A comparison of response rates in the English Longitudinal Study of Ageing and the Health and Retirement Study

PubMed Central

Cheshire, Hayley; Ofstedal, Mary Beth; Scholes, Shaun; Schroeder, Mathis

2013-01-01

Survey response rates are an important measure of the quality of a survey; this is true for both longitudinal and cross-sectional surveys. However, the concept of a response rate in the context of a panel survey is more complex than is the case for a cross-sectional survey. There are typically many different response rates that can be calculated for a panel survey, each of which may be relevant for a specific purpose. The main objective of our paper is to document and compare response rates for two long-term panel studies of ageing, the English Longitudinal Study of Ageing (ELSA) and the Health and Retirement Study (HRS) in the United States. To guide our selection and calculation of response rates for the two studies, we use a framework that was developed by Peter Lynn (2005) and present several different types of longitudinal response rates for the two surveys. We discuss similarities and differences in the study designs and protocols and how some of the differences affect comparisons of response rates across the two studies. PMID:24432049

MDMA does not alter responses to the Trier Social Stress Test in humans

PubMed Central

Bershad, Anya K.; Miller, Melissa A.; de Wit, Harriet

2018-01-01

Rationale ±3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a stimulant-psychedelic drug with unique social effects. It may dampen reactivity to negative social stimuli such as social threat and rejection. Perhaps because of these effects, MDMA has shown promise as a treatment for post-traumatic stress disorder (PTSD). However, the effect of single doses of MDMA on responses to an acute psychosocial stressor has not been tested. Objectives In this study, we sought to test the effects of MDMA on responses to stress in healthy adults using a public speaking task. We hypothesized that the drug would reduce responses to the stressful task. Methods Volunteers (N = 39) were randomly assigned to receive placebo (N = 13), 0.5 mg/kg MDMA (N = 13), or 1.0 mg/kg MDMA (N = 13) during a stress and a no-stress session. Dependent measures included subjective reports of drug effects and emotional responses to the task, as well as salivary cortisol, heart rate, and blood pressure. Results The stress task produced its expected increase in physiological responses (cortisol, heart rate) and subjective ratings of stress in all three groups, and MDMA produced its expected subjective and physiological effects. MDMA alone increased ratings of subjective stress, heart rate, and saliva cortisol concentrations, but contrary to our hypothesis, it did not moderate responses to the Trier Social Stress Test. Conclusions Despite its efficacy in PTSD and anxiety, MDMA did not reduce either the subjective or objective responses to stress in this controlled study. The conditions under which MDMA relieves responses to negative events or memories remain to be determined. PMID:28432376

Combination chemotherapy of carboplatin and paclitaxel for advanced/metastatic salivary gland carcinoma patients: differences in responses by different pathological diagnoses.

PubMed

Nakano, Kenji; Sato, Yukiko; Sasaki, Tohru; Shimbashi, Wataru; Fukushima, Hirofumi; Yonekawa, Hiroyuki; Mitani, Hiroki; Kawabata, Kazuyoshi; Takahashi, Shunji

2016-09-01

A standard chemotherapy for recurrent/metastatic salivary gland cancers has not been established. Combination chemotherapy of carboplatin and paclitaxel should be evaluated as a treatment option. This study retrospectively reviewed salivary gland cancer patients who received combination chemotherapy of carboplatin and paclitaxel. The differences in objective responses and in the prognoses according to the different pathological diagnoses were evaluated. A total of 38 patients were enrolled in the study; of them, 18 had salivary duct carcinomas (SDCs), nine had adenoid cystic carcinomas (ACCs), and 11 had other pathological diagnoses. Objective responses were observed in 15 (39%) patients. The median progression-free survival (PFS) was 6.5 months, and the median overall survival (OS) was 26.5 months. ACC patients had relatively low response rates (9%), but there were no significant differences in PFS or OS compared to other sub-types. The treatment was well tolerated, with few adverse events. Salivary gland cancer patients showed a moderate clinical response to the combination chemotherapy of carboplatin and paclitaxel. The objective response rates differed according to the pathological diagnoses, but there were no significant differences in prognoses.

Monitoring the athlete training response: subjective self-reported measures trump commonly used objective measures: a systematic review

PubMed Central

Saw, Anna E; Main, Luana C; Gastin, Paul B

2016-01-01

Background Monitoring athlete well-being is essential to guide training and to detect any progression towards negative health outcomes and associated poor performance. Objective (performance, physiological, biochemical) and subjective measures are all options for athlete monitoring. Objective We systematically reviewed objective and subjective measures of athlete well-being. Objective measures, including those taken at rest (eg, blood markers, heart rate) and during exercise (eg, oxygen consumption, heart rate response), were compared against subjective measures (eg, mood, perceived stress). All measures were also evaluated for their response to acute and chronic training load. Methods The databases Academic search complete, MEDLINE, PsycINFO, SPORTDiscus and PubMed were searched in May 2014. Fifty-six original studies reported concurrent subjective and objective measures of athlete well-being. The quality and strength of findings of each study were evaluated to determine overall levels of evidence. Results Subjective and objective measures of athlete well-being generally did not correlate. Subjective measures reflected acute and chronic training loads with superior sensitivity and consistency than objective measures. Subjective well-being was typically impaired with an acute increase in training load, and also with chronic training, while an acute decrease in training load improved subjective well-being. Summary This review provides further support for practitioners to use subjective measures to monitor changes in athlete well-being in response to training. Subjective measures may stand alone, or be incorporated into a mixed methods approach to athlete monitoring, as is current practice in many sport settings. PMID:26423706

Associations of objectively measured physical activity with daily mood ratings and psychophysiological stress responses in women.

PubMed

Poole, Lydia; Steptoe, Andrew; Wawrzyniak, Andrew J; Bostock, Sophie; Mitchell, Ellen S; Hamer, Mark

2011-08-01

The aim of this study was to examine associations of objectively measured physical activity with daily mood ratings and psychophysiological stress responses. We recruited 40 healthy females (aged 28.7 ± 6.1 yrs) who completed a once-a-day mood rating scale for 7 days, along with a 7-day assessment of physical activity using accelerometers and psychophysiological stress testing. The findings suggest that levels of physical activity as measured using an accelerometer are associated with both depressive symptoms over the past 2 weeks (CES-D) (r = - .33, p = .038) and with daily positive emotional style (r = .49, p = .001). The relationship between physical activity and positive emotional style remained after controlling for age, body mass index, and negative emotional style (t = 3.31, p = .002). Physical activity was not related to any psychophysiological stress responses. Copyright © 2011 Society for Psychophysiological Research.

Optimum poultry litter rates for maximum profit vs. yield in cotton production

USDA-ARS?s Scientific Manuscript database

Cotton lint yield responds well to increasing rates of poultry litter fertilization, but little is known of how optimum rates for yield compare with optimum rates for profit. The objectives of this study were to analyze cotton lint yield response to poultry litter application rates, determine and co...

Brentuximab Vedotin in the Front-Line Treatment of Patients With CD30+ Peripheral T-Cell Lymphomas: Results of a Phase I Study

PubMed Central

Fanale, Michelle A.; Horwitz, Steven M.; Forero-Torres, Andres; Bartlett, Nancy L.; Advani, Ranjana H.; Pro, Barbara; Chen, Robert W.; Davies, Andrew; Illidge, Tim; Huebner, Dirk; Kennedy, Dana A.; Shustov, Andrei R.

2014-01-01

Purpose Front-line treatment of peripheral T-cell lymphomas (PTCL) involves regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and results in a 5-year overall survival (OS) rate of less than 50%. This phase I open-label study evaluated the safety and activity of brentuximab vedotin administered sequentially with CHOP or in combination with CHP (CHOP without vincristine) as front-line treatment in patients with CD30+ PTCL. Patients and Methods Patients received sequential treatment (once every 3 weeks) with brentuximab vedotin 1.8 mg/kg (two cycles) followed by CHOP (six cycles) or brentuximab vedotin 1.8 mg/kg plus CHP (BV+CHP) for six cycles (once every 3 weeks). Responders received single-agent brentuximab vedotin for eight to 10 additional cycles (for a total of 16 cycles). The primary objective was assessment of safety; secondary end points included objective response rate, complete remission (CR) rate, progression-free survival rate (PFS), and OS. There were no prespecified comparisons of the two treatment approaches. Results After sequential treatment, 11 (85%) of 13 patients achieved an objective response (CR rate, 62%; estimated 1-year PFS rate, 77%). Grade 3/4 adverse events occurred in eight (62%) of 13 patients. At the end of combination treatment, all patients (n = 26) achieved an objective response (CR rate, 88%; estimated 1-year PFS rate, 71%). All seven patients without anaplastic large-cell lymphoma achieved CR. Grade 3/4 adverse events (≥ 10%) in the combination-treatment group were febrile neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%). Conclusion Brentuximab vedotin, administered sequentially with CHOP or in combination with CHP, had a manageable safety profile and exhibited substantial antitumor activity in newly diagnosed patients with CD30+ PTCL. A randomized phase III trial is under way, comparing BV+CHP with CHOP (clinical trial No. NCT01777152). PMID:25135998

Curriculum development for a national cardiotocography education program: a Delphi survey to obtain consensus on learning objectives.

PubMed

Thellesen, Line; Hedegaard, Morten; Bergholt, Thomas; Colov, Nina P; Hoegh, Stinne; Sorensen, Jette L

2015-08-01

To define learning objectives for a national cardiotocography (CTG) education program based on expert consensus. A three-round Delphi survey. One midwife and one obstetrician from each maternity unit in Denmark were appointed based on CTG teaching experience and clinical obstetric experience. Following national and international guidelines, the research group determined six topics as important when using CTG: fetal physiology, equipment, indication, interpretation, clinical management, and communication/responsibility. In the first Delphi round, participants listed one to five learning objectives within the predefined topics. Responses were analyzed by a directed approach to content analysis. Phrasing was modified in accordance with Bloom's taxonomy. In the second and third Delphi rounds, participants rated each objective on a five-point relevance scale. Consensus was predefined as objectives with a mean rating value of ≥ 3. A prioritized list of CTG learning objectives. A total of 42 midwives and obstetricians from 21 maternity units were invited to participate, of whom 26 completed all three Delphi rounds, representing 18 maternity units. The final prioritized list included 40 objectives. The highest ranked objectives emphasized CTG interpretation and clinical management. The lowest ranked objectives emphasized fetal physiology. Mean ratings of relevance ranged from 3.15 to 5.00. National consensus on CTG learning objectives was achieved using the Delphi methodology. This was an initial step in developing a valid CTG education program. A prioritized list of objectives will clarify which topics to emphasize in a CTG education program. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Use of Portable Digital Devices to Analyze Autonomic Stress Response in Psychology Objective Structured Clinical Examination.

PubMed

Beltrán-Velasco, Ana Isabel; Bellido-Esteban, Alberto; Ruisoto-Palomera, Pablo; Clemente-Suárez, Vicente Javier

2018-01-12

The aim of the present study was to explore changes in the autonomic stress response of Psychology students in a Psychology Objective Structured Clinical Examination (OSCE) and their relationship with OSCE performance. Variables of autonomic modulation by the analysis of heart rate variability in temporal, frequency and non-linear domains, subjective perception of distress strait and academic performance were measured before and after the two different evaluations that composed the OSCE. A psychology objective structured clinical examination composed by two different evaluation scenarios produced a large anxiety anticipatory response, a habituation response in the first of the evaluation scenarios and a in the entire evaluation, and a no habituation response in the second evaluation scenario. Autonomic modulation parameters do not correlate with academic performance of students.

Understanding the Effect of Response Rate and Class Size Interaction on Students Evaluation of Teaching in a Higher Education

ERIC Educational Resources Information Center

Al Kuwaiti, Ahmed; AlQuraan, Mahmoud; Subbarayalu, Arun Vijay

2016-01-01

Objective: This study aims to investigate the interaction between response rate and class size and its effects on students' evaluation of instructors and the courses offered at a higher education Institution in Saudi Arabia. Study Design: A retrospective study design was chosen. Methods: One thousand four hundred and forty four different courses…

Defining Treatment Response and Remission in Child Anxiety: Signal Detection Analysis Using the Pediatric Anxiety Rating Scale

ERIC Educational Resources Information Center

Caporino, Nicole E.; Brodman, Douglas M.; Kendall, Philip C.; Albano, Anne Marie; Sherrill, Joel; Piacentini, John; Sakolsky, Dara; Birmaher, Boris; Compton, Scott N.; Ginsburg, Golda; Rynn, Moira; McCracken, James; Gosch, Elizabeth; Keeton, Courtney; March, John; Walkup, John T.

2013-01-01

Objective: To determine optimal Pediatric Anxiety Rating Scale (PARS) percent reduction and raw score cut-offs for predicting treatment response and remission among children and adolescents with anxiety disorders. Method: Data were from a subset of youth (N = 438; 7-17 years of age) who participated in the Child/Adolescent Anxiety Multimodal Study…

Simple Learned Weighted Sums of Inferior Temporal Neuronal Firing Rates Accurately Predict Human Core Object Recognition Performance.

PubMed

Majaj, Najib J; Hong, Ha; Solomon, Ethan A; DiCarlo, James J

2015-09-30

To go beyond qualitative models of the biological substrate of object recognition, we ask: can a single ventral stream neuronal linking hypothesis quantitatively account for core object recognition performance over a broad range of tasks? We measured human performance in 64 object recognition tests using thousands of challenging images that explore shape similarity and identity preserving object variation. We then used multielectrode arrays to measure neuronal population responses to those same images in visual areas V4 and inferior temporal (IT) cortex of monkeys and simulated V1 population responses. We tested leading candidate linking hypotheses and control hypotheses, each postulating how ventral stream neuronal responses underlie object recognition behavior. Specifically, for each hypothesis, we computed the predicted performance on the 64 tests and compared it with the measured pattern of human performance. All tested hypotheses based on low- and mid-level visually evoked activity (pixels, V1, and V4) were very poor predictors of the human behavioral pattern. However, simple learned weighted sums of distributed average IT firing rates exactly predicted the behavioral pattern. More elaborate linking hypotheses relying on IT trial-by-trial correlational structure, finer IT temporal codes, or ones that strictly respect the known spatial substructures of IT ("face patches") did not improve predictive power. Although these results do not reject those more elaborate hypotheses, they suggest a simple, sufficient quantitative model: each object recognition task is learned from the spatially distributed mean firing rates (100 ms) of ∼60,000 IT neurons and is executed as a simple weighted sum of those firing rates. Significance statement: We sought to go beyond qualitative models of visual object recognition and determine whether a single neuronal linking hypothesis can quantitatively account for core object recognition behavior. To achieve this, we designed a database of images for evaluating object recognition performance. We used multielectrode arrays to characterize hundreds of neurons in the visual ventral stream of nonhuman primates and measured the object recognition performance of >100 human observers. Remarkably, we found that simple learned weighted sums of firing rates of neurons in monkey inferior temporal (IT) cortex accurately predicted human performance. Although previous work led us to expect that IT would outperform V4, we were surprised by the quantitative precision with which simple IT-based linking hypotheses accounted for human behavior. Copyright © 2015 the authors 0270-6474/15/3513402-17$15.00/0.

On a problematic procedure to manipulate response biases in recognition experiments: the case of "implied" base rates.

PubMed

Bröder, Arndt; Malejka, Simone

2017-07-01

The experimental manipulation of response biases in recognition-memory tests is an important means for testing recognition models and for estimating their parameters. The textbook manipulations for binary-response formats either vary the payoff scheme or the base rate of targets in the recognition test, with the latter being the more frequently applied procedure. However, some published studies reverted to implying different base rates by instruction rather than actually changing them. Aside from unnecessarily deceiving participants, this procedure may lead to cognitive conflicts that prompt response strategies unknown to the experimenter. To test our objection, implied base rates were compared to actual base rates in a recognition experiment followed by a post-experimental interview to assess participants' response strategies. The behavioural data show that recognition-memory performance was estimated to be lower in the implied base-rate condition. The interview data demonstrate that participants used various second-order response strategies that jeopardise the interpretability of the recognition data. We thus advice researchers against substituting actual base rates with implied base rates.

Human cortical responses to slow and fast binaural beats reveal multiple mechanisms of binaural hearing.

PubMed

Ross, Bernhard; Miyazaki, Takahiro; Thompson, Jessica; Jamali, Shahab; Fujioka, Takako

2014-10-15

When two tones with slightly different frequencies are presented to both ears, they interact in the central auditory system and induce the sensation of a beating sound. At low difference frequencies, we perceive a single sound, which is moving across the head between the left and right ears. The percept changes to loudness fluctuation, roughness, and pitch with increasing beat rate. To examine the neural representations underlying these different perceptions, we recorded neuromagnetic cortical responses while participants listened to binaural beats at a continuously varying rate between 3 Hz and 60 Hz. Binaural beat responses were analyzed as neuromagnetic oscillations following the trajectory of the stimulus rate. Responses were largest in the 40-Hz gamma range and at low frequencies. Binaural beat responses at 3 Hz showed opposite polarity in the left and right auditory cortices. We suggest that this difference in polarity reflects the opponent neural population code for representing sound location. Binaural beats at any rate induced gamma oscillations. However, the responses were largest at 40-Hz stimulation. We propose that the neuromagnetic gamma oscillations reflect postsynaptic modulation that allows for precise timing of cortical neural firing. Systematic phase differences between bilateral responses suggest that separate sound representations of a sound object exist in the left and right auditory cortices. We conclude that binaural processing at the cortical level occurs with the same temporal acuity as monaural processing whereas the identification of sound location requires further interpretation and is limited by the rate of object representations. Copyright © 2014 the American Physiological Society.

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer.

PubMed

Inman, Brant A; Longo, Thomas A; Ramalingam, Sundhar; Harrison, Michael R

2017-04-15

Atezolizumab (Tecentriq, MPDL3280A; Genentech/Roche) is an FcγR binding-deficient, fully humanized IgG1 mAb designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironment and, consequently, increases T-cell-mediated immunity against the tumor. Atezolizumab has been FDA approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase II trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses. In subjects whose tumors progressed on first-line platinum-based chemotherapy, the objective response rate was 15%, the complete response rate was 5%, and 1-year overall survival was 36%. In subjects that were chemotherapy naïve and cisplatin ineligible, the objective response rate was 24%, the complete response rate was 7%, and 1-year overall survival was 57%. Better responses were associated with higher PD-L1 expression on the tumor-infiltrating leukocytes. These data suggest that patients with advanced bladder cancer treated with atezolizumab have significantly better response rates and survival than historical controls treated with other second-line regimens. The toxicity profile of atezolizumab is also favorable. Trials are currently assessing whether atezolizumab is effective in earlier bladder cancer stages and in the first-line metastatic setting. Clin Cancer Res; 23(8); 1886-90. ©2016 AACR . ©2016 American Association for Cancer Research.

Multivariate objective response detectors (MORD): statistical tools for multichannel EEG analysis during rhythmic stimulation.

PubMed

Felix, Leonardo Bonato; Miranda de Sá, Antonio Mauricio Ferreira Leite; Infantosi, Antonio Fernando Catelli; Yehia, Hani Camille

2007-03-01

The presence of cerebral evoked responses can be tested by using objective response detectors. They are statistical tests that provide a threshold above which responses can be assumed to have occurred. The detection power depends on the signal-to-noise ratio (SNR) of the response and the amount of data available. However, the correlation within the background noise could also affect the power of such detectors. For a fixed SNR, the detection can only be improved at the expense of using a longer stretch of signal. This can constitute a limitation, for instance, in monitored surgeries. Alternatively, multivariate objective response detection (MORD) could be used. This work applies two MORD techniques (multiple coherence and multiple component synchrony measure) to EEG data collected during intermittent photic stimulation. They were evaluated throughout Monte Carlo simulations, which also allowed verifying that correlation in the background reduces the detection rate. Considering the N EEG derivations as close as possible to the primary visual cortex, if N = 4, 6 or 8, multiple coherence leads to a statistically significant higher detection rate in comparison with multiple component synchrony measure. With the former, the best performance was obtained with six signals (O1, O2, T5, T6, P3 and P4).

[¹³¹I]Metaiodobenzylguanidine therapy in neural crest tumors: varying outcome in different histopathologies.

PubMed

Rachh, Swati Hiren; Abhyankar, Suman; Basu, Sandip

2011-12-01

To evaluate the response of [¹³¹I] metaiodobenzylguanidine ([¹³¹I]MIBG) therapy in patients with neuroectodermal tumors and to assess their quality of life using the functional assessment of cancer therapy - general quality-of-life questionnaire for patients who are on follow-up after MIBG therapy. Thirty-two patients diagnosed with various subtypes of neuroectodermal tumors and treated with [¹³¹I]MIBG were included in this retrospective analysis. Response to therapy was evaluated objectively by comparing pretherapy and posttherapy biochemical markers, radiological investigations, and follow-up MIBG scans. Symptomatic response and quality of life were also evaluated in the follow-up visits. In seven patients with stage III neuroblastoma, an objective response rate was seen in 57% and a symptomatic response rate was seen in 29% of the patients. Among 11 patients with stage IV neuroblastoma, an objective response was observed in 36% and a symptomatic response in 36% of the patients. Among 12 patients with pheochomocytoma and paraganglioma, an objective response was noticed in 8%, but symptomatic improvement and stabilization of disease were seen in 75% of the patients belonging to this category. One patient with medullary carcinoma of the thyroid and one patient with mediastinal carcinoid did not show an objective response but had a stable disease; both patients showed symptomatic improvement. Quality of life has improved in all 11 patients who are still on follow-up. [¹³¹I]MIBG therapy can be of significant value in the treatment of patients with chemotherapy-resistant stage III and IV neuroblastomas who demonstrate good tracer uptake in diagnostic scans. MIBG therapy has the potential to stabilize the disease and provide symptomatic improvement in patients with metastatic/recurrent pheochomocytoma/paraganglioma and medullary carcinoma thyroid and carcinoid in which there is evidence of tracer accumulation in the tumor. Both single high dose or multiple fractionated doses are equally effective in improving the quality of life in metastatic/recurrent pheochomocytoma/paraganglioma.

Empowering Malaria Vaccination by Drug Administration

DTIC Science & Technology

2010-01-01

uric acid . J lmmuno/2009, 183:5208-5220. 13. Mestas J, Hughes CCW: Of mice and not men: differences between mouse and human Immunology. J lmmunol 2004...a strategy to meet this objective. Natural acquisition and evasion of malaria immunity Malaria parasites gene rate strong immune responses, and a...epidemiological observation that naturally acquired immunity fails to prevent re-infection even in areas with high infection rates . CDS+ responses

Conducting Field Research in a Primary School Setting: Methodological Considerations for Maximizing Response Rates, Data Quality and Quantity

ERIC Educational Resources Information Center

Trapp, Georgina; Giles-Corti, Billie; Martin, Karen; Timperio, Anna; Villanueva, Karen

2012-01-01

Background: Schools are an ideal setting in which to involve children in research. Yet for investigators wishing to work in these settings, there are few method papers providing insights into working efficiently in this setting. Objective: The aim of this paper is to describe the five strategies used to increase response rates, data quality and…

Efficacy and safety of apatinib combined with transarterial chemoembolization for hepatocellular carcinoma with portal venous tumor thrombus: a retrospective study.

PubMed

Liu, Changfu; Xing, Wenge; Si, Tongguo; Yu, Haipeng; Guo, Zhi

2017-11-21

To investigate the efficacy and safety of combined therapy with apatinib and transarterial chemoembolization (TACE) for hepatocellular carcinoma with portal venous tumor thrombus (PVTT). We retrospectively analyzed 19 patients with hepatocellular carcinoma with PVTT who were treated with apatinib and TACE at a single center between January 2015 and January 2017. Clinical information on the patients was collected. Adverse events, overall survival, progression-free survival, objective response rate, and disease-control rate based on mRECIST criteria (American Association for the Study of Liver Diseases, 2008) were reviewed and evaluated. All patients had complete follow-up records and the median follow-up time was 13 months (1-24 months). Among the 19 patients, 63.16% achieved a partial response and 21.05% achieved stable disease. The objective response and disease-control rates for the tumor were 63.16% and 84.21%, respectively, and the objective response and disease-control rates for PVTT were 10.93% and 89.47%, respectively. The median overall survival was 11.9 months, and the 6-month and 1-year overall survival rates were 94.7% and 48.8%, respectively. The median progression-free survival rate was 8.1 months, and the 6-month and 1-year rates were 73.3% and 22.9%, respectively. The most common apatinib-related adverse events were hand-foot-skin reaction, fatigue, dyspepsia, diarrhea, and hypertension, and the most common TACE-related adverse event was fever. No procedure-related mortality or grade 4 adverse events were observed, but grade 3 adverse events were observed in two patients. This exploratory study suggested that apatinib combined with TACE treatment was safe and might improve overall and progression-free survival in patients with hepatocellular carcinoma with PVTT. Further randomized controlled trials are needed to clarify the potential role of apatinib in hepatocellular carcinoma with PVTT.

Avelumab, an Anti–Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study

PubMed Central

Apolo, Andrea B.; Infante, Jeffrey R.; Balmanoukian, Ani; Patel, Manish R.; Wang, Ding; Kelly, Karen; Mega, Anthony E.; Britten, Carolyn D.; Ravaud, Alain; Mita, Alain C.; Safran, Howard; Stinchcombe, Thomas E.; Srdanov, Marko; Gelb, Arnold B.; Schlichting, Michael; Chin, Kevin; Gulley, James L.

2017-01-01

Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti–programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1–associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1–positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC. PMID:28375787

Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study.

PubMed

Apolo, Andrea B; Infante, Jeffrey R; Balmanoukian, Ani; Patel, Manish R; Wang, Ding; Kelly, Karen; Mega, Anthony E; Britten, Carolyn D; Ravaud, Alain; Mita, Alain C; Safran, Howard; Stinchcombe, Thomas E; Srdanov, Marko; Gelb, Arnold B; Schlichting, Michael; Chin, Kevin; Gulley, James L

2017-07-01

Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti-programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1-associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1-positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC.

Reliability of psychophysiological responses across multiple motion sickness stimulation tests

NASA Technical Reports Server (NTRS)

Stout, C. S.; Toscano, W. B.; Cowings, P. S.

1995-01-01

Although there is general agreement that a high degree of variability exists between subjects in their autonomic nervous system responses to motion sickness stimulation, very little evidence exists that examines the reproducibility of autonomic responses within subjects during motion sickness stimulation. Our objectives were to examine the reliability of autonomic responses and symptom levels across five testing occasions using the (1) final minute of testing, (2) change in autonomic response and the change in symptom level, and (3) strength of the relationship between the change in symptom level and the change in autonomic responses across the entire motion sickness test. The results indicate that, based on the final minute of testing, the autonomic responses of heart rate, blood volume pulse, and respiration rate are moderately stable across multiple tests. Changes in heart rate, blood volume pulse, respiration rate, and symptoms throughout the test duration are less stable across the tests. Finally, autonomic responses and symptom levels are significantly related across the entire motion sickness test.

Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial.

PubMed

Fuchs, Charles S; Doi, Toshihiko; Jang, Raymond W; Muro, Kei; Satoh, Taroh; Machado, Manuela; Sun, Weijing; Jalal, Shadia I; Shah, Manish A; Metges, Jean-Phillipe; Garrido, Marcelo; Golan, Talia; Mandala, Mario; Wainberg, Zev A; Catenacci, Daniel V; Ohtsu, Atsushi; Shitara, Kohei; Geva, Ravit; Bleeker, Jonathan; Ko, Andrew H; Ku, Geoffrey; Philip, Philip; Enzinger, Peter C; Bang, Yung-Jue; Levitan, Diane; Wang, Jiangdian; Rosales, Minori; Dalal, Rita P; Yoon, Harry H

2018-05-10

Therapeutic options are needed for patients with advanced gastric cancer whose disease has progressed after 2 or more lines of therapy. To evaluate the safety and efficacy of pembrolizumab in a cohort of patients with previously treated gastric or gastroesophageal junction cancer. In the phase 2, global, open-label, single-arm, multicohort KEYNOTE-059 study, 259 patients in 16 countries were enrolled in a cohort between March 2, 2015, and May 26, 2016. Median (range) follow-up was 5.8 (0.5-21.6) months. Patients received pembrolizumab, 200 mg, intravenously every 3 weeks until disease progression, investigator or patient decision to withdraw, or unacceptable toxic effects. Primary end points were objective response rate and safety. Objective response rate was assessed by central radiologic review per Response Evaluation Criteria in Solid Tumors, version 1.1, in all patients and those with programmed cell death 1 ligand 1 (PD-L1)-positive tumors. Expression of PD-L1 was assessed by immunohistochemistry. Secondary end points included response duration. Of 259 patients enrolled, most were male (198 [76.4%]) and white (200 [77.2%]); median (range) age was 62 (24-89) years. Objective response rate was 11.6% (95% CI, 8.0%-16.1%; 30 of 259 patients), with complete response in 2.3% (95% CI, 0.9%-5.0%; 6 of 259 patients). Median (range) response duration was 8.4 (1.6+ to 17.3+) months (+ indicates that patients had no progressive disease at their last assessment). Objective response rate and median (range) response duration were 15.5% (95% CI, 10.1%-22.4%; 23 of 148 patients) and 16.3 (1.6+ to 17.3+) months and 6.4% (95% CI, 2.6%-12.8%; 7 of 109 patients) and 6.9 (2.4 to 7.0+) months in patients with PD-L1-positive and PD-L1-negative tumors, respectively. Forty-six patients (17.8%) experienced 1 or more grade 3 to 5 treatment-related adverse events. Two patients (0.8%) discontinued because of treatment-related adverse events, and 2 deaths were considered related to treatment. Pembrolizumab monotherapy demonstrated promising activity and manageable safety in patients with advanced gastric or gastroesophageal junction cancer who had previously received at least 2 lines of treatment. Durable responses were observed in patients with PD-L1-positive and PD-L1-negative tumors. Further study of pembrolizumab for this group of patients is warranted. clinicaltrials.gov Identifier: NCT02335411.

Amplitude and timing of somatosensory cortex activity in Task Specific Focal Hand Dystonia

PubMed Central

Dolberg, Rebecca; Hinkley, Leighton B. N.; Honma, Susanne; Zhu, Zhao; Findlay, Anne M.; Byl, Nancy N.; Nagarjan, Srikantan S.

2011-01-01

Objective Task-specific focal hand dystonia (tspFHD) is a movement disorder diagnosed in individuals performing repetitive hand behaviors. The extent to which processing anomalies in primary sensory cortex extend to other regions or across the two hemispheres is presently unclear. Methods In response to low/high rate and novel tactile stimuli on the affected and unaffected hands, magnetoencephalography (MEG) was used to elaborate activity timing and amplitude in the primary somatosensory (S1) and secondary somatosensory/parietal ventral (S2/PV) cortices. MEG and clinical performance measures were collected from thirteen patients and matched controls. Results Compared to controls, subjects with tspFHD had increased response amplitude in S2/PV bilaterally in response to high rate and novel stimuli. Subjects with tspFHD also showed increased response latency (low rate, novel) of the affected digits in contralateral S1. For high rate, subjects with tspFHD showed increased response latency in ipsilateral S1 and S2/PV bilaterally. Activation differences correlated with functional sensory deficits (predicting a latency shift in S1), motor speed and muscle strength. Conclusions There are objective differences in the amplitude and timing of activity for both hands across contralateral and ipsilateral somatosensory cortex in patients with tspFHD. Significance Knowledge of cortical processing abnormalities across S1 and S2/PV in dystonia should be applied towards the development of learning based sensorimotor interventions. PMID:21802357

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

Autonomic and Neuroendocrine Responses to a Psychosocial Stressor in Adults with Autistic Spectrum

ERIC Educational Resources Information Center

Jansen, Lucres M. C.; Gispen-de Wied, Christine C.; Wiegant, Victor M.; Westenberg, Herman G. M.; Lahuis, Bertine E.; van Engeland, Herman

2006-01-01

Objective of the study was to replicate in adults our previous findings of decreased heart rate and normal endocrine responses to stress in autistic children and to elucidate the discrepancy between autonomic and endocrine stress responses by including epinephrine, norepinephrine, oxytocin and vasopressin measurements. Ten autistic spectrum…

The impact of intonation and valence on objective and subjective attention capture by auditory alarms.

PubMed

Ljungberg, Jessica K; Parmentier, Fabrice

2012-10-01

The objective was to study the involuntary capture of attention by spoken words varying in intonation and valence. In studies of verbal alarms, the propensity of alarms to capture attention has been primarily assessed with the use of subjective ratings of their perceived urgency. Past studies suggest that such ratings vary with the alarms' spoken urgency and content. We measured attention capture by spoken words varying in valence (negative vs. neutral) and intonation (urgently vs. nonurgently spoken) through subjective ratings and behavioral measures. The key behavioral measure was the response latency to visual stimuli in the presence of spoken words breaking away from the periodical repetition of a tone. The results showed that all words captured attention relative to a baseline standard tone but that this effect was partly counteracted by a relative speeding of responses for urgently compared with nonurgently spoken words. Word valence did not affect behavioral performance. Rating data showed that both intonation and valence increased significantly perceived urgency and attention grabbing without any interaction. The data suggest a congruency between subjective ratings and behavioral performance with respect to spoken intonation but not valence. This study demonstrates the usefulness and feasibility of objective measures of attention capture to help design efficient alarm systems.

Predictors of muscle protein synthesis after severe pediatric burns

USDA-ARS?s Scientific Manuscript database

Objectives: Following a major burn, muscle protein synthesis rate increases but in most patients, this response is not sufficient to compensate the also elevated protein breakdown. Given the long-term nature of the pathophysiologic response to burn injury, we hypothesized that skeletal muscle prot...

Physiological reactivity of pregnant women to evoked fetal startle

PubMed Central

DiPietro, Janet A.; Voegtline, Kristin M.; Costigan, Kathleen A.; Aguirre, Frank; Kivlighan, Katie; Chen, Ping

2013-01-01

Objective The bidirectional nature of mother-child interaction is widely acknowledged during infancy and childhood. Prevailing models during pregnancy focus on unidirectional influences exerted by the pregnant woman on the developing fetus. Prior work has indicated that the fetus also affects the pregnant woman. Our objective was to determine whether a maternal psychophysiological response to stimulation of the fetus could be isolated. Methods Using a longitudinal design, an airborne auditory stimulus was used to elicit a fetal heart rate and motor response at 24 (n = 47) and 36 weeks (n = 45) gestation. Women were blind to condition (stimulus versus sham). Maternal parameters included cardiac (heart rate) and electrodermal (skin conductance) responses. Multilevel modeling of repeated measures with 5 data points per second was used to examine fetal and maternal responses. Results As expected, compared to a sham condition, the stimulus generated a fetal motor response at both gestational ages, consistent with a mild fetal startle. Fetal stimulation was associated with significant, transient slowing of maternal heart rate coupled with increased skin conductance within 10 s of the stimulus at both gestational ages. Nulliparous women showed greater electrodermal responsiveness. The magnitude of the fetal motor response significantly corresponded to the maternal skin conductance response at 5, 10, 15, and 30 s following stimulation. Conclusion Elicited fetal movement exerts an independent influence on the maternal autonomic nervous system. This finding contributes to current models of the dyadic relationship during pregnancy between fetus and pregnant woman. PMID:24119937

Global named patient use program of afatinib in advanced non-small-cell lung carcinoma patients who progressed following prior therapies.

PubMed

Cappuzzo, Federico; Soo, Ross; Hochmair, Maximilian; Schuler, Martin; Lam, Kwok Chi; Stehle, Gerd; Cseh, Agnieszka; Lorence, Robert M; Linden, Stephan; Forman, Nicole D; Hilbe, Wolfgang; Jazieh, Abdul Rahman; Tsai, Chun-Ming

2018-01-29

A global afatinib named patient use program in non-small-cell lung carcinoma (NSCLC) commenced in 2010. Eligible NSCLC patients had progressed after clinical benefit on prior erlotinib/gefitinib and/or had activating EGFR/HER2 mutations, exhausted all other treatments, and were ineligible for afatinib trials. Data, as of January 2016, were reported on 3966 heavily pretreated NSCLC patients (41 countries; 6 continents). Among 2595/3966 (65.4%) patients with tumor EGFR status, 2407 (92.8%) were EGFR mutation positive. Median time to treatment failure (2862/3966 [72.2%] patients with available data) was 4.4 months. Among 1141/2862 (39.9%) patients with response reported, objective response rate was 23.4% (267/1141). Safety findings were as expected. Time to treatment failure durations and objective response rates were encouraging.

Efficacy of chemotherapy after first-line gefitinib therapy in EGFR mutation-positive advanced non-small cell lung cancer-data from a randomized Phase III study comparing gefitinib with carboplatin plus paclitaxel (NEJ002).

PubMed

Miyauchi, Eisaku; Inoue, Akira; Kobayashi, Kunihiko; Maemondo, Makoto; Sugawara, Shunichi; Oizumi, Satoshi; Isobe, Hiroshi; Gemma, Akihiko; Saijo, Yasuo; Yoshizawa, Hirohisa; Hagiwara, Koichi; Nukiwa, Toshihiro

2015-07-01

Epidermal growth factor receptor tyrosine kinase inhibitors are effective as first-line therapy for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations. However, it is unknown whether second-line platinum-based chemotherapy after epidermal growth factor receptor tyrosine kinase inhibitor therapy could lead to better outcomes. We evaluated the efficacy of second-line platinum-based chemotherapy after gefitinib for advanced non-small cell lung cancers harboring epidermal growth factor receptor mutations (the NEJ002 study). Seventy-one non-small cell lung cancers, treated with gefitinib as first-line therapy and then receiving platinum-based chemotherapy as second-line therapy were evaluated in NEJ002. Patients were evaluated for antitumor response to second-line chemotherapy by computed tomography according to the criteria of the Response Evaluation Criteria in Solid Tumors group (version 1.0). Of the 71 patients receiving platinum-based chemotherapy after first-line gefitinib, a partial response was documented in 25.4% (18/71), stable disease in 43.7% (31/71) and progression of disease in 21.1% (15/71). The objective response and disease control rates were 25.4% (18/71) and 69% (49/71), respectively. There was no significant difference between first- and second-line chemotherapy in objective response and disease control rates for advanced non-small cell lung cancer harboring activating epidermal growth factor receptor mutations. In the analysis of epidermal growth factor receptor mutation types, the objective responses of deletions in exon 19 and a point mutation in exon 21 (L858R) were 27.3% (9/33) and 28.1% (9/32), respectively, but these differences between objective response rates were not significant. The efficacy of second-line platinum-based chemotherapy followed at progression by gefitinib was similar to first-line platinum-based chemotherapy, and epidermal growth factor receptor mutation types did not influence the efficacy of second-line platinum-based chemotherapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Preceptors’ Self-Assessment of Their Ability to Perform the Learning Objectives of an Experiential Program

PubMed Central

2012-01-01

Objective. To evaluate preceptors’ perception of their ability to perform the Structured Practical Experiences in Pharmacy (SPEP) learning objectives through a self-assessment activity. Methods. A self-assessment instrument consisting of 28 learning objectives associated with clinic, community, and hospital pharmacy practice experiences were developed. Preceptors rated their performance ability for each of the learning objectives using a 3-point Likert scale. Results. Of the 116 preceptors, 89 (77%) completed the self-assessment survey instrument. The overall preceptor responses to the items on performance of the 28 SPEP learning objectives ranged from good to excellent. Years of experience, practice experience setting, and involvement as a SPEP or SPEP and PharmD preceptor had no influence on their self-reported capabilities. Conclusion. Most preceptors rated their ability to perform the learning objectives for the structured practical experiences in pharmacy as high. Competency areas requiring further preceptor development were identified. PMID:23193333

Oral Appliance Treatment Response and Polysomnographic Phenotypes of Obstructive Sleep Apnea

PubMed Central

Sutherland, Kate; Takaya, Hisashi; Qian, Jin; Petocz, Peter; Ng, Andrew T.; Cistulli, Peter A.

2015-01-01

Study Objectives: Mandibular advancement splints (MAS) are an effective treatment for obstructive sleep apnea (OSA); however, therapeutic response is variable. Younger age, female gender, less obesity, and milder and supine-dependent OSA have variably been associated with treatment success in relatively small samples. Our objective was to utilize a large cohort of MAS treated patients (1) to compare efficacy across patients with different phenotypes of OSA and (2) to assess demographic, anthropometric, and polysomnography variables as treatment response predictors. Methods: Retrospective analysis of MAS-treated patients participating in clinical trials in sleep centers in Sydney, Australia between years 2000–2013. All studies used equivalent customized two-piece MAS devices and treatment protocols. Treatment response was defined as (1) apnea-hypopnea index (AHI) < 5/h, (2) AHI < 10/h and ≥ 50% reduction, and (3) ≥ 50% AHI reduction. Results: A total of 425 patients (109 female) were included (age 51.2 ± 10.9 years, BMI 29.2 ± 5.0 kg/m2). MAS reduced AHI by 50.3% ± 50.7% across the group. Supine-predominant OSA patients had lower treatment response rates than non-positional OSA (e.g., 36% vs. 59% for AHI < 10/h). REM-predominant OSA showed a lower response rate than either NREM or non-stage dependent OSA. In prediction modelling, age, baseline AHI, and anthropometric variables were predictive of MAS treatment outcome but not OSA phenotype. Gender was not associated with treatment outcome. Conclusions: Lower MAS treatment response rates were observed in supine and REM sleep. In a large sample, we confirm that demographic, anthropometric, and polysomnographic data only weakly inform about MAS efficacy, supporting the need for alternative objective prediction methods to reliably select patients for MAS treatment. Citation: Sutherland K, Takaya H, Qian J, Petocz P, Ng AT, Cistulli PA. Oral appliance treatment response and polysomnographic phenotypes of obstructive sleep apnea. J Clin Sleep Med 2015;11(8):861–868. PMID:25845897

Probability assessment with response times and confidence in perception and knowledge.

PubMed

Petrusic, William M; Baranski, Joseph V

2009-02-01

In both a perceptual and a general knowledge comparison task, participants categorized the time they took to decide, selecting one of six categories ordered from "Slow" to Fast". Subsequently, they rated confidence on a six-category scale ranging from "50%" to "100%". Participants were able to accurately scale their response times thus enabling the treatment of the response time (RT) categories as potential confidence categories. Probability assessment analyses of RTs revealed indices of over/underconfidence, calibration, and resolution, each subject to the "hard-easy" effect, comparable to those obtained with the actual confidence ratings. However, in both the perceptual and knowledge domains, resolution (i.e., the ability to use the confidence categories to distinguish correct from incorrect decisions) was significantly better with confidence ratings than with RT categorization. Generally, comparable results were obtained with scaling of the objective RTs, although subjective categorization of RTs provided probability assessment indices superior to those obtained from objective RTs. Taken together, the findings do not support the view that confidence arises from a scaling of decision time.

Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial.

PubMed

Cefalo, Graziella; Massimino, Maura; Ruggiero, Antonio; Barone, Giuseppe; Ridola, Vita; Spreafico, Filippo; Potepan, Paolo; Abate, Massimo E; Mascarin, Maurizio; Garrè, Maria Luisa; Perilongo, Giorgio; Madon, Enrico; Colosimo, Cesare; Riccardi, Riccardo

2014-05-01

The aim of this study was to assess the objective response rate (ORR) of children and young adults with recurrent medulloblastoma/primitive neuroectodermal tumor (MB/PNET) treated with temozolomide (TMZ). The secondary purpose was to analyze the toxicity profile of TMZ when administered orally for 5 days in 3 divided daily doses every 28 days. Forty-two patients with recurrent MB/PNET, aged 21 years and younger, were recruited. Patients were treated with oral TMZ. Starting doses ranged from 120 to 200 mg/m(2)/day based on previous treatments. A craniospinal MRI was performed prior to the first cycle of TMZ and following every 2 cycles of treatment. Median age was 10 years (range, 2-21 years). Forty of 42 patients were assessed for response and toxicity. The objective response rate was 42.5%: 6 patients achieved a complete response, 11 had a partial response, and 10 had stable disease. Progression-free survival rates for all patients at 6 and 12 months were 30% and 7.5%, respectively. Their median overall survival rates at 6 and 12 months were 42.5% and 17.5%, respectively. No major extrahematological effects or life-threatening events were reported. The most common grade 3/4 toxicity included thrombocytopenia (17.5%), neutropenia (7.5%), and anemia (2.5%). TMZ proved to be an effective agent in children and young adults with MB/PNET, heavily pre-treated, with a tolerable toxicity profile.

Visual Attention and Math Performance in Survivors of Childhood Acute Lymphoblastic Leukemia.

PubMed

Richard, Annette E; Hodges, Elise K; Heinrich, Kimberley P

2018-01-24

Attentional and academic difficulties, particularly in math, are common in survivors of childhood acute lymphoblastic leukemia (ALL). Of cognitive deficits experienced by survivors of childhood ALL, attention deficits may be particularly responsive to intervention. However, it is unknown whether deficits in particular aspects of attention are associated with deficits in math skills. The current study investigated relationships between math calculation skills, performance on an objective measure of sustained attention, and parent- and teacher-reported attention difficulties. Twenty-four survivors of childhood ALL (Mage = 13.5 years, SD= 2.8 years) completed a computerized measure of sustained attention and response control and a written measure of math calculation skills in the context of a comprehensive clinical neuropsychological evaluation. Parent and teacher ratings of inattention and impulsivity were obtained. Visual response control and visual attention accounted for 26.4% of the variance observed among math performance scores after controlling for IQ (p < .05). Teacher-rated, but not parent-rated, inattention was significantly negatively correlated with math calculation scores. Consistency of responses to visual stimuli on a computerized measure of attention is a unique predictor of variance in math performance among survivors of childhood ALL. Objective testing of visual response control, rather than parent-rated attentional problems, may have clinical utility in identifying ALL survivors at risk for math difficulties. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

General autonomic components of motion sickness

NASA Technical Reports Server (NTRS)

Cowings, Patricia S.; Suter, Steve; Toscano, William B.; Kamiya, Joe; Naifeh, Karen

1986-01-01

This report refers to a body of investigations directed toward the examination of autonomic nervous system responses to motion sickness. Heart rate, respiration rate, finger pulse volume, and basal skin resistance were measured on 127 men and women before, during, and after exposure to a nauseogenic rotating chair test. Significant changes in all autonomic responses were observed across the tests (p less than .05). Significant differences in autonomic responses among groups divided according to motion sickness susceptibility were also observed (p less than .05). Results suggest that the examination of autonomic responses as an objective indicator of motion sickness malaise is warranted and may contribute to the overall understanding of the syndrome.

High Strain-Rate and Temperature Effects on the Response of Composites

NASA Technical Reports Server (NTRS)

Gilat, Amos

2004-01-01

The objective of the research is to expand the experimental study of the effect of strain rate on mechanical response (deformation and failure) of epoxy resins and carbon fibers/epoxy matrix composites, to include elevated temperature tests. The experimental data provide the information needed for NASA scientists for the development of a nonlinear, strain rate and temperature dependent deformation and strength models for composites that can subsequently be used in design. This year effort was directed into the development and testing of the epoxy resin at elevated temperatures. Two types of epoxy resins were tested in shear at high strain rates of about 700 per second and elevated temperatures of 50 and 80 C. The results show that the temperature significantly affects the response of epoxy.

Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.

PubMed

van der Heijde, Désirée; Deodhar, Atul; Wei, James C; Drescher, Edit; Fleishaker, Dona; Hendrikx, Thijs; Li, David; Menon, Sujatha; Kanik, Keith S

2017-08-01

To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001); tofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. NCT01786668. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Maize yield response to nitrogen as influenced by spatio-temporal variations of soil-water-topography dynamics

USDA-ARS?s Scientific Manuscript database

Reducing N loss from agricultural lands and applying N fertilizer at rates that satisfy both economic and environmental objectives is critical for sustainable agricultural management. This study investigated spatial variability in maize yield response to N and its controlling factors along a typical...

Climate variability and nitrogen rate interactions affecting corn nitrogen use efficiency in Alabama

USDA-ARS?s Scientific Manuscript database

Nitrogen (N) fertilization is an important practice to increase yield; however, plant–soil interactions to in-season changes in climatic conditions result on site-specific responses of corn to nitrogen rates. The objective of this study was to evaluate the effect of different climatic conditions and...

Gemcitabine or gemcitabine plus oxaliplatin in the first-line treatment of patients with advanced transitional cell carcinoma of the urothelium unfit for cisplatin-based chemotherapy: a randomized phase 2 study of the French Genitourinary Tumor Group (GETUG V01).

PubMed

Culine, Stéphane; Fléchon, Aude; Guillot, Aline; Le Moulec, Sylvestre; Pouessel, Damien; Rolland, Frédéric; Ravaud, Alain; Houédé, Nadine; Mignot, Laurent; Joly, Florence; Oudard, Stéphane; Gourgou, Sophie

2011-12-01

The optimal chemotherapy for patients with advanced transitional cell carcinoma of the urothelium who are not eligible for cisplatin remains to be defined. To assess the activity of gemcitabine alone (GEM) or in combination with oxaliplatin (GEMOX) in a randomized phase 2 trial. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors criteria. The sample size was based on a two-stage Fleming design with p0=35% and p1=55%. At the end of the first stage designed to register 20 patients on each treatment arm, the observation of seven or more objective responses would have led to the inclusion of 30 more patients in each arm. From July 2004 to March 2009, 44 patients in 10 centers were randomly assigned into the GEM or the GEMOX arm, 22 on each treatment arm. The median age was 76 yr. Seven patients were included for a performance status (PS) of 2 only. The remaining 37 patients had an impaired renal function, 11 of whom also had a PS of 2. The median creatinine clearance was 45 ml/min (range: 30-80 ml/min). The trial was closed after the first part because the GEMOX arm did not reach the targeted objective response rate to proceed further. Oxaliplatin does not add any significant activity (in terms of response rates) compared with gemcitabine alone in patients with advanced transitional cell carcinoma of the urothelium who are ineligible for cisplatin. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Meta-analysis of ceftriaxone compared with penicillin for the treatment of syphilis.

PubMed

Liang, Zhen; Chen, Ya-Ping; Yang, Chun-Sheng; Guo, Wen; Jiang, Xiao-Xiao; Xu, Xi-Feng; Feng, Shou-Xin; Liu, Yan-Qun; Jiang, Guan

2016-01-01

Penicillin is the gold standard for treating syphilis. However, allergic reactions, poor drug tolerance and limited efficacy in patients remain a challenging problem. The objective of this meta-analysis was to compare the efficacy of ceftriaxone and penicillin based on data obtained from published randomised controlled trials (RCTs). The Cochrane Library, Medline, EBSCO, EMBASE and Ovid databases were searched for RCTs of ceftriaxone vs. penicillin for the treatment of syphilis. Estimated risk ratios (RRs) and 95% confidence intervals (CIs) were used to investigate the following outcome measures: 3-month response rate; 6-month response rate; 12-month response rate; relapse rate; serofast rate; and failure rate. Seven RCTs involving 281 participants (159 patients who received ceftriaxone and 122 patients who received penicillin) were included in the meta-analysis. There were no significant differences in 3-month response rate (RR=1.12, 95% CI 0.89-1.42), 6-month response rate (RR=1.02, 95% CI 0.75-1.38), 12-month response rate (RR=1.04, 95% CI 0.82-1.32), relapse rate (RR=0.91, 95% CI 0.45-1.84), serofast rate (RR=0.69, 95% CI 0.22-2.12) or failure rate (RR=0.66, 95% CI 0.03-15.76) in patients treated with ceftriaxone compared with those treated with penicillin. In conclusion, there is no evidence in the literature that ceftriaxone is less efficient than penicillin. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Application of dragonfly algorithm for optimal performance analysis of process parameters in turn-mill operations- A case study

NASA Astrophysics Data System (ADS)

Vikram, K. Arun; Ratnam, Ch; Lakshmi, VVK; Kumar, A. Sunny; Ramakanth, RT

2018-02-01

Meta-heuristic multi-response optimization methods are widely in use to solve multi-objective problems to obtain Pareto optimal solutions during optimization. This work focuses on optimal multi-response evaluation of process parameters in generating responses like surface roughness (Ra), surface hardness (H) and tool vibration displacement amplitude (Vib) while performing operations like tangential and orthogonal turn-mill processes on A-axis Computer Numerical Control vertical milling center. Process parameters like tool speed, feed rate and depth of cut are considered as process parameters machined over brass material under dry condition with high speed steel end milling cutters using Taguchi design of experiments (DOE). Meta-heuristic like Dragonfly algorithm is used to optimize the multi-objectives like ‘Ra’, ‘H’ and ‘Vib’ to identify the optimal multi-response process parameters combination. Later, the results thus obtained from multi-objective dragonfly algorithm (MODA) are compared with another multi-response optimization technique Viz. Grey relational analysis (GRA).

TAKING THE PULSE OF PROLONGED EXPOSURE THERAPY: PHYSIOLOGICAL REACTIVITY TO TRAUMA IMAGERY AS AN OBJECTIVE MEASURE OF TREATMENT RESPONSE.

PubMed

Wangelin, Bethany C; Tuerk, Peter W

2015-12-01

Physiological reactivity to trauma-related cues is a primary symptom of PTSD and can be assessed objectively using script-driven imagery paradigms. However, subjective self-reported symptom measures are the most common outcome indices utilized in PTSD treatment trials and clinic settings. We examined physiological reactivity during a short trauma imagery task as an objective index of response to PTSD treatment, optimized for use in routine clinical care settings. Participants were 35 male combat veterans receiving prolonged exposure (PE) therapy in a Veterans Affairs outpatient clinic. In addition to traditional subjective self-reported and clinician-rated symptom measures, patients also completed a script-driven imagery task in which heart rate (HR) and skin conductance (SC) were recorded at three assessment points across treatment. We examined changes in subjective symptom measures and objective trauma-specific physiological reactivity over the course of PE, and investigated the association between pretreatment physiological reactivity and treatment response. Patients who completed PE showed significantly diminished HR and SC reactivity to trauma imagery across therapy. Additionally, individuals showing greater trauma-specific HR reactivity at pretreatment showed greater reductions in subjectively reported PTSD symptoms at posttreatment. Findings support the utility of physiological reactivity during trauma imagery as an objective outcome measure that has the potential to be incorporated into evidence-based PTSD treatment in routine clinical settings, or prospective studies related to the individualization of care at pretreatment. © 2015 Wiley Periodicals, Inc.

A modern approach to superradiance

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

Endlich, Solomon; Penco, Riccardo

In this paper, we provide a simple and modern discussion of rotational super-radiance based on quantum field theory. We work with an effective theory valid at scales much larger than the size of the spinning object responsible for superradiance. Within this framework, the probability of absorption by an object at rest completely determines the superradiant amplification rate when that same object is spinning. We first discuss in detail superradiant scattering of spin 0 particles with orbital angular momentum ℓ = 1, and then extend our analysis to higher values of orbital angular momentum and spin. Along the way, we providemore » a simple derivation of vacuum friction — a ''quantum torque'' acting on spinning objects in empty space. Our results apply not only to black holes but to arbitrary spinning objects. We also discuss superradiant instability due to formation of bound states and, as an illustration, we calculate the instability rate Γ for bound states with massive spin 1 particles. For a black hole with mass M and angular velocity Ω, we find Γ ~ (GMμ) 7Ω when the particle’s Compton wavelength 1/μ is much greater than the size GM of the spinning object. This rate is parametrically much larger than the instability rate for spin 0 particles, which scales like (GM μ) 9Ω. This enhanced instability rate can be used to constrain the existence of ultralight particles beyond the Standard Model.« less

A modern approach to superradiance

DOE PAGES

Endlich, Solomon; Penco, Riccardo

2017-05-10

In this paper, we provide a simple and modern discussion of rotational super-radiance based on quantum field theory. We work with an effective theory valid at scales much larger than the size of the spinning object responsible for superradiance. Within this framework, the probability of absorption by an object at rest completely determines the superradiant amplification rate when that same object is spinning. We first discuss in detail superradiant scattering of spin 0 particles with orbital angular momentum ℓ = 1, and then extend our analysis to higher values of orbital angular momentum and spin. Along the way, we providemore » a simple derivation of vacuum friction — a ''quantum torque'' acting on spinning objects in empty space. Our results apply not only to black holes but to arbitrary spinning objects. We also discuss superradiant instability due to formation of bound states and, as an illustration, we calculate the instability rate Γ for bound states with massive spin 1 particles. For a black hole with mass M and angular velocity Ω, we find Γ ~ (GMμ) 7Ω when the particle’s Compton wavelength 1/μ is much greater than the size GM of the spinning object. This rate is parametrically much larger than the instability rate for spin 0 particles, which scales like (GM μ) 9Ω. This enhanced instability rate can be used to constrain the existence of ultralight particles beyond the Standard Model.« less

Is it really "all in their heads"? How self-esteem predicts partner responsiveness.

PubMed

Cortes, Kassandra; Wood, Joanne V

2018-01-05

Having a responsive partner is important for the well-being of relationships. Unfortunately, people with low self-esteem (LSEs) perceive their partners to be less responsive than do people with high self-esteem (HSEs). Although the common assumption has been that LSEs' negative partner perceptions are "all in their heads"-a reflection of their negative self-projection-we argue that LSEs' views of lower partner responsiveness are, in fact, warranted. Across two studies (N Study1  = 122 couples, M age  = 22.28, 50% female; N Study2  = 73 couples, M age  = 19.96, 51% female), we examined LSEs' and HSEs' perceptions of their partners' responsiveness to their negative self-disclosures, comparing them with partners' reports (Study 1) and ratings from objective coders following a negative experience created in the lab (Study 2). Consistent with our hypothesis, partners of LSEs were less responsive than partners of HSEs to disclosers' negative self-disclosures, as rated by disclosers, listeners, and objective observers. Study 3 (N = 99, M age  = 33.19, 54% female) explored possible mechanisms behind these self-esteem differences. The finding that partners of LSEs (vs. HSEs) are less responsive may contribute to LSEs' poorer relationships. © 2018 Wiley Periodicals, Inc.

Sublethal effects of cadmium on physiological responses in the pocketbook mussel, Lampsilis ventricosa

USGS Publications Warehouse

Naimo, T.J.; Atchison, G.J.; Holland Bartels, L. E.

1992-01-01

Several physiological responses have been used to evaluate the effects of contaminants on marine bivalves. Respiration rate, food clearance rate, ammonia excretion rate, and food assimilation efficiency can be quantified and incorporated into a bioenergetics model known as scope for growth. This model estimates an organism's instantaneous energy budget and quantifies the available energy for growth and reproduction. We applied some of these physiological techniques to freshwater mussels to determine the sublethal effects of cadmium. The objective of our study was to quantify the physiological responses of adult pocketbook mussels, Lampsilis ventricosa , exposed to sublethal concentrations of cadmium. We selected L. ventricosa for study because it is abundant in the upper Mississippi River and its life history has been partially documented.

Impact of CYP2D6 polymorphisms on clinical efficacy & tolerability of metoprolol tartrate

PubMed Central

Hamadeh, Issam S.; Langaee, Taimour Y.; Dwivedi, Ruti; Garcia, Sofia; Burkley, Ben M.; Chapman, Arlene B.; Gums, John G.; Turner, Stephen T.; Gong, Yan; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.

2014-01-01

Metoprolol is a selective β-1 adrenergic receptor blocker that undergoes extensive metabolism by the polymorphic enzyme, CYP2D6. Our objective was to investigate the influence of CYP2D6 polymorphisms on efficacy and tolerability of metoprolol tartrate. 281 study participants with uncomplicated hypertension received 50 mg of metoprolol twice daily followed by response guided titration to 100 mg twice daily. Phenotypes were assigned based on results of CYP2D6 genotyping and copy number variation assays. Clinical response to metoprolol and adverse effect rates were analyzed in relation to CYP2D6 phenotypes by using appropriate statistical tests. Heart rate response differed significantly by CYP2D6 phenotype (p-value <0.0001) with poor metabolizers & intermediate metabolizers showing greater HR reduction. However, blood pressure response and adverse effect rates were not significantly different by CYP2D6 phenotype. Other than a significant difference in heart rate response, CYP2D6 polymorphisms were not a determinant of the variability in response or tolerability to metoprolol. PMID:24637943

Maize (Zea mays L.) yield response to nitrogen as influenced by spatio-temporal variations of soil-water-topography dynamics

USDA-ARS?s Scientific Manuscript database

Reducing nitrogen (N) loss from agricultural lands and applying N fertilizer at rates that satisfy both economic and environmental objectives is critical for sustainable agricultural management. This study investigated spatial variability in maize yield response to N and its controlling factors alon...

Physiological responses induced by emotion-eliciting films.

PubMed

Fernández, Cristina; Pascual, Juan C; Soler, Joaquim; Elices, Matilde; Portella, Maria J; Fernández-Abascal, Enrique

2012-06-01

Emotion-eliciting films are commonly used to evoke subjective emotional responses in experimental settings. The main aim of the present study was to investigate whether a set of film clips with discrete emotions were capable to elicit measurable objective physiological responses. The convergence between subjective and objective measures was evaluated. Finally, the effect of gender on emotional responses was investigated. A sample of 123 subjects participated in the study. Individuals were asked to view a set of emotional film clips capable to induce seven emotions: anger, fear, sadness, disgust, amusement, tenderness and neutral state. Skin conductance level (SCL), heart rate (HR) and subjective emotional responses were measured for each film clip. In comparison with neutral films, SCL was significantly increased after viewing fear films, and HR was also significantly incremented for anger and fear films. Physiological variations were associated with arousal measures indicating a convergence between subjective and objective reactions. Women appeared to display significantly greater SCL and HR responses for films inducing sadness. The findings suggest that physiological activation would be more easily induced by emotion-eliciting films that tap into emotions with higher subjective arousal such as anger and fear.

Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial

PubMed Central

Cefalo, Graziella; Massimino, Maura; Ruggiero, Antonio; Barone, Giuseppe; Ridola, Vita; Spreafico, Filippo; Potepan, Paolo; Abate, Massimo E.; Mascarin, Maurizio; Garrè, Maria Luisa; Perilongo, Giorgio; Madon, Enrico; Colosimo, Cesare; Riccardi, Riccardo

2014-01-01

Background The aim of this study was to assess the objective response rate (ORR) of children and young adults with recurrent medulloblastoma/primitive neuroectodermal tumor (MB/PNET) treated with temozolomide (TMZ). The secondary purpose was to analyze the toxicity profile of TMZ when administered orally for 5 days in 3 divided daily doses every 28 days. Methods Forty-two patients with recurrent MB/PNET, aged 21 years and younger, were recruited. Patients were treated with oral TMZ. Starting doses ranged from 120 to 200 mg/m2/day based on previous treatments. A craniospinal MRI was performed prior to the first cycle of TMZ and following every 2 cycles of treatment. Results Median age was 10 years (range, 2–21 years). Forty of 42 patients were assessed for response and toxicity. The objective response rate was 42.5%: 6 patients achieved a complete response, 11 had a partial response, and 10 had stable disease. Progression-free survival rates for all patients at 6 and 12 months were 30% and 7.5%, respectively. Their median overall survival rates at 6 and 12 months were 42.5% and 17.5%, respectively. No major extrahematological effects or life-threatening events were reported. The most common grade 3/4 toxicity included thrombocytopenia (17.5%), neutropenia (7.5%), and anemia (2.5%). Conclusions TMZ proved to be an effective agent in children and young adults with MB/PNET, heavily pre-treated, with a tolerable toxicity profile. PMID:24482446

Boar sperm quality in lines of pigs selected for either ovulation rate or uterine capacity

USDA-ARS?s Scientific Manuscript database

Selection for 11 generations in swine for ovulation rate (OR) or uterine capacity (UC) resulted in significant changes in component traits of litter size. Our objective was to conserve the unique germplasm for the future and to characterize sperm quality as a correlated response to the selection cr...

Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial.

PubMed

Rosenberg, Jonathan E; Hoffman-Censits, Jean; Powles, Tom; van der Heijden, Michiel S; Balar, Arjun V; Necchi, Andrea; Dawson, Nancy; O'Donnell, Peter H; Balmanoukian, Ani; Loriot, Yohann; Srinivas, Sandy; Retz, Margitta M; Grivas, Petros; Joseph, Richard W; Galsky, Matthew D; Fleming, Mark T; Petrylak, Daniel P; Perez-Gracia, Jose Luis; Burris, Howard A; Castellano, Daniel; Canil, Christina; Bellmunt, Joaquim; Bajorin, Dean; Nickles, Dorothee; Bourgon, Richard; Frampton, Garrett M; Cui, Na; Mariathasan, Sanjeev; Abidoye, Oyewale; Fine, Gregg D; Dreicer, Robert

2016-05-07

Patients with metastatic urothelial carcinoma have few treatment options after failure of platinum-based chemotherapy. In this trial, we assessed treatment with atezolizumab, an engineered humanised immunoglobulin G1 monoclonal antibody that binds selectively to programmed death ligand 1 (PD-L1), in this patient population. For this multicentre, single-arm, two-cohort, phase 2 trial, patients (aged ≥18 years) with inoperable locally advanced or metastatic urothelial carcinoma whose disease had progressed after previous platinum-based chemotherapy were enrolled from 70 major academic medical centres and community oncology practices in Europe and North America. Key inclusion criteria for enrolment were Eastern Cooperative Oncology Group performance status of 0 or 1, measurable disease defined by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), adequate haematological and end-organ function, and no autoimmune disease or active infections. Formalin-fixed paraffin-embedded tumour specimens with sufficient viable tumour content were needed from all patients before enrolment. Patients received treatment with intravenous atezolizumab (1200 mg, given every 3 weeks). PD-L1 expression on tumour-infiltrating immune cells (ICs) was assessed prospectively by immunohistochemistry. The co-primary endpoints were the independent review facility-assessed objective response rate according to RECIST v1.1 and the investigator-assessed objective response rate according to immune-modified RECIST, analysed by intention to treat. A hierarchical testing procedure was used to assess whether the objective response rate was significantly higher than the historical control rate of 10% at an α level of 0·05. This study is registered with ClinicalTrials.gov, number NCT02108652. Between May 13, 2014, and Nov 19, 2014, 486 patients were screened and 315 patients were enrolled into the study. Of these patients, 310 received atezolizumab treatment (five enrolled patients later did not meet eligibility criteria and were not dosed with study drug). The PD-L1 expression status on infiltrating immune cells (ICs) in the tumour microenvironment was defined by the percentage of PD-L1-positive immune cells: IC0 (<1%), IC1 (≥1% but <5%), and IC2/3 (≥5%). The primary analysis (data cutoff May 5, 2015) showed that compared with a historical control overall response rate of 10%, treatment with atezolizumab resulted in a significantly improved RECIST v1.1 objective response rate for each prespecified immune cell group (IC2/3: 27% [95% CI 19-37], p<0·0001; IC1/2/3: 18% [13-24], p=0·0004) and in all patients (15% [11-20], p=0·0058). With longer follow-up (data cutoff Sept 14, 2015), by independent review, objective response rates were 26% (95% CI 18-36) in the IC2/3 group, 18% (13-24) in the IC1/2/3 group, and 15% (11-19) overall in all 310 patients. With a median follow-up of 11·7 months (95% CI 11·4-12·2), ongoing responses were recorded in 38 (84%) of 45 responders. Exploratory analyses showed The Cancer Genome Atlas (TCGA) subtypes and mutation load to be independently predictive for response to atezolizumab. Grade 3-4 treatment-related adverse events, of which fatigue was the most common (five patients [2%]), occurred in 50 (16%) of 310 treated patients. Grade 3-4 immune-mediated adverse events occurred in 15 (5%) of 310 treated patients, with pneumonitis, increased aspartate aminotransferase, increased alanine aminotransferase, rash, and dyspnoea being the most common. No treatment-related deaths occurred during the study. Atezolizumab showed durable activity and good tolerability in this patient population. Increased levels of PD-L1 expression on immune cells were associated with increased response. This report is the first to show the association of TCGA subtypes with response to immune checkpoint inhibition and to show the importance of mutation load as a biomarker of response to this class of agents in advanced urothelial carcinoma. F Hoffmann-La Roche Ltd. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tactile discrimination and representations of texture, shape, and softness

NASA Technical Reports Server (NTRS)

Srinivasan, M. A.; Lamotte, R. H.

1991-01-01

We present here some of the salient results on the tactual discriminabilities of human subjects obtained through psychophysical experiments, and the associated peripheral neural codes obtained through electrophysiological recordings from monkey single nerve fibers. Humans can detect the presence of a 2 micron high single dot on a smooth glass plate stroked on the skin, based on the responses of Meissner type rapidly adapting fibers (RAs). They can also detect a 0.06 micron high grating on the plate, owing to the response of Pacinian corpuscle fibers. Among all the possible representations of the shapes of objects, the surface curvature distribution seems to be the most relevant for tactile sensing. Slowly adapting fibers respond to both the change and rate of change of curvature of the skin surface at the most sensitive spot in their receptive fields, whereas RAs respond only to the rate of change of curvature. Human discriminability of compliance of objects depends on whether the object has a deformable or rigid surface. When the surface is deformable, the spatial pressure distribution within the contact region is dependent on object compliance, and hence information from cutaneous mechanoreceptors is sufficient for discrimination of subtle differences in compliance. When the surface is rigid, kinesthetic information is necessary for discrimination, and the discriminability is much poorer than that for objects with deformable surfaces.

Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies

PubMed Central

2014-01-01

Background Brentuximab vedotin is a CD30-directed antibody-drug conjugate. Retreatment with brentuximab vedotin monotherapy was investigated in patients with CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (ALCL) who relapsed after achieving complete or partial remission (CR or PR) with initial brentuximab vedotin therapy in a previous study (ClinicalTrials.gov NCT00947856). Methods Twenty-one patients with HL and 8 patients with systemic ALCL were retreated; 3 patients with systemic ALCL were retreated twice. Patients generally received brentuximab vedotin 1.8 mg/kg intravenously approximately every 3 weeks over 30 minutes as an outpatient infusion. The primary objectives of this study were to assess safety and to estimate antitumor activity of brentuximab vedotin retreatment. Results The objective response rate was 60% (30% CR) in HL patients and 88% (63% CR) in systemic ALCL patients. The estimated median duration of response for patients with an objective response was 9.5 months (range, 0.0+ to 28.0+ months) at the time of study closure. Of the 19 patients with objective response, 7 patients had not had an event of disease progression or death at the time of study closure; duration of response for these patients ranged from 3.5 to 28 months. Of the 11 patients with CR, 45% had response durations of over 1 year. Adverse events (AEs) occurring in ≥25% of patients during the retreatment period were generally similar in type and frequency to those observed in the pivotal trials of brentuximab vedotin monotherapy, with the exception of peripheral neuropathy, which is known to have a cumulative effect. Grade 3 or higher events were observed in 48% of patients; these were generally transient and managed by dose modifications or delays. Deaths due to AEs occurred in 3 HL patients; none were considered to be related to brentuximab vedotin retreatment. Discussion With the exception of a higher rate of peripheral motor neuropathy, retreatment with brentuximab vedotin was associated with similar side effects seen in the pivotal trials. Conclusions Retreatment with brentuximab vedotin monotherapy is associated with response rates in 68% (39% CR) of patients with relapsed HL and systemic ALCL. Trial registration United States registry and results database ClinicalTrials.gov NCT00947856. PMID:24642247

Do psychiatric patients know what is good for them?

PubMed Central

Babiker, I E; Thorne, P

1993-01-01

The paper reports the findings of a medical audit exercise which monitored 192 consecutive psychiatric admissions. Approximately two-thirds of patients, consultants and referrers provided information on admission objectives and the degree to which they were attained. One-third of the patients furnished information on social problems and satisfaction with treatment. Sanctuary was rated as an important admission objective by patients but neglected by consultants and referrers. Patient satisfaction with treatment was significantly correlated with attainment of patient as well as consultant objectives, and negatively correlated with social problems. Agreement between consultant and patient on admission objectives was inversely related to both duration of contact with psychiatric services and number of previous admissions suggesting that congruence with consultants may be lost over time. The limitations imposed by variable response rates are acknowledged. It is concluded that serious note should be taken of psychiatric patients' own treatment objectives. PMID:8423572

Role of a looming-sensitive neuron in triggering the defense behavior of the praying mantis Tenodera aridifolia.

PubMed

Sato, Keiichiro; Yamawaki, Yoshifumi

2014-08-01

In responses to looming objects, the praying mantis shows a defense behavior, which consists of retracting forelegs under the prothorax. The role of a looming-sensitive neuron in triggering this behavior was investigated by simultaneously recording the activity and behavioral responses of the neuron. The mantis initiated the defense behavior earlier in response to larger and slower looming stimuli. The time remaining to collision at defense initiation was linearly correlated with the ratio of the half-size of an approaching object to its speed (l/|v|), suggesting that the defense behavior occurred a fixed delay after the stimuli had reached a fixed angular threshold. Furthermore, the results suggested that high-frequency spikes of the looming-sensitive neuron were involved in triggering the defense behavior: the distribution of maximum firing rate for trials with defense was shifted to larger rates compared with trials without defense; the firing rate of the neuron exceeded 150 Hz ∼100 ms before the defense initiation regardless of stimulus parameters; when a looming stimulus ceased approach prematurely, high-frequency spikes were removed, and the occurrence of defense was reduced. Copyright © 2014 the American Physiological Society.

Material properties of rat middle cerebral arteries at high strain rates.

PubMed

Bell, E David; Converse, Matthew; Mao, Haojie; Unnikrishnan, Ginu; Reifman, Jaques; Monson, Kenneth L

2018-03-19

Traumatic brain injury (TBI), resulting from either impact- or non-impact blast-related mechanisms, is a devastating cause of death and disability. The cerebral blood vessels, which provide critical support for brain tissue in both health and disease, are commonly injured in TBI. However, little is known about how vessels respond to traumatic loading, particularly at rates relevant to blast. To better understand vessel responses to trauma, the objective of this project was to characterize the high-rate response of passive cerebral arteries. Rat middle cerebral arteries were isolated and subjected to high-rate deformation in the axial direction. Vessels were perfused at physiological pressures and stretched to failure at strain rates ranging from approximately 100 to 1300 s-1. Although both in vivo stiffness and failure stress increased significantly with strain rate, failure stretch did not depend on rate.

Atezolizumab as first-line therapy in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial

PubMed Central

Balar, Arjun V; Galsky, Matthew D; Rosenberg, Jonathan E; Powles, Thomas; Petrylak, Daniel P; Bellmunt, Joaquim; Loriot, Yohann; Necchi, Andrea; Hoffman-Censits, Jean; Perez-Gracia, Jose Luis; Dawson, Nancy A; van der Heijden, Michiel S; Dreicer, Robert; Srinivas, Sandy; Retz, Margitta M; Joseph, Richard W; Drakaki, Alexandra; Vaishampayan, Ulka N; Sridhar, Srikala S; Quinn, David I; Durán, Ignacio; Shaffer, David R; Eigl, Bernhard J; Grivas, Petros D; Yu, Evan Y; Li, Shi; Kadel, Edward E; Boyd, Zachary; Bourgon, Richard; Hegde, Priti S; Mariathasan, Sanjeev; Thåström, AnnChristine; Abidoye, Oyewale O; Fine, Gregg D; Bajorin, Dean F

2017-01-01

Summary Background First-line chemotherapy for patients with cisplatin-ineligible locally-advanced or metastatic urothelial carcinoma (mUC) is associated with short response duration, poor survival, and high toxicity. This multicenter, 2-cohort phase 2 study evaluated atezolizumab (anti–programmed death-ligand 1 [PD-L1]) as treatment for mUC in this setting, as well as in later lines. Methods In a cohort of previously untreated patients who were cisplatin ineligible, atezolizumab was given 1200 mg every 3 weeks until progression. The primary endpoint was independently confirmed objective response rate per Response Evaluation Criteria In Solid Tumors v1.1 (central review), evaluated in pre-specified subgroups based on PD-L1 expression and in all patients. Secondary endpoints included response duration, progression-free survival, overall survival, and safety. Exploratory analyses included biomarker correlates of response and survival. This study is registered with ClinicalTrials.gov, number NCT02108652. Findings Of 119 patients who received atezolizumab in the first-line setting, 83 (70%) had baseline renal impairment, and 24 (20%) had Eastern Cooperative Oncology Group performance status 2. At 17·2 months’ median follow-up, the objective response rate was 23% (95% CI 16–31), the complete response rate was 9%, and 19 of 27 responses were ongoing. Median response duration was not reached. Responses occurred across all PD-L1 and poor prognostic factor subgroups. Median progression-free survival was 2·7 months. Median overall survival was 15·9 months. Tumour mutation load was associated with response. Treatment-related adverse events ≥10% were fatigue, diarrhoea, and pruritus. One treatment-related death (sepsis) occurred. Nine patients (8%) had an adverse event leading to treatment discontinuation. Immune-mediated events occurred in 14 (12%) patients. Interpretation Atezolizumab demonstrated encouraging durable response rates, survival, and tolerability, supporting its therapeutic use in untreated mUC. Funding F. Hoffmann-La Roche Ltd./Genentech, Inc., a member of the Roche Group. PMID:27939400

Objective benefits, participant perceptions and retention rates of a New Zealand community-based, older-adult exercise programme.

