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.

Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases.

PubMed

Lucidi, Valerio; Hendlisz, Alain; Van Laethem, Jean-Luc; Donckier, Vincent

2016-04-21

In oncosurgical approach to colorectal liver metastases, surgery remains considered as the only potentially curative option, while chemotherapy alone represents a strictly palliative treatment. However, missing metastases, defined as metastases disappearing after chemotherapy, represent a unique model to evaluate the curative potential of chemotherapy and to challenge current therapeutic algorithms. We reviewed recent series on missing colorectal liver metastases to evaluate incidence of this phenomenon, predictive factors and rates of cure defined by complete pathologic response in resected missing metastases and sustained clinical response when they were left unresected. According to the progresses in the efficacy of chemotherapeutic regimen, the incidence of missing liver metastases regularly increases these last years. Main predictive factors are small tumor size, low marker level, duration of chemotherapy, and use of intra-arterial chemotherapy. Initial series showed low rates of complete pathologic response in resected missing metastases and high recurrence rates when unresected. However, recent reports describe complete pathologic responses and sustained clinical responses reaching 50%, suggesting that chemotherapy could be curative in some cases. Accordingly, in case of missing colorectal liver metastases, the classical recommendation to resect initial tumor sites might have become partially obsolete. Furthermore, the curative effect of chemotherapy in selected cases could lead to a change of paradigm in patients with unresectable liver-only metastases, using intensive first-line chemotherapy to intentionally induce missing metastases, followed by adjuvant surgery on remnant chemoresistant tumors and close surveillance of initial sites that have been left unresected.

What Happens After Referral For Sedation?

PubMed Central

Boyle, Carole A; Newton, Tim; Heaton, Lisa; Afzali, Sonita; Milgrom, Peter

2013-01-01

Objective To follow up 100 referrals to the sedation clinic examining dental anxiety and background of patients and assess how many patients attended for treatment planning, initial treatment, and completed treatment and describe their characteristics. Among those who attended for initial treatment, which type of sedation they received at initial treatment and what level of clinician they saw. Design Descriptive, cross sectional survey and review of case notes. Subjects and Methods Subjects were 100 consecutive new patients in Sedation and Special Care Guy’s and St Thomas NHS Foundation Trust. The notes were analysed by an experienced member of staff (CAB) and data entered into an Excel spreadsheet and an SPSS datafile created. These data were merged with a dataset containing their responses to the intake questionnaire and medical history for analysis. Results Of the 100 patients initially referred, 72 attended the treatment planning session, 66 of the 72 (92%) attended for initial dental treatment, and 33 of 66 (50%) completed treatment. Dental Fear Survey (DFS) scores were related to attendance at the initial treatment visit but not to completion of treatment. Patients with mental health problems encountered more barriers. Only 33 of 100 patients referred completed treatment. Conclusions Attendance for treatment planning and initial treatment was high. Attendance is related to fear and mental health. Overall completion of treatment from referral was 33 percent. PMID:20512107

Comparison of content of FDA letters not approving applications for new drugs and associated public announcements from sponsors: cross sectional study

PubMed Central

Chahal, Harinder S; Sigelman, Daniel W; Stacy, Sylvie; Sclar, Joshua; Ddamulira, Barbara

2015-01-01

Objectives To describe the content of non-public complete response letters issued by the US Food and Drug Administration (FDA) when they do not approve marketing applications from sponsors (drug companies) and to compare them with the content any subsequent press releases issued by those sponsors Design Cross sectional study. Data sources All applications for which FDA’s Center for Drug Evaluation and Research initially issued complete response letters (n=61) from 11 August 2008 to 27 June 2013. Complete response letters and press releases were divided into discrete statements related to seven domains and 64 subdomains and assessed to determine whether they matched. Results 48% (29) of complete response letters cited deficiencies in both the safety and efficacy domains, and only 13% cited neither safety nor efficacy deficiencies. No press release was issued for 18% (11) of complete response letters, and 21% (13) of press releases did not match any statements from the letters. Press release statements matched 93 of the 687 statements (14%), including 16% (30/191) of efficacy and 15% (22/150) of safety statements. Of 32 complete response letters that called for a new clinical trial for safety or efficacy, 59% (19) had matching press release statements. Seven complete response letters reported higher mortality rates in treated participants; only one associated press release mentioned this fact. Conclusions FDA generally issued complete response letters to sponsors for multiple substantive reasons, most commonly related to safety and/or efficacy deficiencies. In many cases, press releases were not issued in response to those letters and, when they were, omitted most of the statements in the complete response letters. Press releases are incomplete substitutes for the detailed information contained in complete response letters. PMID:26063327

Development and Initial Validation of the Adolescent Responses to Body Dissatisfaction Measure

ERIC Educational Resources Information Center

Maxwell, Melissa A.; Cole, David A.

2012-01-01

One community sample (N = 607) of youths generated self-reported responses to body dissatisfaction, from which the Adolescent Responses to Body Dissatisfaction (ARBD) inventory was constructed. A 2nd, similar sample (N = 830) completed this measure as well as measures of coping, body dissatisfaction, body mass index, depressive symptoms, and…

User compliance with documenting on a track and trigger-based observation and response chart: a two-phase multi-site audit study.

PubMed

Elliott, Doug; Allen, Emily; McKinley, Sharon; Perry, Lin; Duffield, Christine; Fry, Margaret; Gallagher, Robyn; Iedema, Rick; Roche, Michael

2017-12-01

To examine user compliance and completeness of documentation with a newly designed observation and response chart and whether a rapid response system call was triggered when clinically indicated. Timely recognition and responses to patient deterioration in hospital general wards remain a challenge for healthcare systems globally. Evaluating practice initiatives to improve recognition and response are required. Two-phase audit. Following introduction of the charts in ten health service sites in Australia, an audit of chart completion was conducted during a short trial for initial usability (Phase 1; 2011). After chart adoption as routine use in practice, retrospective and prospective chart audits were conducted (Phase 2; 2012). Overall, 818 and 1,058 charts were audited during the two phases respectively. Compliance was mixed but improved with the new chart (4%-14%). Contrary to chart guidelines, numbers rather than dots were written in the graphing section in 60% of cases. Rates of recognition of abnormal vital signs improved slightly with new charts in use, particularly for higher levels of surveillance and clinical review. Based on local calling criteria, an emergency call was initiated in 33% of cases during the retrospective audit and in 41% of cases with the new chart. User compliance was less than optimal, limiting full function of the chart sections and compliance with local calling criteria. Overcoming apparent behavioural and work culture barriers may improve chart completion, aiding identification of abnormal vital signs and triggering a rapid response system activation when clinical deterioration is detected. © 2017 The Authors. Journal of Advanced Nursing Published by John Wiley & Sons Ltd.

Go or No-Go? Developmental Improvements in the Efficiency of Response Inhibition in Mid-Childhood

ERIC Educational Resources Information Center

Cragg, Lucy; Nation, Kate

2008-01-01

This experiment used a modified go/no-go paradigm to investigate the processes by which response inhibition becomes more efficient during mid-childhood. The novel task, which measured trials on which a response was initiated but not completed, was sensitive to developmental changes in response inhibition. The effect of inducing time pressure by…

Screening for Homelessness in the Veterans Health Administration: Monitoring Housing Stability through Repeat Screening.

PubMed

Byrne, Thomas; Fargo, Jamison D; Montgomery, Ann Elizabeth; Roberts, Christopher B; Culhane, Dennis P; Kane, Vincent

2015-01-01

This study examined veterans' responses to the Veterans Health Administration's (VHA's) universal screen for homelessness and risk of homelessness during the first 12 months of implementation. We calculated the baseline annual frequency of homelessness and risk of homelessness among all veterans who completed an initial screen during the study period. We measured changes in housing status among veterans who initially screened positive and then completed a follow-up screen, assessed factors associated with such changes, and identified distinct risk profiles of veterans who completed a follow-up screen. More than 4 million veterans completed an initial screen; 1.8% (n=77,621) screened positive for homelessness or risk of homelessness. Of those who initially screened positive for either homelessness or risk of homelessness and who completed a second screen during the study period, 85.0% (n=15,060) resolved their housing instability prior to their second screen. Age, sex, race, VHA eligibility, and screening location were all associated with changes in housing stability. We identified four distinct risk profiles for veterans with ongoing housing instability. To address homelessness among veterans, efforts should include increased and targeted engagement of veterans experiencing persistent housing instability.

Training Master's Thesis Supervisors within a Professional Learning Community

ERIC Educational Resources Information Center

Fossøy, Ingrid; Haara, Frode Olav

2016-01-01

Completion of a master's degree has changed significantly from being the specific responsibility of the candidate and his/her supervisor to being the responsibility of the whole educational institution. As a consequence, we have initiated an internal training course for professional development related to the supervision of master's theses. In…

Identification of non-response to treatment using narrative data in an electronic health record inflammatory bowel disease cohort

PubMed Central

Ananthakrishnan, Ashwin N.; Cagan, Andrew; Cai, Tianxi; Gainer, Vivian S.; Shaw, Stanley Y; Savova, Guergana; Churchill, Susanne; Karlson, Elizabeth W.; Murphy, Shawn N.; Liao, Katherine P.; Kohane, Isaac

2016-01-01

Introduction Electronic health records (EHR), increasingly a part of healthcare, provide a wealth of untapped narrative free text data that has the potential to accurately inform clinical outcomes. Methods From a validated cohort of patients with Crohn’s disease (CD) or ulcerative colitis (UC), we identified patients with ≥ 1 coded or narrative mention of monoclonal antibodies to tumor necrosis factor α (anti-TNF). Chart review by ascertained true use of therapy, time of initiation and cessation of treatment, as well as clinical response stratified as non-response, partial, or complete response at one year. Internal consistency was assessed in an independent validation cohort. Results A total of 3,087 patients had a mention of an anti-TNF. Actual therapy initiation was within 60 days of the first coded mention in 74% of patients. In the derivation cohort, 18% of anti-TNF starts were classified as non-response at 1 year, 21% as partial, and 56% as complete response. On multivariate analysis, the number of narrative mentions of diarrhea (OR 1.08, 95% CI 1.02 – 1.14) and fatigue (OR 1.16, 95% CI 1.02 – 1.32) were independently associated with non-response at 1 year (AUC 0.82). A likelihood of non-response score comprising a weighted sum of both demonstrated a good dose response relationship across non-responders (2.18), partial (1.20), and complete (0.50) responders (p < 0.0001) and correlated well with need for surgery or hospitalizations. Conclusions Narrative data in an EHR offers considerable potential to define temporally evolving disease outcomes such as non-response to treatment. PMID:26332313

Parental consanguineous marriages and clinical response to chemotherapy in locally advanced breast cancer patients.

PubMed

Saadat, Mostafa; Khalili, Maryam; Omidvari, Shahpour; Ansari-Lari, Maryam

2011-03-28

The main aim of the present study was investigating the association between parental consanguinity and clinical response to chemotherapy in females affected with locally advanced breast cancer. A consecutive series of 92 patients were prospectively included in this study. Clinical assessment of treatment was accomplished by comparing initial tumor size with preoperative tumor size using revised RECIST guideline (version 1.1). Clinical response defined as complete response, partial response and no response. The Kaplan-Meier survival analysis were used to evaluate the association of parental marriages (first cousin vs unrelated marriages) and clinical response to chemotherapy (complete and partial response vs no response). Number of courses of chemotherapy was considered as time, in the analysis. Kaplan-Meier analysis revealed that offspring of unrelated marriages had poorer response to chemotherapy (log rank statistic=5.10, df=1, P=0.023). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Flight demonstration of laser diode initiated ordnance

NASA Technical Reports Server (NTRS)

Boucher, Craig J.; Schulze, Norman R.

1995-01-01

A program has been initiated by NASA Headquarters to validate laser initiated ordnance in flight applications. The primary program goal is to bring together a team of government and industry members to develop a laser initiated ordnance system having the test and analysis pedigree to be flown on launch vehicles. The culmination of this effort was a flight of the Pegasus launch vehicle which had two fin rockets initiated by this laser system. In addition, a laser initiated ordnance squib was fired into a pressure bomb during thrusting flight. The complete ordnance system comprising a laser diode firing unit, fiber optic cable assembly, laser initiated detonator, and laser initiated squib was designed and built by The Ensign Bickford Company. The hardware was tested to the requirements of the Pegasus launch vehicle and integrated into the vehicle by The Ensign Bickford Company and the Orbital Sciences Corporation. Discussions include initial program concept, contract implementation, team member responsibilities, analysis results, vehicle integration, safing architecture, ordnance interfaces, mission timeline and telemetry data. A complete system description, summary of the analyses, the qualification test results, and the results of flight are included.

Reliability of the Foot Function Index:: A report of the AOFAS Outcomes Committee..

PubMed

Agel, Julie; Beskin, James L; Brage, Michael; Guyton, Gregory P; Kadel, Nancy J; Saltzman, Charles L; Sands, Andrew K; Sangeorzan, Bruce J; SooHoo, Nelson F; Stroud, Chris C; Thordarson, David B

2005-11-01

There currently is no widely used, validated, self-administered instrument for measuring musculoskeletal functional status in individuals with nonsystemic foot disorders. The purpose of this paper was to report on the assessment of reliability of one of these instruments. We wanted to determine if the Foot Function Index (FFI), which has been validated in rheumatoid patients without fixed foot deformity or prior foot surgery, would be reliable for a population of patients with foot complaints without systemic disease. Patients were recruited from five orthopaedic offices where the physicians were members of the American Orthopaedic Foot and Ankle Society. Patients were asked to complete the FFI at the time of their initial office visit and then were given a second copy to complete and return by mail 1 week after their visit. Ninety-six patients completed the first questionnaire, and 54 patients completed the second. Reliability in this population was acceptable with an average of 23.5% of the patients providing retest values within one point of the initial response and an average of 45.3% of the patients providing the same response, for a total of 68.8% of all respondents answering within one point between their initial and second questionnaire. In two of the three categories, there were frequent nonresponses or no applicable responses. Four questions, two in the pain section and two in the activity limitation section, generated 20% or more of the nonapplicable answers. The FFI appears to be a reasonable tool for low functioning individuals with foot disorders. It may not be appropriate for individuals who function at or above the level of independent activities of daily living.

