries, and lattice parameters of gamma and gamma strengthening phase were determined for conventionally heat treated Alloy 10, LSHR, and ME3 superalloys, after electrolytic phase extractions. Several of long term heat treatments were then performed, to allow quantification of the precipitation, content, and size distribution of gamma at a long time interval to approximate equilibrium conditions. Additional coarsening heat treatments were performed at multiple temperatures and shorter time intervals, to allow quantification of the precipitation, contents and size distributions of gamma at conditions diverging from equilibrium. Modest differences in gamma and gamma lattice parameters and their mismatch were observed among the alloys, which varied with heat treatment. Yet, gamma coarsening rates were very similar for all three alloys in the heat treatment conditions examined. Alloy 10 had higher gamma dissolution and formation temperatures than LSHR and ME3, but a lower lattice mismatch, which was slightly positive for all three alloys at room temperature. The gamma precipitates of Alloy 10 appeared to remain coherent at higher temperatures than for LSHR and ME3. Higher coarsening rates were observed for gamma precipitates residing along grain boundaries than for those within grains in all three alloys, during slow-moderate quenching from supersolvus solution heat treatments, and during aging at temperatures of 843 C and higher.

Psychometric Properties of the Pain Numeric Rating Scale When Applied to Multiple Body Regions among Professional Musicians.

PubMed

Saltychev, Mikhail; Vastamäki, Heidi; Mattie, Ryan; McCormick, Zachary; Vastamäki, Martti; Laimi, Katri

2016-01-01

Despite the broad popularity of a numeric rating scale (NRS) its psychometric properties are not well known. The objective was to determine if there is any difference in the discrimination ability of the NRS when used for measuring pain severity separately in different body regions. Cross-sectional survey study of 630 professional musicians. Item Response Theory (IRT) was used to define the psychometric properties of the NRS. The discrimination ability of the pain NRS was dependent on the body area to which it was applied. The discrimination was low 0.5 (95% CI 0.4. to 0.7) for the hand region and perfect for the shoulder and upper part of the neck- 3.2 (95% CI 1.2 to 5.2) and 10.5 (95% CI 10.0 to 10.9), respectively. Both shoulder and neck NRSs showed a great shift towards higher levels of pain severity meaning that the ability of the NRS to discriminate low levels of pain is poor. NRS scores obtained from all other regions did not demonstrate any discrimination ability. The pain NRS might have different psychometric properties depending on the body area to which it is applied. Overall, the modest discrimination ability of the pain NRS implies that it should be used in screening questionnaires with some reservations.

Psychometric Properties of the Pain Numeric Rating Scale When Applied to Multiple Body Regions among Professional Musicians

PubMed Central

2016-01-01

Background Despite the broad popularity of a numeric rating scale (NRS) its psychometric properties are not well known. The objective was to determine if there is any difference in the discrimination ability of the NRS when used for measuring pain severity separately in different body regions. Methods Cross-sectional survey study of 630 professional musicians. Item Response Theory (IRT) was used to define the psychometric properties of the NRS. Results The discrimination ability of the pain NRS was dependent on the body area to which it was applied. The discrimination was low 0.5 (95% CI 0.4. to 0.7) for the hand region and perfect for the shoulder and upper part of the neck– 3.2 (95% CI 1.2 to 5.2) and 10.5 (95% CI 10.0 to 10.9), respectively. Both shoulder and neck NRSs showed a great shift towards higher levels of pain severity meaning that the ability of the NRS to discriminate low levels of pain is poor. NRS scores obtained from all other regions did not demonstrate any discrimination ability. Conclusions The pain NRS might have different psychometric properties depending on the body area to which it is applied. Overall, the modest discrimination ability of the pain NRS implies that it should be used in screening questionnaires with some reservations. PMID:27603011

Determinants of the pace of global innovation in energy technologies.

PubMed

Bettencourt, Luís M A; Trancik, Jessika E; Kaur, Jasleen

2013-01-01

Understanding the factors driving innovation in energy technologies is of critical importance to mitigating climate change and addressing other energy-related global challenges. Low levels of innovation, measured in terms of energy patent filings, were noted in the 1980s and 90s as an issue of concern and were attributed to limited investment in public and private research and development (R&D). Here we build a comprehensive global database of energy patents covering the period 1970-2009, which is unique in its temporal and geographical scope. Analysis of the data reveals a recent, marked departure from historical trends. A sharp increase in rates of patenting has occurred over the last decade, particularly in renewable technologies, despite continued low levels of R&D funding. To solve the puzzle of fast innovation despite modest R&D increases, we develop a model that explains the nonlinear response observed in the empirical data of technological innovation to various types of investment. The model reveals a regular relationship between patents, R&D funding, and growing markets across technologies, and accurately predicts patenting rates at different stages of technological maturity and market development. We show quantitatively how growing markets have formed a vital complement to public R&D in driving innovative activity. These two forms of investment have each leveraged the effect of the other in driving patenting trends over long periods of time.

Determinants of the Pace of Global Innovation in Energy Technologies

PubMed Central

Kaur, Jasleen

2013-01-01

Understanding the factors driving innovation in energy technologies is of critical importance to mitigating climate change and addressing other energy-related global challenges. Low levels of innovation, measured in terms of energy patent filings, were noted in the 1980s and 90s as an issue of concern and were attributed to limited investment in public and private research and development (R&D). Here we build a comprehensive global database of energy patents covering the period 1970–2009, which is unique in its temporal and geographical scope. Analysis of the data reveals a recent, marked departure from historical trends. A sharp increase in rates of patenting has occurred over the last decade, particularly in renewable technologies, despite continued low levels of R&D funding. To solve the puzzle of fast innovation despite modest R&D increases, we develop a model that explains the nonlinear response observed in the empirical data of technological innovation to various types of investment. The model reveals a regular relationship between patents, R&D funding, and growing markets across technologies, and accurately predicts patenting rates at different stages of technological maturity and market development. We show quantitatively how growing markets have formed a vital complement to public R&D in driving innovative activity. These two forms of investment have each leveraged the effect of the other in driving patenting trends over long periods of time. PMID:24155867

Fluoxetine-clonazepam cotherapy for anxious depression: an exploratory, post-hoc analysis of a randomized, double blind study.

PubMed

Papakostas, George I; Clain, Alisabet; Ameral, Victoria E; Baer, Lee; Brintz, Carrie; Smith, Ward T; Londborg, Peter D; Glaudin, Vincent; Painter, John R; Fava, Maurizio

2010-01-01

Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be both common and difficult to treat, with antidepressant monotherapy often yielding modest results. We sought to examine the relative benefits of antidepressant-anxiolytic cotherapy versus antidepressant monotherapy for patients with anxious depression versus without anxious depression. We conducted a post-hoc analysis of an existing dataset (N=80), from a 3-week, randomized, double-blind trial which demonstrated cotherapy with fluoxetine and clonazepam to result in superior efficacy than fluoxetine monotherapy in MDD. The present analysis involved examining whether anxious depression status served as a predictor and moderator of symptom improvement. Anxious depression status was not found to predict symptom improvement, or serve as a moderator of clinical improvement to cotherapy versus monotherapy. However, the advantage in remission rates in favor of cotherapy versus monotherapy was, numerically, much larger for patients with anxious depression (32.2%) than it was for patients without anxious MDD (9.7%). The respective number needed to treat statistic for these two differences in response rates were, approximately, one in three for patients with anxious depression versus one in 10 for patients without anxious depression. The efficacy of fluoxetine-clonazepam cotherapy compared with fluoxetine monotherapy was numerically but not statistically enhanced for patients with anxious depression than those without anxious depression.

Effects of Dietary Protein Source and Quantity during Weight Loss on Appetite, Energy Expenditure, and Cardio-Metabolic Responses.

PubMed

Li, Jia; Armstrong, Cheryl L H; Campbell, Wayne W

2016-01-26

Higher protein meals increase satiety and the thermic effect of feeding (TEF) in acute settings, but it is unclear whether these effects remain after a person becomes acclimated to energy restriction or a given protein intake. This study assessed the effects of predominant protein source (omnivorous, beef/pork vs. lacto-ovo vegetarian, soy/legume) and quantity (10%, 20%, or 30% of energy from protein) on appetite, energy expenditure, and cardio-metabolic indices during energy restriction (ER) in overweight and obese adults. Subjects were randomly assigned to one protein source and then consumed diets with different quantities of protein (4 weeks each) in a randomized crossover manner. Perceived appetite ratings (free-living and in-lab), TEF, and fasting cardio-metabolic indices were assessed at the end of each 4-week period. Protein source and quantity did not affect TEF, hunger, or desire to eat, other than a modestly higher daily composite fullness rating with 30% vs. 10% protein diet (p = 0.03). While the 20% and 30% protein diets reduced cholesterol, triacylglycerol, and APO-B vs. 10% protein (p < 0.05), protein source did not affect cardio-metabolic indices. In conclusion, diets varying in protein quantity with either beef/pork or soy/legume as the predominant source have minimal effects on appetite control, energy expenditure and cardio-metabolic risk factors during ER-induced weight loss.