PubMed

Keogh, Justin W; Rice, John; Taylor, Denise; Kilding, Andrew

2014-06-01

Most exercise studies for older adults have been university- or hospital-based. Little is known about the benefits and factors influencing long-term participation in community-based exercise programmes, especially in New Zealand. To quantify the objective benefits, participant perceptions and retention rates of a New Zealand community-based exercise programme for adults (60 years or older). Study 1 involved assessing the benefits of 12 weeks' training on a convenience sample of 62 older adults commencing the never2old Active Ageing programme. Study 2 assessed the perceptions of 150 current participants on a variety of programme components that could act as barriers or facilitators to continued engagement. Study 3 assessed the retention rates of 264 participants in the programme over a two-year period. Significant improvements in many physical functional scores were observed in Study 1 (5-30 percentile points; p<0.05). Questionnaire responses from participants in Study 2 indicated many perceived benefits (positive responses from 67-95% on various questions) and that core components of the programme were rated very highly (64-99% on various components). Retention rates were high, with Study 3 finding 57% of participants still engaging in the programme at the end of the two-year period. A community-based exercise programme for older adults can improve many objective and subjective measures of physical fitness and functional performance and have good retention rates. General practitioners and other allied health professionals in New Zealand should consider promoting programmes, such as the never2old Active Ageing programme, to their older patients.

A new, objective, quantitative scale for measuring local skin responses following topical actinic keratosis therapy with ingenol mebutate.

PubMed

Rosen, Robert; Marmur, Ellen; Anderson, Lawrence; Welburn, Peter; Katsamas, Janelle

2014-12-01

Local skin responses (LSRs) are the most common adverse effects of topical actinic keratosis (AK) therapy. There is currently no method available that allows objective characterization of LSRs. Here, the authors describe a new scale developed to quantitatively and objectively assess the six most common LSRs resulting from topical AK therapy with ingenol mebutate. The LSR grading scale was developed using a 0-4 numerical rating, with clinical descriptors and representative photographic images for each rating. Good inter-observer grading concordance was demonstrated in peer review during development of the tool. Data on the use of the scale are described from four phase III double-blind studies of ingenol mebutate (n = 1,005). LSRs peaked on days 4 (face/scalp) or 8 (trunk/extremities), with mean maximum composite LSR scores of 9.1 and 6.8, respectively, and a rapid return toward baseline by day 15 in most cases. Mean composite LSR score at day 57 was generally lower than at baseline. The LSR grading scale is an objective tool allowing practicing dermatologists to characterize and compare LSRs to existing and, potentially, future AK therapies.

Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma.

PubMed

Yamamoto, Yoshiaki; Tsunedomi, Ryouichi; Fujita, Yusuke; Otori, Toru; Ohba, Mitsuyoshi; Kawai, Yoshihisa; Hirata, Hiroshi; Matsumoto, Hiroaki; Haginaka, Jun; Suzuki, Shigeo; Dahiya, Rajvir; Hamamoto, Yoshihiko; Matsuyama, Kenji; Hazama, Shoichi; Nagano, Hiroaki; Matsuyama, Hideyasu

2018-03-30

We investigated the relationship between axitinib pharmacogenetics and clinical efficacy/adverse events in advanced renal cell carcinoma (RCC) and established a model to predict clinical efficacy and adverse events using pharmacokinetic and gene polymorphisms related to drug metabolism and efflux in a phase II trial. We prospectively evaluated the area under the plasma concentration-time curve (AUC) of axitinib, objective response rate, and adverse events in 44 consecutive advanced RCC patients treated with axitinib. To establish a model for predicting clinical efficacy and adverse events, polymorphisms in genes including ABC transporters ( ABCB1 and ABCG2 ), UGT1A , and OR2B11 were analyzed by whole-exome sequencing, Sanger sequencing, and DNA microarray. To validate this prediction model, calculated AUC by 6 gene polymorphisms was compared with actual AUC in 16 additional consecutive patients prospectively. Actual AUC significantly correlated with the objective response rate ( P = 0.0002) and adverse events (hand-foot syndrome, P = 0.0055; and hypothyroidism, P = 0.0381). Calculated AUC significantly correlated with actual AUC ( P < 0.0001), and correctly predicted objective response rate ( P = 0.0044) as well as adverse events ( P = 0.0191 and 0.0082, respectively). In the validation study, calculated AUC prior to axitinib treatment precisely predicted actual AUC after axitinib treatment ( P = 0.0066). Our pharmacogenetics-based AUC prediction model may determine the optimal initial dose of axitinib, and thus facilitate better treatment of patients with advanced RCC.

Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma

PubMed Central

Yamamoto, Yoshiaki; Tsunedomi, Ryouichi; Fujita, Yusuke; Otori, Toru; Ohba, Mitsuyoshi; Kawai, Yoshihisa; Hirata, Hiroshi; Matsumoto, Hiroaki; Haginaka, Jun; Suzuki, Shigeo; Dahiya, Rajvir; Hamamoto, Yoshihiko; Matsuyama, Kenji; Hazama, Shoichi; Nagano, Hiroaki; Matsuyama, Hideyasu

2018-01-01

We investigated the relationship between axitinib pharmacogenetics and clinical efficacy/adverse events in advanced renal cell carcinoma (RCC) and established a model to predict clinical efficacy and adverse events using pharmacokinetic and gene polymorphisms related to drug metabolism and efflux in a phase II trial. We prospectively evaluated the area under the plasma concentration–time curve (AUC) of axitinib, objective response rate, and adverse events in 44 consecutive advanced RCC patients treated with axitinib. To establish a model for predicting clinical efficacy and adverse events, polymorphisms in genes including ABC transporters (ABCB1 and ABCG2), UGT1A, and OR2B11 were analyzed by whole-exome sequencing, Sanger sequencing, and DNA microarray. To validate this prediction model, calculated AUC by 6 gene polymorphisms was compared with actual AUC in 16 additional consecutive patients prospectively. Actual AUC significantly correlated with the objective response rate (P = 0.0002) and adverse events (hand-foot syndrome, P = 0.0055; and hypothyroidism, P = 0.0381). Calculated AUC significantly correlated with actual AUC (P < 0.0001), and correctly predicted objective response rate (P = 0.0044) as well as adverse events (P = 0.0191 and 0.0082, respectively). In the validation study, calculated AUC prior to axitinib treatment precisely predicted actual AUC after axitinib treatment (P = 0.0066). Our pharmacogenetics-based AUC prediction model may determine the optimal initial dose of axitinib, and thus facilitate better treatment of patients with advanced RCC. PMID:29682213

The Influence of Noise Reduction on Speech Intelligibility, Response Times to Speech, and Perceived Listening Effort in Normal-Hearing Listeners.

PubMed

van den Tillaart-Haverkate, Maj; de Ronde-Brons, Inge; Dreschler, Wouter A; Houben, Rolph

2017-01-01

Single-microphone noise reduction leads to subjective benefit, but not to objective improvements in speech intelligibility. We investigated whether response times (RTs) provide an objective measure of the benefit of noise reduction and whether the effect of noise reduction is reflected in rated listening effort. Twelve normal-hearing participants listened to digit triplets that were either unprocessed or processed with one of two noise-reduction algorithms: an ideal binary mask (IBM) and a more realistic minimum mean square error estimator (MMSE). For each of these three processing conditions, we measured (a) speech intelligibility, (b) RTs on two different tasks (identification of the last digit and arithmetic summation of the first and last digit), and (c) subjective listening effort ratings. All measurements were performed at four signal-to-noise ratios (SNRs): -5, 0, +5, and +∞ dB. Speech intelligibility was high (>97% correct) for all conditions. A significant decrease in response time, relative to the unprocessed condition, was found for both IBM and MMSE for the arithmetic but not the identification task. Listening effort ratings were significantly lower for IBM than for MMSE and unprocessed speech in noise. We conclude that RT for an arithmetic task can provide an objective measure of the benefit of noise reduction. For young normal-hearing listeners, both ideal and realistic noise reduction can reduce RTs at SNRs where speech intelligibility is close to 100%. Ideal noise reduction can also reduce perceived listening effort.

Higher Crash and Near-Crash Rates in Teenaged Drivers With Lower Cortisol Response

PubMed Central

Ouimet, Marie Claude; Brown, Thomas G.; Guo, Feng; Klauer, Sheila G.; Simons-Morton, Bruce G.; Fang, Youjia; Lee, Suzanne E.; Gianoulakis, Christina; Dingus, Thomas A.

2014-01-01

IMPORTANCE Road traffic crashes are one of the leading causes of injury and death among teenagers worldwide. Better understanding of the individual pathways to driving risk may lead to better-targeted intervention in this vulnerable group. OBJECTIVE To examine the relationship between cortisol, a neurobiological marker of stress regulation linked to risky behavior, and driving risk. DESIGN, SETTING, AND PARTICIPANTS The Naturalistic Teenage Driving Study was designed to continuously monitor the driving behavior of teenagers by instrumenting vehicles with kinematic sensors, cameras, and a global positioning system. During 2006–2008, a community sample of 42 newly licensed 16-year-old volunteer participants in the United States was recruited and driving behavior monitored. It was hypothesized in teenagers that higher cortisol response to stress is associated with (1) lower crash and near-crash (CNC) rates during their first 18 months of licensure and (2) faster reduction in CNC rates over time. MAIN OUTCOMES AND MEASURES Participants’ cortisol response during a stress-inducing task was assessed at baseline, followed by measurement of their involvement in CNCs and driving exposure during their first 18 months of licensure. Mixed-effect Poisson longitudinal regression models were used to examine the association between baseline cortisol response and CNC rates during the follow-up period. RESULTS Participants with a higher baseline cortisol response had lower CNC rates during the follow-up period (exponential of the regression coefficient, 0.93; 95%CI, 0.88–0.98) and faster decrease in CNC rates over time (exponential of the regression coefficient, 0.98; 95%, CI, 0.96–0.99). CONCLUSIONS AND RELEVANCE Cortisol is a neurobiological marker associated with teenaged-driving risk. As in other problem-behavior fields, identification of an objective marker of teenaged-driving risk promises the development of more personalized intervention approaches. PMID:24710522

BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma.

PubMed

Niesvizky, Ruben; Jayabalan, David S; Christos, Paul J; Furst, Jessica R; Naib, Tara; Ely, Scott; Jalbrzikowski, Jessica; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Larow, April; Lent, Richard; Mark, Tomer; Cho, Hearn J; Shore, Tsiporah; Tepler, Jeffrey; Harpel, John; Schuster, Michael W; Mathew, Susan; Leonard, John P; Mazumdar, Madhu; Chen-Kiang, Selina; Coleman, Morton

2008-02-01

This trial determined the safety and efficacy of the combination regimen clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) as first-line therapy for multiple myeloma. Patients received BiRD in 28-day cycles. Dexamethasone (40 mg) was given orally once weekly, clarithromycin (500 mg) was given orally twice daily, and lenalidomide (25 mg) was given orally daily on days 1 to 21. Objective response was defined by standard criteria (ie, decrease in serum monoclonal protein [M-protein] by at least 50%, and a decrease in urine M-protein by at least 90%). Of the 72 patients enrolled, 65 had an objective response (90.3%). A combined stringent and conventional complete response rate of 38.9% was achieved, and 73.6% of the patients achieved at least a 90% decrease in M-protein levels. This regimen did not interfere with hematopoietic stem-cell harvest. Fifty-two patients who did not go on to receive transplants received continued therapy (complete response, 37%; very good partial response, 33%). The major adverse events were thromboembolic events, corticosteroid-related morbidity, and cytopenias. BiRD is an effective regimen with manageable side effects in the treatment of symptomatic, newly diagnosed multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00151203.

Exploratory Cross-Sectional Study of Factors Associated with the Healthfulness of Parental Responses to Child Food Purchasing Requests.

PubMed

Calloway, Eric E; Ranjit, Nalini; Sweitzer, Sara J; Roberts-Gray, Cindy; Romo-Palafox, Maria J; McInnis, Katie A; Briley, Margaret E

2016-08-01

Objective The main objective of this study was to investigate the relationship between various factors (e.g., sociodemographic, child, and parental factors) and the healthfulness of parental responses to child in-store food purchasing requests. Additionally, a secondary objective is to describe "resist strategies" used by parents to respond to child food-purchasing requests and their efficacy in avoiding conflict. Methods Parent-child dyads (children aged 2-6 years) completed an audio-/visual-recoded food shopping trip at their usual grocery store and time. Recordings of trips were coded for behavioral and environmental factors. Parental healthful response rate (i.e., percent of responses that were healthful) was the primary outcome variable. A healthful response occurred when a parent yielded to a healthful child request, or resisted a non-healthful request. Parents also completed a questionnaire. Kruskal-Wallis tests were used to assess the relationship between the main outcome variable and sociodemographic, child, and parent factors. Results Parents (n = 39) responded healthfully to 62.9 % (±26.7 %) of child food purchasing requests. Low- and middle-income parents, and black and white parents, had significantly higher healthful response rates compared to high-income parents (p = 0.03) and Hispanic/Indian-descent parents (p = 0.02), respectively. Using the "ignore" strategy proved an effective resist strategy in this study, leading to no parent-child conflicts. Conclusions Programming that seeks to improve the healthfulness of food purchasing in families with young children should address unhealthful response behaviors in Hispanic/Indian-descent parents and high-income parents; although, the needs of these groups are different. Further research is needed to confirm and expand on these findings.

Do Physicians Respond to Web-Based Patient Ratings? An Analysis of Physicians’ Responses to More Than One Million Web-Based Ratings Over a Six-Year Period

PubMed Central

Sauter, Lisa; Jablonski, Lisa; Sander, Uwe; Taheri-Zadeh, Fatemeh

2017-01-01

Background Physician-rating websites (PRWs) may lead to quality improvements in case they enable and establish a peer-to-peer communication between patients and physicians. Yet, we know little about whether and how physicians respond on the Web to patient ratings. Objective The objective of this study was to describe trends in physicians’ Web-based responses to patient ratings over time, to identify what physician characteristics influence Web-based responses, and to examine the topics physicians are likely to respond to. Methods We analyzed physician responses to more than 1 million patient ratings displayed on the German PRW, jameda, from 2010 to 2015. Quantitative analysis contained chi-square analyses and the Mann-Whitney U test. Quantitative content techniques were applied to determine the topics physicians respond to based on a randomly selected sample of 600 Web-based ratings and corresponding physician responses. Results Overall, physicians responded to 1.58% (16,640/1,052,347) of all Web-based ratings, with an increasing trend over time from 0.70% (157/22,355) in 2010 to 1.88% (6377/339,919) in 2015. Web-based ratings that were responded to had significantly worse rating results than ratings that were not responded to (2.15 vs 1.74, P<.001). Physicians who respond on the Web to patient ratings differ significantly from nonresponders regarding several characteristics such as gender and patient recommendation results (P<.001 each). Regarding scaled-survey rating elements, physicians were most likely to respond to the waiting time within the practice (19.4%, 99/509) and the time spent with the patient (18.3%, 110/600). Almost one-third of topics in narrative comments were answered by the physicians (30.66%, 382/1246). Conclusions So far, only a minority of physicians have taken the chance to respond on the Web to patient ratings. This is likely because of (1) the low awareness of PRWs among physicians, (2) the fact that only a few PRWs enable physicians to respond on the Web to patient ratings, and (3) the lack of an active moderator to establish peer-to-peer communication. PRW providers should foster more frequent communication between the patient and the physician and encourage physicians to respond on the Web to patient ratings. Further research is needed to learn more about the motivation of physicians to respond or not respond to Web-based patient ratings. PMID:28747292

Emotional reasoning and parent-based reasoning in normal children.

PubMed

Morren, Mattijn; Muris, Peter; Kindt, Merel

2004-01-01

A previous study by Muris, Merckelbach, and Van Spauwen demonstrated that children display emotional reasoning irrespective of their anxiety levels. That is, when estimating whether a situation is dangerous, children not only rely on objective danger information but also on their own anxiety-response. The present study further examined emotional reasoning in children aged 7-13 years (N = 508). In addition, it was investigated whether children also show parent-based reasoning, which can be defined as the tendency to rely on anxiety-responses that can be observed in parents. Children completed self-report questionnaires of anxiety, depression, and emotional and parent-based reasoning. Evidence was found for both emotional and parent-based reasoning effects. More specifically, children's danger ratings were not only affected by objective danger information, but also by anxiety-response information in both objective danger and safety stories. High levels of anxiety and depression were significantly associated with the tendency to rely on anxiety-response information, but only in the case of safety scripts.

Treatment-Resistant Depressed Youth Show a Higher Response Rate If Treatment Ends during Summer School Break

ERIC Educational Resources Information Center

Shamseddeen, Wael; Clarke, Gregory; Wagner, Karen Dineen; Ryan, Neal D.; Birmaher, Boris; Emslie, Graham; Asarnow, Joan Rosenbaum; Porta, Giovanna; Mayes, Taryn; Keller, Martin B.; Brent, David A.

2011-01-01

Objective: There is little work on the effect of school on response to treatment of depression, with available research suggesting that children and adolescents with school difficulties are less likely to respond to fluoxetine compared with those with no school difficulties. Method: Depressed adolescents in the Treatment of Resistant Depression in…

Physiological and Growth Responses of Midrotation Loblolly Pine to Treatments of Fire, Herbicide, and Fertilizer

Treesearch

Emily J. Goodwin; Lisa M. Marino McInnis; Hans M. Williams; Brian P. Oswald; Kenneth W. Farrish

2004-01-01

The objectives of this study were to examine the effects of fertilizer and understory vegetation control (herbicide and prescribed fire) on mature tree physiology and to link observed physiological responses with tree growth. Photosynthetic rate (photosynthesis), transpiration, stomatal conductance, stem diameter, and crown area were measured in two midrotation...

Pooled Systemic Efficacy and Safety Data from the Pivotal Phase II Studies (NP28673 and NP28761) of Alectinib in ALK-positive Non-Small Cell Lung Cancer.

PubMed

Yang, James Chih-Hsin; Ou, Sai-Hong Ignatius; De Petris, Luigi; Gadgeel, Shirish; Gandhi, Leena; Kim, Dong-Wan; Barlesi, Fabrice; Govindan, Ramaswamy; Dingemans, Anne-Marie C; Crino, Lucio; Lena, Herve; Popat, Sanjay; Ahn, Jin Seok; Dansin, Eric; Golding, Sophie; Bordogna, Walter; Balas, Bogdana; Morcos, Peter N; Zeaiter, Ali; Shaw, Alice T

2017-10-01

Alectinib demonstrated clinical efficacy and an acceptable safety profile in two phase II studies (NP28761 and NP28673). Here we report the pooled efficacy and safety data after 15 and 18 months more follow-up than in the respective primary analyses. Enrolled patients had ALK receptor tyrosine kinase gene (ALK)-positive NSCLC and had progressed while taking, or could not tolerate, crizotinib. Patients received oral alectinib, 600 mg twice daily. The primary end point in both studies was objective response rate assessed by an independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included disease control rate, duration of response, progression-free survival, overall survival, and safety. The pooled data set included 225 patients (n = 138 in NP28673 and n = 87 in NP28761). The response-evaluable population included 189 patients (84% [n = 122 in NP28673 and n = 67 in NP28761]). In the response-evaluable population, objective response rate as assessed by the IRC was 51.3% (95% confidence interval [CI]: 44.0-58.6 [all PRs]), the disease control rate was 78.8% (95% CI: 72.3-84.4), and the median duration of response was 14.9 months (95% CI: 11.1-20.4) after 58% of events. Median progression-free survival as assessed by the IRC was 8.3 months (95% CI: 7.0-11.3) and median overall survival was 26.0 months (95% CI: 21.4-not estimable). Grade 3 or higher adverse events (AEs) occurred in 40% of patients, 6% of patients had treatment withdrawn on account of AEs, and 33% had AEs leading to dose interruptions/modification. This pooled data analysis confirmed the robust systemic efficacy of alectinib in ALK-positive NSCLC with a durable response rate. Alectinib also had an acceptable safety profile with a longer duration of follow-up. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Nivolumab Monotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer

PubMed Central

Rizvi, Naiyer A.; Chow, Laura Q.; Borghaei, Hossein; Brahmer, Julie; Ready, Neal; Gerber, David E.; Shepherd, Frances A.; Antonia, Scott; Goldman, Jonathan W.; Juergens, Rosalyn A.; Laurie, Scott A.; Nathan, Faith E.; Shen, Yun; Harbison, Christopher T.; Hellmann, Matthew D.

2016-01-01

Purpose Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non–small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial. Methods Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point. Results Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD–ligand 1 expression and 14% (two of 14) in patients with no PD–ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively. Conclusion First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC. PMID:27354485

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer.

PubMed

Gettinger, Scott; Rizvi, Naiyer A; Chow, Laura Q; Borghaei, Hossein; Brahmer, Julie; Ready, Neal; Gerber, David E; Shepherd, Frances A; Antonia, Scott; Goldman, Jonathan W; Juergens, Rosalyn A; Laurie, Scott A; Nathan, Faith E; Shen, Yun; Harbison, Christopher T; Hellmann, Matthew D

2016-09-01

Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial. Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point. Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD-ligand 1 expression and 14% (two of 14) in patients with no PD-ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively. First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC. © 2016 by American Society of Clinical Oncology.

Sensory Over-Responsivity, Psychopathology, and Family Impairment in School-Aged Children

ERIC Educational Resources Information Center

Carter, Alice S.; Ben-Sasson, Ayelet; Briggs-Gowan, Margaret J.

2011-01-01

Objective: To establish the diagnostic validity of sensory overresponsivity (SOR), there is a need to document rates of SOR and the co-occurrence of SOR with other psychiatric disorders. Although this was not a diagnostic study of SOR, this study was designed to investigate rates of elevated SOR symptoms and associations between elevated SOR…

Heat conduction errors and time lag in cryogenic thermometer installations

NASA Technical Reports Server (NTRS)

Warshawsky, I.

1973-01-01

Installation practices are recommended that will increase rate of heat exchange between the thermometric sensing element and the cryogenic fluid and that will reduce the rate of undesired heat transfer to higher-temperature objects. Formulas and numerical data are given that help to estimate the magnitude of heat-conduction errors and of time lag in response.

Automated Pilot Performance Assessment in the T-37: A Feasibility Study. Final Report (May 1968-April 1971).

ERIC Educational Resources Information Center

Knoop, Patricia A.; Welde, William L.

Air Force investigators conducted a three year program to develop a capability for automated quantification and assessment of in-flight pilot performance. Such a capability enhances pilot training by making ratings more objective, valid, reliable and sensitive, and by freeing instructors from rating responsibilities, allowing them to concentrate…

Objectification of steering feel around straight-line driving for vehicle/tyre design

NASA Astrophysics Data System (ADS)

Kim, Jungsik; Yoon, Yong-San

2015-02-01

This paper presents the objectification techniques for the assessment of steering feel including {on-centre} feel and steering response by measurement data. Here, new objective parameters are developed by considering not only the process by which the steering feel is evaluated subjectively but also by the ergonomic perceptive sensitivity of the driver. In order to validate such objective parameters, subjective tests are carried out by professional drivers. Objective measurements are also performed for several cars at a proving ground. The linear correlation coefficients between the subjective ratings and the objective parameters are calculated. As one of new objective parameters, steering wheel angle defined by ergonomic perception sensitivity shows high correlation with the subjective questionnaires of on-center responses. Newly defined steering torque curvature also shows high correlation with the subjective questionnaires of on-center effort. These correlation results conclude that the subjective assessment of steering feel can be successfully explained and objectified by means of the suggested objective parameters.

Predictors of Response Rates to a Long Term Follow-Up Mail out Survey

PubMed Central

Koloski, Natasha A.; Jones, Michael; Eslick, Guy; Talley, Nicholas J.

2013-01-01

Objective Very little is known about predictors of response rates to long-term follow-up mail-out surveys, including whether the timing of an incentive affects response rates. We aimed to determine whether the timing of the incentive affects response rates and what baseline demographic and psychological factors predict response rates to a 12 year follow-up survey. Study design and setting: Participants were 450 randomly selected people from the Penrith population, Australia who had previously participated in a mail-out survey 12 years earlier. By random allocation, 150 people received no incentive, 150 received a lottery ticket inducement with the follow-up survey and 150 received a lottery ticket inducement on the return of a completed survey. Results The overall response rate for the study was 63%. There were no significant differences in terms of response rates between the no incentive (58.8%;95%CI 49.8%,67.3%), incentive with survey (65.1%;95%CI 56.2%,73.3%) and promised incentive (65.3%;95%CI 56.1%,73.7%) groups. Independent predictors of responding to the 12 year survey were being older (OR=1.02, 95%CI 1.01,1.05,P=0.001) and being less neurotic as reported on the first survey 12 years earlier (OR=0.92, 95%CI 0.86,0.98, P=0.010). Conclusions Psychological factors may play a role in determining who responds to long-term follow-up surveys although timing of incentives does not. PMID:24223902

Response rates for mailout survey-driven studies in patients waiting for thyroid surgery.

PubMed

Eskander, Antoine; Freeman, Jeremy; Rotstein, Lorne; Higgins, Kevin; Enepekides, Danny; Gilbert, Ralph; Brown, Dale; Gullane, Patrick; Irish, Jonathan; Sawka, Anna M; Goldstein, David P

2011-12-01

In the surgical literature, mailout survey studies are becoming more prevalent. The objective of this article is to summarize response rates in patients waiting for thyroid surgery and to document the methodology of mailout survey questionnaires. The results reported here are from a study assessing clinical and sociodemographic factors associated with high levels of anxiety while patients are waiting for thyroid surgery. The surveys used in this study include a sociodemographic patient opinion questionnaire, the Hospital Anxiety Depression Scale (HADS), the Illness Intrusiveness Ratings Scale (IIRS), the Perceived Stress Scale (PSS), and the Impact of Events Scale-Revised (IES-R). A modified Dillman tailored design approach was used. Assessment of nonresponders was performed. The methods used yielded a response rate of 54% with this patient population. Some differences were noted among responders and nonresponders. This response rate is comparable to but in the lower spectrum of that stated in the oncology literature likely owing to the increase in the length of the survey, number of sensitive questions, limitations in the number of mailouts, and limited familiarity with the surgeon requesting participation in research.

Time-dependent behavior of passive skeletal muscle

NASA Astrophysics Data System (ADS)

Ahamed, T.; Rubin, M. B.; Trimmer, B. A.; Dorfmann, L.

2016-03-01

An isotropic three-dimensional nonlinear viscoelastic model is developed to simulate the time-dependent behavior of passive skeletal muscle. The development of the model is stimulated by experimental data that characterize the response during simple uniaxial stress cyclic loading and unloading. Of particular interest is the rate-dependent response, the recovery of muscle properties from the preconditioned to the unconditioned state and stress relaxation at constant stretch during loading and unloading. The model considers the material to be a composite of a nonlinear hyperelastic component in parallel with a nonlinear dissipative component. The strain energy and the corresponding stress measures are separated additively into hyperelastic and dissipative parts. In contrast to standard nonlinear inelastic models, here the dissipative component is modeled using an evolution equation that combines rate-independent and rate-dependent responses smoothly with no finite elastic range. Large deformation evolution equations for the distortional deformations in the elastic and in the dissipative component are presented. A robust, strongly objective numerical integration algorithm is used to model rate-dependent and rate-independent inelastic responses. The constitutive formulation is specialized to simulate the experimental data. The nonlinear viscoelastic model accurately represents the time-dependent passive response of skeletal muscle.

Polarized object detection in crabs: a two-channel system.

PubMed

Basnak, Melanie Ailín; Pérez-Schuster, Verónica; Hermitte, Gabriela; Berón de Astrada, Martín

2018-05-25

Many animal species take advantage of polarization vision for vital tasks such as orientation, communication and contrast enhancement. Previous studies have suggested that decapod crustaceans use a two-channel polarization system for contrast enhancement. Here, we characterize the polarization contrast sensitivity in a grapsid crab . We estimated the polarization contrast sensitivity of the animals by quantifying both their escape response and changes in heart rate when presented with polarized motion stimuli. The motion stimulus consisted of an expanding disk with an 82 deg polarization difference between the object and the background. More than 90% of animals responded by freezing or trying to avoid the polarized stimulus. In addition, we co-rotated the electric vector (e-vector) orientation of the light from the object and background by increments of 30 deg and found that the animals' escape response varied periodically with a 90 deg period. Maximum escape responses were obtained for object and background e-vectors near the vertical and horizontal orientations. Changes in cardiac response showed parallel results but also a minimum response when e-vectors of object and background were shifted by 45 deg with respect to the maxima. These results are consistent with an orthogonal receptor arrangement for the detection of polarized light, in which two channels are aligned with the vertical and horizontal orientations. It has been hypothesized that animals with object-based polarization vision rely on a two-channel detection system analogous to that of color processing in dichromats. Our results, obtained by systematically varying the e-vectors of object and background, provide strong empirical support for this theoretical model of polarized object detection. © 2018. Published by The Company of Biologists Ltd.

Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program.

PubMed

González-Cao, M; Arance, A; Piulats, J M; Marquez-Rodas, I; Manzano, J L; Berrocal, A; Crespo, G; Rodriguez, D; Perez-Ruiz, E; Berciano, M; Soria, A; Castano, A G; Espinosa, E; Montagut, C; Alonso, L; Puertolas, T; Aguado, C; Royo, M A; Blanco, R; Rodríguez, J F; Muñoz, E; Mut, P; Barron, F; Martin-Algarra, S

2017-06-01

The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group. Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events. Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases.

Sample Design, Sample Augmentation, and Estimation for Wave 2 of the NSHAP

PubMed Central

English, Ned; Pedlow, Steven; Kwok, Peter K.

2014-01-01

Objectives. The sample for the second wave (2010) of National Social Life, Health, and Aging Project (NSHAP) was designed to increase the scientific value of the Wave 1 (2005) data set by revisiting sample members 5 years after their initial interviews and augmenting this sample where possible. Method. There were 2 important innovations. First, the scope of the study was expanded by collecting data from coresident spouses or romantic partners. Second, to maximize the representativeness of the Wave 2 data, nonrespondents from Wave 1 were again approached for interview in the Wave 2 sample. Results. The overall unconditional response rate for the Wave 2 panel was 74%; the conditional response rate of Wave 1 respondents was 89%; the conditional response rate of partners was 84%; and the conversion rate for Wave 1 nonrespondents was 26%. Discussion. The inclusion of coresident partners enhanced the study by allowing the examination of how intimate, household relationships are related to health trajectories and by augmenting the size of the NSHAP sample size for this and future waves. The uncommon strategy of returning to Wave 1 nonrespondents reduced potential bias by ensuring that to the extent possible the whole of the original sample forms the basis for the field effort. NSHAP Wave 2 achieved its field objectives of consolidating the panel, recruiting their resident spouses or romantic partners, and converting a significant proportion of Wave 1 nonrespondents. PMID:25360016

Subjective and objective effects of coffee consumption - caffeine or expectations?

PubMed

Dömötör, Zs; Szemerszky, R; Köteles, F

2015-03-01

Impact of 5 mg/kg caffeine, chance of receiving caffeine (stimulus expectancies), and expectations of effects of caffeine (response expectancies) on objective (heart rate (HR), systolic/diastolic blood pressure (SBP/DBP), measures of heart rate variability (HRV), and reaction time (RT)) and subjective variables were investigated in a double-blind, placebo-controlled experiment with a no-treatment group. Participants were 107 undergraduate university students (mean age 22.3 ± 3.96 years). Consumption of 5 mg/kg caffeine had an impact on participants' SBP, standard deviation of normal heartbeat intervals, HR (decrease), and subjective experience 40 minutes later even after controlling for respective baseline values, stimulus and response expectancies, and habitual caffeine consumption. No effects on DBP, high frequency component of HRV, the ratio of low- and high-frequency, and RT were found. Beyond actual caffeine intake, response expectancy score was also a determinant of subjective experience which refers to a placebo component in the total effect. Actual autonomic (SBP, HR) changes and somatosensory amplification tendency, however, had no significant impact on subjective experience. Placebo reaction plays a role in the subjective changes caused by caffeine consumption but it has no impact on objective variables. Conditional vs deceptive administration of caffeine (i.e. stimulus expectancies) had no impact on any assessed variable.

Response Rates and Response Bias for 50 Surveys of Pediatricians

PubMed Central

Cull, William L; O'Connor, Karen G; Sharp, Sanford; Tang, Suk-fong S

2005-01-01

Research Objective To track response rates across time for surveys of pediatricians, to explore whether response bias is present for these surveys, and to examine whether response bias increases with lower response rates. Data Source/Study Setting A total of 63,473 cases were gathered from 50 different surveys of pediatricians conducted by the American Academy of Pediatrics (AAP) since 1994. Thirty-one surveys targeted active U.S. members of the AAP, six targeted pediatric residents, and the remaining 13 targeted AAP-member and nonmember pediatric subspecialists. Information for the full target samples, including nonrespondents, was collected using administrative databases of the AAP and the American Board of Pediatrics. Study Design To assess bias for each survey, age, gender, location, and AAP membership type were compared for respondents and the full target sample. Correlational analyses were conducted to examine whether surveys with lower response rates had increasing levels of response bias. Principal Findings Response rates to the 50 surveys examined declined significantly across survey years (1994–2002). Response rates ranged from 52 to 81 percent with an average of 68 percent. Comparisons between respondents and the full target samples showed the respondent group to be younger, to have more females, and to have less specialty-fellow members. Response bias was not apparent for pediatricians' geographical location. The average response bias, however, was fairly small for all factors: age (0.45 years younger), gender (1.4 percentage points more females), and membership type (1.1 percentage points fewer specialty-fellow members). Gender response bias was found to be inversely associated with survey response rates (r=−0.38). Even for the surveys with the lowest response rates, amount of response bias never exceeded 5 percentage points for gender, 3 years for age, or 3 percent for membership type. Conclusions While response biases favoring women, young physicians, and nonspecialty-fellow members were found across the 52–81 percent response rates examined in this study, the amount of bias was minimal for these factors that could be tested. At least for surveys of pediatricians, more attention should be devoted by investigators to assessments of response bias rather than relying on response rates as a proxy of response bias. PMID:15663710

The Neural Circuit Mechanisms Underlying the Retinal Response to Motion Reversal

PubMed Central

Chen, Eric Y.; Chou, Janice; Park, Jeongsook; Schwartz, Greg

2014-01-01

To make up for delays in visual processing, retinal circuitry effectively predicts that a moving object will continue moving in a straight line, allowing retinal ganglion cells to anticipate the object's position. However, a sudden reversal of motion triggers a synchronous burst of firing from a large group of ganglion cells, possibly signaling a violation of the retina's motion prediction. To investigate the neural circuitry underlying this response, we used a combination of multielectrode array and whole-cell patch recordings to measure the responses of individual retinal ganglion cells in the tiger salamander to reversing stimuli. We found that different populations of ganglion cells were responsible for responding to the reversal of different kinds of objects, such as bright versus dark objects. Using pharmacology and designed stimuli, we concluded that ON and OFF bipolar cells both contributed to the reversal response, but that amacrine cells had, at best, a minor role. This allowed us to formulate an adaptive cascade model (ACM), similar to the one previously used to describe ganglion cell responses to motion onset. By incorporating the ON pathway into the ACM, we were able to reproduce the time-varying firing rate of fast OFF ganglion cells for all experimentally tested stimuli. Analysis of the ACM demonstrates that bipolar cell gain control is primarily responsible for generating the synchronized retinal response, as individual bipolar cells require a constant time delay before recovering from gain control. PMID:25411485

Visual stimuli induced by self-motion and object-motion modify odour-guided flight of male moths (Manduca sexta L.).

PubMed

Verspui, Remko; Gray, John R

2009-10-01

Animals rely on multimodal sensory integration for proper orientation within their environment. For example, odour-guided behaviours often require appropriate integration of concurrent visual cues. To gain a further understanding of mechanisms underlying sensory integration in odour-guided behaviour, our study examined the effects of visual stimuli induced by self-motion and object-motion on odour-guided flight in male M. sexta. By placing stationary objects (pillars) on either side of a female pheromone plume, moths produced self-induced visual motion during odour-guided flight. These flights showed a reduction in both ground and flight speeds and inter-turn interval when compared with flight tracks without stationary objects. Presentation of an approaching 20 cm disc, to simulate object-motion, resulted in interrupted odour-guided flight and changes in flight direction away from the pheromone source. Modifications of odour-guided flight behaviour in the presence of stationary objects suggest that visual information, in conjunction with olfactory cues, can be used to control the rate of counter-turning. We suggest that the behavioural responses to visual stimuli induced by object-motion indicate the presence of a neural circuit that relays visual information to initiate escape responses. These behavioural responses also suggest the presence of a sensory conflict requiring a trade-off between olfactory and visually driven behaviours. The mechanisms underlying olfactory and visual integration are discussed in the context of these behavioural responses.

Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer.

PubMed

Vogel, Charles L; Cobleigh, Melody A; Tripathy, Debu; Gutheil, John C; Harris, Lyndsay N; Fehrenbacher, Louis; Slamon, Dennis J; Murphy, Maureen; Novotny, William F; Burchmore, Michael; Shak, Steven; Stewart, Stanford J; Press, Michael

2002-02-01

To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer. One hundred fourteen women with HER2-overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly. The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ HER2 overexpression by immunohistochemistry (IHC) were 35% (95% CI, 24.4% to 44.7%) and none (95% CI, 0% to 15.5%), respectively. The clinical benefit rates in assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%, respectively. The response rates in 108 assessable patients with and without HER2 gene amplification by fluorescence in situ hybridization (FISH) analysis were 34% (95% CI, 23.9% to 45.7%) and 7% (95% CI, 0.8% to 22.8%), respectively. Seventeen (57%) of 30 patients with an objective response and 22 (51%) of 43 patients with clinical benefit had not experienced disease progression at follow-up at 12 months or later. The most common treatment-related adverse events were chills (25% of patients), asthenia (23%), fever (22%), pain (18%), and nausea (14%). Cardiac dysfunction occurred in two patients (2%); both had histories of cardiac disease and did not require additional intervention after discontinuation of trastuzumab. There was no clear evidence of a dose-response relationship for response, survival, or adverse events. Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 3+ overexpression by IHC or gene amplification by FISH.

Weekly Docetaxel, Cisplatin, and Cetuximab in Palliative Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck.

PubMed

Trieu, Vanessa; Pinto, Harlan; Riess, Jonathan W; Lira, Ruth; Luciano, Richard; Coty, Jessie; Boothroyd, Derek; Colevas, A Dimitrios

2018-03-14

Chemotherapy for recurrent, metastatic squamous cell carcinoma of the head and neck need not be known for extreme toxicity.The weekly regimen studied here has been demonstrated to be tolerable and effective. The objective of this study was to establish the response rate, progression-free survival (PFS) and overall survival (OS), and safety profile of weekly docetaxel, platinum, and cetuximab (TPC) in patients with relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-nine patients with metastatic or recurrent SCCHN with an Eastern Cooperative Oncology Group (ECOG) performance status <3 were enrolled in an institutional review board-approved phase II trial. This study permitted prior chemoradiation, radiation, and/or surgery, provided that 3 months had elapsed since the end of the potentially curative treatment. Patients received cisplatin 30 mg/m 2 or carboplatin area under the curve (AUC) 2, docetaxel 30 mg/m 2 , and cetuximab 250 mg/m 2 weekly for 3 weeks, followed by a break during the fourth week, for a 28-day cycle. Planned intrapatient dose modifications were based on individual toxicity. Twenty-seven patients received TPC and were evaluable for response and toxicity. Rates of complete response (CR), partial response (PR), and confirmed PR were 3%, 52%, and 30%, respectively. The overall objective response rate was 56%. Estimated median PFS and OS were 4.8 and 14.7 months, respectively. The rates of grade 3 and 4 worst-grade adverse events (AEs) per patient were 85% and 7%, respectively. Dose density through cycle 4 was preserved for all patients; however, treatment beyond cycle 6 with the TPC regimen proved unfeasible. Weekly docetaxel, cisplatin, and cetuximab is an effective regimen for patients with metastatic or recurrent SCCHN. Response rates, PFS, and OS compare favorably with other combination chemotherapy treatments. Grade 4 toxicity rates observed in this study were substantially lower than those described with regimens using less frequent, higher-dose chemotherapy schedules. © AlphaMed Press; the data published online to support this summary is the property of the authors.

Neural responses to facial expression and face identity in the monkey amygdala.

PubMed

Gothard, K M; Battaglia, F P; Erickson, C A; Spitler, K M; Amaral, D G

2007-02-01

The amygdala is purported to play an important role in face processing, yet the specificity of its activation to face stimuli and the relative contribution of identity and expression to its activation are unknown. In the current study, neural activity in the amygdala was recorded as monkeys passively viewed images of monkey faces, human faces, and objects on a computer monitor. Comparable proportions of neurons responded selectively to images from each category. Neural responses to monkey faces were further examined to determine whether face identity or facial expression drove the face-selective responses. The majority of these neurons (64%) responded both to identity and facial expression, suggesting that these parameters are processed jointly in the amygdala. Large fractions of neurons, however, showed pure identity-selective or expression-selective responses. Neurons were selective for a particular facial expression by either increasing or decreasing their firing rate compared with the firing rates elicited by the other expressions. Responses to appeasing faces were often marked by significant decreases of firing rates, whereas responses to threatening faces were strongly associated with increased firing rate. Thus global activation in the amygdala might be larger to threatening faces than to neutral or appeasing faces.

Assessment of two different types of bias affecting the results of outcome-based evaluation in undergraduate medical education.

PubMed

Schiekirka, Sarah; Anders, Sven; Raupach, Tobias

2014-07-21

Estimating learning outcome from comparative student self-ratings is a reliable and valid method to identify specific strengths and shortcomings in undergraduate medical curricula. However, requiring students to complete two evaluation forms (i.e. one before and one after teaching) might adversely affect response rates. Alternatively, students could be asked to rate their initial performance level retrospectively. This approach might threaten the validity of results due to response shift or effort justification bias. Two consecutive cohorts of medical students enrolled in a six-week cardio-respiratory module were enrolled in this study. In both cohorts, performance gain was estimated for 33 specific learning objectives. In the first cohort, outcomes calculated from ratings provided before (pretest) and after (posttest) teaching were compared to outcomes derived from comparative self-ratings collected after teaching only (thentest and posttest). In the second cohort, only thentests and posttests were used to calculate outcomes, but data collection tools differed with regard to item presentation. In one group, thentest and posttest ratings were obtained sequentially on separate forms while in the other, both ratings were obtained simultaneously for each learning objective. Using thentest ratings to calculate performance gain produced slightly higher values than using true pretest ratings. Direct comparison of then- and posttest ratings also yielded slightly higher performance gain than sequential ratings, but this effect was negligibly small. Given the small effect sizes, using thentests appears to be equivalent to using true pretest ratings. Item presentation in the posttest does not significantly impact on results.

Assessment of two different types of bias affecting the results of outcome-based evaluation in undergraduate medical education

PubMed Central

2014-01-01

Background Estimating learning outcome from comparative student self-ratings is a reliable and valid method to identify specific strengths and shortcomings in undergraduate medical curricula. However, requiring students to complete two evaluation forms (i.e. one before and one after teaching) might adversely affect response rates. Alternatively, students could be asked to rate their initial performance level retrospectively. This approach might threaten the validity of results due to response shift or effort justification bias. Methods Two consecutive cohorts of medical students enrolled in a six-week cardio-respiratory module were enrolled in this study. In both cohorts, performance gain was estimated for 33 specific learning objectives. In the first cohort, outcomes calculated from ratings provided before (pretest) and after (posttest) teaching were compared to outcomes derived from comparative self-ratings collected after teaching only (thentest and posttest). In the second cohort, only thentests and posttests were used to calculate outcomes, but data collection tools differed with regard to item presentation. In one group, thentest and posttest ratings were obtained sequentially on separate forms while in the other, both ratings were obtained simultaneously for each learning objective. Results Using thentest ratings to calculate performance gain produced slightly higher values than using true pretest ratings. Direct comparison of then- and posttest ratings also yielded slightly higher performance gain than sequential ratings, but this effect was negligibly small. Conclusions Given the small effect sizes, using thentests appears to be equivalent to using true pretest ratings. Item presentation in the posttest does not significantly impact on results. PMID:25043503

National survey of physicians to determine the effect of unconditional incentives on response rates of physician postal surveys

PubMed Central

Abdulaziz, Kasim; Brehaut, Jamie; Taljaard, Monica; Émond, Marcel; Sirois, Marie-Josée; Lee, Jacques S; Wilding, Laura; Perry, Jeffrey J

2015-01-01

Objectives Physicians are a commonly targeted group in health research surveys, but their response rates are often relatively low. The goal of this paper was to evaluate the effect of unconditional incentives in the form of a coffee card on physician postal survey response rates. Design Following 13 key informant interviews and eight cognitive interviews a survey questionnaire was developed. Participants A random sample of 534 physicians, stratified by physician group (geriatricians, family physicians, emergency physicians) was selected from a national medical directory. Setting Using computer generated random numbers; half of the physicians in each stratum were allocated to receive a coffee card to a popular national coffee chain together with the first survey mailout. Interventions The intervention was a $10 Tim Hortons gift card given to half of the physicians who were randomly allocated to receive the incentive. Results 265 (57.0%) physicians completed the survey. The response rate was significantly higher in the group allocated to receive the incentive (62.7% vs 51.3% in the control group; p=0.01). Conclusions Our results indicate that an unconditional incentive in the form of a coffee gift card can substantially improve physician response rates. Future research can look at the effect of varying amounts of cash on the gift cards on response rates. PMID:25694460

The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma.

PubMed

Dummer, Reinhard; Guminski, Alexander; Gutzmer, Ralf; Dirix, Luc; Lewis, Karl D; Combemale, Patrick; Herd, Robert M; Kaatz, Martin; Loquai, Carmen; Stratigos, Alexander J; Schulze, Hans-Joachim; Plummer, Ruth; Gogov, Sven; Pallaud, Celine; Yi, Tingting; Mone, Manisha; Chang, Anne Lynn S; Cornélis, Frank; Kudchadkar, Ragini; Trefzer, Uwe; Lear, John T; Sellami, Dalila; Migden, Michael R

2016-07-01

The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study. This report provides long-term follow-up data collected up to 12 months after the last patient was randomized. In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review. Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6 months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800 mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively). No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved. With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Childhood Maltreatment and Differential Treatment Response and Recurrence in Adult Major Depressive Disorder

ERIC Educational Resources Information Center

Harkness, Kate L.; Bagby, R. Michael; Kennedy, Sidney H.

2012-01-01

Objective: A substantial number of patients with major depressive disorder (MDD) do not respond to treatment, and recurrence rates remain high. The purpose of this study was to examine a history of severe childhood abuse as a moderator of response following a 16-week acute treatment trial, and of recurrence over a 12-month follow-up. Method:…

Measuring End-of-Life Care Processes in Nursing Homes

ERIC Educational Resources Information Center

Temkin-Greener, Helena; Zheng, Nan; Norton, Sally A.; Quill, Timothy; Ladwig, Susan; Veazie, Peter

2009-01-01

Purpose: The objectives of this study were to develop measures of end-of-life (EOL) care processes in nursing homes and to validate the instrument for measuring them. Design and Methods: A survey of directors of nursing was conducted in 608 eligible nursing homes in New York State. Responses were obtained from 313 (51.5% response rate) facilities.…

Women's self-rated attraction to male faces does not correspond with physiological arousal.

PubMed

Hagerman, S; Woolard, Z; Anderson, K; Tatler, B W; Moore, F R

2017-10-19

There has been little work to determine whether attractiveness ratings of faces correspond to sexual or more general attraction. We tested whether a measure of women's physiological arousal (pupil diameter change) was correlated with ratings of men's facial attractiveness. In Study 1, women rated the faces of men for whom we also measured salivary testosterone. They rated each face for attractiveness, and for desirability for friendship and long- and short-term romantic relationships. Pupil diameter change was not related to subjective ratings of attractiveness, but was positively correlated with the men's testosterone. In Study 2 we compared women's pupil diameter change in response to the faces of men with high versus low testosterone, as well as in response to non-facial images pre-rated as either sexually arousing or threatening. Pupil dilation was not affected by testosterone, and increased relatively more in response to sexually arousing than threatening images. We conclude that self-rated preferences may not provide a straightforward and direct assessment of sexual attraction. We argue that future work should identify the constructs that are tapped via attractiveness ratings of faces, and support the development of methodology which assesses objective sexual attraction.

The Role of Left Hemispheric Structures for Emotional Processing as a Monitor of Bodily Reaction and Felt Chill - a Case-Control Functional Imaging Study.

PubMed

Grunkina, Viktoria; Holtz, Katharina; Klepzig, Kai; Neubert, Jörg; Horn, Ulrike; Domin, Martin; Hamm, Alfons O; Lotze, Martin

2016-01-01

Background: The particular function of the left anterior human insula on emotional arousal has been illustrated with several case studies. Only after left hemispheric insula lesions, patients lose their pleasure in habits such as listening to joyful music. In functional magnetic resonance imaging studies (fMRI) activation in the left anterior insula has been associated with both processing of emotional valence and arousal. Tight interactions with different areas of the prefrontal cortex are involved in bodily response monitoring and cognitive appraisal of a given stimulus. Therefore, a large left hemispheric lesion including the left insula should impair the bodily response of chill experience (objective chill response) but leave the cognitive aspects of chill processing (subjective chill response) unaffected. Methods: We investigated a patient (MC) with a complete left hemispheric media cerebral artery stroke, testing fMRI representation of pleasant (music) and unpleasant (harsh sounds) chill response. Results: Although chill response to both pleasant and unpleasant rated sounds was confirmed verbally at passages also rated as chilling by healthy participants, skin conductance response was almost absent in MC. For a healthy control (HC) objective and subjective chill response was positively associated. Bilateral prefrontal fMRI-response to chill stimuli was sustained in MC whereas insula activation restricted to the right hemisphere. Diffusion imaging together with lesion maps revealed that left lateral tracts were completely damaged but medial prefrontal structures were intact. Conclusion: With this case study we demonstrate how bodily response and cognitive appraisal are differentially participating in the internal monitor of chill response.

Item Response Theory Analyses of Parent and Teacher Ratings of the ADHD Symptoms for Recoded Dichotomous Scores

ERIC Educational Resources Information Center

Gomez, Rapson; Vance, Alasdair; Gomez, Andre

2011-01-01

Objective: The two-parameter logistic model (2PLM) was used to evaluate the psychometric properties of the inattention (IA) and hyperactivity/impulsivity (HI) symptoms. Method: To accomplish this, parents and teachers completed the Disruptive Behavior Rating Scale (DBRS) for a group of 934 primary school-aged children. Results: The results for the…

Heat conduction errors and time lag in cryogenic thermometer installations

NASA Technical Reports Server (NTRS)

Warshawsky, I.

1973-01-01

Installation practices are recommended that will increase rate of heat exchange between the thermometric sensing element and the cryogenic fluid, in addition to bringing about a reduction in the rate of undesired heat transfer to higher temperature objects. Formulas and numerical data are given that help to estimate the magnitude of heat conduction errors and of time lag in response.

Doxorubicin chemotherapy for presumptive cardiac hemangiosarcoma in dogs†.

PubMed

Mullin, C M; Arkans, M A; Sammarco, C D; Vail, D M; Britton, B M; Vickery, K R; Risbon, R E; Lachowicz, J; Burgess, K E; Manley, C A; Clifford, C A

2016-12-01

Sixty-four dogs were treated with single-agent doxorubicin (DOX) for presumptive cardiac hemangiosarcoma (cHSA). The objective response rate (CR + PR) was 41%, and the biologic response rate (CR + PR + SD), or clinical benefit, was 68%. The median progression-free survival (PFS) for treated dogs was 66 days. The median survival time (MST) for this group was 116 days and was significantly improved compared to a MST of 12 days for untreated control dogs (P = 0.0001). Biologic response was significantly associated with improved PFS (P < 0.0001) and OS (P < 0.0001). Univariate analysis identified larger tumour size as a variable negatively associated with PFS. The high rate of clinical benefit and improved MST suggest that DOX has activity in canine cHSA. © 2014 John Wiley & Sons Ltd.

Pathological response to neoadjuvant chemotherapy: a new prognosis tool for the curative management of peritoneal colorectal carcinomatosis.

PubMed

Passot, Guillaume; You, Benoît; Boschetti, Gilles; Fontaine, Juliette; Isaac, Sylvie; Decullier, Evelyne; Maurice, Christele; Vaudoyer, Delphine; Gilly, François-Noël; Cotte, Eddy; Glehen, Olivier

2014-08-01

The primary objective of this study was to determine the incidence rate of pathological complete responses (pCRs) following neoadjuvant systemic chemotherapy for the treatment of peritoneal carcinomatosis (PC) of colorectal origin. The secondary objective was to evaluate whether pathological response assessments predict survival of patients treated with curative intent by complete cytoreductive surgery (CRS). A retrospective review was performed of 115 patients who underwent preoperative irinotecan- or oxaliplatin-based chemotherapy, followed by 124 procedures of complete CRS alone or combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The pathological response was defined as the mean percentage of cancer cells remaining within all specimens. Univariate and multivariate analyses were performed to identify predictors of survival and pathological response outcome. Twelve procedures (9.7 %) resulted in pCRs, defined as no residual cancer cells in all specimens, 25 (20.2 %) resulted in major responses (1 to 49 % residual cancer cells), and 87 (70.1 %) resulted in minor or no responses (>50 % residual cancer cells). The cumulative 5-year survival rates were 75 and 57 % for patients with pCR and major responses, respectively. Using multivariate analysis, pathological response was the only independent predictor of survival (P = 0.01; major response: hazard ratio [HR] = 4.91; minor response: HR = 13.46). No significant predictor of pathological response was identified. Pathological complete response can be achieved with preoperative systemic chemotherapy for patients with PC of colorectal origin. The degree of pathological response can be assessed and represented as a new outcome for prognosis following treatment with curative intent.

[Survey among readers of the Tijdschrift voor Psychiatrie].

PubMed

Brandt-Dominicus, J C; van Harten, P N

2006-01-01

The editorial board has defined the objectives of this journal as follows: to provide its readers with refreshing information, to report the results of scientific research and to build bridges between research and everyday practice. To find out what readers want and whether they support the board's objectives, and to use this information in planning the contents of future issues of the journal. All readers were invited to complete a questionnaire either on paper or via the website. Questionnaires were completed by 255 readers (response rate 5.7%). The average rating on a 5-point Likert scale was 3.8. Thematic issues and issues devoted to book reviews were given a high rating. There seems to be a demandfor evidence-based medicine, the inclusion of scientific results reported in other journals and practice-based articles. No significant differences were found between the views expressed by readers who had previously submitted an article for publication and those who had not, nor between Flemish readers and Dutch readers. The website was not visited very often. The Tijdschrift voor Psychiatrie is greatly appreciated by its readers. They are largely in agreement with the objectives formulated by the editorial board. Thematic issues are highly rated and many subjects are mentioned by the readers for future issues. The low response to the survey can affect its representativity. The editorial board will take readers' wishes into consideration when selecting material for future issues of the journal.

Relationship between xerostomia and salivary flow rates in HIV-infected individuals.

PubMed

Nittayananta, Wipawee; Chanowanna, Nilnara; Pruphetkaew, Nannapat; Nauntofte, Birgitte

2013-08-01

The aim of the present study was to determine the relationship between self-reported xerostomia and salivary flow rates among HIV-infected individuals. A cross-sectional study was performed on 173 individuals (81 HIV-infected individuals, mean age: 32 years, and 92 non-HIV controls, mean age: 30 years). Subjective complaints of dry mouth, based on a self-report of xerostomia questions, and dry mouth, based on a visual analogue scale (VAS), were recorded along with measurements of salivary flow rate of both unstimulated and wax-stimulated whole saliva. The relationship between subjective responses to the xerostomia questions, the VAS of dry mouth, and objective measurements of salivary flow rates were analyzed. Responses to the questions--Do you carry water or a saliva substitute? and Have you had taste disturbance?--were significantly different between HIV-infected and non-HIV individuals (P < 0.05). Individuals' responses to questions concerning dry mouth were significantly correlated with a low unstimulated salivary flow rate. A significant correlation between the VAS of dry mouth and salivary flow rates was observed (P = 0.023). Responses to self-reported xerostomia questions reflects low unstimulated salivary flow rates. Thus, questions concerning dry mouth might be useful tools to identify HIV-infected individuals with hyposalivation, especially at a resting stage. © 2013 Wiley Publishing Asia Pty Ltd.

Object permanence development in infants with motor handicaps.

PubMed

Fetters, L

1981-03-01

This study was an investigation of the effects of a motor handicap on the development of object permanence in the young child. Motor abilities were evaluated for 12 infants aged 13 to 29 months. Based on this evaluation, the children were described as manipulators or nonmanipulators in reference to their upper extremity skills. Their stage of object permanence was assessed using traditional and nontraditional assessments. Heart rate and visual tracking were recorded during the nontraditional assessment. Heart rate did not significantly relate to visual fixation or search response. There was, however, a significant difference (p less than .02) between stage achievement with traditional testing and age-appropriate levels. There was no significant difference between the nontraditional assessment and the age-appropriate levels. In addition, there was no significant difference in the development of object permanence between infants described as manipulators and those described as nonmanipulators. The last two findings suggest that infants with motor handicaps may develop object permanence at the expected ages, according to a nontraditional assessment.

Docetaxel/S-1 Versus Docetaxel/Capecitabine as First-Line Treatment for Advanced Breast Cancer

PubMed Central

Li, Jinyu; You, Junhao; Si, Wen; Zhu, Yanyun; Chen, Yi; Yang, Bo; Han, Chun; Linghu, Ruixia; Zhang, Xingyang; Jiao, Shunchang; Yang, Junlan

2015-01-01

Abstract The treatment efficacy of advanced breast cancer is still not promising. This study aimed to compare the efficacy and safety of docetaxel/S-1 (DS1) versus docetaxel/capecitabine (DX) as the first-line treatment for advanced breast cancer. From June 2008 to June 2013, 22 patients with advanced breast cancer were treated with the DS1 regimen. Another 26 age- and disease status-matched patients treated with the DX regimen served as controls. The 2 groups were compared in terms of time to progression (TTP), objective response rate, disease control rate, clinical benefit rate, and safety profiles. Median TTP did not differ significantly between the DS1 group and the DX group (9.04 vs 10.94 months, P = 0.473). There were no significant differences in objective response rate, disease control rate, and clinical benefit rate between the 2 groups. Both the DS1 and the DX regimens showed good tolerability. The 2 regimens showed no significant difference in adverse events except degree III hand-foot syndrome (DS1 0 vs DX 23.1%, P = 0.025). For the first-line treatment of advanced breast cancer, the DS1 and the DX regimens showed similar efficacy and safety. The DS1 regimen had less severe hand-foot syndrome than the DX regimen. PMID:26469889

Docetaxel/S-1 Versus Docetaxel/Capecitabine as First-Line Treatment for Advanced Breast Cancer: A Retrospective Study.

PubMed

Li, Jinyu; You, Junhao; Si, Wen; Zhu, Yanyun; Chen, Yi; Yang, Bo; Han, Chun; Linghu, Ruixia; Zhang, Xingyang; Jiao, Shunchang; Yang, Junlan

2015-10-01

The treatment efficacy of advanced breast cancer is still not promising. This study aimed to compare the efficacy and safety of docetaxel/S-1 (DS1) versus docetaxel/capecitabine (DX) as the first-line treatment for advanced breast cancer.From June 2008 to June 2013, 22 patients with advanced breast cancer were treated with the DS1 regimen. Another 26 age- and disease status-matched patients treated with the DX regimen served as controls. The 2 groups were compared in terms of time to progression (TTP), objective response rate, disease control rate, clinical benefit rate, and safety profiles.Median TTP did not differ significantly between the DS1 group and the DX group (9.04 vs 10.94 months, P = 0.473). There were no significant differences in objective response rate, disease control rate, and clinical benefit rate between the 2 groups. Both the DS1 and the DX regimens showed good tolerability. The 2 regimens showed no significant difference in adverse events except degree III hand-foot syndrome (DS1 0 vs DX 23.1%, P = 0.025).For the first-line treatment of advanced breast cancer, the DS1 and the DX regimens showed similar efficacy and safety. The DS1 regimen had less severe hand-foot syndrome than the DX regimen.

Effects of larkspur (Delphinium barbeyi) on heart rate and electrically evoked electromyographic response of the external anal sphincter in cattle.

PubMed

Green, Benedict T; Pfister, James A; Cook, Daniel; Welch, Kevin D; Stegelmeier, Bryan L; Lee, Stephen T; Gardner, Dale R; Knoppel, Edward L; Panter, Kip E

2009-04-01

OBJECTIVE-To determine whether larkspur-derived N-(methylsuccinimido) anthranoyllycoctonine (MSAL)-type alkaloids alter heart rate and electrically evoked electromyographic (eEMG) response of the external anal sphincter (EAS) in cattle and whether these effects can be reversed by acetylcholinesterase inhibitors. ANIMALS-12 beef heifers and 4 cows. PROCEDURES-3 or 4 heifers were used in 1 or 2 of 7 dose-response experiments; heart rate and EAS eEMG response were assessed before and 24 hours after oral treatment with larkspur (doses equivalent to 0.5 to 15 mg of MSAL-type alkaloids/kg). In 3 subsequent experiments, 3 heifers (1 of which was replaced with another heifer in the control experiment) each received 10 mg of MSAL-type alkaloids/kg and were injected IV with physostigmine (0.04 mg/kg), neostigmine (0.04 mg/kg), or saline (0.9% NaCl) solution 24 hours later, prior to assessment. Additionally, EAS eEMG response was measured in 4 cows before and after epidural administration of 2% lidocaine hydrochloride. RESULTS-Larkspur-treated heifers developed dose-related increases in heart rate and decreases in EAS eEMG response. Twenty-four hours after administration of MSAL-type alkaloids, neostigmine decreased heart rate but did not affect eEMG response, whereas physostigmine did not affect heart rate but caused a 2-fold increase in eEMG response. In cows, epidural anesthesia did not alter eEMG response, suggesting that transdermal stimulation of the EAS pudendal innervation did not occur. CONCLUSIONS AND CLINICAL RELEVANCE-In cattle, cardiac effects and muscle weakness or loss of EAS eEMG response induced by larkspur-derived MSAL-type alkaloids were reversed by neostigmine or physostigmine, respectively. Treatment with anticholinesterase inhibitors may alter the clinical effects of larkspur poisoning in cattle.

The Effect of Repeated Virtual Nicotine Cue Exposure Therapy on the Psychophysiological Responses: A Preliminary Study

PubMed Central

Choi, Jung-Seok; Park, Sumi; Lee, Jun-Young; Jung, Hee-Yeon; Lee, Hae-Woo; Jin, Chong-Hyeon

2011-01-01

Objective Smoking related cues may elicit smoking urges and psychophysiological responses in subjects with nicotine dependence. This study aimed to investigate the effect of repeated virtual cue exposure therapy using the surround-screen based projection wall system on the psychophysiological responses in nicotine dependence. Methods The authors developed 3-dimensional neutral and smoking-related environments using virtual reality (VR) technology. Smoking-related environment was a virtual bar, which comprised both object-related and social situation cues. Ten subjects with nicotine dependence participated in 4-week (one session per week) virtual cue exposure therapy. Psychophysiological responses [electromyography (EMG), skin conductance (SC), and heart rate] and subjective nicotine craving were acquired during each session. Results VR nicotine cue elicited greater psychophysiological responses and subjective craving for smoking than did neutral cue, and exposure to social situation cues showed greater psychophysiological responses in SC and EMG than did object-related cues. This responsiveness decreased during the course of repeated therapy. Conclusion The present study found that both psychophysiological responses and subjective nicotine craving were greater to nicotine cue exposure via projection wall VR system than to neutral cues and that enhanced cue reactivity decreased gradually over the course of repeated exposure therapy. These results suggest that VR cue exposure therapy combined with psychophysiological response monitoring may be an alternative treatment modality for smoking cessation, although the current findings are preliminary. PMID:21852993

Reliability of a Parallel Pipe Network

NASA Technical Reports Server (NTRS)

Herrera, Edgar; Chamis, Christopher (Technical Monitor)

2001-01-01

The goal of this NASA-funded research is to advance research and education objectives in theoretical and computational probabilistic structural analysis, reliability, and life prediction methods for improved aerospace and aircraft propulsion system components. Reliability methods are used to quantify response uncertainties due to inherent uncertainties in design variables. In this report, several reliability methods are applied to a parallel pipe network. The observed responses are the head delivered by a main pump and the head values of two parallel lines at certain flow rates. The probability that the flow rates in the lines will be less than their specified minimums will be discussed.

The Effects of Elevated Temperatures on the Response of Resins Under Dynamic and Static Loadings

NASA Technical Reports Server (NTRS)

Gilat, Amos

2005-01-01

The overall objective of the research is to experimentally study the combined effects of temperature and strain rate on the response of two resins that are commonly used for the matrix material in composites. The resins are loaded at various temperatures in shear and in tension over a wide range of strain rates. These two types of loadings provide an opportunity to examine also the effect that temperature might have on the effects of the hydrostatic stress component on the material response. The experimental data provide the information needed for NASA scientists for the development of a nonlinear, strain rate, and temperature dependent deformation and strength models for composites that can subsequently be used in design. This year effort was directed into the development and testing of the epoxy resin at elevated temperatures. Two types of epoxy resins were tested in shear at high strain rates of about 10(exp-4)/s and elevated temperatures of 50 and 8OC. The results show that the temperature significantly affects the response of epoxy.

Effects of Social versus Musical Antecedents on Communication Responsiveness in Five Children with Developmental Disabilities.

PubMed

Braithwaite; Sigafoos

1999-01-01

The present study involved a comparison of social versus musical antecedents on communication responsiveness in five children with developmental disabilities. During the social antecedent condition, the teacher presented opportunities for the children to greet, name objects, and request materials. In the musical antecedent condition, these same opportunities were embedded within a music/singing activity. A reversal design was used to compare the percentage of opportunities with appropriate communication responses across the two conditions. For three of the five children, the musical antecedent condition was associated with higher percentages of appropriate communication responses. For the other two children, the two conditions were associated with approximately equal rates of appropriate communication. Across both conditions, appropriate responses were more likely during opportunities for greeting and requesting than during opportunities to name objects. The results suggest that embedding communication opportunities within a musical activity may lead to increased appropriate communication responses for some children with developmental disabilities.

Prognostic significance of clinical presentation, induction and rescue treatment in 42 cases of canine centroblastic diffuse large B-cell multicentric lymphoma in the United Kingdom.

PubMed

Davies, O; Szladovits, B; Polton, G; Garden, O A; Leo, C; Lara-Garcia, A

2018-06-01

Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B-cell lymphoma treated with either a COP-type (35%) or CHOP-type (64%) induction chemotherapy. The objective response rate to induction therapy was 94%; entire dogs had a greater rate of complete vs partial remissions than neutered dogs (P = .017). Median progression-free survival for the first remission (PFS1) was 182 days; absence of anaemia at diagnosis (P = .002) and pretreatment neutrophil:lymphocyte ratio (NLR) below 9.44 (P = .015) were independently predictive of longer PFS1. Fifty-eight percent of dogs received rescue protocols with an objective response rate of 81%; 31% of dogs received further rescue protocols (up to a total of 5) and the median number of protocols administered were 2. Median overall survival (OS) was 322 days, the 1-year survival rate was 38% and the 2-year survival rate was 9%. Lymphocyte:monocyte ratio above 1.43 (P = .031), NLR below 11.44 (P = .009), the combination of induction and rescue therapy (P = .030) and the total number of doxorubicin doses used (P = .002) were independently predictive of longer OS. Use of a COP-type protocol induction compared with CHOP did not undermine OS providing doxorubicin was used as rescue therapy. © 2017 John Wiley & Sons Ltd.

Reliability of Autonomic Responses and Malaise Across Multiple Motion Sickness Stimulation Tests

NASA Technical Reports Server (NTRS)

Stout, Cynthia S.; Toscano, William B.; Cowings, Patricia S.

1993-01-01

There is general agreement that a high degree of variability exists between subjects in their autonomic nervous system responses to motion sickness stimulation. Additionally, a paucity of data exists that examines the variability within an individual across repeated motion sickness tests. Investigators have also examined the relationship of autonomic responses to motion sickness development. These investigations have used analyses at discrete points in time to describe this relationship. This approach fails to address the time course of autonomic responses and malaise development throughout the motion sickness test. Our objectives were to examine the reliability of autonomic responses and malaise using the final minute of the motion sickness test across five testing occasions, to examine the reliability of the change in autonomic responses and the change in malaise across five testing occasions, and to examine the relationship between changes in autonomic responses and changes in malaise level across the entire motion sickness test. Our results indicate that, based on the final minute of testing, the autonomic responses of heart rate, blood volume pulse, and respiration rate are moderately stable across multiple tests. Changes in heart rate, blood volume pulse, respiration rate, and malaise throughout the test duration were less stable across the tests. We attribute this instability to variations in individual susceptibility and the error associated with estimating a measure of autonomic gain.

Clinical outcome and prognosis of carbon ion radiotherapy on thoracic malignant tumors

NASA Astrophysics Data System (ADS)

Li, Sha

Objective To evaluate the therapeutic efficacy and side-response of high-LET carbon ion radiotherapy on thoracic malignant tumors. Methods Ten patients with pathological confirmed thoracic malignant tumors received treatment using heavy ion accelerator, which included 6 cases with non-small lung cancer, one case with small lung cancer, 2 cases with metastatic sarcomas and one case with invasive thymoma. The applied regimen included fractioned dose (5.5-6.8GyE/Fraction), one faction/day, and 7 fractions/week. The total dose ranged from 55 to 70 GyE. Results The short-term results showed that the response rate (the complete response (CR) rate +the partial response (PR) rate) was 10% at the first month, 40% at the third month and 90% at the sixth month. The overall response rate was 90% and the rate of stable disease was 10%. There was no relation between the response rate and tumor pathology (P>0.05) while significance between the response rate and the tumor volume.At median follow-up of 27 months (range, 6 to 36 months), the local control rate and free-disease rate were respectively 100% an 90% at the first year, 90% and 80% at the secondary year, 80% and 70% at the third year. The death rate due to disease progression was 20% and the non-specific death rate was 10%. Side and toxicity effects: Grade I skin effect occurred in three cases and Grade I lung effect occurred in two cases. The blood counts didn’t reach significance among pre-radiation course, peri-radiation course and post-radiation course (P>0.05). The subgoups of T cells detected in humoral immunity and cytoimmunity didn’t change between pre-radiation and post radiation(P>0.05). Conclusions Carbon ion radiotherapy is effective and safe in the management of patients with thoracic malignant tumors. There were no obvious side effects. The long term of clinical outcome and the late effect need to be further observed.

Causal reports: Context-dependent contributions of intuitive physics and visual impressions of launching.

PubMed

Vicovaro, Michele

2018-05-01

Everyday causal reports appear to be based on a blend of perceptual and cognitive processes. Causality can sometimes be perceived automatically through low-level visual processing of stimuli, but it can also be inferred on the basis of an intuitive understanding of the physical mechanism that underlies an observable event. We investigated how visual impressions of launching and the intuitive physics of collisions contribute to the formation of explicit causal responses. In Experiment 1, participants observed collisions between realistic objects differing in apparent material and hence implied mass, whereas in Experiment 2, participants observed collisions between abstract, non-material objects. The results of Experiment 1 showed that ratings of causality were mainly driven by the intuitive physics of collisions, whereas the results of Experiment 2 provide some support to the hypothesis that ratings of causality were mainly driven by visual impressions of launching. These results suggest that stimulus factors and experimental design factors - such as the realism of the stimuli and the variation in the implied mass of the colliding objects - may determine the relative contributions of perceptual and post-perceptual cognitive processes to explicit causal responses. A revised version of the impetus transmission heuristic provides a satisfactory explanation for these results, whereas the hypothesis that causal responses and intuitive physics are based on the internalization of physical laws does not. Copyright © 2018 Elsevier B.V. All rights reserved.

Behavioral demand modulates object category representation in the inferior temporal cortex

PubMed Central

Emadi, Nazli

2014-01-01

Visual object categorization is a critical task in our daily life. Many studies have explored category representation in the inferior temporal (IT) cortex at the level of single neurons and population. However, it is not clear how behavioral demands modulate this category representation. Here, we recorded from the IT single neurons in monkeys performing two different tasks with identical visual stimuli: passive fixation and body/object categorization. We found that category selectivity of the IT neurons was improved in the categorization compared with the passive task where reward was not contingent on image category. The category improvement was the result of larger rate enhancement for the preferred category and smaller response variability for both preferred and nonpreferred categories. These specific modulations in the responses of IT category neurons enhanced signal-to-noise ratio of the neural responses to discriminate better between the preferred and nonpreferred categories. Our results provide new insight into the adaptable category representation in the IT cortex, which depends on behavioral demands. PMID:25080572

Family doctors' views of pharmaceutical sales representatives: assessment scale development.

PubMed

Kersnik, Janko; Klemenc-Ketis, Zalika; Petek-Ster, Marija; Tusek-Bunc, Ksenija; Poplas-Susic, Tonka; Kolsek, Marko

2011-08-01

The prescribing patterns depend on the physicians' attitudes and their subjective norms towards prescribing a particular drug, as well as on their personal experience with a particular drug. The physicians are affected by their interactions with pharmaceutical industry. The objectives were to develop a scale for assessment of pharmaceutical sales representatives (PSRs) by the family doctors (FDs) and to determine factors for their evaluation. Cross-sectional anonymous postal study. We included a random sample of 250 Slovenian FDs. Settings. Slovenian FDs' surgeries. The score of various items regarding FDs' assessment of PSRs on a 7-point Likert scale. We got 163 responses (65.2% response rate). The most important characteristic of PSRs, as rated by respondents on the scale from 1 to 7, was the fact that they did not mislead when presenting products' information. The second most important characteristic was the ability to provide objective information about the product. The first three most important characteristics, as rated by the respondents by themselves, were 'Shows good knowledge on the promoted subject', 'Provides objective product information' and 'Makes brief and exact visits'. Cronbach's alpha of the composite scale was 0.844. Factor analysis revealed three PSRs' factors: selling skills, communicating skills and sense of trustworthiness. FDs evaluate PSRs mainly by their managerial skills and trustworthiness. The scale proved to be a reliable tool for assessing PSRs by FDs.

MDMA does not alter responses to the Trier Social Stress Test in humans.

PubMed

Bershad, Anya K; Miller, Melissa A; de Wit, Harriet

2017-07-01

±3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a stimulant-psychedelic drug with unique social effects. It may dampen reactivity to negative social stimuli such as social threat and rejection. Perhaps because of these effects, MDMA has shown promise as a treatment for post-traumatic stress disorder (PTSD). However, the effect of single doses of MDMA on responses to an acute psychosocial stressor has not been tested. In this study, we sought to test the effects of MDMA on responses to stress in healthy adults using a public speaking task. We hypothesized that the drug would reduce responses to the stressful task. Volunteers (N = 39) were randomly assigned to receive placebo (N = 13), 0.5 mg/kg MDMA (N = 13), or 1.0 mg/kg MDMA (N = 13) during a stress and a no-stress session. Dependent measures included subjective reports of drug effects and emotional responses to the task, as well as salivary cortisol, heart rate, and blood pressure. The stress task produced its expected increase in physiological responses (cortisol, heart rate) and subjective ratings of stress in all three groups, and MDMA produced its expected subjective and physiological effects. MDMA alone increased ratings of subjective stress, heart rate, and saliva cortisol concentrations, but contrary to our hypothesis, it did not moderate responses to the Trier Social Stress Test. Despite its efficacy in PTSD and anxiety, MDMA did not reduce either the subjective or objective responses to stress in this controlled study. The conditions under which MDMA relieves responses to negative events or memories remain to be determined.

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

Rubin, M. B.; Vorobiev, O.; Vitali, E.

Here, a large deformation thermomechanical model is developed for shock loading of a material that can exhibit elastic and inelastic anisotropy. Use is made of evolution equations for a triad of microstructural vectors m i(i=1,2,3) which model elastic deformations and directions of anisotropy. Specific constitutive equations are presented for a material with orthotropic elastic response. The rate of inelasticity depends on an orthotropic yield function that can be used to model weak fault planes with failure in shear and which exhibits a smooth transition to isotropic response at high compression. Moreover, a robust, strongly objective numerical algorithm is proposed formore » both rate-independent and rate-dependent response. The predictions of the continuum model are examined by comparison with exact steady-state solutions. Also, the constitutive equations are used to obtain a simplified continuum model of jointed rock which is compared with high fidelity numerical solutions that model a persistent system of joints explicitly in the rock medium.« less

How does aging affect the types of error made in a visual short-term memory ‘object-recall’ task?

PubMed Central

Sapkota, Raju P.; van der Linde, Ian; Pardhan, Shahina

2015-01-01

This study examines how normal aging affects the occurrence of different types of incorrect responses in a visual short-term memory (VSTM) object-recall task. Seventeen young (Mean = 23.3 years, SD = 3.76), and 17 normally aging older (Mean = 66.5 years, SD = 6.30) adults participated. Memory stimuli comprised two or four real world objects (the memory load) presented sequentially, each for 650 ms, at random locations on a computer screen. After a 1000 ms retention interval, a test display was presented, comprising an empty box at one of the previously presented two or four memory stimulus locations. Participants were asked to report the name of the object presented at the cued location. Errors rates wherein participants reported the names of objects that had been presented in the memory display but not at the cued location (non-target errors) vs. objects that had not been presented at all in the memory display (non-memory errors) were compared. Significant effects of aging, memory load and target recency on error type and absolute error rates were found. Non-target error rate was higher than non-memory error rate in both age groups, indicating that VSTM may have been more often than not populated with partial traces of previously presented items. At high memory load, non-memory error rate was higher in young participants (compared to older participants) when the memory target had been presented at the earliest temporal position. However, non-target error rates exhibited a reversed trend, i.e., greater error rates were found in older participants when the memory target had been presented at the two most recent temporal positions. Data are interpreted in terms of proactive interference (earlier examined non-target items interfering with more recent items), false memories (non-memory items which have a categorical relationship to presented items, interfering with memory targets), slot and flexible resource models, and spatial coding deficits. PMID:25653615

How does aging affect the types of error made in a visual short-term memory 'object-recall' task?