Neoadjuvant conformal chemoradiation with induction chemotherapy for rectal adenocarcinoma. A prospective observational study.

PubMed

Fekete, Zsolt; Muntean, Alina-Simona; Hica, Ştefan; Rancea, Alin; Resiga, Liliana; Csutak, Csaba; Todor, Nicolae; Nagy, Viorica Magdalena

2014-06-01

The purpose of this prospective observational study was to evaluate the rate and the prognostic factors for down-staging and complete response for rectal adenocarcinoma after induction chemotherapy and neoadjuvant chemoradiation followed by surgery, and to analyze the rate of sphincter-saving surgery. We included from March 2011 to October 2013 a number of 88 patients hospitalized with locally advanced rectal adenocarcinoma in the Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj. The treatment schedule included 2-4 cycles of Oxaliplatin plus a fluoropyrimidine followed by concomitant chemoradiation with a dose of 50 Gy in 25 fractions combined with a fluoropyrimidine monotherapy. The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p<0.01), cN0 (p<0.01), distance from anal verge >5 cm (p<0.01), initial CEA <6.2 ng/ml (p<0.01), higher number of chemotherapy cycles with Oxaliplatin (pROC=0.05) and protraction of radiotherapy of >35 days (p<0.01). Nine patients from 81 (11.1%) presented complete response (7 pathological and 2 clinical); the independent prognostic factors were stage cT2 versus cT3-4 (p<0.01), initial tumor size ≤3.5 cm and distance from anal verge >5 cm (p=0.03). Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure. Induction chemotherapy with neoadjuvant chemoradiation produced important down-staging in rectal adenocarcinoma. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA, the number of Oxaliplatin cycles and duration of radiotherapy; for complete response: cT2, initial tumor size and distance from the anal verge.

Annual report to Congress. Department of Energy activities relating to the Defense Nuclear Facilities Safety Board, calendar year 2000

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

None

2001-03-01

This Annual Report to the Congress describes the Department of Energy's activities in response to formal recommendations and other interactions with the Defense Nuclear Facilities Safety Board. During 2000, the Department completed its implementation and proposed closure of one Board recommendation and completed all implementation plan milestones associated with two additional Board recommendations. Also in 2000, the Department formally accepted two new Board recommendations and developed implementation plans in response to those recommendations. The Department also made significant progress with a number of broad-based safety initiatives. These include initial implementation of integrated safety management at field sites and within headquartersmore » program offices, issuance of a nuclear safety rule, and continued progress on stabilizing excess nuclear materials to achieve significant risk reduction.« less

Tocilizumab for the treatment of severe steroid-refractory acute graft-versus-host disease of the lower gastrointestinal tract.

PubMed

Ganetsky, Alex; Frey, Noelle V; Hexner, Elizabeth O; Loren, Alison W; Gill, Saar I; Luger, Selina M; Mangan, James K; Martin, Mary Ellen; Babushok, Daria V; Drobyski, William R; Smith, Jacqueline; Timlin, Colleen; Freyer, Craig W; Stadtmauer, Edward A; Porter, David L

2018-05-24

Steroid-refractory (SR) acute gastrointestinal (GI) graft-versus-host disease (GVHD) is associated with significant mortality in allogeneic hematopoietic cell transplantation recipients. We retrospectively evaluated the efficacy of tocilizumab for the treatment of SR biopsy-proven acute lower GI GVHD in 16 consecutive adult transplant recipients between October 2015 and July 2016. Tocilizumab 8 mg/kg was administered every 2 weeks until achievement of complete response, defined as resolution of all manifestations of GI GVHD, or until patients had progression or initiation of other therapy. Ten of 16 patients (62.5%; 95% CI, 0.39-82) achieved a complete response after a median time of 11 days (range, 2-28 days) from tocilizumab initiation. The median time to response onset (improvement in stage by at least 1) was 1 day (range, 1-4 days). Tocilizumab was administered at a median of 9 days (range, 3-75 days) from GVHD diagnosis and 10 days (range, 3-75 days) from initiation of high-dose steroids. At a median follow-up of 7.6 months (range, 0.8-27.7 months) from initiation of tocilizumab, 6/16 (37.5%) patients are alive and free of their underlying hematologic malignancy. Tocilizumab appears to be a highly active agent for the treatment of severe SR lower GI acute GVHD.

Reduced Nicotine Content Expectancies Affect Initial Responses to Smoking.

PubMed

Mercincavage, Melissa; Smyth, Joshua M; Strasser, Andrew A; Branstetter, Steven A

2016-10-01

We sought to determine if negative responses to reduced nicotine content (RNC) cigarettes during open-label trials result from smokers' (negative) expectancies. We examined the effects of nicotine content description - independent of actual nicotine content - on subjective responses (craving reduction, withdrawal suppression, mood changes, and sensory ratings) and smoking behaviors (topography measures and carbon monoxide [CO] boost). Thirty-six 12-hour-abstinent daily smokers completed a 3-session crossover trial. During each session, participants smoked their preferred brand cigarette - blinded and described as containing "usual," "low," and "very low" nicotine content - through a topography device and completed CO and subjective response assessments. Although nicotine content was identical, compared to the "usual" content cigarette, participants experienced less craving reduction after smoking the "very low" nicotine cigarette, and rated its smoke as weaker (p < .05). Participants took shallower puffs of the "low" nicotine cigarette (p < .05), and rated the "low" and "very low" nicotine cigarettes as weaker and too mild (p < .01). Negative responses to RNC cigarettes may be due, in part, to negative expectancies about using cigarettes containing less nicotine. In this context, RNC cigarette marketing and labeling are likely important considerations if a federal nicotine reduction policy is initiated.

Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma.

PubMed

Yu, Jeong Il; Yoo, Gyu Sang; Cho, Sungkoo; Jung, Sang Hoon; Han, Youngyih; Park, Seyjoon; Lee, Boram; Kang, Wonseok; Sinn, Dong Hyun; Paik, Yong-Han; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Park, Hee Chul

2018-03-01

This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of 62-92 GyE 10 . Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma

PubMed Central

Yu, Jeong Il; Yoo, Gyu Sang; Cho, Sungkoo; Jung, Sang Hoon; Han, Youngyih; Park, Seyjoon; Lee, Boram; Kang, Wonseok; Sinn, Dong Hyun; Paik, Yong-Han; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Park, Hee Chul

2018-01-01

Purpose This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. Materials and Methods HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of 62–92 GyE10. Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. Conclusion PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted. PMID:29580046

Radiation or chemoradiation: initial utility study of selected therapy for local advanced stadium cervical cancer

NASA Astrophysics Data System (ADS)

Pramitasari, D. A.; Gondhowiardjo, S.; Nuranna, L.

2017-08-01

This study aimed to compare radiation only or chemo radiation treatment of local advanced cervical cancers by examining the initial response of tumors and acute side effects. An initial assessment employed value based medicine (VBM) by obtaining utility values for both types of therapy. The incidences of acute lower gastrointestinal, genitourinary, and hematology side effects in patients undergoing chemoradiation did not differ significantly from those undergoing radiation alone. Utility values for patients who underwent radiation alone were higher compared to those who underwent chemoradiation. It was concluded that the complete response of patients who underwent chemoradiation did not differ significantly from those who underwent radiation alone.

Parenting Predictors of Cognitive Skills and Emotion Knowledge in Socioeconomically Disadvantaged Preschoolers

PubMed Central

Merz, Emily C.; Zucker, Tricia A.; Landry, Susan H.; Williams, Jeffrey M.; Assel, Michael; Taylor, Heather B.; Lonigan, Christopher J.; Phillips, Beth M.; Clancy-Menchetti, Jeanine; Barnes, Marcia A.; Eisenberg, Nancy; de Villiers, Jill

2014-01-01

This study examined the concurrent and longitudinal associations of parental responsiveness and inferential language input with cognitive skills and emotion knowledge among socioeconomically disadvantaged preschoolers. Parents and 2- to 4-year-old children (mean age = 3.21 years; N=284) participated in a parent-child free play session, and children completed cognitive (language, early literacy, early mathematics) and emotion knowledge assessments. One year later, children completed the same assessment battery. Parental responsiveness was coded from the videotaped parent-child free play sessions, and parental inferential language input was coded from transcripts of a subset of 127 of these sessions. All analyses controlled for child age, gender, and parental education, and longitudinal analyses controlled for initial skill level. Parental responsiveness significantly predicted all concurrent cognitive skills as well as literacy, math, and emotion knowledge one year later. Parental inferential language input was significantly positively associated with children's concurrent emotion knowledge. In longitudinal analyses, an interaction was found such that for children with stronger initial language skills, higher levels of parental inferential language input facilitated greater vocabulary development, whereas for children with weaker initial language skills, there was no association between parental inferential language input and change in children's vocabulary skills. These findings further our understanding of the roles of parental responsiveness and inferential language input in promoting children's school readiness skills. PMID:25576967

Teacher-Course Evaluation: A Longitudinal Study of Response Stability and Instrument Reliability.

ERIC Educational Resources Information Center

McCollester, Charles W.; And Others

The temporal context within which a teacher and course evaluation (TCE) is completed did not appear to be of crucial importance in affecting TCE responses. A sample of students was asked to evaluate, initially as freshmen and retrospectively as seniors, a specific teacher and course. Additional data on the student's academic status characteristics…

Training Rapid Stepping Responses in an Individual With Stroke

PubMed Central

Inness, Elizabeth L.; Komar, Janice; Biasin, Louis; Brunton, Karen; Lakhani, Bimal; McIlroy, William E.

2011-01-01

Background and Purpose Compensatory stepping reactions are important responses to prevent a fall following a postural perturbation. People with hemiparesis following a stroke show delayed initiation and execution of stepping reactions and often are found to be unable to initiate these steps with the more-affected limb. This case report describes a targeted training program involving repeated postural perturbations to improve control of compensatory stepping in an individual with stroke. Case Description Compensatory stepping reactions of a 68-year-old man were examined 52 days after left hemorrhagic stroke. He required assistance to prevent a fall in all trials administered during his initial examination because he showed weight-bearing asymmetry (with more weight borne on the more-affected right side), was unable to initiate stepping with the right leg (despite blocking of the left leg in some trials), and demonstrated delayed response times. The patient completed 6 perturbation training sessions (30–60 minutes per session) that aimed to improve preperturbation weight-bearing symmetry, to encourage stepping with the right limb, and to reduce step initiation and completion times. Outcomes Improved efficacy of compensatory stepping reactions with training and reduced reliance on assistance to prevent falling were observed. Improvements were noted in preperturbation asymmetry and step timing. Blocking the left foot was effective in encouraging stepping with the more-affected right foot. Discussion This case report demonstrates potential short-term adaptations in compensatory stepping reactions following perturbation training in an individual with stroke. Future work should investigate the links between improved compensatory step characteristics and fall risk in this vulnerable population. PMID:21511992

Deficits in inhibitory control and conflict resolution on cognitive and motor tasks in Parkinson's disease.

PubMed

Obeso, Ignacio; Wilkinson, Leonora; Casabona, Enrique; Bringas, Maria Luisa; Álvarez, Mario; Álvarez, Lázaro; Pavón, Nancy; Rodríguez-Oroz, Maria-Cruz; Macías, Raúl; Obeso, Jose A; Jahanshahi, Marjan

2011-07-01

Recent imaging studies in healthy controls with a conditional stop signal reaction time (RT) task have implicated the subthalamic nucleus (STN) in response inhibition and the pre-supplementary motor area (pre-SMA) in conflict resolution. Parkinson's disease (PD) is characterized by striatal dopamine deficiency and overactivity of the STN and underactivation of the pre-SMA during movement. We used the conditional stop signal RT task to investigate whether PD produced similar or dissociable effects on response initiation, response inhibition and response initiation under conflict. In addition, we also examined inhibition of prepotent responses on three cognitive tasks: the Stroop, random number generation and Hayling sentence completion. PD patients were impaired on the conditional stop signal reaction time task, with response initiation both in situations with or without conflict and response inhibition all being significantly delayed, and had significantly greater difficulty in suppressing prepotent or habitual responses on the Stroop, Hayling and random number generation tasks relative to controls. These results demonstrate the existence of a generalized inhibitory deficit in PD, which suggest that PD is a disorder of inhibition as well as activation and that in situations of conflict, executive control over responses is compromised.

Middle School Students' Reactions to a 1:1 iPad Initiative and a Paperless Curriculum

ERIC Educational Resources Information Center

Ferguson, Janet M.

2017-01-01

In this study, 676 middle school students in grades 6, 7 and 8 were asked to complete a survey online, during class time, which asked them their opinions on using iPads in school. Responses to the survey questions were generally positive however comments written at the end were very critical of the initiative. Significant differences were found…

Extended Survival after Complete Pathological Response in Metastatic Pancreatic Ductal Adenocarcinoma Following Induction Chemotherapy, Chemoradiotherapy, and a Novel Immunotherapy Agent, IMM-101

PubMed Central

Giakoustidis, Alex; Stamp, Gordon; Gaya, Andy; Mudan, Satvinder

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types.​ We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and off-protocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy.​ PMID:26870619

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

Mimura, Hidefumi, E-mail: mimura@marianna-u.ac.jp; Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp; Yamakado, Koichiro, E-mail: yama@clin.medic.mie-u.ac.jp

PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a furthermore » 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.« less

Radiosensitivity of cancer-initiating cells and normal stem cells (or what the Heisenberg uncertainly principle has to do with biology).