Using milk fat to reduce the irritation and bitter taste of ibuprofen

PubMed Central

Bennett, Samantha M.; Zhou, Lisa; Hayes, John E.

2012-01-01

Bitterness and irritation elicited by pharmaceutically active molecules remain problematic for pediatric medications, fortified foods and dietary supplements. Few effective methods exist for reducing these unpalatable sensations, negatively impacting medication compliance and intake of beneficial phytonutrients. A physicochemical approach to masking these sensations may be the most successful approach for generalizability to a wide range of structurally and functionally unique compounds. Here, solutions of the non-steroidal anti- inflammatory drug, ibuprofen, were prepared in milk products with varying fat content. Our hypothesis, based on other reports of similar phenomena, was that increasing the fat content would cause ibuprofen to selectively partition into the fat phase, thereby reducing interaction with sensory receptors and decreasing adversive sensations. Quantification of the aqueous concentration of ibuprofen was performed using an isocratic HPLC method coupled with an external standard curve. Sensory testing showed a modest but significant decrease (~20%) in irritation ratings between the skim milk (0% fat) and the half-and-half (11% fat) samples, indicating that increased fat may contribute to a reduced sensory response. Bitterness was not reduced, remaining constant over all fat levels. The HPLC results indicate a constant amount of ibuprofen remained in the aqueous phase regardless of fat level, so a simple partitioning hypothesis cannot explain the reduced irritancy ratings. Association of ionized ibuprofen with continuous phase solutes such as unabsorbed protein should be explored in future work. PMID:23527314

Use of near-IR to monitor the influence of external heating on dental composite photopolymerization.

PubMed

Trujillo, Marianela; Newman, Sheldon M; Stansbury, Jeffrey W

2004-10-01

This study was conducted to determine the effect of modest external heating on the photopolymerization kinetics and conversion of commercial dental composite restorative materials. A transmission-mode, real-time near-infrared spectroscopic technique was used to monitor the photopolymerization process in the composite materials at various temperatures between 23 and 70 degrees C. Several light curing units, differing in spectral output and power densities were compared at the different cure temperatures. Several significantly different commercial composites were compared for their response. Regardless of the curing light or composite material used, photopolymerization at a moderate curing temperature of 54.5 degrees C resulted in significantly higher immediate and final conversion values compared with room temperature photocuring. Contrary to the room temperature cured materials, at the elevated cure temperature the extent of post-cure was minor and different curing lights produced very uniform conversion values within a given material. The time required to reach a given level of conversion, established as full conversion with the room temperature cure, was reduced typically by 80-90% using the elevated curing conditions. Complementary kinetic studies confirmed the effect of cure temperature on increasing the polymerization rate in dental composites as significant. Increasing the temperature of composite resin within potentially biologically compatible limits can significantly influences resin polymerization. These increased rates and conversion could lead to improved properties of composite restorative materials.

Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis.

PubMed

Fleischmann, Roy; Wollenhaupt, Jürgen; Cohen, Stanley; Wang, Lisy; Fan, Haiyun; Bandi, Vara; Andrews, John; Takiya, Liza; Bananis, Eustratios; Weinblatt, Michael E

2018-06-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the effect of concomitant methotrexate (MTX) or glucocorticoid (GC) use on tofacitinib clinical efficacy. Data were pooled from two open-label, long-term extension studies of tofacitinib 5 or 10 mg twice daily in patients with RA. Response according to Clinical Disease Activity Index (CDAI) was assessed separately in patients who discontinued (no MTX/GC use within 30 days prior to year-3 visit; assessment at month 3/year 3) or initiated (on/before year 3; assessment at initiation and year 3) MTX/GC. By year 3, among patients receiving background MTX at baseline, 186/1608 (11.6%) discontinued MTX, and 319/1434 (22.2%) patients receiving GC at baseline discontinued GC. Overall, 70.4/69.1% of patients who discontinued/continued MTX and 72.7/65.9% who discontinued/continued GC achieved CDAI remission or low disease activity (LDA) at year 3. Month 3 remission/LDA rates were maintained at year 3 in the majority of patients, irrespective of MTX/GC discontinuation/continuation. By year 3, 6.2% of patients receiving tofacitinib without MTX at baseline had initiated concomitant MTX, and 25.1% receiving tofacitinib without GC initiated GC; 69.0% and 45.4% initiating MTX or GC, respectively, had a CDAI-defined incomplete response prior to initiation. RA signs/symptoms improved following MTX initiation; only modest improvement was observed with GC initiation. Patients achieving remission/LDA with tofacitinib may discontinue MTX or GC and maintain treatment response. Patients with an incomplete response may benefit from adding concomitant MTX. Pfizer Inc. Study A3921024 [NCT00413699] and Study A3921041 [NCT00661661].

Survivin as prognostic and predictive factor in patients treated with gemcitabine, dexamethasone, and cisplatin for relapsed or refractory aggressive NHL.

PubMed

el Aziz, Lamiss Mohamed Abd

2014-11-01

The prognosis of relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) after front-line therapy remains poor. The development of more effective and less toxic salvage regimens remains a major challenge. Survivin is a member of the family of inhibitors of apoptosis, and survivin was associated with short survival and bad prognosis. This study was to evaluate the efficacy of GDP regimen (gemcitabine, dexamethasone and cisplatin) on relapsed or refractory aggressive NHL and various prognostic factors with special emphasis on survivin and observe the . Forty-six patients with relapsed and refractory NHL, intermediate or high-grade NHL (Revised European American Lymphoma Classification), who at least one regimen were enrolled into this study, which was carried out at Department, , Tanta University from July 2012 to July 2014. The patients were treated with GDP regimen (gemcitabine 1,000 mg/m(2) on days one and eight, dexamethasone 40 mg on days 1-3, and cisplatin 25 mg/m(2) on days 1-3) every 3 weeks. The efficacy and adverse events were evaluated according to the WHO criteria. All patients were assessed for efficacy and toxicity. The overall response rate was 58.7 %. Fourteen patients showed a complete response, thirteen partial responses, twelve stable diseases, and seven progressive disease. The 24-month overall survival was 50.8 %. Survivin is associated with low overall response and shorter overall survival. Grade 3 anemia was observed in four patients, grade 3 leucopenia in six patients, grade 3 neutropenia in six patients, and grade 3 thrombocytopenia in four patients. Non-hematologic toxicity included grade 3 infection in four patients. The present schedule of GDP showed modest efficacy and mild toxicity in patients with relapsed or refractory aggressive NHL.

Therapeutic drug monitoring of vedolizumab in inflammatory bowel disease: current data and future directions.

PubMed

Ward, Mark G; Sparrow, Miles P; Roblin, Xavier

2018-01-01

The introduction of vedolizumab, a lymphocyte adhesion inhibitor, has expanded the relatively limited therapeutic armamentarium available for Crohn's disease and ulcerative colitis. Despite its effectiveness, both primary nonresponse and secondary loss of response to vedolizumab do occur, as is observed with the use of anti-tumour necrosis factor (TNF) therapy. Further, in a proportion, onset of efficacy may be relatively slow. A large body of data support an exposure-response relationship with anti-TNF drug levels, which has led to therapeutic drug monitoring becoming incorporated into everyday clinical management. The influence of patient and disease factors on the pharmacokinetics of anti-TNF levels, including immunogenicity, has also been examined. The role of therapeutic drug monitoring with vedolizumab is less clear. This review summarizes the available evidence on the pharmacokinetics and pharmacodynamics of vedolizumab in inflammatory bowel disease and how drug levels, immunogenicity and other factors influence clinical outcomes. Vedolizumab clearance is increased with very high body weight and hypoalbuminaemia, but is not influenced by the addition of an immunomodulator. Immunogenicity is uncommon. α4β7 receptor saturation occurs at low serum vedolizumab drug levels, and measuring it alone is insufficient to predict clinical outcomes. Using quartile analysis of vedolizumab drug levels, there appears to be a modest exposure-response relationship during induction. Drug levels at week 6 of approximately >20 μg/ml have been shown to be associated with improved clinical outcomes, including subsequent mucosal healing rates during maintenance and avoiding the need to dose escalate due to lack of response. There are currently insufficient data to support the routine use of therapeutic drug monitoring during maintenance therapy. Further studies to elucidate the role of therapeutic drug monitoring of vedolizumab are needed.

Adrenocortical and behavioural response to chronic restraint stress in neurokinin-1 receptor knockout mice.