PubMed

Sapkota, Raju P; van der Linde, Ian; Pardhan, Shahina

2014-01-01

This study examines how normal aging affects the occurrence of different types of incorrect responses in a visual short-term memory (VSTM) object-recall task. Seventeen young (Mean = 23.3 years, SD = 3.76), and 17 normally aging older (Mean = 66.5 years, SD = 6.30) adults participated. Memory stimuli comprised two or four real world objects (the memory load) presented sequentially, each for 650 ms, at random locations on a computer screen. After a 1000 ms retention interval, a test display was presented, comprising an empty box at one of the previously presented two or four memory stimulus locations. Participants were asked to report the name of the object presented at the cued location. Errors rates wherein participants reported the names of objects that had been presented in the memory display but not at the cued location (non-target errors) vs. objects that had not been presented at all in the memory display (non-memory errors) were compared. Significant effects of aging, memory load and target recency on error type and absolute error rates were found. Non-target error rate was higher than non-memory error rate in both age groups, indicating that VSTM may have been more often than not populated with partial traces of previously presented items. At high memory load, non-memory error rate was higher in young participants (compared to older participants) when the memory target had been presented at the earliest temporal position. However, non-target error rates exhibited a reversed trend, i.e., greater error rates were found in older participants when the memory target had been presented at the two most recent temporal positions. Data are interpreted in terms of proactive interference (earlier examined non-target items interfering with more recent items), false memories (non-memory items which have a categorical relationship to presented items, interfering with memory targets), slot and flexible resource models, and spatial coding deficits.

Increasing the response rate of text messaging data collection: a delayed randomized controlled trial

PubMed Central

Li, Ye; Wang, Wei; Wu, Qiong; van Velthoven, Michelle Helena; Chen, Li; Du, Xiaozhen; Zhang, Yanfeng; Rudan, Igor; Car, Josip

2015-01-01

Objective To test the effectiveness of multiple interventions on increasing the response rate of text messaging for longitudinal data collection. Methods Our cohort included 283 caregivers of children aged 6–12 months who were participating in an anemia program in rural China. Using text messages to collect data on anemia medication adherence, we conducted a delayed randomized controlled trial to test multiple interventions (an additional four reminders; a ¥5.0 (US$0.79) credit reward for replying; and a feedback text message). After a 6-week pilot study with week 7 as the baseline measurement, we randomly allocated all participants into two groups: group 1 (n = 142) and group 2 (n = 141). During weeks 8–11, we introduced the interventions to group 1, and in weeks 12–15 the intervention was introduced to both groups. We compared the response rates between groups and explored factors affecting the response rate. Results During weeks 8–11, the response rates in group 1 increased and were significantly higher than in group 2 (p<0.05). During weeks 12–15, the response rate increased significantly in group 2 (p>0.05) and slightly decreased in group 1. Younger participants or participants who had children with lower hemoglobin concentration were more likely to reply (p = 0.02). Sending four reminders on the second day contributed to only 286 (11.7%) extra text messages. Discussion Our study showed that multiple interventions were effective in increasing response rate of text messaging data collection in rural China. Conclusions Larger multi-site studies are needed to find the most effective way of using these interventions to allow usage of text messaging data collection for health research. PMID:25332355

Topical tretinoin in the treatment of vulvar lichen sclerosus: an advisable option?

PubMed

Borghi, Alessandro; Corazza, Monica; Minghetti, Sara; Virgili, Annarosa

2015-01-01

To assess the effectiveness and safety of a 24-week application of tretinoin 0.025% cream, with an alternate-day regimen, in achieving control of VLS signs and symptoms. 17 patients affected with VLS were included. The main efficacy parameters were the response rate, as defined by protocol parameters, the rate of patients achieving an improvement from baseline of ≥75% in the subjective and objective scores, and the mean reduction in subjective and objective scores throughout the treatment. The safety of the treatment was also assessed. By the end of the 24-week treatment, 12 patients (70.6%) experienced a response; 35.3% and 17.6% of patients achieved an improvement of at least 75% in subjective and objective scores, respectively. Mean scores of itching, leukoderma (pallor) and hyperkeratosis decreased significantly in the study patients, and none presented itching-related excoriations. Erythema increased compared with baseline. Six patients (35.29%) experienced some side effects related to tretinoin, mainly mild erythema and burning. None of the subjects discontinued the treatment because of side effects. Tretinoin 0.025% cream applied for 24 weeks may represent a useful alternative option to corticosteroids in the treatment of active VLS, acting particularly on hyperkeratosis and pallor.

The Effects of Prenatal Maternal Stress on Early Temperament: The 2011 Queensland Flood Study.

PubMed

Simcock, Gabrielle; Elgbeili, Guillaume; Laplante, David P; Kildea, Sue; Cobham, Vanessa; Stapleton, Helen; Austin, Marie-Paule; Brunet, Alain; King, Suzanne

2017-06-01

This study examined the effects of disaster-related prenatal maternal stress on infant temperament and whether the sex of the infant or the timing of the stressor in pregnancy would moderate the effects. Mothers' objective experiences of a sudden-onset flood in Queensland, Australia, their subjective emotional reactions, and cognitive appraisal of the event were assessed. At 6 months postpartum, 121 mothers reported their infant's temperament on the 5 dimensions of the Short Temperament Scale for Infants. When controlling for postnatal maternal factors, subjective prenatal maternal stress and cognitive appraisal of the disaster were associated with easier aspects of infant temperament. However, several interesting interactions emerged showing negative effects of the flood. With higher levels of objective hardship in pregnancy, boys (but not girls) received more irritable temperament ratings. When the flood occurred early in pregnancy, higher levels of objective hardship predicted more arrhythmic infant temperament. Finally, mothers whose emotional response to the flood exceeded the hardship they endured reported significantly more active-reactive infants. Prenatal maternal stress from a natural disaster predicted more difficult temperament ratings that were moderated by infant sex, timing of the flood in gestation, and mother's emotional response to the disaster.

Dual physiological rate measurement instrument

NASA Technical Reports Server (NTRS)

Cooper, Tommy G. (Inventor)

1990-01-01

The object of the invention is to provide an instrument for converting a physiological pulse rate into a corresponding linear output voltage. The instrument which accurately measures the rate of an unknown rectangular pulse wave over an extended range of values comprises a phase-locked loop including a phase comparator, a filtering network, and a voltage-controlled oscillator, arranged in cascade. The phase comparator has a first input responsive to the pulse wave and a second input responsive to the output signal of the voltage-controlled oscillator. The comparator provides a signal dependent on the difference in phase and frequency between the signals appearing on the first and second inputs. A high-input impedance amplifier accepts an output from the filtering network and provides an amplified output DC signal to a utilization device for providing a measurement of the rate of the pulse wave.

A physiologically based nonhomogeneous Poisson counter model of visual identification.

PubMed

Christensen, Jeppe H; Markussen, Bo; Bundesen, Claus; Kyllingsbæk, Søren

2018-04-30

A physiologically based nonhomogeneous Poisson counter model of visual identification is presented. The model was developed in the framework of a Theory of Visual Attention (Bundesen, 1990; Kyllingsbæk, Markussen, & Bundesen, 2012) and meant for modeling visual identification of objects that are mutually confusable and hard to see. The model assumes that the visual system's initial sensory response consists in tentative visual categorizations, which are accumulated by leaky integration of both transient and sustained components comparable with those found in spike density patterns of early sensory neurons. The sensory response (tentative categorizations) feeds independent Poisson counters, each of which accumulates tentative object categorizations of a particular type to guide overt identification performance. We tested the model's ability to predict the effect of stimulus duration on observed distributions of responses in a nonspeeded (pure accuracy) identification task with eight response alternatives. The time courses of correct and erroneous categorizations were well accounted for when the event-rates of competing Poisson counters were allowed to vary independently over time in a way that mimicked the dynamics of receptive field selectivity as found in neurophysiological studies. Furthermore, the initial sensory response yielded theoretical hazard rate functions that closely resembled empirically estimated ones. Finally, supplied with a Naka-Rushton type contrast gain control, the model provided an explanation for Bloch's law. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population*

PubMed Central

Hong, Wei; Wang, Kai; Zhang, Yi-ping; Kou, Jun-yan; Hong, Dan; Su, Dan; Mao, Wei-min; Yu, Xin-min; Xie, Fa-jun; Wang, Xiao-jian

2013-01-01

Objective: The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C677T excision repair cross-complementation group 1 (ERCC1) genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Methods: A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regimens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 C118T were genotyped using the TaqMan methods. Results: The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype (TT or CT) (41.2% versus 19.1%, P=0.01). Median time to progression (TTP) of patients with MTHFR CC genotype was longer than that of patients with variant genotype (7.6 months versus 5.0 months, P=0.003). No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. Conclusions: Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum. PMID:23463763

Squamous NSCLC Improves with Atezolizumab Plus Chemo.

PubMed

2018-06-08

A combination of chemotherapy and the PD-L1 inhibitor atezolizumab may be an effective initial therapy for patients with advanced squamous non-small cell lung cancer. In a clinical trial, patients who received the combination had longer progression-free survival, a higher objective response rate, and a longer duration of response than patients who received chemotherapy alone, regardless of PD-L1 expression level. ©2018 American Association for Cancer Research.

Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial.

PubMed

Balar, Arjun V; Galsky, Matthew D; Rosenberg, Jonathan E; Powles, Thomas; Petrylak, Daniel P; Bellmunt, Joaquim; Loriot, Yohann; Necchi, Andrea; Hoffman-Censits, Jean; Perez-Gracia, Jose Luis; Dawson, Nancy A; van der Heijden, Michiel S; Dreicer, Robert; Srinivas, Sandy; Retz, Margitta M; Joseph, Richard W; Drakaki, Alexandra; Vaishampayan, Ulka N; Sridhar, Srikala S; Quinn, David I; Durán, Ignacio; Shaffer, David R; Eigl, Bernhard J; Grivas, Petros D; Yu, Evan Y; Li, Shi; Kadel, Edward E; Boyd, Zachary; Bourgon, Richard; Hegde, Priti S; Mariathasan, Sanjeev; Thåström, AnnChristine; Abidoye, Oyewale O; Fine, Gregg D; Bajorin, Dean F

2017-01-07

First-line chemotherapy for patients with cisplatin-ineligible locally advanced or metastatic urothelial carcinoma is associated with short response duration, poor survival, and high toxicity. This study assessed atezolizumab (anti-programmed death-ligand 1 [PD-L1]) as treatment for metastatic urothelial cancer in cisplatin-ineligible patients. For this single-arm, multicentre, phase 2 study, in 47 academic medical centres and community oncology practices in seven countries in North America and Europe, we recruited previously untreated patients with locally advanced or metastatic urothelial cancer who were cisplatin ineligible. Patients were given 1200 mg intravenous atezolizumab every 21 days until progression. The primary endpoint was independently confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (central review), assessed in prespecified subgroups based on PD-L1 expression and in all patients. All participants who received one or more doses of atezolizumab were included in the primary and safety analyses. This study was registered with ClinicalTrials.gov, number NCT02108652. Between June 9, 2014, and March 30, 2015, we enrolled 123 patients, of whom 119 received one or more doses of atezolizumab. At 17·2 months' median follow-up, the objective response rate was 23% (95% CI 16 to 31), the complete response rate was 9% (n=11), and 19 of 27 responses were ongoing. Median response duration was not reached. Responses occurred across all PD-L1 and poor prognostic factor subgroups. Median progression-free survival was 2·7 months (2·1 to 4·2). Median overall survival was 15·9 months (10·4 to not estimable). Tumour mutation load was associated with response. Treatment-related adverse events that occurred in 10% or more of patients were fatigue (36 [30%] patients), diarrhoea (14 [12%] patients), and pruritus (13 [11%] patients). One treatment-related death (sepsis) occurred. Nine (8%) patients had an adverse event leading to treatment discontinuation. Immune-mediated events occurred in 14 (12%) patients. Atezolizumab showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use in untreated metastatic urothelial cancer. F Hoffmann-La Roche, Genentech. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensitivity to systemic therapy for metastatic breast cancer in CHEK2 1100delC mutation carriers.

PubMed

Kriege, Mieke; Jager, Agnes; Hollestelle, Antoinette; Berns, Els M J J; Blom, Jannet; Meijer-van Gelder, Marion E; Sieuwerts, Anieta M; van den Ouweland, Ans; Collée, J Margriet; Kroep, Judith R; Martens, John W M; Hooning, Maartje J; Seynaeve, Caroline

2015-10-01

The role of CHEK2 in DNA repair by homologous recombination suggests that CHEK2-associated breast cancer (BC) patients might be more sensitive to chemotherapy inducing double-strand DNA breaks, but results hereon are lacking. We compared the sensitivity to first-line chemotherapy and endocrine therapy between CHEK2 1100delC and non-CHEK2 metastatic breast cancer (MBC) patients. Sixty-two CHEK2 1100delC MBC patients were selected from three cohorts genotyped for CHEK2 1100delC (one non-BRCA1/2 cohort and two sporadic cohorts). Controls were 62 non-CHEK2 MBC patients, matched for age at and year of primary BC diagnosis, and year of metastatic disease. Objective response rate (complete and partial response) to, and progression-free survival (PFS) and overall survival (OS) after start of first-line chemotherapy and endocrine therapy were compared between CHEK2 and non-CHEK2 patients. Median age at BC diagnosis was 46 and 51 years at MBC diagnosis. First-line chemotherapy consisted of anthracycline-based chemotherapy (n = 73), taxanes (n = 16), CMF(-like) chemotherapy (n = 33) and taxane/anthracycline regimens (n = 2). CHEK2 and non-CHEK2 patients had a comparable objective response rate (44 vs. 52 %). Also, PFS and OS after start of chemotherapy were comparable between both patient groups (hazard ratio 0.91; 95 % confidence interval 0.63-1.30 and 1.03; 95 % CI 0.71-1.49, respectively). Thirty-six CHEK2 and 32 non-CHEK2 patients received first-line endocrine therapy (mainly tamoxifen) for MBC. No significant differences were observed in objective response rate to, and PFS and OS after start of endocrine therapy. No differential efficacy of chemotherapy and endocrine therapy given for MBC was observed in CHEK2 versus non-CHEK2 patients.

Heart Rate Response to a Timed Walk & Cardiovascular Outcomes in Older Adults: The Cardiovascular Health Study

PubMed Central

Girotra, Saket; Kitzman, Dalane W.; Kop, Willem J.; Stein, Phyllis K.; Gottdiener, John S.; Mukamal, Kenneth J.

2012-01-01

OBJECTIVES To determine the relationship between heart rate response during low-grade physical exertion (six-minute walk) with mortality and adverse cardiovascular outcomes in the elderly. METHODS Participants in the Cardiovascular Health Study, who completed a six-minute walk test, were included. We used delta heart rate (difference between post-walk heart rate and resting heart rate) as a measure of chronotropic response and examined its association with 1) all-cause mortality and 2) incident coronary heart disease (CHD) event, using multivariable Cox regression models. RESULTS We included 2224 participants (mean age 77±4 years; 60% women, 85% white). The average delta heart rate was 26 beats/min. Participants in the lowest tertile of delta heart rate (<20 beats/min) had higher risk-adjusted mortality (hazard ratio [HR] 1.18; 95% confidence interval [CI][1.00, 1.40]) and incident CHD (HR 1.37; 95% CI[1.05, 1.78]) compared to subjects in the highest tertile (≥30 beats/min), with a significant linear trend across tertiles (P for trend <0.05 for both outcomes). This relationship was not significant after adjustment for distance walked. CONCLUSION Impaired chronotropic response during six-minute walk test was associated with an increased risk of mortality and incident CHD among the elderly. This association was attenuated after adjusting for distance walked. PMID:22722364

Personality and Differential Treatment Response in Major Depression: A Randomized Controlled Trial Comparing Cognitive-Behavioural Therapy and Pharmacotherapy

PubMed Central

Bagby, R Michael; Quilty, Lena C; Segal, Zindel V; McBride, Carolina C; Kennedy, Sidney H; Costa, Paul T

2008-01-01

Objective Effective treatments for major depressive disorder exist, yet some patients fail to respond, or achieve only partial response. One approach to optimizing treatment success is to identify which patients are more likely to respond best to which treatments. The objective of this investigation was to determine if patient personality characteristics are predictive of response to either cognitive-behavioural therapy (CBT) or pharmacotherapy (PHT). Method Depressed patients completed the Revised NEO Personality Inventory, which measures the higher-order domain and lower-order facet traits of the Five-Factor Model of Personality, and were randomized to receive either CBT or PHT. Result Four personality traits—the higher-order domain neuroticism and 3 lower-order facet traits: trust, straightforwardness, and tendermindedness—were able to distinguish a differential response rate to CBT, compared with PHT. Conclusion The assessment of patient dimensional personality traits can assist in the selection and optimization of treatment response for depressed patients. PMID:18616856

Shindigs, brunches, and rodeos: the neural basis of event words.

PubMed

Bedny, Marina; Dravida, Swethasri; Saxe, Rebecca

2014-09-01

Events (e.g., "running" or "eating") constitute a basic type within human cognition and human language. We asked whether thinking about events, as compared to other conceptual categories, depends on partially independent neural circuits. Indirect evidence for this hypothesis comes from previous studies showing elevated posterior temporal responses to verbs, which typically label events. Neural responses to verbs could, however, be driven either by their grammatical or by their semantic properties. In the present experiment, we separated the effects of grammatical class (verb vs. noun) and semantic category (event vs. object) by measuring neural responses to event nouns (e.g., "the hurricane"). Participants rated the semantic relatedness of event nouns, as well as of two categories of object nouns-animals (e.g., "the alligator") and plants (e.g., "the acorn")-and three categories of verbs-manner of motion (e.g., "to roll"), emission (e.g., "to sparkle"), and perception (e.g., "to gaze"). As has previously been observed, we found larger responses to verbs than to object nouns in the left posterior middle (LMTG) and superior (LSTG) temporal gyri. Crucially, we also found that the LMTG responds more to event than to object nouns. These data suggest that part of the posterior lateral temporal response to verbs is driven by their semantic properties. By contrast, a more superior region, at the junction of the temporal and parietal cortices, responded more to verbs than to all nouns, irrespective of their semantic category. We concluded that the neural mechanisms engaged when thinking about event and object categories are partially dissociable.

Response to an Online Version of a PRAMS-like Survey in South Dakota.

PubMed

Binkley, Teresa; Beare, Tianna; Minett, Maggie; Koepp, Kriston; Wey, Howard; Specker, Bonny

2017-02-01

Objectives Increasing response rates for research surveys is challenging, especially in minority populations. A unique minority group in South Dakota is the American Indian (AI) representing about 9 % of the state's population and 15 % of the births. The purpose of this study was to determine race differences among White, AI, and Other Races (OR) in contact, participation, and response rates in the South Dakota Pregnancy Risk Assessment Monitoring System (SDPRAMS). We determined response rates of an online version and evaluated demographic characteristics associated with online response. Methods The SDPRAMS was sent to 1814 mothers randomly sampled from 2014 birth certificate files. Results The weighted response rate was 71.3 %, and varied significantly among the three races: 79.1 % for White race, 48.6 % for AI race, and 60.6 % for OR (p < 0.01). A higher percent of White mothers responded online than AI and OR (35, 25 and 26 %, respectively; p = 0.001); no difference between AI and OR. Online responders were more likely to be married, educated beyond high school and having annual incomes ≥$25,000 (p ≤ 0.01 for all), but only education (p < 0.001) and income (p = 0.05) remained significant in the logistic models. 26 % of White, 43 % of AI, and 46 % of OR online respondents used a smartphone to respond (p = 0.01). Conclusions Response rates differed among races. An online version of the PRAMS is a viable method of response to offer participants. Response to the online version via smartphone may increase response from minority populations, emphasizing the importance of mobile friendly formats.

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

Survey Methods to Optimize Response Rate in the National Dental Practice-Based Research Network.

PubMed

Funkhouser, Ellen; Vellala, Kavya; Baltuck, Camille; Cacciato, Rita; Durand, Emily; McEdward, Deborah; Sowell, Ellen; Theisen, Sarah E; Gilbert, Gregg H

2017-09-01

Surveys of health professionals typically have low response rates, and these rates have been decreasing in the recent years. We report on the methods used in a successful survey of dentist members of the National Dental Practice-Based Research Network. The objectives were to quantify the (1) increase in response rate associated with successive survey methods, (2) time to completion with each successive step, (3) contribution from the final method and personal contact, and (4) differences in response rate and mode of response by practice/practitioner characteristics. Dentist members of the network were mailed an invitation describing the study. Subsequently, up to six recruitment steps were followed: initial e-mail, two e-mail reminders at 2-week intervals, a third e-mail reminder with postal mailing a paper questionnaire, a second postal mailing of paper questionnaire, and staff follow-up. Of the 1,876 invited, 160 were deemed ineligible and 1,488 (87% of 1,716 eligible) completed the survey. Completion by step: initial e-mail, 35%; second e-mail, 15%; third e-mail, 7%; fourth e-mail/first paper, 11%; second paper, 15%; and staff follow-up, 16%. Overall, 76% completed the survey online and 24% on paper. Completion rates increased in absolute numbers and proportionally with later methods of recruitment. Participation rates varied little by practice/practitioner characteristics. Completion on paper was more likely by older dentists. Multiple methods of recruitment resulted in a high participation rate: Each step and method produced incremental increases with the final step producing the largest increase.

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

Increased pathological complete response rate after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or progesterone receptor-positive breast cancer

PubMed Central

Allevi, G; Strina, C; Andreis, D; Zanoni, V; Bazzola, L; Bonardi, S; Foroni, C; Milani, M; Cappelletti, M R; Gussago, F; Aguggini, S; Giardini, R; Martinotti, M; Fox, S B; Harris, A L; Bottini, A; Berruti, A; Generali, D

2013-01-01

Background: The objective of this study was to determine the optimal scheduling of 2.5 mg daily letrozole in neoadjuvant breast cancer patients to obtain pathological complete response (pathCR) and assess Ki-67 expression as an early predictor of response. Patients and methods: This single institution study comprised 120 oestrogen receptor (ER)-positive postmenopausal women with primary breast cancer (clinical stage ⩾T2, N0–1), from three sequential cohorts (cohort A of 40, cohort B of 40 and cohort C of 40 patients, respectively) based on different duration of the neoadjuvant letrozole. Biological markers such as ER, progesterone receptor, HER2 and Ki-67 expression were tested at diagnosis and at definitive surgery. Results: A total of 89 patients (75.4%) achieved an objective response with 44 (37.3%) clinical CRs and 45 (38.1%) partial responses. The clinical CRs were significantly observed in cohort C (23 out of 40 patients, 57.5%) and B (16 out of 38 patients, 42.1%) compared with cohort A (5 out of 40 patients, 12.5%) (P-value for trend <0.001). Letrozole induced a similar significant reduction in Ki-67 index after treatment in all cohorts. The pathCR rate was significantly more frequent in cohort C (7 out of 40 patients, 17.5%) than in cohort A (1 out of 40 patients, 2.5%) and B (2 out of 40 patients, 5.0%) (P-value for trend <0.04). Conclusion: One-year neoadjuvant letrozole therapy leads to a higher pathCR rate and may be the optimal length of drug exposure. PMID:23579222

Use of technology to facilitate physical activity in children with autism spectrum disorders: A pilot study.

PubMed

Bittner, Melissa D; Rigby, B Rhett; Silliman-French, Lisa; Nichols, David L; Dillon, Suzanna R

2017-08-01

Deficits in social behavior and communication skills are correlated with reduced gross motor skills in children with autism spectrum disorders (ASD). The ExerciseBuddy application (EB app) was designed to communicate these motor skills to those with ASD and integrates evidence-based practices such as visual support and video modeling supported by The National Professional Development Center on Autism Spectrum Disorders. The purpose of this study was to determine the effectiveness of the EB app in facilitating increased physiologic responses to physical activity via a continuous measurement of energy expenditure and heart rate versus practice-style teaching methods in children with ASD. Six children, ages 5 to 10years, diagnosed with ASD were recruited. Each participant performed a variety of locomotor or object control skills as defined by the Test of Gross Motor Development-2 once per week for 4weeks. Motor skills were communicated and demonstrated using either practice-style teaching methods or the instructional section of the EB app. Energy expenditure and heart rate were measured continuously during each 12-minute session. A Wilcoxon signed-rank test was performed to assess any differences between the use of the app and practice-style teaching methods. The use of the EB app elicited greater values for peak energy expenditure (p=0.043) and peak heart rate response (p=0.028) while performing locomotor skills but no differences were observed while performing object control skills. Similarities were observed with average physiologic responses between the use of the EB app and practice-style teaching methods. The use of the EB app may allow for a greater peak physiologic response during more dynamic movements and a similar average cardiovascular and metabolic response when compared to practice-style teaching methods in children with ASD. Published by Elsevier Inc.

Acoustic vibrations of metal nano-objects: Time-domain investigations

NASA Astrophysics Data System (ADS)

Crut, Aurélien; Maioli, Paolo; Del Fatti, Natalia; Vallée, Fabrice

2015-01-01

Theoretical and time-domain experimental investigations of the vibrational acoustic response of nano-objects are described focusing on metallic ones. Acoustic vibrations are modeled using a macroscopic-like approach based on continuum mechanics with the proper boundary conditions, a model which yields results in excellent agreement with the experimental ones and those of atomistic calculations, down to the nanometric scale. Vibrational mode excitation and detection mechanisms and the associated mode selection in ultrafast pump-probe spectroscopy are discussed, and the measured time-dependent signals in single and ensemble of nanoparticles modeled. The launched modes, their period and their damping rate are compared to experimental results obtained on ensembles of nano-objects with different composition, morphology and environment, and with size ranging from one to hundreds of nanometers. Recent extension of time-domain spectroscopy to individual nano-objects has shed new light on the vibrational responses of isolated nanoparticles, in particular on their damping, but also raises questions on the origin of its large particle to particle dispersion.

Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single arm, phase 2 trial

PubMed Central

Rosenberg, Jonathan E.; Hoffman-Censits, Jean; Powles, Tom; van der Heijden, Michiel S.; Balar, Arjun V.; Necchi, Andrea; Dawson, Nancy; O’Donnell, Peter H.; Balmanoukian, Ani; Loriot, Yohann; Srinivas, Sandy; Retz, Margitta M.; Grivas, Petros; Joseph, Richard W.; Galsky, Matthew D.; Fleming, Mark T.; Petrylak, Daniel P.; Perez-Gracia, Jose Luis; Burris, Howard A.; Castellano, Daniel; Canil, Christina; Bellmunt, Joaquim; Bajorin, Dean; Nickles, Dorothee; Bourgon, Richard; Frampton, Garrett M.; Cui, Na; Mariathasan, Sanjeev; Abidoye, Oyewale; Fine, Gregg D.; Dreicer, Robert

2017-01-01

Summary Background Patients with metastatic urothelial carcinoma have limited treatment options after failure of platinum-based chemotherapy. This multicenter, single-arm phase 2 trial evaluated atezolizumab, an engineered humanized IgG1 monoclonal antibody that binds selectively to programmed death–ligand 1 (PD-L1), in this population. Methods Three hundred and ten patients received atezolizumab (1200 mg, every 3 weeks). PD-L1 expression on tumor-infiltrating immune cells (IC) was prospectively assessed by immunohistochemistry. The co-primary endpoints were the objective response rate by RECIST v1.1 and immune modified RECIST. A hierarchical testing procedure was used to test whether the objective response rate was significantly higher than the historical control of 10% at alpha level of 0·05. Exploratory analyses included assessing the association between The Cancer Genome Atlas (TCGA) molecular subtypes, CD8+ T cell infiltration, mutation load, and clinical outcomes. Findings By independent review, objective response rates were 26% (95% CI 18 to 36) in the IC2/3 group, 18% (95% CI 13 to 24) in the IC1/2/3 group and 15% (95% CI 11 to 19) in all patients. With a median follow-up of 11·7 months, ongoing responses were observed in 84% of responders. The median duration of response was not reached (range 2·0*, 13·7* months, *censored). The median overall survival was 11·4 months (95% CI 9·0 to not estimable) in the IC2/3 group, 8·8 months (95% CI 7·1 to 10·6) in the IC1/2/3, and 7·9 months (95% CI 6·6 to 9·3) in all patients. Grade 3–4 related treatment-related adverse events occurred in 16% and grade 3–4 immune-mediated adverse events occurred in 5% of treated patients. Exploratory analyses showed TCGA subtypes and mutation load to be independently predictive for response to atezolizumab. Interpretation Atezolizumab demonstrated durable activity and good tolerability in this population. PD-L1 expression on immune cells was associated with response. This is the first report to show the association of TCGA subtypes with response to immune checkpoint inhibition and demonstrate the importance of mutation load as a biomarker of response to this class of agents in advanced urothelial carcinoma. Funding F. Hoffmann-La Roche Ltd. PMID:26952546

Statistical Application and Cost Saving in a Dental Survey

PubMed Central

Chyou, Po-Huang; Schroeder, Dixie; Schwei, Kelsey; Acharya, Amit

2017-01-01

Objective To effectively achieve a robust survey response rate in a timely manner, an alternative approach to survey distribution, informed by statistical modeling, was applied to efficiently and cost-effectively achieve the targeted rate of return. Design A prospective environmental scan surveying adoption of health information technology utilization within their practices was undertaken in a national pool of dental professionals (N=8000) using an alternative method of sampling. The piloted approach to rate of cohort sampling targeted a response rate of 400 completed surveys from among randomly targeted eligible providers who were contacted using replicated subsampling leveraging mailed surveys. Methods Two replicated subsample mailings (n=1000 surveys/mailings) were undertaken to project the true response rate and estimate the total number of surveys required to achieve the final target. Cost effectiveness and non-response bias analyses were performed. Results The final mailing required approximately 24% fewer mailings compared to targeting of the entire cohort, with a final survey capture exceeding the expected target. An estimated $5000 in cost savings was projected by applying the alternative approach. Non-response analyses found no evidence of bias relative to demographics, practice demographics, or topically-related survey questions. Conclusion The outcome of this pilot study suggests that this approach to survey studies will accomplish targeted enrollment in a cost effective manner. Future studies are needed to validate this approach in the context of other survey studies. PMID:28373286

Transarterial Chemoembolization for Hepatocellular Carcinoma with a New Generation of Beads: Clinical–Radiological Outcomes and Safety Profile

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

Spreafico, Carlo, E-mail: carlo.spreafico@istitutotumori.mi.it; Cascella, Tommaso, E-mail: tommaso.cascella@istitutotumori.mi.it; Facciorusso, Antonio, E-mail: antonio.facciorusso@istitutotumori.mi.it

PurposeTo evaluate the short-term safety and efficacy of the new generation of 70–150 µm drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) as a primary therapy or as a bridge to liver transplantation (LT).MethodsForty-five consecutive patients underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was assessed by computed tomographic scan according to the modified response evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was scheduled within 6 weeks in case of a noncomplete response.ResultsAll patients had well-compensated cirrhosismore » (97.7 % Child A, 44.4 % hepatitis C virus, median age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer class B disease; the median number of nodules and their sum of diameters were 2 (range 1–6) and 43 mm (range 10–190), respectively. The mean number of TACE procedures per patient was 1.4. Objective response rate (complete + partial response) was 77.7 % with a median time to best response of 3 months (95 % confidence interval 2–4). In 13 patients, DEBDOX/M1 TACE served as a bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the grade 3/4 adverse event rate was low (1 of 65 procedures).ConclusionDEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.« less

Turning on the alarm: the neural mechanisms of the transition from innocuous to painful sensation.

PubMed

Johnstone, Tom; Salomons, Tim V; Backonja, Miroslav Misha; Davidson, Richard J

2012-01-16

The experience of pain occurs when the level of a stimulus is sufficient to elicit a marked affective response, putatively to warn the organism of potential danger and motivate appropriate behavioral responses. Understanding the biological mechanisms of the transition from innocuous to painful levels of sensation is essential to understanding pain perception as well as clinical conditions characterized by abnormal relationships between stimulation and pain response. Thus, the primary objective of this study was to characterize the neural response associated with this transition and the correspondence between that response and subjective reports of pain. Towards this goal, this study examined BOLD response profiles across a range of temperatures spanning the pain threshold. 14 healthy adults underwent functional magnetic resonance imaging (fMRI) while a range of thermal stimuli (44-49°C) were applied. BOLD responses showed a sigmoidal profile along the range of temperatures in a network of brain regions including insula and mid-cingulate, as well as a number of regions associated with motor responses including ventral lateral nuclei of the thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD responses in these regions explained up to 85% of the variance in individual pain ratings, and yielded an estimate of the temperature of steepest transition from non-painful to painful heat that was nearly identical to that generated by subjective ratings. These results demonstrate a precise characterization of the relationship between objective levels of stimulation, resulting neural activation, and subjective experience of pain and provide direct evidence for a neural mechanism supporting the nonlinear transition from innocuous to painful levels along the sensory continuum. Copyright © 2011 Elsevier Inc. All rights reserved.

50 ways to trace your veteran: increasing response rates can be cheap and effective

PubMed Central

Fear, Nicola Townsend; Van Staden, Lauren; Iversen, Amy; Hall, John; Wessely, Simon

2010-01-01

Background while low response rates need not introduce bias into research, having a lower percentage of responders does increase the potential for this to occur. This is of particular concern given the decline that has been occurring in response rates since the 1950s. However, there are various methods that can be incorporated into the study design, which can assist in increasing levels of participation. Objective To outline the methods used by the King's Centre for Military Health Research (KCMHR) when conducting a recent telephone survey of serving and ex-Service military personnel. Design Using participants who had already taken part in a questionnaire-based study on the health effects of serving in the UK Armed Forces (n=10,272), a subsample was selected for an in-depth telephone interview-based follow-up study. The subsample consisted of 1,105 participants, selected on the basis of their mental health status. An adjusted response rate of 76% was achieved (n=821). Results Various methods of contact were used in this study to ensure an adequate response rate was achieved. Conclusions Simple research strategies increase response rates and are likely to reduce bias. Use of multiple simultaneous tracing methods and customisation of the approach to the target population increases rapport between participants, ensuring that those who take part feel valued as members of the study. In the current climate of decreasing participation in studies, research teams need to engage with their study population and devise innovative strategies to keep participants involved in the research being undertaken. PMID:22893795

Immunogenicity and safety of a new hexavalent vaccine (DTaP5-IPV-HB-Hib) administered in a mixed primary series schedule with a pentavalent vaccine (DTaP5-IPV-Hib).

PubMed

Martinón-Torres, Federico; Boisnard, Florence; Thomas, Stéphane; Sadorge, Christine; Borrow, Ray

2017-06-27

DTaP5-IPV-HB-Hib vaccine is a fully-liquid, combination hexavalent vaccine. This phase III, open-label, multicentre study conducted in Spain, evaluated the immune response to all DTaP5-IPV-HB-Hib antigens when the vaccine was used in a mixed hexa/penta/hexa primary series. Infants (who had received one dose of hepatitis B vaccine at birth) received a mixed schedule including DTaP5-IPV-HB-Hib (PRP-OMP conjugate) at 2 and 6months of age, DTaP5-IPV-Hib at 4months, meningococcal serogroup C conjugate (MCC) vaccine at 2 and 4months, and routine rotavirus and pneumococcal vaccination. One month post-dose 3 of the mixed schedule, response rates were considered acceptable if the lower bound of the two-sided 95% confidence interval around the post-vaccination response rate was >90% for hepatitis B and >80% for Haemophilus influenzae type b (Hib). Secondary immunogenicity objectives included description of the antibody response to all hexavalent antigens one month after completion of the mixed schedule, and to MCC antigen one month after the second MCC dose. The safety profile after each dose of study vaccine was described. Of 385 healthy infants enrolled, 384 completed the study. The primary objective was achieved for both hepatitis B and Hib; the lower bound of the 2-sided 95% CI of the response rates (97.2% and 99.0%, respectively) were greater than the pre-specified acceptability thresholds. One month post-dose 3 of the mixed schedule, all participants were seroprotected against diphtheria, tetanus and polio. The mixed schedule induced a robust immune response to all hexavalent antigens. The co-administration of the hexavalent vaccine in a mixed schedule with MCC vaccine did not reduce the immune response to vaccine antigens. Vaccines were well tolerated. In conclusion, the acceptability of response rates against Hib and hepatitis B were demonstrated one month post-dose 3 of the mixed schedule; robust immune responses against all other hexavalent antigens were observed. clinicaltrial.gov: NCT01839188; EudraCT: 2012-004221-25. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phase I/II evaluation of RV1001, a novel PI3Kδ inhibitor, in spontaneous canine lymphoma.

PubMed

Gardner, Heather L; Rippy, Sarah B; Bear, Misty D; Cronin, Kim L; Heeb, Heather; Burr, Holly; Cannon, Claire M; Penmetsa, Kumar V; Viswanadha, Srikant; Vakkalanka, Swaroop; London, Cheryl A

2018-01-01

RV1001 is a novel, potent, and selective PI3Kδ inhibitor. The purpose of this study was to evaluate the safety and efficacy of RV1001 in canine Non-Hodgkin lymphoma (NHL). Inhibition of endogenous pAKT by RV1001 in primary canine NHL cells was determined by Western blotting. A phase I study of RV1001 was performed in 21 dogs with naïve and drug resistant T and B-cell NHL to assess safety, pharmacokinetic profile, and response to therapy. The objective response rate was 62% (complete response (CR) n = 3; partial response (PR) n = 10), and responses were observed in both naïve and chemotherapy-resistant B and T cell NHL. This study provided the recommended starting dose for a phase II, non-pivotal, exploratory, open label multi-centered clinical trial in 35 dogs with naïve and drug resistant T and B-cell NHL, to further define the efficacy and safety profile of RV1001. The objective response rate in the phase II study was 77% (CR n = 1; PR n = 26). Clinical toxicities were primarily hepatobiliary and gastrointestinal, and were responsive to dose modifications and/or temporary drug discontinuation. Hepatotoxicity was the primary dose limiting toxicity. RV1001 exhibits good oral bioavailability, an acceptable safety profile, and biologic activity with associated inhibition of pAKT in dogs with B and T cell NHL. Data from these studies can be leveraged to help inform the design of future studies involving isoform-selective PI3K inhibitors in humans.

Exploring how to increase response rates to surveys of older people.

PubMed

Palonen, Mira; Kaunonen, Marja; Åstedt-Kurki, Päivi

2016-05-01

To address the special considerations that need to be taken into account when collecting data from older people in healthcare research. An objective of all research studies is to ensure there is an adequate sample size. The final sample size will be influenced by methods of recruitment and data collection, among other factors. There are some special considerations that need to be addressed when collecting data among older people. Quantitative surveys of people aged 60 or over in 2009-2014 were analysed using statistical methods. A quantitative study of patients aged 75 or over in an emergency department was used as an example. A methodological approach to analysing quantitative studies concerned with older people. The best way to ensure high response rates in surveys involving people aged 60 or over is to collect data in the presence of the researcher; response rates are lowest in posted surveys and settings where the researcher is not present when data are collected. Response rates do not seem to vary according to the database from which information about the study participants is obtained or according to who is responsible for recruitment to the survey. Implications for research/practice To conduct coherent studies with older people, the data collection process should be carefully considered.

General Automatic Components of Motion Sickness

NASA Technical Reports Server (NTRS)

Suter, S.; Toscano, W. B.; Kamiya, J.; Naifeh, K.

1985-01-01

A body of investigations performed in support of experiments aboard the space shuttle, and designed to counteract the symptoms of Space Adaptation Syndrome, which resemble those of motion sickness on Earth is reviewed. For these supporting studies, the automatic manifestations of earth-based motion sickness was examined. Heart rate, respiration rate, finger pulse volume and basal skin resistance were measured on 127 men and women before, during and after exposure to nauseogenic rotating chair tests. Significant changes in all autonomic responses were observed across the tests. Significant differences in autonomic responses among groups divided according to motion sickness susceptibility were also observed. Results suggest that the examination of autonomic responses as an objective indicator of motion sickness malaise is warranted and may contribute to the overall understanding of the syndrome on Earth and in Space.

Shock-loading response of advanced materials

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

Gray, G.T. III

1993-08-01

Advanced materials, such as composites (metal, ceramic, or polymer-matrix), intermetallics, foams (metallic or polymeric-based), laminated materials, and nanostructured materials are receiving increasing attention because their properties can be custom tailored specific applications. The high-rate/impact response of advanced materials is relevant to a broad range of service environments such as the crashworthiness of civilian/military vehicles, foreign-object-damage in aerospace, and light-weight armor. Increased utilization of these material classes under dynamic loading conditions requires an understanding of the relationship between high-rate/shock-wave response as a function of microstructure if we are to develop models to predict material behavior. In this paper the issues relevantmore » to defect generation, storage, and the underlying physical basis needed in predictive models for several advanced materials will be reviewed.« less

The effectiveness of recruitment strategies on general practitioner’s survey response rates – a systematic review

PubMed Central

2014-01-01

Background Low survey response rates in general practice are common and lead to loss of power, selection bias, unexpected budgetary constraints and time delays in research projects. Methods Objective: To assess the effectiveness of recruitment strategies aimed at increasing survey response rates among GPs. Design: Systematic review. Search methods: MEDLINE (OVIDSP, 1948-2012), EMBASE (OVIDSP, 1980-2012), Evidence Based Medicine Reviews (OVIDSP, 2012) and references of included papers were searched. Major search terms included GPs, recruitment strategies, response rates, and randomised controlled trials (RCT). Selection criteria: Cluster RCTs, RCTs and factorial trial designs that evaluate recruitment strategies aimed at increasing GP survey response rates. Data collection and analysis: Abstracts identified by the search strategy were reviewed and relevant articles were retrieved. Each full-text publication was examined to determine whether it met the predetermined inclusion criteria. Data extraction and study quality was assessed by using predetermined checklists. Results Monetary and nonmonetary incentives were more effective than no incentive with monetary incentives having a slightly bigger effect than nonmonetary incentives. Large incentives were more effective than small incentives, as were upfront monetary incentives compared to promised monetary incentives. Postal surveys were more effective than telephone or email surveys. One study demonstrated that sequentially mixed mode (online survey followed by a paper survey with a reminder) was more effective than an online survey or the combination of an online and paper survey sent similtaneously in the first mail out. Pre-contact with a phonecall from a peer, personalised packages, sending mail on Friday, and using registered mail also increased response rates in single studies. Pre-contact by letter or postcard almost reached statistical signficance. Conclusions GP survey response rates may improve by using the following strategies: monetary and nonmonetary incentives, larger incentives, upfront monetary incentives, postal surveys, pre-contact with a phonecall from a peer, personalised packages, sending mail on Friday, and using registered mail. Mail pre-contact may also improve response rates and have low costs. Improved reporting and further trials, including sequential mixed mode trials and social media, are required to determine the effectiveness of recruitment strategies on GPs' response rates to surveys. PMID:24906492

Does Price Transparency Legislation Allow the Uninsured to Shop for Care?

PubMed Central

Farrell, Kate Stockwell; Finocchio, Leonard J.; Trivedi, Amal N.

2009-01-01

Background The majority of states have enacted price transparency laws to allow patients to shop for care and to prevent price discrimination of the uninsured. In California, hospitals must provide a price estimate to a requesting uninsured patient and cannot bill for an amount greater than the reimbursement the hospital would receive from a government payer. Objective To assess the response rate of California hospitals to a patient price request and to compare the price estimates received to Medicare reimbursement. Design We sent letters to California acute-care hospitals from a fictional uninsured patient requesting an estimate for one of three common elective procedures: a laparoscopic cholecystectomy, a hysterectomy, or routine screening colonoscopy. Participants Three hundred and fifty-three hospitals in California. Measurements Hospital response rates, difference between price estimates received, and Medicare reimbursement for equivalent procedures. Results Only 28% (98/353) of hospitals responded and their response varied in content. Of the 98 responses, 15 (15%) did not provide a quote and instead asked for more information such as the billing code, 55 (56%) provided a price estimate for hospital services only, 10 (10%) included both physician and hospital services, and 18 (18%) did not specify what was covered. The median discounted price estimate was higher than Medicare reimbursement rates for all procedures: hysterectomy ($17,403 vs. $5,569; p < 0.001), cholecystectomy ($14,014 vs. $7,196; p < 0.001) and colonoscopy ($2,017 vs. $216; p < 0.001). Conclusions Current California legislation fails to meet its objective of enabling uninsured patients to compare prices for hospital-based health care services. PMID:19936845

Policy impacts on agricultural irrigation electricity demand in the Columbia Basin

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

Martin, M.; Cox, L.; Nakamoto, S.

Accurately estimating the price elasticity of demand for irrigation electricity is important to major electricity suppliers such as the Bonneville Power Administration (BPA) of the Pacific Northwest. The BPA has a revenue maximization objective, and the elasticity of demand is central to its rate setting process. Several studies have attempted to estimate demand for irrigation electricity, but none has explicitly included federal agricultural policy and program variables. Tins paper discusses how agricultural programs may influence farmers' irrigation decisions and thus their demand for irrigation electricity. It suggests that existing programs serve to make farmers more responsive to electricity rate increasesmore » than would otherwise be the case. Thus, studies that fail to include them may underestimate the responsiveness of farmers to electricity rate increases.« less

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis

PubMed Central

Zou, Guangyong; Parker, Claire E.; Macdonald, John K.; Mosli, Mahmoud H.; Khanna, Reena; Shackelton, Lisa M.; Vandervoort, Margaret K.; AlAmeel, Turki; Al Beshir, Mohammad; AlMadi, Majid; Al-Taweel, Talal; Atkinson, Nathan S. S.; Biswas, Sujata; Chapman, Thomas P.; Dulai, Parambir S.; Glaire, Mark A.; Hoekman, Daniel; Koutsoumpas, Andreas; Minas, Elizabeth; Samaan, Mark A.; Travis, Simon; D’Haens, Geert; Levesque, Barrett G.; Sandborn, William J.; Feagan, Brian G.

2016-01-01

Background and Aims: Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and remission rates in UC RCTs and identify trial design factors influencing them. Methods: MEDLINE, EMBASE, and the Cochrane Library were searched from inception through April 2014 for placebo-controlled trials in adult patients with UC of a biological agent, corticosteroid, immunosuppressant, or aminosalicylate. Data were independently doubly extracted. Quality was assessed using the Cochrane risk of bias tool. Results: In all, 51 trials [48 induction and 10 maintenance phases] were identified. Placebo response and remission rates were pooled according to random-effects models, and mixed-effects meta-regression models were used to evaluate effects of study-level characteristics on these rates. Pooled estimates of placebo remission and response rates for induction trials were 10% (95% confidence interval [CI] 7-13%) and 33% [95% CI 29-37%], respectively. Corresponding values for maintenance trials were 19% [95% CI 11-30%] and 22% [95% CI 17-28%]. Trials enrolling patients with more active disease confirmed by endoscopy [endoscopy subscore ≥ 2] were associated with lower placebo rates. Conversely, placebo rates increased with increasing trial duration and number of study visits. Conclusions: Objective assessment of greater disease activity at trial entry by endoscopy lowered placebo rates, whereas increasing trial duration and more interactions with healthcare providers increased placebo rates. These findings have important implications for design and conduct of clinical trials. PMID:26746169

Design and operation of the national home health aide survey: 2007-2008.

PubMed

Bercovitz, Anita; Moss, Abigail J; Sengupta, Manisha; Harris-Kojetin, Lauren D; Squillace, Marie R; Emily, Rosenoff; Branden, Laura

2010-03-01

This report provides an overview of the National Home Health Aide Survey (NHHAS), the first national probability survey of home health aides. NHHAS was designed to provide national estimates of home health aides who provided assistance in activities of daily living (ADLs) and were directly employed by agencies that provide home health and/or hospice care. This report discusses the need for and objectives of the survey, the design process, the survey methods, and data availability. METHODS NHHAS, a multistage probability sample survey, was conducted as a supplement to the 2007 National Home and Hospice Care Survey (NHHCS). Agencies providing home health and/or hospice care were sampled, and then aides employed by these agencies were sampled and interviewed by telephone. Survey topics included recruitment, training, job history, family life, client relations, work-related injuries, and demographics. NHHAS was virtually identical to the 2004 National Nursing Assistant Survey of certified nursing assistants employed in sampled nursing homes with minor changes to account for differences in workplace environment and responsibilities. RESULTS From September 2007 to April 2008, interviews were completed with 3,416 aides. A public-use data file that contains the interview responses, sampling weights, and design variables is available. The NHHAS overall response rate weighted by the inverse of the probability of selection was 41 percent. This rate is the product of the weighted first-stage agency response rate of 57 percent (i.e., weighted response rate of 59 percent for agency participation in NHHCS times the weighted response rate of 97 percent for agencies participating in NHHCS that also participated in NHHAS) and the weighted second-stage aide response rate of 72 percent to NHHAS.

Sexual Health Education: A Psychiatric Resident's Perspective

ERIC Educational Resources Information Center

Waineo, Eva; Arfken, Cynthia L.; Morreale, Mary K.

2010-01-01

Objective: This report discusses psychiatric residents' perceptions of sexual health education and their opinions regarding curricular improvements. Methods: An anonymous, web-based survey was sent to residents in one general psychiatry program (N = 33). The response rate was 69.7%. Results: Residents reported inadequate experience in multiple…

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer.

PubMed

Goetz, Matthew P; Toi, Masakazu; Campone, Mario; Sohn, Joohyuk; Paluch-Shimon, Shani; Huober, Jens; Park, In Hae; Trédan, Olivier; Chen, Shin-Cheh; Manso, Luis; Freedman, Orit C; Garnica Jaliffe, Georgina; Forrester, Tammy; Frenzel, Martin; Barriga, Susana; Smith, Ian C; Bourayou, Nawel; Di Leo, Angelo

2017-11-10

Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm ( P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v 1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.

Neural biomarkers for assessing different types of imagery in pictorial health warning labels for cigarette packaging: a cross-sectional study

PubMed Central

Newman-Norlund, Roger D; Thrasher, James F; Fridriksson, Johann; Brixius, William; Froeliger, Brett; Hammond, David; Cummings, Michael K

2014-01-01

Objective Countries around the world have increasingly adopted pictorial health warning labels (HWLs) for tobacco packages to warn consumers about smoking-related risks. Research on how pictorial HWLs work has primarily analysed self-reported responses to HWLs; studies at the neural level comparing the brain's response to different types of HWLs may provide an important complement to prior studies, especially if self-reported responses are systematically biased. In this study we characterise the brain's response to three types of pictorial HWLs for which prior self-report studies indicated different levels of efficacy. Methods Current smokers rated pictorial HWLs and then observed the same HWLs during functional MRI (fMRI) scanning. Fifty 18–50-year-old current adult smokers who were free from neurological disorders were recruited from the general population and participated in the study. Demographics, smoking-related behaviours and self-reported ratings of pictorial HWL stimuli were obtained prior to scanning. Brain responses to HWLs were assessed using fMRI, focusing on a priori regions of interest. Results Pictorial HWL stimuli elicited activation in a broad network of brain areas associated with visual processing and emotion. Participants who rated the stimuli as more emotionally arousing also showed greater neural responses at these sites. Conclusions Self-reported ratings of pictorial HWLs are correlated with neural responses in brain areas associated with visual and emotional processing. Study results cross-validate self-reported ratings of pictorial HWLs and provide insights into how pictorial HWLs are processed. PMID:25552613

Cosmos 1887 - Science overview

NASA Technical Reports Server (NTRS)

Grindeland, R. E.

1990-01-01

Twenty two groups of U.S. investigators participated in joint studies of ten male rats flown on the Cosmos 1887 biosatellite. A summary of these studies embracing skeletal muscle, bone, endocrine, neural, intestinal, metabolic, immunology, cardiac, and gonadal investigations is presented. Three general objectives of the rat experiments are outlined - verification of previous observations of the biological responses to microgravity; clarification of the effects of microgravity on both the tissues investigated and the measurements performed; and relation of biological responses to flight duration. It is concluded that the first objective is met fully and the second with a varying degree of success. The confounding effects of overshooting the designated landing site and delayed recovery of the animals largely precluded meeting the last objective. It is also noted that investigations were performed for the first time on brain and spinal cord enzymes, a neurotransmitter, transmitter receptors, hypothalamic regulatory factors, pineal metabolites, atrial granules, liver histology, and jejunal mitotic rate in spaceflight animals.

Anticipating the effects of gravity when intercepting moving objects: differentiating up and down based on nonvisual cues.

PubMed

Senot, Patrice; Zago, Myrka; Lacquaniti, Francesco; McIntyre, Joseph

2005-12-01

Intercepting an object requires a precise estimate of its time of arrival at the interception point (time to contact or "TTC"). It has been proposed that knowledge about gravitational acceleration can be combined with first-order, visual-field information to provide a better estimate of TTC when catching falling objects. In this experiment, we investigated the relative role of visual and nonvisual information on motor-response timing in an interceptive task. Subjects were immersed in a stereoscopic virtual environment and asked to intercept with a virtual racket a ball falling from above or rising from below. The ball moved with different initial velocities and could accelerate, decelerate, or move at a constant speed. Depending on the direction of motion, the acceleration or deceleration of the ball could therefore be congruent or not with the acceleration that would be expected due to the force of gravity acting on the ball. Although the best success rate was observed for balls moving at a constant velocity, we systematically found a cross-effect of ball direction and acceleration on success rate and response timing. Racket motion was triggered on average 25 ms earlier when the ball fell from above than when it rose from below, whatever the ball's true acceleration. As visual-flow information was the same in both cases, this shift indicates an influence of the ball's direction relative to gravity on response timing, consistent with the anticipation of the effects of gravity on the flight of the ball.

Novel therapy in multiple myeloma.

PubMed

Avilés, Agustin; Neri, Natividad; Nambo, M Jesús; Cleto, Sergio; Castañeda, Claudia; González, Martha; Talavera, Alejandra; Huerta-Guzmán, Judith

2005-10-01

Treatment in patients with multiple myeloma remain to be defined. Younger patients (defined as a cut-off level < 65 years old) will be treated with chemotherapy and transplant procedures. However, most patients > 65 years old are not candidates for this therapeutic approach and the use of intensive chemotherapy could be associated to severe toxicity. We developed an new, not-cytotoxic regimen with dexamethasone 30 mg/m(2), iv, days 1 to 4, all trans retinoic acid 45 mg/m(2), po, days 5 to 14 and interferon alfa 2a 4.5 MU, sc, daily, days 5 to 14 (DAI regimen) administered every 28 days in number of 6 cycles, at this point patients were restaging, if they showed complete response, objective response or partial response they were conducted to received thalidomide 100-200 mg po, daily and dexamethasone 10 mg/2, po days 1 to 4 at monthly intervals, for 18 months. Forty one patients were enrolled in an Phase II study. In an intent to treat analysis all patients were evaluable. Complete response was observed in 18 cases (43%), objective response in 10 patients (24%) and partial response in 5 patients (12%), overall response rate was 80%. Eight patients were considered failures. At an median of 36 months, no relapse of progression disease has been observed, thus actuarial curves at 3-years showed that event free survival is 100% and overall survival is 91%. Toxicity was mild, all patients received the planned dose in time. This regimen appear to be useful in older patients with multiple myeloma, the response rate is higher and toxicity was mild. Controlled clinical trials comparing with conventional chemotherapy will be conducted to define the role of this therapeutic approach.

Auditory steady-state responses in cochlear implant users: Effect of modulation frequency and stimulation artifacts.

PubMed

Gransier, Robin; Deprez, Hanne; Hofmann, Michael; Moonen, Marc; van Wieringen, Astrid; Wouters, Jan

2016-05-01

Previous studies have shown that objective measures based on stimulation with low-rate pulse trains fail to predict the threshold levels of cochlear implant (CI) users for high-rate pulse trains, as used in clinical devices. Electrically evoked auditory steady-state responses (EASSRs) can be elicited by modulated high-rate pulse trains, and can potentially be used to objectively determine threshold levels of CI users. The responsiveness of the auditory pathway of profoundly hearing-impaired CI users to modulation frequencies is, however, not known. In the present study we investigated the responsiveness of the auditory pathway of CI users to a monopolar 500 pulses per second (pps) pulse train modulated between 1 and 100 Hz. EASSRs to forty-three modulation frequencies, elicited at the subject's maximum comfort level, were recorded by means of electroencephalography. Stimulation artifacts were removed by a linear interpolation between a pre- and post-stimulus sample (i.e., blanking). The phase delay across modulation frequencies was used to differentiate between the neural response and a possible residual stimulation artifact after blanking. Stimulation artifacts were longer than the inter-pulse interval of the 500pps pulse train for recording electrodes ipsilateral to the CI. As a result the stimulation artifacts could not be removed by artifact removal on the bases of linear interpolation for recording electrodes ipsilateral to the CI. However, artifact-free responses could be obtained in all subjects from recording electrodes contralateral to the CI, when subject specific reference electrodes (Cz or Fpz) were used. EASSRs to modulation frequencies within the 30-50 Hz range resulted in significant responses in all subjects. Only a small number of significant responses could be obtained, during a measurement period of 5 min, that originate from the brain stem (i.e., modulation frequencies in the 80-100 Hz range). This reduced synchronized activity of brain stem responses in long-term severely-hearing impaired CI users could be an attribute of processes associated with long-term hearing impairment and/or electrical stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Time-Driven Effects on Processing Relative Clauses

ERIC Educational Resources Information Center

Schremm, Andrea; Horne, Merle; Roll, Mikael

2016-01-01

The present response time study investigated how a hypothesized time-based working memory constraint of 2-3 s affects the resolution of grammatical and semantic dependencies. Congruent and incongruent object relative (OR) and subject relative sentences were read at different presentation rates so that the distance between dependent words was…

Burnout Comparison among Residents in Different Medical Specialties

ERIC Educational Resources Information Center

Martini, Shahm; Arfken, Cynthia L.; Churchill, Amy; Balon, Richard

2004-01-01

Objective: To investigate resident burnout in relation to work and home-related factors. Method: Maslach Burnout Inventory was mailed to residents in eight different medical specialties, with a response rate of 35%. Results: Overall, 50% of residents met burnout criteria, ranging from 75% (obstetrics/gynecology) to 27% (family medicine). The first…

The Role of Prepositioned Stocks: Sustaining and Responding to Foreign Humanitarian Assistance and Disaster Relief (HADR) Operations

DTIC Science & Technology

2015-06-12

only emphasize on the response objectives regarding military and interagency focus. Limitations The USG has specified tasks and benchmarks that must...rates. Past data regarding supply and humanitarian services expended allows for accurate forecasting based off the severity of catastrophic damage

Basal area growth, carbon isotope discrimination, and intrinsic water use efficiency after fertilization of Douglas-fir in the Oregon Coast Range

EPA Science Inventory

Many hectares of intensively managed Douglas-fir (Pseudotsuga menziesii Mirb. Franco) stands in western North America are fertilized with nitrogen to increase growth rates. Understanding the mechanisms of response facilitates prioritization of stands for treatment. The objective ...

Polymorphism within thyroid hormone responsive (THRSP) associated with weaning-to-oestrus interval in swine

USDA-ARS?s Scientific Manuscript database

The objective of this study was to assess polymorphisms within lipogenic-related candidate genes for association with the reproductive traits; age at puberty (AP), ovulation rate (OR), and weaning-to-estrus interval (WEI). Variations within the anorectic gene Cocaine- and Amphetamine-Regulated Trans...

Hydrodynamical simulations of strong tides in astrophysical systems

NASA Astrophysics Data System (ADS)

Guillochon, James

2013-07-01

At the simplest level, gravitational sources are considered to be point-like and in solitude, with a radial force that falls off as r -2. In reality, all astrophysical objects aside from black holes are extended in space, and can be deformed by the tidal forces arising from the proximity of companion objects with large average densities. When these forces are weak, the response of an object to a tide can be through a decomposition into basis functions, but this approach fails when the tide is strong enough to deform an object by a distance equal to its own size. Under these circumstances, a hydrodynamical representation of the object is required to understand the true tidal response. In this thesis, we present a number of examples of physical systems in which tides dominate the dynamics. First, we consider the case of a star that encounters a supermassive black hole (SMBH) in a deeply penetrating encounter, resulting in a dramatic compression that produces shocks that would be observable in the X-ray. Second, we present the results of hydrodynamical simulations that demonstrate a new mechanism for igniting Type Ia supernovae from binary systems composed of two white dwarfs undergoing Roche-lobe overflow. Third, we investigate the survival prospects of giant planets that have been scattered into highly eccentricity orbits and are exposed to a strong tide applied by their parent star. Fourth, we systematically map the fallback rate resulting from the tidal disruptions of stars by SMBHs. Finally, we use what we have learned about the feeding rate to model determine the highest-likelihood model for an observed prototypical tidal disruption event.

Evaluation of neophobia and its potential impact upon predator control techniques: a study on two sympatric foxes in southern Patagonia.

PubMed

Travaini, Alejandro; Vassallo, Aldo Iván; García, Germán Oscar; Echeverría, Alejandra Isabel; Zapata, Sonia Cristina; Nielsen, Sigrid

2013-01-01

An alternative approach to increase the efficiency of predator control and selectivity is to consider the natural behavioural repertoire of the target species and how such behaviours may increase their vulnerability. Neophobia, or the hesitancy to approach a novel food item, object, or place, is an important factor influencing the investigative behaviour of animals, and its incorporation to predator control techniques may help to reduce losses of livestock to predators. In this study, we simultaneously evaluated the existence and intensity of neophobic responses in two sympatric fox species, the Culpeo (Pseudalopex culpaeus) and the Grey (P. griseus) foxes in southern Patagonia, Argentina. For this purpose, we used bait stations to compare fox behavioural responses in the absence (pre-treatment), presence (treatment) and removal (post-treatment) of a novel stimulus, which consisted of an orange PVC-traffic cone. Both fox species showed a neophobic response: bait-station visitation rates decreased (P=0.005 and P=0.048, for Culpeo and Grey foxes, respectively) in the presence of the novel object. The intensity of the response differed between species being higher for Culpeo foxes (approximately 80% of reduction in visitation rate during treatment for Culpeo foxes vs. 10% for Grey foxes). However, the bait-station visitation pattern after novel object removal indicated that animals probably increased exploration of the station. The high level of neophobia achieved by the Culpeo fox, together with an increase in post-treatment site exploration, suggests that behavioural manipulations (reduction of neophobia and its consequent increase in risk taking) could improve selective and efficient fox control in rural areas where livestock production is a major economic activity. Copyright © 2012 Elsevier B.V. All rights reserved.

Phase II study of a novel taxane (Cabazitaxel-XRP 6258) in previously treated advanced non-small cell lung cancer (NSCLC) patients.

PubMed

Madan, Ankit; Jones, Benjamin S; Bordoni, Rodolfo; Saleh, Mansoor N; Jerome, Mary S; Miley, Deborah K; Jackson, Bradford E; Robert, Francisco

2016-09-01

Given the success of cabazitaxel in patients with prostate cancer who progressed after receiving prior chemotherapy, its preclinical efficacy in various cell lines and possible ability to cross blood-brain barrier, cabazitaxel was hypothesized to increase objective response rate (ORR) in second-line setting in non-small cell lung cancer (NSCLC). This was a phase II 2-stage trial in 28 patients using two different treatment schedules (A: 20 mg/m(2) every 3 weeks intravenously and B: 8.4 mg/m(2) intravenously weekly) to determine the ORR of cabazitaxel with secondary end points including progression-free survival (PFS), safety, and overall survival (OS). There was one objective response in schedule B. PFS and OS of schedule A was 3 and 6 months, respectively. PFS and OS of schedule B was 3 and 13 months, respectively. The stable disease rate was higher in schedule A (SD = 69.23 %; 95 % CL 38.57, 90.90) as compared to schedule B (SD = 38.46 %; 95 % CL 13.86, 68.42), but this difference was not statistically significant (P value = 0.1156). There were two grade 5 toxicities from sepsis. Hematuria of any grade developed in greater percentage of patients (35%) as compared to previous cabazitaxel phase 3 trial and led to change in our protocol. Response to cabazitaxel in NSCLC was not as robust as seen in prostate cancer and not superior to currently used agents such as docetaxel, pemetrexed, and erlotinib. In absence of significant objective responses, the second stage of the study was not undertaken.

Sudden Cardiac Arrest in Athletic Medicine

PubMed Central

Kyle, James M.; Ellis, James M.; Cantwell, John; Courson, Ron; Medlin, Ron

2001-01-01

Objective: To emphasize the importance of decreasing the response time by a trained target responder to increase the survival rate among athletes experiencing sudden cardiac arrest at an athletic event. Background: Death due to sudden cardiac arrest that is witnessed is preventable in many cases. However, most people who experience this condition die because of a prolonged response time from onset of the fatal arrhythmia to defibrillation by trained treatment providers. If athletic trainers or other members of the athletic care medical team are trained as target responders and equipped with automated electronic defibrillators, they can immediately treat an athlete who experiences a sudden, life-threatening tachyarrhythmia. This prompt response to the life-threatening emergency should result in a higher survival rate. Description: We review the causes of sudden cardiac arrest during athletic events, note some unusual clinical presentations, discuss improved methods of response and new equipment for treatment, and define the athletic trainer's role as a target responder trained to treat people experiencing sudden cardiac arrest at an athletic event. Clinical Advantages: An athletic care team willing to become part of an emergency response team can help improve the survival rate of athletes experiencing sudden cardiac arrest at an athletic event. PMID:12937464

Heart rate autonomic regulation system at rest and during paced breathing among patients with CRPS as compared to age-matched healthy controls.

PubMed

Bartur, Gadi; Vatine, Jean-Jacques; Raphaely-Beer, Noa; Peleg, Sara; Katz-Leurer, Michal

2014-09-01

The objective of this study is to assess the autonomic nerve heart rate regulation system at rest and its immediate response to paced breathing among patients with complex regional pain syndrome (CRPS) as compared with age-matched healthy controls. Quasiexperimental. Outpatient clinic. Ten patients with CRPS and 10 age- and sex-matched controls. Participants underwent Holter ECG (NorthEast Monitoring, Inc., Maynard, MA, USA) recording during rest and biofeedback-paced breathing session. Heart rate variability (HRV), time, and frequency measures were assessed. HRV and time domain values were significantly lower at rest among patients with CRPS as compared with controls. A significant association was noted between pain rank and HRV frequency measures at rest and during paced breathing; although both groups reduced breathing rate significantly during paced breathing, HRV time domain parameters increased only among the control group. The increased heart rate and decreased HRV at rest in patients with CRPS suggest a general autonomic imbalance. The inability of the patients to increase HRV time domain values during paced breathing may suggest that these patients have sustained stress response with minimal changeability in response to slow-paced breathing stimuli. Wiley Periodicals, Inc.

Directing driver attention with augmented reality cues

PubMed Central

Rusch, Michelle L.; Schall, Mark C.; Gavin, Patrick; Lee, John D.; Dawson, Jeffrey D.; Vecera, Shaun; Rizzo, Matthew

2013-01-01

This simulator study evaluated the effects of augmented reality (AR) cues designed to direct the attention of experienced drivers to roadside hazards. Twenty-seven healthy middle-aged licensed drivers with a range of attention capacity participated in a 54 mile (1.5 hour) drive in an interactive fixed-base driving simulator. Each participant received AR cues to potential roadside hazards in six simulated straight (9 mile long) rural roadway segments. Drivers were evaluated on response time for detecting a potentially hazardous event, detection accuracy for target (hazard) and non-target objects, and headway with respect to the hazards. Results showed no negative outcomes associated with interference. AR cues did not impair perception of non-target objects, including for drivers with lower attentional capacity. Results showed near significant response time benefits for AR cued hazards. AR cueing increased response rate for detecting pedestrians and warning signs but not vehicles. AR system false alarms and misses did not impair driver responses to potential hazards. PMID:24436635

Evaluating Survey Quality in Health Services Research: A Decision Framework for Assessing Nonresponse Bias

PubMed Central

Halbesleben, Jonathon R B; Whitman, Marilyn V

2013-01-01

Objective To address the issue of nonresponse as problematic and offer appropriate strategies for assessing nonresponse bias. Study Design A review of current strategies used to assess the quality of survey data and the challenges associated with these strategies is provided along with appropriate post-data collection techniques that researchers should consider. Principal Findings Response rates are an incomplete assessment of survey data quality, and quick reactions to response rate should be avoided. Based on a five-question decision making framework, we offer potential ways to assess nonresponse bias, along with a description of the advantages and disadvantages to each. Conclusions It is important that the quality of survey data be considered to assess the relative contribution to the literature of a given study. Authors and funding agencies should consider the potential effects of nonresponse bias both before and after survey administration and report the results of assessments of nonresponse bias in addition to response rates. PMID:23046097

Dependence of behavioral performance on material category in an object grasping task with monkeys.

PubMed

Yokoi, Isao; Tachibana, Atsumichi; Minamimoto, Takafumi; Goda, Naokazu; Komatsu, Hidehiko

2018-05-02

Material perception is an essential part of our cognitive function that enables us to properly interact with our complex daily environment. One important aspect of material perception is its multimodal nature. When we see an object, we generally recognize its haptic properties as well as its visual properties. Consequently, one must examine behavior using real objects that are perceived both visually and haptically to fully understand the characteristics of material perception. As a first step, we examined whether there is any difference in the behavioral responses to different materials in monkeys trained to perform an object grasping task in which they saw and grasped rod-shaped real objects made of various materials. We found that the monkeys' behavior in the grasping task, measured based on the success rate and the pulling force, differed depending on the material category. Monkeys easily and correctly grasped objects of some materials, such as metal and glass, but failed to grasp objects of other materials. In particular, monkeys avoided grasping fur-covered objects. The differences in the behavioral responses to the material categories cannot be explained solely based on the degree of familiarity with the different materials. These results shed light on the organization of multimodal representation of materials, where their biological significance is an important factor. In addition, a monkey that avoided touching real fur-covered objects readily touched images of the same objects presented on a CRT display. This suggests employing real objects is important when studying behaviors related to material perception.

Don't judge me: Psychophysiological evidence of gender differences to social evaluative feedback.

PubMed

Vanderhasselt, Marie-Anne; De Raedt, Rudi; Nasso, Selene; Puttevils, Louise; Mueller, Sven C

2018-05-01

Human beings have a basic need for esteemed social connections, and receiving negative self-evaluative feedback induces emotional distress. The aim of the current study is to measure eye movements (a physiological marker of attention allocation) and pupillary responses (a physiological marker of cognitive and emotional processing) as online and objective indices of participants' reaction to positive/negative social evaluations from the same or opposite sex. Following the paradigm, subjective mood ratings and heart rate variability (HRV) - as an objective index of regulatory effort- were measured. Results demonstrate clear gender-specific results in all measures. Eye-movements demonstrate that male participants respond more with other-focused attention (and specifically to male participants), whereas women respond more with self-focused attention following negative social evaluative feedback. Pupillary responses show that social evaluative feedback is specifically eliciting cognitive/affective processes in male participants to regulate emotional responses when provided by the opposite gender. Finally, following the paradigm, female (as compared to male) participants were more subjectively reactive to the paradigm (i.e., self-reports), and were less able to engage contextual- and goal related regulatory control of emotional responses (reduced HRV). Although the current study focused on psychiatrically healthy young adults, results may contribute to our understanding of sex differences in internalizing mental problems, such as rumination. Copyright © 2018 Elsevier B.V. All rights reserved.

Pivotal ERIVANCE basal cell carcinoma (BCC) study: 12-month update of efficacy and safety of vismodegib in advanced BCC.

PubMed

Sekulic, Aleksandar; Migden, Michael R; Lewis, Karl; Hainsworth, John D; Solomon, James A; Yoo, Simon; Arron, Sarah T; Friedlander, Philip A; Marmur, Ellen; Rudin, Charles M; Chang, Anne Lynn S; Dirix, Luc; Hou, Jeannie; Yue, Huibin; Hauschild, Axel

2015-06-01

Primary analysis from the pivotal ERIVANCE BCC study resulted in approval of vismodegib, a Hedgehog pathway inhibitor indicated for treatment of adults with metastatic or locally advanced basal cell carcinoma (BCC) that has recurred after surgery or for patients who are not candidates for surgery or radiation. An efficacy and safety analysis was conducted 12 months after primary analysis. This was a multinational, multicenter, nonrandomized, 2-cohort study in patients with measurable and histologically confirmed locally advanced or metastatic BCC taking oral vismodegib (150 mg/d). Primary outcome measure was objective response rate (complete and partial responses) assessed by independent review facility. After 12 months of additional follow-up, median duration of exposure to vismodegib was 12.9 months. Objective response rate increased from 30.3% to 33.3% in patients with metastatic disease, and from 42.9% to 47.6% in patients with the locally advanced form. Median duration of response in patients with locally advanced BCC increased from 7.6 to 9.5 months. No new safety signals emerged with extended treatment duration. Limitations include low prevalence of advanced BCC and challenges of designing a study with heterogenous manifestations. The 12-month update of the study confirms the efficacy and safety of vismodegib in management of advanced BCC. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Slower Rate of Binocular Rivalry in Autism

PubMed Central

Kravitz, Dwight J.; Freyberg, Jan; Baron-Cohen, Simon; Baker, Chris I.

2013-01-01

An imbalance between cortical excitation and inhibition is a central component of many models of autistic neurobiology. We tested a potential behavioral footprint of this proposed imbalance using binocular rivalry, a visual phenomenon in which perceptual experience is thought to mirror the push and pull of excitatory and inhibitory cortical dynamics. In binocular rivalry, two monocularly presented images compete, leading to a percept that alternates between them. In a series of trials, we presented separate images of objects (e.g., a baseball and a broccoli) to each eye using a mirror stereoscope and asked human participants with autism and matched control subjects to continuously report which object they perceived, or whether they perceived a mixed percept. Individuals with autism demonstrated a slower rate of binocular rivalry alternations than matched control subjects, with longer durations of mixed percepts and an increased likelihood to revert to the previously perceived object when exiting a mixed percept. Critically, each of these findings was highly predictive of clinical measures of autistic symptomatology. Control “playback” experiments demonstrated that differences in neither response latencies nor response criteria could account for the atypical dynamics of binocular rivalry we observed in autistic spectrum conditions. Overall, these results may provide an index of atypical cortical dynamics that may underlie both the social and nonsocial symptoms of autism. PMID:24155303

A model of blended learning in a preclinical course in prosthetic dentistry.

PubMed

Reissmann, Daniel R; Sierwald, Ira; Berger, Florian; Heydecke, Guido

2015-02-01

The aim of this study was to evaluate the use of blending learning that added online tools to traditional learning methods in a preclinical course in prosthetic dentistry at one dental school in Germany. The e-learning modules were comprised of three main components: fundamental principles, additional information, and learning objective tests. Video recordings of practical demonstrations were prepared and cut into sequences meant to achieve single learning goals. The films were accompanied by background information and, after digital processing, were made available online. Additionally, learning objective tests and learning contents were integrated. Evaluations of 71 of 89 students (response rate: 80%) in the course with the integrated e-learning content were available for the study. Compared with evaluation results of the previous years, a substantial and statistically significant increase in satisfaction with learning content (from 30% and 34% to 86%, p<0.001) and learning effect (from 65% and 63% to 83%, p<0.05) was observed. Satisfaction ratings stayed on a high level in three subsequent courses with the modules. Qualitative evaluation revealed mostly positive responses, with not a single negative comment regarding the blended learning concept. The results showed that the e-learning tool was appreciated by the students and suggest that learning objective tests can be successfully implemented in blended learning.

The Novel Object and Unusual Name (NOUN) Database: A collection of novel images for use in experimental research.

PubMed

Horst, Jessica S; Hout, Michael C

2016-12-01

Many experimental research designs require images of novel objects. Here we introduce the Novel Object and Unusual Name (NOUN) Database. This database contains 64 primary novel object images and additional novel exemplars for ten basic- and nine global-level object categories. The objects' novelty was confirmed by both self-report and a lack of consensus on questions that required participants to name and identify the objects. We also found that object novelty correlated with qualifying naming responses pertaining to the objects' colors. The results from a similarity sorting task (and a subsequent multidimensional scaling analysis on the similarity ratings) demonstrated that the objects are complex and distinct entities that vary along several featural dimensions beyond simply shape and color. A final experiment confirmed that additional item exemplars comprised both sub- and superordinate categories. These images may be useful in a variety of settings, particularly for developmental psychology and other research in the language, categorization, perception, visual memory, and related domains.