PubMed

Woodward, Wendy Ann; Bristow, Robert Glen

2009-04-01

Mounting evidence suggests that parallels between normal stem cell biology and cancer biology may provide new targets for cancer therapy. Prospective identification and isolation of cancer-initiating cells from solid tumors has promoted the descriptive and functional identification of these cells allowing for characterization of their response to contemporary cancer therapies, including chemotherapy and radiation. In clinical radiation therapy, the failure to clinically eradicate all tumor cells (eg, a lack of response, partial response, or nonpermanent complete response by imaging) is considered a treatment failure. As such, biologists have explored the characteristics of the small population of clonogenic cancer cells that can survive and are capable of repopulating the tumor after subcurative therapy. Herein, we discuss the convergence of these clonogenic studies with contemporary radiosensitivity studies that use cell surface markers to identify cancer-initiating cells. Implications for and uncertainties regarding incorporation of these concepts into the practice of modern radiation oncology are discussed.

American Indian Substance Use: The Hazards for Substance Use Initiation and Progression for Adolescents Aged 14 to 20 Years

ERIC Educational Resources Information Center

Novins, Douglas K.; Baron, Anna E.

2004-01-01

Objective: To describe the risks and risk factors for substance use initiation and progression among a large sample of American Indian (AI) adolescents. Method: Data came from surveys completed by 2,356 AI adolescents aged 14 to 20 years who participated in two or more consecutive waves of a longitudinal study between 1993 and 1996 (response rate…

A Preliminary Investigation of Pathways to Inflated Responsibility Beliefs in Children with Obsessive Compulsive Disorder.

PubMed

Collins, Lindsey M; Coles, Meredith E

2018-05-01

Cognitive theorists posit that inflated responsibility beliefs contribute to the development of obsessive compulsive disorder (OCD). Salkovskis et al. (1999) proposed that experiencing heightened responsibility, overprotective parents and rigid rules, and thinking one influenced or caused a negative life event act as 'pathways' to the development of inflated responsibility beliefs, thereby increasing risk for OCD. Studies in adults with OCD and non-clinical adolescents support the link between these experiences and responsibility beliefs (Coles et al., 2015; Halvaiepour and Nosratabadi, 2015), but the theory has never been tested in youth with current OCD. We provided an initial test of the theory by Salkovskis et al. (1999) in youth with OCD. We predicted that childhood experiences proposed by Salkovskis et al. (1999) would correlate positively with responsibility and harm beliefs and OCD symptom severity. Twenty youth with OCD (age 9‒16 years) completed a new child-report measure of the experiences hypothesized by Salkovskis et al. (1999), the Pathways to Inflated Responsibility Beliefs Scale-Child Version (PIRBS-CV). Youth also completed the Obsessive Beliefs Questionnaire-Child Version (Coles et al., 2010) and the Obsessive Compulsive Inventory-Child Version (Foa et al., 2010). Consistent with hypotheses, the PIRBS-CV was significantly related to responsibility and harm beliefs and OCD symptom severity. Results provide initial support for the theory proposed by Salkovskis et al. (1999) as applied to youth with OCD. Future studies are needed to further assess the model in early-onset OCD.

The South African Tuberculosis Care Cascade: Estimated Losses and Methodological Challenges

PubMed Central

Naidoo, Pren; Theron, Grant; Rangaka, Molebogeng X; Chihota, Violet N; Vaughan, Louise; Brey, Zameer O; Pillay, Yogan

2017-01-01

Abstract Background While tuberculosis incidence and mortality are declining in South Africa, meeting the goals of the End TB Strategy requires an invigorated programmatic response informed by accurate data. Enumerating the losses at each step in the care cascade enables appropriate targeting of interventions and resources. Methods We estimated the tuberculosis burden; the number and proportion of individuals with tuberculosis who accessed tests, had tuberculosis diagnosed, initiated treatment, and successfully completed treatment for all tuberculosis cases, for those with drug-susceptible tuberculosis (including human immunodeficiency virus (HIV)–coinfected cases) and rifampicin-resistant tuberculosis. Estimates were derived from national electronic tuberculosis register data, laboratory data, and published studies. Results The overall tuberculosis burden was estimated to be 532005 cases (range, 333760–764480 cases), with successful completion of treatment in 53% of cases. Losses occurred at multiple steps: 5% at test access, 13% at diagnosis, 12% at treatment initiation, and 17% at successful treatment completion. Overall losses were similar among all drug-susceptible cases and those with HIV coinfection (54% and 52%, respectively, successfully completed treatment). Losses were substantially higher among rifampicin- resistant cases, with only 22% successfully completing treatment. Conclusion Although the vast majority of individuals with tuberculosis engaged the public health system, just over half were successfully treated. Urgent efforts are required to improve implementation of existing policies and protocols to close gaps in tuberculosis diagnosis, treatment initiation, and successful treatment completion. PMID:29117342

Hyberbaric oxygen as sole treatment for severe radiation - induced haemorrhagic cystitis

PubMed Central

Dellis, Athanasios; Papatsoris, Athanasios; Kalentzos, Vasileios; Deliveliotis, Charalambos; Skolarikos, Andreas

2017-01-01

ABSTRACT Purpose To examine the safety and efficacy of hyperbaric oxygen as the primary and sole treatment for severe radiation-induced haemorrhagic cystitis. Materials and methods Hyperbaric oxygen was prospectively applied as primary treatment in 38 patients with severe radiation cystitis. Our primary endpoint was the incidence of complete and partial response to treatment, while the secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival. Results All patients completed therapy without complications with a mean follow-up of 29.33 months. Median number of sessions needed was 33. Complete and partial response rate was 86.8% and 13.2%, respectively. All 33 patients with complete response received therapy within 6 months of the haematuria onset. One patient needed cystectomy, while 33 patients were alive at the end of follow-up. Conclusions Our study suggests the early primary use of hyperbaric oxygen for radiation-induced severe cystitis as an effective and safe treatment option. PMID:28338304

Cognitive and Neural Sciences Division. 1988 Programs

DTIC Science & Technology

1988-08-01

the P.I. uses a delayed reinforcement autoshaping procedure which incorporates features of both classical and operant conditioning paradigms...Progress: The PT has completed initial dose-response study of effects of TMT on autoshaping and has submitted a paper that separates "non-specific

Effects of suspension on tissue levels of glucocorticoid receptors

NASA Technical Reports Server (NTRS)

Steffen, J. M.

1984-01-01

Differential muscle responses can be simulated by hypokinetic/hypodynamic (H/H) suspension of rats with complete unloading of the hindlimb muscles. Since mechanism(s) underlying these atrophic effects were not clearly elucidated, experiments were initiated to investigate a possible role for glucocorticoids in the physiological and biochemical responses to H/H. The principal objective was to assess the potential for alterations in peripheral responsiveness to glucocorticoids in response to H/H. Studies have initially focused on the determination of tissue levels of glucocorticoid receptors as one index of hormonal sensitivity at the cellular level. Four hindlimb muscles (soleus, gastrocnemius, plantaris and EDL), previously demonstrated to exhibit differential responses to H/H, were investigated. Receptor levels in other glucocorticoid sensitive tissues (heart, liver, and kidney) were determined. Male rats (180-200g) were suspended for 7 or 14 days, sacrificed by cervical dislocation, and the tissues excised.

Blade loss transient dynamic analysis of turbomachinery

NASA Technical Reports Server (NTRS)

Stallone, M. J.; Gallardo, V.; Storace, A. F.; Bach, L. J.; Black, G.; Gaffney, E. F.

1982-01-01

This paper reports on work completed to develop an analytical method for predicting the transient non-linear response of a complete aircraft engine system due to the loss of a fan blade, and to validate the analysis by comparing the results against actual blade loss test data. The solution, which is based on the component element method, accounts for rotor-to-casing rubs, high damping and rapid deceleration rates associated with the blade loss event. A comparison of test results and predicted response show good agreement except for an initial overshoot spike not observed in test. The method is effective for analysis of large systems.

Effect of Initial Stress on the Dynamic Response of a Multi-Layered Plate-Strip Subjected to an Arbitrary Inclined Time-Harmonic Force

NASA Astrophysics Data System (ADS)

Daşdemir, A.

2017-08-01

The forced vibration of a multi-layered plate-strip with initial stress under the action of an arbitrary inclined time-harmonic force resting on a rigid foundation is considered. Within the framework of the piecewise homogeneous body model with the use of the three-dimensional linearized theory of elastic waves in initially stressed bodies (TLTEWISB), a mathematical modelling is presented in plane strain state. It is assumed that there exists the complete contact interaction at the interface between the layers and the materials of the layer are linearly elastic, homogeneous and isotropic. The governing system of the partial differential equations of motion for the considered problem is solved approximately by employing the Finite Element Method (FEM). Further, the influence of the initial stress parameter on the dynamic response of the plate-strip is presented.

[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.

Color vision abnormality as an initial presentation of the complete type of congenital stationary night blindness.

PubMed

Tan, Xue; Aoki, Aya; Yanagi, Yasuo

2013-01-01

Patients with the complete form of congenital stationary night blindness (CSNB) often have reduced visual acuity, myopia, impaired night vision, and sometimes nystagmus and strabismus, however, they seldom complain of color vision abnormality. A 17-year-old male who was at technical school showed abnormalities in the color perception test for employment, and was referred to our hospital for a detailed examination. He had no family history of color vision deficiency and no other symptoms. During the initial examination, his best-corrected visual acuity was 1.2 in both eyes. His fundus showed no abnormalities except for somewhat yellowish reflex in the fovea of both eyes. Electroretinogram (ERG) showed a good response in cone ERG and 30 Hz flicker ERG, however, the bright flash, mixed rod and cone ERG showed a negative type with a reduced b-wave (positive deflection). There was no response in the rod ERG, either. From the findings of the typical ERG, the patient was diagnosed with complete congenital stationary night blindness. This case underscores the importance of ERG in order to diagnose the cause of a color vision anomaly.

Seasonal Prediction with the GEOS GCM

NASA Technical Reports Server (NTRS)

Suarez, Max; Schubert, S.; Chang, Y.

1999-01-01

A number of ensembles of seasonal forecasts have recently been completed as part of NASA's Seasonal to Interannual Prediction Project (NSIPP). The focus is on the extratropical response of the atmosphere to observed SST anomalies during boreal winter. Each prediction consists of nine forecasts starting from slightly different initial conditions. Forecasts are done for every winter from 1981 to 1995 using Version 2 of the GEOS GCM. Comparisons with six long-term integrations (1978-1995) using the same model are used to separate the contributions of initial and boundary conditions to forecast skill. The forecasts also allow us to isolate the SSt forced response (the signal) from the atmosphere's natural variability (the noise).

Meso-beta scale numerical simulation studies of terrain-induced jet streak mass/momentum perturbations

NASA Technical Reports Server (NTRS)

Lin, Yuh-Lang; Kaplan, Michael L.

1993-01-01

The first section is on 3-D numerical modeling of terrain-induced circulations and covers the following: (1) additional insights into gravity wave generation mechanisms based on the control simulation; (2) ongoing nested-grid numerical simulations; (3) work to be completed during the remainder of FY-93; and (4) work objectives for FY-94. The second section is on linear theory and theoretical modeling and covers the following: (1) the free response of a uniform barotropic flow to an initially stationary unbalanced (ageostrophic) zonal wind anomaly; and (2) the free response of a uniform barotropic flow to an initially stationary balanced zonal wind anomaly.

Nurses' Interest in Independently Initiating End-of-Life Conversations and Palliative Care Consultations in a Suburban, Community Hospital.

PubMed

Mehta, Ambereen K; Wilks, Steven; Cheng, M Jennifer; Baker, Karen; Berger, Ann

2018-03-01

Patients who receive early palliative care consults have clinical courses and outcomes more consistent with their goals. Nurses have been shown to be advocates for early palliative care involvement and are able to lead advanced care planning discussions. The purpose of this study was to assess whether after a brief educational session, nurses at a suburban, community hospital could demonstrate knowledge of palliative care principles, would want to independently initiate end-of-life conversations with patients and families, and would want to place specialty palliative care consults. Four 1 hour presentations were made at 4 nursing leadership council meetings from November through December 2015. Anonymous pre- and post-presentation surveys were distributed and collected in person. Setting/Participant: Nonprofit, suburban, community hospital in Maryland. Participants were full-time or part-time hospital employees participating in a nursing leadership council who attended the presentation. We compared responses from pre- and post-presentation surveys. Fifty nurses (19 departments) completed pre-presentation surveys (100% response rate) and 49 nurses completed post-presentation surveys (98% response rate). The average score on 7 index questions increased from 71% to 90%. After the presentations, 86% strongly agreed or agreed that nurses should be able to independently order a palliative care consult and 88% strongly agreed or agreed with feeling comfortable initiating an end-of-life conversation. Brief educational sessions can teach palliative care principles to nurses. Most participants of the study would want to be able to directly consult palliative care and would feel comfortable initiating end-of-life conversations after this educational session.

Comparison of the effects of the antiestrogens EM-800 and tamoxifen on the growth of human breast ZR-75-1 cancer xenografts in nude mice.