PubMed

Delgado-Morales, Raúl; del Río, Eva; Gómez-Román, Almudena; Bisagno, Verónica; Nadal, Roser; de Felipe, Carmen; Armario, Antonio

2012-02-01

Brain substance P and its receptor (neurokinin-1, NK1) have a widespread brain distribution and are involved in an important number of behavioural and physiological responses to emotional stimuli. However, the role of NK1 receptors in the consequences of exposure to chronic stress has not been explored. The present study focused on the role of these receptors in the hypothalamic-pituitary-adrenal (HPA) response to daily repeated restraint stress (evaluated by plasma corticosterone levels), as well as on the effect of this procedure on anxiety-like behaviour, spatial learning and memory in the Morris water maze (MWM), a hippocampus-dependent task. Adult null mutant NK1-/- mice, with a C57BL/6J background, and the corresponding wild-type mice showed similar resting corticosterone levels and, also, did not differ in corticosterone response to a first restraint. Nevertheless, adaptation to the repeated stressor was faster in NK1-/- mice. Chronic restraint modestly increased anxiety-like behaviour in the light-dark test, irrespective of genotype. Throughout the days of the MWM trials, NK1-/- mice showed a similar learning rate to that of wild-type mice, but had lower levels of thigmotaxis and showed a better retention in the probe trial. Chronic restraint stress did not affect these variables in either genotype. These results indicate that deletion of the NK1 receptor does not alter behavioural susceptibility to chronic repeated stress in mice, but accelerates adaptation of the HPA axis. In addition, deletion may result in lower levels of thigmotaxis and improved short-term spatial memory, perhaps reflecting a better learning strategy in the MWM. Copyright © 2011 Elsevier Inc. All rights reserved.

Differential transcriptomic responses of Biomphalaria glabrata (Gastropoda, Mollusca) to bacteria and metazoan parasites, Schistosoma mansoni and Echinostoma paraensei (Digenea, Platyhelminthes)

PubMed Central

Adema, Coen M; Hanington, Patrick C.; Lun, Cheng-Man; Rosenberg, George H.; Aragon, Anthony D; Stout, Barbara A; Richard, Mara L. Lennard; Gross, Paul S.; Loker, Eric S

2009-01-01

A 70-mer oligonucleotide-based microarray (1152 features) that emphasizes stress and immune responses factors was constructed to study transcriptomic responses of the snail Biomphalaria glabrata to different immune challenges. In addition to sequences with relevant putative ID and Gene Ontology (GO) annotation, the array features non-immune factors and unknown B. glabrata ESTs for functional gene discovery. The transcription profiles of B. glabrata (3 biological replicates, each a pool of 5 snails) were recorded at 12 hours post wounding, exposure to Gram negative or Gram positive bacteria (Escherichia coli and Micrococcus luteus, respectively), or infection with compatible trematode parasites (S. mansoni or E. paraensei, 20 miracidia/snail), relative to controls, using universal reference RNA. The data were subjected to Significance Analysis for Microarrays (SAM), with a false positive rate (FPR) ≤10%. Wounding yielded a modest differential expression profile (27 up/21 down) with affected features mostly dissimilar from other treatments. Partially overlapping, yet distinct expression profiles were recorded from snails challenged with E. coli (83 up/20 down) or M. luteus (120 up/42 down), mostly showing up-regulation of defense and stress-related features. Significantly altered expression of selected immune features indicates that B. glabrata detects and responds differently to compatible trematodes. Echinostoma paraensei infection was associated mostly with down regulation of many (immune-) transcripts (42 up/68 down), whereas S. mansoni exposure yielded a preponderance of up-regulated features (140 up/23 down), with only few known immune genes affected. These observations may reflect the divergent strategies developed by trematodes during their evolution as specialized pathogens of snails to negate host defense responses. Clearly, the immune defenses of B. glabrata distinguish and respond differently to various immune challenges. PMID:19962194

A phase II evaluation of ixabepilone in the treatment of recurrent/persistent carcinosarcoma of the uterus, an NRG Oncology/Gynecologic Oncology Group study.

PubMed

McCourt, Carolyn K; Deng, Wei; Dizon, Don S; Lankes, Heather A; Birrer, Michael J; Lomme, Michele M; Powell, Matthew A; Kendrick, James E; Saltzman, Joel N; Warshal, David; Tenney, Meaghan E; Kushner, David M; Aghajanian, Carol

2017-01-01

The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (UCS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS. Patients had measurable disease; up to two prior chemotherapeutic regimens were allowed, but must have included a taxane. Women received ixabepilone 40mg/m 2 as a 3hour IV infusion on day 1 of a 21daycycle. Treatment was continued until disease progression or unacceptable toxicity occurred. Forty-two women were enrolled, with 34 eligible and evaluable. Median age was 68years. ECOG performance status was 0 in 56% of women, 38% had received radiation, and 15% had received 2 lines of chemotherapy. Overall ORR was 11.8% (4/34, 90% CI 4.2-25.1%); all were partial responses. Stable disease for at least 8weeks was achieved in 8 patients (23.5%). Median PFS and OS were 1.7mo and 7.7mo, respectively, with a median follow-up of 37mo. Six month PFS was 20.6%. Major grade≥3 toxicities were neutropenia (47%), fatigue (15%), dehydration (15%), hypertension (15%), and hyponatremia (15%); grade 2 peripheral neuropathy was reported in 18%. In this small sample size, class III beta tubulin expression in the primary tumor was not associated with the response to ixabepilone, PFS, or OS. In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity. Copyright © 2016. Published by Elsevier Inc.

A phase II evaluation of ixabepilone in the treatment of recurrent/persistent carcinosarcom a of the uterus, an NRG Oncology/Gynecologic Oncology Group study☆

PubMed Central

McCourt, Carolyn K.; Deng, Wei; Dizon, Don S.; Lankes, Heather A.; Birrer, Michael J.; Lomme, Michele M.; Powell, Matthew A.; Kendrick, James E.; Saltzman, Joel N.; Warshal, David; Tenney, Meaghan E.; Kushner, David M.; Aghajanian, Carol

2017-01-01

Background The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (UCS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS. Methods Patients had measurable disease; up to two prior chemotherapeutic regimens were allowed, but must have included a taxane. Women received ixabepilone 40 mg/m2 as a 3 hour IV infusion on day 1 of a 21 day cycle. Treatment was continued until disease progression or unacceptable toxicity occurred. Results Forty-two women were enrolled, with 34 eligible and evaluable. Median age was 68 years. ECOGperformance status was 0 in 56% of women, 38% had received radiation, and 15% had received 2 lines of chemotherapy. Overall ORR was 11.8%(4/34, 90%CI 4.2–25.1%); all were partial responses. Stable disease for at least 8 weeks was achieved in 8 patients (23.5%). Median PFS and OS were 1.7 mo and 7.7 mo, respectively, with a median follow-up of 37 mo. Six month PFS was 20.6%. Major grade ≥ 3 toxicities were neutropenia (47%), fatigue (15%), dehydration (15%), hypertension (15%), and hyponatremia (15%); grade 2 peripheral neuropathy was reported in 18%. In this small sample size, class III beta tubulin expression in the primary tumor was not associated with the response to ixabepilone, PFS, or OS. Conclusion In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity. PMID:28029447

Nonrandom Acts of Kindness: Parasympathetic and Subjective Empathic Responses to Sadness Predict Children’s Prosociality

PubMed Central

Miller, Jonas G.; Nuselovici, Jacob N.; Hastings, Paul D.

2016-01-01

How does empathic physiology unfold as a dynamic process, and which aspect of empathy predicts children’s kindness? In response to empathy induction videos, 4–6 year-old children (N = 180) showed an average pattern of dynamic respiratory sinus arrhythmia (RSA) change characterized by early RSA suppression followed by RSA recovery, and modest subsequent suppression during positive resolution of the empathic event. Children’s capacity for this pattern of flexible RSA change was associated with their subjective empathic feelings, which were concurrently associated with more sympathetic and prosocial responses to others. Conversely, only children’s dynamic RSA change longitudinally predicted prosocial behavior two years later. These findings have implications for understanding the dynamic and multifaceted nature of empathy, and its relation with prosocial development. PMID:28262932

Extraordinary sediment delivery and rapid geomorphic response following the 2008–2009 eruption of Chaitén Volcano, Chile

USGS Publications Warehouse

Major, Jon J.; Bertin, Daniel; Pierson, Thomas C.; Amigo, Alvaro; Iroume, Andres; Ulloa, Hector; Castro, Jonathan M.

2016-01-01

The 10 day explosive phase of the 2008–2009 eruption of Chaitén volcano, Chile, draped adjacent watersheds with a few cm to >1 m of tephra. Subsequent lava-dome collapses generated pyroclastic flows that delivered additional sediment. During the waning phase of explosive activity, modest rainfall triggered an extraordinary sediment flush which swiftly aggraded multiple channels by many meters. Ten kilometer from the volcano, Chaitén River channel aggraded 7 m and the river avulsed through a coastal town. That aggradation and delta growth below the abandoned and avulsed channels allow estimates of postdisturbance traction-load transport rate. On the basis of preeruption bathymetry and remotely sensed measurements of delta-surface growth, we derived a time series of delta volume. The initial flush from 11 to 14 May 2008 deposited 0.5–1.5 × 106 m3 of sediment at the mouth of Chaitén River. By 26 May, after channel avulsion, a second delta amassed about 2 × 106 m3 of sediment; by late 2011 it amassed about 11 × 106 m3. Accumulated sediment consists of low-density vesicular pumice and lithic rhyolite sand. Rates of channel aggradation and delta growth, channel width, and an assumed deposit bulk density of 1100–1500 kg m−3 indicate mean traction-load transport rate just before and shortly after avulsion (∼14–15 May) was very high, possibly as great as several tens of kg s−1 m−1. From October 2008 to December 2011, mean traction-load transport rate declined from about 7 to 0.4 kg−1 m−1. Despite extraordinary sediment delivery, disturbed channels recovered rapidly (a few years).