RESPONSIVENESS OF THE ACTIVITIES OF DAILY LIVING SCALE OF THE KNEE OUTCOME SURVEY AND NUMERIC PAIN RATING SCALE IN PATIENTS WITH PATELLOFEMORAL PAIN

PubMed Central

Piva, Sara R.; Gil, Alexandra B.; Moore, Charity G.; Fitzgerald, G. Kelley

2016-01-01

Objective To assess internal and external responsiveness of the Activity of Daily Living Scale of the Knee Outcome Survey and Numeric Pain Rating Scale on patients with patellofemoral pain. Design One group pre-post design. Subjects A total of 60 individuals with patellofemoral pain (33 women; mean age 29.9 (standard deviation 9.6) years). Methods The Activity of Daily Living Scale and the Numeric Pain Rating Scale were assessed before and after 8 weeks of physical therapy program. Patients completed a global rating of change scale at the end of therapy. The standardized effect size, Guyatt responsiveness index, and the minimum clinical important difference were calculated. Results Standardized effect size of the Activity of Daily Living Scale was 0.63, Guyatt responsiveness index was 1.4, area under the curve was 0.83 (95% confidence interval: 0.72, 0.94), and the minimum clinical important difference corresponded to an increase of 7.1 percentile points. Standardized effect size of the Numeric Pain Rating Scale was 0.72, Guyatt responsiveness index was 2.2, area under the curve was 0.80 (95% confidence interval: 0.70, 0.92), and the minimum clinical important difference corresponded to a decrease of 1.16 points. Conclusion Information from this study may be helpful to therapists when evaluating the effectiveness of rehabilitation intervention on physical function and pain, and to power future clinical trials on patients with patellofemoral pain. PMID:19229444

A randomized controlled trial comparing three invitation strategies in a breast cancer screening program.

PubMed

Segura, J M; Castells, X; Casamitjana, M; Macià, F; Porta, M; Katz, S J

2001-10-01

The objective of this study was to compare the response received by a population-based breast cancer screening program, according to three different invitation strategies: letters sent by mail from the program (program group), letters sent by mail from the Primary Health Care Team (PHT group), and direct contact through a trained professional (direct contact group). We used a cluster-randomized controlled trial with assignment to invitation group using home address. Nine hundred eighty-six women of Barcelona (Spain), ages 50 to 64 years, were invited to participate in the program. The main outcome used was the response rate after the first invitation. Five hundred sixty-four women accepted the invitation (57.2%). The highest response rate was achieved in the direct contact group (63.5%), followed by the PHT group (55.6%), the program group being the one that attained the lowest response rate (52.1%). The direct contact group had a higher probability of participating than the PHT group (RR = 1.14, P = 0.037) or the program group (RR = 1.22, P = 0.003). The response rate in the direct contact group was 72.1% when the letter was received by the subject herself. The increase in response occurred particularly among women of lower educational level. Inviting women to participate in a breast cancer screening program through direct contact by trained personnel increased participation rate compared with mailed-letter methods. The positive effect appeared restricted to women with lower educational levels. Copyright 2001 American Health Foundation and Academic Press.

Prevalence and Predictors of Burnout Among Hospice and Palliative Care Clinicians in the U.S

PubMed Central

Kamal, Arif H.; Bull, Janet H.; Wolf, Steven P.; Swetz, Keith M.; Shanafelt, Tait D.; Ast, Katherine; Kavalieratos, Dio; Sinclair, Christian T.; Abernethy, Amy P.

2016-01-01

Context Many clinical disciplines report high rates of burnout, which lead to low quality of care. Palliative care clinicians routinely manage patients with significant suffering, aiming to improve quality of life. As a major role of palliative care clinicians involves educating patients and caregivers regarding identifying priorities and balancing stress, we wondered how clinician self-management of burnout matches against the emotionally exhaustive nature of the work. Objectives We sought to understand the prevalence and predictors of burnout using a discipline-wide survey. Methods We asked American Academy of Hospice and Palliative Medicine clinician members to complete an electronic survey querying demographic factors, job responsibilities, and the Maslach Burnout Inventory. We performed univariate and multivariate regression analyses to identify predictors of high rates of burnout. Results We received 1357 responses (response rate 30%). Overall, we observed a burnout rate of 62%, with higher rates reported by nonphysician clinicians. Most burnout stemmed from emotional exhaustion, with depersonalization comprising a minor portion. Factors associated with higher rates of burnout include working in smaller organizations, working longer hours, being younger than 50 years, and working weekends. We did not observe different rates between palliative care clinicians and hospice clinicians. Higher rated self-management activities to mitigate burnout include participating in interpersonal relationships and taking vacations. Conclusions Burnout is a major issue facing the palliative care clinician workforce. Strategies at the discipline-wide and individual levels are needed to sustain the delivery of responsive, available, high-quality palliative care for all patients with serious illness. PMID:26620234

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis.

PubMed

Jairath, Vipul; Zou, Guangyong; Parker, Claire E; Macdonald, John K; Mosli, Mahmoud H; Khanna, Reena; Shackelton, Lisa M; Vandervoort, Margaret K; AlAmeel, Turki; Al Beshir, Mohammad; AlMadi, Majid; Al-Taweel, Talal; Atkinson, Nathan S S; Biswas, Sujata; Chapman, Thomas P; Dulai, Parambir S; Glaire, Mark A; Hoekman, Daniel; Koutsoumpas, Andreas; Minas, Elizabeth; Samaan, Mark A; Travis, Simon; D'Haens, Geert; Levesque, Barrett G; Sandborn, William J; Feagan, Brian G

2016-05-01

Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and remission rates in UC RCTs and identify trial design factors influencing them. MEDLINE, EMBASE, and the Cochrane Library were searched from inception through April 2014 for placebo-controlled trials in adult patients with UC of a biological agent, corticosteroid, immunosuppressant, or aminosalicylate. Data were independently doubly extracted. Quality was assessed using the Cochrane risk of bias tool. In all, 51 trials [48 induction and 10 maintenance phases] were identified. Placebo response and remission rates were pooled according to random-effects models, and mixed-effects meta-regression models were used to evaluate effects of study-level characteristics on these rates. Pooled estimates of placebo remission and response rates for induction trials were 10% (95% confidence interval [CI] 7-13%) and 33% [95% CI 29-37%], respectively. Corresponding values for maintenance trials were 19% [95% CI 11-30%] and 22% [95% CI 17-28%]. Trials enrolling patients with more active disease confirmed by endoscopy [endoscopy subscore ≥ 2] were associated with lower placebo rates. Conversely, placebo rates increased with increasing trial duration and number of study visits. Objective assessment of greater disease activity at trial entry by endoscopy lowered placebo rates, whereas increasing trial duration and more interactions with healthcare providers increased placebo rates. These findings have important implications for design and conduct of clinical trials. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A Phase II study of Dovitinib in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma

PubMed Central

Dillon, Patrick M.; Petroni, Gina R.; Horton, Bethany J.; Moskaluk, Christopher A.; Fracasso, Paula M.; Douvas, Michael G; Varhegyi, Nikole; Zaja-Milatovic, Snjezana; Thomas, Christopher Y.

2017-01-01

Purpose Genetic and preclinical studies have implicated fibroblast growth factor receptor (FGFR) signaling in the pathogenesis of adenoid cystic carcinoma (ACC). Dovitinib, a suppressor FGFR activity, may be active in ACC. Methods In a two-stage phase II study, 35 patients with progressive ACC were treated with dovitinib 500mg orally for 5 of 7 days continuously. The primary endpoints were objective response rate (ORR) and change in tumor growth rate (TGR). Progression-free survival (PFS), overall survival (OS), metabolic response, biomarker and QOL were secondary endpoints. Results Of thirty-four evaluable patients, two (6%) had a partial response and 22 (65%) had stable disease >4 months. Median PFS was 8.2 months and OS was 20.6 months. The slope of the overall TGR fell from 1.95 to 0.63 on-treatment (p<0.001). Toxicity was moderate; 63% of patients developed grade 3–4 toxicity, 94% required dose modifications, and 21% stopped treatment early. An early metabolic response based on 18FDG-PET scans was seen in 3/15 patients but did not correlate with RECIST response. MYB gene translocation was observed and significantly correlated with over-expression of MYB but did not correlate with FGFR1 phosphorylation or clinical response to dovitinib. Conclusion Dovitinib produced few objective responses in patients with ACC but did suppress the TGR with a PFS that compares favorably to those reported with other targeted agents. Future studies of more potent and selective FGFR inhibitors in biomarker-selected patients will be required to determine if FGFR signaling is a valid therapeutic target in ACC. PMID:28377480

Margin Status Remains an Important Determinant of Survival after Surgical Resection of Colorectal Liver Metastases in the Era of Modern Chemotherapy

PubMed Central

Andreou, Andreas; Aloia, Thomas A.; Brouquet, Antoine; Dickson, Paxton V.; Zimmitti, Giuseppe; Maru, Dipen M.; Kopetz, Scott; Loyer, Evelyne M.; Curley, Steven A.; Abdalla, Eddie K.; Vauthey, Jean-Nicolas

2013-01-01

Objective To determine the impact of surgical margin status on overall survival (OS) of patients undergoing hepatectomy for colorectal liver metastases (CLM) after modern preoperative chemotherapy. Summary Background Data In the era of effective chemotherapy for CLM, the association between surgical margin status and survival has become controversial. Methods Clinicopathologic data and outcomes for 378 patients treated with modern preoperative chemotherapy and hepatectomy were analyzed. The effect of positive margins on OS was analyzed in relation to pathologic and computed tomography-based morphologic response to chemotherapy. Results Fifty-two of 378 resections (14%) were R1 resections (tumor-free margin < 1 mm). The 5-year OS rates for patients with R0 resection (margin ≥ 1 mm) and R1 resection were 55% and 26%, respectively (P=0.017). Multivariate analysis identified R1 resection (P=0.03) and minor pathologic response to chemotherapy (P=0.002) as the 2 factors independently associated with worse survival. The survival benefit associated with negative margins (R0 vs. R1 resection) was greater in patients with suboptimal morphologic response (5-year OS rate: 62% vs. 11%, P=0.007) than in patients with optimal response (3-year OS rate: 92% vs. 88%, P=0.917) and greater in patients with minor pathologic response (5-year OS rate: 46% vs. 0%, P=0.002) than in patients with major response (5-year OS rate: 63% vs. 67%, P=0.587). Conclusions In the era of modern chemotherapy, negative margins remain an important determinant of survival and should be the primary goal of surgical therapy. The impact of positive margins is most pronounced in patients with suboptimal response to systemic therapy. PMID:23426338

Pulmonary Artery Wedge Pressure Relative to Exercise Work Rate in Older Men and Women.

PubMed

Esfandiari, Sam; Wright, Stephen P; Goodman, Jack M; Sasson, Zion; Mak, Susanna

2017-07-01

An augmented pulmonary artery wedge pressure (PAWP) response may explain exercise intolerance in some humans. However, routine use of exercise hemodynamic testing is limited by a lack of data from normal older men and women. Our objective was to evaluate the exercise PAWP response and the potential for sexual dimorphism in healthy, nondyspneic older adults. Thirty-six healthy volunteers (18 men [54 ± 7 yr] and 18 women [58 ± 6 yr]) were studied at rest (control) and during two stages of semi-upright cycle ergometry, at heart rates of 100 bpm (light exercise) and 120 bpm (moderate exercise). Right heart catheterization was performed to measure pulmonary pressures. The PAWP response to exercise was assessed in context of exercise work rate and body size. At control, PAWP was similar between men and women. Work rates were significantly smaller in women at comparable HR (P < 0.001). PAWP increased similarly at light exercise, with no further increase at moderate exercise. When indexed to work rate alone or work rate adjusted to body weight and height, the PAWP response at light and moderate exercise was significantly elevated in women compared with men (P < 0.05 condition-sex interaction). The change in PAWP relative to the increase in cardiac output did not exceed 2 mm Hg·L·min in any volunteer at moderate exercise. The similar rise in the PAWP response to submaximal exercise occurs despite lower work rate in healthy older women compared with men, even when adjusted for smaller body size. It is important to consider sex in the development of normal reference ranges for exercise hemodynamic testing.

Efficacy of single-agent bortezomib vs. single-agent thalidomide in patients with relapsed or refractory multiple myeloma: a systematic comparison

PubMed Central

Prince, H Miles; Adena, Michael; Smith, Dell Kingsford; Hertel, Judy

2007-01-01

Objective: To conduct a systematic review of the efficacy of single-agent bortezomib vs. single-agent thalidomide in patients with relapsed/refractory multiple. Methods: Publications in English from 1966 to June 2005 (MEDLINE, EMBASE, Cochrane library), publication reference lists, Janssen-Cilag data-on-file and abstracts from recent multiple myeloma conferences were reviewed. Prospective studies containing at least a single arm of either treatment group with n ≥ 30 were included. Studies adding dexamethasone for non-responders were excluded. Statistical pooling was performed for response rate and overall survival. Results: One bortezomib study (n = 333, NEJM 2005, 352; 2487–98) and 15 thalidomide (n = 1007) studies met these criteria and were included. Patient baseline characteristics including age, gender, IgG:IgA, disease duration and beta-2 microglobulin were well matched except that 48% of bortezomib patients had received prior thalidomide. Response rate, defined as serum M-protein reduction ≥ 50%, was 53% for patients receiving bortezomib vs. 32% for thalidomide (P < 0.001, n = 10 studies). Response rate determined by European Group for Blood and Marrow Transplantation (EBMT) criteria was 41% for patients receiving bortezomib vs. 22% for thalidomide (P < 0.001, n = 4 studies). Conclusion: Bortezomib was associated with a significantly higher response rate and complete remission rate using both M-protein and EBMT criteria. PMID:17608711

Rapid response radiation sensors for homeland security applications

NASA Astrophysics Data System (ADS)

Mukhopadhyay, Sanjoy; Maurer, Richard; Guss, Paul

2014-09-01

The National Security Technologies, LLC, Remote Sensing Laboratory is developing a rapid response radiation detection system for homeland security field applications. The intelligence-driven system is deployed only when non-radiological information about the target is verifiable. The survey area is often limited, so the detection range is small; in most cases covering a distance of 10 meters or less suffices. Definitive response is required in no more than 3 seconds and should minimize false negative alarms, but can err on the side of positive false alarms. The detection system is rapidly reconfigurable in terms of size, shape, and outer appearance; it is a plug-and-play system. Multiple radiation detection components (viz., two or more sodium iodide scintillators) are used to independently "over-determine" the existence of the threat object. Rapid response electronic dose rate meters are also included in the equipment suite. Carefully studied threat signatures are the basis of the decision making. The use of Rad-Detect predictive modeling provides information on the nature of the threat object. Rad-Detect provides accurate dose rate from heavily shielded large sources; for example those lost in Mexico were Category 1 radiation sources (~3,000 Ci of 60Co), the most dangerous of five categories defined by the International Atomic Energy Agency. Taken out of their shielding containers, Category 1 sources can kill anyone who is exposed to them at close range for a few minutes to an hour. Whenever possible sub-second data acquisition will be attempted, and, when deployed, the system will be characterized for false alarm rates. Although the radiation detection materials selected are fast (viz., faster scintillators), their speed is secondary to sensitivity, which is of primary importance. Results from these efforts will be discussed and demonstrated.

Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: A phase II Southwest Oncology Group Study (S0415)

PubMed Central

Gold, Philip J.; Goldman, Bryan; Iqbal, Syma; Leichman, Lawrence P.; Zhang, Wu; Lenz, Heinz-Josef; Blanke, Charles D.

2010-01-01

Introduction Esophageal adenocarcinomas commonly express the Epidermal Growth Factor Receptor (EGFR). This trial assessed the six month overall survival probability in metastatic esophageal cancer patients treated with cetuximab as second line therapy. Methods This was a multicenter, open-label phase II study of single agent cetuximab for metastatic esophageal adenocarcinoma patients who failed one prior chemotherapy regimen. Adequate organ function and Zubrod performance status of 0-2 were required. Patients received cetuximab 400mg/m2 IV on week one, and 250 mg/m2 IV weekly thereafter. The primary objective was to determine 6 month overall survival. Secondary endpoints included progression-free survival, response rate, and toxicity. Tumor tissue was collected for correlative studies. Results Sixty-three patients were registered, with 8 ineligible or never treated. Fifty-five eligible patients (male=49, female=6; median age=61.2 years [range 30.7-88.5]) were enrolled. Twenty patients survived > 6 months for a 6-month overall survival rate of 36% (95% CI: 24%, 50%). The median overall survival was 4.0 months (95% CI: 3.2, 5.9). Median progression-free survival was 1.8 months (95% CI: 1.7, 1.9). One partial response and 2 unconfirmed partial responses were observed. Two patients experienced grade 4 fatigue. There was one treatment-related death due to pneumonitis. Germline polymorphisms of EGFR, EGF, IL-8, COX-2, VEGF, CCND1, NRP1 and Kras mutational status were not associated with response or survival. Conclusions The 6-month overall survival rate of 36% observed on this study failed to meet the primary survival objective. Thus, cetuximab alone cannot be recommended in the second-line treatment of metastatic esophageal cancer. PMID:20631636

Prolonged Administration of Azacitidine With or Without Entinostat for Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-Related Changes: Results of the US Leukemia Intergroup Trial E1905

PubMed Central

Prebet, Thomas; Sun, Zhuoxin; Figueroa, Maria E.; Ketterling, Rhett; Melnick, Ari; Greenberg, Peter L.; Herman, James; Juckett, Mark; Smith, Mitchell R.; Malick, Lisa; Paietta, Elisabeth; Czader, Magdalena; Litzow, Mark; Gabrilove, Janice; Erba, Harry P.; Gore, Steven D.; Tallman, Martin S.

2014-01-01

Purpose Although azacitidine (AZA) improves survival in patients with high-risk myelodysplastic syndrome, the overall response remains approximately 50%. Entinostat is a histone deacetylase inhibitor that has been combined with AZA with significant clinical activity in a previous phase I dose finding study. Design Open label phase II randomized trial comparing AZA 50 mg/m2/d given for 10 days ± entinostat 4 mg/m2/d day 3 and day 10. All subtypes of myelodysplasia, chronic myelomonocytic leukemia, and acute myeloid leukemia with myelodysplasia-related changes were eligible for the study. The primary objective was the rate of hematologic normalization (HN; complete remission + partial remission + trilineage hematological improvement). Results One hundred forty-nine patients were analyzed, including 97 patients with myelodysplastic syndrome and 52 patients with acute myeloid leukemia. In the AZA group, 32% (95% CI, 22% to 44%) experienced HN and 27% (95% CI, 17% to 39%) in the AZA + entinostat group. Both arms exceeded the HN rate of historical control (Cancer and Leukemia Group B 9221 trial), but only the AZA group fulfilled the primary objective of the study. Rates of overall hematologic response were 46% and 44%, respectively. Median overall survivals were 18 months for the AZA group and 13 months for the AZA + entinostat group. The combination arm led to less demethylation compared with the monotherapy arm, suggesting pharmacodynamic antagonism. Conclusion Addition of entinostat to AZA did not increase clinical response as defined by the protocol and was associated with pharmacodynamic antagonism. However, the prolonged administration of AZA by itself seems to increase HN rate compared with standard dosing and warrants additional investigation. PMID:24663049

How should the psychological well-being of zoo elephants be objectively investigated?

PubMed

Mason, Georgia J; Veasey, Jake S

2010-01-01

Animal welfare (sometimes termed "well-being") is about feelings - states such as "suffering" or "contentment" that we can infer but cannot measure directly. Welfare indices have been developed from two main sources: studies of suffering humans, and of research animals deliberately subjected to challenges known to affect emotional state. We briefly review the resulting indices here, and discuss how well they are understood for elephants, since objective welfare assessment should play a central role in evidence-based elephant management. We cover behavioral and cognitive responses (approach/avoidance; intention, redirected and displacement activities; vigilance/startle; warning signals; cognitive biases, apathy and depression-like changes; stereotypic behavior); physiological responses (sympathetic responses; corticosteroid output - often assayed non-invasively via urine, feces or even hair; other aspects of HPA function, e.g. adrenal hypertrophy); and the potential negative effects of prolonged stress on reproduction (e.g. reduced gametogenesis; low libido; elevated still-birth rates; poor maternal care) and health (e.g. poor wound-healing; enhanced disease rates; shortened lifespans). The best validated, most used welfare indices for elephants are corticosteroid outputs and stereotypic behavior. Indices suggested as valid, partially validated, and/or validated but not yet applied within zoos include: measures of preference/avoidance; displacement movements; vocal/postural signals of affective (emotional) state; startle/vigilance; apathy; salivary and urinary epinephrine; female acyclity; infant mortality rates; skin/foot infections; cardio-vascular disease; and premature adult death. Potentially useful indices that have not yet attracted any validation work in elephants include: operant responding and place preference tests; intention and vacuum movements; fear/stress pheromone release; cognitive biases; heart rate, pupil dilation and blood pressure; corticosteroid assay from hair, especially tail-hairs (to access endocrine events up to a year ago); adrenal hypertrophy; male infertility; prolactinemia; and immunological changes.

Randomized, phase II study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 in patients with advanced soft tissue sarcoma.

PubMed

Baker, Laurence H; Rowinsky, Eric K; Mendelson, David; Humerickhouse, Rod A; Knight, Raymond A; Qian, Jiang; Carr, Robert A; Gordon, Gary B; Demetri, George D

2008-12-01

Sarcomas are among the most proangiogenic malignancies in preclinical models. Phase I study results for ABT-510, which inhibits angiogenesis via a novel thrombospondin-mimetic mechanism, suggested activity in soft tissue sarcoma (STS) patients. This phase II study further evaluated the safety and efficacy of ABT-510 in advanced STS patients. Patients with metastatic or unresectable STS were randomly assigned to treatment with one of two ABT-510 dose schedules (20 mg once a day [20 mg], n = 42; or 100 mg twice a day [200 mg], n = 46), which were self-administered subcutaneously in 28-day treatment periods. End points included progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and safety. Median PFS for the 20-mg arm was 94 days, with 4- and 6-month PFS rate estimates of 42% and 24%, respectively. Median PFS for the 200-mg arm was 64 days, with 4- and 6-month PFS rate estimates of 41% and 32%, respectively. Although only one objective response was noted, stable disease was observed in 52% (20 mg) and 48% (200 mg) of patients. Median OS was 431 days (20 mg) and 295 days (200 mg). ABT-510 was well tolerated. Rare treatment-related grade 3 or 4 adverse events were one event each of hypotension, deep vein thrombosis, and hypophosphatemia. ABT-510 pharmacokinetics were dose proportional, time independent, and consistent with those in previous studies. ABT-510 had a favorable safety profile, and the rate of disease control and OS times were encouraging. However, with low ORR and lack of dose response, the study failed to yield compelling evidence of strong single-agent activity in STS.

Prolonged administration of azacitidine with or without entinostat for myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes: results of the US Leukemia Intergroup trial E1905.

PubMed

Prebet, Thomas; Sun, Zhuoxin; Figueroa, Maria E; Ketterling, Rhett; Melnick, Ari; Greenberg, Peter L; Herman, James; Juckett, Mark; Smith, Mitchell R; Malick, Lisa; Paietta, Elisabeth; Czader, Magdalena; Litzow, Mark; Gabrilove, Janice; Erba, Harry P; Gore, Steven D; Tallman, Martin S

2014-04-20

Although azacitidine (AZA) improves survival in patients with high-risk myelodysplastic syndrome, the overall response remains approximately 50%. Entinostat is a histone deacetylase inhibitor that has been combined with AZA with significant clinical activity in a previous phase I dose finding study. Open label phase II randomized trial comparing AZA 50 mg/m(2)/d given for 10 days ± entinostat 4 mg/m(2)/d day 3 and day 10. All subtypes of myelodysplasia, chronic myelomonocytic leukemia, and acute myeloid leukemia with myelodysplasia-related changes were eligible for the study. The primary objective was the rate of hematologic normalization (HN; complete remission + partial remission + trilineage hematological improvement). One hundred forty-nine patients were analyzed, including 97 patients with myelodysplastic syndrome and 52 patients with acute myeloid leukemia. In the AZA group, 32% (95% CI, 22% to 44%) experienced HN and 27% (95% CI, 17% to 39%) in the AZA + entinostat group. Both arms exceeded the HN rate of historical control (Cancer and Leukemia Group B 9221 trial), but only the AZA group fulfilled the primary objective of the study. Rates of overall hematologic response were 46% and 44%, respectively. Median overall survivals were 18 months for the AZA group and 13 months for the AZA + entinostat group. The combination arm led to less demethylation compared with the monotherapy arm, suggesting pharmacodynamic antagonism. Addition of entinostat to AZA did not increase clinical response as defined by the protocol and was associated with pharmacodynamic antagonism. However, the prolonged administration of AZA by itself seems to increase HN rate compared with standard dosing and warrants additional investigation.

Quickly updatable hologram images with high performance photorefractive polymer composites

NASA Astrophysics Data System (ADS)

Tsutsumi, Naoto; Kinashi, Kenji; Nonomura, Asato; Sakai, Wataru

2012-02-01

We present here quickly updatable hologram images using high performance photorefractive (PR) polymer composite based on poly(N-vinyl carbazole) (PVCz). PVCz is one of the pioneer materials for photoconductive polymer. PVCz/7- DCST/CzEPA/TNF (44/35/20/1 by wt) gives high diffraction efficiency of 68 % at E = 45 V/μm with fast response speed. Response speed of optical diffraction is the key parameter for real-time 3D holographic display. Key parameter for obtaining quickly updatable hologram images is to control the glass transition temperature lower enough to enhance chromophore orientation. Object image of the reflected coin surface recorded with reference beam at 532 nm (green beam) in the PR polymer composite is simultaneously reconstructed using a red probe beam at 642 nm. Instead of using coin object, object image produced by a computer was displayed on a spatial light modulator (SLM) is used as an object for hologram. Reflected object beam from a SLM interfered with reference beam on PR polymer composite to record a hologram and simultaneously reconstructed by a red probe beam. Movie produced in a computer was recorded as a realtime hologram in the PR polymer composite and simultaneously clearly reconstructed with a video rate.

The stability of individual patterns of autonomic responses to motion sickness stimulation

NASA Technical Reports Server (NTRS)

Cowings, Patricia S.; Toscano, William B.; Naifeh, Karen H.

1990-01-01

As part of a program to develop a treatment for motion sickness based on self-regulation of autonomic nervous system (ANS) activity, this study examined the stability of an individual's pattern of ANS responses to motion sickness stimulation on repeated occasions. Motion sickness symptoms were induced in 58 people during two rotating chair test. Physiological responses measured were heart rate, finger pulse volume, respiration rate, and skin conductance. Using standard scores, stability of responses of specific magnitudes across both tests is as examined. Correlational analyses, analysis of variance, and a components of variance analysis all revealed marked, but quite stable, individual differences in ANS responses to both mild and severe motion sickness. These findings confirm the prior observation that people are sufficiently unique in their ANS responses to motion sickness provocation to make it nesessary to individually tailor self-regulation training. Further, these data support the contention that individual ANS patterns are sufficiently consistent from test to test so as to serve as an objective indicator of individual motion sickness malaise levels.

Cannabis and Ecstasy/ MDMA: empirical measures of creativity in recreational users.

PubMed

Jones, Katy A; Blagrove, M; Parrott, A C

2009-12-01

This study investigated the associations between chronic cannabis and Ecstasy/MDMA use and one objective and two subjective measure of creativity. Fifteen abstinent Ecstasy users, 15 abstinent cannabis users, and 15 nondrug-user controls, completed three measures of creativity: the Consequences behavioral test of creativity, self-assessed performance on the Consequences test, and Gough's Trait Self-Report Creative Adjective Checklist. The Consequences test involved five scenarios where possible consequences had to be devised; scoring was conducted by the standard blind rating (by two independent judges) for "remoteness" and "rarity," and by a frequency and rarity of responses method. Cannabis users had significantly more "rare-creative" responses than controls (Tukey, p < 0.05); this effect remained significant with gender as a covariate. There were no significant differences between the groups on the number of standard scoring "remote-creative" ideas or for fluency of responses. On self-rated creativity, there was a significant ANOVA group difference (p < 0.05), with Ecstasy users tending to rate their answers as more creative than controls (Tukey comparison; p = 0.058, two-tailed). Ecstasy users did not differ from controls on the behavioral measures of creativity, although there was a borderline trend for self-assessment of greater creativity. Cannabis users produced significantly more "rare-creative" responses, but did not rate themselves as more creative.

GWM-a ground-water management process for the U.S. Geological Survey modular ground-water model (MODFLOW-2000)

USGS Publications Warehouse

Ahlfeld, David P.; Barlow, Paul M.; Mulligan, Anne E.

2005-01-01

GWM is a Ground?Water Management Process for the U.S. Geological Survey modular three?dimensional ground?water model, MODFLOW?2000. GWM uses a response?matrix approach to solve several types of linear, nonlinear, and mixed?binary linear ground?water management formulations. Each management formulation consists of a set of decision variables, an objective function, and a set of constraints. Three types of decision variables are supported by GWM: flow?rate decision variables, which are withdrawal or injection rates at well sites; external decision variables, which are sources or sinks of water that are external to the flow model and do not directly affect the state variables of the simulated ground?water system (heads, streamflows, and so forth); and binary variables, which have values of 0 or 1 and are used to define the status of flow?rate or external decision variables. Flow?rate decision variables can represent wells that extend over one or more model cells and be active during one or more model stress periods; external variables also can be active during one or more stress periods. A single objective function is supported by GWM, which can be specified to either minimize or maximize the weighted sum of the three types of decision variables. Four types of constraints can be specified in a GWM formulation: upper and lower bounds on the flow?rate and external decision variables; linear summations of the three types of decision variables; hydraulic?head based constraints, including drawdowns, head differences, and head gradients; and streamflow and streamflow?depletion constraints. The Response Matrix Solution (RMS) Package of GWM uses the Ground?Water Flow Process of MODFLOW to calculate the change in head at each constraint location that results from a perturbation of a flow?rate variable; these changes are used to calculate the response coefficients. For linear management formulations, the resulting matrix of response coefficients is then combined with other components of the linear management formulation to form a complete linear formulation; the formulation is then solved by use of the simplex algorithm, which is incorporated into the RMS Package. Nonlinear formulations arise for simulated conditions that include water?table (unconfined) aquifers or head?dependent boundary conditions (such as streams, drains, or evapotranspiration from the water table). Nonlinear formulations are solved by sequential linear programming; that is, repeated linearization of the nonlinear features of the management problem. In this approach, response coefficients are recalculated for each iteration of the solution process. Mixed?binary linear (or mildly nonlinear) formulations are solved by use of the branch and bound algorithm, which is also incorporated into the RMS Package. Three sample problems are provided to demonstrate the use of GWM for typical ground?water flow management problems. These sample problems provide examples of how GWM input files are constructed to specify the decision variables, objective function, constraints, and solution process for a GWM run. The GWM Process runs with the MODFLOW?2000 Global and Ground?Water Flow Processes, but in its current form GWM cannot be used with the Observation, Sensitivity, Parameter?Estimation, or Ground?Water Transport Processes. The GWM Process is written with a modular structure so that new objective functions, constraint types, and solution algorithms can be added.

Response audit of an Internet survey of health care providers and administrators: implications for determination of response rates.

PubMed

Dobrow, Mark J; Orchard, Margo C; Golden, Brian; Holowaty, Eric; Paszat, Lawrence; Brown, Adalsteinn D; Sullivan, Terrence

2008-10-16

Internet survey modalities often compare unfavorably with traditional survey modalities, particularly with respect to response rates. Response to Internet surveys can be affected by the distribution options and response/collection features employed as well as the existence of automated (out-of-office) replies, automated forwarding, server rejection, and organizational or personal spam filters. However, Internet surveys also provide unparalleled opportunities to track study subjects and examine many of the factors influencing the determination of response rates. Tracking data available for Internet surveys provide detailed information and immediate feedback on a significant component of response that other survey modalities cannot match. This paper presents a response audit of a large Internet survey of more than 5000 cancer care providers and administrators in Ontario, Canada. Building upon the CHEcklist for Reporting Results of Internet E-Surveys (CHERRIES), the main objectives of the paper are to (a) assess the impact of a range of factors on the determination of response rates for Internet surveys and (b) recommend steps for improving published descriptions of Internet survey methods. We audited the survey response data, analyzing the factors that affected the numerator and denominator in the ultimate determination of response. We also conducted a sensitivity analysis to account for the inherent uncertainty associated with the impact of some of the factors on the response rates. The survey was initially sent out to 5636 health care providers and administrators. The determination of the numerator was influenced by duplicate/unattached responses and response completeness. The numerator varied from a maximum of 2031 crude (unadjusted) responses to 1849 unique views, 1769 participants, and 1616 complete responses. The determination of the denominator was influenced by forwarding of the invitation email to unknown individuals, server rejections, automated replies, spam filters, and 'opt out' options. Based on these factors, the denominator varied from a minimum of 5106 to a maximum of 5922. Considering the different assumptions for the numerator and the denominator, the sensitivity analysis resulted in a 12.5% variation in the response rate (from minimum of 27.3% to maximum of 39.8%) with a best estimate of 32.8%. Depending on how the numerator and denominator are chosen, the resulting response rates can vary widely. The CHERRIES statement was an important advance in identifying key characteristics of Internet surveys that can influence response rates. This response audit suggests the need to further clarify some of these factors when reporting on Internet surveys for health care providers and administrators, particularly when using commercially available Internet survey packages for specified, rather than convenience, samples.

Subjective and objective measurements of postoperative pain in cats.

PubMed

Cambridge, A J; Tobias, K M; Newberry, R C; Sarkar, D K

2000-09-01

To evaluate the ability of various subjective and objective measurements to determine the presence and degree of postoperative pain in cats. Randomized controlled prospective clinical study. 18 healthy client-owned cats. Cats were randomly assigned to 3 groups of 6: control, tenectomy, and onychectomy. Jugular catheters were placed the day prior to surgery. All surgeries were performed by the same surgeon, and all observations were made by the same blinded trained observer. One hour prior to surgery and at assigned intervals for 36 hours after surgery, heart rate, respiratory rate, and rectal temperature were measured. Scores were assigned for 3 interaction responses, including response to palpation, by use of simple descriptive scales, and to 2 pain assessments by use of visual analogue scales. Blood was collected to measure plasma beta-endorphin and cortisol concentrations. Butorphanol was administered to all cats before surgery and to any cat subjectively assessed to be experiencing pain after surgery. Only visual analogue scale scores and response to palpation scores differed significantly between control and surgical groups. Determination of the presence of pain in cats can be made on the basis of observation and interaction by a trained observer. Physiologic measurements, including plasma cortisol and beta-endorphin concentrations, did not differentiate between control cats and cats that underwent surgery.

76 FR 3609 - Proposed Information Collection; Comment Request; Census in Schools and Partnership Program Research

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-20

... in Schools and Partnership Program Research AGENCY: U.S. Census Bureau, Commerce. ACTION: Notice... Schools (CIS) Program and the Partnership Program (PP) with three primary objectives: (1) To increase the mail-back response rate of census forms; (2) to improve the accuracy and reduce differential undercount...

Outcome Measures of Triple Board Graduates, 1991-2003

ERIC Educational Resources Information Center

Warren, Marla J.; Dunn, David W.; Rushton, Jerry

2006-01-01

Objective: To describe program outcomes for the Combined Training Program in Child and Adolescent Psychiatry, Pediatrics, and Psychiatry (Triple Board Program). Method: All Triple Board Program graduates to date (1991-2003) were asked to participate in a 37-item written survey from February to April 2004. Results: The response rate was 80.7%. Most…

The Effects of State Funding on Property Tax Rates and School Construction

ERIC Educational Resources Information Center

Plummer, Elizabeth

2006-01-01

In response to concerns over funding for school construction, the state of Texas has implemented two programs to assist school districts with construction-related debt. This paper examines whether these programs have accomplished their objectives of reducing property taxes (the Existing Debt Allotment (EDA) program) and increasing capital outlays…

Development, Evaluation, and Validation of Environmental Assessment Tools to Evaluate the College Nutrition Environment

ERIC Educational Resources Information Center

Freedman, Marjorie R.

2010-01-01

Objective: To develop, evaluate, and validate 2 nutrition environment assessment tools (surveys), for specific use in combating overweight on college/university campuses. Participants and Methods: Invitations to complete surveys were e-mailed to food service and health center directors at 47 universities, Winter 2008. Overall response rate was…

Combination Lithium and Divalproex Sodium in Pediatric Bipolar Symptom Restabilization

ERIC Educational Resources Information Center

Findling, Robert L.; McNamara, Nora K.; Stansbrey, Robert; Gracious, Barbara L.; Whipkey, Resaca E.; Demeter, Christine A.; Reed, Michael D.; Youngstrom, Eric A.; Calabrese, Joseph R.

2006-01-01

Objective: It has been reported that bipolar disorder may become less responsive to previously effective treatment with each symptomatic relapse. The primary goal of this study was to assess the rate of restabilization after the resumption of lithium ([Li[superscript +]) plus divalproex (DVPX) following relapse on either agent as monotherapy.…

Serum Elimination Profiles of Methyllycaconitine and Deltaline in Cattle Following Oral Administration of Larkspur (Delphinium barbeyi)

USDA-ARS?s Scientific Manuscript database

The objectives of this study were to describe the simple elimination kinetics of two abundant norditerpenoid alkaloids in larkspur, MLA and deltaline, and measure the heart rate response of intoxicated cattle over 96 hours. Five Angus steers halter broke, gentled, and habituated to metabolism crate...

Projected outcomes of a public-industry partnership for enhancing corn nitrogen research and datasets

USDA-ARS?s Scientific Manuscript database

Research is needed over a wide geographic range of soil and weather scenarios to evaluate methods and tools for corn N fertilizer applications. The objectives of this research were to conduct standardized corn N rate response field studies to evaluate the performance of multiple public-domain N deci...

Substance Use and Attitudes on Professional Conduct among Medical Students: A Single-Institution Study

ERIC Educational Resources Information Center

Choi, Daisi; Tolova, Vera; Socha, Edward; Samenow, Charles P.

2013-01-01

Objective: This study sought to examine how specific substance-use behavior, including nonmedical prescription stimulant (NPS) use, among U.S. medical students correlates with their attitudes and beliefs toward professionalism. Method: An anonymous survey was distributed to all medical students at a private medical university (46% response rate).…

Deconstructing Pediatric Depression Trials: An Analysis of the Effects of Expectancy and Therapeutic Contact

ERIC Educational Resources Information Center

Rutherford, Bret R.; Sneed, Joel R.; Tandler, Jane M.; Rindskopf, David; Peterson, Bradley S.; Roose, Steven P.

2011-01-01

Objective: This study investigated how study type, mean patient age, and amount of contact with research staff affected response rates to medication and placebo in acute antidepressant trials for pediatric depression. Method: Data were extracted from nine open, four active comparator, and 18 placebo-controlled studies of antidepressants for…

Confirmatory Factor Analysis on the Professional Suitability Scale for Social Work Practice

ERIC Educational Resources Information Center

Tam, Dora M. Y.; Twigg, Robert C.; Boey, Kam-Wing; Kwok, Siu-Ming

2013-01-01

Objective: This article presents a validation study to examine the factor structure of an instrument designed to measure professional suitability for social work practice. Method: Data were collected from registered social workers in a provincial mailed survey. The response rate was 23.2%. After eliminating five cases with multivariate outliers,…

Education and Child Welfare Supervisor Performance: Does a Social Work Degree Matter?

ERIC Educational Resources Information Center

Perry, Robin E.

2006-01-01

Objective: To empirically examine whether the educational background of child welfare supervisors in Florida affects performance evaluations of their work. Method: A complete population sample (yielding a 58.5% response rate) of administrator and peer evaluations of child welfare workers' supervisors. ANOVA procedures were utilized to test if…

Environmental heat stress modulates thyroid status and its response to repeated endotoxin (LPS) challenge in steers

USDA-ARS?s Scientific Manuscript database

Thyroid hormones are important in the adaptation to heat stress, allowing the adjustment of metabolic rates in favor of decreased energy utilization and heat production. Thyroid status is compromised in a variety of acute and chronic infections and toxin-mediated disease states. Our objective was to...

Biomechanical models for radial distance determination by the rat vibrissal system.

PubMed

Birdwell, J Alexander; Solomon, Joseph H; Thajchayapong, Montakan; Taylor, Michael A; Cheely, Matthew; Towal, R Blythe; Conradt, Jorg; Hartmann, Mitra J Z

2007-10-01

Rats use active, rhythmic movements of their whiskers to acquire tactile information about three-dimensional object features. There are no receptors along the length of the whisker; therefore all tactile information must be mechanically transduced back to receptors at the whisker base. This raises the question: how might the rat determine the radial contact position of an object along the whisker? We developed two complementary biomechanical models that show that the rat could determine radial object distance by monitoring the rate of change of moment (or equivalently, the rate of change of curvature) at the whisker base. The first model is used to explore the effects of taper and inherent whisker curvature on whisker deformation and used to predict the shapes of real rat whiskers during deflections at different radial distances. Predicted shapes closely matched experimental measurements. The second model describes the relationship between radial object distance and the rate of change of moment at the base of a tapered, inherently curved whisker. Together, these models can account for recent recordings showing that some trigeminal ganglion (Vg) neurons encode closer radial distances with increased firing rates. The models also suggest that four and only four physical variables at the whisker base -- angular position, angular velocity, moment, and rate of change of moment -- are needed to describe the dynamic state of a whisker. We interpret these results in the context of our evolving hypothesis that neural responses in Vg can be represented using a state-encoding scheme that includes combinations of these four variables.

Effect of feature-selective attention on neuronal responses in macaque area MT

PubMed Central

Chen, X.; Hoffmann, K.-P.; Albright, T. D.

2012-01-01

Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color). PMID:22170961

Effect of feature-selective attention on neuronal responses in macaque area MT.

PubMed

Chen, X; Hoffmann, K-P; Albright, T D; Thiele, A

2012-03-01

Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color).

Naltrexone for impulse control disorders in Parkinson disease

PubMed Central

Papay, Kimberly; Xie, Sharon X.; Stern, Matthew; Hurtig, Howard; Siderowf, Andrew; Duda, John E.; Minger, James

2014-01-01

Objective: Impulse control disorders (ICDs) in Parkinson disease (PD) are common and can be difficult to manage. The objective of this study was to determine the efficacy and tolerability of naltrexone, an opioid antagonist, for the treatment of ICDs in PD. Methods: Patients with PD (n = 50) and an ICD were enrolled in an 8-week, randomized (1:1), double-blind, placebo-controlled study of naltrexone 50–100 mg/d (flexible dosing). The primary outcome measure was response based on the Clinical Global Impression–Change score, and the secondary outcome measure was change in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease–Rating Scale (QUIP-RS) ICD score. Results: Forty-five patients (90%) completed the study. The Clinical Global Impression–Change response rate difference favoring naltrexone in completers was 19.8% (95% confidence interval [CI] −8.7% to 44.2%). While this difference was not significant (odds ratio = 1.6, 95% CI 0.5–5.2, Wald χ2 [df] = 0.5 [1], p = 0.5), naltrexone treatment led to a significantly greater decrease in QUIP-RS ICD score over time compared with placebo (regression coefficient for interaction term in linear mixed-effects model = −7.37, F[df] = 4.3 [1, 49], p = 0.04). The estimated changes in QUIP-RS ICD scores from baseline to week 8 were 14.9 points (95% CI 9.9–19.9) for naltrexone and 7.5 points (95% CI 2.5–12.6) for placebo. Conclusions: Naltrexone treatment was not efficacious for the treatment of ICDs in PD using a global assessment of response, but findings using a PD-specific ICD rating scale support further evaluation of opioid antagonists for the treatment of ICD symptoms in PD. Classification of evidence: This study provides Class I evidence that in patients with PD and an ICD, naltrexone does not significantly increase the probability of achieving response. However, the study lacked the precision to exclude an important difference in response rates. PMID:25037206

A Prospective Phase 2 Multicenter Study for the Efficacy of Radiation Therapy Following Incomplete Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma

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

Choi, Chihwan; Koom, Woong Sub; Kim, Tae Hyun

2014-12-01

Purpose: The purpose of this study was to investigate the efficacy and toxicity of radiation therapy (RT) following incomplete transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC). Methods and Materials: The study was designed as a prospective phase 2 multicenter trial. Patients with unresectable HCC, who had viable tumor after TACE of no more than 3 courses, were eligible. Three-dimensional conformal RT (3D-CRT) was added for HCC treatment with incomplete uptake of iodized oil, and the interval from TACE to RT was 4 to 6 weeks. The primary endpoint of this study was the tumor response after RT following incomplete TACEmore » in unresectable HCC. Secondary endpoints were patterns of failure, progression-free survival (PFS), time to tumor progression (TTP), overall survival (OS) rates at 2 years, and treatment-associated toxicity. Survival was calculated from the start of RT. Results: Between August 2008 and December 2010, 31 patients were enrolled. RT was delivered at a median dose of 54 Gy (range, 46-59.4 Gy) at 1.8 to 2 Gy per fraction. A best objective in-field response rate was achieved in 83.9% of patients, with complete response (CR) in 22.6% of patients and partial response in 61.3% of patients within 12 weeks post-RT. A best objective overall response rate was achieved in 64.5% of patients with CR in 19.4% of patients and PR in 45.1% of patients. The 2-year in-field PFS, PFS, TTP, and OS rates were 45.2%, 29.0%, 36.6%, and 61.3%, respectively. The Barcelona Clinic liver cancer stage was a significant independent prognostic factor for PFS (P=.023). Classic radiation-induced liver disease was not observed. There were no treatment-related deaths or hepatic failure. Conclusions: Early 3D-CRT following incomplete TACE is a safe and practical treatment option for patients with unresectable HCC.« less

Enhancing Response Rates in Physician Surveys: The Limited Utility of Electronic Options

PubMed Central

Nicholls, Keith; Chapman, Kathryn; Shaw, Thomas; Perkins, Allen; Sullivan, Margaret Murray; Crutchfield, Susan; Reed, Eddie

2011-01-01

Objective To evaluate the utility of offering physicians electronic options as alternatives to completing mail questionnaires. Data Source A survey of colorectal cancer screening practices of Alabama primary care physicians, conducted May–June 2010. Study Design In the follow-up to a mail questionnaire, physicians were offered options of completing surveys by telephone, fax, email, or online. Data Collection Method Detailed records were kept on the timing and mode of completion of surveys. Principal Findings Eighty-eight percent of surveys were returned by mail, 10 percent were returned by fax, and only 2 percent were completed online; none were completed by telephone or email. Conclusions Offering fax options increases response rates, but providing other electronic options does not. PMID:21492157

Categorizing moving objects into film genres: the effect of animacy attribution, emotional response, and the deviation from non-fiction.

PubMed

Visch, Valentijn T; Tan, Ed S

2009-02-01

The reported study follows the footsteps of Heider, and Simmel (1944) [Heider, F., & Simmel, M. (1944). An experimental study of apparent behavior. American Journal of Psychology, 57, 243-249] and Michotte (1946/1963) [Michotte, A. (1963). The perception of causality (T.R. Miles & E. Miles, Trans.). London: Methuen (Original work published 1946)] who demonstrated the role of object movement in attributions of life-likeness to figures. It goes one step further in studying the categorization of film scenes as to genre as a function of object movements. In an animated film scene portraying a chase, movements of the chasing object were systematically varied as to parameters: velocity, efficiency, fluency, detail, and deformation. The object movements were categorized by viewers into genres: non-fiction, comedy, drama, and action. Besides this categorization, viewers rated their animacy attribution and emotional response. Results showed that non-expert viewers were consistent in categorizing the genres according to object movement parameters. The size of its deviation from the unmanipulated movement scene determined the assignment of any target scene to one of the fiction genres: small and moderate deviations resulted in categorization as drama and action, and large deviations as comedy. The results suggest that genre classification is achieved by, at least, three distinct cognitive processes: (a) animacy attribution, which influences the fiction versus non-fiction classification; (b) emotional responses, which influences the classification of a specific fiction genre; and (c) the amount of deviation from reality, at least with regard to movements.

A System for Rapidly and Accurately Collecting Patients’ Race and Ethnicity

PubMed Central

Baker, David W.; Cameron, Kenzie A.; Feinglass, Joseph; Thompson, Jason A.; Georgas, Patricia; Foster, Shawn; Pierce, Deborah; Hasnain-Wynia, Romana

2006-01-01

Objectives. We assessed the feasibility of collecting race/ethnicity data from patients using their own preferred racial/ethnic terms. Methods. The 424 patients described their race/ethnicity using their own categories, and we compared their descriptions with their responses to the questions (1) “Do you consider yourself Latino or Hispanic?” and (2) “Which category best describes your race?” (7 response options in our computer interview). We also determined patients’ preferences between the 2 approaches. Results.seconds. Rates of missing values and categorization as “other” race were lower than with the closed questions. Agreement between racial/ethnic categorization with open-ended and closed responses was 93% (κ =0.88). Latino/Hispanic and multiracial/multiethnic individuals were more likely to prefer using their own categories to describe their race/ethnicity. Conclusions. Collecting race/ethnicity data using patients’ own racial/ethnic categories is feasible with the use of computerized systems to capture verbatim responses and results in lower rates of missing and unusable data than do standard questions. PMID:16449590

Prediction of surface roughness and cutting force under MQL turning of AISI 4340 with nano fluid by using response surface methodology

NASA Astrophysics Data System (ADS)

Patole, Pralhad B.; Kulkarni, Vivek V.

2018-06-01

This paper presents an investigation into the minimum quantity lubrication mode with nano fluid during turning of alloy steel AISI 4340 work piece material with the objective of experimental model in order to predict surface roughness and cutting force and analyze effect of process parameters on machinability. Full factorial design matrix was used for experimental plan. According to design of experiment surface roughness and cutting force were measured. The relationship between the response variables and the process parameters is determined through the response surface methodology, using a quadratic regression model. Results show how much surface roughness is mainly influenced by feed rate and cutting speed. The depth of cut exhibits maximum influence on cutting force components as compared to the feed rate and cutting speed. The values predicted from the model and experimental values are very close to each other.

Quantifying the Physiological Stress Response to Simulated Maritime Pilotage Tasks

PubMed Central

Main, Luana C.; Wolkow, Alexander; Chambers, Timothy P.

2017-01-01

Objective: The aim of this study was to quantify the stress associated with performing maritime pilotage tasks in a high-fidelity simulator. Methods: Eight trainee and 13 maritime pilots completed two simulated pilotage tasks of varying complexity. Salivary cortisol samples were collected pre- and post-simulation for both trials. Heart rate was measured continuously throughout the study. Results: Significant changes in salivary cortisol (P = 0.000, η2 = 0.139), average (P = 0.006, η2 = 0.087), and peak heart rate (P = 0.013, η2 = 0.077) from pre- to postsimulation were found. Varying task complexity did partially influence stress response; average (P = 0.016, η2 = 0.026) and peak heart rate (P = 0.034, η2 = 0.020) were higher in the experimental condition. Trainees also recorded higher average (P = 0.000, η2 = 0.054) and peak heart rates (P = 0.027, η2 = 0.022). Conclusion: Performing simulated pilotage tasks evoked a measurable stress response in both trainee and expert maritime pilots. PMID:28922309

The efficacy of anti-PD-1 agents in acral and mucosal melanoma.

PubMed

Shoushtari, Alexander N; Munhoz, Rodrigo R; Kuk, Deborah; Ott, Patrick A; Johnson, Douglas B; Tsai, Katy K; Rapisuwon, Suthee; Eroglu, Zeynep; Sullivan, Ryan J; Luke, Jason J; Gangadhar, Tara C; Salama, April K S; Clark, Varina; Burias, Clare; Puzanov, Igor; Atkins, Michael B; Algazi, Alain P; Ribas, Antoni; Wolchok, Jedd D; Postow, Michael A

2016-11-15

Therapeutic antibodies against programmed cell death receptor 1 (PD-1) are considered front-line therapy in metastatic melanoma. The efficacy of PD-1 blockade for patients with biologically distinct melanomas arising from acral and mucosal surfaces has not been well described. A multi-institutional, retrospective cohort analysis identified adults with advanced acral and mucosal melanoma who received treatment with nivolumab or pembrolizumab as standard clinical practice through expanded access programs or published prospective trials. Objective responses were determined using investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival and overall survival were assessed using the Kaplan-Meier method. Sixty individuals were identified, including 25 (42%) with acral melanoma and 35 (58%) with mucosal melanoma. Fifty-one patients (85%) had received previous therapy, including 77% who had previously received ipilimumab. Forty patients (67%) received pembrolizumab at a dose of 2 mg/kg or 10 mg/kg, and 20 (33%) received nivolumab at a doses ranging from 0.3 to 10 mg/kg every 2 to 3 weeks. The objective response rate was 32% (95% confidence interval, 15%-54%) in patients with acral melanoma and 23% (95% confidence interval, 10%-40%) in those with mucosal melanoma. After a median follow-up of 20 months in the acral melanoma group and 10.6 months in the mucosal melanoma group, the median progression-free survival was 4.1 months and 3.9 months, respectively. Only 2 patients (3%) discontinued treatment because of toxicity. Response rates to PD-1 blockade in patients with acral and mucosal melanomas were comparable to the published rates in patients with cutaneous melanoma and support the routine use of PD-1 blockade in clinical practice. Further investigation is needed to identify the mechanisms of response and resistance to therapy in these subtypes. Cancer 2016;122:3354-3362. © 2016 American Cancer Society. © 2016 American Cancer Society.

Role of nocturnal penile erection test on response to daily sildenafil in patients with erectile dysfunction due to pelvic fracture urethral disruption: a single-center experience.

PubMed

Peng, Jing; Zhang, Zhichao; Cui, Wanshou; Yuan, Yiming; Gao, Bing; Song, Weidong; Xin, Zhongcheng

2014-12-01

To evaluate the results of nocturnal penile erection test and response to daily sildenafil in patients with erectile dysfunction (ED) due to pelvic fracture urethral disruption. From January 2010 to January 2012, we included 38 patients with ED due to pelvic fracture urethral disruption. The mean age was 33.1 years (range, 22-49 years). All were evaluated subjectively and objectively by the International Index of Erectile Function-5, nocturnal penile tumescence and rigidity (NPTR) test, and penile Doppler ultrasonography. Patients received daily sildenafil 50 mg for 3 months. Thirty-one patients were followed up: 54.8% showed response to sildenafil defined as reporting successful vaginal penetration and intercourse. Patients with neurogenic, arterial, and venous EDs did not differ in efficiency rates (P = .587). However, the penile erectile rigidity recorded by NPTR test affected efficiency significantly (P = .046). Patients with tip rigidity >40% had the highest response rate (76.9%), but the response rate for patients with tip rigidity <20% was only 22.2%. NPTR recording can reveal resident erectile function in patients with ED due to trauma and is significant for selecting pharmacologic treatment as optimal therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation

NASA Astrophysics Data System (ADS)

Nguyen, T. A. K.; DiGiovanna, J.; Cavuscens, S.; Ranieri, M.; Guinand, N.; van de Berg, R.; Carpaneto, J.; Kingma, H.; Guyot, J.-P.; Micera, S.; Perez Fornos, A.

2016-08-01

Objective. The vestibular system provides essential information about balance and spatial orientation via the brain to other sensory and motor systems. Bilateral vestibular loss significantly reduces quality of life, but vestibular implants (VIs) have demonstrated potential to restore lost function. However, optimal electrical stimulation strategies have not yet been identified in patients. In this study, we compared the two most common strategies, pulse amplitude modulation (PAM) and pulse rate modulation (PRM), in patients. Approach. Four subjects with a modified cochlear implant including electrodes targeting the peripheral vestibular nerve branches were tested. Charge-equivalent PAM and PRM were applied after adaptation to baseline stimulation. Vestibulo-ocular reflex eye movement responses were recorded to evaluate stimulation efficacy during acute clinical testing sessions. Main results. PAM evoked larger amplitude eye movement responses than PRM. Eye movement response axes for lateral canal stimulation were marginally better aligned with PRM than with PAM. A neural network model was developed for the tested stimulation strategies to provide insights on possible neural mechanisms. This model suggested that PAM would consistently cause a larger ensemble firing rate of neurons and thus larger responses than PRM. Significance. Due to the larger magnitude of eye movement responses, our findings strongly suggest PAM as the preferred strategy for initial VI modulation.

Real-world Efficacy and Safety of Nivolumab for Advanced Non-Small-cell Lung Cancer: A Retrospective Multicenter Analysis.

PubMed

Kobayashi, Keigo; Nakachi, Ichiro; Naoki, Katsuhiko; Satomi, Ryosuke; Nakamura, Morio; Inoue, Takashi; Tateno, Hiroki; Sakamaki, Fumio; Sayama, Koichi; Terashima, Takeshi; Koh, Hidefumi; Abe, Takayuki; Nishino, Makoto; Arai, Daisuke; Yasuda, Hiroyuki; Kawada, Ichiro; Soejima, Kenzo; Betsuyaku, Tomoko

2018-05-01

Nivolumab, an immune checkpoint inhibitor, is now a standard treatment for previously treated advanced non-small-cell lung cancer based on the results from phase III clinical trials. We evaluated the real-world efficacy and safety of nivolumab in a nonselected population and identified the clinical characteristics that influence efficacy. A total of 142 patients with advanced non-small-cell lung cancer who were administered nivolumab at Keio University and affiliated hospitals in Japan from January to July 2016 were enrolled. The treatment efficacy and adverse events were retrospectively reviewed, and the clinical characteristics associated with the nivolumab response were evaluated using univariate and stratified analyses and the Cochran-Mantel-Haenszel test. The objective response rate was 17.0% (95% confidence interval [CI], 12.0%-24.0%), the median progression-free survival (PFS) was 58 days (95% CI, 50-67 days), and the proportion of patients with adverse events of any grade was 45.0%. EGFR/ALK mutation status was inversely associated with the treatment response (P < .05), and the difference in PFS for the mutation-positive versus mutation-negative patients was statistically significant (49 vs. 63 days; hazard ratio, 1.9; 95% CI, 1.1-5.2; P = .029). Previous radiotherapy also had a positive association with the treatment response (P = .012). The objective response rate, PFS, and adverse event profiles were comparable to those observed in previous clinical trials. EGFR/ALK mutation-negative status and previous radiotherapy might be key clinical characteristics associated with a positive treatment response. Our findings could aid in the efficient immunotherapeutic management of lung cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Vancomycin Ophthalmic Ointment 1% for methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis infections: a case series

PubMed Central

Sotozono, Chie; Fukuda, Masahiko; Ohishi, Masao; Yano, Keiko; Origasa, Hideki; Saiki, Yoshinori; Shimomura, Yoshikazu; Kinoshita, Shigeru

2013-01-01

Objectives To investigate the efficacy and safety of Vancomycin Ophthalmic Ointment 1% (Toa Pharmaceutical Co., Ltd, Toyama, Japan) in patients with external ocular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE). Design A case series. Setting This study was a multicentre, open-label, uncontrolled study in Japan approved as orphan drug status. Participants Patients with MRSA or MRSE external ocular infections unresponsive to the treatment of fluoroquinolone eye drops. Interventions Vancomycin Ophthalmic Ointment 1% was administered four times daily. Primary and secondary outcome measures The subjective and objective clinical scores and bacterial cultures were collected at days 0 (baseline), 3, 7 and 14. The primary outcome was clinical response evaluation (efficacy rate) determined as complete response, partial response, no response and worsening. Secondary outcome was the eradication of the bacteria. Safety was assessed by adverse events including cases in which neither MRSA nor MRSE was detected. Results Twenty-five cases with MRSA (20) or MRSE (5) infections were enrolled. Of these 25 cases, 4 discontinued the treatment due to the negative results for bacterial culture during screening or at baseline. Of the 21 cases with conjunctivitis (14), blepharitis (3), meibomitis (1), dacryocystitis (2) or keratitis (1), 14 (66.7%) cases were evaluated as being excellently (complete response, 2 cases) or well (partial response, 12 cases) treated. The eradication rates were 68.4% in MRSA (13 of 19 cases) and 100% in MRSE (2 of 2 cases). Ten adverse events occurred in 7 (28.0%) of 25 cases at the local administration site. Conclusions Vancomycin Ophthalmic Ointment 1% was considered to be useful for the treatment of intractable ocular MRSA/MRSE infections. PMID:23364319

Effects of physiological and/or disease status on the response of postpartum dairy cows to synchronization of estrus using an intravaginal progesterone device.

PubMed

McNally, Julie C; Crowe, Mark A; Roche, James F; Beltman, Marijke E

2014-12-01

Progesterone treatments are used to increase submission rates in postpartum dairy cows; however, in many cases the protocol is used as a blanket therapy for all cows without regard for physiological or disease state. The objective of this study was to identify the physiological or disease classes of cows that respond well (or not) to synchronization of estrus via progesterone. Dairy cows (n = 402) were monitored peri and postpartum to establish their physiological or disease status. Animals were classified as having negative energy balance, clinical lameness, uterine infection (UI), anovulatory anestrus, high somatic cell counts, and healthy (H). Blood samples were collected at five different time points and analyzed for metabolites. All animals received an 8-day controlled internal drug release protocol, which included GnRH at insertion and PGF2α the day before removal. Response to the protocol was determined by visual observation of estrus synchronization. Conception rate was determined by ultrasonography between Days 32 and 35 after artificial insemination. Animals without UI were 1.9 times more likely to respond and two times more likely to be confirmed pregnant than those with UI. There was no relationship between negative energy balance and clinical lameness in the visual estrous response, but both conditions were associated with reduced conception rates. Dairy cows in anovulatory anestrus responded successfully to the protocol in both estrous response and conception rates. High glutathione peroxidase concentrations had a positive effect on conception rates, whereas high non-esterified fatty acids and beta-hydroxybutyrate had a negative effect on the estrous response. In conclusion, disease and physiological states of dairy cows determined the response to progesterone-based synchronization. The more disease or physiological problems the cows had, the lower the estrous response and conception rates; cows with these problems were not ideal candidates for synchronization. Both anestrus and healthy dairy cows were good responders to progesterone-based synchronization. Copyright © 2014 Elsevier Inc. All rights reserved.

Validation of standard ASTM F2732 and comparison with ISO 11079 with respect to comfort temperature ratings for cold protective clothing.

PubMed

Gao, Chuansi; Lin, Li-Yen; Halder, Amitava; Kuklane, Kalev; Holmér, Ingvar

2015-01-01

American standard ASTM F2732 estimates the lowest environmental temperature for thermal comfort for cold weather protective clothing. International standard ISO 11079 serves the same purpose but expresses cold stress in terms of required clothing insulation for a given cold climate. The objective of this study was to validate and compare the temperature ratings using human subject tests at two levels of metabolic rates (2 and 4 MET corresponding to 116.4 and 232.8 W/m(2)). Nine young and healthy male subjects participated in the cold exposure at 3.4 and -30.6 °C. The results showed that both standards predict similar temperature ratings for an intrinsic clothing insulation of 1.89 clo and for 2 MET activity. The predicted temperature rating for 2 MET activity is consistent with test subjects' thermophysiological responses, perceived thermal sensation and thermal comfort. For 4 MET activity, however, the whole body responses were on the cold side, particularly the responses of the extremities. ASTM F2732 is also limited due to its omission and simplification of three climatic variables (air velocity, radiant temperature and relative humidity) and exposure time in the cold which are of practical importance. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Effects of smoke exposure and other lifestyle factors on pain response to electrical stimulation in women.

PubMed

Wee, J Y; Hopman, W M

2008-01-01

A relationship between smoking and development of pain syndromes has been suggested in the literature. The present study examined associations between smoke exposure and other related variables, and pain response to suprathreshold electrical stimulation. Subjects were prospectively recruited from a population referred to an electrodiagnostic clinic. Information about age, smoke exposure, caffeine and alcohol consumption was obtained, as well as documented objective signs of stress through physical assessment. One investigator applied two standardized 0.1 ms electrical stimulations (50 mA followed by 100 mA) to asymptomatic extremities at the beginning of each electrodiagnostic session, using consistent technique. Subjects used a visual analogue scale to indicate the level of pain felt after each stimulation. Two hundred fifteen women were included. Current smokers and those currently exposed to second-hand smoke had significantly higher pain ratings (P=0.003 for 50 mA, P=0.005 for 100 mA) than those not currently exposed to smoke. Time since exposure was negatively associated with pain ratings. Those with objective signs of stress reported higher levels of pain, which was significant for the 100 mA stimulation (P=0.046). Linear regression modelling indicated that current smoke exposure and alcohol use were associated with higher pain ratings at both 50 mA and 100 mA, while stress was associated with higher pain ratings and older age was associated with lower pain ratings at 100 mA only. Exposure to cigarette smoke is significantly related to higher reported levels of pain experienced in response to electrical stimulation in this study population. Exposure to smoke can add 10 points to the 100-point visual analogue scale compared with subjects without exposure, with alcohol use adding another eight points. Reported pain decreases as length of time since previous exposure to smoke increases.

Physicians' and nurses' expectations and objections toward a clinical ethics committee.

PubMed

Jansky, Maximiliane; Marx, Gabriella; Nauck, Friedemann; Alt-Epping, Bernd

2013-11-01

The study aimed to explore the subjective need of healthcare professionals for ethics consultation, their experience with ethical conflicts, and expectations and objections toward a Clinical Ethics Committee. Staff at a university hospital took part in a survey (January to June 2010) using a questionnaire with open and closed questions. Descriptive data for physicians and nurses (response rate = 13.5%, n = 101) are presented. Physicians and nurses reported similar high frequencies of ethical conflicts but rated the relevance of ethical issues differently. Nurses stated ethical issues as less important to physicians than to themselves. Ethical conflicts were mostly discussed with staff from one's own profession. Respondents predominantly expected the Clinical Ethics Committee to provide competent support. Mostly, nurses feared it might have no influence on clinical practice. Findings suggest that experiences of ethical conflicts might reflect interprofessional communication patterns. Expectations and objections against Clinical Ethics Committees were multifaceted, and should be overcome by providing sufficient information. The Clinical Ethics Committee needs to take different perspectives of professions into account.

Modified cisplatin/interferon α-2b/doxorubicin/5-fluorouracil (PIAF) chemotherapy in patients with no hepatitis or cirrhosis is associated with improved response rate, resectability, and survival of initially unresectable hepatocellular carcinoma.

PubMed

Kaseb, Ahmed O; Shindoh, Junichi; Patt, Yehuda Z; Roses, Robert E; Zimmitti, Giuseppe; Lozano, Richard D; Hassan, Manal M; Hassabo, Hesham M; Curley, Steven A; Aloia, Thomas A; Abbruzzese, James L; Vauthey, Jean-Nicolas

2013-09-15

The purpose of this study was to evaluate the factors associated with response rate, resectability, and survival after cisplatin/interferon α-2b/doxorubicin/5-fluorouracil (PIAF) combination therapy in patients with initially unresectable hepatocellular carcinoma. The study included 2 groups of patients treated with conventional high-dose PIAF (n = 84) between 1994 and 2003 and those without hepatitis or cirrhosis treated with modified PIAF (n = 33) between 2003 and 2012. Tolerance of chemotherapy, best radiographic response, rate of conversion to curative surgery, and overall survival were analyzed and compared between the 2 groups, and multivariate and logistic regression analyses were applied to identify predictors of response and survival. The modified PIAF group had a higher median number of PIAF cycles (4 versus 2, P = .049), higher objective response rate (36% versus 15%, P = .013), higher rate of conversion to curative surgery (33% versus 10%, P = .004), and longer median overall survival (21.3 versus 10.6 months, P = .002). Multivariate analyses confirmed that positive hepatitis B serology (hazard ratio [HR] = 1.68; 95% confidence interval [CI] = 1.08-2.59) and Eastern Cooperative Oncology Group performance status ≥ 2 (HR = 1.75; 95% CI = 1.04-2.93) were associated with worse survival whereas curative surgical resection after PIAF treatment (HR = 0.15; 95% CI = 0.07-0.35) was associated with improved survival. In patients with initially unresectable hepatocellular carcinoma, the modified PIAF regimen in patients with no hepatitis or cirrhosis is associated with improved response, resectability, and survival. © 2013 American Cancer Society.

Modified Cisplatin/Interferon α-2b/Doxorubicin/Fluorouracil (PIAF) chemotherapy in patients with no hepatitis or cirrhosis is associated with improved response rate, resectability and survival of initially unresectable hepatocellular carcinoma

PubMed Central

Kaseb, Ahmed O.; Shindoh, Junichi; Patt, Yehuda Z.; Roses, Robert E.; Zimmitti, Giuseppe; Lozano, Richard D.; Hassan, Manal M.; Hassabo, Hesham M.; Curley, Steven A.; Aloia, Thomas A.; Abbruzzese, James L.; Vauthey, Jean-Nicolas

2013-01-01

Purpose The purposes of this study was to evaluate the factors associated with response rate, resectability, and survival after cisplatin/interferon α-2b/doxorubicin/5-flurouracil (PIAF) combination therapy in patients with initially unresectable hepatocellular carcinoma (HCC). Patients and Methods The study included two groups of patients treated with conventional high-dose PIAF (n=84) between 1994 and 2003 and those without hepatitis or cirrhosis treated with modified PIAF (n=33) between 2003 and 2012. Tolerance of chemotherapy, best radiographic response, rate of conversion to curative surgery, and overall survival were analyzed and compared between the two groups, and multivariate and logistic regression analyses were applied to identify predictors of response and survival. Results The modified PIAF group had a higher median number of PIAF cycles (4 vs. 2, P = .049), higher objective response rate (36% vs. 15%, P = .013), higher rate of conversion to curative surgery (33% vs. 10%, P = .004), and longer median overall survival (21.3 vs. 10.6 months, P = .002). Multivariate analyses confirmed that positive hepatitis B serology (hazard ratio [HR], 1.68; 95% CI, 1.08 to 2.59) and Eastern Cooperative Oncology Group performance status ≥2 (HR, 1.75; 95% CI 1.04 to 2.93) were associated with worse survival while curative surgical resection after PIAF treatment (HR, 0.15; 95% CI, 0.07 to 0.35) was associated with improved survival. Conclusions In patients with initially unresectable HCC, the modified PIAF regimen in patients with no hepatitis or cirrhosis is associated with improved response, resectability, and survival. PMID:23821538

Phase II study of biweekly plitidepsin as second-line therapy for advanced or metastatic transitional cell carcinoma of the urothelium.

PubMed

Dumez, Herlinde; Gallardo, Enrique; Culine, Stephane; Galceran, Joan Carles; Schöffski, Patrick; Droz, Jean P; Extremera, Sonia; Szyldergemajn, Sergio; Fléchon, Aude

2009-09-16

The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m(2)) administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting > or = 6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting.

Frequency and Types of Partner Violence among Mexican American College Women

ERIC Educational Resources Information Center

Coker, Ann L.; Sanderson, Maureen; Cantu, Ethel; Huerta, Debbie; Fadden, Mary Kay

2008-01-01

Objective and Participants: The authors studied the prevalence of partner violence, by type, among Mexican American college women aged 18 to 35 years (N = 149; response rate = 85%). Results: Twelve percent of women who reported a dating partner in the past year were physically or sexually assaulted, 12.1% were stalked, and 9.1% scored as…

Parent Ratings of ADHD Symptoms: Generalized Partial Credit Model Analysis of Differential Item Functioning across Gender

ERIC Educational Resources Information Center

Gomez, Rapson

2012-01-01

Objective: Generalized partial credit model, which is based on item response theory (IRT), was used to test differential item functioning (DIF) for the "Diagnostic and Statistical Manual of Mental Disorders" (4th ed.), inattention (IA), and hyperactivity/impulsivity (HI) symptoms across boys and girls. Method: To accomplish this, parents completed…

Predicting Posttraumatic Stress Symptoms in Children after Road Traffic Accidents

ERIC Educational Resources Information Center

Landolt, Markus A.; Vollrath, Margarete; Timm, Karin; Gnehm, Hanspeter E.; Sennhauser, Felix H.

2005-01-01

Objective: To prospectively assess the prevalence, course, and predictors of posttraumatic stress symptoms (PTSSs) in children after road traffic accidents (RTAs). Method: Sixty-eight children (6.5-14.5 years old) were interviewed 4-6 weeks and 12 months after an RTA with the Child PTSD Reaction Index (response rate 58.6%). Their mothers (n = 60)…

Re-Visit to the School Nurse and Adolescents' Medicine Use

ERIC Educational Resources Information Center

Borup, Ina K.; Andersen, Anette; Holstein, Bjorn E.

2011-01-01

Objective: To examine if students who re-visit the school nurse use medicines differently than other students when exposed to aches and psychological problems. Methods: The study includes all 11-, 13- and 15-year-old students from a random sample of schools in Denmark, response rate 87 per cent, n = 5,205. The data collection followed the…

Transition from Sensorimotor Stage 5 to Stage 6 by Down Syndrome Children: A Response to Gibson.

ERIC Educational Resources Information Center

Mervis, Carolyn B.; Cardoso-Martins, Claudia

1984-01-01

The study compared longitudinally performance of six Down syndrome and six nonretarded children on Object Permanence and Means-Ends Relations Scales. Results indicated that Down syndrome children progressed from Sensorimotor Stage 5 to Stage 6 at the same rate as nonretarded children, once Down's Ss slower developmental pace was considered.…

Teacher Academy Induction Learning Community: Guiding Teachers through Their Zone of Proximal Development

ERIC Educational Resources Information Center

Flores, Belinda Bustos; Hernandez, Arcelia; Garcia, Claudia Trevino; Claeys, Lorena

2011-01-01

This is a preliminary analysis of The Academy for Teacher Excellence (ATE) induction support provided through the Teacher Academy Induction Learning Community (TAILC). In response to current US teacher attrition rates, ATE-TAILC's primary objective is to retain teachers in the classroom and provide support to ensure they are fully prepared to meet…

Impact of Death by Suicide of Patients on Thai Psychiatrists

ERIC Educational Resources Information Center

Thomyangkoon, Prakarn; Leenaars, Antoon

2008-01-01

The objective of this study was to identify the impact of a patient's suicide on psychiatrists in Thailand. A confidential coded postal questionnaire survey was sent to 320 eligible psychiatrists; with a response rate of 52.18%. The results showed that 94 (56.28%) of responding psychiatrists had a patient die by suicide, consistent with high rates…

Economic Impact of the Critical Access Hospital Program on Kentucky's Communities

ERIC Educational Resources Information Center

Ona, Lucia; Davis, Alison

2011-01-01

Context: In 1997, the Medicare Rural Hospital Flexibility Grant Program created the Critical Access Hospital (CAH) Program as a response to the financial distress of rural hospitals. It was believed that this program would reduce the rate of rural hospital closures and improve access to health care services in rural communities. Objective: The…

Cluster Supervision Practices in Primary School of Jimma Zone

ERIC Educational Resources Information Center

Afework, E. A.; Frew, A. T.; Abeya, G. G.

2017-01-01

The main objective of this study was to assess the supervisory practice of cluster resource centre (CRC) supervisors in Jimma Zone primary schools. To achieve this purpose, the descriptive survey design was employed. Data were collected from 238 randomly selected teachers, and 60 school principals with a response rate of 98.6%. Moreover, 12 CRC…

Binge Drinking and Drinking and Driving among South Korean International College Students in the USA

ERIC Educational Resources Information Center

Sa, J.; Seo, D.-C.; Nelson, T. F.; Lohrmann, D. K.; Ellis, N. T.

2015-01-01

Objective: To investigate two risky behaviours (i.e. binge drinking and drinking and driving) and their individual- and college-level correlates among South Korean international college students in the USA Design: Cross-sectional online survey (student response rate = 41.6%). Setting: South Korean college students (N = 1201) were recruited from 52…

The Power Transistor: A Module on Heat Transfer. Tech Physics Series.

ERIC Educational Resources Information Center

Technical Education Research Center, Cambridge, MA.

This module is intended to provide an understanding of the principles related to heat transfer. The objectives are designed to enable the learner to select and install a device for measuring the temperature of a power transistor, determine power ratings, measure the transient response for a power level and its final equilibrium temperature. Other…

New efficient stimuli for evoking frequency-specific auditory steady-state responses.

PubMed

Stürzebecher, Ekkehard; Cebulla, Mario; Elberling, Claus; Berger, Thomas

2006-06-01

ASSR is a promising tool for the objective frequency-specific assessment of hearing thresholds in children. The stimulus generally used for ASSR recording (single amplitude-modulated carrier) only activates a small area on the basilar membrane. Therefore, the response amplitude is low. A stimulus with a broader frequency spectrum can be composed by adding several cosines whose frequency intervals comply with the desired stimulus repetition rate. Compensation of the travelling wave delay on the basilar membrane is possible with a stimulus of this type. Through this, a better synchronization of the neural response can be obtained and, as a result, higher response amplitudes can be expected, particularly for low-frequency stimuli. The additional introduction of a frequency offset enables the use of a q-sample test for the response detection, especially important at 500 Hz. The results of investigations carried out on a large group of normally hearing test subjects have confirmed the efficiency of this stimulus design. The new stimuli lead to significantly improved ASSRs with higher SNRs and thus higher detection rates and shorter detection times.

Autonomic responses to tonic pain are more closely related to stimulus intensity than to pain intensity.

PubMed

Nickel, Moritz M; May, Elisabeth S; Tiemann, Laura; Postorino, Martina; Ta Dinh, Son; Ploner, Markus

2017-11-01

Pain serves the protection of the body by translating noxious stimulus information into a subjective percept and protective responses. Such protective responses rely on autonomic responses that allocate energy resources to protective functions. However, the precise relationship between objective stimulus intensity, subjective pain intensity, autonomic responses, and brain activity is not fully clear yet. Here, we addressed this question by continuously recording pain ratings, skin conductance, heart rate, and electroencephalography during tonic noxious heat stimulation of the hand in 39 healthy human subjects. The results confirmed that pain intensity dissociates from stimulus intensity during 10 minutes of noxious stimulation. Furthermore, skin conductance measures were significantly related to stimulus intensity but not to pain intensity. Correspondingly, skin conductance measures were significantly related to alpha and beta oscillations in contralateral sensorimotor cortex, which have been shown to encode stimulus intensity rather than pain intensity. No significant relationships were found between heart rate and stimulus intensity or pain intensity. The findings were consistent for stimulation of the left and the right hands. These results suggest that sympathetic autonomic responses to noxious stimuli in part directly result from nociceptive rather than from perceptual processes. Beyond, these observations support concepts of pain and emotions in which sensory, motor, and autonomic components are partially independent processes that together shape emotional and painful experiences.