PubMed

Couillard, S; Gutman, M; Labrie, C; Bélanger, A; Candas, B; Labrie, F

1998-01-01

Although estrone supplementation in ovariectomized (OVX) nude mice bearing ZR-75-1 xenografts caused a 365% increase in average tumor size during the 4-month treatment period, administration of the antiestrogen EM-800 at the daily oral doses of 50, 150, or 400 microg completely prevented estrogen-stimulated tumor growth. At the same doses of tamoxifen, tumor size was inhibited to 189, 117, and 120% above pretreatment values. However, when EM-800 (150 microg/day) was added to the daily 150- and 400-microg doses of tamoxifen, final tumor size was decreased further to 12 and 38% above pretreatment values, respectively. EM-800 (400 microg daily) administered to estrone-supplemented OVX mice caused complete, partial, and stable responses in 11, 22, and 49% of estrone-stimulated tumors, respectively, whereas 19% (7 of 37) progressed. At the same dose of tamoxifen, the corresponding responses were 3% (complete response), 3% (partial response), and 25% (no change), whereas 69% (22 of 32) of tumors progressed. In the absence of estrone supplementation, tamoxifen (400 microg) alone administered to OVX mice stimulated tumor growth to 161% compared with initial size whereas the same dose of EM-800 reduced tumor size by 55%, a value superimposable to that observed in OVX control animals. The agonistic effect of tamoxifen is thus illustrated by the observation that 73% of tumors progressed when tamoxifen was administered alone to OVX animals whereas no tumor progressed with EM-800. The present data strongly suggest that at least part of the initial lack of response and resistance to tamoxifen during tamoxifen treatment in women is due to the estrogenic activity of this compound, whereas the new antiestrogen EM-800 exerts pure antagonistic action.

Different response of human glioma tumor-initiating cells to epidermal growth factor receptor kinase inhibitors.

PubMed

Griffero, Fabrizio; Daga, Antonio; Marubbi, Daniela; Capra, Maria Cristina; Melotti, Alice; Pattarozzi, Alessandra; Gatti, Monica; Bajetto, Adriana; Porcile, Carola; Barbieri, Federica; Favoni, Roberto E; Lo Casto, Michele; Zona, Gianluigi; Spaziante, Renato; Florio, Tullio; Corte, Giorgio

2009-03-13

Because a subpopulation of cancer stem cells (tumor-initiating cells, TICs) is believed to be responsible for the development, progression, and recurrence of many tumors, we evaluated the in vitro sensitivity of human glioma TICs to epidermal growth factor receptor (EGFR) kinase inhibitors (erlotinib and gefitinib) and possible molecular determinants for their effects. Cells isolated from seven glioblastomas (GBM 1-7) and grown using neural stem cell permissive conditions were characterized for in vivo tumorigenicity, expression of tumor stem cell markers (CD133, nestin), and multilineage differentiation properties, confirming that these cultures are enriched in TICs. TIC cultures were challenged with increasing concentrations of erlotinib and gefitinib, and their survival was evaluated after 1-4 days. In most cases, a time- and concentration-dependent cell death was observed, although GBM 2 was completely insensitive to both drugs, and GBM 7 was responsive only to the highest concentrations tested. Using a radioligand binding assay, we show that all GBM TICs express EGFR. Erlotinib and gefitinib inhibited EGFR and ERK1/2 phosphorylation/activation in all GBMs, irrespective of the antiproliferative response observed. However, under basal conditions GBM 2 showed a high Akt phosphorylation that was completely insensitive to both drugs, whereas GBM 7 was completely insensitive to gefitinib, and Akt inactivation occurred only for the highest erlotinib concentration tested, showing a precise relationship with the antiproliferative effects of the drug. Interestingly, in GBM 2, phosphatase and tensin homolog expression was significantly down-regulated, possibly accounting for the insensitivity to the drugs. In conclusion, glioma TICs are responsive to anti-EGFR drugs, but phosphatase and tensin homolog expression and Akt inhibition seem to be necessary for such effect.

Breast cancer: complete response with the combination of sunitinib and trastuzumab in a patient with grade III ductal carcinoma.

PubMed

Puente, Javier; Manzano, Aranzazu; Martin, Miguel; López-Tarruella, Sonia; Díaz-Rubio, Eduardo

2010-01-01

In August 2000, a previously healthy postmenopausal 52-year-old woman was diagnosed with grade III invasive ductal carcinoma. The tumor had an ER -, PR -, and HER2 + profile. Adjuvant treatment with FEC was initiated followed by radiotherapy. In October 2004, the patient presented a clinically asymptomatic supraclavicular and mediastinal lymph node recurrence and treatment with paclitaxel and trastuzumab was initiated. A complete response was achieved after 20 weeks of treatment, and in January 2006 treatment was interrupted due to toxicity. After a 34-month free-of-relapse period, a local recurrence was detected in the chest wall. In September 2007, the patient joined a phase II trial with sunitinib (37.5 mg once a day in 28 days cycles) and trastuzumab (6 mg/kg every 3 weeks), after having verified a normal cardiac function. After two courses, a partial cutaneous response and a complete radiological response were obtained. The most relevant toxicities included cutaneous hyperpigmentation, dysgeusia, mucositis, grade II diarrhea and hypertension. The development of grade III diarrhea led to sunitinib dose reduction (25mg/day). In January 2008, the patient developed hypothyroidism and a significant drop in the left ventricular ejection fraction that led to treatment interruption. In March 2008, once cardiac function was recovered, treatment at the same dose was reinitiated. After two months of treatment, a new descent in cardiac function was noted which led to the suspension of sunitinib, and the interruption of the trastuzumab treatment until recovery of normal cardiac function. In July 2008, trastuzumab monotherapy was resumed and since then no cardiac events have been reported, while maintaining a radiological and clinical response.

Efficacy of OK-432 sclerotherapy in treatment of lymphatic malformations: long-term follow-up results.

PubMed

Weitz-Tuoretmaa, Annamaria; Rautio, Riitta; Valkila, Jan; Keski-Säntti, Harri; Keski-Nisula, Leo; Laranne, Jussi

2014-02-01

Lymphatic malformations (LMs) are rare congenital tumors of the lymphatic system often affecting the head and neck area. Because of cosmetic and functional symptoms most patients need to be treated. Traditionally surgical treatment has been considered to be the first-line treatment for LM. However, it is challenging because of the need for complete excision. The risk of poor cosmetic result and damage to surrounding structures is high. Since Ogita presented OK-432 as a treatment for LM in 1987, it has been widely used as the primary treatment. Many papers have been published on this topic but with relatively short follow-up times. We present a material of 36 LMs treated with OK-432 during the period of 1999-2009 and with an average follow-up time of 6 years. Immediate post-treatment results were compared with the late follow-up findings. Primary and late response to therapy was evaluated with an MRI scan by measuring the change in lesion size. At the follow-up visit, all patients were clinically examined and they answered a symptom questionnaire. Later 26/36 patients were also available for a quality of life questionnaire. Primarily 67% demonstrated a complete or marked response. At the follow-up 64% showed a complete or marked response, in 11% the final response was better than the initially observed and only 2 patients had relapsed. The initial response predicted the long-term outcome accurately and the effect of OK-432 sclerotherapy seems to be long lasting. According to the MRI evaluation 80% and subjectively 94% of the patients benefitted from the treatment. Quality of life questionnaire showed high post-treatment satisfaction. We found OK-432 sclerotherapy to be a safe and effective treatment with a long lasting effect in the management of macrocystic LMs.

Sequential Use of Second-Generation Tyrosine Kinase Inhibitor Treatment and Intensive Chemotherapy Induced Long-Term Complete Molecular Response in Imatinib-Resistant CML Patient Presenting as a Myeloid Blast Crisis

PubMed Central

Uchiyama, Tatsuki; Mizumoto, Chisaki; Takeoka, Tomoharu; Tomo, Kenjiro; Ohno, Tatsuharu

2017-01-01

Myeloid blast crisis of chronic myeloid leukemia (CML-MBC) is rarely seen at presentation and has a poor prognosis. There is no standard therapy for CML-MBC. It is often difficult to distinguish CML-MBC from acute myeloid leukemia expressing the Philadelphia chromosome (Ph+ AML). We present a case in which CML-MBC was seen at the initial presentation in a 75-year-old male. He was treated with conventional AML-directed chemotherapy followed by imatinib mesylate monotherapy, which failed to induce response. However, he achieved long-term complete molecular response after combination therapy involving dasatinib, a second-generation tyrosine kinase inhibitor, and conventional chemotherapy. PMID:29391957

Assessment for self-blame and trauma symptoms during the medical evaluation of suspected sexual abuse.

PubMed

Melville, John D; Kellogg, Nancy D; Perez, Nadia; Lukefahr, James L

2014-05-01

The purpose of this study was to describe behavioural and emotional symptoms and to examine the effect of abuse-related factors, family responses to disclosure, and child self-blame on these symptoms in children presenting for medical evaluations after disclosure of sexual abuse. A retrospective review was conducted of 501 children ages 8-17. Trauma symptoms were determined by two sets of qualitative measures. Abstracted data included gender, ethnicity, and age; severity of abuse and abuser relationship to child; child responses regarding difficulty with sleep, school, appetite/weight, sadness, or self-harm, parent belief in abuse disclosure, and abuse-specific self-blame; responses to the Trauma Symptom Checklist in Children-Alternate; and the parent's degree of belief in the child's sexual abuse disclosure. Overall, 83% of the children had at least one trauma symptom; 60% had difficulty sleeping and one-third had thoughts of self-harm. Child age and abuse severity were associated with 3 of 12 trauma symptoms, and abuse-specific self-blame was associated with 10 trauma symptoms, after controlling for other variables. The children of parents who did not completely believe the initial disclosure of abuse were twice as likely to endorse self-blame as children of parents who completely believed the initial disclosure. Screening for behavioural and emotional problems during the medical assessment of suspected sexual abuse should include assessment of self-blame and family responses to the child's disclosures. In addition, parents should be informed of the importance of believing their child during the initial disclosure of abuse and of the impact this has on the child's emotional response to the abuse. Copyright © 2014 Elsevier Ltd. All rights reserved.

Corrective response times in a coordinated eye-head-arm countermanding task.

PubMed

Tao, Gordon; Khan, Aarlenne Z; Blohm, Gunnar

2018-06-01

Inhibition of motor responses has been described as a race between two competing decision processes of motor initiation and inhibition, which manifest as the reaction time (RT) and the stop signal reaction time (SSRT); in the case where motor initiation wins out over inhibition, an erroneous movement occurs that usually needs to be corrected, leading to corrective response times (CRTs). Here we used a combined eye-head-arm movement countermanding task to investigate the mechanisms governing multiple effector coordination and the timing of corrective responses. We found a high degree of correlation between effector response times for RT, SSRT, and CRT, suggesting that decision processes are strongly dependent across effectors. To gain further insight into the mechanisms underlying CRTs, we tested multiple models to describe the distribution of RTs, SSRTs, and CRTs. The best-ranked model (according to 3 information criteria) extends the LATER race model governing RTs and SSRTs, whereby a second motor initiation process triggers the corrective response (CRT) only after the inhibition process completes in an expedited fashion. Our model suggests that the neural processing underpinning a failed decision has a residual effect on subsequent actions. NEW & NOTEWORTHY Failure to inhibit erroneous movements typically results in corrective movements. For coordinated eye-head-hand movements we show that corrective movements are only initiated after the erroneous movement cancellation signal has reached a decision threshold in an accelerated fashion.

Role of an audience response system in didactic attendance and assessment.

PubMed

Stoneking, Lisa R; Grall, Kristi H; Min, Alice; Dreifuss, Bradley; Spear Ellinwood, Karen C

2014-06-01

The Residency Review Committee for Emergency Medicine mandates conference participation, but tracking attendance is difficult and fraught with errors. Feedback on didactic sessions, if not collected in real time, is challenging to obtain. We assessed whether an audience response system (ARS) would (1) encourage residents to arrive on time for lectures, and (2) increase anonymous real-time audience feedback. The ARS (Poll Everywhere) provided date/time-stamped responses to polls from residents, including a question to verify attendance and questions to gather immediate, anonymous postconference evaluations. Fisher exact test was used to calculate proportions. The proportion of residents who completed evaluations prior to the institution of the ARS was 8.75, and it was 59.42 after (P < .001). The proportion of faculty who completed evaluations prior to using the ARS was 6.12, and it was 85.71 after (P < .001). The proportion of residents who reported they had attended the conference session was 55 for the 3 weeks prior to initiating the ARS, decreasing to 46.67 for the 3 weeks during which the ARS was used to take attendance (P  =  .46). The proportion of faculty who reported attending the conference was 5.56 for the 3 weeks prior to ARS initiation, decreasing to 4.44 for the 3 weeks while using the ARS (P  =  .81). Audience response systems are an effective way to verify attendance and tardiness, eliminating the subjective effect of attendance takers' leniency and increasing completion of evaluations for didactic sessions.

Evaluation and optimization of ethanol production from carob pod extract by Zymomonas mobilis using response surface methodology.

PubMed

Vaheed, Hossein; Shojaosadati, Seyed Abbas; Galip, Hasan

2011-01-01

In this research, ethanol production from carob pod extract (extract) using Zymomonas mobilis with medium optimized by Plackett-Burman (P-B) and response surface methodologies (RSM) was studied. Z. mobilis was recognized as useful for ethanol production from carob pod extract. The effects of initial concentrations of sugar, peptone, and yeast extract as well as agitation rate (rpm), pH, and culture time in nonhydrolyzed carob pod extract were investigated. Significantly affecting variables (P = 0.05) in the model obtained from RSM studies were: weights of bacterial inoculum, initial sugar, peptone, and yeast extract. Acid hydrolysis was useful to complete conversion of sugars to glucose and fructose. Nonhydrolyzed extract showed higher ethanol yield and residual sugar compared with hydrolyzed extract. Ethanol produced (g g(-1) initial sugar, as the response) was not significantly different (P = 0.05) when Z. mobilis performance was compared in hydrolyzed and nonhydrolyzed extract. The maximum ethanol of 0.34 ± 0.02 g g(-1) initial sugar was obtained at 30°C, initial pH 5.2, and 80 rpm, using concentrations (g per 50 mL culture media) of: inoculum bacterial dry weight, 0.017; initial sugar, 5.78; peptone, 0.43; yeast extract, 0.43; and culture time of 36 h.

Cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) combination sequential chemotherapy for advanced diffuse histiocytic lymphoma

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

Sweet, D.L.; Golomb, H.M.; Ultmann, J.E.

A program of combination sequential chemotherapy using cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) was administered to 42 previously untreated patients with advanced diffuse histiocytic lymphoma. Twenty-three patients achieved a complete remission as determined by strict clinical restaging criteria. The observed median duration of survival for the complete responders is longer than 33 months. Eight patients achieved a partial response, with a median survival longer than 21 months. Eleven patients showed no response, with a median survival of 5 months. Toxicity was acceptable. None of the responders have shown central nervous system relapse. There was no difference inmore » response rates between patients with stage III or IV lymphoma or between asymptomatic or symptomatic patients. The COMLA program produces a high rate of complete and durable remissions and should be considered as an initial form of management of patients with advanced diffuse histiocytic lymphoma.« less

Complete unconscious control: Using (in)action primes to demonstrate completely unconscious activation of inhibitory control mechanisms

PubMed Central

Hepler, Justin; Albarracin, Dolores

2018-01-01

Although robust evidence indicates that action initiation can occur unconsciously and unintentionally, the literature on action inhibition suggests that inhibition requires both conscious thought and intentionality. In prior research demonstrating automatic inhibition in response to unconsciously processed stimuli, the unconscious stimuli had previously been consciously associated with an inhibitory response within the context of the experiment, and participants had consciously formed a goal to activate inhibition processes when presented with the stimuli (because task instructions required participants to engage in inhibition when the stimuli occurred). Therefore, prior work suggests that some amount of conscious thought and intentionality are required for inhibitory control. In the present research, we recorded event-related potentials during two go/no-go experiments in which participants were subliminally primed with general action/inaction concepts that had never been consciously associated with task-specific responses. We provide the first demonstration that inhibitory control processes can be modulated completely unconsciously and unintentionally. PMID:23747649

32 CFR 728.112 - Responsibilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... unless patient administration departments take the initial step to complete: (1) DD 7, Report of Treatment Furnished Pay Patients, Hospitalization Furnished (part A). Prepare a separate substantiating DD 7... any pay patient is admitted, submit DD 7's to the collection agent. (2) DD 7A, Report of Treatment...

75 FR 57959 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-23

... perceptions of roles and responsibilities for obesity prevention. The baseline or ``pre-test'' questionnaire will be administered before the initial discussion group, and the ``post-test'' questionnaire will be... from a comparison group of 700 respondents who will complete pre- and post-intervention questionnaires...

Summary Statistics of the National Railroad-Highway Crossing Inventory for Public At-Grade Crossings

DOT National Transportation Integrated Search

1977-09-01

In response to the Federal Railroad Safety Act of 1970, a joint government/industry effort to compile a national inventory of railroad-highway crossings was initiated in 1972 and completed in 1976. The inventory contains data on the physical and oper...

Dynamics of an Overdriven Nitromethane Initiation System

NASA Astrophysics Data System (ADS)

Hároz, E. H.; Rae, P. J.; Armstrong, C. L.; Baca, E. V.; Campbell, C.; Gunderson, J. A.; Holmes, M.; Lopez-Pulliam, I.; Vaughan, L. D.; Dickson, P. M.

2017-06-01

For upcoming large-scale HE experiments, an initiation system is needed to ensure uniform and simultaneous burn. To that end, we developed an initiation system based on nitromethane. Initial, small-scale tests characterized the response of the nitromethane in the proposed cylindrical initiator geometry, indicating robust detonation under a variety of conditions such as a plane wave lenses & cylinders of PBX 9501 into a flyer plate or direct-drive. Detonation velocity, as measured by piezoelectric pin time-of-arrival measurements along the length and at bottom of vessel, shows an overdriven response. All cases show a detonation velocity faster than the literature value of 7.3 km s-1 for nitromethane, with the fastest velocity occurring for the 8-detonator, 8'' cylinder case with a velocity = 7.7 km s-1. Streak camera imaging characterized the curvature of the shock front as it arrived at the bottom of the vessel via spark gap. A final test of the initiator system looked at the expansion of the initiator vessel walls via PDV, showing velocities up to 3.5 km s-1. Finally, our initiator was placed inside a secondary vessel containing 1000 lbs of nitromethane. High-speed photography & pin data indicate complete symmetrical burn of the secondary nitromethane.

The South African Tuberculosis Care Cascade: Estimated Losses and Methodological Challenges.

PubMed

Naidoo, Pren; Theron, Grant; Rangaka, Molebogeng X; Chihota, Violet N; Vaughan, Louise; Brey, Zameer O; Pillay, Yogan

2017-11-06

While tuberculosis incidence and mortality are declining in South Africa, meeting the goals of the End TB Strategy requires an invigorated programmatic response informed by accurate data. Enumerating the losses at each step in the care cascade enables appropriate targeting of interventions and resources. We estimated the tuberculosis burden; the number and proportion of individuals with tuberculosis who accessed tests, had tuberculosis diagnosed, initiated treatment, and successfully completed treatment for all tuberculosis cases, for those with drug-susceptible tuberculosis (including human immunodeficiency virus (HIV)-coinfected cases) and rifampicin-resistant tuberculosis. Estimates were derived from national electronic tuberculosis register data, laboratory data, and published studies. The overall tuberculosis burden was estimated to be 532005 cases (range, 333760-764480 cases), with successful completion of treatment in 53% of cases. Losses occurred at multiple steps: 5% at test access, 13% at diagnosis, 12% at treatment initiation, and 17% at successful treatment completion. Overall losses were similar among all drug-susceptible cases and those with HIV coinfection (54% and 52%, respectively, successfully completed treatment). Losses were substantially higher among rifampicin- resistant cases, with only 22% successfully completing treatment. Although the vast majority of individuals with tuberculosis engaged the public health system, just over half were successfully treated. Urgent efforts are required to improve implementation of existing policies and protocols to close gaps in tuberculosis diagnosis, treatment initiation, and successful treatment completion. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

FDG-PET response of skeletal (bone marrow and bone) involvement after induction chemotherapy in pediatric Hodgkin lymphoma - Are specific response criteria required?

PubMed

Georgi, Thomas Walter; Kluge, Regine; Kurch, Lars; Chavdarova, Lidia; Hasenclever, Dirk; Stoevesandt, Dietrich; Pelz, Tanja; Landman-Parker, Judith; Wallace, Hamish; Karlen, Jonas; Fernandez-Teijeiro, Ana; Cepelova, Michaela; Fossa, Alexander; Balwierz, Walentyna; Attarbaschi, Andishe; Ammann, Roland A; Pears, Jane; Hraskova, Andrea; Uyttebroeck, Anne; Beishuizen, Auke; Dieckmann, Karin; Leblanc, Thierry; Daw, Stephen; Baumann, Julia; Körholz, Dieter; Sabri, Osama; Mauz-Körholz, Christine

2018-04-13

Purpose: This study focused on skeletal involvement in FDG-PET (PET) in Hodgkin lymphoma (HL). We aimed at a systematic evaluation of the different types of skeletal involvement and their PET response after two cycles of chemotherapy (PET-2), to answer the question whether the current PET response criterion for skeletal involvement is suitable. A secondary objective was to observe the influence of initial uptake intensity and metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. Methods: Initial PET scans (PET-0) of 1068 pediatric HL patients from the EuroNet-PHL-C1 (C1) trial were evaluated by central review for skeletal involvement. Three types of skeletal lesions were distinguished: skeletal lesions detected only in PET (PETonly), bone marrow (BM) lesions confirmed by MRI or BM biopsy and bone lesions. Uptake intensity (measured as qPET value) and MTV were calculated for each skeletal lesion. All PET-2 scans were assessed for residual tumor activity. The rates of complete metabolic response in PET-2 of skeletal and nodal involvement were compared. Results: 139/1068 (13%) C1 patients showed skeletal involvement (44/139 PETonly patients, 32/139 BM patients and 63/139 bone patients). 101/139 (73%) patients became PET-2 negative in the skeleton while lymph node involvement was PET-2 negative in 94/139 (68%) patients. Highest skeletal PET-2 negative rate was seen in 42/44 (95%) PETonly patients, followed by 22/32 (69%) BM patients and 37/63 (59%) bone patients. Skeletal lesions who became PET-2 negative showed lower median values for initial qPET (2.74) and MTV (2ml) than lesions who remained PET-2 positive (3.84; 7ml). Conclusion: In this study with pediatric HL patients, the complete response rate in PET-2 of skeletal and nodal involvement was similar. Bone flare seemed to be irrelevant. Overall, the current skeletal PET response criterion - comparison with the local skeletal background - is well suited. Initial uptake intensity and MTV of skeletal lesions were predictive for the PET-2 result. Higher values for both parameters were associated with a worse PET-2 response. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

The segment as the minimal planning unit in speech production and reading aloud: evidence and implications.

PubMed

Kawamoto, Alan H; Liu, Qiang; Kello, Christopher T

2015-01-01

Speech production and reading aloud studies have much in common, especially the last stages involved in producing a response. We focus on the minimal planning unit (MPU) in articulation. Although most researchers now assume that the MPU is the syllable, we argue that it is at least as small as the segment based on negative response latencies (i.e., response initiation before presentation of the complete target) and longer initial segment durations in a reading aloud task where the initial segment is primed. We also discuss why such evidence was not found in earlier studies. Next, we rebut arguments that the segment cannot be the MPU by appealing to flexible planning scope whereby planning units of different sizes can be used due to individual differences, as well as stimulus and experimental design differences. We also discuss why negative response latencies do not arise in some situations and why anticipatory coarticulation does not preclude the segment MPU. Finally, we argue that the segment MPU is also important because it provides an alternative explanation of results implicated in the serial vs. parallel processing debate.

Initial Localization of the Memory Trace for a Basic Form of Learning

NASA Astrophysics Data System (ADS)

McCormick, David A.; Clark, Gregory A.; Lavond, David G.; Thompson, Richard F.

1982-04-01

Electrophysiological recording of neuronal unit activity during paired training trials from various regions of the ipsilateral cerebellum in rabbits well trained in the classically conditioned eyelid/nictitating membrane response have revealed both stimulus-evoked responses and responses that form an amplitude/temporal model of the learned behavioral response. Ablation of the ipsilateral, lateral cerebellum completely and permanently abolished the behavioral conditioned response in well-trained animals but had no effect at all on the unconditioned reflex response. In marked contrast, conditioned responses were easily trained in the eye contralateral to the cerebellar lesion. We suggest that at least part of the essential neuronal plasticity that codes the learned response may be localized to the cerebellum.

The potential influence of radiation-induced microenvironments in neoplastic progression

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

1998-01-01

Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

Evolutionary Technique for Automated Synthesis of Electronic Circuits

NASA Technical Reports Server (NTRS)

Stoica, Adrian (Inventor); Salazar-Lazaro, Carlos Harold (Inventor)

2003-01-01

A method for evolving a circuit comprising configuring a plurality of transistors using a plurality of reconfigurable switches so that each of the plurality of transistors has a terminal coupled to a terminal of another of the plurality of transistors that is controllable by a single reconfigurable switch. The plurality of reconfigurable switches being controlled in response to a chromosome pattern. The plurality of reconfigurable switches may be controlled using an annealing function. As such, the plurality of reconfigurable switches may be controlled by selecting qualitative values for the plurality of reconfigurable switches in response to the chromosomal pattern, selecting initial quantitative values for the selected qualitative values, and morphing the initial quantitative values. Typically, subsequent quantitative values will be selected more divergent than the initial quantitative values. The morphing process may continue to partially or to completely polarize the quantitative values.

Reflex changes in breathing pattern evoked by inhalation of wood smoke in rats

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

Kou, Y.R.; Lai, C.J.

1994-06-01

The acute ventilatory response to inhalation of wood smoke was studied in 58 anesthetized Sprague-Dawley rats. Wood smoke ([approximately]6 ml) was inhaled spontaneously via a tracheal cannula. Within the first two breaths of smoke inhalation, either a slowing of respiration (SR) (n=39) or an augmented inspiration (AI) (n=19) was elicited consistently in each rat. The SR was primarily due to a prolongation of expiratory duration, whereas the AI was characterized by a two-step inspiratory flow leading to an exceedingly large tidal volume. Both initial responses, usually accompanied by bradycardia and hypotension, were reduced by inhaling smoke at a decreased concentration.more » After these initial responses, a delayed tachypnea developed and reached its peak 6-10 breaths after inhalation of smoke. Both the SR and AI were completely abolished by bilateral cervical vagotomy. In contrast, the delayed tachypneic response was not prevented by vagotomy but was significantly attenuated by denervation of peripheral chemoreceptors. The authors conclude that the initial responses to inhalation of several tidal breaths of wood smoke are mediated through vagal bronchopulmonary afferents, whereas the delayed tachypnea may involve nonvagal mechanisms that include a stimulation of peripheral chemoreceptors.« less

Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01).