Dehydration decreases saliva antimicrobial proteins important for mucosal immunity.

PubMed

Fortes, Matthew B; Diment, Bethany C; Di Felice, Umberto; Walsh, Neil P

2012-10-01

The aim of the study was to investigate the effect of exercise-induced dehydration and subsequent overnight fluid restriction on saliva antimicrobial proteins important for host defence (secretory IgA (SIgA), α-amylase, and lysozyme). On two randomized occasions, 13 participants exercised in the heat, either without fluid intake to evoke progressive body mass losses (BML) of 1%, 2%, and 3% with subsequent overnight fluid restriction until 0800 h in the following morning (DEH) or with fluids to offset losses (CON). Participants in the DEH trial rehydrated from 0800 h until 1100 h on day 2. BML, plasma osmolality (Posm), and urine specific gravity (USG) were assessed as hydration indices. Unstimulated saliva samples were assessed for flow rate (SFR), SIgA, α-amylase, and lysozyme concentrations. Posm and USG increased during dehydration and remained elevated after overnight fluid restriction (BML = 3.5% ± 0.3%, Posm = 297 ± 6 mosmol·kg⁻¹, and USG = 1.026 ± 0.002; P < 0.001). Dehydration decreased SFR (67% at 3% BML, 70% at 0800 h; P < 0.01) and increased SIgA concentration, with no effect on SIgA secretion rate. SFR and SIgA responses remained unchanged in the CON trial. Dehydration did not affect α-amylase or lysozyme concentration but decreased secretion rates of α-amylase (44% at 3% BML, 78% at 0800 h; P < 0.01) and lysozyme (46% at 3% BML, 61% at 0800 h; P < 0.01), which were lower than in CON at these time points (P < 0.05). Rehydration returned all saliva variables to baseline. In conclusion, modest dehydration (~3% BML) decreased SFR, α-amylase, and lysozyme secretion rates. Whether the observed magnitude of decrease in saliva AMPs during dehydration compromises host defence remains to be shown.

Momentary assessment of affect, physical feeling states, and physical activity in children.

PubMed

Dunton, Genevieve F; Huh, Jimi; Leventhal, Adam M; Riggs, Nathaniel; Hedeker, Donald; Spruijt-Metz, Donna; Pentz, Mary Ann

2014-03-01

Most research on the interplay of affective and physical feelings states with physical activity in children has been conducted under laboratory conditions and fails to capture intraindividual covariation. The current study used Ecological Momentary Assessment (EMA) to bidirectionally examine how affective and physical feeling states are related to objectively measured physical activity taking place in naturalistic settings during the course of children's everyday lives. Children (N = 119, ages 9-13 years, 52% male, 32% Hispanic) completed 8 days of EMA monitoring, which measured positive affect (PA), negative affect (NA), feeling tired, and feeling energetic up to 7 times per day. EMA responses were time-matched to accelerometer assessed moderate-to-vigorous physical activity (MVPA) in the 30 min before and after each EMA survey. Higher ratings of feeling energetic and lower ratings of feeling tired were associated with more MVPA in the 30 min after the EMA prompt. More MVPA in the 30 min before the EMA prompt was associated with higher ratings of PA and feeling energetic and lower ratings of NA. Between-subjects analyses indicated that mean hourly leisure-time MVPA was associated with less intraindividual variability in PA and NA. Physical feeling states predict subsequent physical activity levels, which in turn, predict subsequent affective states in children. Active children demonstrated higher positive and negative emotional stability. Although the strength of these associations were of modest magnitude and their clinical relevance is unclear, understanding the antecedents to and consequences of physical activity may have theoretical and practical implications for the maintenance and promotion of physical activity and psychological well-being in children. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Optimization of pelvic heating rate distributions with electromagnetic phased arrays.

PubMed

Paulsen, K D; Geimer, S; Tang, J; Boyse, W E

1999-01-01

Deep heating of pelvic tumours with electromagnetic phased arrays has recently been reported to improve local tumour control when combined with radiotherapy in a randomized clinical trial despite the fact that rather modest elevations in tumour temperatures were achieved. It is reasonable to surmise that improvements in temperature elevation could lead to even better tumour response rates, motivating studies which attempt to explore the parameter space associated with heating rate delivery in the pelvis. Computational models which are based on detailed three-dimensional patient anatomy are readily available and lend themselves to this type of investigation. In this paper, volume average SAR is optimized in a predefined target volume subject to a maximum allowable volume average SAR outside this zone. Variables under study include the position of the target zone, the number and distribution of radiators and the applicator operating frequency. The results show a clear preference for increasing frequency beyond 100 MHz, which is typically applied clinically, especially as the number of antennae increases. Increasing both the number of antennae per circumferential distance around the patient, as well as the number of independently functioning antenna bands along the patient length, is important in this regard, although improvements were found to be more significant with increasing circumferential antenna density. However, there is considerable site specific variation and cases occur where lower numbers of antennae spread out over multiple longitudinal bands are more advantageous. The results presented here have been normalized relative to an optimized set of antenna array amplitudes and phases operating at 100 MHz which is a common clinical configuration. The intent is to provide some indications of avenues for improving the heating rate distributions achievable with current technology.

Cross-sectional study of factors associated with community health centre use in a recently urbanised community in Chengdu, China.

PubMed

Liu, Danping; Meng, Hongdao; Dobbs, Debra; Conner, Kyaien O; Hyer, Kathryn; Li, Ningxiu; Ren, Xiaohui; Gao, Bo

2017-06-08

Public investment in community health centres (CHCs) has been increasing as a response to rapid urbanisation in China. The objectives of this study were: (1) to examine factors associated with CHC use among residents from a recently urbanised community in western China and (2) to describe satisfaction with CHC among users. Cross-sectional design. A community recently converted to urban status with a newly constructed CHC in Southwest China. A random sample of 2259 adults in the Hezuo community in Chengdu, China, completed the survey in 2013. Trained staff interviewed study participants in their homes using structured questionnaires. The survey included questions regarding sociodemographics, health status, access to and usage of healthcare, health behaviours and CHC use. The Andersen's behavioural model of health service use was used to guide multivariable logistic regression modelling in identifying predisposing, enabling and need factors associated with the likelihood of using CHC. Descriptive statistics were used to describe residents' satisfaction with the CHC. A total of 71.8% of the respondents reported using the CHC during the past year. Factors influencing adults' CHC use included: gender, marital status, education level and knowledge of one's blood pressure (predisposing factors); annual household per capita income and walking time to the CHC (enabling factors) and self-rated health as well as physical activities (need factors). CHC users reported modest satisfaction across various aspects of the CHC. Neighbourhood CHC in urban areas provides important services to these residents living in a recently urbanised community. All three categories of factors in the Andersen model help explain the likelihood of CHC use. There is much room for improvement in CHC to enhance customer satisfaction. Future research is needed to improve access to CHCs and promote their use in urbanised populations with low to modest education. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Associations between owner personality and psychological status and the prevalence of canine behavior problems

PubMed Central

Dodman, Nicholas H.; Brown, Dorothy C.

2018-01-01

Behavioral problems are a major source of poor welfare and premature mortality in companion dogs. Previous studies have demonstrated associations between owners’ personality and psychological status and the prevalence and/or severity of their dogs’ behavior problems. However, the mechanisms responsible for these associations are currently unknown. Other studies have detected links between the tendency of dogs to display behavior problems and their owners’ use of aversive or confrontational training methods. This raises the possibility that the effects of owner personality and psychological status on dog behavior are mediated via their influence on the owner’s choice of training methods. We investigated this hypothesis in a self-selected, convenience sample of 1564 current dog owners using an online battery of questionnaires designed to measure, respectively, owner personality, depression, emotion regulation, use of aversive/confrontational training methods, and owner-reported dog behavior. Multivariate linear and logistic regression analyses identified modest, positive associations between owners’ use of aversive/confrontational training methods and the prevalence/severity of the following dog behavior problems: owner-directed aggression, stranger-directed aggression, separation problems, chasing, persistent barking, and house-soiling (urination and defecation when left alone). The regression models also detected modest associations between owners’ low scores on four of the ‘Big Five’ personality dimensions (Agreeableness, Emotional Stability, Extraversion & Conscientiousness) and their dogs’ tendency to display higher rates of owner-directed aggression, stranger-directed fear, and/or urination when left alone. The study found only weak evidence to support the hypothesis that these relationships between owner personality and dog behavior were mediated via the owners’ use of punitive training methods, but it did detect a more than five-fold increase in the use of aversive/confrontational training techniques among men with moderate depression. Further research is needed to clarify the causal relationship between owner personality and psychological status and the behavioral problems of companion dogs. PMID:29444154

Associations between owner personality and psychological status and the prevalence of canine behavior problems.