[Analysis of the impact of decitabine treatment cycles on efficacy and safety in patients of myelodysplastic syndrome-refractory anemia with excess blasts].

PubMed

Luo, X P; Xu, Z F; Qin, T J; Zhang, Y; Zhang, H L; Fang, L W; Pan, L J; Hu, N B; Qu, S Q; Li, B; Xiao, Z J

2016-10-14

Objective: To explore the impact of decitabine treatment cycles on efficacy and adverse events(AEs)in patients of myelodysplastic syndrome-refractory anemia with excess blasts(MDSRAEB). Methods: A total of fifty-six patients with MDS-RAEB who received decitabine 20 mg·m -2 ·d -1 by IV infusion daily for 5 consecutive days every 4 weeks at a single institute in China were enrolled from December 2008 to March 2016. Their clinical features, efficacy, predictors of efficacy and AEs were analyzed retrospectively. Results: Of the 56 patients enrolled, 25 cases were MDS- RAEB1, another 31 were MDS-RAEB2. A median of 3 cycles(range, 1-15 cycles)were delivered. The overall response rate was 67.9%(10 complete responses, 8 marrow complete responses without hematologic improvement, 17 marrow complete responses with hematologic improvements, and 3 hematologic improvements). With a median follow-up duration of 7.9(1.0-56.3)months, the median overall survival was 21.1(95% CI 16.0- 26.1)months. Compared with RAEB-2, RAEB-1 predicted higher overall response rates in a multivariate analysis. Of the 38 patients who experienced clinical responses, initial responses were detected by the end of two cycles in 37 patients. Twenty- five of the 38 patients who experienced clinical responses had their best response within the first two cycles, and 37 cases of the patients achieved best response by the end of fourth cycles. Grade 3 or 4 cytopenia and infection were the most prevalent AEs, which occurred frequently in the early courses and decreased later, and other non- hematologic AEs were rare. Conclusion: Decitabine treatment was favorable in patients with MDS- RAEB. In most of the cases, initial responses were observed within 2 cycles, and best response was achieved by the end of 4 th cycles. The most common AEs were grade 3 or 4 cytopenia and infection, which were observed frequently in first 2 cycles and decreased later as objective response were achieved.

Experimental and analytical studies in fluids

NASA Technical Reports Server (NTRS)

Goglia, Gene L.; Ibrahim, Adel

1984-01-01

The first objective was to analyze and design a true airspeed sensor which will replace the conventional pitot-static pressure transducer for small commercial aircraft. The second objective was to obtain a numerical solution and predict the frequency response which is generated by the vortex whistle at a certain airspeed. It was concluded flow rate measurements indicate that the vortex tube sound frequency is linearly proportional to the frequency response. The vortex tube whistle frequency is dependent upon geometrical parameters to such an extent that: an increase in vortex tube length produces a decrease in frequency response and that an increase in the exhaust nozzle length produces an increase in the frequency precession. An increase in the vortex tube diameter produces a decrease in frequency precession. An increase in swirler diameter produces a decrease in frequency. An increase in the location distance of the microphone pickup signal point from the inside edge of the exit nozzle produces an increase in frequency response. The experimental results indicate that those parameters most significantly effecting frequency are in descending order of importance microphone location, vortex tube diameter, exit nozzle length, vortex tube length, and swirler diameter.

Teamwork in the NICU setting and its association with healthcare-associated infections in very low birth weight infants

PubMed Central

Profit, Jochen; Sharek, Paul J.; Kan, Peiyi; Rigdon, Joseph; Desai, Manisha; Nisbet, Courtney C.; Tawfik, Daniel S.; Thomas, Eric J.; Lee, Henry C.; Sexton, J. Bryan

2018-01-01

Background and Objective Teamwork may affect clinical care in the neonatal intensive care unit (NICU) setting. The objective of this study was to assess teamwork climate across NICUs and to test scale level and item level associations with healthcare-associated infection (HAI) rates in very low birth weight (VLBW) infants. Methods Cross-sectional study of the association between HAI rates, defined as any bacterial or fungal infection during the birth hospitalization, among 6663 VLBW infants cared for in 44 NICUs between 2010 and 2012. NICU HAI rates were correlated with teamwork climate ratings obtained in 2011 from 2073 of 3294 eligible (response rate 63%) NICU health professionals. The relation between HAI rates and NICU teamwork climate was assessed using logistic regression models including NICU as a random effect. Results Across NICUs, 36 to 100% (mean 66%) of respondents reported good teamwork. HAI rates were significantly and independently associated with teamwork climate (OR [95% CI] 0.82 [0.73-0.92], p = 0.005), such that the odds of an infant contracting a HAI decreased by 18% with each 10% rise in NICU respondents reporting good teamwork. Conclusion Improving teamwork may be an important element in infection control efforts. PMID:28395366

A randomized trial found online questionnaires supplemented by postal reminders generated a cost-effective and generalizable sample but don't forget the reminders.

PubMed

Loban, Amanda; Mandefield, Laura; Hind, Daniel; Bradburn, Mike

2017-12-01

The objective of this study was to compare the response rates, data completeness, and representativeness of survey data produced by online and postal surveys. A randomized trial nested within a cohort study in Yorkshire, United Kingdom. Participants were randomized to receive either an electronic (online) survey questionnaire with paper reminder (N = 2,982) or paper questionnaire with electronic reminder (N = 2,855). Response rates were similar for electronic contact and postal contacts (50.9% vs. 49.7%, difference = 1.2%, 95% confidence interval: -1.3% to 3.8%). The characteristics of those responding to the two groups were similar. Participants nevertheless demonstrated an overwhelming preference for postal questionnaires, with the majority responding by post in both groups. Online survey questionnaire systems need to be supplemented with a postal reminder to achieve acceptable uptake, but doing so provides a similar response rate and case mix when compared to postal questionnaires alone. For large surveys, online survey systems may be cost saving. Copyright © 2017 Elsevier Inc. All rights reserved.

A thermomechanical anisotropic model for shock loading of elastic-plastic and elastic-viscoplastic materials with application to jointed rock

DOE PAGES

Rubin, M. B.; Vorobiev, O.; Vitali, E.

2016-04-21

Here, a large deformation thermomechanical model is developed for shock loading of a material that can exhibit elastic and inelastic anisotropy. Use is made of evolution equations for a triad of microstructural vectors m i(i=1,2,3) which model elastic deformations and directions of anisotropy. Specific constitutive equations are presented for a material with orthotropic elastic response. The rate of inelasticity depends on an orthotropic yield function that can be used to model weak fault planes with failure in shear and which exhibits a smooth transition to isotropic response at high compression. Moreover, a robust, strongly objective numerical algorithm is proposed formore » both rate-independent and rate-dependent response. The predictions of the continuum model are examined by comparison with exact steady-state solutions. Also, the constitutive equations are used to obtain a simplified continuum model of jointed rock which is compared with high fidelity numerical solutions that model a persistent system of joints explicitly in the rock medium.« less

The relationship between change in subjective outcome and change in disease: a potential paradox.

PubMed

Kievit, Wietske; Hendrikx, Jos; Stalmeier, Peep F M; van de Laar, Mart A F J; Van Riel, Piet L C M; Adang, Eddy M

2010-09-01

Response shift theory suggests that improvements in health lead patients to change their internal standards and re-assess former health states as worse than initially rated when using retrospective ratings via the then-test. The predictions of response shift theory can be illustrated using prospect theory, whereby a change in current health causes a change in reference frame. Therefore, if health deteriorates, the former health state will receive a better rating, whereas if it improves, the former health state will receive a worse rating. To explore the predictions of response shift and prospect theory by relating subjective change to objective change. Baseline and 3-month follow-up data from a cohort of rheumatoid arthritis patients (N = 197) starting on TNFalpha-blocking agents were used. Objective disease change was classified according to a disease-specific clinical outcome measure (DAS28). Visual analogue scales (VAS) for general health (GH) and pain were used as self-reported measures. Three months after starting on anti-TNFalpha, patients used the then-test to re-rate their baseline health with regard to general health and pain. Differences between then-test value and baseline values were calculated and tested between improved, non-improved and deteriorated patients by the Student t-test. At 3 months, 51 (25.9%) patients had good improvement in health, 83 (42.1%) had moderate improvement, and 63 (32.0%) had no improvement or deteriorated in health. All patients no matter whether they improved, did not improve, or even became worse rated their health as worse retrospectively. The difference between the then-test rating and the baseline value was similarly sized in all groups. More positive ratings of retrospective health are independent of disease change. This suggests that patients do not necessarily change their standards in line with their disease change, and therefore it is inappropriate to use the then-test to correct for such a change. If a then-test is used to correct for shifts in internal standards, it might lead to the paradoxical result that patients who do not improve or even deteriorate increase significantly on self-reported health and pain. An alternative explanation for differences in retrospective and prospective ratings of health is the implicit theory of change which is more successful in explaining our results than prospect theory.

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.

Amplitude and timing of somatosensory cortex activity in task-specific focal hand dystonia.

PubMed

Dolberg, Rebecca; Hinkley, Leighton B N; Honma, Susanne; Zhu, Zhao; Findlay, Anne M; Byl, Nancy N; Nagarajan, Srikantan S

2011-12-01

Task-specific focal hand dystonia (tspFHD) is a movement disorder diagnosed in individuals performing repetitive hand behaviors. The extent to which processing anomalies in primary sensory cortex extend to other regions or across the two hemispheres is presently unclear. In response to low/high rate and novel tactile stimuli on the affected and unaffected hands, magnetoencephalography (MEG) was used to elaborate activity timing and amplitude in the primary somatosensory (S1) and secondary somatosensory/parietal ventral (S2/PV) cortices. MEG and clinical performance measures were collected from 13 patients and matched controls. Compared to controls, subjects with tspFHD had increased response amplitude in S2/PV bilaterally in response to high rate and novel stimuli. Subjects with tspFHD also showed increased response latency (low rate, novel) of the affected digits in contralateral S1. For high rate, subjects with tspFHD showed increased response latency in ipsilateral S1 and S2/PV bilaterally. Activation differences correlated with functional sensory deficits (predicting a latency shift in S1), motor speed and muscle strength. There are objective differences in the amplitude and timing of activity for both hands across contralateral and ipsilateral somatosensory cortex in patients with tspFHD. Knowledge of cortical processing abnormalities across S1 and S2/PV in dystonia should be applied towards the development of learning-based sensorimotor interventions. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A framework for evaluating the appropriateness of clinical decision support alerts and responses

PubMed Central

Waitman, Lemuel R; Lewis, Julia B; Wright, Julie A; Choma, David P; Miller, Randolph A; Peterson, Josh F

2011-01-01

Objective Alerting systems, a type of clinical decision support, are increasingly prevalent in healthcare, yet few studies have concurrently measured the appropriateness of alerts with provider responses to alerts. Recent reports of suboptimal alert system design and implementation highlight the need for better evaluation to inform future designs. The authors present a comprehensive framework for evaluating the clinical appropriateness of synchronous, interruptive medication safety alerts. Methods Through literature review and iterative testing, metrics were developed that describe successes, justifiable overrides, provider non-adherence, and unintended adverse consequences of clinical decision support alerts. The framework was validated by applying it to a medication alerting system for patients with acute kidney injury (AKI). Results Through expert review, the framework assesses each alert episode for appropriateness of the alert display and the necessity and urgency of a clinical response. Primary outcomes of the framework include the false positive alert rate, alert override rate, provider non-adherence rate, and rate of provider response appropriateness. Application of the framework to evaluate an existing AKI medication alerting system provided a more complete understanding of the process outcomes measured in the AKI medication alerting system. The authors confirmed that previous alerts and provider responses were most often appropriate. Conclusion The new evaluation model offers a potentially effective method for assessing the clinical appropriateness of synchronous interruptive medication alerts prior to evaluating patient outcomes in a comparative trial. More work can determine the generalizability of the framework for use in other settings and other alert types. PMID:21849334

Recognition memory strength is predicted by pupillary responses at encoding while fixation patterns distinguish recollection from familiarity.

PubMed

Kafkas, Alexandros; Montaldi, Daniela

2011-10-01

Thirty-five healthy participants incidentally encoded a set of man-made and natural object pictures, while their pupil response and eye movements were recorded. At retrieval, studied and new stimuli were rated as novel, familiar (strong, moderate, or weak), or recollected. We found that both pupil response and fixation patterns at encoding predict later recognition memory strength. The extent of pupillary response accompanying incidental encoding was found to be predictive of subsequent memory. In addition, the number of fixations was also predictive of later recognition memory strength, suggesting that the accumulation of greater visual detail, even for single objects, is critical for the creation of a strong memory. Moreover, fixation patterns at encoding distinguished between recollection and familiarity at retrieval, with more dispersed fixations predicting familiarity and more clustered fixations predicting recollection. These data reveal close links between the autonomic control of pupil responses and eye movement patterns on the one hand and memory encoding on the other. Moreover, the data illustrate quantitative as well as qualitative differences in the incidental visual processing of stimuli, which are differentially predictive of the strength and the kind of memory experienced at recognition.

Parkinson’s disease patients show impaired corrective grasp control and eye-hand coupling when reaching to grasp virtual objects

PubMed Central

Lukos, Jamie R.; Snider, Joseph; Hernandez, Manuel E.; Tunik, Eugene; Hillyard, Steven; Poizner, Howard

2013-01-01

The effect of Parkinson’s disease on hand-eye coordination and corrective response control during reach-to-grasp tasks remains unclear. Moderately impaired Parkinson’s disease patients (PD, n=9) and age-matched controls (n=12) reached to and grasped a virtual rectangular object, with haptic feedback provided to the thumb and index fingertip by two 3-degree of freedom manipulanda. The object rotated unexpectedly on a minority of trials, requiring subjects to adjust their grasp aperture. On half the trials, visual feedback of finger positions disappeared during the initial phase of the reach, when feedforward mechanisms are known to guide movement. PD patients were tested without (OFF) and with (ON) medication to investigate the effects of dopamine depletion and repletion on eye-hand coordination online corrective response control. We quantified eye-hand coordination by monitoring hand kinematics and eye position during the reach. We hypothesized that if the basal ganglia are important for eye-hand coordination and online corrections to object perturbations, then PD patients tested OFF medication would show reduced eye-hand spans and impoverished arm-hand coordination responses to the perturbation, which would be further exasperated when visual feedback of the hand was removed. Strikingly, PD patients tracked their hands with their gaze, and their movements became destabilized when having to make online corrective responses to object perturbations exhibiting pauses and changes in movement direction. These impairments largely remained even when tested in the ON state, despite significant improvement on the Unified Parkinson’s Disease Rating Scale. Our findings suggest that basal ganglia-cortical loops are essential for mediating eye-hand coordination and adaptive online responses for reach-to-grasp movements, and that restoration of tonic levels of dopamine may not be adequate to remediate this coordinative nature of basal ganglia modulated function. PMID:24056196

Recruitment methods for survey research: Findings from the Mid-South Clinical Data Research Network.

PubMed

Heerman, William J; Jackson, Natalie; Roumie, Christianne L; Harris, Paul A; Rosenbloom, S Trent; Pulley, Jill; Wilkins, Consuelo H; Williams, Neely A; Crenshaw, David; Leak, Cardella; Scherdin, Jon; Muñoz, Daniel; Bachmann, Justin; Rothman, Russell L; Kripalani, Sunil

2017-11-01

The objective of this study was to report survey response rates and demographic characteristics of eight recruitment approaches to determine acceptability and effectiveness of large-scale patient recruitment among various populations. We conducted a cross sectional analysis of survey data from two large cohorts. Patients were recruited from the Mid-South Clinical Data Research Network using clinic-based recruitment, research registries, and mail, phone, and email approaches. Response rates are reported as patients who consented for the survey divided by the number of eligible patients approached. We contacted more than 90,000 patients and 13,197 patients completed surveys. Median age was 56.3years (IQR 40.9, 67.4). Racial/ethnic distribution was 84.1% White, non-Hispanic; 9.9% Black, non-Hispanic; 1.8% Hispanic; and 4.0% other, non-Hispanic. Face-to-face recruitment had the highest response rate of 94.3%, followed by participants who "opted-in" to a registry (76%). The lowest response rate was for unsolicited emails from the clinic (6.1%). Face-to-face recruitment enrolled a higher percentage of participants who self-identified as Black, non-Hispanic compared to other approaches (18.6% face-to-face vs. 8.4% for email). Technology-enabled recruitment approaches such as registries and emails are effective for recruiting but may yield less racial/ethnic diversity compared to traditional, more time-intensive approaches. Copyright © 2017. Published by Elsevier Inc.

Patient Safety Culture Assessment in Oman

PubMed Central

Al-Mandhari, Ahmed; Al-Zakwani, Ibrahim; Al-Kindi, Moosa; Tawilah, Jihane; Dorvlo, Atsu S.S.; Al-Adawi, Samir

2014-01-01

Objective To illustrate the patient safety culture in Oman as gleaned via 12 indices of patient safety culture derived from the Hospital Survey on Patient Safety Culture (HSPSC) and to compare the average positive response rates in patient safety culture between Oman and the USA, Taiwan, and Lebanon. Methods This was a cross-sectional research study employed to gauge the performance of HSPSC safety indices among health workers representing five secondary and tertiary care hospitals in the northern region of Oman. The participants (n=398) represented different professional designations of hospital staff. Analyses were performed using univariate statistics. Results The overall average positive response rate for the 12 patient safety culture dimensions of the HSPSC survey in Oman was 58%. The indices from HSPSC that were endorsed the highest included ‘organizational learning and continuous improvement’ while conversely, ‘non-punitive response to errors’ was ranked the least. There were no significant differences in average positive response rates between Oman and the United States (58% vs. 61%; p=0.666), Taiwan (58% vs. 64%; p=0.386), and Lebanon (58% vs. 61%; p=0.666). Conclusion This study provides the first empirical study on patient safety culture in Oman which is similar to those rates reported elsewhere. It highlights the specific strengths and weaknesses which may stem from the specific milieu prevailing in Oman. PMID:25170407

Factors influencing the response latencies of subnormal children in naming pictures.

PubMed

Elliott, C

1978-08-01

The times taken to name 56 drawings of objects on five separate occasions were analysed for 21 ESN(M) and 21 ESN(S) children, matched for picture-naming vocabulary. The ESN(S) group not only had a higher mean response latency but also showed greater inter- and intra-subject variance. Nine objects were selected whose names have a Thorndike-Lorge language frequency of 50 words per million or greater, and nine others were selected with a frequency of less than 50 words per million. Each object was drawn in two ways, one giving a two-dimensional outline with the addition of important detail, the other drawing also incorporating cues indicating the depth of the object. An analysis of variance of the children's latencies in naming the selected 36 pictures of 18 objects over five trials indicated that the method of drawing had no effect upon naming latencies. Pictures with high-frequency names were named faster than those with lower frequency names, the ESN(S) group showing a greater rate of increase in naming latency for the lower frequency words than the ESN(M) children. Results were discussed in terms of the Oldfield and Lachman models of lexical memory storage and of the search processes required for the retrieval of names.

A Cortical Network for the Encoding of Object Change

PubMed Central

Hindy, Nicholas C.; Solomon, Sarah H.; Altmann, Gerry T.M.; Thompson-Schill, Sharon L.

2015-01-01

Understanding events often requires recognizing unique stimuli as alternative, mutually exclusive states of the same persisting object. Using fMRI, we examined the neural mechanisms underlying the representation of object states and object-state changes. We found that subjective ratings of visual dissimilarity between a depicted object and an unseen alternative state of that object predicted the corresponding multivoxel pattern dissimilarity in early visual cortex during an imagery task, while late visual cortex patterns tracked dissimilarity among distinct objects. Early visual cortex pattern dissimilarity for object states in turn predicted the level of activation in an area of left posterior ventrolateral prefrontal cortex (pVLPFC) most responsive to conflict in a separate Stroop color-word interference task, and an area of left ventral posterior parietal cortex (vPPC) implicated in the relational binding of semantic features. We suggest that when visualizing object states, representational content instantiated across early and late visual cortex is modulated by processes in left pVLPFC and left vPPC that support selection and binding, and ultimately event comprehension. PMID:24127425

Impact of the canine double-deletion β1 adrenoreceptor polymorphisms on protein structure and heart rate response to atenolol, a β1-selective β-blocker.

PubMed

Meurs, Kathryn M; Stern, Josh A; Reina-Doreste, Yamir; Maran, Brian A; Chdid, Lhoucine; Lahmers, Sunshine; Keene, Bruce W; Mealey, Katrina L

2015-09-01

β-Adrenergic receptor antagonists are widely utilized for the management of cardiac diseases in dogs. We have recently identified two deletion polymorphisms in the canine adrenoreceptor 1 (ADRB1) gene.We hypothesized that canine ADRB1 deletions would alter the structure of the protein, as well as the heart rate response to the β-adrenergic receptor antagonist, atenolol. The objectives of this study were to predict the impact of these deletions on the predicted structure of the protein and on the heart rate response to atenolol in a population of healthy adult dogs. Eighteen apparently healthy, mature dogs with (11) and without (seven) ADRB1 deletions were evaluated. The heart rate of the dogs was evaluated with a baseline ambulatory ECG before and 14-21 days after atenolol therapy (1 mg/kg orally q12 h). Minimum, average, and maximum heart rates were compared between groups of dogs (deletions, controls) using an unpaired t-test and within each group of dogs using a paired t-test. The protein structure of ADRB1 was predicted by computer modeling. Deletions were predicted to alter the structure of the ADRB1 protein. The heart rates of the dogs with deletions were lower than those of the control dogs (the average heart rates were significantly lower). ADRB1 deletions appear to have structural and functional consequences. Individual genome-based treatment recommendations could impact the management of dogs with heart disease.

Efficacy of TACE in TIPS Patients: Comparison of Treatment Response to Chemoembolization for Hepatocellular Carcinoma in Patients With and Without a Transjugular Intrahepatic Portosystemic Shunt

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

Kuo, Yuo-Chen, E-mail: yuo-chen.kuo@ucsf.edu; Kohi, Maureen P., E-mail: maureen.kohi@ucsf.edu; Naeger, David M., E-mail: david.naeger@ucsf.edu

Purpose: To compare treatment response after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in patients with and without a transjugular intrahepatic portosystemic shunt (TIPS). Materials and Methods: A retrospective review of patients who underwent conventional TACE for HCC between January 2005 and December 2009 identified 10 patients with patent TIPS. From the same time period, 23 patients without TIPS were selected to control for comparable Model for End-Stage Liver Disease and Child-Pugh-Turcotte scores. The two groups showed similar distribution of Barcelona Clinic Liver Cancer and United Network of Organ Sharing stages. Target HCC lesions were evaluated according to the modifiedmore » response evaluation criteria in solid tumors (mRECIST) guidelines. Transplantation rate, time to tumor progression, and overall survival (OS) were documented. Results: After TACE, the rate of complete response was significantly greater in non-TIPS patients compared with TIPS patients (74 vs. 30 %, p = 0.03). Objective response rate (complete and partial response) trended greater in the non-TIPS group (83 vs. 50 %, p = 0.09). The liver transplantation rate was 80 and 74 % in the TIPS and non-TIPS groups, respectively (p = 1.0). Time to tumor progression was similar (p = 0.47) between the two groups. OS favored the non-TIPS group (p = 0.01) when censored for liver transplantation. Conclusion: TACE is less effective in achieving complete or partial response using mRECIST criteria in TIPS patients compared with those without a TIPS. Nevertheless, similar clinical outcomes may be achieved, particularly in TIPS patients who are liver-transplantation candidates.« less

Visual adaptation provides objective electrophysiological evidence of facial identity discrimination.

PubMed

Retter, Talia L; Rossion, Bruno

2016-07-01

Discrimination of facial identities is a fundamental function of the human brain that is challenging to examine with macroscopic measurements of neural activity, such as those obtained with functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Although visual adaptation or repetition suppression (RS) stimulation paradigms have been successfully implemented to this end with such recording techniques, objective evidence of an identity-specific discrimination response due to adaptation at the level of the visual representation is lacking. Here, we addressed this issue with fast periodic visual stimulation (FPVS) and EEG recording combined with a symmetry/asymmetry adaptation paradigm. Adaptation to one facial identity is induced through repeated presentation of that identity at a rate of 6 images per second (6 Hz) over 10 sec. Subsequently, this identity is presented in alternation with another facial identity (i.e., its anti-face, both faces being equidistant from an average face), producing an identity repetition rate of 3 Hz over a 20 sec testing sequence. A clear EEG response at 3 Hz is observed over the right occipito-temporal (ROT) cortex, indexing discrimination between the two facial identities in the absence of an explicit behavioral discrimination measure. This face identity discrimination occurs immediately after adaptation and disappears rapidly within 20 sec. Importantly, this 3 Hz response is not observed in a control condition without the single-identity 10 sec adaptation period. These results indicate that visual adaptation to a given facial identity produces an objective (i.e., at a pre-defined stimulation frequency) electrophysiological index of visual discrimination between that identity and another, and provides a unique behavior-free quantification of the effect of visual adaptation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Finite-Element Methods for Real-Time Simulation of Surgery

NASA Technical Reports Server (NTRS)

Basdogan, Cagatay

2003-01-01

Two finite-element methods have been developed for mathematical modeling of the time-dependent behaviors of deformable objects and, more specifically, the mechanical responses of soft tissues and organs in contact with surgical tools. These methods may afford the computational efficiency needed to satisfy the requirement to obtain computational results in real time for simulating surgical procedures as described in Simulation System for Training in Laparoscopic Surgery (NPO-21192) on page 31 in this issue of NASA Tech Briefs. Simulation of the behavior of soft tissue in real time is a challenging problem because of the complexity of soft-tissue mechanics. The responses of soft tissues are characterized by nonlinearities and by spatial inhomogeneities and rate and time dependences of material properties. Finite-element methods seem promising for integrating these characteristics of tissues into computational models of organs, but they demand much central-processing-unit (CPU) time and memory, and the demand increases with the number of nodes and degrees of freedom in a given finite-element model. Hence, as finite-element models become more realistic, it becomes more difficult to compute solutions in real time. In both of the present methods, one uses approximate mathematical models trading some accuracy for computational efficiency and thereby increasing the feasibility of attaining real-time up36 NASA Tech Briefs, October 2003 date rates. The first of these methods is based on modal analysis. In this method, one reduces the number of differential equations by selecting only the most significant vibration modes of an object (typically, a suitable number of the lowest-frequency modes) for computing deformations of the object in response to applied forces.

Savings sharing: rewarding staff for responsible decision-making.

PubMed

Jones, Debi

2005-04-01

Shortages of professional nurses create a "buyer's market" in which nurses accept temporary assignments for the highest rates and offer little additional time to the primary employer. Use of temporary personnel use salary dollars at an inordinate rate while offering little continuity or support for the organization's standards. Methods for placing decision-making in the hands of the nurses are needed along with a reward system for establishing a pattern of sound decision-making. The author describes a savings sharing program that is gaining credibility in one organization for addressing both objectives.

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PubMed

Elting, L S; Rubenstein, E B; Rolston, K; Cantor, S B; Martin, C G; Kurtin, D; Rodriguez, S; Lam, T; Kanesan, K; Bodey, G

2000-11-01

To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

Impact of Coal Mining on Self-Rated Health among Appalachian Residents

PubMed Central

Woolley, Shannon M.; Bear, Todd M.; Balmert, Lauren C.; Talbott, Evelyn O.; Buchanich, Jeanine M.

2015-01-01

Objective. To determine the impact of coal mining, measured as the number of coal mining-related facilities nearby one's residence or employment in an occupation directly related to coal mining, on self-rated health in Appalachia. Methods. Unadjusted and adjusted ordinal logistic regression models calculated odds ratio estimates and associated 95% confidence intervals for the probability of having an excellent self-rated health response versus another response. Covariates considered in the analyses included number of coal mining-related facilities nearby one's residence and employment in an occupation directly related to coal mining, as well as potential confounders age, sex, BMI, smoking status, income, and education. Results. The number of coal mining facilities near the respondent's residence was not a statistically significant predictor of self-rated health. Employment in a coal-related occupation was a statistically significant predictor of self-rated health univariably; however, after adjusting for potential confounders, it was no longer a significant predictor. Conclusions. Self-rated health does not seem to be associated with residential proximity to coal mining facilities or employment in the coal industry. Future research should consider additional measures for the impact of coal mining. PMID:26240577

A fresh look at the predictors of naming accuracy and errors in Alzheimer's disease.

PubMed

Cuetos, Fernando; Rodríguez-Ferreiro, Javier; Sage, Karen; Ellis, Andrew W

2012-09-01

In recent years, a considerable number of studies have tried to establish which characteristics of objects and their names predict the responses of patients with Alzheimer's disease (AD) in the picture-naming task. The frequency of use of words and their age of acquisition (AoA) have been implicated as two of the most influential variables, with naming being best preserved for objects with high-frequency, early-acquired names. The present study takes a fresh look at the predictors of naming success in Spanish and English AD patients using a range of measures of word frequency and AoA along with visual complexity, imageability, and word length as predictors. Analyses using generalized linear mixed modelling found that naming accuracy was better predicted by AoA ratings taken from older adults than conventional ratings from young adults. Older frequency measures based on written language samples predicted accuracy better than more modern measures based on the frequencies of words in film subtitles. Replacing adult frequency with an estimate of cumulative (lifespan) frequency did not reduce the impact of AoA. Semantic error rates were predicted by both written word frequency and senior AoA while null response errors were only predicted by frequency. Visual complexity, imageability, and word length did not predict naming accuracy or errors. ©2012 The British Psychological Society.

The Impact of a Topical Sexual Enhancement Cream on the Female Sexual Response and Its Relationship to Clitoral Blood Flow.

PubMed

Pelekanos, Michael; Stofman, Guy M; Niren, Neil

2016-12-13

The aim of this investigation was to determine, through two Investigational Review Board (IRB)-approved studies, if a new topical vasodilating cream (NTVC; Life Science Enhancement Corporation, Pittsburgh PA) could improve female sexual response. Study I subjectively evaluated sexual female response as accessed by a modification of the Female Intervention Efficacy Index (FIEI). FIEI was developed at the University of California as an immediate outcome measure of medical intervention to treat female sexual dysfunction.1 In Study II, 10 randomly selected positive responders from Study I were subsequently analyzed objectively with clitoral plethysmography in order to determine the effect of the NTVC and placebo on blood flow.2 RESULTS: In the subjective Study I (81 patients ranging in age from 18 to 63), a positive response trend for the NTVC was demonstrated compared to the placebo. In the objective Study II, 10 randomly selected patients who responded positive in Study I were objectively evaluated for response of increased blood flow in the clitoris after application of both the NTVC and placebo. The clitoral blood flow was shown to have increased with statistical significance for the NTVC in all 10 patients compared to the placebo, with the NTVC exhibiting an average 69% increase in clitoral blood flow. The female sexual response is complex. In the subjective Study I, the NTVC demonstrated positive trends for enhanced lubrication, genital sensation, intercourse, and overall sexual experience. In the objective Study II, 10 of the positive subjective responders from Study I were randomly selected to evaluate their response to the NTVC compared to the placebo. This was done via Doppler plethysmography (DP). All 10 patients demonstrated a statistically significant response rate for increase in clitoral blood flow using the NTVC compared to the placebo, with an average blood flow increase of 69%. This portion of the investigation demonstrates a significant positive end organ response to the NTVC. The positive subjective trends combined with the significant and substantial increase in clitoral blood flow may result in enhanced female sexual satisfaction.

Single-exposure visual memory judgments are reflected in inferotemporal cortex

PubMed Central

Meyer, Travis

2018-01-01

Our visual memory percepts of whether we have encountered specific objects or scenes before are hypothesized to manifest as decrements in neural responses in inferotemporal cortex (IT) with stimulus repetition. To evaluate this proposal, we recorded IT neural responses as two monkeys performed a single-exposure visual memory task designed to measure the rates of forgetting with time. We found that a weighted linear read-out of IT was a better predictor of the monkeys’ forgetting rates and reaction time patterns than a strict instantiation of the repetition suppression hypothesis, expressed as a total spike count scheme. Behavioral predictions could be attributed to visual memory signals that were reflected as repetition suppression and were intermingled with visual selectivity, but only when combined across the most sensitive neurons. PMID:29517485

COLOSTOMY CARE

PubMed Central

Lee Marsh, Robert

1955-01-01

Psychic preparation of the patient for the necessity of colostomy is a long first step toward his adjustment to living with an artificial anus. Proper surgical placement of the outlet will ease care of the bowel. Control of fecal consistency and peristaltic rate should ideally produce constipation responsive only to habit or enemata. The object of the enema is to produce an evacuation thorough enough to prevent soiling for a day or two. The object of dietary variations is to produce a manageable volume and consistency of fecal stream. The technique of enemas and choice of diet can be individualized when the underlying principles are understood. PMID:13230924

Risk and safety perception on urban and rural roads: Effects of environmental features, driver age and risk sensitivity.

PubMed

Cox, Jolene A; Beanland, Vanessa; Filtness, Ashleigh J

2017-10-03

The ability to detect changing visual information is a vital component of safe driving. In addition to detecting changing visual information, drivers must also interpret its relevance to safety. Environmental changes considered to have high safety relevance will likely demand greater attention and more timely responses than those considered to have lower safety relevance. The aim of this study was to explore factors that are likely to influence perceptions of risk and safety regarding changing visual information in the driving environment. Factors explored were the environment in which the change occurs (i.e., urban vs. rural), the type of object that changes, and the driver's age, experience, and risk sensitivity. Sixty-three licensed drivers aged 18-70 years completed a hazard rating task, which required them to rate the perceived hazardousness of changing specific elements within urban and rural driving environments. Three attributes of potential hazards were systematically manipulated: the environment (urban, rural); the type of object changed (road sign, car, motorcycle, pedestrian, traffic light, animal, tree); and its inherent safety risk (low risk, high risk). Inherent safety risk was manipulated by either varying the object's placement, on/near or away from the road, or altering an infrastructure element that would require a change to driver behavior. Participants also completed two driving-related risk perception tasks, rating their relative crash risk and perceived risk of aberrant driving behaviors. Driver age was not significantly associated with hazard ratings, but individual differences in perceived risk of aberrant driving behaviors predicted hazard ratings, suggesting that general driving-related risk sensitivity plays a strong role in safety perception. In both urban and rural scenes, there were significant associations between hazard ratings and inherent safety risk, with low-risk changes perceived as consistently less hazardous than high-risk impact changes; however, the effect was larger for urban environments. There were also effects of object type, with certain objects rated as consistently more safety relevant. In urban scenes, changes involving pedestrians were rated significantly more hazardous than all other objects, and in rural scenes, changes involving animals were rated as significantly more hazardous. Notably, hazard ratings were found to be higher in urban compared with rural driving environments, even when changes were matched between environments. This study demonstrates that drivers perceive rural roads as less risky than urban roads, even when similar scenarios occur in both environments. Age did not affect hazard ratings. Instead, the findings suggest that the assessment of risk posed by hazards is influenced more by individual differences in risk sensitivity. This highlights the need for driver education to account for appraisal of hazards' risk and relevance, in addition to hazard detection, when considering factors that promote road safety.

Application of an IRT Polytomous Model for Measuring Health Related Quality of Life

ERIC Educational Resources Information Center

Tejada, Antonio J. Rojas; Rojas, Oscar M. Lozano

2005-01-01

Background: The Item Response Theory (IRT) has advantages for measuring Health Related Quality of Life (HRQOL) as opposed to the Classical Tests Theory (CTT). Objectives: To present the results of the application of a polytomous model based on IRT, specifically, the Rating Scale Model (RSM), to measure HRQOL with the EORTC QLQ-C30. Methods: 103…

Serious Emotional and Behavioral Problems and Mental Health Contacts in American and British Children and Adolescents

ERIC Educational Resources Information Center

Mojtabai, Ramin

2006-01-01

Objective: To compare prevalence of serious emotional and behavioral problems and mental health contacts for these problems among American and British children and adolescents. Method: Data on children and adolescents ages 5 to 16 years were drawn from the 2004 U.S. National Health Interview Survey (response rate = 79.4%) and the 2004 survey of…

The Effects of Observation of Learn Units during Reinforcement and Correction Conditions on the Rate of Learning Math Algorithms by Fifth Grade Students

ERIC Educational Resources Information Center

Neu, Jessica Adele

2013-01-01

I conducted two studies on the comparative effects of the observation of learn units during (a) reinforcement or (b) correction conditions on the acquisition of math objectives. The dependent variables were the within-session cumulative numbers of correct responses emitted during observational sessions. The independent variables were the…

Parental Reports of Somatic Symptoms in Preschool Children: Prevalence and Associations in a Spanish Sample.

ERIC Educational Resources Information Center

Domenech-Llaberia, Edelmira; Jane, Claustre; Canals, Josepa; Ballespi, Sergi; Esparo, Griselda; Garralda, Elena

2004-01-01

Objective: To document prevalence and associations of somatic symptoms in Spanish preschool children. Method: Subjects were 3- to 5-year-olds attending nurseries (8 urban, 30 rural). Parental questionnaires (response rate 77%) were used to inquire about somatic symptoms in the child in the 2 weeks prior to assessment, about preschool absence and…

Prison Field Trips: Can White-Collar Criminals Positively Affect the Ethical and Legal Behavior of Marketing and MBA Students?

ERIC Educational Resources Information Center

Castleberry, Stephen B.

2007-01-01

Marketing educators bear some responsibility for teaching ethics and legal issues to their students. Visits to white-collar criminals in a federal prison camp are one method of achieving this task. This article develops and empirically assesses ten objectives for such a visit by MBA and undergraduate marketing classes. Undergraduates rated the…

The Role of Early Symptom Trajectories and Pretreatment Variables in Predicting Treatment Response to Cognitive Behavioral Therapy

ERIC Educational Resources Information Center

Lewis, Cara C.; Simons, Anne D.; Kim, Hyoun K.

2012-01-01

Objective: Research has focused on 2 different approaches to answering the question, "Which clients will respond to cognitive behavioral therapy (CBT) for depression?" One approach focuses on rates of symptom change within the 1st few weeks of treatment, whereas the 2nd approach looks to pretreatment client variables (e.g., hopelessness) to…

Implementation of Multi-Agent Object Attention System Based on Biologically Inspired Attractor Selection

NASA Astrophysics Data System (ADS)

Hashimoto, Ryoji; Matsumura, Tomoya; Nozato, Yoshihiro; Watanabe, Kenji; Onoye, Takao

A multi-agent object attention system is proposed, which is based on biologically inspired attractor selection model. Object attention is facilitated by using a video sequence and a depth map obtained through a compound-eye image sensor TOMBO. Robustness of the multi-agent system over environmental changes is enhanced by utilizing the biological model of adaptive response by attractor selection. To implement the proposed system, an efficient VLSI architecture is employed with reducing enormous computational costs and memory accesses required for depth map processing and multi-agent attractor selection process. According to the FPGA implementation result of the proposed object attention system, which is accomplished by using 7,063 slices, 640×512 pixel input images can be processed in real-time with three agents at a rate of 9fps in 48MHz operation.

Tradeoff studies in multiobjective insensitive design of airplane control systems

NASA Technical Reports Server (NTRS)

Schy, A. A.; Giesy, D. P.

1983-01-01

A computer aided design method for multiobjective parameter-insensitive design of airplane control systems is described. Methods are presented for trading off nominal values of design objectives against sensitivities of the design objectives to parameter uncertainties, together with guidelines for designer utilization of the methods. The methods are illustrated by application to the design of a lateral stability augmentation system for two supersonic flight conditions of the Shuttle Orbiter. Objective functions are conventional handling quality measures and peak magnitudes of control deflections and rates. The uncertain parameters are assumed Gaussian, and numerical approximations of the stochastic behavior of the objectives are described. Results of applying the tradeoff methods to this example show that stochastic-insensitive designs are distinctly different from deterministic multiobjective designs. The main penalty for achieving significant decrease in sensitivity is decreased speed of response for the nominal system.

Optimization of cladding parameters for resisting corrosion on low carbon steels using simulated annealing algorithm

NASA Astrophysics Data System (ADS)

Balan, A. V.; Shivasankaran, N.; Magibalan, S.

2018-04-01

Low carbon steels used in chemical industries are frequently affected by corrosion. Cladding is a surfacing process used for depositing a thick layer of filler metal in a highly corrosive materials to achieve corrosion resistance. Flux cored arc welding (FCAW) is preferred in cladding process due to its augmented efficiency and higher deposition rate. In this cladding process, the effect of corrosion can be minimized by controlling the output responses such as minimizing dilution, penetration and maximizing bead width, reinforcement and ferrite number. This paper deals with the multi-objective optimization of flux cored arc welding responses by controlling the process parameters such as wire feed rate, welding speed, Nozzle to plate distance, welding gun angle for super duplex stainless steel material using simulated annealing technique. Regression equation has been developed and validated using ANOVA technique. The multi-objective optimization of weld bead parameters was carried out using simulated annealing to obtain optimum bead geometry for reducing corrosion. The potentiodynamic polarization test reveals the balanced formation of fine particles of ferrite and autenite content with desensitized nature of the microstructure in the optimized clad bead.

Optimizing DER Participation in Inertial and Primary-Frequency Response

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

Dall-Anese, Emiliano; Zhao, Changhong; Guggilam, Swaroop

This paper develops an approach to enable the optimal participation of distributed energy resources (DERs) in inertial and primary-frequency response alongside conventional synchronous generators. Leveraging a reduced-order model description of frequency dynamics, DERs' synthetic inertias and droop coefficients are designed to meet time-domain performance objectives of frequency overshoot and steady-state regulation. Furthermore, an optimization-based method centered around classical economic dispatch is developed to ensure that DERs share the power injections for inertial- and primary-frequency response in proportion to their power ratings. Simulations for a modified New England test-case system composed of ten synchronous generators and six instances of the IEEEmore » 37-node test feeder with frequency-responsive DERs validate the design strategy.« less

Front-line window therapy with cisplatin in patients with primary disseminated Ewing sarcoma: A study by the Associazione Italiana di Ematologia ed Oncologia Pediatrica and Italian Sarcoma Group.

PubMed

Luksch, Roberto; Grignani, Giovanni; D'Angelo, Paolo; Prete, Arcangelo; Puma, Nadia; Podda, Marta; Casanova, Michela; Ferrari, Andrea; Morosi, Carlo; Fagioli, Franca; Aglietta, Massimo; Ferrari, Stefano; Picci, Piero; Massimino, Maura

2017-12-01

The aim was to assess the activity of cisplatin (CDDP) in Ewing sarcoma (ES). The study consisted of front-line window therapy with CDDP 120 mg/sqm every 3 weeks for two courses in children and young adults with primary disseminated ES. Response was assessed using the Response Evaluation Criteria in Solid Tumours criteria, and Simon's two-stage design was applied. Twelve consecutive patients were enrolled in stage 1. Only one objective response was observed. Since the target response rate was not achieved, accrual was stopped and CDDP as a single agent in ES was judged unworthy of further assessment. © 2017 Wiley Periodicals, Inc.

On the validity and robustness of the scale error phenomenon in early childhood.

PubMed

DeLoache, Judy S; LoBue, Vanessa; Vanderborght, Mieke; Chiong, Cynthia

2013-02-01

Scale errors is a term referring to very young children's serious efforts to perform actions on miniature replica objects that are impossible due to great differences in the size of the child's body and the size of the target objects. We report three studies providing further documentation of scale errors and investigating the validity and robustness of the phenomenon. In the first, we establish that 2-year-olds' behavior in response to prompts to "pretend" with miniature replica objects differs dramatically from scale errors. The second and third studies address the robustness of the phenomenon and its relative imperviousness to attempts to influence the rate of scale errors. Copyright © 2012 Elsevier Inc. All rights reserved.

Ill-posed problem and regularization in reconstruction of radiobiological parameters from serial tumor imaging data

NASA Astrophysics Data System (ADS)

Chvetsov, Alevei V.; Sandison, George A.; Schwartz, Jeffrey L.; Rengan, Ramesh

2015-11-01

The main objective of this article is to improve the stability of reconstruction algorithms for estimation of radiobiological parameters using serial tumor imaging data acquired during radiation therapy. Serial images of tumor response to radiation therapy represent a complex summation of several exponential processes as treatment induced cell inactivation, tumor growth rates, and the rate of cell loss. Accurate assessment of treatment response would require separation of these processes because they define radiobiological determinants of treatment response and, correspondingly, tumor control probability. However, the estimation of radiobiological parameters using imaging data can be considered an inverse ill-posed problem because a sum of several exponentials would produce the Fredholm integral equation of the first kind which is ill posed. Therefore, the stability of reconstruction of radiobiological parameters presents a problem even for the simplest models of tumor response. To study stability of the parameter reconstruction problem, we used a set of serial CT imaging data for head and neck cancer and a simplest case of a two-level cell population model of tumor response. Inverse reconstruction was performed using a simulated annealing algorithm to minimize a least squared objective function. Results show that the reconstructed values of cell surviving fractions and cell doubling time exhibit significant nonphysical fluctuations if no stabilization algorithms are applied. However, after applying a stabilization algorithm based on variational regularization, the reconstruction produces statistical distributions for survival fractions and doubling time that are comparable to published in vitro data. This algorithm is an advance over our previous work where only cell surviving fractions were reconstructed. We conclude that variational regularization allows for an increase in the number of free parameters in our model which enables development of more-advanced parameter reconstruction algorithms.

Stimulant-Responsive and Stimulant-Refractory Aggressive Behavior Among Children with ADHD

PubMed Central

Blader, Joseph C.; Pliszka, Steven R.; Jensen, Peter S.; Schooler, Nina R.; Kafantaris, Vivian

2010-01-01

OBJECTIVES The objective of this study was to examine factors that are associated with aggression that is responsive versus refractory to individualized optimization of stimulant monotherapy among children with attention-deficit/hyperactivity disorder (ADHD). METHODS Children who were aged 6 to 13 years and had ADHD, either oppositional defiant disorder or conduct disorder, significant aggressive behavior, and a history of insufficient response to stimulants completed an open stimulant monotherapy optimization protocol. Stimulant titration with weekly assessments of behavior and tolerability identified an optimal regimen for each child. Families also received behavioral therapy. Parents completed the Retrospective-Modified Overt Aggression Scale (R-MOAS) at each visit. Children were classified as having stimulant-refractory aggression on the basis of R-MOAS ratings and clinician judgment. Differences that pertained to treatment, demographic, and psychopathology between groups with stimulant monotherapy–responsive and –refractory aggression were evaluated. RESULTS Aggression among 32 (49.3%) of 65 children was reduced sufficiently after stimulant dosage adjustment and behavioral therapy to preclude adjunctive medication. Those who responded to stimulant monotherapy were more likely to benefit from the protocol’s methylphenidate preparation (once-daily, triphasic release), showed a trend for lower average dosages, and received fewer behavioral therapy sessions than did children with stimulant-refractory aggression. Boys, especially those with higher ratings of baseline aggression and of depressive and manic symptoms, more often exhibited stimulant-refractory aggression. CONCLUSIONS Among children whose aggressive behavior develops in the context of ADHD and of oppositional defiant disorder or conduct disorder, and who had insufficient response to previous stimulant treatment in routine clinical care, systematic, well-monitored titration of stimulant monotherapy often culminates in reduced aggression that averts the need for additional agents. PMID:20837589

A Survey of Hospice Volunteer Coordinators: Training Methods and Objectives of Current Hospice Volunteer Training Programs.

PubMed

Brock, Cara M; Herndon, Christopher M

2017-06-01

Currently more than 5800 hospice organizations operate in the United States. 1 Hospice organizations are required by the Centers for Medicare and Medicaid Services (CMS) to use volunteers for services provided to patients. 2 Although CMS regulates the amount of hours hospice volunteers should provide, there are currently no national requirements for objectives of training. 3 The purpose of this study was to gather information from a sample of hospices regarding volunteer coordinator background, current training for volunteers, importance of training objectives, and any comments regarding additional objectives. Representative state hospice organizations were contacted by e-mail requesting their participation and distribution of the survey throughout their member hospices. The survey asked demographical questions, along with ratings of training components based on perceived level of importance and time spent on each objective. A total of 90 surveys were received, and the response rate was undeterminable. Results showed the majority of hospices were nonprofit, had less than 100 currently trained volunteers, and maintained an average daily patient census of less than 50. Questions regarding training programs indicated that most use live lecture methods of approximately 19 hours or less in duration. Overall, responding hospice organizations agreed that all objectives surveyed were important in training volunteers. The small number of respondents to this survey makes generalization nationwide difficult, however it is a strong starting point for the development of further surveys on hospice volunteer training and achieving a standardized set of training objectives and delivery methods.

Responder Status Criterion for Stepped Care Trauma-Focused Cognitive Behavioral Therapy for Young Children

PubMed Central

Salloum, Alison; Scheeringa, Michael S.; Cohen, Judith A.; Storch, Eric A.

2014-01-01

Background In order to develop Stepped Care Trauma-Focused Cognitive Behavioral Therapy (TF-CBT), a definition of early response/non-response is needed to guide decisions about the need for subsequent treatment. Objective The purpose of this article is to (1) establish criterion for defining an early indicator of response/nonresponse to the first step within Stepped Care TF-CBT, and (2) to explore the preliminary clinical utility of the early response/non-response criterion. Method Data from two studies were used: (1) treatment outcome data from a clinical trial in which 17 young children (ages 3 to 6 years) received therapist-directed CBT for children with PTSS were examined to empirically establish the number of posttraumatic stress symptoms to define early treatment response/non-response; and (2) three case examples with young children in Stepped Care TF-CBT were used to explore the utility of the treatment response criterion. Results For defining the responder status criterion, an algorithm of either 3 or fewer PTSS on a clinician-rated measure or being below the clinical cutoff score on a parent-rated measure of childhood PTSS, and being rated as improved, much improved or free of symptoms functioned well for determining whether or not to step up to more intensive treatment. Case examples demonstrated how the criterion were used to guide subsequent treatment, and that responder status criterion after Step One may or may not be aligned with parent preference. Conclusion Although further investigation is needed, the responder status criterion for young children used after Step One of Stepped Care TF-CBT appears promising. PMID:25663796

Impact and Costs of Incentives to Reduce Attrition in Online Trials: Two Randomized Controlled Trials

PubMed Central

Murray, Elizabeth; Kalaitzaki, Eleftheria; White, Ian R; McCambridge, Jim; Thompson, Simon G; Wallace, Paul; Godfrey, Christine

2011-01-01

Background Attrition from follow-up is a major methodological challenge in randomized trials. Incentives are known to improve response rates in cross-sectional postal and online surveys, yet few studies have investigated whether they can reduce attrition from follow-up in online trials, which are particularly vulnerable to low follow-up rates. Objectives Our objective was to determine the impact of incentives on follow-up rates in an online trial. Methods Two randomized controlled trials were embedded in a large online trial of a Web-based intervention to reduce alcohol consumption (the Down Your Drink randomized controlled trial, DYD-RCT). Participants were those in the DYD pilot trial eligible for 3-month follow-up (study 1) and those eligible for 12-month follow-up in the DYD main trial (study 2). Participants in both studies were randomly allocated to receive an offer of an incentive or to receive no offer of an incentive. In study 1, participants in the incentive arm were randomly offered a £5 Amazon.co.uk gift voucher, a £5 charity donation to Cancer Research UK, or entry in a prize draw for £250. In study 2, participants in the incentive arm were offered a £10 Amazon.co.uk gift voucher. The primary outcome was the proportion of participants who completed follow-up questionnaires in the incentive arm(s) compared with the no incentive arm. Results In study 1 (n = 1226), there was no significant difference in response rates between those participants offered an incentive (175/615, 29%) and those with no offer (162/611, 27%) (difference = 2%, 95% confidence interval [CI] –3% to 7%). There was no significant difference in response rates among the three different incentives offered. In study 2 (n = 2591), response rates were 9% higher in the group offered an incentive (476/1296, 37%) than in the group not offered an incentive (364/1295, 28%) (difference = 9%, 95% CI 5% to 12%, P < .001). The incremental cost per extra successful follow-up in the incentive arm was £110 in study 1 and £52 in study 2. Conclusion Whereas an offer of a £10 Amazon.co.uk gift voucher can increase follow-up rates in online trials, an offer of a lower incentive may not. The marginal costs involved require careful consideration. Trial registration ISRCTN31070347; http://www.controlled-trials.com/ISRCTN31070347 (Archived by WebCite at http://www.webcitation.org/5wgr5pl3s) PMID:21371988

Exposure-Response Modeling to Characterize the Relationship Between Ixekizumab Serum Drug Concentrations and Efficacy Responses at Week 12 in Patients With Moderate to Severe Plaque Psoriasis.

PubMed

Chigutsa, Emmanuel; de Mendizabal, Nieves Velez; Chua, Laiyi; Heathman, Michael; Friedrich, Stuart; Jackson, Kimberley; Reich, Kristian

2018-06-07

Ixekizumab, a high-affinity monoclonal antibody, selectively targets interleukin-17A and has been shown to be efficacious in the treatment of moderate to severe psoriasis. The objective was to describe the relationship between ixekizumab concentrations and efficacy response (static Physician Global Assessment [sPGA] and the Psoriasis Activity and Severity Index [PASI) scores] after 12 weeks of ixekizumab treatment in psoriasis patients from 3 phase 3 studies. Data from 2888 psoriasis patients randomized to receive placebo or 80 mg ixekizumab every 2 weeks or every 4 weeks were analyzed. Separate logistic regression models describing the relationship between ixekizumab concentrations and sPGA or PASI scores at week 12 were used to determine the probability of patients achieving a response and to investigate the impact of various patient factors other than drug concentrations on response rates. Both dosing regimens were efficacious, with higher rates of response achieved with the higher range of observed ixekizumab concentrations after every-2-week dosing. Although higher bodyweight, palmoplantar involvement, lower baseline disease state, or high baseline C-reactive protein were associated with slightly lower response rates, the magnitude of effect of these factors on sPGA(0,1) response was small, with all subgroups able to achieve high levels of response. Other factors tested had no effect including age, sex, and antidrug antibody status. Logistic regression modeling of ixekizumab concentration and efficacy data accurately identified the proportion of responders using sPGA or PASI end points. The higher concentration ranges achieved with 80 mg every 2 weeks versus every 4 weeks were associated with higher response levels. © 2018, The American College of Clinical Pharmacology.

A prospective randomized study of Chop versus Chop plus alpha-2B interferon in patients with intermediate and high grade non-Hodgkin's lymphoma: the International Oncology Study Group NHL1 Study .

PubMed

Giles, F J; Shan, J; Advani, S H; Akan, H; Aydogdu, I; Aziz, Z; Azim, H A; Bapsy, P P; Buyukkececi, F; Chaimongkol, B; Chen, P M; Cheong, S K; Ferhanoglu, B; Hamza, R; Khalid, H M; Intragumtornchai, T; Kim, S W; Kim, S Y; Koc, H; Kumar, L; Kumar, R; Lei, K I; Lekhakula, A; Muthalib, A; Patel, M; Poovalingam, V P; Prayoonwiwat, W; Rana, F; Reksodiputro, A H; Ruff, P; Sagar, T G; Schwarer, A P; Song, H S; Suh, C W; Suharti, C; Supindiman, I; Tee, G Y; Thamprasit, T; Villalon, A H; Wickham, N R; Wong, J E; Yalcin, A; Jootar, S

2000-12-01

The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin's lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

Nursing and dental students' and pediatric dentistry residents' responses to experiences with interprofessional education.

PubMed

Czarnecki, Gail A; Kloostra, Stephanie J; Boynton, James R; Inglehart, Marita R

2014-09-01

Interprofessional education (IPE) has received increasingly more attention over recent years. The objectives of this study were to assess 1) how nursing students' considerations concerning their own oral health and oral health-related knowledge changed from before to after experiencing IPE; 2) how nursing students', dental students', and pediatric dentistry residents' IPE-related attitudes and Readiness for Interprofessional Learning Scale (RIPLS) scores changed after experiencing an IPE rotation; and 3) how these groups' attitudes and RIPLS scores were related. Data were collected from three groups who participated in an IPE rotation: thirty-eight of forty third-year dental students (95 percent response rate), all thirty-three nursing students (100 percent), and all six pediatric dentistry residents (100 percent) prior to the rotation, and 100 percent of each group after the rotation. As a control group, data were also collected at the beginning of the winter term from first-year dental students (104 out of 105; 99 percent response rate) and second-year dental students (102 out of 116; 88 percent); the same groups were surveyed at the end of term, with response rates of 98 percent for first-year students and 89 percent for second-year students. After the rotation, the nursing students' tooth brushing frequency increased, and their comfort level with dental visits and oral health-related knowledge improved. The dental students rated the importance of nurses' having oral health-related knowledge and skills lower than did the nursing students and pediatric dentistry residents. The groups' RIPLS scores correlated with these importance ratings. Overall, while the nursing students showed positive responses to IPE, the dental students' attitudes and RIPLS scores did not change as a result of the IPE experience. Future research should explore the conditions under which dental students are impacted by IPE.

Open-label Bendamustine Monotherapy for Pediatric Patients With Relapsed or Refractory Acute Leukemia: Efficacy and Tolerability

PubMed Central

Brown, Patrick; Megason, Gail; Ahn, Hyo Seop; Cho, Bin; Kirov, Ivan; Frankel, Lawrence; Aplenc, Richard; Bensen-Kennedy, Debra; Munteanu, Mihaela; Weaver, Jennifer; Harker-Murray, Paul

2014-01-01

This open-label, single-arm, phase I/II, dose-escalation study was designed to determine the recommended phase II dose (RP2D), pharmacokinetics, tolerability, and efficacy of bendamustine in pediatric patients (age ranging from 1 to 20 y) with histologically proven relapsed/refractory acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Patients (27 with ALL, 16 with AML) received intravenous bendamustine on days 1 and 2 of each treatment cycle. Phase I involved planned dose escalation of bendamustine to establish the RP2D for phase II. Objectives included overall response rate, duration of response, and tolerability. Eleven patients were treated in phase I, and the RP2D was 120 mg/m2. In phase II, 32 patients received bendamustine 120 mg/m2. Two patients with ALL (bendamustine 90 mg/m2) experienced complete response (CR). Among patients who received bendamustine 120 mg/m2, 2 experienced partial response (PR); 7 had stable disease. The overall response rate (CR+CR without platelet recovery [CRp]) was 4.7% and biological activity rate (CR+CRp+PR) was 9.3%. No AML patients responded. The most common adverse events were anemia, neutropenia, thrombocytopenia, pyrexia, nausea, vomiting, and diarrhea. Bendamustine monotherapy has acceptable tolerability in heavily pretreated children with relapsed/refractory ALL or AML and appears to have some activity in ALL, warranting further studies in combination trials. PMID:24072240

Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study.

PubMed

Moore, Kathleen N; Martin, Lainie P; O'Malley, David M; Matulonis, Ursula A; Konner, Jason A; Perez, Raymond P; Bauer, Todd M; Ruiz-Soto, Rodrigo; Birrer, Michael J

2017-04-01

Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Eligibility included a minimum requirement of FRα positivity by immunohistochemistry (≥ 25% of tumor cells with at least 2+ staining intensity). Adverse events, tumor response (via Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), and progression-free survival (PFS) were determined. Results Forty-six patients were enrolled. Adverse events were generally mild (≤ grade 2), with diarrhea (44%), blurred vision (41%), nausea (37%), and fatigue (30%) being the most commonly observed treatment-related toxicities. Grade 3 fatigue and hypotension were reported in two patients each (4%). For all evaluable patients, the confirmed objective response rate was 26%, including one complete and 11 partial responses, and the median PFS was 4.8 months. The median duration of response was 19.1 weeks. Notably, in the subset of patients who had received three or fewer prior lines of therapy (n = 23), an objective response rate of 39%, PFS of 6.7 months, and duration of response of 19.6 weeks were observed. Conclusion IMGN853 exhibited a manageable safety profile and was active in platinum-resistant ovarian cancer, with the strongest signals of efficacy observed in less heavily pretreated individuals. On the basis of these findings, the dose, schedule, and target population were identified for a phase III trial of IMGN853 monotherapy in patients with platinum-resistant disease.

Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha–Targeting Antibody–Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study

PubMed Central

Martin, Lainie P.; O’Malley, David M.; Matulonis, Ursula A.; Konner, Jason A.; Perez, Raymond P.; Bauer, Todd M.; Ruiz-Soto, Rodrigo; Birrer, Michael J.

2017-01-01

Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody–drug conjugate consisting of a humanized anti–folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Eligibility included a minimum requirement of FRα positivity by immunohistochemistry (≥ 25% of tumor cells with at least 2+ staining intensity). Adverse events, tumor response (via Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), and progression-free survival (PFS) were determined. Results Forty-six patients were enrolled. Adverse events were generally mild (≤ grade 2), with diarrhea (44%), blurred vision (41%), nausea (37%), and fatigue (30%) being the most commonly observed treatment-related toxicities. Grade 3 fatigue and hypotension were reported in two patients each (4%). For all evaluable patients, the confirmed objective response rate was 26%, including one complete and 11 partial responses, and the median PFS was 4.8 months. The median duration of response was 19.1 weeks. Notably, in the subset of patients who had received three or fewer prior lines of therapy (n = 23), an objective response rate of 39%, PFS of 6.7 months, and duration of response of 19.6 weeks were observed. Conclusion IMGN853 exhibited a manageable safety profile and was active in platinum-resistant ovarian cancer, with the strongest signals of efficacy observed in less heavily pretreated individuals. On the basis of these findings, the dose, schedule, and target population were identified for a phase III trial of IMGN853 monotherapy in patients with platinum-resistant disease. PMID:28029313

The Effect of a Surgical Skills Course on Confidence Levels of Rural General Practitioners: An Observational Study.

PubMed

Byrd, Pippa; Ward, Olga; Hamdorf, Jeffrey

2016-10-01

Objective  To investigate the effect of a short surgical skills course on general practitioners' confidence levels to perform procedural skills. Design  Prospective observational study. Setting  The Clinical Evaluation and Training Centre, a practical skills-based educational facility, at The University of Western Australia. Participants  Medical practitioners who participated in these courses. Nurses, physiotherapists, and medical students were excluded. The response rate was 61% with 61 participants providing 788 responses for pre- and postcourse confidence levels regarding various surgical skills. Intervention  One- to two-day surgical skills courses consisting of presentations, demonstrations, and practical stations, facilitated by specialists. Main Outcome Measures  A two-page precourse and postcourse questionnaire was administered to medical practitioners on the day. Participants rated their confidence levels to perform skills addressed during the course on a 4-point Likert scale. Results  Of the 788 responses regarding confidence levels, 621 were rated as improved postcourse, 163 were rated as no change, and 4 were rated as lower postcourse. Seven of the courses showed a 25% median increase in confidence levels, and one course demonstrated a 50% median increase. All courses showed statistically significant results ( p  < 0.001). Conclusion  A short surgical skills course resulted in a statistically significant improvement in the confidence levels of rural general practitioners to perform these skills.

Emotion dysregulation in alexithymia: Startle reactivity to fearful affective imagery and its relation to heart rate variability.

PubMed

Panayiotou, Georgia; Constantinou, Elena

2017-09-01

Alexithymia is associated with deficiencies in recognizing and expressing emotions and impaired emotion regulation, though few studies have verified the latter assertion using objective measures. This study examined startle reflex modulation by fearful imagery and its associations with heart rate variability in alexithymia. Fifty-four adults (27 alexithymic) imagined previously normed fear scripts. Startle responses were assessed during baseline, first exposure, and reexposure. During first exposure, participants, in separate trials, engaged in either shallow or deep emotion processing, giving emphasis on descriptive or affective aspects of imagery, respectively. Resting heart rate variability was assessed during 2 min of rest prior to the experiment, with high alexithymic participants demonstrating significantly higher LF/HF (low frequency/high frequency) ratio than controls. Deep processing was associated with nonsignificantly larger and faster startle responses at first exposure for alexithymic participants. Lower LF/HF ratio, reflecting higher parasympathetic cardiac activity, predicted greater startle amplitude habituation for alexithymia but lower habituation for controls. Results suggest that, when exposed to prolonged threat, alexithymics may adjust poorly, showing a smaller initial defensive response but slower habituation. This pattern seems related to their low emotion regulation ability as indexed by heart rate variability. © 2017 Society for Psychophysiological Research.

Characterization and prediction of rate-dependent flexibility in lumbar spine biomechanics at room and body temperature.

PubMed

Stolworthy, Dean K; Zirbel, Shannon A; Howell, Larry L; Samuels, Marina; Bowden, Anton E

2014-05-01

The soft tissues of the spine exhibit sensitivity to strain-rate and temperature, yet current knowledge of spine biomechanics is derived from cadaveric testing conducted at room temperature at very slow, quasi-static rates. The primary objective of this study was to characterize the change in segmental flexibility of cadaveric lumbar spine segments with respect to multiple loading rates within the range of physiologic motion by using specimens at body or room temperature. The secondary objective was to develop a predictive model of spine flexibility across the voluntary range of loading rates. This in vitro study examines rate- and temperature-dependent viscoelasticity of the human lumbar cadaveric spine. Repeated flexibility tests were performed on 21 lumbar function spinal units (FSUs) in flexion-extension with the use of 11 distinct voluntary loading rates at body or room temperature. Furthermore, six lumbar FSUs were loaded in axial rotation, flexion-extension, and lateral bending at both body and room temperature via a stepwise, quasi-static loading protocol. All FSUs were also loaded using a control loading test with a continuous-speed loading-rate of 1-deg/sec. The viscoelastic torque-rotation response for each spinal segment was recorded. A predictive model was developed to accurately estimate spine segment flexibility at any voluntary loading rate based on measured flexibility at a single loading rate. Stepwise loading exhibited the greatest segmental range of motion (ROM) in all loading directions. As loading rate increased, segmental ROM decreased, whereas segmental stiffness and hysteresis both increased; however, the neutral zone remained constant. Continuous-speed tests showed that segmental stiffness and hysteresis are dependent variables to ROM at voluntary loading rates in flexion-extension. To predict the torque-rotation response at different loading rates, the model requires knowledge of the segmental flexibility at a single rate and specified temperature, and a scaling parameter. A Bland-Altman analysis showed high coefficients of determination for the predictive model. The present work demonstrates significant changes in spine segment flexibility as a result of loading rate and testing temperature. Loading rate effects can be accounted for using the predictive model, which accurately estimated ROM, neutral zone, stiffness, and hysteresis within the range of voluntary motion. Copyright © 2014 Elsevier Inc. All rights reserved.

Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Vaccine Coadministered With Seasonal Influenza Vaccine in Adults Aged 50 Years or Older.

PubMed

Schwarz, Tino F; Aggarwal, Naresh; Moeckesch, Beate; Schenkenberger, Isabelle; Claeys, Carine; Douha, Martine; Godeaux, Olivier; Grupping, Katrijn; Heineman, Thomas C; Fauqued, Marta Lopez; Oostvogels, Lidia; Van den Steen, Peter; Lal, Himal

2017-12-12

The immunogenicity and safety of an adjuvanted herpes zoster subunit (HZ/su) vaccine when coadministered with a quadrivalent seasonal inactivated influenza vaccine (IIV4) was investigated in a phase 3, open-label, randomized clinical trial in adults aged ≥50 years. Subjects were randomized 1:1 to receive either HZ/su (varicella zoster virus glycoprotein E; AS01B Adjuvant System) and IIV4 at day 0 followed by a second HZ/su dose at month 2 (coadministration group), or IIV4 at month 0 and HZ/su at months 2 and 4 (control group). The primary objectives were the HZ/su vaccine response rate in the coadministration group and the noninferiority of the antibody responses to HZ/su and IIV4 in the coadministration compared with the control group. Safety information was collected throughout the duration of the study. A total of 413 subjects were vaccinated in the coadministration group and 415 in the control group. The HZ/su vaccine response rate in the coadministration group was 95.8% (95% confidence interval, 93.3%-97.6%) and the anti-glycoprotein E GMCControl/Coadmin ratio was 1.08 (.97-1.20). The primary noninferiority objectives were met. No safety concerns were observed. No interference in the immune responses to either vaccine was observed when the vaccines were coadministered, and no safety concerns were identified. NCT01954251. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Light beam range finder

DOEpatents

McEwan, Thomas E.

1998-01-01

A "laser tape measure" for measuring distance which includes a transmitter such as a laser diode which transmits a sequence of electromagnetic pulses in response to a transmit timing signal. A receiver samples reflections from objects within the field of the sequence of visible electromagnetic pulses with controlled timing, in response to a receive timing signal. The receiver generates a sample signal in response to the samples which indicates distance to the object causing the reflections. The timing circuit supplies the transmit timing signal to the transmitter and supplies the receive timing signal to the receiver. The receive timing signal causes the receiver to sample the reflection such that the time between transmission of pulses in the sequence in sampling by the receiver sweeps over a range of delays. The transmit timing signal causes the transmitter to transmit the sequence of electromagnetic pulses at a pulse repetition rate, and the received timing signal sweeps over the range of delays in a sweep cycle such that reflections are sampled at the pulse repetition rate and with different delays in the range of delays, such that the sample signal represents received reflections in equivalent time. The receiver according to one aspect of the invention includes an avalanche photodiode and a sampling gate coupled to the photodiode which is responsive to the received timing signal. The transmitter includes a laser diode which supplies a sequence of visible electromagnetic pulses. A bright spot projected on to the target clearly indicates the point that is being measured, and the user can read the range to that point with precision of better than 0.1%.

Light beam range finder

DOEpatents

McEwan, T.E.

1998-06-16

A ``laser tape measure`` for measuring distance is disclosed which includes a transmitter such as a laser diode which transmits a sequence of electromagnetic pulses in response to a transmit timing signal. A receiver samples reflections from objects within the field of the sequence of visible electromagnetic pulses with controlled timing, in response to a receive timing signal. The receiver generates a sample signal in response to the samples which indicates distance to the object causing the reflections. The timing circuit supplies the transmit timing signal to the transmitter and supplies the receive timing signal to the receiver. The receive timing signal causes the receiver to sample the reflection such that the time between transmission of pulses in the sequence in sampling by the receiver sweeps over a range of delays. The transmit timing signal causes the transmitter to transmit the sequence of electromagnetic pulses at a pulse repetition rate, and the received timing signal sweeps over the range of delays in a sweep cycle such that reflections are sampled at the pulse repetition rate and with different delays in the range of delays, such that the sample signal represents received reflections in equivalent time. The receiver according to one aspect of the invention includes an avalanche photodiode and a sampling gate coupled to the photodiode which is responsive to the received timing signal. The transmitter includes a laser diode which supplies a sequence of visible electromagnetic pulses. A bright spot projected on to the target clearly indicates the point that is being measured, and the user can read the range to that point with precision of better than 0.1%. 7 figs.

An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR) in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 1 (GT1)

PubMed Central

Asselah, Tarik; Moreno, Christophe; Sarrazin, Christoph; Gschwantler, Michael; Foster, Graham R.; Craxí, Antonio; Buggisch, Peter; Ryan, Robert; Lenz, Oliver; Scott, Jane; Van Dooren, Gino; Lonjon-Domanec, Isabelle; Schlag, Michael; Buti, Maria

2016-01-01

Background Shortening duration of peginterferon-based HCV treatment reduces associated burden for patients. Primary objectives of this study were to assess the efficacy against the minimally acceptable response rate 12 weeks post-treatment (SVR12) and safety of simeprevir plus PR in treatment-naïve HCV GT1 patients treated for 12 weeks. Additional objectives included the investigation of potential associations of rapid viral response and baseline factors with SVR12. Methods In this Phase III, open-label study in treatment-naïve HCV GT1 patients with F0–F2 fibrosis, patients with HCV-RNA <25 IU/mL (detectable/undetectable) at Week 2, and undetectable HCV-RNA at Weeks 4 and 8, stopped all treatment at Week 12. All other patients continued PR for a further 12 weeks. Baseline factors significantly associated with SVR12 were identified through logistic regression. Results Of 163 patients who participated in the study, 123 (75%) qualified for 12-week treatment; of these, 81 (66%) achieved SVR12. Baseline factors positively associated with SVR12 rates in patients receiving the 12-week regimen were: IL28B CC genotype: (94% SVR12); HCV RNA ≤800,000 IU/mL (82%); F0–F1 fibrosis (74%). Among all 163 patients, 94% experienced ≥1 adverse event (AE), 4% a serious AE, and 2.5% discontinued due to an AE. Reduced impairment in patient-reported outcomes was observed in the 12-week vs >12-week regimen. Conclusions Overall SVR12 rate (66%) was below the target of 80%, indicating that shortening of treatment with simeprevir plus PR to 12 weeks based on very early response is not effective. However, baseline factors associated with higher SVR12 rates were identified. Therefore, while Week 2 response alone is insufficient to predict efficacy, GT1 patients with favourable baseline factors may benefit from a shortened simeprevir plus PR regimen. Trial Registration ClinicalTrials.gov NCT01846832 PMID:27428331

Characteristics, Access, Utilization, Satisfaction, and Outcomes of Healthy Start Participants in Eight Sites

PubMed Central

O’Neil, So; Cook, Benjamin; Trebino, Lisa; Walker, Deborah Klein

2009-01-01

To describe the characteristics, access, utilization, satisfaction, and outcomes of Healthy Start participants in eight selected sites, a survey of Healthy Start participants with infants ages 6–12-months-old at time of interview was conducted between October 2006 and January 2007. The response rate was 66% (n = 646), ranging from 37% in one site to >70% in seven sites. Healthy Start participants’ outcomes were compared to two national benchmarks. Healthy Start participants reported that they were satisfied with the program (>90% on five measures). Level of unmet need was 6% or less for most services, except for dental appointments (11%), housing (13%), and child care (11%). Infants had significantly better access to medical care than did their mothers, with higher rates of insurance coverage, medical homes, and checkups, and fewer unmet needs for health care. Healthy Start participants’ rates of ever breastfeeding (72%) and putting infants to sleep on their backs (70%) were at or near the Healthy People 2010 objectives, and considerably higher than rates among low-income mothers in the ECLS. The high rate of health education (>90%) may have contributed to these outcomes. Elimination of smoking among Healthy Start participants (46%) fell short of the Healthy People 2010 objective (99%). The low-birth weight (LBW) rate among Black Healthy Start participants (14%) was three times higher than the rate for Whites and Hispanics (5% each). Overall, the LBW rate in the eight sites (7.5%) was similar to the rate for low-income mothers in the ECLS, but both rates were above the Healthy People 2010 objective (5%). Challenges remain in reducing disparities in maternal and child health outcomes. Further attention to risk factors associated with LBW (especially smoking) may help close the gaps. The life course theory suggests that improved outcomes may require longer-term investments. Healthy Start’s emerging focus on interconception care has the potential to address longer-term needs of participants. PMID:19590941

VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Relapsed and Refractory Multiple Myeloma.

PubMed

Siegel, David S; Dimopoulos, Meletios; Jagannath, Sundar; Goldschmidt, Hartmut; Durrant, Simon; Kaufman, Jonathan L; Leleu, Xavier; Nagler, Arnon; Offner, Fritz; Graef, Thorsten; Eid, Joseph E; Houp, Jennifer; Gause, Christine; Vuocolo, Scott; Anderson, Kenneth C

2016-06-01

The present global, open-label, single-arm, multicenter, phase IIb study was designed to determine the efficacy and tolerability of oral vorinostat combined with standard doses of bortezomib in patients with multiple myeloma considered refractory to novel myeloma agents. Eligible patients were age ≥ 18 years, had received ≥ 2 previous regimens, had disease refractory to ≥ 1 previous bortezomib-containing regimen, and had received ≥ 1 dose of an immunomodulatory drug (thalidomide or lenalidomide)-based regimen. The patients received 21-day cycles of bortezomib (1.3 mg/m(2) intravenously on days 1, 4, 8, and 11) plus oral vorinostat (400 mg/d on days 1-14). Oral dexamethasone, 20 mg, on the day of and the day after each dose of bortezomib could be added for patients with progressive disease after 2 cycles or no change after 4 cycles. The primary endpoint was the objective response rate. The objective response rate was 11.3% (95% confidence interval, 6.6%-17.7%), and the median duration of response was 211 days (range, 64-550 days). The median overall survival duration was 11.2 months (95% confidence interval, 8.5-14.4 months), with a 2-year survival rate of 32%. The frequently reported adverse events were thrombocytopenia (69.7%), nausea (57.0%), diarrhea (53.5%), anemia (52.1%), and fatigue (48.6%); the overall safety profile was consistent with that of bortezomib and vorinostat. The combination of vorinostat and bortezomib is active in patients with multiple myeloma refractory to novel treatment modalities and offers a new therapeutic option for this difficult-to-treat patient population (ClinicalTrials.gov identifier, NCT00773838). Copyright © 2016 Elsevier Inc. All rights reserved.

A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naïve patients with advanced melanoma.