PubMed

Suenaga, Mitsukuni; Fujimoto, Yoshiya; Matsusaka, Satoshi; Shinozaki, Eiji; Akiyoshi, Takashi; Nagayama, Satoshi; Fukunaga, Yosuke; Oya, Masatoshi; Ueno, Masashi; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu

2015-01-01

Perioperative chemotherapy combined with surgery for liver metastases is considered an active strategy in metastatic colorectal cancer (CRC). However, its impact on initially unresectable, previously untreated advanced CRC, regardless of concurrent metastases, remains to be clarified. A Phase II study was conducted to evaluate the safety and efficacy of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced CRC. Patients with previously untreated advanced colon or rectal cancer initially diagnosed as unresectable advanced CRC (TNM stage IIIb, IIIc, or IV) but potentially resectable after neoadjuvant chemotherapy (NAC) were studied. Preoperatively, patients received six cycles of NAC (five cycles of neoadjuvant FOLFOX4 plus bevacizumab followed by one cycle of FOLFOX4 alone). The interval between the last dose of bevacizumab and surgery was at least 5 weeks. Six cycles of adjuvant FOLFOX4 plus bevacizumab were given after surgery. The completion rate of NAC and feasibility of curative surgery were the primary endpoints. An interim analysis was performed at the end of NAC in the 12th patient to assess the completion rate of NAC. The median follow-up time was 56 months. The characteristics of the patients were as follows: sex, eight males and four females; tumor location, sigmoid colon in three, ascending colon in one, and rectum (above the peritoneal reflection) in eight; stage, III in eight and IV in four (liver or lymph nodes). All patients completed six cycles of NAC. There were no treatment-related severe adverse events or deaths. An objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection, including metastatic lesions. In December 2012, this Phase II study was terminated because of slow registration. Perioperative FOLFOX4 plus bevacizumab is well tolerated and has a promising response rate leading to curative surgery, which offers a survival benefit in initially unresectable advanced CRC with concurrent metastatic lesions.

Response of lower genital tract flora to external pelvic irradiation

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

Gordon, A.N.; Martens, M.; LaPread, Y.

1989-11-01

Endocervical and vaginal cultures were obtained every week from patients undergoing external pelvic irradiation for gynecologic malignancy. Gram-positive aerobes accounted for 52 to 56% of isolates, gram-negative aerobes accounted for 15 to 16%, and anaerobes accounted for 29 to 32% of all isolates prior to therapy. No significant changes occurred during or after completion of radiation for the group. In individual patients, however, over 50% of organisms found on initial culture were no longer present on completion of external therapy.

Significant variations in nutritional supplementation amongst neonates in the United Kingdom.

PubMed

Gordon, Morris; Isaji, Sahira; Tyacke, Fiona

2016-08-08

To ascertain United Kingdom adherence to European society of Paediatric Gastroenterology, Hepatology and Nutrition guidance (ESPGHAN). A national cross sectional questionnaire study of neonatal units across England was completed between January and March 2014. All 174 units in the country were attempted to be contacted to complete a telephone survey. This included all level 1, 2 and 3 units. They were initially contacted by phone and asking any senior member of the team about their current practice and procedures. The first ten telephone interviews were completed with two researchers present to ensure consistency of approach. If no response was received or no details were available, one further attempt was made to contact the unit. The results were recorded in a proforma and then collated and entered into a spreadsheet for analysis. Comparison to United Kingdom adherence to ESPGHAN guidance was completed. Response rate was 53%. There was variation in use of all supplements. The survey collected data from 91 neonatal units (53% response rate). It was found that 10% of neonatal units had no fixed policy on supplements. The protocols regarding supplementation involved predominantly folic acid, vitamin A, vitamin D and iron, with much variation in doses and regimens. The criteria for prescribing supplements was largely based on age (47%) with only 7% using a weight targets to initiate supplements. Summary data regarding the appropriateness of each nutritional supplement for a variety of different weights are presented, as well as comparison to ESPGHAN guidance which suggests issues with both underdoing of Breast Fed infants and overdosing of infants on several artificial formulas which already contain significant amounts of these nutritional elements. There is significant heterogeneity in neonatal policies when prescribing supplements to neonates. National policies which take international guidance into account are recommended.

Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis.

PubMed

Wang, Yini; Huang, Wenqiu; Hu, Liangding; Cen, Xinan; Li, Lihong; Wang, Jijun; Shen, Jianliang; Wei, Na; Wang, Zhao

2015-11-05

Hemophagocytic lymphohistiocytosis (HLH) is a refractory immune disorder with a significant risk of death. Although standard therapy has dramatically improved survival in HLH patients, approximately 30%, especially adults, show no response to current treatment strategies. This prospective study aimed to investigate the efficacy of liposomal doxorubicin treatment combined with etoposide and methylprednisolone (doxorubicin-etoposide-methylprednisolone; DEP) as a salvage therapy for adult refractory HLH. Adult patients who did not achieve at least partial response 2 weeks after initial standard HLH therapy were enrolled in this study between June 2013 and June 2014. Response to salvage therapy was assessed at 2 and 4 weeks after initiation of DEP therapy and patients were followed until death or until November 2014. Sixty-three refractory HLH patients were enrolled, including 29 cases of lymphoma-associated HLH, 22 cases of Epstein-Barr virus-associated HLH, and 4 cases of familial HLH. There were 8 cases with unknown underlying diseases. Seventeen cases (27.0%) achieved complete response and 31 cases (49.2%) achieved partial response. The overall response was 76.2% (48/63). Patients who showed no response to DEP died within 4 weeks after salvage therapy. Twenty-nine of the 48 patients who achieved partial or complete response survived to subsequent chemotherapy, allogenic hematopoietic stem cell transplantation, or splenectomy. Our study suggests that DEP regimen is an effective salvage regimen for adult refractory HLH, which can prolong patient survival as we continue to understand the responsible mechanisms and bridge the gap between HLH and its underlying diseases. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR-IPC-14005514. © 2015 by The American Society of Hematology.

Return on investment. What is ROI and how to use it.

PubMed

Cotter, Steve

2014-08-01

Formulated and interpreted correctly, ROI tools and techniques can be very useful for EMS managers when evaluating various competing projects and initiatives within the organization. More so, decision makers and elected bodies responsible for approving the financial support of these initiatives are demanding that they be presented with a more complete picture of the return for any dollars allocated under ever-tightening financial considerations that all organizations face today. ROI can be a powerful tool in supporting your organization when competing for limited dollars.

System analysis of the dynamic response of the coronary circulation to a sudden change in heart rate.

PubMed

Dankelman, J; Stassen, H G; Spaan, J A

1990-03-01

In this study the response of driving pressure/flow ration on an abrupt change in heart rate was analysed. The difference between the response obtained with constant pressure and constant flow perfusion was also studied. The responses show a fast initial reversed phase followed by a slow phase caused by regulation. To test whether the initial phase could be the result of mechanical changes in the coronary circulation, a model for regulation was extended by the addition of four different mechanical models originating from the literature. These extended models were able to explain the fast initial phase. However, the mechanical model consisting of an intramyocardial compliance (C = 0.08 ml mm Hg-1 100 g-1) with a variable venous resistance, and the model consisting of a waterfall and a small compliance (C = 0.007 ml mm Hg-1 100g-1) both explained these responses best. The analysis showed that there is no direct relationship between rate of change of vascular tone and rate of change of pressure/flow ratio. However, on the basis of the two extended models, it can be predicted that the half-time for the response of regulation to be complete is about 9s with constant pressure perfusion and 15 s with constant flow perfusion.

Factors Associated with PMTCT Cascade Completion in Four African Countries.

PubMed

Dionne-Odom, Jodie; Welty, Thomas K; Westfall, Andrew O; Chi, Benjamin H; Ekouevi, Didier Koumavi; Kasaro, Margaret; Tih, Pius M; Tita, Alan T N

2016-01-01

Background. Many countries are working to reduce or eliminate mother-to-child transmission (MTCT) of HIV. Prevention efforts have been conceptualized as steps in a cascade but cascade completion rates during and after pregnancy are low. Methods. A cross-sectional survey was performed across 26 communities in Cameroon, Cote d'Ivoire, South Africa, and Zambia. Women who reported a pregnancy within two years were enrolled. Participant responses were used to construct the PMTCT cascade with all of the following steps required for completion: at least one antenatal visit, HIV testing performed, HIV testing result received, initiation of maternal prophylaxis, and initiation of infant prophylaxis. Factors associated with cascade completion were identified using multivariable logistic regression modeling. Results. Of 976 HIV-infected women, only 355 (36.4%) completed the PMTCT cascade. Although most women (69.2%) did not know their partner's HIV status; awareness of partner HIV status was associated with cascade completion (aOR 1.4, 95% CI 1.01-2.0). Completion was also associated with receiving an HIV diagnosis prior to pregnancy compared with HIV diagnosis during or after pregnancy (aOR 14.1, 95% CI 5.2-38.6). Conclusions. Pregnant women with HIV infection in Africa who were aware of their partner's HIV status and who were diagnosed with HIV before pregnancy were more likely to complete the PMTCT cascade.

Factors Associated with PMTCT Cascade Completion in Four African Countries

PubMed Central

Welty, Thomas K.; Westfall, Andrew O.; Chi, Benjamin H.; Ekouevi, Didier Koumavi; Tih, Pius M.; Tita, Alan T. N.

2016-01-01

Background. Many countries are working to reduce or eliminate mother-to-child transmission (MTCT) of HIV. Prevention efforts have been conceptualized as steps in a cascade but cascade completion rates during and after pregnancy are low. Methods. A cross-sectional survey was performed across 26 communities in Cameroon, Cote d'Ivoire, South Africa, and Zambia. Women who reported a pregnancy within two years were enrolled. Participant responses were used to construct the PMTCT cascade with all of the following steps required for completion: at least one antenatal visit, HIV testing performed, HIV testing result received, initiation of maternal prophylaxis, and initiation of infant prophylaxis. Factors associated with cascade completion were identified using multivariable logistic regression modeling. Results. Of 976 HIV-infected women, only 355 (36.4%) completed the PMTCT cascade. Although most women (69.2%) did not know their partner's HIV status; awareness of partner HIV status was associated with cascade completion (aOR 1.4, 95% CI 1.01–2.0). Completion was also associated with receiving an HIV diagnosis prior to pregnancy compared with HIV diagnosis during or after pregnancy (aOR 14.1, 95% CI 5.2–38.6). Conclusions. Pregnant women with HIV infection in Africa who were aware of their partner's HIV status and who were diagnosed with HIV before pregnancy were more likely to complete the PMTCT cascade. PMID:27872760

Impact of 18F-fluorodeoxyglucose positron emission tomography before and after definitive radiation therapy in patients with apparently solitary plasmacytoma.

PubMed

Kim, Paul J; Hicks, Rodney J; Wirth, Andrew; Ryan, Gail; Seymour, John F; Prince, H Miles; Mac Manus, Michael P

2009-07-01

To evaluate the impact of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) on management of patients with apparently isolated plasmacytoma. Twenty-one patients with apparently solitary plasmacytoma who underwent FDG-PET for staging or restaging were identified from a central PET database. They were either candidates for or had received definitive radiation therapy (RT). Seventeen patients had initial staging scans for bone (n = 11) or soft tissue (n = 6) plasmacytomas, and 11 had PET scans after RT. Only 1 of 14 known untreated sites of plasmacytoma was not identified on staging PET (lesion sensitivity = 93%). Three plasmacytomas were excised before PET. Staging PET influenced management in 6 of 17 patients (35%) by showing multiple myeloma (n = 1), discouraging RT after complete resection (n = 1), excluding plasmacytoma at a second site (n = 1), by increasing RT fields (n = 2), or by suggesting sarcoidosis (n = 1). Fifteen of 17 patients with initial staging PET scans received definitive RT. Restaging PET scans after RT showed complete metabolic response in 8 of 11 cases and progressive disease in 2. Two patients with either no response or partial metabolic response had late responses. Staging sestamibi and PET scans were concordant in five of six occasions (one sestamibi scan was false negative). FDG-PET has value for staging and RT planning in plasmacytoma and potentially could have a role in response-assessment after RT. Slow resolution of FDG uptake posttreatment does not necessarily imply an adverse prognosis.

Summary Statistics of the National Railroad - Highway Crossing Inventory for Public At-Grade Crossings. Second Edition : Inventory Status as of May 78

DOT National Transportation Integrated Search

1978-09-01

In response to the Federal Railroad Safety Act of 1970, a joint government/industry effort to compile a national inventory of railroad-highway crossings was initiated in 1972 and completed in 1976. The inventory contains data on the physical and oper...

Course Compression and School Partnership in Pre-Service Primary Teacher Education.

ERIC Educational Resources Information Center

Hope, John

In response to a serious shortage of elementary school teachers, New Zealand's government introduced competitive contracts for new and established providers to develop initial teacher education programs that could be completed over 12-18 months. The University of Auckland developed a compressed, three-semester, post-graduate program taught in…

43 CFR 3809.420 - What performance standards apply to my notice or plan of operations?

Code of Federal Regulations, 2014 CFR

2014-10-01

... by BLM to protect public lands. (5) Concurrent reclamation. You must initiate and complete... migration controls do not prove effective. You are responsible for any costs associated with water treatment... containment system that will minimize the release of leaching solutions to the environment. You must monitor...

43 CFR 3809.420 - What performance standards apply to my notice or plan of operations?

Code of Federal Regulations, 2011 CFR

2011-10-01

... by BLM to protect public lands. (5) Concurrent reclamation. You must initiate and complete... migration controls do not prove effective. You are responsible for any costs associated with water treatment... containment system that will minimize the release of leaching solutions to the environment. You must monitor...