PubMed

Dodman, Nicholas H; Brown, Dorothy C; Serpell, James A

2018-01-01

Behavioral problems are a major source of poor welfare and premature mortality in companion dogs. Previous studies have demonstrated associations between owners' personality and psychological status and the prevalence and/or severity of their dogs' behavior problems. However, the mechanisms responsible for these associations are currently unknown. Other studies have detected links between the tendency of dogs to display behavior problems and their owners' use of aversive or confrontational training methods. This raises the possibility that the effects of owner personality and psychological status on dog behavior are mediated via their influence on the owner's choice of training methods. We investigated this hypothesis in a self-selected, convenience sample of 1564 current dog owners using an online battery of questionnaires designed to measure, respectively, owner personality, depression, emotion regulation, use of aversive/confrontational training methods, and owner-reported dog behavior. Multivariate linear and logistic regression analyses identified modest, positive associations between owners' use of aversive/confrontational training methods and the prevalence/severity of the following dog behavior problems: owner-directed aggression, stranger-directed aggression, separation problems, chasing, persistent barking, and house-soiling (urination and defecation when left alone). The regression models also detected modest associations between owners' low scores on four of the 'Big Five' personality dimensions (Agreeableness, Emotional Stability, Extraversion & Conscientiousness) and their dogs' tendency to display higher rates of owner-directed aggression, stranger-directed fear, and/or urination when left alone. The study found only weak evidence to support the hypothesis that these relationships between owner personality and dog behavior were mediated via the owners' use of punitive training methods, but it did detect a more than five-fold increase in the use of aversive/confrontational training techniques among men with moderate depression. Further research is needed to clarify the causal relationship between owner personality and psychological status and the behavioral problems of companion dogs.

Predictive evaluation of size restrictions as management strategies for tennessee reservoir crappie fisheries

USGS Publications Warehouse

Isermann, D.A.; Sammons, S.M.; Bettoli, P.W.; Churchill, T.N.

2002-01-01

We evaluated the potential effect of minimum size restrictions on crappies Pomoxis spp. in 12 large Tennessee reservoirs. A Beverton-Holt equilibrium yield model was used to predict and compare the response of these fisheries to three minimum size restrictions: 178 mm (i.e., pragmatically, no size limit), 229 mm, and the current statewide limit of 254 mm. The responses of crappie fisheries to size limits differed among reservoirs and varied with rates of conditional natural mortality (CM). Based on model results, crappie fisheries fell into one of three response categories: (1) In some reservoirs (N = 5), 254-mm and 229-mm limits would benefit the fishery in terms of yield if CM were low (30%); the associated declines in the number of crappies harvested would be significant but modest when compared with those in other reservoirs. (2) In other reservoirs (N = 6), little difference in yield existed among size restrictions at low to intermediate rates of CM (30-40%). In these reservoirs, a 229-mm limit was predicted to be a more beneficial regulation than the current 254-mm limit. (3) In the remaining reservoir, Tellico, size limits negatively affected all three harvest statistics. Generally, yield was negatively affected by size limits in all populations at a CM of 50%. The number of crappies reaching 300 mm was increased by size limits in most model scenarios: however, associated declines in the total number of crappies harvested often outweighed the benefits to size structure when CM was 40% or higher. When crappie growth was fast (reaching 254 mm in less than 3 years) and CM was low (30%), size limits were most effective in balancing increases in yield and size structure against declines in the total number of crappies harvested. The variability in predicted size-limit responses observed among Tennessee reservoirs suggests that using a categorical approach to applying size limits to crappie fisheries within a state or region would likely be a more effective management strategy than implementing a single, areawide regulation.

Cell-Type-Specific Modulation of Sensory Responses in Olfactory Bulb Circuits by Serotonergic Projections from the Raphe Nuclei

PubMed Central

Brunert, Daniela; Tsuno, Yusuke; Rothermel, Markus; Shipley, Michael T.

2016-01-01

Serotonergic neurons in the brainstem raphe nuclei densely innervate the olfactory bulb (OB), where they can modulate the initial representation and processing of olfactory information. Serotonergic modulation of sensory responses among defined OB cell types is poorly characterized in vivo. Here, we used cell-type-specific expression of optical reporters to visualize how raphe stimulation alters sensory responses in two classes of GABAergic neurons of the mouse OB glomerular layer, periglomerular (PG) and short axon (SA) cells, as well as mitral/tufted (MT) cells carrying OB output to piriform cortex. In PG and SA cells, brief (1–4 s) raphe stimulation elicited a large increase in the magnitude of responses linked to inhalation of ambient air, as well as modest increases in the magnitude of odorant-evoked responses. Near-identical effects were observed when the optical reporter of glutamatergic transmission iGluSnFR was expressed in PG and SA cells, suggesting enhanced excitatory input to these neurons. In contrast, in MT cells imaged from the dorsal OB, raphe stimulation elicited a strong increase in resting GCaMP fluorescence with only a slight enhancement of inhalation-linked responses to odorant. Finally, optogenetically stimulating raphe serotonergic afferents in the OB had heterogeneous effects on presumptive MT cells recorded extracellularly, with an overall modest increase in resting and odorant-evoked responses during serotonergic afferent stimulation. These results suggest that serotonergic afferents from raphe dynamically modulate olfactory processing through distinct effects on multiple OB targets, and may alter the degree to which OB output is shaped by inhibition during behavior. SIGNIFICANCE STATEMENT Modulation of the circuits that process sensory information can profoundly impact how information about the external world is represented and perceived. This study investigates how the serotonergic system modulates the initial processing of olfactory information by the olfactory bulb, an obligatory relay between sensory neurons and cortex. We find that serotonergic projections from the raphe nuclei to the olfactory bulb dramatically enhance the responses of two classes of inhibitory interneurons to sensory input, that this effect is mediated by increased glutamatergic drive onto these neurons, and that serotonergic afferent activation alters the responses of olfactory bulb output neurons in vivo. These results elucidate pathways by which neuromodulatory systems can dynamically regulate brain circuits during behavior. PMID:27335411

Comparing individual differences in inconsistency and plasticity as predictors of cognitive function in older adults.

PubMed

Grand, Jacob H G; Stawski, Robert S; MacDonald, Stuart W S

2016-01-01

Recent theorizing differentiates key constraints on cognition, including one's current range of processing efficiency (i.e., flexibility or inconsistency) as well as the capacity to expand flexibility over time (i.e., plasticity). The present study uses intensive assessment of response time data to examine the interplay between markers of intraindividual variability (inconsistency) and gains across biweekly retest sessions (plasticity) in relation to age-related cognitive function. Participants included 304 adults (aged 64 to 92 years: M = 74.02, SD = 5.95) from Project MIND, a longitudinal burst design study assessing performance across micro and macro intervals (response latency trials, weekly bursts, annual retests). For two reaction time (RT) measures (choice RT and one-back choice RT), baseline measures of RT inconsistency (intraindividual standard deviation, ISD, across trials at the first testing session) and plasticity (within-person performance gains in average RT across the 5 biweekly burst sessions) were computed and were then employed in linear mixed models as predictors of individual differences in cognitive function and longitudinal (6-year) rates of cognitive change. Independent of chronological age and years of education, higher RT inconsistency was associated uniformly with poorer cognitive function at baseline and with increased cognitive decline for measures of episodic memory and crystallized verbal ability. In contrast, predictive associations for plasticity were more modest for baseline cognitive function and were absent for 6-year cognitive change. These findings underscore the potential utility of response times for articulating inconsistency and plasticity as dynamic predictors of cognitive function in older adults.

Dose-response relationship of the cardiovascular adaptation to endurance training in healthy adults: how much training for what benefit?

PubMed

Iwasaki, Ken-Ichi; Zhang, Rong; Zuckerman, Julie H; Levine, Benjamin D

2003-10-01

Occupational or recreational exercise reduces mortality from cardiovascular disease. The potential mechanisms for this reduction may include changes in blood pressure (BP) and autonomic control of the circulation. Therefore, we conducted the present long-term longitudinal study to quantify the dose-response relationship between the volume and intensity of exercise training, and regulation of heart rate (HR) and BP. We measured steady-state hemodynamics and analyzed dynamic cardiovascular regulation by spectral and transfer function analysis of cardiovascular variability in 11 initially sedentary subjects during 1 yr of progressive endurance training sufficient to allow them to complete a marathon. From this, we found that 1) moderate exercise training for 3 mo decreased BP, HR, and total peripheral resistance, and increased cardiovascular variability and arterial baroreflex sensitivity; 2) more prolonged and intense training did not augment these changes further; and 3) most of these changes returned to control values at 12 mo despite markedly increased training duration and intensity equivalent to that routinely observed in competitive athletes. In conclusion, increases in R-wave-R-wave interval and cardiovascular variability indexes are consistent with an augmentation of vagal modulation of HR after exercise training. It appears that moderate doses of training for 3 mo are sufficient to achieve this response as well as a modest hypotensive effect from decreasing vascular resistance. However, more prolonged and intense training does not necessarily lead to greater enhancement of circulatory control and, therefore, may not provide an added protective benefit via autonomic mechanisms against death by cardiovascular disease.

The association of pain and depression in preadolescent girls: moderation by race and pubertal stage.