PubMed

Hersh, Evan M; O'Day, Steven J; Powderly, John; Khan, Khuda D; Pavlick, Anna C; Cranmer, Lee D; Samlowski, Wolfram E; Nichol, Geoffrey M; Yellin, Michael J; Weber, Jeffrey S

2011-06-01

Ipilimumab is a fully human, anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody that has demonstrated antitumor activity in advanced melanoma. We evaluated the safety and efficacy of ipilimumab alone and in combination with dacarbazine (DTIC) in patients with unresectable, metastatic melanoma. Chemotherapy-naïve patients were randomized in this multicenter, phase II study to receive ipilimumab at 3 mg/kg every 4 weeks for four doses either alone or with up to six 5-day courses of DTIC at 250 mg/m(2)/day. The primary efficacy endpoint was objective response rate. Seventy-two patients were treated per-protocol (ipilimumab plus DTIC, n = 35; ipilimumab, n = 37). The objective response rate was 14.3% (95% CI, 4.8-30.3) with ipilimumab plus DTIC and was 5.4% (95% CI, 0.7-18.2) with ipilimumab alone. At a median follow-up of 20.9 and 16.4 months for ipilimumab plus DTIC (n = 32) and ipilimumab alone (n = 32), respectively, median overall survival was 14.3 months (95% CI, 10.2-18.8) and 11.4 months (95% CI, 6.1-15.6); 12-month, 24-month, and 36-month survival rates were 62%, 24% and 20% for the ipilimumab plus DTIC group and were 45%, 21% and 9% for the ipilimumab alone group, respectively. Immune-related adverse events were, in general, medically manageable and occurred in 65.7% of patients in the combination group versus 53.8% in the monotherapy group, with 17.1% and 7.7% ≥grade 3, respectively. Ipilimumab therapy resulted in clinically meaningful responses in advanced melanoma patients, and the results support further investigations of ipilimumab in combination with DTIC.

Perceptions of the Inpatient Training Experience: A Nationwide Survey of Gastroenterology Program Directors and Fellows.

PubMed

Kumar, Navin L; Perencevich, Molly L; Trier, Jerry S

2017-10-01

Inpatient training is a key component of gastroenterology (GI) fellowship programs nationwide, yet little is known about perceptions of the inpatient training experience. To compare the content, objectives and quality of the inpatient training experience as perceived by program directors (PD) and fellows in US ACGME-accredited GI fellowship programs. We conducted a nationwide, online-based survey of GI PDs and fellows at the conclusion of the 2016 academic year. We queried participants about (1) the current models of inpatient training, (2) the content, objectives, and quality of the inpatient training experience, and (3) the frequency and quality of educational activities on the inpatient service. We analyzed five-point Likert items and rank assessments as continuous variables by an independent t test and compared proportions using the Chi-square test. Survey response rate was 48.4% (75/155) for PDs and a total of 194 fellows completed the survey, with both groups reporting the general GI consult team (>90%) as the primary model of inpatient training. PDs and fellows agreed on the ranking of all queried responsibilities of the inpatient fellow to develop during the inpatient service. However, fellows indicated that attendings spent less time teaching and provided less formal feedback than that perceived by PDs (p < 0.0001). PDs rated the overall quality of the inpatient training experience (p < 0.0001) and education on the wards (p = 0.0003) as better than overall ratings by fellows. Although GI fellows and PDs agree on the importance of specific fellow responsibilities on the inpatient service, fellows report experiencing less teaching and feedback from attendings than that perceived by PDs. Committing more time to education and assessment may improve fellows' perceptions of the inpatient training experience.

Automated assessment of levodopa-induced dyskinesia: Evaluating the responsiveness of video-based features.

PubMed

Li, Michael H; Mestre, Tiago A; Fox, Susan H; Taati, Babak

2018-05-05

Technological solutions for quantifying Parkinson's disease (PD) symptoms may provide an objective means to track response to treatment, including side effects such as levodopa-induced dyskinesia. Vision-based systems are advantageous as they do not require physical contact with the body and have minimal instrumentation compared to wearables. We have developed a vision-based system to quantify a change in dyskinesia as reported by patients using 2D videos of clinical assessments during acute levodopa infusions. Nine participants with PD completed a total of 16 levodopa infusions, where they were asked to report important changes in dyskinesia (i.e. onset and remission). Participants were simultaneously rated using the UDysRS Part III (from video recordings analyzed post-hoc). Body joint positions and movements were tracked using a state-of-the-art deep learning pose estimation algorithm applied to the videos. 416 features (e.g. kinematics, frequency distribution) were extracted to characterize movements. The sensitivity and specificity of each feature to patient-reported changes in dyskinesia severity was computed and compared with physician-rated results. Features achieved similar or superior performance to the UDysRS for detecting the onset and remission of dyskinesia. The best AUC for detecting onset of dyskinesia was 0.822 and for remission of dyskinesia was 0.958, compared to 0.826 and 0.802 for the UDysRS. Video-based features may provide an objective means of quantifying the severity of levodopa-induced dyskinesia, and have responsiveness as good or better than the clinically-rated UDysRS. The results demonstrate encouraging evidence for future integration of video-based technology into clinical research and eventually clinical practice. Copyright © 2018 Elsevier Ltd. All rights reserved.

Response to environmental change in rainbow trout selected for divergent stress coping styles.

PubMed

Ruiz-Gomez, Maria de Lourdes; Huntingford, Felicity A; Øverli, Øyvind; Thörnqvist, Per-Ove; Höglund, Erik

2011-03-01

An extensive literature has documented differences in the way individual animals cope with environmental challenges and stressors. Two broad patterns of individual variability in behavioural and physiological stress responses are described as the proactive and reactive stress coping styles. In addition to variability in the stress response, contrasting coping styles may encompass a general difference in behavioural flexibility as opposed to routine formation in response to more subtle environmental changes and non-threatening novelties. In the present study two different manipulations, relocating food from a previously learned location, and introducing a novel object yielded contrasting responses in rainbow trout selected for high (HR) and low (LR) post stress plasma cortisol levels. No difference was seen in the rate of learning the original food location; however, proactive LR fish were markedly slower than reactive HR fish in altering their food seeking behaviour in response to relocated food. In contrast, LR fish largely ignored a novel object which disrupted feeding in HR fish. Hence, it appears that the two lines appraise environmental cues differently. This observation suggests that differences in responsiveness to environmental change are an integral component of heritable stress coping styles, which in this particular case, had opposite effects on foraging efficiency in different situations. Context dependent fitness effects may thus explain the persistence of stable divergence of this evolutionary widespread trait complex. 2010 Elsevier Inc. All rights reserved.

Multivariate evoked response detection based on the spectral F-test.

PubMed

Rocha, Paulo Fábio F; Felix, Leonardo B; Miranda de Sá, Antonio Mauricio F L; Mendes, Eduardo M A M

2016-05-01

Objective response detection techniques, such as magnitude square coherence, component synchrony measure, and the spectral F-test, have been used to automate the detection of evoked responses. The performance of these detectors depends on both the signal-to-noise ratio (SNR) and the length of the electroencephalogram (EEG) signal. Recently, multivariate detectors were developed to increase the detection rate even in the case of a low signal-to-noise ratio or of short data records originated from EEG signals. In this context, an extension to the multivariate case of the spectral F-test detector is proposed. The performance of this technique is assessed using Monte Carlo. As an example, EEG data from 12 subjects during photic stimulation is used to demonstrate the usefulness of the proposed detector. The multivariate method showed detection rates consistently higher than those ones when only one signal was used. It is shown that the response detection in EEG signals with the multivariate technique was statistically significant if two or more EEG derivations were used. Copyright © 2016 Elsevier B.V. All rights reserved.

Qualities of Single Electrode Stimulation as a Function of Rate and Place of Stimulation with a Cochlear Implant

PubMed Central

Landsberger, David M.; Vermeire, Katrien; Claes, Annes; Van Rompaey, Vincent; Van de Heyning, Paul

2015-01-01

Objectives Although it has been previously shown that changes in temporal coding produce changes in pitch in all cochlear regions, research has suggested that temporal coding might be best encoded in relatively apical locations. We hypothesized that although temporal coding may provide useable information at any cochlear location, low rates of stimulation might provide better sound quality in apical regions that are more likely to encode temporal information in the normal ear. In the present study, sound qualities of single electrode pulse trains were scaled to provide insight into the combined effects of cochlear location and stimulation rate on sound quality. Design Ten long term users of MED-EL cochlear implants with 31 mm electrode arrays (Standard or FLEXSOFT) were asked to scale the sound quality of single electrode pulse trains in terms of how “Clean”, “Noisy”, “High”, and “Annoying” they sounded. Pulse trains were presented on most electrodes between 1 and 12 representing the entire range of the long electrode array at stimulation rates of 100, 150, 200, 400, or 1500 pulses per second. Results While high rates of stimulation are scaled as having a “Clean” sound quality across the entire array, only the most apical electrodes (typically 1 through 3) were considered “Clean” at low rates. Low rates on electrodes 6 through 12 were not rated as “Clean” while the low rate quality of electrodes 4 and 5 were typically in between. Scaling of “Noisy” responses provided an approximately inverse pattern as “Clean” responses. “High” responses show the trade-off between rate and place of stimulation on pitch. Because “High” responses did not correlate with “Clean” responses, subjects were not rating sound quality based on pitch. Conclusions If explicit temporal coding is to be provided in a cochlear implant, it is likely to sound better when provided apically. Additionally, the finding that low rates sound clean only at apical places of stimulation is consistent with previous findings that a change in rate of stimulation corresponds to an equivalent change in perceived pitch at apical locations. Collectively, the data strongly suggests that temporal coding with a cochlear implant is optimally provided by electrodes placed well into the second cochlear turn. PMID:26583480

Osimertinib in Pretreated T790M-Positive Advanced Non-Small-Cell Lung Cancer: AURA Study Phase II Extension Component.

PubMed

Yang, James Chih-Hsin; Ahn, Myung-Ju; Kim, Dong-Wan; Ramalingam, Suresh S; Sequist, Lecia V; Su, Wu-Chou; Kim, Sang-We; Kim, Joo-Hang; Planchard, David; Felip, Enriqueta; Blackhall, Fiona; Haggstrom, Daniel; Yoh, Kiyotaka; Novello, Silvia; Gold, Kathryn; Hirashima, Tomonori; Lin, Chia-Chi; Mann, Helen; Cantarini, Mireille; Ghiorghiu, Serban; Jänne, Pasi A

2017-04-20

Purpose Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for both EGFR-TKI sensitizing ( EGFRm) and T790M resistance mutations. AURA (NCT01802632) is a phase I/II clinical trial to determine the dose, safety, and efficacy of osimertinib. This article reports the results from the phase II extension component. Patients and Methods Patients with EGFR-TKI-pretreated EGFRm- and T790M-positive advanced non-small-cell lung cancer (NSCLC) received once-daily osimertinib 80 mg. T790M status was confirmed by central testing from a tumor sample taken after the most recent disease progression. Patients with asymptomatic, stable CNS metastases that did not require corticosteroids were allowed to enroll. The primary end point was objective response rate (ORR) by independent radiology assessment. Secondary end points were disease control rate, duration of response, progression-free survival (PFS), and safety. Patient-reported outcomes comprised an exploratory objective. Results In total, 201 patients received treatment, with a median treatment duration of 13.2 months at the time of data cutoff (November 1, 2015). In evaluable patients (n = 198), ORR was 62% (95% CI, 54% to 68%), and the disease control rate was 90% (95% CI, 85 to 94). Median duration of response in 122 responding patients was 15.2 months (95% CI, 11.3 to not calculable). Median PFS was 12.3 months (95% CI, 9.5 to 13.8). The most common possibly causally related adverse events (investigator assessed) were diarrhea (43%; grade ≥ 3, < 1%) and rash (grouped terms; 40%; grade ≥ 3, < 1%). Interstitial lung disease (grouped terms) was reported in eight patients (4%; grade 1, n = 2; grade 3, n = 3; grade 5, n = 3). Conclusion In patients with EGFRm T790M advanced NSCLC who progress after EGFR-TKI treatment, osimertinib provides a high ORR, encouraging PFS, and durable response.

Is stress a trigger factor for migraine?

PubMed

Schoonman, G G; Evers, D J; Ballieux, B E; de Geus, E J; de Kloet, E R; Terwindt, G M; van Dijk, J G; Ferrari, M D

2007-06-01

Although mental stress is commonly considered to be an important trigger factor for migraine, experimental evidence for this belief is yet lacking. To study the temporal relationship between changes in stress-related parameters (both subjective and objective) and the onset of a migraine attack. This was a prospective, ambulatory study in 17 migraine patients. We assessed changes in perceived stress and objective biological measures for stress (saliva cortisol, heart rate average [HRA], and heart rate variability [low-frequency power and high-frequency power]) over 4 days prior to the onset of spontaneous migraine attacks. Analyses were repeated for subgroups of patients according to whether or not they felt their migraine to be triggered by stress. There were no significant temporal changes over time for the whole group in perceived stress (p=0.50), morning cortisol (p=0.73), evening cortisol (p=0.55), HRA (p=0.83), low-frequency power (p=0.99) and high-frequency power (p=0.97) prior to or during an attack. Post hoc analysis of the subgroup of nine stress-sensitive patients who felt that >2/3 of their migraine attacks were triggered by psychosocial stress, revealed an increase for perceived stress (p=0.04) but no changes in objective stress response measures. At baseline, this group also showed higher scores on the Penn State Worry Questionnaire (p=0.003) and the Cohen Perceived Stress Scale (p=0.001) compared to non-stress-sensitive patients. Although stress-sensitive patients, in contrast to non-stress-sensitive patients, may perceive more stress in the days before an impending migraine attack, we failed to detect any objective evidence for a biological stress response before or during migraine attacks.

Do Changes in Hospital Outpatient Payments Affect the Setting of Care?

PubMed Central

He, Daifeng; Mellor, Jennifer M

2013-01-01

Objective To examine whether decreases in Medicare outpatient payment rates under the Outpatient Prospective Payment System (OPPS) caused outpatient care to shift toward the inpatient setting. Data Sources/Study Setting Hospital inpatient and outpatient discharge files from the Florida Agency for Health Care Administration from 1997 through 2008. Study Design This study focuses on inguinal hernia repair surgery, one of the most commonly performed surgical procedures in the United States. We estimate multivariate regressions of inguinal hernia surgery counts in the outpatient setting and in the inpatient setting. The key explanatory variable is the time-varying Medicare payment rate specific to the procedure and hospital. Control variables include time-varying hospital and county characteristics and hospital and year-fixed effects. Principal Findings Outpatient hernia surgeries fell in response to OPPS-induced rate cuts. The volume of inpatient hernia repair surgeries did not increase in response to reductions in the outpatient reimbursement rate. Conclusions Potential substitution from the outpatient setting to the inpatient setting does not pose a serious threat to Medicare's efforts to contain hospital outpatient costs. PMID:23701048

Monitoring stage fright outside the laboratory: an example in a professional musician using wearable sensors.

PubMed

Kusserow, Martin; Candia, Victor; Amft, Oliver; Hildebrandt, Horst; Folkers, Gerd; Tröster, Gerhard

2012-03-01

We implemented and tested a wearable sensor system to measure patterns of stress responses in a professional musician under public performance conditions. Using this sensor system, we monitored the cellist's heart activity, the motion of multiple body parts, and their gradual changes during three repeated performances of a skill-demanding piece in front of a professional audience. From the cellist and her teachers, we collected stage fright self-reports and performance ratings that were related to our sensor data analysis results. Concomitant to changes in body motion and heart rate, the cellist perceived a reduction in stage fright. Performance quality was objectively improved, as technical playing errors decreased throughout repeated renditions. In particular, from performance 1 to 3, the wearable sensors measured a significant increase in the cellist's bowing motion dynamics of approximately 6% and a decrease in heart rate. Bowing motion showed a marginal correlation to the observed heart rate patterns during playing. The wearable system did not interfere with the cellist's performance, thereby allowing investigation of stress responses during natural public performances.

Stereotactic body radiotherapy for de novo spinal metastases: systematic review.

PubMed

Husain, Zain A; Sahgal, Arjun; De Salles, Antonio; Funaro, Melissa; Glover, Janis; Hayashi, Motohiro; Hiraoka, Masahiro; Levivier, Marc; Ma, Lijun; Martínez-Alvarez, Roberto; Paddick, J Ian; Régis, Jean; Slotman, Ben J; Ryu, Samuel

2017-09-01

OBJECTIVE The aim of this systematic review was to provide an objective summary of the published literature pertaining to the use of stereotactic body radiation therapy (SBRT) specific to previously untreated spinal metastases. METHODS The authors performed a systematic review, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, of the literature found in a search of Medline, PubMed, Embase, and the Cochrane Library up to March 2015. The search strategy was limited to publications in the English language. RESULTS A total of 14 full-text articles were included in the analysis. All studies were retrospective except for 2 studies, which were prospective. A total of 1024 treated spinal lesions were analyzed. The median follow-up time ranged from 9 to 49 months. A range of dose-fractionation schemes was used, the most common of which were 16-24 Gy/1 fraction (fx), 24 Gy/2 fx, 24-27 Gy/3 fx, and 30-35 Gy/5 fx. In studies that reported crude results regarding in-field local tumor control, 346 (85%) of 407 lesions remained controlled. For studies that reported actuarial values, the weighted average revealed a 90% 1-year local control rate. Only 3 studies reported data on complete pain response, and the weighted average of these results yielded a complete pain response rate of 54%. The most common toxicity was new or progressing vertebral compression fracture, which was observed in 9.4% of cases; 2 cases (0.2%) of neurologic injury were reported. CONCLUSION There is a paucity of prospective data specific to SBRT in patients with spinal metastases not otherwise irradiated. This systematic review found that SBRT is associated with favorable rates of local control (approximately 90% at 1 year) and complete pain response (approximately 50%), and low rates of serious adverse events were found. Practice guidelines are summarized based on these data and International Stereotactic Radiosurgery Society consensus.

Learning to perceive differences in solid shape through vision and touch.

PubMed

Norman, J Farley; Clayton, Anna Marie; Norman, Hideko F; Crabtree, Charles E

2008-01-01

A single experiment was designed to investigate perceptual learning and the discrimination of 3-D object shape. Ninety-six observers were presented with naturally shaped solid objects either visually, haptically, or across the modalities of vision and touch. The observers' task was to judge whether the two sequentially presented objects on any given trial possessed the same or different 3-D shapes. The results of the experiment revealed that significant perceptual learning occurred in all modality conditions, both unimodal and cross-modal. The amount of the observers' perceptual learning, as indexed by increases in hit rate and d', was similar for all of the modality conditions. The observers' hit rates were highest for the unimodal conditions and lowest in the cross-modal conditions. Lengthening the inter-stimulus interval from 3 to 15 s led to increases in hit rates and decreases in response bias. The results also revealed the existence of an asymmetry between two otherwise equivalent cross-modal conditions: in particular, the observers' perceptual sensitivity was higher for the vision-haptic condition and lower for the haptic-vision condition. In general, the results indicate that effective cross-modal shape comparisons can be made between the modalities of vision and active touch, but that complete information transfer does not occur.

Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort.

PubMed

Mazières, Julien; Zalcman, Gérard; Crinò, Lucio; Biondani, Pamela; Barlesi, Fabrice; Filleron, Thomas; Dingemans, Anne-Marie C; Léna, Hervé; Monnet, Isabelle; Rothschild, Sacha I; Cappuzzo, Federico; Besse, Benjamin; Thiberville, Luc; Rouvière, Damien; Dziadziuszko, Rafal; Smit, Egbert F; Wolf, Jurgen; Spirig, Christian; Pecuchet, Nicolas; Leenders, Frauke; Heuckmann, Johannes M; Diebold, Joachim; Milia, Julie D; Thomas, Roman K; Gautschi, Oliver

2015-03-20

Approximately 1% of lung adenocarcinomas are driven by oncogenic ROS1 rearrangement. Crizotinib is a potent inhibitor of both ROS1 and ALK kinase domains. In the absence of a prospective clinical trial in Europe, we conducted a retrospective study in centers that tested for ROS1 rearrangement. Eligible patients had stage IV lung adenocarcinoma, had ROS1 rearrangement according to fluorescent in situ hybridization, and had received crizotinib therapy through an individual off-label use. Best response was assessed locally using RECIST (version 1.1). All other data were analyzed centrally. We identified 32 eligible patients. One patient was excluded because next-generation sequencing was negative for ROS1 fusion. Median age was 50.5 years, 64.5% of patients were women, and 67.7% were never-smokers. Thirty patients were evaluable for progression-free survival (PFS), and 29 patients were evaluable for best response. We observed four patients with disease progression, two patients with stable disease, and objective response in 24 patients, including five complete responses (overall response rate, 80%; disease control rate, 86.7%). Median PFS was 9.1 months, and the PFS rate at 12 months was 44%. No unexpected adverse effects were observed. Twenty-six patients received pemetrexed (either alone or in combination with platinum and either before or after crizotinib) and had a response rate of 57.7% and a median PFS of 7.2 months. Crizotinib was highly active at treating lung cancer in patients with a ROS1 rearrangement, suggesting that patients with lung adenocarcinomas should be tested for ROS1. Prospective clinical trials with crizotinib and other ROS1 inhibitors are ongoing or planned. © 2015 by American Society of Clinical Oncology.

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.

Effects of a Financial Incentive on Health Researchers’ Response to an Online Survey: a Randomized Controlled Trial

PubMed Central

Petticrew, Mark; Calnan, Mike; Nazareth, Irwin

2010-01-01

Background Nonresponse to questionnaires can affect the validity of surveys and introduce bias. Offering financial incentives can increase response rates to postal questionnaires, but the effect of financial incentives on response rates to online surveys is less clear. Objective As part of a survey, we aimed to test whether knowledge of a financial incentive would increase the response rate to an online questionnaire. Methods A randomized controlled trial of 485 UK-based principal investigators of publicly funded health services and population health research. Participants were contacted by email and invited to complete an online questionnaire via an embedded URL. Participants were randomly allocated to groups with either “knowledge of” or “no knowledge of” a financial incentive (£10 Amazon gift voucher) to be provided on completion of the survey. At the end of the study, gift vouchers were given to all participants who completed the questionnaire regardless of initial randomization status. Four reminder emails (sent from the same email address as the initial invitation) were sent out to nonrespondents at one, two, three, and four weeks; a fifth postal reminder was also undertaken. The primary outcome measure for the trial was the response rate one week after the second reminder. Response rate was also measured at the end of weeks one, two, three, four, and five, and after a postal reminder was sent. Results In total, 243 (50%) questionnaires were returned (232 completed, 11 in which participation was declined). One week after the second reminder, the response rate in the “knowledge” group was 27% (66/244) versus 20% (49/241) in the “no knowledge” group (χ21 = 3.0, P = .08). The odds ratio for responding among those with knowledge of an incentive was 1.45 (95% confidence interval [CI] 0.95 - 2.21). At the third reminder, participants in the “no knowledge” group were informed about the incentive, ending the randomized element of the study. However we continued to follow up all participants, and from reminder three onwards, no significant differences were observed in the response rates of the two groups. Conclusions Knowledge of a financial incentive did not significantly increase the response rate to an online questionnaire. Future surveys should consider including a randomized element to further test the utility of offering incentives of other types and amounts to participate in online questionnaires. Trial Registration ISRCTN59912797; http://www.controlled-trials.com/ISRCTN59912797 (Archived by WebCite at http://www.webcitation.org/5iPPLbT7s) PMID:20457556

Teamwork in the NICU Setting and Its Association with Health Care-Associated Infections in Very Low-Birth-Weight Infants.

PubMed

Profit, Jochen; Sharek, Paul J; Kan, Peiyi; Rigdon, Joseph; Desai, Manisha; Nisbet, Courtney C; Tawfik, Daniel S; Thomas, Eric J; Lee, Henry C; Sexton, J Bryan

2017-08-01

Background and Objective  Teamwork may affect clinical care in the neonatal intensive care unit (NICU) setting. The objective of this study was to assess teamwork climate across NICUs and to test scale-level and item-level associations with health care-associated infection (HAI) rates in very low-birth-weight (VLBW) infants. Methods  Cross-sectional study of the association between HAI rates, defined as any bacterial or fungal infection during the birth hospitalization, among 6,663 VLBW infants cared for in 44 NICUs between 2010 and 2012. NICU HAI rates were correlated with teamwork climate ratings obtained in 2011 from 2,073 of 3,294 eligible NICU health professionals (response rate 63%). The relation between HAI rates and NICU teamwork climate was assessed using logistic regression models including NICU as a random effect. Results  Across NICUs, 36 to 100% (mean 66%) of respondents reported good teamwork. HAI rates were significantly and independently associated with teamwork climate (odds ratio, 0.82; 95% confidence interval, 0.73-0.92, p  = 0.005), such that the odds of an infant contracting a HAI decreased by 18% with each 10% rise in NICU respondents reporting good teamwork. Conclusion  Improving teamwork may be an important element in infection control efforts. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Perirhinal cortical inactivation impairs object-in-place memory and disrupts task-dependent firing in hippocampal CA1, but not in CA3.

PubMed

Lee, Inah; Park, Seong-Beom

2013-01-01

Objects and their locations can associatively define an event and a conjoint representation of object-place can form an event memory. Remembering how to respond to a certain object in a spatial context is dependent on both hippocampus and perirhinal cortex (PER). However, the relative functional contributions of the two regions are largely unknown in object-place associative memory. We investigated the PER influence on hippocampal firing in a goal-directed object-place memory task by comparing the firing patterns of CA1 and CA3 of the dorsal hippocampus between conditions of PER muscimol inactivation and vehicle control infusions. Rats were required to choose one of the two objects in a specific spatial context (regardless of the object positions in the context), which was shown to be dependent on both hippocampus and PER. Inactivation of PER with muscimol (MUS) severely disrupted performance of well-trained rats, resulting in response bias (i.e., choosing any object on a particular side). MUS did not significantly alter the baseline firing rates of hippocampal neurons. We measured the similarity in firing patterns between two trial conditions in which the same target objects were chosen on opposite sides within the same arm [object-in-place (O-P) strategy] and compared the results with the similarity in firing between two trial conditions in which the rat chose any object encountered on a particular side [response-in-place (R-P) strategy]. We found that the similarity in firing patterns for O-P trials was significantly reduced with MUS compared to control conditions (CTs). Importantly, this was largely because MUS injections affected the O-P firing patterns in CA1 neurons, but not in CA3. The results suggest that PER is critical for goal-directed organization of object-place associative memory in the hippocampus presumably by influencing how object information is associated with spatial information in CA1 according to task demand.

Determining the mechanical constitutive properties of metals as a function of strain rate and temperature: A combined experimental and modeling approach

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

I. M. Robertson; A. Beaudoin; J. Lambros

2004-01-05

OAK-135 Development and validation of constitutive models for polycrystalline materials subjected to high strain rate loading over a range of temperatures are needed to predict the response of engineering materials to in-service type conditions (foreign object damage, high-strain rate forging, high-speed sheet forming, deformation behavior during forming, response to extreme conditions, etc.). To account accurately for the complex effects that can occur during extreme and variable loading conditions, requires significant and detailed computational and modeling efforts. These efforts must be closely coupled with precise and targeted experimental measurements that not only verify the predictions of the models, but also providemore » input about the fundamental processes responsible for the macroscopic response. Achieving this coupling between modeling and experimentation is the guiding principle of this program. Specifically, this program seeks to bridge the length scale between discrete dislocation interactions with grain boundaries and continuum models for polycrystalline plasticity. Achieving this goal requires incorporating these complex dislocation-interface interactions into the well-defined behavior of single crystals. Despite the widespread study of metal plasticity, this aspect is not well understood for simple loading conditions, let alone extreme ones. Our experimental approach includes determining the high-strain rate response as a function of strain and temperature with post-mortem characterization of the microstructure, quasi-static testing of pre-deformed material, and direct observation of the dislocation behavior during reloading by using the in situ transmission electron microscope deformation technique. These experiments will provide the basis for development and validation of physically-based constitutive models, which will include dislocation-grain boundary interactions for polycrystalline systems. One aspect of the program will involve the dire ct observation of specific mechanisms of micro-plasticity, as these will indicate the boundary value problem that should be addressed. This focus on the pre-yield region in the quasi-static effort (the elasto-plastic transition) is also a tractable one from an experimental and modeling viewpoint. In addition, our approach will minimize the need to fit model parameters to experimental data to obtain convergence. These are critical steps to reach the primary objective of simulating and modeling material performance under extreme loading conditions. In this annual report, we describe the progress made in the first year of this program.« less

Risk to space sustainability from large constellations of satellites

NASA Astrophysics Data System (ADS)

Bastida Virgili, B.; Dolado, J. C.; Lewis, H. G.; Radtke, J.; Krag, H.; Revelin, B.; Cazaux, C.; Colombo, C.; Crowther, R.; Metz, M.

2016-09-01

The number of artificial objects in orbit continues to increase and, with it, a key threat to space sustainability. In response, space agencies have identified a set of mitigation guidelines aimed at enabling space users to reduce the generation of space debris by, for example, limiting the orbital lifetime of their spacecraft and launcher stages after the end of their mission. Planned, large constellations of satellites in low Earth orbit (LEO), though addressing the lack of basic internet coverage in some world regions, may disrupt the sustainability of the space environment enabled by these mitigation practices. We analyse the response of the space object population to the introduction of a large constellation conforming to the post-mission disposal guideline with differing levels of success and with different disposal orbit options. The results show that a high success rate of post-mission disposal by constellation satellites is a key driver for space sustainability.

Supporting Simple Activity Engagement in Persons With Moderate to Severe Alzheimer's Disease Through a Technology-Aided Program.

PubMed

Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; D'Amico, Fiora; Pinto, Katia; Chiapparino, Claudia

2017-05-01

These 2 studies assessed a technology-aided program to support mild physical exercise or simple occupational activity in participants with moderate to severe Alzheimer's disease. Study 1 included 11 participants who were to perform a leg-raising response. Study 2 included 10 participants who were to sort objects into different containers. The program ensured that they received positive stimulation contingent on the responses and reminders/prompts after periods of nonresponding. Each study was carried out according to a nonconcurrent multiple baseline design across participants. The program was successful in supporting mild physical exercise and activity with objects in the 2 groups of participants, respectively. The participants also showed signs of positive involvement (eg, smiles and verbalizations) during the sessions. Moreover, staff personnel rated the program and its impact positively. The program may be considered a practical resource for supporting positive engagement in persons with moderate to severe Alzheimer's disease.

Question order sensitivity of subjective well-being measures: focus on life satisfaction, self-rated health, and subjective life expectancy in survey instruments.

PubMed

Lee, Sunghee; McClain, Colleen; Webster, Noah; Han, Saram

2016-10-01

This study examines the effect of question context created by order in questionnaires on three subjective well-being measures: life satisfaction, self-rated health, and subjective life expectancy. We conducted two Web survey experiments. The first experiment (n = 648) altered the order of life satisfaction and self-rated health: (1) life satisfaction asked immediately after self-rated health; (2) self-rated health immediately after life satisfaction; and (3) two items placed apart. We examined their correlation coefficient by experimental condition and further examined its interaction with objective health. The second experiment (n = 479) asked life expectancy before and after parental mortality questions. Responses to life expectancy were compared by order using ANOVA, and we examined interaction with parental mortality status using ANCOVA. Additionally, response time and probes were examined. Correlation coefficients between self-rated health and life satisfaction differed significantly by order: 0.313 (life satisfaction first), 0.508 (apart), and 0.643 (self-rated health first). Differences were larger among respondents with chronic conditions. Response times were the shortest when self-rated health was asked first. When life expectancy asked after parental mortality questions, respondents reported considering parents more for answering life expectancy; and respondents with deceased parents reported significantly lower expectancy, but not those whose parents were alive. Question context effects exist. Findings suggest placing life satisfaction and self-rated health apart to avoid artificial attenuation or inflation in their association. Asking about parental mortality prior to life expectancy appears advantageous as this leads respondents to consider parental longevity more, an important factor for true longevity.

Decreasing racial disparity with the combination of ledipasvir-sofosbuvir for the treatment of chronic hepatitis C.

PubMed

Naylor, Paul H; Mutchnick, Milton

2017-01-01

African Americans (AA) in the US are twice as likely to be infected with hepatitis C virus (HCV) compared to the non-Hispanic-white US population (Cau). They are also more likely to be infected with HCV genotype 1, more likely to develop hepatocellular carcinoma, and, in addition, have a lower response rate to interferon-based therapies. With the increase in response rates reported for combinations of direct-acting antivirals, the possibility that racial disparity would be eliminated by agents that directly inhibit virus replication has become a reality. The objective of this review is to evaluate the literature from clinical studies and retrospective analysis with respect to the response of AA to the most prescribed antiviral combination sofosbuvir plus ledipasvir. While few studies have focused on AA patients, sufficient information is availed from the literature and studies in our predominately AA clinic population to confirm that ledipasvir-sofosbuvir has a similar effectiveness in AA as compared to Cau.

Clinical effects of laser immunotherapy on metastatic cancer patients

NASA Astrophysics Data System (ADS)

Naylor, Mark F.; Lam, Anh K.; Bahavar, Cody F.; Nordquist, Robert E.; Chen, Wei R.

2016-03-01

Clinical trials of late-stage breast cancer patients and late-stage melanoma patients treated by laser immunotherapy (LIT) have shown promising results. In a 2010 study of Li et al, eleven late-stage melanoma patients received LIT in one or multiple 6-week treatment cycles applied to a 200-cm2 treatment site, which usually contained multiple cutaneous metastases. Long-term, positive response was observed in six patients. All lesions in the treatment area of the patients responded to LIT, eight of which achieved complete local response (CLR). CLR was observed in the non-treatment site (regional) lesions in four patients. Five patients were still alive at the time of last follow-up. The probability of 12-month overall survival was 70%.2 In 2011, Li et al, treated ten late stage breast cancer patients with LIT.1 In 8 patients available for evaluation, the objective response rate was 62.5% and the clinical beneficial response rate was 75%.1 This review demonstrates that LIT is safe and well tolerated, so it can be easily applied on an outpatient basis and can be combined with other pharmaceutical modalities to improve the therapeutic response of metastatic cancers.

Application of grey-fuzzy approach in parametric optimization of EDM process in machining of MDN 300 steel

NASA Astrophysics Data System (ADS)

Protim Das, Partha; Gupta, P.; Das, S.; Pradhan, B. B.; Chakraborty, S.

2018-01-01

Maraging steel (MDN 300) find its application in many industries as it exhibits high hardness which are very difficult to machine material. Electro discharge machining (EDM) is an extensively popular machining process which can be used in machining of such materials. Optimization of response parameters are essential for effective machining of these materials. Past researchers have already used Taguchi for obtaining the optimal responses of EDM process for this material with responses such as material removal rate (MRR), tool wear rate (TWR), relative wear ratio (RWR), and surface roughness (SR) considering discharge current, pulse on time, pulse off time, arc gap, and duty cycle as process parameters. In this paper, grey relation analysis (GRA) with fuzzy logic is applied to this multi objective optimization problem to check the responses by an implementation of the derived parametric setting. It was found that the parametric setting derived by the proposed method results in better a response than those reported by the past researchers. Obtained results are also verified using the technique for order of preference by similarity to ideal solution (TOPSIS). The predicted result also shows that there is a significant improvement in comparison to the results of past researchers.

Sizing Single Cantilever Beam Specimens for Characterizing Facesheet/Core Peel Debonding in Sandwich Structure

NASA Technical Reports Server (NTRS)

Ratcliffe, James G.

2010-01-01

This paper details part of an effort focused on the development of a standardized facesheet/core peel debonding test procedure. The purpose of the test is to characterize facesheet/core peel in sandwich structure, accomplished through the measurement of the critical strain energy release rate associated with the debonding process. The specific test method selected for the standardized test procedure utilizes a single cantilever beam (SCB) specimen configuration. The objective of the current work is to develop a method for establishing SCB specimen dimensions. This is achieved by imposing specific limitations on specimen dimensions, with the objectives of promoting a linear elastic specimen response, and simplifying the data reduction method required for computing the critical strain energy release rate associated with debonding. The sizing method is also designed to be suitable for incorporation into a standardized test protocol. Preliminary application of the resulting sizing method yields practical specimen dimensions.

Objective and subjective measures indicate that orthographically similar words produce a blocking experience.

PubMed

Leynes, P Andrew; Brown, Jaime; Landau, Joshua D

2011-01-01

Memory blocks are a common experience characterised by inappropriate retrieval of information that impairs memory search processes. In five studies, memory blocks were induced via exposure to orthographically similar words (Smith & Tindell, 1997) while participants reported their subjective experiences to determine whether the memory block effect (MBE) paradigm produces a feeling of being blocked. Experiments 1 and 3 provided evidence that the MBE is associated with more blocked experiences. In Experiments 2 and 4 increased blocking experiences correlated with blocked fragments when the experimental manipulation was disguised, which demonstrates that ratings were not contaminated by demand characteristics. Experiment 5 demonstrated that blocking happens even when there is no study list. Collectively, the subjective retrieval ratings and the objective response data provide converging evidence that exposure to orthographically similar words induces a memory block characterised by an ineffective memory search that perseverates on interfering information.

Evidence for the activation of sensorimotor information during visual word recognition: the body-object interaction effect.

PubMed

Siakaluk, Paul D; Pexman, Penny M; Aguilera, Laura; Owen, William J; Sears, Christopher R

2008-01-01

We examined the effects of sensorimotor experience in two visual word recognition tasks. Body-object interaction (BOI) ratings were collected for a large set of words. These ratings assess perceptions of the ease with which a human body can physically interact with a word's referent. A set of high BOI words (e.g., mask) and a set of low BOI words (e.g., ship) were created, matched on imageability and concreteness. Facilitatory BOI effects were observed in lexical decision and phonological lexical decision tasks: responses were faster for high BOI words than for low BOI words. We discuss how our findings may be accounted for by (a) semantic feedback within the visual word recognition system, and (b) an embodied view of cognition (e.g., Barsalou's perceptual symbol systems theory), which proposes that semantic knowledge is grounded in sensorimotor interactions with the environment.

An exploratory study on scientific investigations in homeopathy using medical analyzer.

PubMed

Mishra, Nirupama; Muraleedharan, K Charan; Paranjpe, Akalpita Sriniwas; Munta, Devendra Kumar; Singh, Hari; Nayak, Chaturbhuja

2011-08-01

The action of homeopathic medicines, in ultra-high dilution, is not directly observable. An attempt was made to explore autonomic response of selective homeopathic medicines, in healthy persons, using Medical Analyzer System (Electronics Division, Bhabha Atomic Research Centre, Mumbai, India). The objective of the study was to observe the action of homeopathic medicines on physiologic variability of heart rate and blood flow. Pre- and postinterventional variability spectra of heart rate and blood flow of 77 subjects were recorded with the Medical Analyzer System, administering homeopathic preparations of Aconitum napellus (6c, 10M), Arsenicum album (200c, 1M), Gelsemium sempervirens (200c, 1M), Phosphorus (200c, 1M), Pulsatilla nigricans (200c) and Sulphur (200c, 1M) versus placebo control. The amplitude of the peaks viz. low-frequency, medium-frequency, and high-frequency was measured for postintervention analysis. An increase in the amplitude of any valid peak by 100% or a decrease by 50% was considered as significant change. Aconitum napellus produced a response in heart rate variability (HRV) with 30c potency and in blood flow variability with 1M potency. Sulphur 200c and 1M, Gelsemium 200c and Pulsatilla 200c, produced a 62.5% response in HRV against the placebo response of 16.6%. Gelsemium, Phosphorus, and Sulphur produced a response in blood flow variability with a 1M potency, similar to the response of Aconitum napellus 1M. These data suggest that it is possible to record the response of homeopathic medicines on physiologic parameters of the autonomic nervous system.

Objective Measures of Emotion Related to Brand Attitude: A New Way to Quantify Emotion-Related Aspects Relevant to Marketing

PubMed Central

Walla, Peter; Brenner, Gerhard; Koller, Monika

2011-01-01

With this study we wanted to test the hypothesis that individual like and dislike as occurring in relation to brand attitude can be objectively assessed. First, individuals rated common brands with respect to subjective preference. Then, they volunteered in an experiment during which their most liked and disliked brand names were visually presented while three different objective measures were taken. Participant's eye blinks as responses to acoustic startle probes were registered with electromyography (EMG) (i) and their skin conductance (ii) and their heart rate (iii) were recorded. We found significantly reduced eye blink amplitudes related to liked brand names compared to disliked brand names. This finding suggests that visual perception of liked brand names elicits higher degrees of pleasantness, more positive emotion and approach-oriented motivation than visual perception of disliked brand names. Also, skin conductance and heart rate were both reduced in case of liked versus disliked brand names. We conclude that all our physiological measures highlight emotion-related differences depending on the like and dislike toward individual brands. We suggest that objective measures should be used more frequently to quantify emotion-related aspects of brand attitude. In particular, there might be potential interest to introduce startle reflex modulation to measure emotion-related impact during product development, product design and various further fields relevant to marketing. Our findings are discussed in relation to the idea that self reported measures are most often cognitively polluted. PMID:22073192

Objective measures of emotion related to brand attitude: a new way to quantify emotion-related aspects relevant to marketing.

PubMed

Walla, Peter; Brenner, Gerhard; Koller, Monika

2011-01-01

With this study we wanted to test the hypothesis that individual like and dislike as occurring in relation to brand attitude can be objectively assessed. First, individuals rated common brands with respect to subjective preference. Then, they volunteered in an experiment during which their most liked and disliked brand names were visually presented while three different objective measures were taken. Participant's eye blinks as responses to acoustic startle probes were registered with electromyography (EMG) (i) and their skin conductance (ii) and their heart rate (iii) were recorded. We found significantly reduced eye blink amplitudes related to liked brand names compared to disliked brand names. This finding suggests that visual perception of liked brand names elicits higher degrees of pleasantness, more positive emotion and approach-oriented motivation than visual perception of disliked brand names. Also, skin conductance and heart rate were both reduced in case of liked versus disliked brand names. We conclude that all our physiological measures highlight emotion-related differences depending on the like and dislike toward individual brands. We suggest that objective measures should be used more frequently to quantify emotion-related aspects of brand attitude. In particular, there might be potential interest to introduce startle reflex modulation to measure emotion-related impact during product development, product design and various further fields relevant to marketing. Our findings are discussed in relation to the idea that self reported measures are most often cognitively polluted.

Survey of the Prevalence of Burnout, Stress, Depression, and the Use of Supports by Medical Students at One School

ERIC Educational Resources Information Center

Chang, Elaine; Eddins-Folensbee, Florence; Coverdale, John

2012-01-01

Objective: The authors determined the prevalence of stress, depression, and burnout in medical students and the resources used by students in one school to alleviate psychological distress. Methods: A survey was administered to 526 students in the first 3 years of medical school (336 responders; response rate: 70%) at one institution, using a…

Spent CCA treated wood from residential decks can be a resource for reuse and recycling

Treesearch

Robert L Smith; Philip A. Araman; David Bailey; Matthew F. Winn

2005-01-01

The volume of CCA treated wood being disposed of in landfills is growing at an alarming rate. In order to reduce the demand on landfills and timber harvest, more environmentally responsible alternatives for spent CCA treated wood have to be addressed. The objective of this study was to determine feasible products that can be produced from CCA treated wood....

Prospective Study of Posttraumatic Stress Disorder in Parents of Children with Newly Diagnosed Type 1 Diabetes.

ERIC Educational Resources Information Center

Landolt, Markus A.; Vollrath, Margarete; Laimbacher, Joseph; Gnehm, Hanspeter E.; Sennhauser, Felix H.

2005-01-01

Objective: To determine the prevalence, course, and predictors of posttraumatic stress disorder (PTSD) in mothers and fathers of children with newly diagnosed type 1 diabetes. Method: Forty-nine mothers and 48 fathers of 52 children (response rate 65%) with newly diagnosed diabetes (age 6.5-15 years) were assessed at 6 weeks, 6 months, and 12…

Mathematical Models Relating Effects of Xenobiotic Substances on Individuals and Populations

DTIC Science & Technology

1997-09-30

experimental information quantifying the impact of toxicants on the individual organisms within impacted, or potentially impacted populations. OBJECTIVES...The research has two main parts: (i) modeling the consequences for individuals of toxicant -induced changes in the rates of energy acquisition and...In modeling the response of individuals to toxicants , we use dynamic energy budget (DEB) models to describe the rules by which individual organisms

Examining the Prospective Effects of Making a Virginity Pledge among Males across Their 4 Years of College

ERIC Educational Resources Information Center

Williams, Samantha; Thompson, Martie P.

2013-01-01

Objectives: The authors examined prospective associations of making a virginity pledge on sexual behaviors among male college students. Participants: A sample of 795 males was followed for 4 years (2008, 2009, 2010, 2011), with response rates ranging from 72% to 82% across the follow-up years. Methods: Males were surveyed at the end of each of…

Basal area growth, carbon isotope discrimination, and intrinsic water use efficiency after fertilization of Douglas-fir in the Oregon Coast Range

Treesearch

Eladio H. Cornejo-Oviedo; Steven L. Voelker; Douglas B. Mainwaring; Douglas A. Maguire; Frederick C. Meinzer; J. Renée Brooks

2017-01-01

Many hectares of intensively managed Douglas-fir (Pseudotsuga menziesii Mirb. Franco) stands in western North America are fertilized with nitrogen (N) to increase growth rates, but only about ⅔ of all stands respond. Understanding the mechanisms of response facilitates prioritization of stands for treatment. The primary objective of this study was...

D-cycloserine as an augmentation strategy of cognitive behavioral therapy for social anxiety disorder

PubMed Central

Hofmann, Stefan G.; Smits, Jasper A. J.; Rosenfield, David; Simon, Naomi; Otto, Michael W.; Meuret, Alicia E.; Marques, Luana; Fang, Angela; Tart, Candyce; Pollack, Mark H.

2014-01-01

OBJECTIVE To test whether d-cycloserine, a partial agonist at the glutamatergic N-methyl-D-aspartate receptor, augments and accelerates a full course of comprehensive cognitive behavioral therapy (CBT) in medication-free adults with generalized social anxiety disorder. METHOD A randomized placebo-controlled efficacy-study conducted at Boston University, Massachusetts General Hospital, and Southern Methodist University between 9/2007 and 12/2011 of 169 medication-free adults with generalized social anxiety disorder; 144 completed treatment, and 131 completed the follow-up assessments. Patients were randomized to receive 50 mg of d-cycloserine or placebo 1 hour before each of 5 exposure sessions that were part of a 12-session cognitive behavioral group treatment. Response and remission status was determined at baseline, throughout treatment, post-treatment, and at 1, 3, and 6-month follow-up assessments rated by assessors who were blind to treatment condition. RESULTS D-cycloserine-augmented and placebo-augmented CBT were associated with similar completion rates (87% and 82%), response rates (79.3% and 73.3%), and remission rates (34.5% and 24.4%) at post-treatment that were largely maintained at follow-up. Although d-cycloserine was associated with a 24–33% faster rate of improvement in symptom severity and remission rates relative to placebo during the 12-week treatment phase, the groups did not differ in response and remission rates. CONCLUSIONS D-cycloserine did not augment a full course of comprehensive CBT for social anxiety disorder. TRIAL REGISTRATION http://www.ClinicalTrials.gov, ID# NCT00633984, http://www.clinicaltrials.gov/ct2/show/NCT00633984 PMID:23599046

Grouping principles in direct competition.

PubMed

Schmidt, Filipp; Schmidt, Thomas

2013-08-09

We (1) introduce a primed flanker task as an objective method to measure perceptual grouping, and (2) use it to directly compare the efficiency of different grouping cues in rapid visuomotor processing. In two experiments, centrally presented primes were succeeded by flanking targets with varying stimulus-onset asynchronies (SOAs). Primes and targets were grouped by the same or by different grouping cues (Exp. 1: brightness/shape, Exp. 2: brightness/size) and were consistent or inconsistent with respect to the required response. Subjective grouping strength was varied to identify its influence on overall response times, error rates, and priming effects, that served as a measure of visual feedforward processing. Our results show that stronger grouping in the targets enhanced overall response times while stronger grouping in the primes enhanced priming effects in motor responses. Also, we obtained differences between rapid visuomotor processing and the subjective impression with cues of brightness and shape but not with cues of brightness and size. Our findings establish the primed flanker task as an objective method to study the speeded visuomotor processing of grouping cues, making it a useful method for the comparative study of feedforward-transmitted base groupings (Roelfsema & Houtkamp, 2011). Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of stimulation by foliage plant display images on prefrontal cortex activity: a comparison with stimulation using actual foliage plants.

PubMed

Igarashi, Miho; Song, Chorong; Ikei, Harumi; Miyazaki, Yoshifumi

2015-01-01

Natural scenes like forests and flowers evoke neurophysiological responses that can suppress anxiety and relieve stress. We examined whether images of natural objects can elicit neural responses similar to those evoked by real objects by comparing the activation of the prefrontal cortex during presentation of real foliage plants with a projected image of the same foliage plants. Oxy-hemoglobin concentrations in the prefrontal cortex were measured using time-resolved near-infrared spectroscopy while the subjects viewed the real plants or a projected image of the same plants. Compared with a projected image of foliage plants, viewing the actual foliage plants significantly increased oxy-hemoglobin concentrations in the prefrontal cortex. However, using the modified semantic differential method, subjective emotional response ratings ("comfortable vs. uncomfortable" and "relaxed vs. awakening") were similar for both stimuli. The frontal cortex responded differently to presentation of actual plants compared with images of these plants even when the subjective emotional response was similar. These results may help explain the physical and mental health benefits of urban, domestic, and workplace foliage. © 2014 The Authors. Journal of Neuroimaging published by the American Society of Neuroimaging.

Randomized Multicenter Feasibility Trial of Myofascial Physical Therapy for Treatment of Urologic Chronic Pelvic Pain Syndrome

PubMed Central

FitzGerald, Mary P; Anderson, Rodney U; Potts, Jeannette; Payne, Christopher K; Peters, Kenneth M; Clemens, J Quentin; Kotarinos, Rhonda; Fraser, Laura; Cosby, Annamarie; Fortman, Carole; Neville, Cynthia; Badillo, Suzanne; Odabachian, Lisa; Sanfield, Anna; O’Dougherty, Betsy; Halle-Podell, Rick; Cen, Liyi; Chuai, Shannon; Landis, J Richard; Kusek, John W; Nyberg, Leroy M

2010-01-01

Objectives To determine the feasibility of conducting a randomized clinical trial designed to compare two methods of manual therapy (myofascial physical therapy (MPT) and global therapeutic massage (GTM)) among patients with urologic chronic pelvic pain syndromes. Materials and Methods Our goal was to recruit 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at six clinical centers. Eligible patients were randomized to either MPT or GTM and were scheduled to receive up to 10 weekly treatments, each 1 hour in duration. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events which occurred during study treatment, and rate of response to therapy as assessed by the Patient Global Response Assessment (GRA). Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. Results Twenty-three (49%) men and 24 (51%) women were randomized over a six month period. Twenty-four (51%) patients were randomized to GTM, 23 (49%) to MPT; 44 (94%) patients completed the study. Therapist adherence to the treatment protocols was excellent. The GRA response rate of 57% in the MPT group was significantly higher than the rate of 21% in the GTM treatment group (p=0.03). Conclusions The goals to judge feasibility of conducting a full-scale trial of physical therapy methods were met. The preliminary findings of a beneficial effect of MPT warrants further study. PMID:19535099

Defining competency-based evaluation objectives in family medicine

PubMed Central

Allen, Tim; Brailovsky, Carlos; Rainsberry, Paul; Lawrence, Katherine; Crichton, Tom; Carpentier, Marie-Pierre; Visser, Shaun

2011-01-01

Abstract Objective To develop a definition of competence in family medicine sufficient to guide a review of Certification examinations by the Board of Examiners of the College of Family Physicians of Canada. Design Delphi analysis of responses to a 4-question postal survey. Setting Canadian family practice. Participants A total of 302 family physicians who have served as examiners for the College of Family Physicians of Canada’s Certification examination. Methods A survey comprising 4 short-answer questions was mailed to the 302 participating family physicians asking them to list elements that define competence in family medicine among newly certified family physicians beginning independent practice. Two expert groups used a modified Delphi consensus process to analyze responses and generate 2 basic components of this definition of competence: first, the problems that a newly practising family physician should be competent to handle; second, the qualities, behaviour, and skills that characterize competence at the start of independent practice. Main findings Response rate was 54%; total number of elements among all responses was 5077, for an average 31 per respondent. Of the elements, 2676 were topics or clinical situations to be dealt with; the other 2401 were skills, behaviour patterns, or qualities, without reference to a specific clinical problem. The expert groups identified 6 essential skills, the phases of the clinical encounter, and 99 priority topics as the descriptors used by the respondents. More than 20% of respondents cited 30 of the topics. Conclusion Family physicians define the domain of competence in family medicine in terms of 6 essential skills, the phases of the clinical encounter, and priority topics. This survey represents the first level of definition of evaluation objectives in family medicine. Definition of the interactions among these elements will permit these objectives to become detailed enough to effectively guide assessment. PMID:21918130

UXO Engineering Design. Technical Specification and ConceptualDesign

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

Beche, J-F.; Doolittle, L.; Greer, J.

2005-04-23

The design and fabrication of the UXO detector has numerous challenges and is an important component to the success of this study. This section describes the overall engineering approach, as well as some of the technical details that brought us to the present design. In general, an array of sensor coils is measuring the signal generated by the UXO object in response to a stimulation provided by the driver coil. The information related to the location, shape and properties of the object is derived from the analysis of the measured data. Each sensor coil is instrumented with a waveform digitizermore » operating at a nominal digitization rate of 100 kSamples per second. The sensor coils record both the large transient pulse of the driver coil and the UXO object response pulse. The latter is smaller in amplitude and must be extracted from the large transient signal. The resolution required is 16 bits over a dynamic range of at least 140 dB. The useful signal bandwidth of the application extends from DC to 40 kHz. The low distortion of each component is crucial in order to maintain an excellent linearity over the full dynamic range and to minimize the calibration procedure. The electronics must be made as compact as possible so that the response of its metallic parts has a minimum signature response. Also because of a field system portability requirement, the power consumption of the instrument must be kept as low as possible. The theory and results of numerical and experimental studies that led to the proof-of-principle multitransmitter-multireceiver Active ElectroMagnetic (AEM) system, that can not only accurately detect but also characterize and discriminate UXO targets, are summarized in LBNL report-53962: ''Detection and Classification of Buried Metallic Objects, UX-1225''.« less

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

Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin

PubMed Central

Advani, Ranjana H.; Bartlett, Nancy L.; Jacobsen, Eric D.; Sharman, Jeff P.; O’Connor, Owen A.; Siddiqi, Tanya; Kennedy, Dana A.; Oki, Yasuhiro

2014-01-01

This phase 2, open-label, multicenter study evaluated the efficacy and safety of brentuximab vedotin, a CD30-directed antibody-drug conjugate, in relapsed/refractory CD30+ non-Hodgkin lymphomas. The primary end point was objective response rate (ORR). Key secondary end points included safety, correlation of CD30 expression with response, response duration, and progression-free survival (PFS). Brentuximab vedotin 1.8 mg/kg was administered every 3 weeks until progression or unacceptable toxicity. This planned subset analysis included patients with peripheral T-cell lymphomas (PTCLs; n = 35), specifically angioimmunoblastic T-cell lymphoma (AITL; n = 13) and PTCL not otherwise specified (n = 22). Median age was 64 years; 63% were refractory to most recent therapy. Of 34 evaluable patients, ORR was 41% (8 complete remissions [CRs], 6 partial remissions [PRs]), and ORR was 54% in AITL (5 CRs, 2 PRs) with median PFS of 6.7 months thus far. No correlation between CD30 expression per central review and response was observed. Safety data were consistent with the known profile of brentuximab vedotin, and included at least grade 3 events of neutropenia (14%), peripheral sensory neuropathy, and hyperkalemia (9% each). In summary, brentuximab vedotin showed antitumor activity in patients with relapsed PTCL particularly AITL. This trial was registered at www.clinicaltrials.gov as #NCT01421667. PMID:24652992

Conflict in object affordance revealed by grip force

PubMed Central

McBride, Jennifer; Sumner, Petroc; Husain, Masud

2011-01-01

Viewing objects can result in automatic, partial activation of motor plans associated with them—“object affordance”. Here, we recorded grip force simultaneously from both hands in an object affordance task to investigate the effects of conflict between coactivated responses. Participants classified pictures of objects by squeezing force transducers with their left or right hand. Responses were faster on trials where the object afforded an action with the same hand that was required to make the response (congruent trials) compared to the opposite hand (incongruent trials). In addition, conflict between coactivated responses was reduced if it was experienced on the preceding trial, just like Gratton adaptation effects reported in “conflict” tasks (e.g., Eriksen flanker). This finding suggests that object affordance demonstrates conflict effects similar to those shown in other stimulus–response mapping tasks and thus could be integrated into the wider conceptual framework on overlearnt stimulus–response associations. Corrected erroneous responses occurred more frequently when there was conflict between the afforded response and the response required by the task, providing direct evidence that viewing an object activates motor plans appropriate for interacting with that object. Recording continuous grip force, as here, provides a sensitive way to measure coactivated responses in affordance tasks. PMID:21824035

Advantages and disadvantages of an objective selection process for early intervention in employees at risk for sickness absence

PubMed Central

Duijts, Saskia FA; Kant, IJmert; Swaen, Gerard MH

2007-01-01

Background It is unclear if objective selection of employees, for an intervention to prevent sickness absence, is more effective than subjective 'personal enlistment'. We hypothesize that objectively selected employees are 'at risk' for sickness absence and eligible to participate in the intervention program. Methods The dispatch of 8603 screening instruments forms the starting point of the objective selection process. Different stages of this process, throughout which employees either dropped out or were excluded, were described and compared with the subjective selection process. Characteristics of ineligible and ultimately selected employees, for a randomized trial, were described and quantified using sickness absence data. Results Overall response rate on the screening instrument was 42.0%. Response bias was found for the parameters sex and age, but not for sickness absence. Sickness absence was higher in the 'at risk' (N = 212) group (42%) compared to the 'not at risk' (N = 2503) group (25%) (OR 2.17 CI 1.63–2.89; p = 0.000). The selection process ended with the successful inclusion of 151 eligible, i.e. 2% of the approached employees in the trial. Conclusion The study shows that objective selection of employees for early intervention is effective. Despite methodological and practical problems, selected employees are actually those at risk for sickness absence, who will probably benefit more from the intervention program than others. PMID:17474980

Phase I / II study of brentuximab vedotin in Japanese patients with relapsed or refractory CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma

PubMed Central

Ogura, Michinori; Tobinai, Kensei; Hatake, Kiyohiko; Ishizawa, Kenichi; Uike, Naokuni; Uchida, Toshiki; Suzuki, Tatsuya; Aoki, Tomohiro; Watanabe, Takashi; Maruyama, Dai; Yokoyama, Masahiro; Takubo, Takatoshi; Kagehara, Hideaki; Matsushima, Takafumi

2014-01-01

Brentuximab vedotin is an antibody–drug conjugate that selectively delivers the antimicrotubule agent monomethyl auristatin E into CD30-expressing cells. To assess its safety, pharmacokinetics, and efficacy in Japanese patients with refractory or relapsed CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma, we carried out a phase I/II study. Brentuximab vedotin was given i.v. on day 1 of each 21-day cycle up to 16 cycles. In the phase I part of a dose-escalation design, three patients per cohort were treated at doses of 1.2 and 1.8 mg/kg. In the phase II part, a dose of 1.8 mg/kg was given to 14 patients (nine with Hodgkin's lymphoma and five with systemic anaplastic large-cell lymphoma). The median number of treatment cycles was 16 (range, 4–16). In the phase I part, no dose-limiting toxicity event was observed. In the total population, common adverse events included lymphopenia (80%), neutropenia (65%), leukopenia (65%), and peripheral sensory neuropathy (60%). Grade 3/4 adverse events in more than two patients were lymphopenia (50%) and neutropenia (15%). The pharmacokinetic profile was similar to that observed in the previous studies in the USA. In the phase II part, six patients (67%) with Hodgkin's lymphoma achieved an objective response with 56% of complete response rate, and five patients (100%) with systemic anaplastic large-cell lymphoma achieved an objective response with 80% of complete response rate. These results show that brentuximab vedotin has an acceptable safety profile and promising antitumor activity in the Japanese population. This trial was registered in JAPIC Clinical Trials Information (JapicCTI-111650). This phase I/II study was to investigate the tolerability, safety and efficacy of brentuximab vedotin. This study indicates that 1.8 mg/kg brentuximab vedotin given every 3 weeks has a manageable safety profile and has high overall tumor response rate in Japanese patients with relapsed or refractory Hodgkin lymphoma or systemic anaplastic large-cell lymphoma. PMID:24814862

An Immuno-epidemiological Model of Paratuberculosis

NASA Astrophysics Data System (ADS)

Martcheva, M.

2011-11-01

The primary objective of this article is to introduce an immuno-epidemiological model of paratuberculosis (Johne's disease). To develop the immuno-epidemiological model, we first develop an immunological model and an epidemiological model. Then, we link the two models through time-since-infection structure and parameters of the epidemiological model. We use the nested approach to compose the immuno-epidemiological model. Our immunological model captures the switch between the T-cell immune response and the antibody response in Johne's disease. The epidemiological model is a time-since-infection model and captures the variability of transmission rate and the vertical transmission of the disease. We compute the immune-response-dependent epidemiological reproduction number. Our immuno-epidemiological model can be used for investigation of the impact of the immune response on the epidemiology of Johne's disease.

Estimating Children's Soil/Dust Ingestion Rates through ...

EPA Pesticide Factsheets

Background: Soil/dust ingestion rates are important variables in assessing children’s health risks in contaminated environments. Current estimates are based largely on soil tracer methodology, which is limited by analytical uncertainty, small sample size, and short study duration. Objectives: The objective was to estimate site-specific soil/dust ingestion rates through reevaluation of the lead absorption dose–response relationship using new bioavailability data from the Bunker Hill Mining and Metallurgical Complex Superfund Site (BHSS) in Idaho, USA. Methods: The U.S. Environmental Protection Agency (EPA) in vitro bioavailability methodology was applied to archived BHSS soil and dust samples. Using age-specific biokinetic slope factors, we related bioavailable lead from these sources to children’s blood lead levels (BLLs) monitored during cleanup from 1988 through 2002. Quantitative regression analyses and exposure assessment guidance were used to develop candidate soil/dust source partition scenarios estimating lead intake, allowing estimation of age-specific soil/dust ingestion rates. These ingestion rate and bioavailability estimates were simultaneously applied to the U.S. EPA Integrated Exposure Uptake Biokinetic Model for Lead in Children to determine those combinations best approximating observed BLLs. Results: Absolute soil and house dust bioavailability averaged 33% (SD ± 4%) and 28% (SD ± 6%), respectively. Estimated BHSS age-specific soil/du

SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer - a multicenter, randomized phase III trial.

PubMed

Rochlitz, Christoph; Bigler, Martin; von Moos, Roger; Bernhard, Jürg; Matter-Walstra, Klazien; Wicki, Andreas; Zaman, Khalil; Anchisi, Sandro; Küng, Marc; Na, Kyung-Jae; Bärtschi, Daniela; Borner, Markus; Rordorf, Tamara; Rauch, Daniel; Müller, Andreas; Ruhstaller, Thomas; Vetter, Marcus; Trojan, Andreas; Hasler-Strub, Ursula; Cathomas, Richard; Winterhalder, Ralph

2016-10-10

Adding bevacizumab to chemotherapy improves response rates and progression-free survival (PFS) in metastatic breast cancer (mBC). We aimed to demonstrate decreased toxicity with metronomic chemotherapy/bevacizumab compared with paclitaxel/bevacizumab. This multicenter, randomized phase III trial compared bevacizumab with either paclitaxel (arm A) or daily oral capecitabine-cyclophosphamide (arm B) as first-line treatment in patients with HER2-negative advanced breast cancer. The primary endpoint was the incidence of selected grade 3-5 adverse events (AE) including: febrile neutropenia, infection, sensory/motor neuropathy, and mucositis. Secondary endpoints included objective response rate, disease control rate, PFS, overall survival (OS), quality of life (QoL), and pharmacoeconomics. The study was registered prospectively with ClinicalTrials.gov, number NCT01131195 on May 25, 2010. Between September 2010 and December 2012, 147 patients were included at 22 centers. The incidence of primary endpoint-defining AEs was similar in arm A (25 % [18/71]; 95 % CI 15-35 %) and arm B (24 % [16/68]; 95 % CI 13-34 %; P = 0.96). Objective response rates were 58 % (42/73; 95 % CI 0.46-0.69) and 50 % (37/74; 95 % CI 0.39-0.61) in arms A and B, respectively (P = 0.45). Median PFS was 10.3 months (95 % CI 8.7-11.3) in arm A and 8.5 months (95 % CI 6.5-11.9) in arm B (P = 0.90). Other secondary efficacy endpoints were not significantly different between study arms. The only statistically significant differences in QoL were less hair loss and less numbness in arm B. Treatment costs between the two arms were equivalent. This trial failed to meet its primary endpoint of a reduced rate of prespecified grade 3-5 AEs with metronomic bevacizumab, cyclophosphamide and capecitabine.

The pupillary response discriminates between subjective and objective familiarity and novelty.

PubMed

Kafkas, Alexandros; Montaldi, Daniela

2015-10-01

The pupil response discriminates between old and new stimuli, with old stimuli characterized by larger pupil dilation patterns than new stimuli. We sought to explore the cause of the pupil old/new effect and discount the effect of targetness, effort, recollection retrieval, and complexity of the recognition decision. Two experiments are reported in which the pupil response and the eye fixation patterns were measured, while participants identified novel and familiar object stimuli, in two separate tasks, emphasizing either novelty or familiarity detection. In Experiment 1, familiarity and novelty decisions were taken using a rating scale, while in Experiment 2 a simpler yes/no decision was used. In both experiments, we found that detection of target familiar stimuli resulted in greater pupil dilation than the detection of target novel stimuli, while the duration of the first fixation discriminated between familiar and novel stimuli as early as within 320 ms after stimulus onset. Importantly, the pupil response distinguished between the objective (during an earlier temporal component) and the subjective (during a later temporal component) status of the stimulus for misses and false alarms. In the light of previous findings, we suggest that the pupil and fixation old/new effects reflect the distinct neural and cognitive mechanisms involved in the familiarity and novelty decisions. The findings also have important implications for the use of pupil dilation and eye movement patterns to explore explicit and implicit memory processes. © 2015 The Authors. Psychophysiology published by Wiley Periodicals, Inc. on behalf of Society for Psychophysiological Research.

Active opioid use does not attenuate the humoral responses to inactivated influenza vaccine

PubMed Central

Moroz, Ekaterina; Albrecht, Randy A.; Aden, Brandon; Beeder, Ann Bordwine; Yuan, Jianda; García-Sastre, Adolfo; Edlin, Brian R.; Salvatore, Mirella

2016-01-01

Background Influenza vaccination is recommended for vulnerable individuals, including active drug users, to prevent influenza complications and decrease influenza spread. Recent studies suggest that opioids negatively regulate immune responses in experimental models, but the extent to which opioid use will affect the humoral responses to influenza vaccine in humans is unknown. This information is critical in maximizing vaccination efforts. Objective To determine whether there is a difference in antibody response after influenza vaccination in heroin or methadone users compared to control subjects. Methods We studied active heroin users, subjects on methadone maintenance treatment (MMT) and subjects that did not use any drugs before and 1 and 4 weeks after vaccination with trivalent influenza vaccine (TIV). We measured hemagglutination inhibition and microneutralization titers, and we compared geometric mean titers (GMT), and rates of seroprotection and seroconversion for each of the vaccine strains among the 3 groups of subjects. Results Heroin users, subjects on MMT and non-user controls mount a similarly robust serologic response to TIV. GMT and rates of seroprotection and seroconversion were not significantly different among groups. Conclusion Our results suggest that opioid use do not significantly alter antibody responses to influenza vaccine supporting the vaccination effort in these populations. PMID:26859239

Cardiac-Activity Measures for Assessing Airport Ramp-Tower Controller's Workload

NASA Technical Reports Server (NTRS)

Hayashi, Miwa; Dulchinos, Victoria

2016-01-01

Heart rate (HR) and heart rate variability (HRV) potentially offer objective, continuous, and non-intrusive measures of human-operators mental workload. Such measurement capability is attractive for workload assessment in complex laboratory simulations or safety-critical field testing. The present study compares mean HR and HRV data with self-reported subjective workload ratings collected during a high-fidelity human-in-the-loop simulation of airport ramp traffic control operations, which involve complex cognitive and coordination tasks. Mean HR was found to be weakly sensitive to the workload ratings, while HRV was not sensitive or even contradictory to the assumptions. Until more knowledge on stress response mechanisms of the autonomic nervous system is obtained, it is recommended that these cardiac-activity measures be used with other workload assessment tools, such as subjective measures.

Cardiac-Activity Measures for Assessing Airport Ramp-Tower Controller's Workload

NASA Technical Reports Server (NTRS)

Hayashi, Miwa; Dulchinos, Victoria L.

2016-01-01

Heart rate (HR) and heart rate variability (HRV) potentially offer objective, continuous, and non-intrusive measures of human-operator's mental workload. Such measurement capability is attractive for workload assessment in complex laboratory simulations or safety-critical field testing. The present study compares mean HR and HRV data with self-reported subjective workload ratings collected during a high-fidelity human-in-the-loop simulation of airport ramp traffic control operations, which involve complex cognitive and coordination tasks. Mean HR was found to be weakly sensitive to the workload ratings, while HRV was not sensitive or even contradictory to the assumptions. Until more knowledge on stress response mechanisms of the autonomic nervous system is obtained, it is recommended that these cardiac-activity measures be used with other workload assessment tools, such as subjective measures.

An objective electrophysiological marker of face individualisation impairment in acquired prosopagnosia with fast periodic visual stimulation.

PubMed

Liu-Shuang, Joan; Torfs, Katrien; Rossion, Bruno

2016-03-01

One of the most striking pieces of evidence for a specialised face processing system in humans is acquired prosopagnosia, i.e. the inability to individualise faces following brain damage. However, a sensitive and objective non-behavioural marker for this deficit is difficult to provide with standard event-related potentials (ERPs), such as the well-known face-related N170 component reported and investigated in-depth by our late distinguished colleague Shlomo Bentin. Here we demonstrate that fast periodic visual stimulation (FPVS) in electrophysiology can quantify face individualisation impairment in acquired prosopagnosia. In Experiment 1 (Liu-Shuang et al., 2014), identical faces were presented at a rate of 5.88 Hz (i.e., ≈ 6 images/s, SOA=170 ms, 1 fixation per image), with different faces appearing every 5th face (5.88 Hz/5=1.18 Hz). Responses of interest were identified at these predetermined frequencies (i.e., objectively) in the EEG frequency-domain data. A well-studied case of acquired prosopagnosia (PS) and a group of age- and gender-matched controls completed only 4 × 1-min stimulation sequences, with an orthogonal fixation cross task. Contrarily to controls, PS did not show face individualisation responses at 1.18 Hz, in line with her prosopagnosia. However, her response at 5.88 Hz, reflecting general visual processing, was within the normal range. In Experiment 2 (Rossion et al., 2015), we presented natural (i.e., unsegmented) images of objects at 5.88 Hz, with face images shown every 5th image (1.18 Hz). In accordance with her preserved ability to categorise a face as a face, and despite extensive brain lesions potentially affecting the overall EEG signal-to-noise ratio, PS showed 1.18 Hz face-selective responses within the normal range. Collectively, these findings show that fast periodic visual stimulation provides objective and sensitive electrophysiological markers of preserved and impaired face processing abilities in the neuropsychological population. Copyright © 2015 Elsevier Ltd. All rights reserved.

Icotinib in Patients with Pretreated Advanced Esophageal Squamous Cell Carcinoma with EGFR Overexpression or EGFR Gene Amplification: A Single-Arm, Multicenter Phase 2 Study.

PubMed

Huang, Jing; Fan, Qingxia; Lu, Ping; Ying, Jianming; Ma, Changwu; Liu, Wei; Liu, Ying; Tan, Fenlai; Sun, Yan

2016-06-01

Epidermal growth factor receptor (EGFR) has been reported to be overexpressed and amplified in a high percentage of patients with esophageal squamous cell carcinoma (ESCC). The activity of icotinib, an EGFR tyrosine kinase inhibitor, was assessed in previously treated ESCC with EGFR overexpression or amplification. For this phase 2, single-arm, multicenter trial undertaken at six hospitals in China, we included Chinese patients with previously treated, histologically confirmed advanced ESCC and EGFR overexpression (immunohistochemical staining sore of 3+) or amplification (positive fluorescence in situ hybridization result). These patients received oral icotinib (250 mg, three times daily).The primary end point was the proportion of patients with objective responses as assessed by an independent radiology review committee. Between December 5, 2013, and May 28, 2015, a total of 281 patients were screened. Fifty-four eligible patients were enrolled. Nine responses were observed, including one complete response and eight partial responses, and 16 patients had stable disease, resulting in a 16.7% objective response rate (95% confidence interval [CI]: 6.7-26.6) and 46.3% disease control rate (95% CI: 33.0-59.6). The median progression-free survival and overall survival times were 52 (95% CI: 40-95) days and 153 (95% CI: 139-218) days, respectively. A total of 43 patients experienced at least one adverse event, but most were only grade 1 to 2 in severity. The most frequent was rash (48.1%), followed by diarrhea (22.2%). Icotinib showed favorable activity in patients with advanced, previously treated ESCC with EGFR overexpression or amplification. These findings suggest further research into EGFR overexpression or amplification for selecting responsive patients. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Providing rapid feedback to residents on their teaching skills: an educational strategy for contemporary trainees

PubMed Central

Baer, Tamar G.; Gershel, Jeffrey C.

2016-01-01

Objectives The objective of this study was to assess the attitudes of contemporary residents toward receiving rapid feedback on their teaching skills from their medical student learners. Methods Participants consisted of 20 residents in their second post-graduate training year. These residents facilitated 44 teaching sessions with medical students within our Resident-as-Teacher program. Structured, written feedback from students was returned to the resident within 3 days following each session. Residents completed a short survey about the utility of the feedback, whether they would make a change to future teaching sessions based on the feedback, and what specifically they might change. The survey utilized a 4-point scale (“Not helpful/likely=1” to “Very helpful/likely=4”), and allowed for one free-text response. Free-text responses were hand-coded and underwent qualitative analysis to identify themes.   Results There were 182 student feedback encounters resulting from 44 teaching sessions. The survey response rate was 73% (32/44). Ninety-four percent of residents rated the rapid feedback as “very helpful,” and 91% would “very likely” make a change to subsequent sessions based on student feedback. Residents’ proposed changes included modifications to session content and/or their personal teaching style.    Conclusions Residents found that rapid feedback received from medical student learners was highly valuable to them in their roles as teachers. A rapid feedback strategy may facilitate an optimal educational environment for contemporary trainees. PMID:26995390

Inhibitors of Cytotoxic T Lymphocyte Antigen 4 and Programmed Death 1/Programmed Death 1 Ligand for Metastatic Melanoma, Dual Versus Monotherapy-Summary of Advances and Future Directions for Studying These Drugs.

PubMed

Loo, Kimberly; Daud, Adil I

Immense progress in the field of cancer immunotherapy has garnered several novel and successful treatments for metastatic melanoma. Beginning with therapies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4), objective response rates, overall survival, and long-term survival were significantly increased when compared with glycoprotein 100 vaccine therapies. Expanding the breadth of therapies aimed to "release the breaks" on the active immune system, anti-programmed death 1 (PD-1) and anti-programmed death 1 ligand (PD-L1) therapies further improved overall survival, progression-free survival, and objective tumor response while exhibiting more favorable safety profiles compared with ipilimumab and to chemotherapy agents. Given the power of these agents as monotherapies, a combination approach sought to combine the anti-CTLA agent ipilimumab and anti-PD-1 agent, nivolumab, to form a double-pronged attack and target several mechanisms within the active immune system. Given the promise in elevated response rates and progression-free survival, the future appears promising along the immunotherapy front. Continuing the push for progress, biomarkers to uncover the profile of responders to the various therapies will become vital in the treatment of metastatic melanoma patients. Here, we highlight the advances of CTLA-4 and PD-1/PD-L1 inhibitors in the metastatic melanoma setting and discuss future directions for uncovering the full potential of these therapies.

Role of bevacizumab in uterine leiomyosarcoma.

PubMed

Bogani, Giorgio; Ditto, Antonino; Martineli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Fonatella, Caterina; Sanfilippo, Roberta; Leone Roberti Maggiore, Umberto; Ferrero, Simone; Lorusso, Domenica; Raspagliesi, Francesco

2018-06-01

In the recent years, angiogenetic inhibitors have emerged for the treatment of several malignancies. In particular, bevacizumab has proved to be effective in many types of cancers (including sarcoma), but the limitations of antiangiogenic therapy have been shown in practice. Here, we sought to review the current evidence on the role and efficacy of bevacizumab in patients affected by uterine leiomyosarcoma. On April 2017, Literature was searched in order to identify studies reporting outcomes of patients affected either by early stage or advanced/recurred uterine leiomyosarcoma undergoing treatment with bevacizumab, alone or in combination with other chemotherapeutic regimens. Searching the literature data of 69 patients affected by metastatic, unresectable uterine leiomyosarcoma were retrieved; on the contrary, no data regarding the use of bevacizumab in patients with early-stage uterine leiomyosarcoma was published. Current evidence suggested that the addiction of bevacizumab to standard treatment modality does not increase grade 3 or worse toxicity (assessed by CTCAE). Pooled data regarding response rate suggested that 35%, 28%, 26% and 11% of patients experienced objective cure (complete + partial response), stable disease, progressive disease and unknown response, respectively. Data from the only one randomized controlled trial suggested that objective cure rate does not differ from standard chemotherapy treatment, thus limiting the indication to add bevacizumab in patients affected by metastatic, unresectable uterine leiomyosarcoma. The current evidence does not justify the use of bevacizumab into clinical practice. Further randomized studies testing the role of bevacizumab are warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer

PubMed Central

Shen, Yan-Wei; Zhang, Xiao-Man; Li, Shu-Ting; Lv, Meng; Yang, Jiao; Wang, Fan; Chen, Zhe-Ling; Wang, Bi-Yuan; Li, Pan; Chen, Ling; Yang, Jin

2016-01-01

Background and objective Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation. Patients and methods Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi’an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Results Among the 35 patients, the tumor objective response rate (ORR) and disease control rate were 62.9% (22/35) and 88.6% (31/35), respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2–11.8 months), and median overall survival was 21.0 months (95% CI: 20.1–21.9 months). The most common drug-related toxicities were rashes (eleven patients) and diarrhea (nine patients), but these were generally manageable and reversible. Conclusion Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation. PMID:26966381

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.