Performance of finishing beef steers in response to anabolic implant dose and zilpaterol hydrochloride

USDA-ARS?s Scientific Manuscript database

British × Continental steers (n = 168; 7 pens/treatment; initial BW = 362 kg) were used to evaluate the dose of trenbolone acetate (TBA) and estradiol-17ß (E2) and feeding of zilpaterol hydrochloride (ZH) on performance and carcass characteristics. A randomized complete block design was used with a ...

Herbivore responses to plants grown in enriched carbon dioxide atmospheres

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

Lincoln, D.E.

1990-05-01

Our initial study of sagebrush and grasshopper responses to elevated and historical carbon dioxide atmospheres is complete and has been accepted for publication. The study on Biomass Allocation Patterns of Defoliated Sagebrush Grown Under Two Levels of Carbon Dioxide has completed and the manuscript has been submitted for publication. We have completed the study of plant growth under two nutrient and carbon dioxide regimes and grasshopper feeding responses. The study of a specialist feeding caterpillar, the cabbage butterfly, and a mustard hostplant has recently been completed. We were able to identify the principal allelochemicals of the mustard plants, butenyl andmore » pentenyl isothiocyanates, by combined gas chromatography and mass spectrometry. Measurement of these chemicals has been a critical component of this study since these compounds contain nitrogen and sulphur and act as a feeding stimulant to the caterpillar. This insect responds to elevated carbon dioxide by consuming more leaves and we can now say that this is not due to a change in the feeding stimulants. Reduced leaf protein content is a critical factor for even specialist feeding insect herbivores under elevated carbon dioxide conditions. The study on Grasshopper Population Responses to Enriched Carbon Dioxide Concentration is currently in progress at the Duke University Phytotron. We have changed hostplant species in order to complement the investigations of carbon dioxide effects on tallgrass prairie. Specifically, we are using big bluestem, Andropogon geradii, as the host plant to feed to the grasshoppers. This experiment will be completed in July 1990.« less

Case of relentless chronic phase of chronic myeloid leukaemia.

PubMed

Chan, Onyee; Chen, Hao; Krishnadasan, Ravitharan; Anwer, Faiz

2016-06-22

Initial treatment of chronic phase chronic myeloid leukaemia is straightforward in today's era of tyrosine kinase inhibitors. However, managing refractory cases remain a major challenge due to the multiple factors that can influence decision-making, including medication tolerance, disease burden, mutation status, comorbidities, availability of donor, and fitness for an ablative conditioning. We report a male patient presenting with chronic phase chronic myeloid leukaemia who was treated with 5 different tyrosine kinase inhibitors either due to intolerance and/or failed response. He subsequently received 2 haploidentical haematopoietic stem cells transplants before achieving complete remission. This case highlights various treatment options, need for vigilant disease monitoring, and the possibility of complete positive response even after many lines of therapy failure. 2016 BMJ Publishing Group Ltd.

Evaluation of factors associated with second remission in dogs with lymphoma undergoing retreatment with a cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy protocol: 95 cases (2000-2007).

PubMed

Flory, Andrea B; Rassnick, Kenneth M; Erb, Hollis N; Garrett, Laura D; Northrup, Nicole C; Selting, Kim A; Phillips, Brenda S; Locke, Jennifer E; Chretin, John D

2011-02-15

To evaluate factors associated with second remission in dogs with lymphoma retreated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) protocol after relapse following initial treatment with a first-line 6-month CHOP protocol. Retrospective case series. 95 dogs with lymphoma. Medical records were reviewed. Remission duration was estimated by use of the Kaplan-Meier method. Factors potentially associated with prognosis were examined. Median remission duration after the first-line CHOP protocol was 289 days (range, 150 to 1,457 days). Overall, 78% (95% confidence interval [CI], 69% to 86%) of dogs achieved a complete remission following retreatment, with a median second remission duration of 159 days (95% CI, 126 to 212 days). Duration of time off chemotherapy was associated with likelihood of response to retreatment; median time off chemotherapy was 140 days for dogs that achieved a complete remission after retreatment and 84 days for dogs that failed to respond to retreatment. Second remission duration was associated with remission duration after initial chemotherapy; median second remission duration for dogs with initial remission duration ≥ 289 days was 214 days (95% CI, 168 to 491 days), compared with 98 days (95% CI, 70 to 144 days) for dogs with initial remission duration < 289 days. Findings suggested that retreatment with the CHOP protocol can be effective in dogs with lymphoma that successfully complete an initial 6-month CHOP protocol.

Infliximab Versus Adalimumab in the Treatment of Refractory Inflammatory Uveitis: A Multicenter Study From the French Uveitis Network.

PubMed

Vallet, Hélène; Seve, Pascal; Biard, Lucie; Baptiste Fraison, Jean; Bielefeld, Philip; Perard, Laurent; Bienvenu, Boris; Abad, Sébastien; Rigolet, Aude; Deroux, Alban; Sene, Damien; Perlat, Antoinette; Marie, Isabelle; Feurer, Elodie; Hachulla, Eric; Fain, Olivier; Clavel, Gaëlle; Riviere, Sophie; Bouche, Pierre-Alban; Gueudry, Julie; Pugnet, Gregory; Le Hoang, Phuc; Resche Rigon, Matthieu; Cacoub, Patrice; Bodaghi, Bahram; Saadoun, David

2016-06-01

To analyze the factors associated with response to anti-tumor necrosis factor (anti-TNF) treatment and compare the efficacy and safety of infliximab (IFX) and adalimumab (ADA) in patients with refractory noninfectious uveitis. This was a multicenter observational study of 160 patients (39% men and 61% women; median age 31 years [interquartile range 21-42]) with uveitis that had been refractory to other therapies, who were treated with anti-TNF (IFX 5 mg/kg at weeks 0, 2, 6, and then every 5-6 weeks [n = 98] or ADA 40 mg every 2 weeks [n = 62]). Factors associated with complete response were assessed by multivariate analysis. Efficacy and safety of IFX versus ADA were compared using a propensity score approach with baseline characteristics taken into account. Subdistribution hazard ratios (SHRs) and 95% confidence intervals (95% CIs) were calculated. The main etiologies of uveitis included Behçet's disease (BD) (36%), juvenile idiopathic arthritis (22%), spondyloarthropathy (10%), and sarcoidosis (6%). The overall response rate at 6 and 12 months was 87% (26% with complete response) and 93% (28% with complete response), respectively. The median time to complete response was 2 months. In multivariate analysis, BD and occurrence of >5 uveitis flares before anti-TNF initiation were associated with complete response to anti-TNF (SHR 2.52 [95% CI 1.35-4.71], P = 0.004 and SHR 1.97 [95% CI 1.02-3.84], P = 0.045, respectively). Side effects were reported in 28% of patients, including serious adverse events in 13%. IFX and ADA did not differ significantly in terms of occurrence of complete response (SHR 0.65 [95% CI 0.25-1.71], P = 0.39), serious side effects (SHR 0.22 [95% CI 0.04-1.25], P = 0.089), or event-free survival (SHR 0.55 [95% CI 0.28-1.08], P = 0.083). Anti-TNF treatment is highly effective in refractory inflammatory uveitis. BD is associated with increased odds of response. IFX and ADA appear to be equivalent in terms of efficacy. © 2016, American College of Rheumatology.

Practice Makes Progress? Homework Assignments and Outcome in Treatment of Cocaine Dependence

PubMed Central

Carroll, Kathleen M.; Nich, Charla; Ball, Samuel A.

2008-01-01

The relationship between treatment outcome and the extent to which participants completed homework assignments was evaluated among 60 cocaine-dependent individuals assigned to cognitive–behavioral therapy (CBT). Homework was assigned in 72% of all sessions and initiated by participants in 48% of the sessions in which it was assigned. Completion of homework was unrelated to participants' baseline characteristics and several indicators of treatment compliance. Participants who completed more homework assignments demonstrated significantly greater increases in the quantity and quality of their coping skills and used significantly less cocaine during treatment and through a 1-year follow-up. These data suggest that the extent to which participants are willing to complete extrasession assignments may be an important mediator of response to CBT. PMID:16173864

18F-FDG PET/CT for Monitoring Response of Merkel Cell Carcinoma to the Novel Programmed Cell Death Ligand 1 Inhibitor Avelumab.

PubMed

Eshghi, Naghmehossadat; Lundeen, Tamara F; MacKinnon, Lea; Avery, Ryan; Kuo, Phillip H

2018-05-01

An 85-year-old man with stage IIIA Merkel cell carcinoma of the left arm was initially treated with local excision and axillary node dissection followed by radiation therapy. Eight months after surgery, whole-body FDG PET/CT demonstrated intensely hypermetabolic hepatic metastases and abdominal lymphadenopathy. Given his age and comorbidities, he was considered a poor candidate for chemotherapy, and therefore the novel programmed cell death ligand 1 inhibitor avelumab was initiated. FDG PET/CT after 4 cycles showed complete resolution of hepatic and nodal metastases. Whole-body FDG PET/CT can be used for monitoring response of multisystem metastases from Merkel cell carcinoma to active immunotherapy.

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

Patient's perceptions of an anesthesia preoperative computerized patient interview.

PubMed

Vitkun, S A; Halpern-Lewis, J G; Williams, S A; Gage, J S; Poppers, P J

1999-12-01

Our desire to elicit a more complete medical history from our patients led to the implementation of a preoperative computerized interview. We previously demonstrated the effectiveness of the interview by computing its mean completion time for the overall patient population (n = 120), and further examined the effects of age, gender, and educational level. In this study, we investigated patient perception of the interview itself. Before and after taking the computer interview, we asked the patients to complete a paper and pencil questionnaire comprised of sixteen questions, expressing their feelings toward the computer interview. Responses elicited prior to taking the computer interview were compared with those obtained afterward. The Stuart-Maxwell test was used to determine statistically significant differences in answers before and after the interview. Initial questionnaire responses reflected a positive attitude toward computer usage which became even stronger after the interview. The only negative responses elicited were really more "doctor positive" than "computer negative." We conclude that patients looked favorably upon participating in a computerized medical interview provided that physician-patient contact is maintained.

Postirradiation squamous cell carcinoma in situ of the vagina: treatment by topical 20 percent 5-fluorouracil cream

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

Piver, M.S.; Barlow, J.J.; Tsukada, Y.

1979-10-01

Eight patients with squamous cell carcinoma in situ of the vagina were treated with monthly 5 day courses of 20% 5-fluorouracil cream applied to the vagina. Seven (87.5%) of the women had an initial complete response; however, three subsequently developed recurrence after the treatment was stopped. They were retreated, and two of these three patients achieved a subsequent complete response. The overall response to therapy was 75% (6/8) with the six women off therapy from 1.1 to 6.9 years. Total follow-up of all patients was 3.1 to 6.9 years with no patients having developed invasive carcinoma. Because of the highmore » success rate with no associated serious sequelae, this is believed to be a satisfactory method of therapy for women with squamous cell carcinoma in situ of the vagina occurring after pelvic irradiation.« less

Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas

PubMed Central

Müller, Sören; Agnihotri, Sameer; Shoger, Karsen E.; Myers, Max I.; Chaparala, Srilakshmi; Villanueva, Clarence R.; Chattopadhyay, Ansuman; Butterfield, Lisa H.; Okada, Hideho; Pollack, Ian F.

2018-01-01

Low-grade gliomas (LGGs) are the most common brain tumor affecting children. We recently reported an early phase clinical trial of a peptide-based vaccine, which elicited consistent antigen-specific T cell responses in pediatric LGG patients. Additionally, we observed radiologic responses of stable disease (SD), partial response (PR), and near-complete/complete response (CR) following therapy. To identify biomarkers of clinical response in peripheral blood, we performed RNA sequencing on PBMC samples collected at multiple time points. Patients who showed CR demonstrated elevated levels of T cell activation markers, accompanied by a cytotoxic T cell response shortly after treatment initiation. At week 34, patients with CR demonstrated both IFN signaling and Poly-IC:LC adjuvant response patterns. Patients with PR demonstrated a unique, late monocyte response signature. Interestingly, HLA-V expression, before or during therapy, and an early monocytic hematopoietic response were strongly associated with SD. Finally, low IDO1 and PD-L1 expression before treatment and early elevated levels of T cell activation markers were associated with prolonged progression-free survival. Overall, our data support the presence of unique peripheral immune patterns in LGG patients associated with different radiographic responses to our peptide vaccine immunotherapy. Future clinical trials, including our ongoing phase II LGG vaccine immunotherapy, should monitor these response patterns. PMID:29618666

Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using (11)C-choline PET/CT.

PubMed

García, J R; Cozar, M; Soler, M; Bassa, P; Riera, E; Ferrer, J

2016-01-01

To assess the prognostic value of the therapeutic response by (11)C-choline PET/CT in prostate cancer patients with biochemical recurrence in which (11)C-choline PET/CT indicated radio-guided radiotherapy. The study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. (11)C-choline PE/CT detected infra-diaphragmatic lymph-node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings. One year after treatment patients underwent PSA and (11)C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. (11)C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimetre in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimetre and 10 (27.0%) only less than a centimetre in size. The response by (11)C-choline PET/CT was categorised one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression. The response was concordant between the PSA result and (11)C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%). New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). (11)C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique. The evaluation of therapeutic response by (11)C-choline PET/CT has prognostic significance. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Dynamic stability and handling qualities tests on a highly augmented, statically unstable airplane

NASA Technical Reports Server (NTRS)

Gera, Joseph; Bosworth, John T.

1987-01-01

This paper describes some novel flight tests and analysis techniques in the flight dynamics and handling qualities area. These techniques were utilized during the initial flight envelope clearance of the X-29A aircraft and were largely responsible for the completion of the flight controls clearance program without any incidents or significant delays. The resulting open-loop and closed-loop frequency responses and the time history comparison using flight and linear simulation data are discussed.