PubMed

Keenan, Kate; Hipwell, Alison E; Hinze, Amanda E; Babinski, Dara E

2009-08-01

To test whether an association between pain response and depression in females is present during preadolescence using a controlled pain stimulus and a clinically relevant assessment of depressive symptoms. In a sample of 232 girls, pain threshold and tolerance were assessed at age 10 years using the cold pressor task, and a diagnostic interview was used to assess depression symptoms at 10 and 11 years of age. Response to pain at age 10 was associated with depressive symptoms at ages 10 and 11; race and pubertal stage moderated the association. Pain response and depression were more strongly associated among girls who had reached advanced stages of pubertal development and among European American girls. The results add to the existing literature on the co-occurrence of depression and pain by demonstrating modest but consistent concurrent and prospective associations between response to pain and depression among girls during preadolescence.

Nonlinear site response in medium magnitude earthquakes near Parkfield, California

USGS Publications Warehouse

Rubinstein, Justin L.

2011-01-01

Careful analysis of strong-motion recordings of 13 medium magnitude earthquakes (3.7 ≤ M ≤ 6.5) in the Parkfield, California, area shows that very modest levels of shaking (approximately 3.5% of the acceleration of gravity) can produce observable changes in site response. Specifically, I observe a drop and subsequent recovery of the resonant frequency at sites that are part of the USGS Parkfield dense seismograph array (UPSAR) and Turkey Flat array. While further work is necessary to fully eliminate other models, given that these frequency shifts correlate with the strength of shaking at the Turkey Flat array and only appear for the strongest shaking levels at UPSAR, the most plausible explanation for them is that they are a result of nonlinear site response. Assuming this to be true, the observation of nonlinear site response in small (M M 6.5 San Simeon earthquake and the 2004 M 6 Parkfield earthquake).

Sex Differences in Pharmacokinetics and Pharmacodynamics

PubMed Central

Soldin, OP; Mattison, DR

2013-01-01

Males and females differ in their response to drug treatment. These differences can be critical in response to drug treatment. It is therefore essential to understand those differences to appropriately conduct risk assessment and to design safe and effective treatments. Even from that modest perspective, how and when we use drugs can result in unwanted and unexpected outcomes. We summarize the sex differences that impact pharmacokinetics and pharmacodynamics and include a general comparison of clinical pharmacology as it applies to men, pregnant and non-pregnant women. Since this is an area rapidly evolving, it is essential for the practitioner to review drug prescribing information and recent literature to understand fully the impact of sex differences in clinical therapeutics. PMID:19385708

R&D policy, agency costs and innovation in personalized medicine.

PubMed

Yin, Wesley

2009-09-01

The Orphan Drug Act (ODA) was designed to spur the development of drugs for rare diseases. In principle, its design also incentivizes pharmaceutical firms to develop drugs for "rare" subdivisions of more prevalent diseases. I find that in response to this incentive, firms develop drugs for ODA-qualifying subdivisions of non-rare diseases. The impact in these tailored drug markets represents half of the total R&D response to the ODA. I also find that 10-percent of the innovation in subdivided disease drugs induced by the ODA would have been conducted without the policy. While modest in size, this inefficiency suggests that agency problems should be considered when designing innovation policy.

Geomorphic response of the North Fork Stillaguamish River to the State Route 530 landslide near Oso, Washington

USGS Publications Warehouse

Anderson, Scott W.; Keith, Mackenzie K.; Magirl, Christopher S.; Wallick, J. Rose; Mastin, Mark C.; Foreman, James R.

2017-08-03

On March 22, 2014, the State Route 530 Landslide near Oso, Washington mobilized 8 million cubic meters of unconsolidated Pleistocene material, creating a valley‑spanning deposit that fully impounded the North Fork Stillaguamish River. The river overtopped the 8-meter high debris impoundment within 25 hours and began steadily incising a new channel through the center of the deposit. Repeat topographic surveys, sediment transport measurements, bedload transport models, and observations of downstream channel change were used to document the establishment of that new channel through the landslide and assess the potential for downstream aggradation or channel change that might increase downstream flood hazards.Efficient erosion of the landslide deposit, associated with the steep knickzone formed by the downstream edge of the deposit, resulted in the re-establishment of a 20–40 meters wide, deeply inset channel through the entire deposit by May 2014, 2 months after the landslide. The mean water-surface elevation of the channel through the landslide decreased 7 meters during that 2-month period, and was about 1 meter above the pre-landslide profile in July 2014. The 2014–15 flood season, which included flows near the 0.5 annual exceedance probability discharge (2-year flood), widened the channel tens of meters, and further lowered the water-surface profile 0.5 meter. The planform position evolved slowly as a result of 5–20-meter high banks predominantly composed of clay-rich, cohesive lacustrine material. Erosion of the landslide deposit delivered a total of 820 thousand metric tons of sediment to the North Fork Stillaguamish River over the 18 months following the landslide. The sediment delivery from the deposit was predominantly fine grained: 77 percent (by mass) of the eroded material was silt or clay (less than 0.063 millimeter [mm]), 19 percent sand (0.063–2 mm), and 4 percent pebbles and cobbles (greater than 2 mm).Over the 18 months following the landslide, the bedload at a site 5 kilometers downstream of the landslide was estimated to be 310±65 thousand metric tons, and the suspended load at that same site was estimated to be 990±110 thousand metric tons. These loads represent the combined input from the landslide and ambient upstream sources; over the study interval, landslide sediment made up about 20–40 percent of the bedload, and 65–85 percent of the suspended-sediment load at this site. At a site 70 kilometers downstream of the landslide, near the mouth of the main‑stem Stillaguamish River, suspended sediment loads were estimated to be about 1,440 thousand metric tons, of which about 600 thousand metric tons, or 30 percent, likely was derived from the landslide. The mass of landslide sediment in suspension at the mouth of the river, and the timing of arrival of that sediment, indicates that about 70 percent of the landslide sediment eroded during the study period was quickly transported through the entire basin, exiting into Puget Sound within weeks of initial entrainment.Empirical bedload transport equations, in conjunction with surficial grain-size data and output from a one‑dimensional hydraulic model, were used to estimate spatial trends in bedload transport capacity, highlighting areas where reach-scale conditions would be most likely to promote deposition of coarse landslide sediment. Transport capacities decreased sharply over a reach about 5 kilometers downstream of the landslide and remained relatively low over the next 10 kilometers downstream. However, the magnitude of calculated transport capacities are large relative to the coarse sediment input from the landslide, suggesting that substantial deposition of landslide sediment was not likely to occur. These assessments were corroborated by observations of channel change, which indicated that the downstream channel response to the landslide was modest and short-lived. The most pronounced downstream effects included a wedge of aggradation just downstream of the landslide, about 1 meter high and extending a kilometer downstream, and a 0.3-meter pulse of aggradation observed 5 kilometers downstream of the landslide. In both locations, peak aggradation and channel response occurred within about a month of the landslide, and both sites had largely recovered to pre-landslide conditions by July 2014. No substantial channel change clearly linked to the landslide was observed after July 2014 except for a modest fining of surficial gravel size distributions and continued recovery and incision of the reach just downstream of the landslide.The muted downstream response of the North Fork Stillaguamish River to the State Route 530 Landslide primarily can be attributed to the cohesive, silt- and clay-rich material that bounded most of the new channel. Although the river efficiently incised a new channel through the deposit, subsequent rates of lateral erosion were slowed by the tall, cohesive banks, limiting the total volume of sediment delivery. Once entrained, however, most landslide material was rapidly transported downstream in suspension with little geomorphic effect. Landslide material coarse enough to travel as bedload was predominantly sand and fine gravel, and sediment transport models and observations of downstream change indicated that the rate of coarse sediment delivery from the landslide did not exceed the rivers ability to transport that material. The generally muted downstream response to sediment delivery from the State Route 530 Landslide, as well as the mechanics of that delivery and response, were generally consistent with observations made following the intentional removal of constructed dams.The rate and efficiency of erosion from the landslide decreased over the period of analysis, as the new channel approached a quasi-equilibrium form. In the absence of additional hillslope activity, rates of erosion from the landslide are likely to be small compared to those over the first 18 months after the landslide. The modest channel response to the highest rates of sediment delivery, and rapid recovery thereafter, indicate that the river should be able to convey the continued supply of landslide-derived sediment effectively with little effect on the downstream morphology and flood risks.

Effect of wearing personal protective clothing and self-contained breathing apparatus on heart rate, temperature and oxygen consumption during stepping exercise and live fire training exercises.

PubMed

Bruce-Low, S S; Cotterrell, D; Jones, G E

2007-01-15

Fire fighter breathing apparatus instructors (BAIs) must possess the ability to respond to both the extrinsic stress of a high temperature environment and the intrinsic stress from wearing personal protective equipment (PPE) and self-contained breathing apparatus (SCBA), repeatedly and regularly, whilst training recruits in live fire training exercises (LFTEs). There are few previous investigations on BAIs in hot environments such as LFTEs, since the main research focus has been on regular fire fighters undertaking exercises in temperate or fire conditions at a moderate to high exercise intensity. In this study, the intrinsic cardiovascular stress effects of wearing PPE + SCBA were first investigated using a step test whilst wearing gym kit (control), weighted gym kit (a rucksack weighted to the equivalent of PPE + SCBA) and full PPE + SCBA (weight plus the effects of protective clothing). The extrinsic effects of the very hot environment were investigated in BIAs in LFTEs compared to mock fire training exercises (MFTEs), where the fire was not ignited. There was an increase in heart rate due to the modest workload imposed on the BAIs through carrying out the MFTEs (25.0 (18.7)%) compared to resting. However, when exposed to fire during the LFTEs, heat storage appears to be significant as the heart rate increased by up to 39.8 (+/-20.1)% over that of the mock LFTEs at temperate conditions. Thus, being able to dissipate heat from the PPE is particularly important in reducing the cardiovascular responses for BAIs during LFTEs.