Post-processing of auditory steady-state responses to correct spectral leakage.

PubMed

Felix, Leonardo Bonato; de Sá, Antonio Mauricio Ferreira Leite Miranda; Mendes, Eduardo Mazoni Andrade Marçal; Moraes, Márcio Flávio Dutra

2009-06-30

Auditory steady-state responses (ASSRs) are electrical manifestations of brain due to high rate sound stimulation. These evoked responses can be used to assess the hearing capabilities of a subject in an objective, automatic fashion. Usually, the detection protocol is accomplished by frequency-domain techniques, such as magnitude-squared coherence, whose estimation is based on the fast Fourier transform (FFT) of several data segments. In practice, the FFT-based spectrum may spread out the energy of a given frequency to its side bins and this escape of energy in the spectrum is called spectral leakage. The distortion of the spectrum due to leakage may severely compromise statistical significance of objective detection. This work presents an offline, a posteriori method for spectral leakage minimization in the frequency-domain analysis of ASSRs using coherent sampling criterion and interpolation in time. The technique was applied to the local field potentials of 10 Wistar rats and the results, together with those from simulated data, indicate that a leakage-free analysis of ASSRs is possible for any dataset if the methods showed in this paper were followed.

Perception, memory and aesthetics of indeterminate art.

PubMed

Ishai, Alumit; Fairhall, Scott L; Pepperell, Robert

2007-07-12

Indeterminate art, in which familiar objects are only suggestive, invokes a perceptual conundrum as apparently detailed and vivid images resist identification. We hypothesized that compared with paintings that depict meaningful content, object recognition in indeterminate images would be delayed, and tested whether aesthetic affect depends on meaningful content. Subjects performed object recognition and judgment of aesthetic affect tasks. Response latencies were significantly longer for indeterminate images and subjects perceived recognizable objects in 24% of these paintings. Although the aesthetic affect rating of all paintings was similar, judgement latencies for the indeterminate paintings were significantly longer. A surprise memory test revealed that more representational than indeterminate paintings were remembered and that affective strength increased the probability of subsequent recall. Our results suggest that perception and memory of art depend on semantic aspects, whereas, aesthetic affect depends on formal visual features. The longer latencies associated with indeterminate paintings reflect the underlying cognitive processes that mediate object resolution. Indeterminate art works therefore comprise a rich set of stimuli with which the neural correlates of visual perception can be investigated.

Determining Possible Professionals and Respective Roles and Responsibilities for a Model Comprehensive Elder Abuse Intervention: A Delphi Consensus Survey

PubMed Central

Du Mont, Janice; Kosa, Daisy; Macdonald, Sheila; Elliot, Shannon; Yaffe, Mark

2015-01-01

Objective We have undertaken a multi-phase, multi-method program of research to develop, implement, and evaluate a comprehensive hospital-based nurse examiner elder abuse intervention that addresses the complex functional, social, forensic, and medical needs of older women and men. In this study, we determined the importance of possible participating professionals and respective roles and responsibilities within the intervention. Methods Using a modified Delphi methodology, recommended professionals and their associated roles and responsibilities were generated from a systematic scoping review of relevant scholarly and grey literatures. These items were reviewed, new items added for review, and rated/re-rated for their importance to the intervention on a 5-point Likert scale by an expert panel during a one day in-person meeting. Items that did not achieve consensus were subsequently re-rated in an online survey. Analysis Those items that achieved a mean Likert rating of 4+ (rated important to very important), and an interquartile range<1 in the first or second round, and/or for which 80% of ratings were 4+ in the second round were retained for the model elder abuse intervention. Results Twenty-two of 31 recommended professionals and 192 of 229 recommended roles and responsibilities rated were retained for our model elder abuse intervention. Retained professionals were: public guardian and trustee (mean rating = 4.88), geriatrician (4.87), police officer (4.87), GEM (geriatric emergency management) nurse (4.80), GEM social worker (4.78), community health worker (4.76), social worker/counsellor (4.74), family physician in community (4.71), paramedic (4.65), financial worker (4.59), lawyer (4.59), pharmacist (4.59), emergency physician (4.57), geriatric psychiatrist (4.33), occupational therapist (4.29), family physician in hospital (4.28), Crown prosecutor (4.24), neuropsychologist (4.24), bioethicist (4.18), caregiver advocate (4.18), victim support worker (4.18), and respite care worker (4.12). Conclusion A large and diverse group of multidisciplinary, intersectoral collaborators was deemed necessary to address the complex needs of abused older adults, each having important roles and responsibilities to fulfill within a model comprehensive elder abuse intervention. PMID:26630030

Factors influencing and modifying the decision to pursue genetic testing for skin cancer risk.

PubMed

Fogel, Alexander L; Jaju, Prajakta D; Li, Shufeng; Halpern-Felsher, Bonnie; Tang, Jean Y; Sarin, Kavita Y

2017-05-01

Across cancers, the decision to pursue genetic testing is influenced more by subjective than objective factors. However, skin cancer, which is more prevalent, visual, and multifactorial than many other malignancies, may offer different motivations for pursuing such testing. The primary objective was to determine factors influencing the decision to receive genetic testing for skin cancer risk. A secondary objective was to assess the impact of priming with health questions on the decision to receive testing. We distributed anonymous online surveys through ResearchMatch.org to assess participant health, demographics, motivations, and interest in pursuing genetic testing for skin cancer risk. Two surveys with identical questions but different question ordering were used to assess the secondary objective. We received 3783 responses (64% response rate), and 85.8% desired testing. Subjective factors, including curiosity, perceptions of skin cancer, and anxiety, were the most statistically significant determinants of the decision to pursue testing (P < .001), followed by history of sun exposure (odds ratio 1.85, P < .01) and history of skin cancer (odds ratio 0.5, P = .01). Age and family history of skin cancer did not influence this decision. Participants increasingly chose testing if first queried about health behaviors (P < .0001). The decision to pursue hypothetical testing may differ from in-clinic decision-making. Self-selected, online participants may differ from the general population. Surveys may be subject to response bias. The decision to pursue genetic testing for skin cancer is primarily determined by subjective factors, such as anxiety and curiosity. Health factors, including skin cancer history, also influenced decision-making. Priming with consideration of objective health factors can increase the desire to pursue testing. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Feasibility of Using a Multilingual Web Survey in Studying the Health of Ethnic Minority Youth

PubMed Central

Malin, Maili; Raisamo, Susanna Ulrika; Lindfors, Pirjo Liisa; Pere, Lasse Antero; Rimpelä, Arja Hannele

2015-01-01

Background Monolingual Web survey is a common tool for studying adolescent health. However, national languages may cause difficulties for some immigrant-origin youths, which lower their participation rate. In national surveys, the number of ethnic minority groups is often too small to assess their well-being. Objective We studied the feasibility of a multilingual Web survey targeted at immigrant-origin youths by selection of response language, and compared participation in different language groups with a monolingual survey. Methods The Adolescent Health and Lifestyle Survey (AHLS), Finland, with national languages (Finnish/Swedish) was modified into a multilingual Web survey targeted at a representative sample of 14- and 16-year olds (N=639) whose registry-based mother tongue was other than the national languages. The survey was conducted in 2010 (16-year olds) and 2011 (14-year olds). The response rate of the multilingual survey in 2011 is compared with the AHLS of 2011. We also describe the translation process and the e-form modification. Results Of the respondents, 57.6% answered in Finnish, whereas the remaining 42.4% used their mother tongue (P=.002). A majority of youth speaking Somali, Middle Eastern, Albanian, and Southeast Asian languages chose Finnish. The overall response rate was 48.7% with some nonsignificant variation between the language groups. The response rate in the multilingual Web survey was higher (51.6%, 163/316) than the survey with national languages (46.5%, 40/86) in the same age group; however, the difference was not significant (P=.47). The adolescents who had lived in Finland for 5 years or less (58.0%, 102/176) had a higher response rate than those having lived in Finland for more than 5 years (45.1%, 209/463; P=.005). Respondents and nonrespondents did not differ according to place of birth (Finland/other) or residential area (capital city area/other). The difference in the response rates of girls and boys was nearly significant (P=.06). Girls of the Somali and Middle Eastern language groups were underrepresented among the respondents. Conclusions A multilingual Web survey is a feasible method for gathering data from ethnic youth, although it does not necessarily yield a higher response rate than a monolingual survey. The respondents answered more often in the official language of the host country than their mother tongue. The varying response rates by time of residence, ethnicity, and gender pose challenges for developing tempting surveys for youth. PMID:25953412

Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma: Review of Safety, Response Evaluation Criteria in Solid Tumors 1.1 Imaging Response and Survival.

PubMed

Swinburne, Nathaniel C; Biederman, Derek M; Besa, Cecilia; Tabori, Nora E; Fischman, Aaron M; Patel, Rahul S; Nowakowski, Francis Scott; Gunasekaran, Ganesh; Schwartz, Myron E; Lookstein, Robert A; Kim, Edward

2017-06-01

The optimal palliative treatment for unresectable intrahepatic cholangiocarcinoma (ICC) remains controversial. While selective internal radiation therapy (SIRT) using yttrium-90 microspheres is a well-accepted treatment for hepatocellular carcinoma, data related to its use for locally advanced ICC remain relatively scarce. Twenty-nine patients (mean age 66 ± 11 years; 15 female) with unresectable biopsy-proven ICC treated with SIRT between June 2008 and April 2015 were retrospectively evaluated for post-treatment toxicity, overall survival, and imaging response using response evaluation criteria in solid tumors (RECIST) 1.1 criteria. RECIST 1.1 response was evaluable following 26 treatments [complete response (CR):0, partial response (PR):3; stable disease (SD):16, progression of disease (PD):7]. Objective response rate (CR+PR) was 12%. Disease control rate (CR+PR+SD) was 73%. Median time to progression was 5.6 [95% confidence interval (CI): 0-12.0] months. Median survival following SIRT was 9.1 (95% CI: 1.7-16.4) months. Post-treatment survival was prolonged in patients with absence of extrahepatic disease (p = 0.03) and correlated with RECIST 1.1 response (p = 0.02). Toxicities were limited to grade I severity and occurred following 27% of treatments. These findings support the safe, effective use of SIRT for unresectable ICC. Post-treatment survival is prolonged in patients with absence of extrahepatic disease at baseline. RECIST 1.1 response following SIRT for ICC is predictive of survival.

Multidisciplinary design optimization of vehicle instrument panel based on multi-objective genetic algorithm

NASA Astrophysics Data System (ADS)

Wang, Ping; Wu, Guangqiang

2013-03-01

Typical multidisciplinary design optimization(MDO) has gradually been proposed to balance performances of lightweight, noise, vibration and harshness(NVH) and safety for instrument panel(IP) structure in the automotive development. Nevertheless, plastic constitutive relation of Polypropylene(PP) under different strain rates, has not been taken into consideration in current reliability-based and collaborative IP MDO design. In this paper, based on tensile test under different strain rates, the constitutive relation of Polypropylene material is studied. Impact simulation tests for head and knee bolster are carried out to meet the regulation of FMVSS 201 and FMVSS 208, respectively. NVH analysis is performed to obtain mainly the natural frequencies and corresponding mode shapes, while the crashworthiness analysis is employed to examine the crash behavior of IP structure. With the consideration of lightweight, NVH, head and knee bolster impact performance, design of experiment(DOE), response surface model(RSM), and collaborative optimization(CO) are applied to realize the determined and reliability-based optimizations, respectively. Furthermore, based on multi-objective genetic algorithm(MOGA), the optimal Pareto sets are completed to solve the multi-objective optimization(MOO) problem. The proposed research ensures the smoothness of Pareto set, enhances the ability of engineers to make a comprehensive decision about multi-objectives and choose the optimal design, and improves the quality and efficiency of MDO.

Caudate neuronal recording in freely behaving animals following acute and chronic dose response methylphenidate exposure

PubMed Central

Claussen, Catherine M; Dafny, Nachum

2016-01-01

The misuse and abuse of the psychostimulant, methylphenidate (MPD) the drug of choice in the treatment of attention deficit hyperactivity disorder (ADHD) has seen a sharp uprising in recent years among both youth and adults for its cognitive enhancing effects and for recreational purposes. This uprise in illicit use has lead to many questions concerning the long term consequences of MPD exposure. The objective of this study was to record animal behavior concomitantly with the caudate nucleus (CN) neuronal activity following acute and repetitive (chronic) dose response exposure to methylphenidate (MPD). A saline control and three MPD dose (0.6, 2.5, and 10.0 mg/kg) groups were used. Behaviorally, the same MPD dose in some animals following chronic MPD exposure elicited behavioral sensitization and other animals elicited behavioral tolerance. Based on this finding, the CN neuronal population recorded from animals expressing behavioral sensitization were also evaluated separately from CN neurons recorded from animals expressing behavioral tolerance to chronic MPD exposure, respectively. Significant differences in CN neuronal population responses between the behaviorally sensitized and the behaviorally tolerant animals was observed for the 2.5 and 10.0 mg/kg MPD exposed groups. For 2.5 mg/kg MPD, behaviorally sensitized animals responded by decreasing their firing rates while behaviorally tolerant animals showed mainly an increase in their firing rates. The CN neuronal responses recorded from the behaviorally sensitized animals following 10.0 mg/kg MPD responded by increasing their firing rates whereas the CN neuronal recordings from the behaviorally tolerant animals showed that approximately half decreased their firing rates in response to 10.0 mg/kg MPD exposure. The comparison of percentage change in neuronal firing rates showed that the behaviorally tolerant animals trended to exhibit increases in their neuronal firing rates at ED1 following initial MPD exposure and oppositely at ED10 MPD rechallenge. While the behaviorally sensitized animals in general increased in their percentage change of firing rats were observed following acute 10.0 mg/kg MPD and the behaviorally sensitized 10.0 mg/kg MPD animals and a robust increase in neuronal firing rates at ED1 and ED10 rechallenge. These results suggest the need to first individually analyze animal behavioral activity, and than to evaluate the neuronal responses to the drug based on the animals behavioral response to chronic MPD exposure. PMID:26101057

Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study

PubMed Central

Tanaka, Yoshiya; Takeuchi, Tsutomu; Yamanaka, Hisashi; Nakamura, Hiroyuki; Toyoizumi, Shigeyuki; Zwillich, Samuel

2015-01-01

Abstract Objectives. To evaluate oral tofacitinib versus placebo for treatment of active rheumatoid arthritis in Japanese patients with inadequate response to disease-modifying antirheumatic drugs. Methods. In this double-blind, placebo-controlled, randomized, parallel-group, 12-week, phase 2 study (clinicaltrials.gov NCT00687193), 317 patients received tofacitinib: 1, 3, 5, 10, or 15 mg as monotherapy or placebo twice daily (BID). Primary endpoint: response rate by American College of Rheumatology (ACR) ≥ 20% improvement criteria (ACR20) at week 12. Results. ACR20 response rates: 37.7% (20/53), 67.9% (36/53), 73.1% (38/52), 84.9% (45/53), and 90.7% (49/54) with tofacitinib: 1, 3, 5, 10, and 15 mg BID, respectively, versus 15.4% (8/52) with placebo (p < 0.01; all doses). Dose-dependent ACR20 responses with tofacitinib versus placebo occurred from week 2 onward (p < 0.05). Changes from baseline in 28-joint disease activity score using erythrocyte sedimentation rate improved with tofacitinib versus placebo from week 4 (p < 0.01; all doses). Six tofacitinib patients experienced treatment-related serious adverse events (AEs). Most common treatment-emergent AEs: nasopharyngitis (10% vs 12%) and hyperlipidemia (5% vs 0%). Serum creatinine, hemoglobin, and total-, low-, and high-density lipoprotein-cholesterol levels increased with tofacitinib. Conclusions. Tofacitinib produced dose-dependent ACR20 responses and reduced disease activity. The safety profile was consistent with that reported from global monotherapy trials. PMID:25496464

Entry Descent and Landing Workshop Proceedings. Volume 1; The Mars Science Laboratory (MSL) Entry, Descent and Landing Instrumentation (MEDLI) Hardware

NASA Technical Reports Server (NTRS)

Munk, Michelle M.; Little, Alan; Kuhl, Chris; Bose, Deepak; Santos, Jose

2013-01-01

Objectives: Measure Pressure: a) Confirm spacecraft aerodynamics. b) Independently measure attitude. c) Determine density profile. d) Determine wind component. Measure Temperature: a) Verify heating levels on spacecraft surface. b) Determine recession amount and rate. c) Validate material response at Mars conditions. The better we understand the Mars entry environment, the better we can design the next spacecraft.

The Federal Forest Stewardship Program and its implications for sustainable forestry on private forest ownerships in the United States

Treesearch

Robert J. Moulton; J. Dixon Esseks

2002-01-01

A 72 percent response rate was achieved in 1998 and 1999 national survey of 1,238 participants in the USDA Forest Service's Forest Stewardship Program, under which 130,000 individual multiple resource plans encompassing 16.5 million acres (6.5 million ha) of privately owned forest lands in the United States had been completed. Objectives were to determine if the...

Virtual Raters for Reproducible and Objective Assessments in Radiology

NASA Astrophysics Data System (ADS)

Kleesiek, Jens; Petersen, Jens; Döring, Markus; Maier-Hein, Klaus; Köthe, Ullrich; Wick, Wolfgang; Hamprecht, Fred A.; Bendszus, Martin; Biller, Armin

2016-04-01

Volumetric measurements in radiologic images are important for monitoring tumor growth and treatment response. To make these more reproducible and objective we introduce the concept of virtual raters (VRs). A virtual rater is obtained by combining knowledge of machine-learning algorithms trained with past annotations of multiple human raters with the instantaneous rating of one human expert. Thus, he is virtually guided by several experts. To evaluate the approach we perform experiments with multi-channel magnetic resonance imaging (MRI) data sets. Next to gross tumor volume (GTV) we also investigate subcategories like edema, contrast-enhancing and non-enhancing tumor. The first data set consists of N = 71 longitudinal follow-up scans of 15 patients suffering from glioblastoma (GB). The second data set comprises N = 30 scans of low- and high-grade gliomas. For comparison we computed Pearson Correlation, Intra-class Correlation Coefficient (ICC) and Dice score. Virtual raters always lead to an improvement w.r.t. inter- and intra-rater agreement. Comparing the 2D Response Assessment in Neuro-Oncology (RANO) measurements to the volumetric measurements of the virtual raters results in one-third of the cases in a deviating rating. Hence, we believe that our approach will have an impact on the evaluation of clinical studies as well as on routine imaging diagnostics.

Dose rate mapping of VMAT treatments

NASA Astrophysics Data System (ADS)

Podesta, Mark; Antoniu Popescu, I.; Verhaegen, Frank

2016-06-01

Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min-1 and 12 Gy min-1 but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates  <1 Gy min-1. Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.

Perception of medical undergraduate students about interactive lectures in an outcome-based integrated curriculum: A cross-sectional study

PubMed Central

Asad, Mohammad Rehan; Amir, Khwaja; Tadvi, Naser Ashraf; Afzal, Kamran; Sami, Waqas; Irfan, Abdul

2017-01-01

OBJECTIVE: The objective of this study is to explore the student's perspectives toward the interactive lectures as a teaching and learning method in an integrated curriculum. MATERIALS AND METHODS: This cross-sectional study was conducted among 1st, 2nd and 3rd year male medical students (n = 121). A self-administered questionnaire based on the Visual, Auditory, Reader, Kinesthetic learning styles, learning theories, and role of feedback in teaching and learning on five-point Likert rating scale was used. The questionnaire was constructed after extensive literature review. RESULTS: There was an 80% response rate in this study. The total number of undergraduate medical students responded in the study were n = 97, 34 students of 1st year, n = 30 students of 2nd year and n = 33 student were in 3rd year, the mean scores of the student responses were calculated using Independent samples Kruskal–Wallis. There was no significant difference in the responses of the students of different years except for the question “The Interactive lectures facilitate effective use of learning resources.” Which showed significant difference in the responses of the 3 years students by Independent samples Kruskal–Wallis test. No significant association was found between the year of study and items of the questionnaire except for the same item, “ The Interactive lectures facilitates effective use of learning resources” by Spearman rank correlation test. CONCLUSION: The students perceive interactive lecture as an effective tool for facilitating visual and auditory learning modes, and for achieving curricular strategies. The student find the feedback given during the interactive lectures is effective in modifying learning attitude and enhancing motivation toward learning. PMID:29296601

Prospective Randomized Study of Doxorubicin-Eluting-Bead Embolization in the Treatment of Hepatocellular Carcinoma: Results of the PRECISION V Study

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

Lammer, Johannes, E-mail: johannes.lammer@meduniwien.ac.a; Malagari, Katarina; Vogl, Thomas

2010-02-15

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomizationmore » was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.« less

Dissociable effects of inter-stimulus interval and presentation duration on rapid face categorization.

PubMed

Retter, Talia L; Jiang, Fang; Webster, Michael A; Rossion, Bruno

2018-04-01

Fast periodic visual stimulation combined with electroencephalography (FPVS-EEG) has unique sensitivity and objectivity in measuring rapid visual categorization processes. It constrains image processing time by presenting stimuli rapidly through brief stimulus presentation durations and short inter-stimulus intervals. However, the selective impact of these temporal parameters on visual categorization is largely unknown. Here, we presented natural images of objects at a rate of 10 or 20 per second (10 or 20 Hz), with faces appearing once per second (1 Hz), leading to two distinct frequency-tagged EEG responses. Twelve observers were tested with three squarewave image presentation conditions: 1) with an ISI, a traditional 50% duty cycle at 10 Hz (50-ms stimulus duration separated by a 50-ms ISI); 2) removing the ISI and matching the rate, a 100% duty cycle at 10 Hz (100-ms duration with 0-ms ISI); 3) removing the ISI and matching the stimulus presentation duration, a 100% duty cycle at 20 Hz (50-ms duration with 0-ms ISI). The face categorization response was significantly decreased in the 20 Hz 100% condition. The conditions at 10 Hz showed similar face-categorization responses, peaking maximally over the right occipito-temporal (ROT) cortex. However, the onset of the 10 Hz 100% response was delayed by about 20 ms over the ROT region relative to the 10 Hz 50% condition, likely due to immediate forward-masking by preceding images. Taken together, these results help to interpret how the FPVS-EEG paradigm sets temporal constraints on visual image categorization. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Randomized Trial Investigating the Efficacy and Safety of Water Soluble Micellar Paclitaxel (Paccal Vet) for Treatment of Nonresectable Grade 2 or 3 Mast Cell Tumors in Dogs

PubMed Central

Vail, D.M.; von Euler, H.; Rusk, A.W.; Barber, L.; Clifford, C.; Elmslie, R.; Fulton, L.; Hirschberger, J.; Klein, M.; London, C.; Martano, M.; McNiel, E.A.; Morris, J.S.; Northrup, N.; Phillips, B.; Polton, G.; Post, G.; Rosenberg, M.; Ruslander, D.; Sahora, A.; Siegel, S.; Thamm, D.; Westberg, S.; Winter, J.; Khanna, C.

2013-01-01

Background Effective treatments for dogs with advanced stage mast cell tumors (MCT) remain a pressing need. A micellar formulation of paclitaxel (paclitaxel [micellar]) has shown promise in early-phase studies. Hypothesis/Objectives The objective was to demonstrate greater activity for paclitaxel (micellar) compared with lomustine. The null hypothesis was μp = μL (ie, proportion of responders for the paclitaxel [micellar] and lomustine groups, respectively). Animals Two hundred and fifty-two dogs with advanced stage nonresectable grade 2 or 3 MCT. Methods Prospective multicenter randomized double-blind positive-controlled clinical trial. The primary endpoint was confirmed overall response rate (CORR) at 14 weeks. A secondary endpoint, biologic observed response rate (BORR), also was calculated. Safety was assessed by the characterization and grading of adverse events (AE). Results Overall CORR (7% versus 1%; P = .048) and BORR (23% versus 10%; P = .012) were greater for paclitaxel (micellar) compared with lomustine. Paclitaxel (micellar)-treated dogs were 6.5 times more likely to have a confirmed response and 3.1 times more likely to experience a biologic observed response. The majority of AE with paclitaxel (micellar) were transient and clinically manageable. Twenty-seven dogs (33%) receiving lomustine were discontinued because of hepatopathy compared with 3 dogs (2%) receiving paclitaxel (micellar) (P < .0001; odds ratio 26.7). Conclusions and Clinical Importance Paclitaxel (micellar)’s activity and safety profile are superior to lomustine. The addition of an active and novel taxane to the veterinary armamentarium could fill a substantial need and, as its mechanism of action and AE profile do not overlap with currently available TKI, its availability could lead to effective combination protocols. PMID:22390318

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.

Cerebral responses to innocuous somatic pressure stimulation following aerobic exercise rehabilitation in chronic pain patients: a functional magnetic resonance imaging study

PubMed Central

Micalos, Peter S; Korgaonkar, Mayuresh S; Drinkwater, Eric J; Cannon, Jack; Marino, Frank E

2014-01-01

Objective The purpose of this research was to assess the functional brain activity and perceptual rating of innocuous somatic pressure stimulation before and after exercise rehabilitation in patients with chronic pain. Materials and methods Eleven chronic pain patients and eight healthy pain-free controls completed 12 weeks of supervised aerobic exercise intervention. Perceptual rating of standardized somatic pressure stimulation (2 kg) on the right anterior mid-thigh and brain responses during functional magnetic resonance imaging (fMRI) were assessed at pre- and postexercise rehabilitation. Results There was a significant difference in the perceptual rating of innocuous somatic pressure stimulation between the chronic pain and control groups (P=0.02) but no difference following exercise rehabilitation. Whole brain voxel-wise analysis with correction for multiple comparisons revealed trends for differences in fMRI responses between the chronic pain and control groups in the superior temporal gyrus (chronic pain > control, corrected P=0.30), thalamus, and caudate (control > chronic, corrected P=0.23). Repeated measures of the regions of interest (5 mm radius) for blood oxygen level-dependent signal response revealed trend differences for superior temporal gyrus (P=0.06), thalamus (P=0.04), and caudate (P=0.21). Group-by-time interactions revealed trend differences in the caudate (P=0.10) and superior temporal gyrus (P=0.29). Conclusion Augmented perceptual and brain responses to innocuous somatic pressure stimulation were shown in the chronic pain group compared to the control group; however, 12-weeks of exercise rehabilitation did not significantly attenuate these responses. PMID:25210471

Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study.

PubMed

González-Martín, A J; Calvo, E; Bover, I; Rubio, M J; Arcusa, A; Casado, A; Ojeda, B; Balañá, C; Martínez, E; Herrero, A; Pardo, B; Adrover, E; Rifá, J; Godes, M J; Moyano, A; Cervantes, A

2005-05-01

The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL). Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis. Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.

Factors associated with career satisfaction and burnout among US neurosurgeons: results of a nationwide survey.

PubMed

McAbee, Joseph H; Ragel, Brian T; McCartney, Shirley; Jones, G Morgan; Michael, L Madison; DeCuypere, Michael; Cheng, Joseph S; Boop, Frederick A; Klimo, Paul

2015-07-01

OBJECT :The object of this study was to identify and quantify predictors of burnout and career satisfaction among US neurosurgeons. All US members (3247) of the American Association of Neurological Surgeons (AANS) were invited to participate in a survey between September and December 2012. Responses were evaluated through univariate analysis. Factors independently associated with burnout and career satisfaction were determined using multivariable logistic regression. Subgroup analysis of academic and nonacademic neurosurgeons was performed as well. The survey response rate was 24% (783 members). The majority of respondents were male, 40-60 years old, in a stable relationship, with children, working in a group or university practice, and trained in a subspecialty. More than 80% of respondents reported being at least somewhat satisfied with their career, and 70% would choose a career in neurosurgery again; however, only 26% of neurosurgeons believed their professional lives would improve in the future, and 52% believed it would worsen. The overall burnout rate was 56.7%. Factors independently associated with both burnout and career satisfaction included achieving a balance between work and life outside the hospital (burnout OR 0.45, satisfaction OR 10.0) and anxiety over future earnings and/or health care reform (burnout OR 1.96, satisfaction OR 0.32). While the burnout rate for nonacademic neurosurgeons (62.9%) was higher than that for academic neurosurgeons (47.7%), academicians who had practiced for over 20 years were less likely to be satisfied with their careers. The rates of burnout and career satisfaction were both high in this survey study of US neurosurgeons. The negative effects of burnout on the lives of surgeons, patients, and their families require further study and probably necessitate the development of interventional programs at local, regional, and even national levels.

Effects of autogenic training on stress response and heart rate variability in nursing students.

PubMed

Lim, Seung-Joo; Kim, Chunmi

2014-12-01

This study was undertaken to confirm the effects of autogenic training (AT) on stress response and heart rate variability in nursing school students experiencing stress related to clinical training. The study was carried out from September 2012 to April 2013 in a quasi-experimental nonequivalent control group using a pretest-posttest design. The participants were 40 nursing students in their third year at either of two nursing colleges. All consented to participate. Nineteen nursing students at one college were assigned to the experimental group and underwent the 8-week AT program, and the other 21 were assigned to the control group and did not undergo any training. Stress response was assessed by questionnaire and HRV was measured three times, that is, before the program, at the end of the program, and 6 months after the end of the AT program. A significant time/group interaction was found for stress response (F = 4.68, p = .012), a subjective indicator. However, no significant interaction was found for the objective indicators of heart rate variability, normalized low frequency (F = 2.59, p = .090), normalized high frequency (F = 2.59, p = .090), or low frequency to high frequency ratio (F = 1.38, p = .257). The results suggest that AT provides an acceptable approach to stress reduction in nursing students. Copyright © 2014. Published by Elsevier B.V.

Assessment of frequency specific auditory steady-state response using amplitude modulation with 2-order exponential envelope.

PubMed

Cevallos-Larrea, Pablo; Pereira, Thobias; Santos, Wagner; Frota, Silvana M; Infantosi, Antonio F; Ichinose, Roberto M; Tierra-Criollo, Carlos

2016-08-01

This study investigated the performance of Frequency Specific Auditory Steady-State Response (FS-ASSR) detection elicited by the amplitude modulated tone with 2-order exponential envelope (AM2), using objective response detection (ORD) techniques of Spectral F-Test (SFT) and Magnitude Squared Coherence (MSC). ASSRs from 24 normal hearing adults were obtained during binaural multi-tone stimulation of amplitude-modulation (AM) and AM2 at intensities of 60, 45 and 30 dBSPL. The carrier frequencies were 500, 1000, 2000, and 4000 Hz, modulated between 77 and 105 Hz. AM2 achieve FS-ASSR amplitudes higher than AM by 16%, 18% and 12% at 60, 45 and 30 dBSPL, respectively, with a major increase at 500 Hz (22.5%). AMS2PL increased the Detection Rate (DR) up to 8.3% at 500 Hz for 30 dBSPL, which is particularly beneficial for FS-ASSR detection near the hearing threshold. In addition, responses in 1000 and 4000 Hz were consistently increased. The MSC and SFT presented no differences in Detection Rate (DR). False Detection Rate (FDR) was close to 5% for both techniques and tones. Detection times to reach DR over 90% were 3.5 and 4.9 min at 60 and 45 dBSPL, respectively. Further investigation concerning efficient multiple FS-ASSR is still necessary, such as testing subjects with hearing loss.

A network meta-analysis on the efficacy of sixteen targeted drugs in combination with chemotherapy for treatment of advanced/metastatic colorectal cancer

PubMed Central

Ba-Sang, Dan-Zeng; Long, Zi-Wen; Teng, Hao; Zhao, Xu-Peng; Qiu, Jian; Li, Ming-Shan

2016-01-01

Objective A network meta-analysis was conducted comparing the short-term efficacies of 16 targeted drugs in combination with chemotherapy for treatment of advanced/metastatic colorectal cancer (CRC). Results Twenty-seven RCTs were ultimately incorporated into this network meta-analysis. Compared with chemotherapy alone, bevacizumab + chemotherapy, panitumumab + chemotherapy and conatumumab + chemotherapy had higher PR rate. Bevacizumab + chemotherapy, cetuximab + chemotherapy, panitumumab + chemotherapy, trebananib + chemotherapy and conatumumab + chemotherapy had higher ORR rate in comparison to chemotherapy alone. Furthermore, bevacizumab + chemotherapy had higher DCR rate than chemotherapy alone. The results of our cluster analysis showed that chemotherapy combined with bevacizumab, cetuximab, panitumumab, conatumumab, ganitumab, or brivanib + cetuximab had better efficacies for the treatment of advanced/metastatic CRC in comparison to chemotherapy alone. Materials and Methods Electronic databases were comprehensively searched for potential and related randomized controlled trials (RCTs). Direct and indirect evidence were incorporated for evaluation of stable disease (SD), progressive disease (PD), complete response (CR), partial response (PR), disease control rate (DCR) and overall response ratio (ORR) by calculating odds ratio (OR) and 95% confidence intervals (CI), and using the surface under the cumulative ranking curve (SUCRA). Conclusions These results indicated that bevacizumab + chemotherapy, panitumumab + chemotherapy, conatumumab + chemotherapy and brivanib + cetuximab + chemotherapy may have better efficacies for the treatment of advanced/metastatic CRC. PMID:27806321

Interactions between imidazoline I2 receptor ligands and acetaminophen in adult male rats: antinociception and schedule-controlled responding

PubMed Central

Siemian, Justin N.; Li, Jiuzhou; Zhang, Yanan; Li, Jun-Xu

2015-01-01

Rationale Recent evidence suggests that imidazoline I2 receptor ligands are suitable for combination therapy with opioids. Quantitative analysis of I2 receptor ligands combined with non-opioid drugs is necessary for justification of alternative pain therapies. Objective This study systematically examined the anti-hyperalgesic and response rate-suppressing effects of selective I2 receptor ligands (2-BFI and phenyzoline) alone and in combination with acetaminophen. Methods Von Frey and Hargreaves tests were used to examine the anti-hyperalgesic effects of drugs in complete Freund’s adjuvant (CFA)-induced inflammatory pain in rats. Food-reinforced schedule-controlled responding was used to assess the rate-suppressing effects of study drugs. Dose-addition and isobolographic analyses were used to assess drug-drug interactions for all assays. Results 2-BFI (3.2–17.8 mg/kg, i.p.), phenyzoline (17.8–100 mg/kg, i.p.), and acetaminophen (56–178 mg/kg, i.p.) all dose-dependently produced significant antinociceptive effects. When studied as combinations, 2-BFI and acetaminophen produced infra-additive to additive interactions while phenyzoline and acetaminophen produced additive to supra-additive interactions. The same drug combinations suppressed response rate in a supra-additive manner. Conclusions Quantitative analysis of the anti-hyperalgesic and response rate-suppressing effects suggests that I2 receptor ligands are not well suited to combination therapy with acetaminophen. PMID:26613734

Brentuximab vedotin in relapsed/refractory Hodgkin’s lymphoma: the Italian experience and results of its use in daily clinical practice outside clinical trials

PubMed Central

Zinzani, Pier Luigi; Viviani, Simonetta; Anastasia, Antonella; Vitolo, Umberto; Luminari, Stefano; Zaja, Francesco; Corradini, Paolo; Spina, Michele; Brusamolino, Ercole; Gianni, Alessandro M.; Santoro, Armando; Botto, Barbara; Derenzini, Enrico; Pellegrini, Cinzia; Argnani, Lisa

2013-01-01

Clinical trial results indicate that brentuximab vedotin brings considerable promise for the treatment of patients with relapsed or refractory Hodgkin’s lymphoma. A retrospective multicenter study was conducted on 65 heavily pretreated patients who underwent therapy through a Named Patient Program in Italy (non trial-setting). The primary study endpoint was the objective response rate; secondary endpoints were safety, overall survival and progression-free survival. The best overall response rate (70.7%), including 21.5% complete responses, was observed at the first restaging after the third cycle of treatment. After a median follow up of 13.2 months, the overall survival rate at 20 months was 73.8% while the progression-free survival rate at 20 months was 24.2%. Globally nine patients are in continuous complete response with a median follow up of 14 months (range, 10–19 months). Four patients proceeded to autotransplantation and nine to allotransplantation. The most frequent extra-hematologic toxicity was peripheral neuropathy, observed in 21.5% of cases (9 patients with grade 1/2 and 5 patients with grade 3/4); neurological toxicity led to discontinuation of treatment in three patients and to dose reduction in four. In general the treatment was well tolerated and toxicities, both hematologic and extra-hematologic, were manageable. This report indicates and confirms that brentuximab vedotin as a single agent is effective and safe also when used in standard, everyday clinical practice outside a clinical trial. Best overall responses were recorded after three or four cycles and showed that brentuximab vedotin provides an effective bridge to further therapeutic interventions. PMID:23645687

Combat Stress Decreases Memory of Warfighters in Action.

PubMed

Delgado-Moreno, Rosa; Robles-Pérez, José Juan; Clemente-Suárez, Vicente Javier

2017-08-01

The present research aimed to analyze the effect of combat stress in the psychophysiological response and attention and memory of warfighters in a simulated combat situation. Variables of blood oxygen saturation, heart rate, blood glucose, blood lactate, body temperature, lower body muscular strength manifestation, cortical arousal, autonomic modulation, state anxiety and memory and attention through a postmission questionnaire were analyzed before and after a combat simulation in 20 male professional Spanish Army warfighters. The combat simulation produces a significant increase (p < 0.05) in explosive leg strength, rated perceived exertion, blood glucose, blood lactate, somatic anxiety, heart rate, and low frequency domain of the HRV (LF) and a significant decrease of high frequency domain of the heart rate variability (HF). The percentage of correct response in the postmission questionnaire parameters show that elements more related with a physical integrity threat are the most correctly remembered. There were significant differences in the postmission questionnaire variables when participants were divided by the cortical arousal post: sounds no response, mobile phone correct, mobile phone no response, odours correct. The correlation analysis showed positive correlations: LF post/body temperature post, HF post/correct sound, body temperature post/glucose post, CFFTpre/lactate post, CFFT post/wrong sound, glucose post/AC pre, AC post/wrong fusil, AS post/SC post and SC post/wrong olfactory; and negative correlations: LF post/correct sound, body temperature post/lactate post and glucose post/lactate post. This data suggest that combat stress actives fight-flight system of soldiers. As conclusion, Combat stress produces an increased psychophysiological response that cause a selective decrease of memory, depending on the nature, dangerous or harmless of the objects.

The Effect of Noseband Tightening on Horses’ Behavior, Eye Temperature, and Cardiac Responses

PubMed Central

Yoon, Samuel; McGreevy, Paul

2016-01-01

Restrictive nosebands are common in equestrian sport. This is concerning, as recent evidence suggests that very tight nosebands can cause a physiological stress response, and may compromise welfare. The objective of the current study was to investigate relationships that noseband tightness has with oral behavior and with physiological changes that indicate a stress response, such as increases in eye temperature (measured with infrared thermography) and heart rate and decreases in heart rate variability (HRV). Horses (n = 12) wearing a double bridle and crank noseband, as is common in dressage at elite levels, were randomly assigned to four treatments: unfastened noseband (UN), conventional area under noseband (CAUN) with two fingers of space available under the noseband, half conventional area under noseband (HCAUN) with one finger of space under the noseband, and no area under the noseband (NAUN). During the tightest treatment (NAUN), horse heart rate increased (P = 0.003), HRV decreased (P < 0.001), and eye temperature increased (P = 0.011) compared with baseline readings, indicating a physiological stress response. The behavioral results suggest some effects from bits alone but the chief findings are the physiological readings that reflect responses to the nosebands at their tightest. Chewing decreased during the HCAUN (P < 0.001) and NAUN (P < 0.001) treatments. Yawning rates were negligible in all treatments. Similarly, licking was eliminated by the NAUN treatment. Following the removal of the noseband and double bridle during the recovery session, yawning (P = 0.015), swallowing (P = 0.003), and licking (P < 0.001) significantly increased compared with baseline, indicating a post-inhibitory rebound response. This suggests a rise in motivation to perform these behaviors and implies that their inhibition may place horses in a state of deprivation. It is evident that a very tight noseband can cause physiological stress responses and inhibit the expression of oral behaviors. PMID:27140187

Low-Dose Radiation Therapy (2 Gy × 2) in the Treatment of Orbital Lymphoma

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

Fasola, Carolina E.; Jones, Jennifer C.; Huang, Derek D.

2013-08-01

Purpose: Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. Methods and Materials: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR). Results: Atmore » a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity. Conclusions: Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.« less

Complete remission of platinium refractory ovarian cancer with second line tegafur with uracil monotherapy: a case report.

PubMed

Camci, Celalettin; Sevinc, Alper; Aslan, Yilmaz; Kalender, Mehmet Emin; Buyukberber, Suleyman

2009-03-01

Ovarian cancer remains one of the most lethal of all gynecologic malignancies, accounting for more deaths than cervical and uterine cancer combined. Advanced ovarian cancer is a chemosensitive tumor and most patients initially respond to platinum-based combination chemotherapy with response rates of about 70%, including a high proportion of complete responses. However, despite aggressive surgery and chemotherapy, more than 80% of patients will relapse and will then be treated with second line chemotherapy with objective responses in about 20% of patients and even lower percentages of complete responses. We observed a 42-months of complete response with administration of 1-[2-tetrahydrofuryl]-5-fluorouracil mixed with uracil (UFT) in patient with platinium refractory ovarian cancer. We report a complete remission of platinium refractory epithelial ovarian cancer with UFT monotherapy that was not reported previously.

Aging and the rate of visual information processing.

PubMed

Guest, Duncan; Howard, Christina J; Brown, Louise A; Gleeson, Harriet

2015-01-01

Multiple methods exist for measuring how age influences the rate of visual information processing. The most advanced methods model the processing dynamics in a task in order to estimate processing rates independently of other factors that might be influenced by age, such as overall performance level and the time at which processing onsets. However, such modeling techniques have produced mixed evidence for age effects. Using a time-accuracy function (TAF) analysis, Kliegl, Mayr, and Krampe (1994) showed clear evidence for age effects on processing rate. In contrast, using the diffusion model to examine the dynamics of decision processes, Ratcliff and colleagues (e.g., Ratcliff, Thapar, & McKoon, 2006) found no evidence for age effects on processing rate across a range of tasks. Examination of these studies suggests that the number of display stimuli might account for the different findings. In three experiments we measured the precision of younger and older adults' representations of target stimuli after different amounts of stimulus exposure. A TAF analysis found little evidence for age differences in processing rate when a single stimulus was presented (Experiment 1). However, adding three nontargets to the display resulted in age-related slowing of processing (Experiment 2). Similar slowing was observed when simply presenting two stimuli and using a post-cue to indicate the target (Experiment 3). Although there was some interference from distracting objects and from previous responses, these age-related effects on processing rate seem to reflect an age-related difficulty in processing multiple objects, particularly when encoding them into visual working memory.

[Methodological design of the National Health and Nutrition Survey 2016].

PubMed

Romero-Martínez, Martín; Shamah-Levy, Teresa; Cuevas-Nasu, Lucía; Gómez-Humarán, Ignacio Méndez; Gaona-Pineda, Elsa Berenice; Gómez-Acosta, Luz María; Rivera-Dommarco, Juan Ángel; Hernández-Ávila, Mauricio

2017-01-01

Describe the design methodology of the halfway health and nutrition national survey (Ensanut-MC) 2016. The Ensanut-MC is a national probabilistic survey whose objective population are the inhabitants of private households in Mexico. The sample size was determined to make inferences on the urban and rural areas in four regions. Describes main design elements: target population, topics of study, sampling procedure, measurement procedure and logistics organization. A final sample of 9 479 completed household interviews, and a sample of 16 591 individual interviews. The response rate for households was 77.9%, and the response rate for individuals was 91.9%. The Ensanut-MC probabilistic design allows valid statistical inferences about interest parameters for Mexico´s public health and nutrition, specifically on overweight, obesity and diabetes mellitus. Updated information also supports the monitoring, updating and formulation of new policies and priority programs.

A crystallographic model for nickel base single crystal alloys

NASA Technical Reports Server (NTRS)

Dame, L. T.; Stouffer, D. C.

1988-01-01

The purpose of this research is to develop a tool for the mechanical analysis of nickel-base single-crystal superalloys, specifically Rene N4, used in gas turbine engine components. This objective is achieved by developing a rate-dependent anisotropic constitutive model and implementing it in a nonlinear three-dimensional finite-element code. The constitutive model is developed from metallurgical concepts utilizing a crystallographic approach. An extension of Schmid's law is combined with the Bodner-Partom equations to model the inelastic tension/compression asymmetry and orientation-dependence in octahedral slip. Schmid's law is used to approximate the inelastic response of the material in cube slip. The constitutive equations model the tensile behavior, creep response and strain-rate sensitivity of the single-crystal superalloys. Methods for deriving the material constants from standard tests are also discussed. The model is implemented in a finite-element code, and the computed and experimental results are compared for several orientations and loading conditions.

Comparative Study of 28 and 18 Years Field Aged Siemens-Arco M55 Modules in Temperate and Hot-Dry Climates

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

Chicca, Matthew; Wohlgemuth, John; TamizhMani, GovindaSamy

The primary objective of this research work is two-fold: (i) determine the degradation rates of Siemens-Arco M55 modules exposed over 18 and 28 years in a hot-dry climate of Arizona and a temperate climate of California, and; (ii) identify the potential modes responsible for these degradation losses. The degradation rates were determined based on the I-V data obtained on exposed modules and on the corresponding control modules which were not exposed in the fields. The degradation modes responsible for these degradations were determined using several nondestructive tests and destructive tests performed on these control and exposed modules. The nondestructive testsmore » included: current-voltage, visual inspection, cell-module quantum efficiency, and module level reflectance spectroscopy. The destructive tests included: transmittance spectroscopy of glass superstrates, and FTIR, DSC and TGA of encapsulant materials.« less

Radiologist Uncertainty and the Interpretation of Screening

PubMed Central

Carney, Patricia A.; Elmore, Joann G.; Abraham, Linn A.; Gerrity, Martha S.; Hendrick, R. Edward; Taplin, Stephen H.; Barlow, William E.; Cutter, Gary R.; Poplack, Steven P.; D’Orsi, Carl J.

2011-01-01

Objective To determine radiologists’ reactions to uncertainty when interpreting mammography and the extent to which radiologist uncertainty explains variability in interpretive performance. Methods The authors used a mailed survey to assess demographic and clinical characteristics of radiologists and reactions to uncertainty associated with practice. Responses were linked to radiologists’ actual interpretive performance data obtained from 3 regionally located mammography registries. Results More than 180 radiologists were eligible to participate, and 139 consented for a response rate of 76.8%. Radiologist gender, more years interpreting, and higher volume were associated with lower uncertainty scores. Positive predictive value, recall rates, and specificity were more affected by reactions to uncertainty than sensitivity or negative predictive value; however, none of these relationships was statistically significant. Conclusion Certain practice factors, such as gender and years of interpretive experience, affect uncertainty scores. Radiologists’ reactions to uncertainty do not appear to affect interpretive performance. PMID:15155014

Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer.

PubMed

Gettinger, Scott N; Horn, Leora; Gandhi, Leena; Spigel, David R; Antonia, Scott J; Rizvi, Naiyer A; Powderly, John D; Heist, Rebecca S; Carvajal, Richard D; Jackman, David M; Sequist, Lecia V; Smith, David C; Leming, Philip; Carbone, David P; Pinder-Schenck, Mary C; Topalian, Suzanne L; Hodi, F Stephen; Sosman, Jeffrey A; Sznol, Mario; McDermott, David F; Pardoll, Drew M; Sankar, Vindira; Ahlers, Christoph M; Salvati, Mark; Wigginton, Jon M; Hellmann, Matthew D; Kollia, Georgia D; Gupta, Ashok K; Brahmer, Julie R

2015-06-20

Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts. We report overall survival (OS), response durability, and long-term safety in patients with non-small-cell lung cancer (NSCLC) receiving nivolumab in this trial. Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. Tumor burden was assessed by RECIST (version 1.0) after each cycle. Median OS across doses was 9.9 months; 1-, 2-, and 3-year OS rates were 42%, 24%, and 18%, respectively, across doses and 56%, 42%, and 27%, respectively, at the 3-mg/kg dose (n = 37) chosen for further clinical development. Among 22 patients (17%) with objective responses, estimated median response duration was 17.0 months. An additional six patients (5%) had unconventional immune-pattern responses. Response rates were similar in squamous and nonsquamous NSCLC. Eighteen responding patients discontinued nivolumab for reasons other than progressive disease; nine (50%) of those had responses lasting > 9 months after their last dose. Grade 3 to 4 treatment-related adverse events occurred in 14% of patients. Three treatment-related deaths (2% of patients) occurred, each associated with pneumonitis. Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing. © 2015 by American Society of Clinical Oncology.

Can Functional Magnetic Resonance Imaging Improve Success Rates in CNS Drug Discovery?

PubMed Central

Borsook, David; Hargreaves, Richard; Becerra, Lino

2011-01-01

Introduction The bar for developing new treatments for CNS disease is getting progressively higher and fewer novel mechanisms are being discovered, validated and developed. The high costs of drug discovery necessitate early decisions to ensure the best molecules and hypotheses are tested in expensive late stage clinical trials. The discovery of brain imaging biomarkers that can bridge preclinical to clinical CNS drug discovery and provide a ‘language of translation’ affords the opportunity to improve the objectivity of decision-making. Areas Covered This review discusses the benefits, challenges and potential issues of using a science based biomarker strategy to change the paradigm of CNS drug development and increase success rates in the discovery of new medicines. The authors have summarized PubMed and Google Scholar based publication searches to identify recent advances in functional, structural and chemical brain imaging and have discussed how these techniques may be useful in defining CNS disease state and drug effects during drug development. Expert opinion The use of novel brain imaging biomarkers holds the bold promise of making neuroscience drug discovery smarter by increasing the objectivity of decision making thereby improving the probability of success of identifying useful drugs to treat CNS diseases. Functional imaging holds the promise to: (1) define pharmacodynamic markers as an index of target engagement (2) improve translational medicine paradigms to predict efficacy; (3) evaluate CNS efficacy and safety based on brain activation; (4) determine brain activity drug dose-response relationships and (5) provide an objective evaluation of symptom response and disease modification. PMID:21765857

An objective method for measuring face detection thresholds using the sweep steady-state visual evoked response

PubMed Central

Ales, Justin M.; Farzin, Faraz; Rossion, Bruno; Norcia, Anthony M.

2012-01-01

We introduce a sensitive method for measuring face detection thresholds rapidly, objectively, and independently of low-level visual cues. The method is based on the swept parameter steady-state visual evoked potential (ssVEP), in which a stimulus is presented at a specific temporal frequency while parametrically varying (“sweeping”) the detectability of the stimulus. Here, the visibility of a face image was increased by progressive derandomization of the phase spectra of the image in a series of equally spaced steps. Alternations between face and fully randomized images at a constant rate (3/s) elicit a robust first harmonic response at 3 Hz specific to the structure of the face. High-density EEG was recorded from 10 human adult participants, who were asked to respond with a button-press as soon as they detected a face. The majority of participants produced an evoked response at the first harmonic (3 Hz) that emerged abruptly between 30% and 35% phase-coherence of the face, which was most prominent on right occipito-temporal sites. Thresholds for face detection were estimated reliably in single participants from 15 trials, or on each of the 15 individual face trials. The ssVEP-derived thresholds correlated with the concurrently measured perceptual face detection thresholds. This first application of the sweep VEP approach to high-level vision provides a sensitive and objective method that could be used to measure and compare visual perception thresholds for various object shapes and levels of categorization in different human populations, including infants and individuals with developmental delay. PMID:23024355

Impact of the 2004-2005 Influenza Vaccine Shortage on Immunization Practices in Long-Term Care Facilities

PubMed Central

Mody, Lona; Langa, Kenneth M.; Malani, Preeti N.

2012-01-01

Objective To assess the response of long-term care facilities (LTCFs) to the 2004-2005 influenza vaccine shortage and the impact on resident and healthcare worker (HCW) immunization rates. Methods A 12-item questionnaire was sent to 824 randomly selected LTCFs in December 2004. The following 2 open-ended questions were also asked: “How did you cope with the vaccine shortage?” and “Who helped you get your supply?” Immunization rates reported by LTCF administrators for 2003-2003 and 2003-2004 were compared with those for 2004-2005. Immunization rates were defined as the proportion of all eligible residents and HCWs who received influenza vaccine. Results Responses were received from 380 LTCFs (46.3%), which had a total of 38,447 beds. Resident mean influenza immunization rates (±SD) decreased from 85% ± 15.3% in 2002-2003 and 85.1% ± 15.3% in 2003-2004 to 81.9% ± 19.4% in the 2004-2005 influenza season (P = .025). The immunization rates among HCWs also decreased from 51% in 2002-2003 and 2003-2004 to 38.4% in 2004-2005 (P < .001). In response to one of the open-ended questions, 96 facilities (25.3%) reported that they obtained vaccine from 2 or more sources. Eight percent commented on specific intensified infection control efforts, and only 2.3% commented on emergency preparedness. Conclusions The influenza vaccine shortage in 2004-2005 impacted immunization practices of LTCFs across the United States, leading to decreases in both resident and HCW vaccination rates. The significant decrease in vaccination rates in LTCFs is of concern and has broad implications for policy makers working on emergency preparedness for a possible pandemic of influenza. PMID:16622817

Mixed oxidizer hybrid propulsion system optimization under uncertainty using applied response surface methodology and Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Whitehead, James Joshua

The analysis documented herein provides an integrated approach for the conduct of optimization under uncertainty (OUU) using Monte Carlo Simulation (MCS) techniques coupled with response surface-based methods for characterization of mixture-dependent variables. This novel methodology provides an innovative means of conducting optimization studies under uncertainty in propulsion system design. Analytic inputs are based upon empirical regression rate information obtained from design of experiments (DOE) mixture studies utilizing a mixed oxidizer hybrid rocket concept. Hybrid fuel regression rate was selected as the target response variable for optimization under uncertainty, with maximization of regression rate chosen as the driving objective. Characteristic operational conditions and propellant mixture compositions from experimental efforts conducted during previous foundational work were combined with elemental uncertainty estimates as input variables. Response surfaces for mixture-dependent variables and their associated uncertainty levels were developed using quadratic response equations incorporating single and two-factor interactions. These analysis inputs, response surface equations and associated uncertainty contributions were applied to a probabilistic MCS to develop dispersed regression rates as a function of operational and mixture input conditions within design space. Illustrative case scenarios were developed and assessed using this analytic approach including fully and partially constrained operational condition sets over all of design mixture space. In addition, optimization sets were performed across an operationally representative region in operational space and across all investigated mixture combinations. These scenarios were selected as representative examples relevant to propulsion system optimization, particularly for hybrid and solid rocket platforms. Ternary diagrams, including contour and surface plots, were developed and utilized to aid in visualization. The concept of Expanded-Durov diagrams was also adopted and adapted to this study to aid in visualization of uncertainty bounds. Regions of maximum regression rate and associated uncertainties were determined for each set of case scenarios. Application of response surface methodology coupled with probabilistic-based MCS allowed for flexible and comprehensive interrogation of mixture and operating design space during optimization cases. Analyses were also conducted to assess sensitivity of uncertainty to variations in key elemental uncertainty estimates. The methodology developed during this research provides an innovative optimization tool for future propulsion design efforts.

The effects of short-term and long-term learning on the responses of lateral intraparietal neurons to visually presented objects.

PubMed

Sigurdardottir, Heida M; Sheinberg, David L

2015-07-01

The lateral intraparietal area (LIP) is thought to play an important role in the guidance of where to look and pay attention. LIP can also respond selectively to differently shaped objects. We sought to understand to what extent short-term and long-term experience with visual orienting determines the responses of LIP to objects of different shapes. We taught monkeys to arbitrarily associate centrally presented objects of various shapes with orienting either toward or away from a preferred spatial location of a neuron. The training could last for less than a single day or for several months. We found that neural responses to objects are affected by such experience, but that the length of the learning period determines how this neural plasticity manifests. Short-term learning affects neural responses to objects, but these effects are only seen relatively late after visual onset; at this time, the responses to newly learned objects resemble those of familiar objects that share their meaning or arbitrary association. Long-term learning affects the earliest bottom-up responses to visual objects. These responses tend to be greater for objects that have been associated with looking toward, rather than away from, LIP neurons' preferred spatial locations. Responses to objects can nonetheless be distinct, although they have been similarly acted on in the past and will lead to the same orienting behavior in the future. Our results therefore indicate that a complete experience-driven override of LIP object responses may be difficult or impossible. We relate these results to behavioral work on visual attention.

Unconfirmed Near-Earth Objects

NASA Astrophysics Data System (ADS)

Vereš, Peter; Payne, Matthew J.; Holman, Matthew J.; Farnocchia, Davide; Williams, Gareth V.; Keys, Sonia; Boardman, Ian

2018-07-01

We studied the Near-Earth Asteroid (NEA) candidates posted on the Minor Planet Center’s Near-Earth Object Confirmation Page (NEOCP) between years 2013 and 2016. Out of more than 17000 NEA candidates, while the majority became either new discoveries or were associated with previously known objects, about 11% were unable to be followed-up or confirmed. We further demonstrate that of the unconfirmed candidates, 926 ± 50 are likely to be NEAs, representing 18% of discovered NEAs in that period. Only 11% (∼93) of the unconfirmed NEA candidates were large (having absolute magnitude H < 22). To identify the reasons why these NEAs were not recovered, we analyzed those from the most prolific asteroid surveys: Pan-STARRS, the Catalina Sky Survey, the Dark Energy Survey, and the Space Surveillance Telescope. We examined the influence of plane-of-sky positions and rates of motion, brightnesses, submission delays, and computed absolute magnitudes, as well as correlations with the phase of the moon and seasonal effects. We find that delayed submission of newly discovered NEA candidate to the NEOCP drove a large fraction of the unconfirmed NEA candidates. A high rate of motion was another significant contributing factor. We suggest that prompt submission of suspected NEA discoveries and rapid response to fast-moving targets and targets with fast growing ephemeris uncertainty would allow better coordination among dedicated follow-up observers, decrease the number of unconfirmed NEA candidates, and increase the discovery rate of NEAs.

Impact of Pretreatment With Antidepressants on the Efficacy of Duloxetine in Terms of Mood Symptoms and Functioning: An Analysis of 15 Pooled Major Depressive Disorder Studies

PubMed Central

Barros, Bruno R.; Schacht, Alexander; Happich, Michael; Televantou, Foula; Berggren, Lovisa; Walker, Daniel J.

2014-01-01

Objective: This post hoc analysis aimed to determine whether patients with major depressive disorder (MDD) in duloxetine trials who were antidepressant naive or who were previously exposed to antidepressants exhibited differences in efficacy and functioning. Method: Data were pooled from 15 double-blind, placebo- and/or active-controlled duloxetine trials of adult patients with MDD conducted by Eli Lilly and Company. The individual studies took place between March 2000 and November 2009. Data were analyzed using 4 pretreatment subgroups: first-episode never treated, multiple-episode never treated, treated previously only with selective serotonin reuptake inhibitors (SSRIs), and previously treated with antidepressants other than just SSRIs. Measures included the 17-item Hamilton Depression Rating Scale (HDRS-17) total and somatic symptom subscale scores, Montgomery-Asberg Depression Rating Scale (MADRS) total score, and Sheehan Disability Scale total score. Response rates (50% and 30%) were based on the HDRS-17 total score and remission rates on either the HDRS-17 or MADRS total score. Results: Response and remission rates were significantly greater (P < .05 in 11 of 12 comparisons) for duloxetine versus placebo in the 4 subgroups. A trend of greater response and remission occurred for first-episode versus multiple-episode patients; both groups were generally higher than the antidepressant-treated groups. Mean changes in efficacy measures were mostly significantly greater (P < .05 in 13 of 16 comparisons) for duloxetine versus placebo within each pretreatment subgroup, with some (P < .05 in 2 of 24 comparisons) significant interaction effects between subgroups on HDRS-17 total and somatic symptoms scores. Conclusions: Duloxetine was generally superior to placebo on response and remission rates and in mean change on efficacy measures. Response and remission rates were numerically greater for first-episode versus multiple-episode and drug-treated patients. Mean change differences on efficacy measures among the 4 subgroups were inconsistent. Duloxetine showed a similar therapeutic effect independent of episode frequency and antidepressant pretreatment. PMID:25667808

Clinical features of Bim deletion polymorphism and its relation with crizotinib primary resistance in Chinese patients with ALK/ROS1 fusion-positive non-small cell lung cancer.

PubMed

Zhang, Limin; Jiang, Tao; Li, Xuefei; Wang, Yan; Zhao, Chao; Zhao, Sha; Xi, Lei; Zhang, Shijia; Liu, Xiaozhen; Jia, Yijun; Yang, Hui; Shi, Jinpeng; Su, Chunxia; Ren, Shengxiang; Zhou, Caicun

2017-08-01

The authors' previous study demonstrated that the B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (BCL2L11) (Bim) deletion polymorphism was associated with poor clinical response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC) with EGFR mutations. The objective of the current study was to investigate the impact of the Bim deletion polymorphism among patients with anaplastic lymphoma kinase (ALK)-positive or ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)-positive NSCLC who were treated with crizotinib. A total of 55 patients with ALK-positive NSCLC and 14 patients with ROS1-positive NSCLC who were treated with crizotinib were enrolled into the current study. The Bim deletion polymorphism was analyzed by polymerase chain reaction. The clinical features of the Bim deletion polymorphism and its impact on the effect of crizotinib were investigated. The Bim deletion polymorphism was present in 9 of 69 patients with ALK-positive or ROS1-positive NSCLC (13.0%). There were no differences noted with regard to clinicopathological features between patients with and without the Bim deletion polymorphism. Patients with the Bim deletion polymorphism had a significantly shorter progression-free survival (PFS) and lower objective response rate compared with those without (median PFS, 182 days vs 377 days [P = .008]) (objective response rate, 44.4% vs 81.7% [P =.041]) in all populations. The significant difference in PFS was observed in patients with ALK-positive NSCLC (83 days vs 305 days [P =.0304]) compared with those with ROS1-positive NSCLC (218 days vs not reached [P =.082]). Multivariate analysis indicated that the Bim deletion polymorphism was an independent predictive factor for patients with ALK-positive NSCLC who were treated with crizotinib (hazard ratio, 4.786 [P =.006]). The Bim deletion polymorphism was found to be associated with poor clinical response to crizotinib in patients with ALK fusion-positive NSCLC. Cancer 2017;123:2927-35. © 2017 American Cancer Society. © 2017 American Cancer Society.

Opioid abusers’ ability to differentiate an opioid from placebo in laboratory challenge testing*

PubMed Central

Antoine, Denis G.; Strain, Eric C.; Tompkins, D. Andrew; Bigelow, George E.

2013-01-01

Background Abuse liability assessments influence drug development, federal regulation, and clinical care. One suggested procedure to reduce variability of assessments is a qualification phase, which assesses whether study applicants adequately distinguish active drug from placebo; applicants failing to make this distinction are disqualified. The present analyses assessed differences between qualification phase qualifiers and non-qualifiers. Methods Data were collected from 23 completers of the qualification phase of an abuse liability study. Opioid abusing participants received 30 mg oxycodone and placebo orally on separate days, and were characterized as qualifiers (vs. non-qualifiers) if their peak visual analog scale liking rating for oxycodone was at least 20 points higher than placebo’s peak rating. Groups were compared on demographic characteristics, drug history, and physiologic, subject and observer ratings. Results 61% of participants were qualifiers and 39% were non-qualifiers. Groups had similar demographic characteristics, drug use histories, and pupillary constriction responses. However, unlike qualifiers, non-qualifiers had an exaggerated placebo response for the liking score (p=0.03) and an attenuated oxycodone response for the liking score (p<.0001). Non-qualifiers’ failure to differentiate oxycodone versus placebo was evident for subject and observer ratings. Conclusion Different subjective responses to identical stimuli support the use of a qualification phase in abuse liability assessments. Further research should explore objective measures that may better account for these differences, determine optimal qualification criteria, and explore the developmental course of drug use. This study also documents certain opioid abusers fail to differentiate 30 mg of oxycodone from placebo, a phenomenon deserving further study. PMID:23369645

The short-term outcomes of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy in patients with poor-risk locally advanced rectal cancer.

PubMed

Beppu, Naohito; Yoshie, Hidenori; Kimura, Fumihiko; Aihara, Tsukasa; Doi, Hiroshi; Kamikonya, Norihiko; Matsubara, Nagahide; Tomita, Naohiro; Yanagi, Hidenori; Yamanaka, Naoki

2016-10-01

To evaluate the safety and efficacy of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy and surgery in patients with poor-risk locally advanced rectal cancer. We enrolled eligible patients with poor-risk rectal cancer defined as T3 lower rectal cancer with mesorectal fascia involvement, T4a or T4b tumors or cases with lateral lymph node swelling. The primary endpoint was a pathological complete response (pCR), and the secondary endpoints were the objective response rate (ORR) and the pathological high response rate (Grade 2 plus 3). Twenty eligible patients were enrolled. The majority (75.0 %, 15/20) of the patients completed four cycles of induction chemotherapy, and all patients completed the radiotherapy (25 Gy/10 fractions/5 days). The global rate of Grade 3-4 toxicities was 30.0 % (6/20 patients). The ORRs were 85.0 % (17/20) and 95.0 % (19/20) in the patients who underwent R0 and R1 resection, respectively. The pathological high response rate was 70.0 % (14/20) and the pCR was 10.0 % (2/20). The regimen of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy is safe and is associated with good tumor regression in patients with poor-risk locally advanced rectal cancer.

Response Rates for Patient-Reported Outcomes Using Web-Based Versus Paper Questionnaires: Comparison of Two Invitational Methods in Older Colorectal Cancer Patients

PubMed Central

Vissers, Pauline AJ; Mols, Floortje; Thong, Melissa SY; van de Poll-Franse, Lonneke V

2015-01-01

Background Improving questionnaire response rates is an everlasting issue for research. Today, the Internet can easily be used to collect data quickly. However, collecting data on the Internet can lead to biased samples because not everyone is able to access or use the Internet. The older population, for example, is much less likely to use the Internet. The Patient-Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship (PROFILES) registry offers a platform to collect Web-based and paper questionnaires and to try different measures to improve response rates. Objective In this study, our aim was to study the influence of two methods of invitation on the response rate. Our second aim was to examine the preference of questionnaire mode of administration (paper or Web-based) for the older patient in particular. Methods To test these two invitational methods, 3406 colorectal cancer patients between ages 18 and 85 years received an invitation containing an access code for the Web-based questionnaire. They could also request a paper questionnaire with an included reply card (paper-optional group). In contrast, 179 randomly selected colorectal cancer patients received a paper questionnaire with the invitation (paper-included group). They could also choose to fill out the Web-based questionnaire with the included access code. Results Response rates did not differ between the paper-optional and the paper-included groups (73.14%, 2491/3406 and 74.9%, 134/179, P=.57). In the paper-optional group, online response was significantly higher when compared to the paper-included group (41.23%, 1027/2491 vs 12.7%, 17/134, P<.001). The majority of online respondents responded after the first invitation (95.33%, 979/1027), which was significantly higher than the paper respondents (52.19%, 764/1464, P<.001). Respondents aged 70 years and older chose to fill out a paper questionnaire more often (71.0%, 677/954). In the oldest age group (≥80 years), 18.2% (61/336) of the respondents filled out a Web-based questionnaire. Conclusions The lack of difference in response rates between invitation modes implies that researchers can leave out a paper questionnaire at invitation without lowering response rates. It may be preferable not to include a paper questionnaire because more respondents then will fill out a Web-based questionnaire, which will lead to faster available data. However, due to respondent preference, it is not likely that paper questionnaires can be left out completely in the near future. PMID:25953059

An experimental study of the job demand-control model with measures of heart rate variability and salivary alpha-amylase: Evidence of increased stress responses to increased break autonomy.

PubMed

O'Donnell, Emma; Landolt, Kathleen; Hazi, Agnes; Dragano, Nico; Wright, Bradley J

2015-01-01

We assessed in an experimental design whether the stress response towards a work task was moderated by the autonomy to choose a break during the assigned time to complete the task. This setting is defined in accordance with the theoretical framework of the job-demand-control (JDC) model of work related stress. The findings from naturalistic investigations of a stress-buffering effect of autonomy (or 'buffer hypothesis') are equivocal and the experimental evidence is limited, especially with relation to physiological indices of stress. Our objective was to investigate if increased autonomy in a particular domain (break time control) was related with adaptive physiology using objective physiological markers of stress; heart rate variability (HRV) and salivary alpha amylase (sAA). We used a within-subject design and the 60 female participants were randomly assigned to an autonomy (free timing of break) and standard conditions (fixed timing of break) of a word processing task in a simulated office environment in a random order. Participants reported increased perceptions of autonomy, no difference in demand and performed worse in the task in the break-time autonomy versus the standard condition. The results revealed support for the manipulation of increased autonomy, but in the opposing direction. Increased autonomy was related with dysregulated physiological reactivity, synonymous with typical increased stress responses. Potentially, our findings may indicate that autonomy is not necessary a resource but could become an additional stressor when it adds additional complexity while the amount of work (demands) remains unchanged. Further, our findings underscore the need to collect objective physiological evidence of stress to supplement self-reported information. Self-report biases may partially explain the inconsistent findings with the buffer hypothesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Automatic Spiral Analysis for Objective Assessment of Motor Symptoms in Parkinson's Disease.

PubMed

Memedi, Mevludin; Sadikov, Aleksander; Groznik, Vida; Žabkar, Jure; Možina, Martin; Bergquist, Filip; Johansson, Anders; Haubenberger, Dietrich; Nyholm, Dag

2015-09-17

A challenge for the clinical management of advanced Parkinson's disease (PD) patients is the emergence of fluctuations in motor performance, which represents a significant source of disability during activities of daily living of the patients. There is a lack of objective measurement of treatment effects for in-clinic and at-home use that can provide an overview of the treatment response. The objective of this paper was to develop a method for objective quantification of advanced PD motor symptoms related to off episodes and peak dose dyskinesia, using spiral data gathered by a touch screen telemetry device. More specifically, the aim was to objectively characterize motor symptoms (bradykinesia and dyskinesia), to help in automating the process of visual interpretation of movement anomalies in spirals as rated by movement disorder specialists. Digitized upper limb movement data of 65 advanced PD patients and 10 healthy (HE) subjects were recorded as they performed spiral drawing tasks on a touch screen device in their home environment settings. Several spatiotemporal features were extracted from the time series and used as inputs to machine learning methods. The methods were validated against ratings on animated spirals scored by four movement disorder specialists who visually assessed a set of kinematic features and the motor symptom. The ability of the method to discriminate between PD patients and HE subjects and the test-retest reliability of the computed scores were also evaluated. Computed scores correlated well with mean visual ratings of individual kinematic features. The best performing classifier (Multilayer Perceptron) classified the motor symptom (bradykinesia or dyskinesia) with an accuracy of 84% and area under the receiver operating characteristics curve of 0.86 in relation to visual classifications of the raters. In addition, the method provided high discriminating power when distinguishing between PD patients and HE subjects as well as had good test-retest reliability. This study demonstrated the potential of using digital spiral analysis for objective quantification of PD-specific and/or treatment-induced motor symptoms.

Manipulation of heart rate variability can modify response to anger-inducing stimuli.

PubMed

Francis, Heather M; Penglis, Kathryn M; McDonald, Skye

2016-10-01

Research suggests that heart rate variability (HRV) is a physiological indicator of the flexibility of the autonomic nervous system and can provide an objective measure of an individual's ability to appropriately match emotional responses to environmental demands. The present study investigated whether angry response to emotional stimuli was related to HRV, and whether manipulation of HRV using biofeedback could change the anger response in a healthy adult population. Fifty-eight participants received HRV biofeedback (n = 29) or an active control condition (n = 29). HRV measures included standard deviation of normal-to-normal intervals (SDNN), low-frequency (LF) and high-frequency (HF) power, and was recorded across three sessions: baseline, training, and anger induction. The anger induction procedure resulted in increased subjective experience of anger, as well as physiological changes. The biofeedback group had higher HRV than active controls both during the training session (SDNN and LF HRV) and during anger induction (LF HRV). HRV during anger induction was significantly associated with self-reported emotional response for participants receiving biofeedback but not for active controls. Results provide support for HRV as an index of emotion regulation, specifically anger. Further research is needed to determine whether long-term HRV biofeedback can have a lasting effect on managing anger.

US primary care physicians' opinions about conscientious refusal: a national vignette experiment.

PubMed

Brauer, Simon G; Yoon, John D; Curlin, Farr A

2016-02-01

Previous research has found that physicians are divided on whether they are obligated to provide a treatment to which they object and whether they should refer patients in such cases. The present study compares several possible scenarios in which a physician objects to a treatment that a patient requests, in order to better characterise physicians' beliefs about what responses are appropriate. We surveyed a nationally representative sample of 1504 US primary care physicians using an experimentally manipulated vignette in which a patient requests a clinical intervention to which the patient's physician objects. We used multivariate logistic regression models to determine how vignette and respondent characteristics affected respondent's judgements. Among eligible respondents, the response rate was 63% (896/1427). When faced with an objection to providing treatment, referring the patient was the action judged most appropriate (57% indicated it was appropriate), while few physicians thought it appropriate to provide treatment despite one's objection (15%). The most religious physicians were more likely than the least religious physicians to support refusing to accommodate the patient's request (38% vs 22%, OR=1.75; 95% CI 1.06 to 2.86). This study indicates that US physicians believe it is inappropriate to provide an intervention that violates one's personal or professional standards. Referring seems to be physicians' preferred way of responding to requests for interventions to which physicians object. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Efficacy of vincristine and etoposide with escalating cyclophosphamide in poor-prognosis pediatric brain tumors1

PubMed Central

Ziegler, David S.; Cohn, Richard J.; McCowage, Geoffrey; Alvaro, Frank; Oswald, Cecilia; Mrongovius, Robert; White, Les

2006-01-01

The objective of this study was to assess the efficacy of the VETOPEC regimen, a regimen of vincristine and etoposide with escalating doses of cyclophosphamide (CPA), in pediatric patients with high-risk brain tumors. Three consecutive studies by the Australia and New Zealand Children’s Cancer Study Group—VETOPEC I, Baby Brain 91, and VETOPEC II—have used a specific chemotherapy regimen of vincristine (VCR), etoposide (VP-16) and escalating CPA in patients with relapsed, refractory, or high-risk solid tumors. Patients in the VETOPEC II cohort were treated with very high dose CPA with peripheral blood stem cell (PBSC) rescue. We analyzed the subset of patients with high-risk brain tumors treated with these intensive VETOPEC-based protocols to assess the response, toxicity, and survival. We also assessed whether the use of very high dose chemotherapy with stem cell rescue improved the response rate or affected toxicity. Seventy-one brain tumor patients were treated with VETOPEC-based protocols. Of the 54 patients evaluable for tumor response, 17 had a complete response (CR) and 20 a partial response (PR) to treatment, which yielded an overall response rate of 69%. The CR + PR was 83% (19/23) for medulloblastomas, 56% (5/9) for primitive neuroectodermal tumors, 55% (6/11) for grade 3 and 4 astrocytomas, and 80% (6/8) for ependymomas. At a median follow-up of 36 months, overall survival for the entire cohort of 71 patients was 32%, with event-free survival of 13%. There were no toxic deaths within the PBSC-supported VETOPEC II cohort, despite higher CPA doses, compared with 7% among the non-PBSC patients. This regimen produces high response rates in a variety of very poor prognosis pediatric brain tumors. The maximum tolerated dose of CPA was not reached. Higher escalation in doses of CPA did not deliver a further improvement in response. With PBSC rescue in the VETOPEC II study, hematologic toxicity was no longer a limiting factor. The response rates observed support further development of this chemotherapy regimen. PMID:16443948

Validation and Use of a Predictive Modeling Tool: Employing Scientific Findings to Improve Responsible Conduct of Research Education.

PubMed

Mulhearn, Tyler J; Watts, Logan L; Todd, E Michelle; Medeiros, Kelsey E; Connelly, Shane; Mumford, Michael D

2017-01-01

Although recent evidence suggests ethics education can be effective, the nature of specific training programs, and their effectiveness, varies considerably. Building on a recent path modeling effort, the present study developed and validated a predictive modeling tool for responsible conduct of research education. The predictive modeling tool allows users to enter ratings in relation to a given ethics training program and receive instantaneous evaluative information for course refinement. Validation work suggests the tool's predicted outcomes correlate strongly (r = 0.46) with objective course outcomes. Implications for training program development and refinement are discussed.