A longitudinal twin study of physical aggression during early childhood: evidence for a developmentally dynamic genome.

PubMed

Lacourse, E; Boivin, M; Brendgen, M; Petitclerc, A; Girard, A; Vitaro, F; Paquin, S; Ouellet-Morin, I; Dionne, G; Tremblay, R E

2014-09-01

Physical aggression (PA) tends to have its onset in infancy and to increase rapidly in frequency. Very little is known about the genetic and environmental etiology of PA development during early childhood. We investigated the temporal pattern of genetic and environmental etiology of PA during this crucial developmental period. Participants were 667 twin pairs, including 254 monozygotic and 413 dizygotic pairs, from the ongoing longitudinal Quebec Newborn Twin Study. Maternal reports of PA were obtained from three waves of data at 20, 32 and 50 months. These reports were analysed using a biometric Cholesky decomposition and linear latent growth curve model. The best-fitting Cholesky model revealed developmentally dynamic effects, mostly genetic attenuation and innovation. The contribution of genetic factors at 20 months substantially decreased over time, while new genetic effects appeared later on. The linear latent growth curve model revealed a significant moderate increase in PA from 20 to 50 months. Two separate sets of uncorrelated genetic factors accounted for the variation in initial level and growth rate. Non-shared and shared environments had no effect on the stability, initial status and growth rate in PA. Genetic factors underlie PA frequency and stability during early childhood; they are also responsible for initial status and growth rate in PA. The contribution of shared environment is modest, and perhaps limited, as it appears only at 50 months. Future research should investigate the complex nature of these dynamic genetic factors through genetic-environment correlation (r GE) and interaction (G×E) analyses.

Long-term and acute effects of temperature and oxygen on metabolism, food intake, growth and heat tolerance in a freshwater gastropod.

PubMed

Hoefnagel, K Natan; Verberk, Wilco C E P

2017-08-01

Temperature affects the physiology and life-history of ectothermic animals, often increasing metabolic rate and decreasing body size. Oxygen limitation has been put forward as a mechanism to explain thermal responses of body size and the ability to survive stress. However the time-scales involved in growth performance and heat tolerance differ radically. In order to increase our understanding of oxygen and temperature effects on body size and heat tolerance and the time scale involved, we reared Lymnaea stagnalis under six combinations of temperature and oxygen tension from hatching up to an age of 300 days and recorded shell length during this whole period. At the end of this period, we determined scope for growth by measuring food intake rate, assimilation efficiency, respiration rate and ammonium excretion rate at two different temperatures. We also measured the snails' ability to survive heat stress (CTmax), both at normoxia and hypoxia. We found that scope for growth and long term growth performance were much more affected by interactions of chronic oxygen and temperature conditions during rearing than by acute conditions during testing. Furthermore, our study shows that individual variation in growth performance can be traced back to individual differences in rates of food and oxygen consumption. Developmental acclimation also gave rise to differences in CTmax, but these were relatively small and were only expressed when CTmax was tested under hypoxia. The large effects of rearing oxygen conditions on growth and other physiological rates compared to modest effects of test oxygen conditions on CTmax suggest that small effects of hypoxia on the short term (e.g. heat tolerance) may nevertheless have large repercussions on the long term (e.g. growth and reproduction), even in a pulmonate snail that can compensate for hypoxia to some extent by aerial respiration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Strain, strain rate, and the force frequency relationship in patients with and without heart failure.

PubMed

Mak, Susanna; Van Spall, Harriette G C; Wainstein, Rodrigo V; Sasson, Zion

2012-03-01

The aim of this study was to examine the effect of heart rate (HR) on indices of deformation in adults with and without heart failure (HF) who underwent simultaneous high-fidelity catheterization of the left ventricle to describe the force-frequency relationship. Right atrial pacing to control HR and high-fidelity recordings of left ventricular (LV) pressure were used to inscribe the force-frequency relationship. Simultaneous two-dimensional echocardiographic imaging was acquired for speckle-tracking analysis. Thirteen patients with normal LV function and 12 with systolic HF (LV ejection fraction, 31 ± 13%) were studied. Patients with HF had depressed isovolumic contractility and impaired longitudinal strain and strain rate. HR-dependent increases in LV+dP/dt(max), the force-frequency relationship, was demonstrated in both groups (normal LV function, baseline to 100 beats/min: 1,335 ± 296 to 1,564 ± 320 mm Hg/sec, P < .0001; HF, baseline to 100 beats/min: 970 ± 207 to 1,083 ± 233 mm Hg/sec, P < .01). Longitudinal strain decreased significantly (normal LV function, baseline to 100 beats/min: 18.0 ± 3.5% to 10.8 ± 6.0%, P < .001; HF: 9.4 ± 4.1% to 7.5 ± 3.4%, P < .01). The decrease in longitudinal strain was related to a decrease in LV end-diastolic dimensions. Strain rate did not change with right atrial pacing. Despite the inotropic effect of increasing HR, longitudinal strain decreases in parallel with stroke volume as load-dependent indices of ejection. Strain rate did not reflect the modest HR-related changes in contractility; on the other hand, the use of strain rate for quantitative stress imaging is also less likely to be confounded by chronotropic responses. Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

How important are work-family support policies? A meta-analytic investigation of their effects on employee outcomes.

PubMed

Butts, Marcus M; Casper, Wendy J; Yang, Tae Seok

2013-01-01

This meta-analysis examines relationships between work-family support policies, which are policies that provide support for dependent care responsibilities, and employee outcomes by developing a conceptual model detailing the psychological mechanisms through which policy availability and use relate to work attitudes. Bivariate results indicated that availability and use of work-family support policies had modest positive relationships with job satisfaction, affective commitment, and intentions to stay. Further, tests of differences in effect sizes showed that policy availability was more strongly related to job satisfaction, affective commitment, and intentions to stay than was policy use. Subsequent meta-analytic structural equation modeling results indicated that policy availability and use had modest effects on work attitudes, which were partially mediated by family-supportive organization perceptions and work-to-family conflict, respectively. Additionally, number of policies and sample characteristics (percent women, percent married-cohabiting, percent with dependents) moderated the effects of policy availability and use on outcomes. Implications of these findings and directions for future research on work-family support policies are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Menin regulates the function of hematopoietic stem cells and lymphoid progenitors

PubMed Central

Chen, Ya-Xiong; Friedman, Ann; Yang, Yuqing; Tubbs, Anthony T.; Shestova, Olga; Pear, Warren S.

2009-01-01

Men1 is a tumor suppressor gene mutated in endocrine neoplasms. Besides its endocrine role, the Men1 gene product menin interacts with the mixed lineage leukemia (MLL) protein, a histone H3 lysine 4 methyltransferase. Although menin and MLL fusion proteins cooperate to activate Homeobox (Hox) gene expression during transformation, little is known about the normal hematopoietic functions of menin. Here, we studied hematopoiesis after Men1 ablation. Menin loss modestly impaired blood neutrophil, lymphocyte, and platelet counts. Without hematopoietic stress, multilineage and myelo-erythroid bone marrow progenitor numbers were preserved, while B lymphoid progenitors were decreased. In contrast, competitive transplantation revealed a marked functional defect of long-term hematopoietic stem cells (HSC) in the absence of menin, despite normal initial homing of progenitors to the bone marrow. HoxA9 gene expression was only modestly decreased in menin-deficient HSCs. These observations reveal a novel and essential role for menin in HSC homeostasis that was most apparent during situations of hematopoietic recovery, suggesting that menin regulates molecular pathways that are essential during the adaptive HSC response to stress. PMID:19228930

Cost-effectiveness of a program to prevent depression relapse in primary care.

PubMed

Simon, Gregory E; Von Korff, Michael; Ludman, Evette J; Katon, Wayne J; Rutter, Carolyn; Unützer, Jürgen; Lin, Elizabeth H B; Bush, Terry; Walker, Edward

2002-10-01

Evaluate the incremental cost-effectiveness of a depression relapse prevention program in primary care. Primary care patients initiating antidepressant treatment completed a standardized telephone assessment 6-8 weeks later. Those recovered from the current episode but at high risk for relapse (based on history of recurrent depression or dysthymia) were offered randomization to usual care or a relapse prevention intervention. The intervention included systematic patient education, two psychoeducational visits with a depression prevention specialist, shared decision-making regarding maintenance pharmacotherapy, and telephone and mail monitoring of medication adherence and depressive symptoms. Outcomes in both groups were assessed via blinded telephone assessments at 3, 6, 9, and 12 months and health plan claims and accounting data. Intervention patients experienced 13.9 additional depression-free days during a 12-month period (95% CI, -1.5 to 29.3). Incremental costs of the intervention were $273 (95% CI, $102 to $418) for depression treatment costs only and $160 (95% CI, -$173 to $512) for total outpatient costs. Incremental cost-effectiveness ratio was $24 per depression-free day (95% CI, -$59 to $496) for depression treatment costs only and $14 per depression-free day (95% CI, -$35 to $248) for total outpatient costs. A program to prevent depression relapse in primary care yields modest increases in days free of depression and modest increases in treatment costs. These modest differences reflect high rates of treatment in usual care. Along with other recent studies, these findings suggest that improved care of depression in primary care is a prudent investment of health care resources.