Do Physicians Respond to Web-Based Patient Ratings? An Analysis of Physicians' Responses to More Than One Million Web-Based Ratings Over a Six-Year Period.

PubMed

Emmert, Martin; Sauter, Lisa; Jablonski, Lisa; Sander, Uwe; Taheri-Zadeh, Fatemeh

2017-07-26

Physician-rating websites (PRWs) may lead to quality improvements in case they enable and establish a peer-to-peer communication between patients and physicians. Yet, we know little about whether and how physicians respond on the Web to patient ratings. The objective of this study was to describe trends in physicians' Web-based responses to patient ratings over time, to identify what physician characteristics influence Web-based responses, and to examine the topics physicians are likely to respond to. We analyzed physician responses to more than 1 million patient ratings displayed on the German PRW, jameda, from 2010 to 2015. Quantitative analysis contained chi-square analyses and the Mann-Whitney U test. Quantitative content techniques were applied to determine the topics physicians respond to based on a randomly selected sample of 600 Web-based ratings and corresponding physician responses. Overall, physicians responded to 1.58% (16,640/1,052,347) of all Web-based ratings, with an increasing trend over time from 0.70% (157/22,355) in 2010 to 1.88% (6377/339,919) in 2015. Web-based ratings that were responded to had significantly worse rating results than ratings that were not responded to (2.15 vs 1.74, P<.001). Physicians who respond on the Web to patient ratings differ significantly from nonresponders regarding several characteristics such as gender and patient recommendation results (P<.001 each). Regarding scaled-survey rating elements, physicians were most likely to respond to the waiting time within the practice (19.4%, 99/509) and the time spent with the patient (18.3%, 110/600). Almost one-third of topics in narrative comments were answered by the physicians (30.66%, 382/1246). So far, only a minority of physicians have taken the chance to respond on the Web to patient ratings. This is likely because of (1) the low awareness of PRWs among physicians, (2) the fact that only a few PRWs enable physicians to respond on the Web to patient ratings, and (3) the lack of an active moderator to establish peer-to-peer communication. PRW providers should foster more frequent communication between the patient and the physician and encourage physicians to respond on the Web to patient ratings. Further research is needed to learn more about the motivation of physicians to respond or not respond to Web-based patient ratings. ©Martin Emmert, Lisa Sauter, Lisa Jablonski, Uwe Sander, Fatemeh Taheri-Zadeh. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 26.07.2017.

The effects of short-term and long-term learning on the responses of lateral intraparietal neurons to visually presented objects

PubMed Central

Sigurdardottir, Heida M.; Sheinberg, David L.

2015-01-01

The lateral intraparietal area (LIP) of the dorsal visual stream is thought to play an important role in visually directed orienting, or the guidance of where to look and pay attention. LIP can also respond selectively to differently shaped objects. We sought to understand how and to what extent short-term and long-term experience with visual orienting can determine the nature of responses of LIP neurons to objects of different shapes. We taught monkeys to arbitrarily associate centrally presented objects of various shapes with orienting either toward or away from a preferred peripheral spatial location of a neuron. For some objects the training lasted for less than a single day, while for other objects the training lasted for several months. We found that neural responses to visual objects are affected both by such short-term and long-term experience, but that the length of the learning period determines exactly how this neural plasticity manifests itself. Short-term learning over the course of a single training session affects neural responses to objects, but these effects are only seen relatively late after visual onset; at this time, the neural responses to newly learned objects start to resemble those of familiar over-learned objects that share their meaning or arbitrary association. Long-term learning, on the other hand, affects the earliest and apparently bottom-up responses to visual objects. These responses tend to be greater for objects that have repeatedly been associated with looking toward, rather than away from, LIP neurons’ preferred spatial locations. Responses to objects can nonetheless be distinct even though the objects have both been similarly acted on in the past and will lead to the same orienting behavior in the future. Our results therefore also indicate that a complete experience-driven override of LIP object responses is difficult or impossible. PMID:25633647

First Simulations of Designing Stratospheric Sulfate Aerosol Geoengineering to Meet Multiple Simultaneous Climate Objectives

NASA Astrophysics Data System (ADS)

Kravitz, Ben; MacMartin, Douglas G.; Mills, Michael J.; Richter, Jadwiga H.; Tilmes, Simone; Lamarque, Jean-Francois; Tribbia, Joseph J.; Vitt, Francis

2017-12-01

We describe the first simulations of stratospheric sulfate aerosol geoengineering using multiple injection locations to meet multiple simultaneous surface temperature objectives. Simulations were performed using CESM1(WACCM), a coupled atmosphere-ocean general circulation model with fully interactive stratospheric chemistry, dynamics (including an internally generated quasi-biennial oscillation), and a sophisticated treatment of sulfate aerosol formation, microphysical growth, and deposition. The objectives are defined as maintaining three temperature features at their 2020 levels against a background of the RCP8.5 scenario over the period 2020-2099. These objectives are met using a feedback mechanism in which the rate of sulfur dioxide injection at each of the four locations is adjusted independently every year of simulation. Even in the presence of uncertainties, nonlinearities, and variability, the objectives are met, predominantly by SO2 injection at 30°N and 30°S. By the last year of simulation, the feedback algorithm calls for a total injection rate of 51 Tg SO2 per year. The injections are not in the tropics, which results in a greater degree of linearity of the surface climate response with injection amount than has been found in many previous studies using injection at the equator. Because the objectives are defined in terms of annual mean temperature, the required geongineering results in "overcooling" during summer and "undercooling" during winter. The hydrological cycle is also suppressed as compared to the reference values corresponding to the year 2020. The demonstration we describe in this study is an important step toward understanding what geoengineering can do and what it cannot do.

CFD-Based Design Optimization for Single Element Rocket Injector

NASA Technical Reports Server (NTRS)

Vaidyanathan, Rajkumar; Tucker, Kevin; Papila, Nilay; Shyy, Wei

2003-01-01

To develop future Reusable Launch Vehicle concepts, we have conducted design optimization for a single element rocket injector, with overall goals of improving reliability and performance while reducing cost. Computational solutions based on the Navier-Stokes equations, finite rate chemistry, and the k-E turbulence closure are generated with design of experiment techniques, and the response surface method is employed as the optimization tool. The design considerations are guided by four design objectives motivated by the consideration in both performance and life, namely, the maximum temperature on the oxidizer post tip, the maximum temperature on the injector face, the adiabatic wall temperature, and the length of the combustion zone. Four design variables are selected, namely, H2 flow angle, H2 and O2 flow areas with fixed flow rates, and O2 post tip thickness. In addition to establishing optimum designs by varying emphasis on the individual objectives, better insight into the interplay between design variables and their impact on the design objectives is gained. The investigation indicates that improvement in performance or life comes at the cost of the other. Best compromise is obtained when improvements in both performance and life are given equal importance.

The National Aeronautics and Space Administration-U.S. Public Health Service Health Evaluation and Enhancement Program - Summary of results.

NASA Technical Reports Server (NTRS)

Durbeck, D. C.; Heinzelmann, F.; Schacter, J.; Haskell, W. L.; Payne, G. H.; Moxley, R. T., III; Nemiroff, M.; Limoncelli, D. D.; Arnoldi, L. B.; Fox, S. M., III

1972-01-01

An exercise program was initiated in a federal agency to assess the feasibility of such a program, and to identify the factors that influenced joining, adherence to, and effectiveness of the program. The program was utilized by 237 of the 998 eligible federal employees; mean attendance rate was 1.3 days/week. Those who volunteered perceived a need for increased physical activity, believed they had sufficient time to participate and derived subjective as well as objective benefits. Significant improvements were found in heart rate response to the standard exercise test, body weight, skinfold measurements and triglyceride levels.

Identification of core objectives for teaching sustainable healthcare education.

PubMed

Teherani, Arianne; Nishimura, Holly; Apatira, Latifat; Newman, Thomas; Ryan, Susan

2017-01-01

Physicians will be called upon to care for patients who bear the burden of disease from the impact of climate change and ecologically irresponsible practices which harm ecosystems and contribute to climate change. However, physicians must recognize the connection between the climate, ecosystems, sustainability, and health and their responsibility and capacity in changing the status quo. Sustainable healthcare education (SHE), defined as education about the impact of climate change and ecosystem alterations on health and the impact of the healthcare industry on the aforementioned, is vital to prevention of adverse health outcomes due to the changing climate and environment. To systematically determine which and when a set of SHE objectives should be included in the medical education continuum. Fifty-two SHE experts participated in a two-part modified-Delphi study. A survey was developed based on 21 SHE objectives. Respondents rated the importance of each objective and when each objective should be taught. Descriptive statistics and an item-level content validity index (CVI) were used to analyze data. Fifteen of the objectives achieved a content validity index of 78% or greater. The remaining objectives had content validity indices between 58% and 77%. The preclinical years of medical school were rated as the optimal time for introducing 13 and the clinical years for introducing six of the objectives. Respondents noted the definition of environmental sustainability should be learned prior to medical school and identifying ways to improve the environmental sustainability of health systems in post-graduate training. This study proposes SHE objectives for the continuum of medical education. These objectives ensure the identity of the physician includes the requisite awareness and competence to care for patients who experience the impact of climate and environment on health and advocate for sustainability of the health systems in which they work. CVI: Content validity index; SHE: Sustainable healthcare education.

Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma

PubMed Central

Russell, Jeffery; Lebbé, Céleste; Chmielowski, Bartosz; Gambichler, Thilo; Grob, Jean-Jacques; Kiecker, Felix; Rabinowits, Guilherme; Terheyden, Patrick; Zwiener, Isabella; Bajars, Marcis; Hennessy, Meliessa; Kaufman, Howard L.

2018-01-01

Importance Merkel cell carcinoma (MCC) is an aggressive skin cancer that is associated with poor survival outcomes in patients with distant metastatic disease. Results of part A of the JAVELIN Merkel 200 trial (avelumab in patients with Merkel cell carcinoma) showed that avelumab, an anti–programmed cell death ligand 1 (PD-L1) antibody, demonstrated efficacy in second-line or later treatment of patients with metastatic MCC (mMCC). Objective To evaluate the efficacy and safety of avelumab as first-line treatment for patients with distant mMCC. Design, Setting, and Participants JAVELIN Merkel 200 part B is an international, multicenter, single-arm, open-label clinical trial of first-line avelumab monotherapy. Eligible patients were adults with mMCC who had not received prior systemic treatment for metastatic disease. Patients were not selected for PD-L1 expression or Merkel cell polyomavirus status. Data were collected from April 15, 2016, to March 24, 2017, and enrollment is ongoing. Interventions Patients received avelumab, 10 mg/kg, by 1-hour intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxic effects, or withdrawal occurred. Main Outcomes and Measures Tumor status was assessed every 6 weeks and evaluated by independent review committee per Response Evaluation Criteria in Solid Tumors version 1.1. The primary end point was durable response, defined as an objective response with a duration of at least 6 months. Secondary end points include best overall response, duration of response, progression-free survival, safety, and tolerability. Results As of March 24, 2017, 39 patients were enrolled (30 men and 9 women; median age, 75 years [range, 47-88 years]), with a median follow-up of 5.1 months (range, 0.3-11.3 months). In a preplanned analysis, efficacy was assessed in 29 patients with at least 3 months of follow-up; the confirmed objective response rate was 62.1% (95% CI, 42.3%-79.3%), with 14 of 18 responses (77.8%) ongoing at the time of analysis. In responding patients, the estimated proportion with duration of response of at least 3 months was 93% (95% CI, 61%-99%); duration of response of at least 6 months, 83% (95% CI, 46%-96%). First-line avelumab treatment was generally well tolerated, and no treatment-related deaths or grade 4 adverse events occurred. Conclusions and Relevance High rates of response to first-line avelumab therapy in patients with distant mMCC build on previously reported antitumor activity after second-line or later treatment, and maturing progression-free survival data suggest that responses are durable. These data further support avelumab’s approval in the United States and European Union and use as a standard-of-care treatment for mMCC. Trial Registration clinicaltrials.gov Identifier: NCT02155647 PMID:29566106

The relationship between back pain and lead apron use in radiologists.

PubMed

Moore, B; vanSonnenberg, E; Casola, G; Novelline, R A

1992-01-01

Anecdotal experience has suggested that back pain in radiologists may result from extensive wearing of lead aprons. To investigate this possibility, we sent questionnaires to 688 radiologists in various subspecialties whose use of lead aprons varied from none to moderate to extensive. The questionnaire included both objective items that quantitated apron use and back pain and subjective items that asked, for example, if the respondent believed that lead aprons were responsible for his or her back pain. We received 236 responses (34% response rate). Objective data from those radiologists who had experienced no back pain before wearing a lead apron (179 radiologists, 26% of those surveyed) were tabulated; respondents were grouped according to age, time spent wearing a lead apron, and degree of back pain. Odds ratios were calculated. Answers to subjective questions for all respondents were tabulated. Back pain was reported by 52% of those who estimated their lead apron use at greater than or equal to 10 hr per week, the mean response, as opposed to 46% of those who wore lead aprons fewer than 10 hr a week. These and related results were not statistically significant. Our study does not prove that wearing a lead apron is a significant risk factor for the development of back pain.

Piezoelectric vibrator-stimulated potential and heart rate accelerations detected from the fetus.

PubMed

Matsuoka, Rina; Lee, Sinyoung; Sato, Miho; Hibiya, Remi; Shimanuki, Yota; Kasai, Misato; Kamiya, Kazusaku; Itakura, Atsuo; Koike, Takuji; Ikeda, Katsuhisa

2017-10-01

The fetus is well known to have a substantial capacity for sound recognition in the uterine environment. The aim of this study was to develop a sound stimulus system equipped with a piezoelectric vibrator (PV), record the PV-stimulated potential (PVSP) of the fetus and monitor changes of the fetal heart rate (FHR) under PV stimulation. The relationship between the input voltage applied to a piezoelectric vibrator and the sound pressure generated in the uterus was calibrated based on a model of the maternal abdomen. Fourteen fetuses for the measurement of the PVSP and 22 fetuses for the measurement of the heart rate changes from low-risk pregnant women were recruited. The PVSP responses were obtained in 9 out of 14 fetuses. All the tested fetuses accelerated the FHR after the 2 kHz tone stimulation at 70 dB intensity generated by PV from 32 to 37 weeks gestational age. Using a newly developed sound stimulus system equipped with PV, the electric responses of a fetus recorded from electrodes placed on the mother's abdomen may be closely related to the auditory evoked response. Significant accelerations of FHR were objectively, accurately and readily obtained after the sound stimulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Management of malignant pleural mesothelioma: a French multicenter retrospective study (GFPC 0802 study).

PubMed

Raynaud, C; Greillier, L; Mazieres, J; Monnet, I; Mastroianni, B; Robinet, G; Fraboulet, G; Dixmier, A; Berard, H; Lamy, R; Letreut, J; Lena, H; Oliviero, G; Botta, S; Vergnenegre, A; Borget, I; Chouaid, C

2015-11-06

Malignant pleural mesothelioma (MPM) is a rare disease with poor prognosis in spite of significant improvement in survival, due to new chemotherapy regimens. We describe here patients' profiles and management in daily practice in France. Observational retrospective study. Data were collected from medical files. All patients with histologically proven MPM diagnosed from January 2005 to December 2008 were included in the participating sites. Four hundred and six patients were included in 37 sites: mean age 68.9 ± 9.8 years, male predominance (sex ratio 3.27), latency of the disease 45.7 years, epithelioïd type 83 %. Diagnosis was made using thoracoscopy in 80.8 % of patients. Radical surgery was performed in 6.2 % of cases. Chemotherapy was administered to 74.6 % of patients. First line regimens consisted mainly of platinum + pemetrexed (91 %) or pemetrexed alone (7 %). Objective response rate was 17.2 % and another 41.6 % of patients experienced disease stabilization. Half of these patients underwent second line chemotherapy (platinium + pemetrexed 31.6 %, pemetrexed alone 24.6 %), resulting in a 6 % response rate. Third-line chemotherapy (56 patients) yielded disease control in 5.4 % of cases. The management of MPM in France is usually in accordance with guidelines. Response rates are somewhat lower than those described in clinical trials.

Unilateral versus bilateral thyroarytenoid Botulinum toxin injections in adductor spasmodic dysphonia: a prospective study

PubMed Central

Upile, Tahwinder; Elmiyeh, Behrad; Jerjes, Waseem; Prasad, Vyas; Kafas, Panagiotis; Abiola, Jesuloba; Youl, Bryan; Epstein, Ruth; Hopper, Colin; Sudhoff, Holger; Rubin, John

2009-01-01

Objectives In this preliminary prospective study, we compared unilateral and bilateral thyroarytenoid muscle injections of Botulinum toxin (Dysport) in 31 patients with adductor spasmodic dysphonia, who had undergone more than 5 consecutive Dysport injections (either unilateral or bilateral) and had completed 5 concomitant self-rated efficacy and complication scores questionnaires related to the previous injections. We also developed a Neurophysiological Scoring (NPS) system which has utility in the treatment administration. Method and materials Data were gathered prospectively on voice improvement (self-rated 6 point scale), length of response and duration of complications (breathiness, cough, dysphagia and total voice loss). Injections were performed under electromyography (EMG) guidance. NPS scale was used to describe the EMG response. Dose and unilateral/bilateral injections were determined by clinical judgment based on previous response. Time intervals between injections were patient driven. Results Low dose unilateral Dysport injection was associated with no significant difference in the patient's outcome in terms of duration of action, voice score (VS) and complication rate when compared to bilateral injections. Unilateral injections were not associated with any post treatment total voice loss unlike the bilateral injections. Conclusion Unilateral low dose Dysport injections are recommended in the treatment of adductor spasmodic dysphonia. PMID:19852852

Salivary habituation to food stimuli in successful weight loss maintainers, obese and normal-weight adults

PubMed Central

Bond, DS; Raynor, HA; McCaffery, JM; Wing, RR

2017-01-01

Objective Research shows that slower habituation of salivary responses to food stimuli is related to greater energy intake and that obese (Ob) individuals habituate slower than those of normal weight (NW). No study has examined habituation rates in weight loss maintainers (WLMs) who have reduced from obese to normal weight, relative to those who are Ob or NW. Design Salivation to two baseline water trials and 10 lemon-flavored lollipop trials were studied in 14 WLMs, 15 Ob and 18 NW individuals comparable in age, gender and ethnicity. Linear mixed models were used to compare WLMs with Ob and NW groups. Results Salivation in the WLM and NW groups decreased significantly (for both P <0.005) across trials, indicative of habituation. Salivary responses in the Ob group did not habituate (P=0.46). When compared with Ob group, WLMs showed a quicker reduction in salivation (P<0.05). WLM and NW groups did not differ in habituation rate (P=0.49). Conclusions WLMs have habituation rates that are comparable to NW individuals without previous history of obesity, and show quicker habituation than those who are currently obese. These results suggest that physiological responses to food may ‘normalize’ with successful weight loss maintenance. PMID:20010900

How Do Microfinance Programs Contribute to Poverty Reduction

DTIC Science & Technology

2016-09-01

areas have experienced statistically higher incidents of crime tied to class conflict.90 Land tax systems under the British were also responsible for...countries.173 This low delinquency rate is credited to the lack of alternative opportunities that are available to the poor.174 According to Muhammad...TOTAL: 909 54.6 60.2 55 Figure 2. Program Duration and Objective Poverty.197 The statistical analysis conducted by Chowdhury, Gosh and Wright finds

Million Degree Plasmas in Extreme Ultraviolet (EUV) Astrophysics. White Paper in Response to Astro2010 Science Call

DTIC Science & Technology

2010-01-01

photometry , timing measurements of suitable cadence, and advanced theory are the keys to understanding the physics of million degree plasmas in...Disentangling these components requires time - and phase- resolved spectroscopic observations of a sample that spans a range of mass accretion rates...many narrow lines, or a continuum with strong, broad absorption features. Key Objective: Obtaining time - and phase- resolved high-resolution EUV

First Spanish version of the Memorial Delirium Assessment Scale: psychometric properties, responsiveness, and factor loadings.

PubMed

Noguera, Antonio; Carvajal, Ana; Alonso-Babarro, Alberto; Chisholm, Gary; Bruera, Eduardo; Centeno, Carlos

2014-01-01

The Memorial Delirium Assessment Scale (MDAS) is a reliable and validated instrument with which to assess delirium. However, MDAS responsiveness has only been investigated in an indirect way. Also, neurobehavioral and global cognitive factors seem to be the MDAS main factor loads. The primary objective of this study was to evaluate MDAS responsiveness and analyze individual factors on this scale. The secondary objective was to confirm concurrent validity and reliability of the Spanish version of the MDAS. The translation-back translation method was used to obtain the Spanish version of the MDAS. Delirium diagnosis was determined by the clinical Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria and with the Confusion Assessment Method. Responsiveness and factor loadings were determined with the Delirium Rating Scale-Revised-98, the Mini-Mental State Examination (MMSE), and the MDAS at baseline (0 hours) and at 72 hours. Variation in the scores of the Delirium Rating Scale-Revised-98 shows a correlation of r = 0.93, with variation in MDAS scores at P < 0.001. Variation in MMSE scores shows a correlation of r = -0.84, with variation in MDAS scores at P = 0.015. Factor I, neurobehavioral (reduced awareness, reduced attention, perceptual disturbance, delusions, altered psychomotor activity, and sleep-wake cycle disturbance), correlated moderately with the MMSE at -0.56. Factor II, global cognitive (disorientation, short-term memory impairment, impaired digit span, and disorganized thinking), correlated strongly with the MMSE at -0.81. Factor II was significantly more reliable than Factor I, rho = 0.7, P = 0.01. The high responsiveness confirms the value of the MDAS for ongoing delirium assessment. Two differentiated factor loadings point to a potential future need for MDAS subscales. Copyright © 2014 U.S. Cancer Pain Relief Committee. All rights reserved.

Impact of tumor size on outcome after stereotactic body radiation therapy for inoperable hepatocellular carcinoma

PubMed Central

Kuo, Hsing-Tao; Que, Jenny; Lin, Li-Ching; Yang, Ching-Chieh; Koay, Lok-Beng; Lin, Chia-Hui

2017-01-01

Abstract Stereotactic body radiation therapy (SBRT) for inoperable hepatocellular carcinoma (HCC) offers excellent local control rates. This study retrospectively analyzed the influence of different tumor size on treatment outcomes after SBRT. Between December 2008 and February 2014, 141 HCC patients were treated with Cyberknife SBRT. Patients were divided into 3 groups namely small tumors (≤4 cm), intermediate-sized (>4–<10 cm), and large (≥10 cm) tumors. Treatment outcomes, prognoses, and safety at each tumor size were compared and analyzed. A total of 52 patients with small tumors, 55 with intermediate tumors, and 34 patients with large tumors were retrospectively analyzed with a median follow-up of 16 months. Objective responses were achieved at 96.15%, 90.90%, and 76.47% for small, intermediate, and large tumors, respectively (P ≤ .0001) and the 3-year local control rates were 97.85%, 71.99%, and 82.14%, respectively (P = .0035). The 3-year overall survival rates were 50.26%, 45.29%, and 33.38% for small, intermediate, and large tumors, respectively (P = .3757). No significant differences were found in overall-survival, intra-hepatic recurrence free survival, disease-progression free survival, or distant metastasis-free survival. SBRT offers the best effective local control rate and response rate for small HCCs. However, tumor size did not significantly affect the overall survival rate, intra-hepatic recurrence free rate, or disease-progression free rate. PMID:29390360

E-learning and the future of dental education: opinions of administrators and information technology specialists.

PubMed

Hillenburg, K L; Cederberg, R A; Gray, S A; Hurst, C L; Johnson, G K; Potter, B J

2006-08-01

The digital revolution and growth of the Internet have led to many innovations in the area of electronic learning (e-learning). To survive and prosper, educators must be prepared to respond creatively to these changes. Administrators and information technology specialists at six dental schools and their parent institutions were interviewed regarding their opinions of the impact that e-learning will have on the future of dental education. Interview questions encompassed vision, rate of change, challenges, role of faculty, resources, enrolment, collaboration, responsibility for course design and content, mission and fate of the institution. The objective of this qualitative study was to sample the opinions of educational administrators and information technology specialists from selected US universities regarding the impact of e-learning on dental education to detect trends in their attitudes. Responses to the survey indicated disagreement between administrators and informational technology specialists regarding the rate of change, generation of resources, impact on enrolment, responsibility for course design and content, mission and fate of the university. General agreement was noted with regard to vision, challenges, role of faculty and need for collaboration.

Modeling of zero gravity venting: Studies of two-phase heat transfer under reduced gravity

NASA Technical Reports Server (NTRS)

Merte, H., Jr.

1986-01-01

The objective is to predict the pressure response of a saturated liquid-vapor system when undergoing a venting or depressurization process in zero gravity at low vent rates. An experimental investigation of the venting of cylindrical containers partially filled with initially saturated liquids was previously conducted under zero-gravity conditions and compared with an analytical model which incorporated the effect of interfacial mass transfer on the ullage pressure response during venting. A new model is presented to improve the estimation of the interfacial mass transfer. Duhammel's superposition integral is incorporated to approximate the transient temperature response of the interface, treating the liquid as a semi-infinite solid with conduction heat transfer. Account is also taken of the condensation taking place within the bulk of a saturated vapor as isentropic expansion takes place. Computational results are presented for the venting of R-11 from a given vessel and initial state for five different venting rates over a period of three seconds, and compared to prior NASA experiments. An improvement in the prediction of the final pressure takes place, but is still considerably below the measurements.

Dietary restraint and impulsivity modulate neural responses to food in adolescents with obesity and healthy adolescents.

PubMed

Hofmann, Johannes; Ardelt-Gattinger, Elisabeth; Paulmichl, Katharina; Weghuber, Daniel; Blechert, Jens

2015-11-01

Despite alarming prevalence rates, surprisingly little is known about neural mechanisms underlying eating behavior in juveniles with obesity. To simulate reactivity to modern food environments, event-related potentials (ERP) to appetizing food images (relative to control images) were recorded in adolescents with obesity and healthy adolescents. Thirty-four adolescents with obesity (patients) and 24 matched healthy control adolescents watched and rated standardized food and object images during ERP recording. Personality (impulsivity) and eating styles (trait craving and dietary restraint) were assessed as potential moderators. Food relative to object images triggered larger early (P100) and late (P300) ERPs. More impulsive individuals had considerably larger food-specific P100 amplitudes in both groups. Controls with higher restraint scores showed reduced food-specific P300 amplitudes and subjective palatability ratings whereas patients with higher restraint scores showed increased P300 and palatability ratings. This first ERP study in adolescents with obesity and controls revealed impulsivity as a general risk factor in the current obesogenic environment by increasing food-cue salience. Dietary restraint showed paradoxical effects in patients, making them more vulnerable to visual food-cues. Salutogenic therapeutic approaches that deemphasize strict dietary restraint and foster healthy food choice might reduce such paradoxical effects. © 2015 The Obesity Society.

Dynamic Creep Buckling: Analysis of Shell Structures Subjected to Time-dependent Mechanical and Thermal Loading

NASA Technical Reports Server (NTRS)

Simitses, G. J.; Carlson, R. L.; Riff, R.

1985-01-01

The objective of the present research is to develop a general mathematical model and solution methodologies for analyzing the structural response of thin, metallic shell structures under large transient, cyclic, or static thermomechanical loads. Among the system responses associated with these loads and conditions are thermal buckling, creep buckling, and ratcheting. Thus geometric and material nonlinearities (of high order) can be anticipated and must be considered in developing the mathematical model. A complete, true ab-initio rate theory of kinematics and kinetics for continuum and curved thin structures, without any restriction on the magnitude of the strains or the deformations, was formulated. The time dependence and large strain behavior are incorporated through the introduction of the time rates of metric and curvature in two coordinate systems: fixed (spatial) and convected (material). The relations between the time derivative and the covariant derivative (gradient) were developed for curved space and motion, so the velocity components supply the connection between the equations of motion and the time rates of change of the metric and curvature tensors.

Effects of icotinib on advanced non-small cell lung cancer with different EGFR phenotypes.

PubMed

Pan, Huiyun; Liu, Rong; Li, Shengjie; Fang, Hui; Wang, Ziwei; Huang, Sheng; Zhou, Jianying

2014-09-01

Icotinib is the first oral epidermal growth factor receptor (EGFR) tyrosine kinase receptor inhibitor, which has been proven to exert significant inhibitory effects on non-small cell lung cancer in vitro. Clinical evidence has showed that the efficacy of Icotinib on retreating advanced non-small cell lung cancer is comparable to Gefitinib. However, different phenotypes of EGFR can affect the therapeutic outcomes of EGFR tyrosine kinase receptor inhibitor. Therefore, our study focused on efficacy and safety of Icotinib in patients with advanced non-small cell lung cancer of different EGPR phenotypes. Clinical data of patients with advanced non-small cell lung cancer who received Icotinib treatment from August, 2011 to May, 2013 were retrospectively analyzed. Kaplan-Meier analysis was used for survival analysis and comparison. 18 wild-type EGFR and 51 mutant type were found in a total of 69 patients. Objective response rate of patients with mutant type EGFR was 54.9 % and disease control rate was 86.3 %. Objective response rate of wild-type patients was 11.1 % (P = 0.0013 vs mutant type), disease control rate was 50.0 % (P = 0.0017). Median progression-free survival (PFS) of mutant type and wild-type patients were 9.7 and 2.6 months, respectively (P < 0.001). Median PFS of exon 19 mutated mutant patients was 11.3 months, mean PFS of exon 21 L858R mutated mutant patients was 8.7 months (P = 0.3145). Median overall survival (OS) of EGFR mutated patients had not reached. OS time of 13 wild-type patients was 12.9 months (P < 0.001). The common adverse reactions of Icotinib included rash, diarrhea, itching skin with occurrence rates of 24.6 % (17/69), 13.0 % (9/69), and 11.6 % (8/69), respectively. Most adverse reactions were grade I-II. Icotinib has great efficacy in EGFR mutated patients, making it an optimal regimen to treat EGFR mutated patients. Furthermore, most of adverse reactions associated with Icotinib treatment were tolerable.

A Pediatric Cardiology Fellowship Boot Camp improves trainee confidence.

PubMed

Allan, Catherine K; Tannous, Paul; DeWitt, Elizabeth; Farias, Michael; Mansfield, Laura; Ronai, Christina; Schidlow, David; Sanders, Stephen P; Lock, James E; Newburger, Jane W; Brown, David W

2016-12-01

Introduction New paediatric cardiology trainees are required to rapidly assimilate knowledge and gain clinical skills to which they have limited or no exposure during residency. The Pediatric Cardiology Fellowship Boot Camp (PCBC) at Boston Children's Hospital was designed to provide incoming fellows with an intensive exposure to congenital cardiac pathology and a broad overview of major areas of paediatric cardiology practice. The PCBC curriculum was designed by core faculty in cardiac pathology, echocardiography, electrophysiology, interventional cardiology, exercise physiology, and cardiac intensive care. Individual faculty contributed learning objectives, which were refined by fellowship directors and used to build a programme of didactics, hands-on/simulation-based activities, and self-guided learning opportunities. A total of 16 incoming fellows participated in the 4-week boot camp, with no concurrent clinical responsibilities, over 2 years. On the basis of pre- and post-PCBC surveys, 80% of trainees strongly agreed that they felt more prepared for clinical responsibilities, and a similar percentage felt that PCBC should be offered to future incoming fellows. Fellows showed significant increase in their confidence in all specific knowledge and skills related to the learning objectives. Fellows rated hands-on learning experiences and simulation-based exercises most highly. We describe a novel 4-week-long boot camp designed to expose incoming paediatric cardiology fellows to the broad spectrum of knowledge and skills required for the practice of paediatric cardiology. The experience increased trainee confidence and sense of preparedness to begin fellowship-related responsibilities. Given that highly interactive activities were rated most highly, boot camps in paediatric cardiology should strongly emphasise these elements.

Efficacy and safety of Apatinib in stage IV sarcomas: experience of a major sarcoma center in China.

PubMed

Li, Feng; Liao, Zhichao; Zhao, Jun; Zhao, Gang; Li, Xubin; Du, Xiaoling; Yang, Yun; Yang, Jilong

2017-09-08

This study was conducted to review the efficacy and safety of Apatinib in stage IV sarcoma patients who failed previous chemotherapy. The clinical information on 16 patients with stage IV sarcomas who failed in prior chemotherapy and subsequently received Apatinib treatment was collected. Apatinib was given 500mg/daily and 4 weeks as a cycle. All patients had at least one measurable extracranial tumor according to Response Evaluation Criteria In Solid Tumors 1.0 criteria. Progression free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and treatment-related adverse effects (AEs) were reviewed and evaluated. Patients was administered Apatinib for 0 to 9 cycles with the median of 3.2 cycles. Median follow-up time was 8.4 months (1 to 12 months). Ten of 16 patients received at least 1 complete cycle of Apatinib treatment were eligible for the efficacy analysis. The median PFS was 8.84 months. Two patients achieved partial response (PR) and 6 patients achieved stable disease (SD). Two patients were evaluated as progression disease (PD) and one patient died of disease progression. The ORR was 20.0% (2/10) and the DCR was 80.0% (8/10). The most common grade 3/4 treatment-related AEs were hypertension (18.7%), hand-foot syndrome (12.5%) and proteinuria (6.3%). No drug-related severe AEs occurred. CApatinib treatment in this exploratory study exhibited objective efficacy and manageable toxicity in stage IV sarcoma patients who failed in chemotherapy. This result supports future random controlled trial to further define Apatinib activity in stage IV sarcomas.

Efficacy of Exemestane in Korean Patients with Metastatic Breast Cancer after Failure of Nonsteroidal Aromatase Inhibitors

PubMed Central

Lee, June Koo; Lee, Daewon; Kim, Ji-Yeon; Lim, Yoojoo; Lee, Eunyoung; Moon, Hyeong-Gon; Kim, Tae-Yong; Han, Sae-Won; Oh, Do-Youn; Lee, Se-Hoon; Han, Wonshik; Kim, Dong-Wan; Kim, Tae-You; Noh, Dong-Young

2013-01-01

Purpose Exemestane has shown good efficacy and tolerability in postmenopausal women with hormone receptor-positive metastatic breast cancer. However, clinical outcomes in Korean patients have not yet been reported. Methods Data on 112 postmenopausal women with metastatic breast cancer were obtained retrospectively. Clinicopathological characteristics and treatment history were extracted from medical records. All patients received 25 mg exemestane daily until objective disease progression. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR=complete response+partial response+stable disease for 6 months). Results The median age of the subjects was 55 years (range, 28-76 years). Exemestane treatment resulted in a median PFS of 5.7 months (95% confidence interval [CI], 4.4-7.0 months) and median OS of 21.9 months (95% CI, 13.6-30.3 months). ORR was 6.4% and CBR was 46.4% for the 110 patients with evaluable lesions. Symptomatic visceral disease was independently associated with shorter PFS (hazard ratio, 3.611; 95% CI, 1.904-6.848; p<0.001), compared with bone-dominant disease in a multivariate analysis of PFS after adjusting for age, hormone receptor, human epidermal growth factor receptor 2, Ki-67 status, dominant metastasis site, and sensitivity to nonsteroidal aromatase inhibitor (AI) treatment. Sensitivity to previous nonsteroidal AI treatment was not associated with PFS, suggesting no cross-resistance between exemestane and nonsteroidal AIs. Conclusion Exemestane was effective in postmenopausal Korean women with hormone receptor-positive metastatic breast cancer who failed previous nonsteroidal AI treatment. PMID:23593084

Measuring methylphenidate response in attention-deficit/hyperactvity disorder: how are laboratory classroom-based measures related to parent ratings?

PubMed

Sonuga-Barke, Edmund J S; Coghill, David; DeBacker, Marc; Swanson, James

2009-12-01

Methylphenidate (MPH) is an efficacious and normally well-tolerated treatment for attention-deficit/hyperactivity disorder (ADHD). Although treatment effects are usually assessed using parent-rating scales, these can be supplemented by more objective methods. Here we examine the associations between ratings and one such method, assessments made across the day in the laboratory classroom. Comparison of Methylphenidates in the Analog Classroom Setting (COMACS) was made in a large (n = 184) placebo-controlled trial comparing Equasym XL/Metadate CD, Concerta, and placebo (PLA) using a Laboratory School protocol. Therapeutic effects were measured using direct observation, scores on a simple math productivity task and parent ratings. Treatment effects were observed on all measures. Laboratory measures were correlated with each other, most strongly between Swanson, Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP) inattention and Permanent Product Measure of Performance (PERMP). Parental ratings were correlated with classroom measures during the main morning period (1.5-4.5 hours after dosing) and to a lesser extent in the afternoon (6.0-7.5 hours after dosing), but not, by and large, immediately after dosing or in the evening. The morning correlations seemed stronger for female than for male participants. The results suggest that parental ratings and direct observations tap different aspects of MPH response and that both may be required for comprehensive assessment.

Depression-related increases and decreases in appetite reveal dissociable patterns of aberrant activity in reward and interoceptive neurocircuitry

PubMed Central

Simmons, W. Kyle; Burrows, Kaiping; Avery, Jason A.; Kerr, Kara L.; Bodurka, Jerzy; Savage, Cary R.; Drevets, Wayne C.

2016-01-01

Objective Appetite and weight changes are common but variable diagnostic markers in major depressive disorder: some depressed individuals manifest increased appetite, while others lose their appetite. Many of the brain regions implicated in appetitive responses to food have also been implicated in depression. It is thus remarkable that there exists no published research comparing the neural responses to food stimuli of depressed patients with increased versus decreased appetites. Method Using functional magnetic resonance imaging we compared brain activity in unmedicated depressed patients with increased or decreased appetite, and healthy control subjects, while viewing photographs of food and non-food objects. We also measured how resting-state functional connectivity related to subjects’ food pleasantness ratings. Results Within putative reward regions, depressed participants with increased appetites exhibited greater hemodynamic activity to food stimuli than both those reporting appetite decreases and healthy control subjects. In contrast, depressed subjects experiencing appetite loss exhibited hypoactivation within a region of the mid-insula implicated in interoception, with no difference observed in this region between healthy subjects and those with depression-related appetite increases. Mid-insula activity was negatively correlated with food pleasantness ratings of depressed participants with increased appetites, and its functional connectivity to reward circuitry was positively correlated with food pleasantness ratings. Conclusions Depression-related increases in appetite are associated with hyperactivation of putative mesocorticolimbic reward circuitry, while depression-related appetite loss is associated with hypoactivation of insular regions that support monitoring the body’s physiological state. Importantly, the interactions among these regions also contribute to individual differences in the depression-related appetite changes. PMID:26806872

Guidance, Navigation, and Control Performance for the GOES-R Spacecraft

NASA Technical Reports Server (NTRS)

Chapel, Jim; Stancliffe, Devin; Bevacqua, TIm; Winkler, Stephen; Clapp, Brian; Rood, Tim; Gaylor, David; Freesland, Doug; Krimchansky, Alexander

2014-01-01

The Geostationary Operational Environmental Satellite-R Series (GOES-R) is the first of the next generation geostationary weather satellites. The series represents a dramatic increase in Earth observation capabilities, with 4 times the resolution, 5 times the observation rate, and 3 times the number of spectral bands. GOES-R also provides unprecedented availability, with less than 120 minutes per year of lost observation time. This paper presents the Guidance Navigation & Control (GN&C) requirements necessary to realize the ambitious pointing, knowledge, and Image Navigation and Registration (INR) objectives of GOES-R. Because the suite of instruments is sensitive to disturbances over a broad spectral range, a high fidelity simulation of the vehicle has been created with modal content over 500 Hz to assess the pointing stability requirements. Simulation results are presented showing acceleration, shock response spectra (SRS), and line of sight (LOS) responses for various disturbances from 0 Hz to 512 Hz. Simulation results demonstrate excellent performance relative to the pointing and pointing stability requirements, with LOS jitter for the isolated instrument platform of approximately 1 micro-rad. Attitude and attitude rate knowledge are provided directly to the instrument with an accuracy defined by the Integrated Rate Error (IRE) requirements. The data are used internally for motion compensation. The final piece of the INR performance is orbit knowledge, which GOES-R achieves with GPS navigation. Performance results are shown demonstrating compliance with the 50 to 75 m orbit position accuracy requirements. As presented in this paper, the GN&C performance supports the challenging mission objectives of GOES-R.

A note on attitudes and knowledge concerning environmental issues in Sweden.

PubMed

Boman, Mattias; Mattsson, Leif

2008-02-01

As part of a larger research effort, the empirical basis for this note is responses to four out of many questions in a mailed survey, which primarily focused on national environmental objectives in Sweden. The results show that out of eight broad areas for use of tax money, five-including environment-are rated as important by over 90% of the respondents. Respondents appear to be less willing to discriminate between different issues covered by national environmental objectives, as all of these are rated as important by more than 80% of the respondents. The function of the ozone layer is an example of an environmental issue where the knowledge among people is relatively high, while this is not the case when it comes to the amount of pesticides used in agriculture. The results also show less support for actions at the individual level to improve the environment, as compared to support for actions taken by society at large through, e.g., technological improvement or policy intervention.

Improvements in Space Surveillance Processing for Wide Field of View Optical Sensors

NASA Astrophysics Data System (ADS)

Sydney, P.; Wetterer, C.

2014-09-01

For more than a decade, an autonomous satellite tracking system at the Air Force Maui Optical and Supercomputing (AMOS) observatory has been generating routine astrometric measurements of Earth-orbiting Resident Space Objects (RSOs) using small commercial telescopes and sensors. Recent work has focused on developing an improved processing system, enhancing measurement performance and response while supporting other sensor systems and missions. This paper will outline improved techniques in scheduling, detection, astrometric and photometric measurements, and catalog maintenance. The processing system now integrates with Special Perturbation (SP) based astrodynamics algorithms, allowing covariance-based scheduling and more precise orbital estimates and object identification. A merit-based scheduling algorithm provides a global optimization framework to support diverse collection tasks and missions. The detection algorithms support a range of target tracking and camera acquisition rates. New comprehensive star catalogs allow for more precise astrometric and photometric calibrations including differential photometry for monitoring environmental changes. This paper will also examine measurement performance with varying tracking rates and acquisition parameters.

Psychophysiological responses to masked auditory stimuli.

PubMed

Borgeat, F; Elie, R; Chaloult, L; Chabot, R

1985-02-01

Psychophysiological responses to masked auditory verbal stimuli of increasing intensities were studied in twenty healthy women. Two experimental sessions corresponding to two stimulation contents (neutral or emotional) were conducted. At each session, two different sets of instructions (attending or not attending to stimuli) were used successively. Verbal stimuli, masked by a 40-dB white noise, were presented to the subject at increasing intensities by increments of 5 dB starting at 0 dB. At each increment, frontal EMG, skin conductance and heart rate were recorded. The data were submitted to analyses of variance and covariance. Psychophysiological responses to stimuli below the thresholds of identification and detection were observed. The instruction not to attend the stimuli modified the patterns of physiological responses. The effect of the affective content of the stimuli on responses was stronger when not attending. The results show the possibility of psychophysiological responses to masked auditory stimuli and suggests that psychophysiological parameters can constitute objective and useful measures for research in auditory subliminal perception.

Venetoclax for Patients With Chronic Lymphocytic Leukemia With 17p Deletion: Results From the Full Population of a Phase II Pivotal Trial.

PubMed

Stilgenbauer, Stephan; Eichhorst, Barbara; Schetelig, Johannes; Hillmen, Peter; Seymour, John F; Coutre, Steven; Jurczak, Wojciech; Mulligan, Stephen P; Schuh, Anna; Assouline, Sarit; Wendtner, Clemens-Martin; Roberts, Andrew W; Davids, Matthew S; Bloehdorn, Johannes; Munir, Talha; Böttcher, Sebastian; Zhou, Lang; Salem, Ahmed Hamed; Desai, Monali; Chyla, Brenda; Arzt, Jennifer; Kim, Su Young; Verdugo, Maria; Gordon, Gary; Hallek, Michael; Wierda, William G

2018-07-01

Purpose Venetoclax is an orally bioavailable B-cell lymphoma 2 inhibitor. US Food and Drug Administration and European Medicines Agency approval for patients with 17p deleted relapsed/refractory chronic lymphocytic leukemia [del(17p) CLL] was based on results from 107 patients. An additional 51 patients were enrolled in a safety expansion cohort. Extended analysis of all enrolled patients, including the effect of minimal residual disease (MRD) negativity on outcome, is now reported. Patients and Methods Overall, 158 patients with relapsed/refractory or previously untreated (n = 5) del(17p) CLL received venetoclax 400 mg per day after an initial dose ramp up. Responses were based on 2008 International Workshop on Chronic Lymphocytic Leukemia criteria, with monthly physical exams and blood counts. Computed tomography scan was mandatory at week 36, after which assessment made was by clinical evaluation. Marrow biopsy was performed when complete remission was suspected. MRD was assessed by flow cytometry. Results Patients had a median of two prior therapies (range, zero to 10 therapies), 71% had TP53 mutation, and 48% had nodes that were ≥ 5 cm. Median time on venetoclax was 23.1 months (range, 0 to 44.2 months) and median time on study was 26.6 months (range, 0 to 44.2 months). For all patients, investigator-assessed objective response rate was 77% (122 of 158 patients; 20% complete remission) and estimated progression-free survival at 24 months was 54% (95% CI, 45% to 62%). For 16 patients who received prior kinase inhibitors, objective response rate was 63% (10 of 16 patients) and 24-month progression-free survival estimate was 50% (95% CI, 25% to 71%). By intent-to-treat analysis, 48 (30%) of 158 patients achieved MRD below the cutoff of 10 -4 in blood. Common grade 3 and 4 adverse events were hematologic and managed with supportive care and/or dose adjustments. Conclusion Venetoclax achieves durable responses and was well tolerated in patients with del(17p) CLL. A high rate of blood MRD < 10 -4 was achieved in this high-risk population.

A Prospective Phase II Study of Cisplatin and Cremophor EL-Free Paclitaxel (Genexol-PM) in Patients with Unresectable Thymic Epithelial Tumors.

PubMed

Kim, Hae Su; Lee, Ji Yun; Lim, Sung Hee; Sun, Jong-Mu; Lee, Se Hoon; Ahn, Jin Seok; Park, Keunchil; Moon, Seung Hwan; Ahn, Myung-Ju

2015-12-01

We conducted a prospective phase II study of cisplatin plus cremophor EL-free paclitaxel (Genexol-PM) in patients with unresectable thymic epithelial tumors to determine the efficacy and tolerability of the combination therapy. Patients were treated with cisplatin (70 mg/m) and Genexol-PM (230 mg/m) on day 1 of a 3-week cycle as first-line palliative chemotherapy. The primary end point of this study was objective response rate, and the secondary end points included toxicity, progression-free survival (PFS), overall survival, correlation between early 18F-fluorodeoxyglucose positron emission tomography/computed tomography response and PFS, and correlation between baseline flurododeoxyglucose uptake and histology. Forty-two patients with unresectable thymoma (n = 14) or thymic carcinoma (n = 28) were enrolled between May 2012 and October 2014. The median age was 59 years (range: 25-77) and 30 patients (71%) were male, and 39 patients (93%) had an ECOG PS of 1. The median number of treatment cycles was six (range: 1-6). For 40 assessable patients, the objective response rate was 62.5% (95% confidence interval [CI]: 47.6-77.4) with rates of 46% (95% CI: 23.3-76.9) for advanced thymoma (n = 13) and 70% (95% CI: 52.0-82.1) for thymic carcinoma (n = 27). With a median follow-up of 15.5 months, the median PFS for all 42 patients was 9.8 months (11.4 months for thymoma versus 8.1 months for thymic carcinoma). The 2-year overall survival was 77.9% for thymoma and 65.9% for thymic carcinoma. There were no treatment-related deaths. The most common grade 3 and 4 treatment-related adverse event was neutropenia in 11 patients (26%). Eight patients (19%) experienced grade 2 hypersensitivity reactions. There was no correlation between early positron emission tomography response and PFS, but tumor histology (thymoma versus thymic carcinoma) was correlated with SUVmax before chemotherapy. These data suggest that combination of cisplatin and Genexol-PM is highly effective and tolerable for the treatment of unresectable thymic epithelial tumors.

EGFR Mutations and ALK Rearrangements Are Associated with Low Response Rates to PD-1 Pathway Blockade in Non-Small Cell Lung Cancer: A Retrospective Analysis.

PubMed

Gainor, Justin F; Shaw, Alice T; Sequist, Lecia V; Fu, Xiujun; Azzoli, Christopher G; Piotrowska, Zofia; Huynh, Tiffany G; Zhao, Ling; Fulton, Linnea; Schultz, Katherine R; Howe, Emily; Farago, Anna F; Sullivan, Ryan J; Stone, James R; Digumarthy, Subba; Moran, Teresa; Hata, Aaron N; Yagi, Yukako; Yeap, Beow Y; Engelman, Jeffrey A; Mino-Kenudson, Mari

2016-09-15

PD-1 inhibitors are established agents in the management of non-small cell lung cancer (NSCLC); however, only a subset of patients derives clinical benefit. To determine the activity of PD-1/PD-L1 inhibitors within clinically relevant molecular subgroups, we retrospectively evaluated response patterns among EGFR-mutant, anaplastic lymphoma kinase (ALK)-positive, and EGFR wild-type/ALK-negative patients. We identified 58 patients treated with PD-1/PD-L1 inhibitors. Objective response rates (ORR) were assessed using RECIST v1.1. PD-L1 expression and CD8(+) tumor-infiltrating lymphocytes (TIL) were evaluated by IHC. Objective responses were observed in 1 of 28 (3.6%) EGFR-mutant or ALK-positive patients versus 7 of 30 (23.3%) EGFR wild-type and ALK-negative/unknown patients (P = 0.053). The ORR among never- or light- (≤10 pack years) smokers was 4.2% versus 20.6% among heavy smokers (P = 0.123). In an independent cohort of advanced EGFR-mutant (N = 68) and ALK-positive (N = 27) patients, PD-L1 expression was observed in 24%/16%/11% and 63%/47%/26% of pre-tyrosine kinase inhibitor (TKI) biopsies using cutoffs of ≥1%, ≥5%, and ≥50% tumor cell staining, respectively. Among EGFR-mutant patients with paired, pre- and post-TKI-resistant biopsies (N = 57), PD-L1 expression levels changed after resistance in 16 (28%) patients. Concurrent PD-L1 expression (≥5%) and high levels of CD8(+) TILs (grade ≥2) were observed in only 1 pretreatment (2.1%) and 5 resistant (11.6%) EGFR-mutant specimens and was not observed in any ALK-positive, pre- or post-TKI specimens. NSCLCs harboring EGFR mutations or ALK rearrangements are associated with low ORRs to PD-1/PD-L1 inhibitors. Low rates of concurrent PD-L1 expression and CD8(+) TILs within the tumor microenvironment may underlie these clinical observations. Clin Cancer Res; 22(18); 4585-93. ©2016 AACRSee related commentary by Gettinger and Politi, p. 4539. ©2016 American Association for Cancer Research.

"Can you see me now?" An objective metric for predicting intelligibility of compressed American Sign Language video

NASA Astrophysics Data System (ADS)

Ciaramello, Francis M.; Hemami, Sheila S.

2007-02-01

For members of the Deaf Community in the United States, current communication tools include TTY/TTD services, video relay services, and text-based communication. With the growth of cellular technology, mobile sign language conversations are becoming a possibility. Proper coding techniques must be employed to compress American Sign Language (ASL) video for low-rate transmission while maintaining the quality of the conversation. In order to evaluate these techniques, an appropriate quality metric is needed. This paper demonstrates that traditional video quality metrics, such as PSNR, fail to predict subjective intelligibility scores. By considering the unique structure of ASL video, an appropriate objective metric is developed. Face and hand segmentation is performed using skin-color detection techniques. The distortions in the face and hand regions are optimally weighted and pooled across all frames to create an objective intelligibility score for a distorted sequence. The objective intelligibility metric performs significantly better than PSNR in terms of correlation with subjective responses.

Neural and behavioural responses to face-likeness of objects in adolescents with autism spectrum disorder.

PubMed

Akechi, Hironori; Kikuchi, Yukiko; Tojo, Yoshikuni; Osanai, Hiroo; Hasegawa, Toshikazu

2014-01-27

Numerous studies have revealed atypical face processing in autism spectrum disorders (ASD) characterized by social interaction and communication difficulties. This study investigated sensitivity to face-likeness in ASD. In Experiment 1, we found a strong positive correlation between the face-likeness ratings of non-face objects in the ASD (11-19 years old) and the typically developing (TD) group (9-21 years old). In Experiment 2 (the scalp-recorded event-related potential experiment), the participants of both groups (ASD, 12-19 years old; TD, 12-18 years old) exhibited an enhanced face-sensitive N170 amplitude to a face-like object. Whereas the TD adolescents showed an enhanced N170 during the face-likeness judgements, adolescents with ASD did not. Thus, both individuals with ASD and TD individuals have a perceptual and neural sensitivity to face-like features in objects. When required to process face-like features, a face-related brain system reacts more strongly in TD individuals but not in individuals with ASD.

Simulation and fitting of complex reaction network TPR: The key is the objective function

DOE PAGES

Savara, Aditya Ashi

2016-07-07

In this research, a method has been developed for finding improved fits during simulation and fitting of data from complex reaction network temperature programmed reactions (CRN-TPR). It was found that simulation and fitting of CRN-TPR presents additional challenges relative to simulation and fitting of simpler TPR systems. The method used here can enable checking the plausibility of proposed chemical mechanisms and kinetic models. The most important finding was that when choosing an objective function, use of an objective function that is based on integrated production provides more utility in finding improved fits when compared to an objective function based onmore » the rate of production. The response surface produced by using the integrated production is monotonic, suppresses effects from experimental noise, requires fewer points to capture the response behavior, and can be simulated numerically with smaller errors. For CRN-TPR, there is increased importance (relative to simple reaction network TPR) in resolving of peaks prior to fitting, as well as from weighting of experimental data points. Using an implicit ordinary differential equation solver was found to be inadequate for simulating CRN-TPR. Lastly, the method employed here was capable of attaining improved fits in simulation and fitting of CRN-TPR when starting with a postulated mechanism and physically realistic initial guesses for the kinetic parameters.« less

AQMAN; linear and quadratic programming matrix generator using two-dimensional ground-water flow simulation for aquifer management modeling

USGS Publications Warehouse

Lefkoff, L.J.; Gorelick, S.M.

1987-01-01

A FORTRAN-77 computer program code that helps solve a variety of aquifer management problems involving the control of groundwater hydraulics. It is intended for use with any standard mathematical programming package that uses Mathematical Programming System input format. The computer program creates the input files to be used by the optimization program. These files contain all the hydrologic information and management objectives needed to solve the management problem. Used in conjunction with a mathematical programming code, the computer program identifies the pumping or recharge strategy that achieves a user 's management objective while maintaining groundwater hydraulic conditions within desired limits. The objective may be linear or quadratic, and may involve the minimization of pumping and recharge rates or of variable pumping costs. The problem may contain constraints on groundwater heads, gradients, and velocities for a complex, transient hydrologic system. Linear superposition of solutions to the transient, two-dimensional groundwater flow equation is used by the computer program in conjunction with the response matrix optimization method. A unit stress is applied at each decision well and transient responses at all control locations are computed using a modified version of the U.S. Geological Survey two dimensional aquifer simulation model. The program also computes discounted cost coefficients for the objective function and accounts for transient aquifer conditions. (Author 's abstract)

Building capacity in health facility management: guiding principles for skills transfer in Liberia.

PubMed

Rowe, Laura A; Brillant, Sister Barbara; Cleveland, Emily; Dahn, Bernice T; Ramanadhan, Shoba; Podesta, Mae; Bradley, Elizabeth H

2010-03-18

Management training is fundamental to developing human resources for health. Particularly as Liberia revives its health delivery system, facility and county health team managers are central to progress. Nevertheless, such management skills are rarely prioritized in health training, and sustained capacity building in this area is limited. We describe a health management delivery program in which a north and south institution collaborated to integrate classroom and field-based training in health management and to transfer the capacity for sustained management development in Liberia. We developed and implemented a 6-month training program in health management skills (i.e. strategic problem solving, financial management, human resource management and leadership) delivered by Yale University and Mother Patern College from Liberia, with support from the Clinton HIV/AIDS Initiative. Over three 6-month cycles, responsibility for course instruction was transferred from the north institution to the south institution. A self-administered survey was conducted of all participants completing the course to measure changes in self-rated management skills, the degree to which the course was helpful and met its stated objectives, and faculty members' responsiveness to participant needs as the transfer process occurred. Respondents (n=93, response rate 95.9%) reported substantial improvement in self-reported management skills, and rated the helpfulness of the course and the degree to which the course met its objectives highly. Levels of improvement and course ratings were similar over the three cohorts as the course was transferred to the south institution. We suggest a framework of five elements for implementing successful management training programs that can be transferred and sustained in resource-limited settings, including: 1) use a short-course format focusing on four key skill areas with practical tools; 2) include didactic training, on-site projects, and on-site mentoring; 3) collaborate with an in-country academic institution, willing and able to scale-up and maintain the training; 4) provide training for the in-country academic faculty; and 5) secure Ministry-level support to ensure participation. Our findings demonstrate key elements for scaling up and replicating educational initiatives that address management skills essential for long-term health systems strengthening in resource-poor settings.

Place and contingency differential responses of monkey septal neurons during conditional place-object discrimination.

PubMed

Kita, T; Nishijo, H; Eifuku, S; Terasawa, K; Ono, T

1995-03-01

To elucidate spatial and cognitive function of the septal nuclei, neural activity was recorded from alert monkeys during performance of a place-dependent go/no-go (PGN) task. Response/reinforcement contingencies of given objects were conditional upon the location of a motorized, movable device (cab) containing a monkey in one of four places. The task was initiated by presentation of the outside view (place phase) followed by presentation of an object (object phase) selected from a total of four. A lever press was reinforced only if the correct object was seen in its corresponding place, and the same object was never reinforced in any of the other three places. Of 430 septal neurons recorded, the responses during the place phase in the four places were significantly different in 58 neurons. Responses of eight of these neurons were also place-differential during the object phase as well as the place phase. Furthermore, when the outside view was not presented before the object phase, differential responses in the object phase disappeared. Responses of 91 neurons in the object phase were differential in terms of go/no-go responses and reward availability. Of these 91 neurons, 72 were further tested on a place-independent asymmetrical go/no-go (AGN) task, which required no conditional discrimination. Forty-three neurons responded differentially only in the PGN task. It is thus concluded that this PGN-specific activity reflected conditional place-object relations. Of the remaining 29 neurons that responded differentially in both tasks, 21 were further tested by a place-independent symmetrical go/no-go task (no-go responses were also rewarded). Responses of 19 of these 21 neurons were related to the reward/nonreward contingency but not to the response contingency. The results suggest that septal nuclei are involved in integrating spatial information, conditional place-object relations, and reward/nonreward contingency.

Cediranib for Metastatic Alveolar Soft Part Sarcoma

PubMed Central

Kummar, Shivaani; Allen, Deborah; Monks, Anne; Polley, Eric C.; Hose, Curtis D.; Ivy, S. Percy; Turkbey, Ismail B.; Lawrence, Scott; Kinders, Robert J.; Choyke, Peter; Simon, Richard; Steinberg, Seth M.; Doroshow, James H.; Helman, Lee

2013-01-01

Purpose Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs). Patients and Methods We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging. Results Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis. Conclusion In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib. PMID:23630200

Efficacy and Safety Outcomes for Originator TNF Inhibitors and Biosimilars in Rheumatoid Arthritis and Psoriasis Trials: A Systematic Literature Review.

PubMed

Moots, Robert J; Curiale, Cinzia; Petersel, Danielle; Rolland, Catherine; Jones, Heather; Mysler, Eduardo

2018-05-22

Regulatory approval of biosimilar versions of originator biotherapeutics requires that new biological products be highly similar to originator products, with no clinically meaningful differences in safety, purity, and potency. In some trials of biosimilars of tumor necrosis factor inhibitors for the treatment of rheumatoid arthritis (RA) and plaque psoriasis (PsO), pre-specified margins for efficacy and safety have been met, but differences in treatment responses between pivotal originator trials and biosimilar trials have been noted. The objective of this systematic review was to examine these differences. Searches were conducted to identify comparative randomized clinical trials of approved or proposed biosimilars of adalimumab, etanercept, and infliximab. Of 83 publications identified, 16 publications were included for analysis (RA: originators, n = 5; biosimilars, n = 6; PsO: originators, n = 2; biosimilars, n = 3). American College of Rheumatology 20% response rates were higher among patients with RA receiving originator biologics and biosimilars in biosimilar trials than among patients receiving the originator biologics in pivotal trials. In etanercept studies in PsO, a difference was observed in Psoriasis Area and Severity Index 75% response rates between biosimilar and pivotal trials. Insufficient efficacy data were available from adalimumab and infliximab biosimilar studies in PsO to determine any differences in treatment responses between pivotal and biosimilar studies. Observed differences in treatment response rates between pivotal originator trials and trials of originator biologics and their respective biosimilars may be attributable to fundamental differences in study design and/or baseline patient characteristics, which require further analysis.

Promoter CpG island hypermethylation of the DNA repair enzyme MGMT predicts clinical response to dacarbazine in a phase II study for metastatic colorectal cancer.

PubMed

Amatu, Alessio; Sartore-Bianchi, Andrea; Moutinho, Catia; Belotti, Alessandro; Bencardino, Katia; Chirico, Giuseppe; Cassingena, Andrea; Rusconi, Francesca; Esposito, Anna; Nichelatti, Michele; Esteller, Manel; Siena, Salvatore

2013-04-15

O(6)-methylguanine-DNA-methyltransferase (MGMT) is a DNA repair protein removing mutagenic and cytotoxic adducts from O(6)-guanine in DNA. Approximately 40% of colorectal cancers (CRC) display MGMT deficiency due to the promoter hypermethylation leading to silencing of the gene. Alkylating agents, such as dacarbazine, exert their antitumor activity by DNA methylation at the O(6)-guanine site, inducing base pair mismatch; therefore, activity of dacarbazine could be enhanced in CRCs lacking MGMT. We conducted a phase II study with dacarbazine in CRCs who had failed standard therapies (oxaliplatin, irinotecan, fluoropyrimidines, and cetuximab or panitumumab if KRAS wild-type). All patients had tumor tissue assessed for MGMT as promoter hypermethylation in double-blind for treatment outcome. Patients received dacarbazine 250 mg/m(2) intravenously every day for four consecutive days, every 21 days, until progressive disease or intolerable toxicity. We used a Simon two-stage design to determine whether the overall response rate would be 10% or more. Secondary endpoints included association of response, progression-free survival, and disease control rate with MGMT status. Sixty-eight patients were enrolled from May 2011 to March 2012. Patients received a median of three cycles of dacarbazine (range 1-12). Grades 3 and 4 toxicities included: fatigue (41%), nausea/vomiting (29%), constipation (25%), platelet count decrease (19%), and anemia (18%). Overall, two patients (3%) achieved partial response and eight patients (12%) had stable disease. Disease control rate (partial response + stable disease) was significantly associated with MGMT promoter hypermethylation in the corresponding tumors. Objective clinical responses to dacarbazine in patients with metastatic CRC are confined to those tumors harboring epigenetic inactivation of the DNA repair enzyme MGMT.

Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice

PubMed Central

Bykerk, Vivian P; Östör, Andrew J K; Alvaro-Gracia, José; Pavelka, Karel; Ivorra, José Andrés Román; Graninger, Winfried; Bensen, William; Nurmohamed, Michael T; Krause, Andreas; Bernasconi, Corrado; Stancati, Andrea; Sibilia, Jean

2012-01-01

Objective To evaluate the safety and efficacy of tocilizumab in clinical practice in patients with rheumatoid arthritis (RA) with inadequate responses (IR) to disease-modifying antirheumatic drugs (DMARDs) or both DMARDs and tumour necrosis factor α inhibitors (TNFis). Methods Patients—categorised as TNFi-naive, TNFi-previous (washout) or TNFi-recent (no washout) —received open-label tocilizumab (8 mg/kg) every 4 weeks ± DMARDs for 24 weeks. Adverse events (AEs) and treatment discontinuations were monitored. Efficacy end points included American College of Rheumatology (ACR) responses, 28-joint disease activity score (DAS28) and European League Against Rheumatism responses. Results Overall, 1681 (976 TNF-naive, 298 TNFi-previous and 407 TNFi-recent) patients were treated; 5.1% discontinued treatment because of AEs. The AE rate was numerically higher in TNFi-recent (652.6/100 patient-years (PY)) and TNFi-previous (653.6/100PY) than in TNFi-naive (551.1/100PY) patients. Serious AE rates were 18.0/100PY, 28.0/100PY and 18.6/100PY; serious infection rates were 6.0/100PY, 6.8/100PY and 4.2/100PY, respectively. At week 4, 36.5% of patients achieved ACR20 response and 14.9% DAS28 remission (<2.6); at week 24, 66.9%, 46.6%, 26.4% and 56.8% achieved ACR20/ACR50/ACR70 responses and DAS28 remission, respectively. Overall, 61.6% (TNFi-naive), 48.5% (TNFi-previous) and 50.4% (TNFi-recent) patients achieved DAS28 remission. Conclusions In patients with RA who were DMARD-IR/TNFi-IR, tocilizumab ± DMARDs provided rapid and sustained efficacy without unexpected safety concerns. PMID:22615456

Factors affecting emergency preparedness competency of public health inspectors: a cross-sectional study in northeastern China

PubMed Central

Ning, Ning; Kang, Zheng; Jiao, Mingli; Hao, Yanhua; Gao, Lijun; Sun, Hong; Wu, Qunhong

2014-01-01

Objectives To determine the emergency preparedness competency specific to public health inspectors (PHIs), preparedness limitations and needs of the workforce, as well as to identify important factors that affect the preparedness competency of PHIs. Setting Cross-sectional survey was conducted in Heilongjiang, a province in northeastern China. Participants A questionnaire was administered to a sample of 368 PHIs from 17 public health inspection agencies, chosen by stratified cluster sampling strategy. 9 PHIs and 6 agency's leaders were invited to participate in an in-depth interview. Outcome measures Self-rated preparedness competency in quantitative study was measured. Multivariate logistic regression model was used to test the associations between individual determinants and self-rated preparedness competency. Key themes relating to preparedness competency of PHIs in qualitative study were analysed. Results Although 82% of PHIs highly rated their general preparedness competency, there were significant differences among the assessment on specific domains of their competency. Comparing with attitude, the domains of skills and knowledge tend to be lower (p=0.000). Awareness on one's own responsibilities regarding emergency response work was identified as the most important factor associated with preparedness competency (adjusted OR=6.33, 95% CI 3.30 to 12.16). Lack of explicit national job requirements, overlapping responsibilities and poor collaboration among agencies, together with poor knowledge and skills level of personnel, led to an ambiguity of responsibility, and hindered the preparedness competency enhancement of PHIs furthermore. Conclusions Ambiguity responsibility in emergency response is still a prominent issue that hinders the further improvement on the preparedness competency for PHIs’ in China. Intensified capacity-building activities targeting at individuals’ weakness in specific knowledge and skills are urgently needed; in addition, capacity building at policy and system level as well as agency levels is of equal importance. PMID:24384897

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.

Survival of patients with intermediate stage hepatocellular carcinoma treated with superselective transarterial chemoembolization using doxorubicin-loaded DC Bead under cone-beam computed tomography control

PubMed Central

Stabuc, Borut; Jansa, Rado; Garbajs, Manca

2016-01-01

Abstract Background The purpose of this retrospective study was to evaluate treatment response, adverse events and survival rates of patients with intermediate stage HCC treated with superselective doxorubicin-loaded DC Bead transarterial chemoembolization (DEBDOX) under cone beam computed tomography (CBCT) control. Patients and methods Between October 2010 and June 2012, 35 consecutive patients with intermediate stage HCC (32 male, 3 female; average age, 67.5 ± 7.8 years; 22 patients Child-Pugh class A, 8 class B, 5 without cirrhosis) were treated with DEBDOX TACE. Portal vein thrombosis was observed in 6 (17.1%) patients. DEBDOX TACE was performed by superselective catheterization of feeding vessels followed by embolization with 100-300 μm microspheres loaded with 50-100 mg of doxorubicin. In all cases, CBCT was used during chemoembolization. Tumor response rates were defined according to mRECIST criteria. Results Overall, 120 procedures were performed (mean, 3.2 per patients). We treated 97 lesions with an average diameter of 4.9 ± 1.9 cm. There were 32 minor and 2 (1.6%) major complications (one liver abscess and one cerebrovascular insult). After a mean follow-up of 27.7 ± 10.5 months, 94.3% of patients achieved an objective response to treatment (42.4% complete response and 57.6% partial response). Mean time to progression was 10.9 ± 5.3 months. Mean overall survival was 33.9 months (95% CI; 28.9 – 38.9 months), with 1- and 2- year survival of 97.1% and 65.7%, respectively. Conclusions Superselective DEBDOX TACE performed under CBCT control is a safe and effective method with high rates of tumor response and overall survival. PMID:27904450

Endocrine Secretory Reserve and Proinsulin Processing in Recipients of Islet of Langerhans Versus Whole Pancreas Transplants

PubMed Central

Elkhafif, Nabeel M.; Borot, Sophie; Morel, Philippe; Demuylder-Mischler, Sandrine; Giovannoni, Laurianne; Toso, Christian; Bosco, Domenico; Berney, Thierry

2013-01-01

OBJECTIVE β-Cells have demonstrated altered proinsulin processing after islet transplantation. We compare β-cell metabolic responses and proinsulin processing in pancreas and islet transplant recipients with respect to healthy control subjects. RESEARCH DESIGN AND METHODS We studied 15 islet and 32 pancreas transplant recipients. Islet subjects were subdivided into insulin-requiring (IR-ISL, n = 6) and insulin-independent (II-ISL, n = 9) groups. Ten healthy subjects served as control subjects. Subjects were administered an intravenous arginine stimulation test, and insulin, C-peptide, total proinsulin, intact proinsulin, and proinsulin fragment levels were determined from serum samples. Acute insulin response (AIR) and proinsulin processing rates were calculated. RESULTS We found that basal insulin and C-peptide levels were higher in the pancreas group than in all other groups. II-ISL patients had basal insulin and C-peptide levels similar to healthy control subjects. The IR-ISL group had significantly lower AIRs than all other groups. Basal processing rates were higher in the pancreas and II-ISL groups than in healthy control subjects and the IR-ISL group. After arginine stimulation, all groups had elevated processing rates, with the exception of the IR-ISL group. CONCLUSIONS Our data suggest that II-ISL transplant recipients can maintain basal metabolic parameters similar to healthy control subjects at the cost of a higher rate of proinsulin processing. IR-ISL transplant recipients, on the other hand, demonstrate both lower insulin response and lower basal rates of proinsulin processing even after arginine stimulation. PMID:24041681

Test-retest reliability of evoked heat stimulation BOLD fMRI.

PubMed

Upadhyay, Jaymin; Lemme, Jordan; Anderson, Julie; Bleakman, David; Large, Thomas; Evelhoch, Jeffrey L; Hargreaves, Richard; Borsook, David; Becerra, Lino

2015-09-30

To date, the blood oxygenated-level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique has enabled an objective and deeper understanding of pain processing mechanisms embedded within the human central nervous system (CNS). In order to further comprehend the benefits and limitations of BOLD fMRI in the context of pain as well as the corresponding subjective pain ratings, we evaluated the univariate response, test-retest reliability and confidence intervals (CIs) at the 95% level of both data types collected during evoked stimulation of 40°C (non-noxious), 44°C (mildly noxious) and a subject-specific temperature eliciting a 7/10 pain rating. The test-retest reliability between two scanning sessions was determined by calculating group-level interclass correlation coefficients (ICCs) and at the single-subject level. Across the three stimuli, we initially observed a graded response of increasing magnitude for both VAS (visual analog score) pain ratings and fMRI data. Test-retest reliability was observed to be highest for VAS pain ratings obtained during the 7/10 pain stimulation (ICC=0.938), while ICC values of pain fMRI data for a distribution of CNS structures ranged from 0.5 to 0.859 (p<0.05). Importantly, the upper and lower confidence interval CI bounds reported herein could be utilized in subsequent trials involving healthy volunteers to hypothesize the magnitude of effect required to overcome inherent variability of either VAS pain ratings or BOLD responses evoked during innocuous or noxious thermal stimulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Irradiation-hyperthermia in canine hemangiopericytomas: large-animal model for therapeutic response.

PubMed

Richardson, R C; Anderson, V L; Voorhees, W D; Blevins, W E; Inskeep, T K; Janas, W; Shupe, R E; Babbs, C F

1984-11-01

Results of irradiation-hyperthermia treatment in 11 dogs with naturally occurring hemangiopericytoma were reported. Similarities of canine and human hemangiopericytomas were described. Orthovoltage X-irradiation followed by microwave-induced hyperthermia resulted in a 91% objective response rate. A statistical procedure was given to evaluate quantitatively the clinical behavior of locally invasive, nonmetastatic tumors in dogs that were undergoing therapy for control of local disease. The procedure used a small sample size and demonstrated distribution of the data on a scaled response as well as transformation of the data through classical parametric and nonparametric statistical methods. These statistical methods set confidence limits on the population mean and placed tolerance limits on a population percentage. Application of the statistical methods to human and animal clinical trials was apparent.

[Evaluation, correction and impact of non-response in studies of childhood obesity].

PubMed

Santiago-Pérez, María Isolina; Pérez-Ríos, Mónica; Malvar, Alberto; Suanzes, Jorge; Hervada, Xurxo

2017-09-25

To evaluate and correct the impact of non-response in the prevalence of underweight, overweight and obesity in children aged 6 to 15 years old using silhouette scales. Cross-sectional study carried out in 2013 among 8,145 Galician schoolchildren aged 6-15 years old. The students who agreed to participate were weighed and measured and, based on body mass index, the prevalence of underweight, overweight and obesity was estimated. Teachers rated all students using silhouette scales. The valuations were used to estimate the prevalence corrected by non-response. Using the Bayes theorem, participation rates were estimated according to weight status. The participation rate was 92.3% in the 6 -to 11-year-old group, and 90% in the 12- to 15-year old age group. In both groups, the prevalence of underweight and overweight were similar between participants and non-participants. However, obesity was higher among non-participants, especially at 12 to 15 years of age (6.3% vs. 12.2% ; p < 0.05). The prevalence did not change when corrected by the teacher's valuation. The participation rate of obese students was lower than the overall rate (82% vs. 90% at 12 to 15 years old; p < 0.05). The presence of participation bias, which was greater at 12-15 years old, was confirmed. However, the impact of the bias on prevalence was negligible due to the high participation rate. In obesity studies with objective measures, it is essential to quantify non-participation, as well as to assess its impact and correct it. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

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

Neurophysiological responses to unpleasant stimuli (acute electrical stimulations and emotional pictures) are increased in patients with schizophrenia

PubMed Central

Duval, Céline Z.; Goumon, Yannick; Kemmel, Véronique; Kornmeier, Jürgen; Dufour, André; Andlauer, Olivier; Vidailhet, Pierre; Poisbeau, Pierrick; Salvat, Eric; Muller, André; Mensah-Nyagan, Ayikoé G.; Schmidt-Mutter, Catherine; Giersch, Anne

2016-01-01

Patients with schizophrenia have often been described as insensitive to nociceptive signals, but objective evidence is sparse. We address this question by combining subjective behavioral and objective neurochemical and neurophysiological measures. The present study involved 21 stabilized and mildly symptomatic patients with schizophrenia and 21 control subjects. We applied electrical stimulations below the pain threshold and assessed sensations of pain and unpleasantness with rating scales, and Somatosensory Evoked Potentials (SEPs/EEG). We also measured attention, two neurochemical stress indices (ACTH/cortisol), and subjective VEPs/EEG responses to visual emotional stimuli. Our results revealed that, subjectively, patients’ evaluations do not differ from controls. However, the amplitude of EEG evoked potentials was greater in patients than controls as early as 50 ms after electrical stimulations and beyond one second after visual processing of emotional pictures. Such responses could not be linked to the stress induced by the stimulations, since stress hormone levels were stable. Nor was there a difference between patients and controls in respect of attention performance and tactile sensitivity. Taken together, all indices measured in patients in our study were either heightened or equivalent relative to healthy volunteers. PMID:26935652

Electroencephalographic evoked pain response is suppressed by spinal cord stimulation in complex regional pain syndrome: a case report.

PubMed

Hylands-White, Nicholas; Duarte, Rui V; Beeson, Paul; Mayhew, Stephen D; Raphael, Jon H

2016-12-01

Pain is a subjective response that limits assessment. The purpose of this case report was to explore how the objectivity of the electroencephalographic response to thermal stimuli would be affected by concurrent spinal cord stimulation. A patient had been implanted with a spinal cord stimulator for the management of complex regional pain syndrome of both hands for 8 years. Following ethical approval and written informed consent we induced thermal stimuli using the Medoc PATHWAY Pain & Sensory Evaluation System on the right hand of the patient with the spinal cord stimulator switched off and with the spinal cord stimulator switched on. The patient reported a clinically significant reduction in thermal induced pain using the numerical rating scale (71.4 % reduction) with spinal cord stimulator switched on. Analysis of electroencephalogram recordings indicated the occurrence of contact heat evoked potentials (N2-P2) with spinal cord stimulator off, but not with spinal cord stimulator on. This case report suggests that thermal pain can be reduced in complex regional pain syndrome patients with the use of spinal cord stimulation and offers objective validation of the reported outcomes with this treatment.