Self-Diffusion of Drops in a Dilute Sheared Emulsion

NASA Technical Reports Server (NTRS)

Loewenberg, Michael; Hinch, E. J.

1996-01-01

Self-diffusion coefficients that describe cross-flow migration of non-Brownian drops in a dilute sheared emulsion were obtained by trajectory calculations. A boundary integral formulation was used to describe pairwise interactions between deformable drops; interactions between undeformed drops were described with mobility functions for spherical drops. The results indicate that drops have large anisotropic self-diffusivities which depend strongly on the drop viscosity and modestly on the shear-rate. Pairwise interactions between drops in shear-flow do not appreciably promote drop breakup.

VALUING LOST HOME PRODUCTION OF DUAL EARNER COUPLES*

PubMed Central

House, Christopher L.; Laitner, John; Stolyarov, Dmitriy

2009-01-01

Using a life-cycle model in which women divide their time between home and market work, we establish a link between retirement wealth and the value of forgone home production. We use data from the Health and Retirement Study to estimate the model’s parameters and adjust the growth rate of GDP to reflect reductions in non-market output. We find that the value of forgone home production is modest – about 25 percent of women’s measured earnings. PMID:20052402

Summary of the Budget and Economic Outlook: 2016 to 2026

DTIC Science & Technology

2016-01-19

year and next. Increases in demand for goods and services are expected to reduce the quantity of underused labor and capital, or “ slack ,” in the... slack will also push up infla- tion and interest rates. Over the following years, CBO projects, output will grow at a more modest pace, con- strained...6 SUMMARY OF THE BUDGET AND ECONOMIC OUTLOOK: 2016 TO 2026 JANUARY 19, 2016 CBOSolid Economic Growth Over the Next Few Years Will Reduce Slack in

The strain-rate sensitivity of high-strength high-toughness steels.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dilmore, M.F.; Crenshaw, Thomas B.; Boyce, Brad Lee

2006-01-01

The present study examines the strain-rate sensitivity of four high strength, high-toughness alloys at strain rates ranging from 0.0002 s-1 to 200 s-1: Aermet 100, a modified 4340, modified HP9-4-20, and a recently developed Eglin AFB steel alloy, ES-1c. A refined dynamic servohydraulic method was used to perform tensile tests over this entire range. Each of these alloys exhibit only modest strain-rate sensitivity. Specifically, the strain-rate sensitivity exponent m, is found to be in the range of 0.004-0.007 depending on the alloy. This corresponds to a {approx}10% increase in the yield strength over the 7-orders of magnitude change in strain-rate.more » Interestingly, while three of the alloys showed a concominant {approx}3-10% drop in their ductility with increasing strain-rate, the ES1-c alloy actually exhibited a 25% increase in ductility with increasing strain-rate. Fractography suggests the possibility that at higher strain-rates ES-1c evolves towards a more ductile dimple fracture mode associated with microvoid coalescence.« less

Mutation rates among RNA viruses

PubMed Central

Drake, John W.; Holland, John J.

1999-01-01

The rate of spontaneous mutation is a key parameter in modeling the genetic structure and evolution of populations. The impact of the accumulated load of mutations and the consequences of increasing the mutation rate are important in assessing the genetic health of populations. Mutation frequencies are among the more directly measurable population parameters, although the information needed to convert them into mutation rates is often lacking. A previous analysis of mutation rates in RNA viruses (specifically in riboviruses rather than retroviruses) was constrained by the quality and quantity of available measurements and by the lack of a specific theoretical framework for converting mutation frequencies into mutation rates in this group of organisms. Here, we describe a simple relation between ribovirus mutation frequencies and mutation rates, apply it to the best (albeit far from satisfactory) available data, and observe a central value for the mutation rate per genome per replication of μg ≈ 0.76. (The rate per round of cell infection is twice this value or about 1.5.) This value is so large, and ribovirus genomes are so informationally dense, that even a modest increase extinguishes the population. PMID:10570172

Self-Reported and Interviewer-Rated Oral Health in Patients With Schizophrenia, Bipolar Disorder, and Major Depressive Disorder.

PubMed

Tang, Li-Rong; Zheng, Wei; Zhu, Hui; Ma, Xin; Chiu, Helen F K; Correll, Christoph U; Ungvari, Gabor S; Xiang, Ying-Qiang; Lai, Kelly Y C; Cao, Xiao-Lan; Li, Yan; Zhong, Bao-Liang; Lok, Ka In; Xiang, Yu-Tao

2016-01-01

To compare self-reported (SR) and interviewer-rated (IR) oral health between schizophrenia (SZ), bipolar disorder (BP), and major depressive disorder (MDD) patients. 356 patients with SZ, BP, or MDD underwent assessments of psychopathology, side effects, SR, and IR oral health status. 118 patients (33.1%) reported poor oral health; the corresponding proportion was 36.4% in BP, 34.8% in SZ, and 25.5% in MD (p = .21). SR and IR oral health correlated only modestly (r = 0.17-0.36) in each group. Psychiatric patients need to be assessed for both SR and IR oral health. © 2014 Wiley Periodicals, Inc.

Some practical aspects of lossless and nearly-lossless compression of AVHRR imagery

NASA Technical Reports Server (NTRS)

Hogan, David B.; Miller, Chris X.; Christensen, Than Lee; Moorti, Raj

1994-01-01

Compression of Advanced Very high Resolution Radiometers (AVHRR) imagery operating in a lossless or nearly-lossless mode is evaluated. Several practical issues are analyzed including: variability of compression over time and among channels, rate-smoothing buffer size, multi-spectral preprocessing of data, day/night handling, and impact on key operational data applications. This analysis is based on a DPCM algorithm employing the Universal Noiseless Coder, which is a candidate for inclusion in many future remote sensing systems. It is shown that compression rates of about 2:1 (daytime) can be achieved with modest buffer sizes (less than or equal to 2.5 Mbytes) and a relatively simple multi-spectral preprocessing step.

Thermal isomerizations of ketenimines to nitriles: evaluations of sigma-Dot (sigma(*)) constants for spin-delocalizations

PubMed

Kim; Zhu; Lee

2000-05-19

Rate constants (k(Y)) of the isomerizations of 11 diphenyl N-(substituted benzyl) ketenimines were measured at 40, 50, 60, and 70 degrees C. Activation parameters DeltaH()(Y) and DeltaS()(Y) were obtained using the Eyring equation. The relative rates (k(Y)/k(H)) were fitted into Hammett single correlations (log k(Y)/k(H) = rhosigma and log k(Y)/k(H) = rho(*)sigma(*)). The single correlations have been compared with Hammett dual correlations (log k(Y)/k(H) = rhosigma + rho(*)sigma(*) ). Separate treatments of para and meta substituents yielded even better correlations. Para substituents control the rates through spin-delocalizations and inductive effects. The former outweighs the latter when the latter exerts a modest but distinct influence on the rates. On the other hand, inductive effects are the "major" or the sole interactions triggered by meta substituents.

Chronic prazosin attenuates the natriuretic response to a modest saline load in anaesthetized rats.

PubMed Central

Penner, S. B.; Smyth, D. D.

1988-01-01

1. The effect of chronic prazosin pretreatment (3 days) on the ability to excrete a modest saline load (i.v. saline, 0.097 ml min-1) was studied in the anaesthetized rat. Three days before the experiment, the drinking water was replaced with 0.5% dextrose (control), 0.015 mg ml-1 prazosin in 0.5% dextrose (low dose) or 0.15 mg ml-1 prazosin in 0.5% dextrose (high dose). 2. The selectivity of the prazosin for alpha 1-adrenoceptors was evaluated in pithed rats. The pressor response to phenylephrine was partially attenuated by the low dose of prazosin and completely attenuated by the high dose of prazosin. The pressor response to clonidine was slightly decreased by the 3 day prazosin pretreatment indicating a selectivity for alpha 1-adrenoceptors. 3. In rats pretreated with the low dose of prazosin, there was a significant decrease in sodium and water, but not potassium excretion as compared to the control group. Captopril failed to alter these effects of the low dose of prazosin. Blood pressure and creatinine clearance were the same in both groups. In rats pretreated with the high dose of prazosin, there was a further decrease in sodium and water but not potassium excretion. However, this dose of prazosin also significantly decreased blood pressure and increased creatinine clearance. A decrease in renal perfusion pressure with an aortic clamp to the same level as that observed with the high prazosin dose also decreased sodium and water but not potassium excretion. The decrease in sodium and water excretion was not as great as that observed with the high dose of prazosin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2896036