Evaluation of chemotherapy response in patients with advanced head and neck cancer using [F-18]fluorodeoxyglucose positron emission tomography.

PubMed

Lowe, V J; Dunphy, F R; Varvares, M; Kim, H; Wittry, M; Dunphy, C H; Dunleavy, T; McDonough, E; Minster, J; Fletcher, J W; Boyd, J H

1997-12-01

[F-18]Fluorodeoxyglucose (FDG)-positron emission tomography (PET) can measure the metabolic activity of tissues; FDG-PET may be able to predict response to chemotherapy by identifying changes in tumor metabolism. Measurement of response to treatment may help improve survival in the management of advanced head and neck cancer. We evaluated this particular use of FDG-PET in patients participating in a neoadjuvant organ-preservation protocol using taxol and carboplatin and compared pathologic response after chemotherapy with changes in tumor metabolism measured by FDG-PET. Serial FDG-PET studies (n = 56) were performed in patients (n = 28) with stage III/IV head and neck cancer participating in a neoadjuvant organ-preservation protocol. The FDG-PET studies were performed before and after chemotherapy. All patients had tissue biopsies before and after chemotherapy. Patients were classified as pathologic complete response (PCR) or residual disease (RD) based on tissue biopsies. Visual analysis of PET scans was performed to identify patients with complete response by PET, and these findings were compared with pathology results. Metabolic changes were also evaluated using standardized uptake ratios (SUR) of FDG. The sensitivity and specificity of PET for residual cancer after therapy was 90% (19/21) and 83% (5/6), respectively. Two patients had initially negative biopsies and positive PET studies for persistent disease. Pathology review and rebiospy led to confirmation of the PET results in these cases, giving a sensitivity of 90% for initial tissue biopsy. In this preliminary analysis, FDG-PET was accurate in classifying response to chemotherapy in most patients. Fluorodeoxyglucose-PET may identify residual viable tumor when it is otherwise undetectable.

Interim Draft: Biological Sampling and Analysis Plan Outline ...

EPA Pesticide Factsheets

Standard Operation Procedures This interim sampling and analysis plan (SAP) outline was developed specifically as an outline of the output that will be generated by a developing on-line tool called the MicroSAP. The goal of the MicroSAP tool is to assist users with development of SAPs needed for site characterization, verification sampling, and post decontamination sampling stages of biological sampling and analysis activities in which the EPA would be responsible for conducting sampling. These activities could include sampling and analysis for a biological contamination incident, a research study, or an exercise. The development of this SAP outline did not consider the initial response of an incident, as it is assumed that the initial response would have been previously completed by another agency during the response, or the clearance phase, as it is assumed that separate committee would be established to make decisions regarding clearing a site. This outline also includes considerations for capturing the associated data quality objectives in the SAP.

Assessing corporate social responsibility in China's sports lottery administration and its influence on consumption behavior.

PubMed

Li, Hai; Zhang, James J; Mao, Luke Lunhua; Min, Sophia D

2012-09-01

The purpose of this study was to identify and examine consumer perception of corporate social responsibility (CSR) in China's sports lottery industry, and the effect of perceived CSR initiatives on sports lottery consumption behavior. Research participants (N = 4,980), selected based on a computer-generated, randomly stratified multistage sampling process, comprised Chinese residents who had purchased sports lottery tickets in the past 12 months. They completed a questionnaire that was derived from a qualitative research process. A factor analysis extracted two factors associated with perceptions of CSR in China's sports lottery administration: Regulatory and Prevention Responsibilities and Product Development Responsibility. Logistic regression analyses revealed that these two factors were influential of consumer behavior (i.e., relative and absolute expenditure, purchasing frequency, and time commitment). This study represents an initial effort to understand the dimensions of perceived CSR associated with Chinese sports lottery. The findings signify the importance of enforcing CSR in sports lottery administration.

A Logistic Regression Analysis of Student Experience Factors for the Enhancement of Developmental Post-Secondary Retention Initiatives

ERIC Educational Resources Information Center

Shenkle, Michael Thomas

2017-01-01

In response to stagnant undergraduate completion rates and growing demands for post-secondary accountability, institutions are actively pursuing effective, broadly applicable methods for promoting student success. One notable scarcity in existing research is found in the tailoring of broad academic interventions to better meet the specific needs…

33 CFR 155.4040 - Response times for each salvage and marine firefighting service.

Code of Federal Regulations, 2010 CFR

2010-07-01

... potential or actual incident. It ends when the service reaches the ship, the outer limit of the nearshore... stability Initial analysis is completed. This is a continual process, but at the time specified an analysis... location by facility name or city and ensure that the marine firefighting resource provider can reach the...

33 CFR 155.4040 - Response times for each salvage and marine firefighting service.

Code of Federal Regulations, 2011 CFR

2011-07-01

... potential or actual incident. It ends when the service reaches the ship, the outer limit of the nearshore... stability Initial analysis is completed. This is a continual process, but at the time specified an analysis... location by facility name or city and ensure that the marine firefighting resource provider can reach the...

Impacts of tree height on leaf hydraulic architecture and stomatal control in Douglas-fir.

Treesearch

D.R. Woodruff; K.A. McCulloh; J.M. Warren; F.C. Meinzer; B.L. Gartner

2007-01-01

We investigated the mechanisms involved in the regulation of stomatal closure in Douglas-fir and evaluated the potential compensatory adjustments in response to increasing tree height. Stomatal closure was initiated at values of leaf water potential corresponding to nearly complete loss of leaf hydraulic conductance. Cryogenic scanning electron microscopic images...

A cost-effective weight loss program at the worksite.

PubMed

Seidman, L S; Sevelius, G G; Ewald, P

1984-10-01

A major focus of Lockheed Missiles and Space Company's wellness program (Sunnyvale, Calif.) was to motivate weight loss in a cost-effective manner. The educationally based "Take It Off '83" campaign was created using the concepts of competition and self-responsibility. Seventy percent of the initial 2,499 participants completed the program, and 90% of these lost weight. Program completion rates and weight lost were higher for men than for women and higher for those who participated as team members rather than as individuals. Encouraging the formation of supportive/competitive teams proved to be a very effective means of promoting weight loss. The cost-effective motivation of weight loss in an industrial setting was accomplished successfully through this program (the cost to the company per initial participant was +5.40). Because of these results, the program will be repeated annually.

TPS In-Flight Health Monitoring Project Progress Report

NASA Technical Reports Server (NTRS)

Kostyk, Chris; Richards, Lance; Hudston, Larry; Prosser, William

2007-01-01

Progress in the development of new thermal protection systems (TPS) is reported. New approaches use embedded lightweight, sensitive, fiber optic strain and temperature sensors within the TPS. Goals of the program are to develop and demonstrate a prototype TPS health monitoring system, develop a thermal-based damage detection algorithm, characterize limits of sensor/system performance, and develop ea methodology transferable to new designs of TPS health monitoring systems. Tasks completed during the project helped establish confidence in understanding of both test setup and the model and validated system/sensor performance in a simple TPS structure. Other progress included complete initial system testing, commencement of the algorithm development effort, generation of a damaged thermal response characteristics database, initial development of a test plan for integration testing of proven FBG sensors in simple TPS structure, and development of partnerships to apply the technology.

Imiquimod 5% cream versus cold knife excision for treatment of VIN 2/3: a five-year follow-up.

PubMed

Frega, A; Sesti, F; Sopracordevole, F; Biamonti, A; Scirpa, P; Milazzo, G N; Catalano, A; Assorgi, C; Lombardi, D; Gentile, M; Maniglio, P; Ricciardi, E; Cozza, G; Marziani, R; Moscarini, M

2013-04-01

Vulvar intraepithelial neoplasia (VIN) is a premalingnant condition. For long time, surgery was considered the first-line therapy in the treatment of high grade VIN. Imiquimod was recently introduced as an alternative to surgery. To compare the overall complete response, the recurrence rate and the risk factors for relapse among patients with VIN 2/3 treated with Imiquimod or surgical excision. Eighty women who had histological diagnosis of VIN 2 and VIN 3 were enrolled in this prospective study. Patients immunocompromised, with recurrent VIN, with well differentiated type VIN or VIN 1 and women treated more than once were excluded from the study. Patients were divided into two groups: group A was treated with Imiquimod, group B underwent surgical excision. Patients' characteristics analyzed were: age, smoking, degree of the primary lesion, state of margins, multifocal disease. We have evaluated the recurrence rate, the relapse rate, and the overall complete response, considering as recurrence the onset of a lesion after an initial complete response to Imiquimod and/or after the surgical treatment and as relapse all patients who had a recurrence plus those with medical treatment failure. Multifocal lesions (p = 0.03) and VIN 3 (p = 0.002) were associated with a higher risk of relapse. The recurrence rate was higher in the group B (p = 0.009), but the relapse rate was higher in the group A (p = 0.04). The overall complete response was better in the group B (p = 0.04). Although the advent of new medical options can decrease the morbidity associated with invasive surgical procedures, surgical treatments remain the best treatment modality for VIN with regard to relapse and overall complete response.

N2 and P3 modulation during partial inhibition in a modified go/nogo task.

PubMed

Nguyen, An T; Moyle, Jonson J; Fox, Allison M

2016-09-01

The neural response following the partial inhibition of responses can provide insight into the processes underlying response inhibition. We examined the N2 and P3 on trials where participants correctly responded to go stimuli, successfully inhibited their response to nogo stimuli, and nogo trials where they initiated but did not complete their response (partial inhibitions) in an adult sample (N=24, M(age)=21.17, SD(age)=3.52). An enhanced and delayed N2 was observed on partially inhibited compared to successfully inhibited nogo trials. Further analysis showed that this modulation was error-related. An enhanced central P3 was observed following successful inhibitions compared to correct go trials, but not following partial inhibitions. The results suggest that the central P3 enhancement is specific to the complete and successful inhibition of responses. Therefore, the absence of a central P3 on partial inhibitions could reflect insufficient inhibition or a monitored failure in inhibiting the response. Although, our findings provide support for the role of P3 in response inhibition, it raises questions about the processes involved in the subsequent inhibition or correction of the erroneous response. Further research examining the neural response following both partial and unsuccessful inhibitions could provide insight regarding these processes. Copyright © 2016 Elsevier B.V. All rights reserved.

The adequate rocuronium dose required for complete block of the adductor muscles of the thigh.

PubMed

Fujimoto, M; Kawano, K; Yamamoto, T

2018-03-01

Rocuronium can prevent the obturator jerk during transurethral resection of bladder tumors. We investigated the adequate rocuronium dose required for complete block of the thigh adductor muscles, and its correlation with individual responses of the adductor pollicis muscle to rocuronium. Eleven patients scheduled for transurethral resection of bladder tumors under general anesthesia were investigated. After general anesthesia induction, neuromuscular monitoring of the adductor pollicis muscle and ultrasonography-guided stimulation of the obturator nerve was commenced. Rocuronium, 0.15 mg/kg, was repeatedly administered intravenously. The adequate rocuronium dose required for complete block of the thigh muscles, defined as the cumulative dose of rocuronium administered until that time, and its correlation with the first twitch response of the adductor pollicis muscle on train-of-four stimulation after initial rocuronium administration was analyzed. The rocuronium dose found adequate for complete block of the thigh muscles was 0.30 mg/kg in seven patients and 0.45 mg/kg in the remaining four patients, which did not correlate with the first twitch response. At the time of complete block of the thigh muscles, the neuromuscular blockade level of the adductor pollicis muscle varied greatly, although the level was never more profound than a post-tetanic count of 1. Although the response of the adductor pollicis muscle to rocuronium cannot be used to determine the adequate rocuronium dose required for complete block of the thigh muscles, intense blockade, with maintenance of post-tetanic count at ≤ 1 in the adductor pollicis muscle is essential to prevent the obturator jerk. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Comparison of Online Survey Recruitment Platforms for Hard-to-Reach Pregnant Smoking Populations: Feasibility Study

PubMed Central

Agas, Jessica Marie; Lee, Melissa; Pan, Julia Lily; Buttenheim, Alison Meredith

2018-01-01

Background Recruiting hard-to-reach populations for health research is challenging. Web-based platforms offer one way to recruit specific samples for research purposes, but little is known about the feasibility of online recruitment and the representativeness and comparability of samples recruited through different Web-based platforms. Objective The objectives of this study were to determine the feasibility of recruiting a hard-to-reach population (pregnant smokers) using 4 different Web-based platforms and to compare participants recruited through each platform. Methods A screener and survey were distributed online through Qualtrics Panel, Soapbox Sample, Reddit, and Amazon Mechanical Turk (mTurk). Descriptive statistics were used to summarize results of each recruitment platform, including eligibility yield, quality yield, income, race, age, and gestational age. Results Of the 3847 participants screened for eligibility across all 4 Web-based platforms, 535 were eligible and 308 completed the survey. Amazon mTurk yielded the fewest completed responses (n=9), 100% (9/9) of which passed several quality metrics verifying pregnancy and smoking status. Qualtrics Panel yielded 14 completed responses, 86% (12/14) of which passed the quality screening. Soapbox Sample produced 107 completed surveys, 67% (72/107) of which were found to be quality responses. Advertising through Reddit produced the highest completion rate (n=178), but only 29.2% (52/178) of those surveys passed the quality metrics. We found significant differences in eligibility yield, quality yield, age, number of previous pregnancies, age of smoking initiation, current smokers, race, education, and income (P<.001). Conclusions Although each platform successfully recruited pregnant smokers, results varied in quality, cost, and percentage of complete responses. Moving forward, investigators should pay careful attention to the percentage yield and cost of online recruitment platforms to maximize internal and external validity. PMID:29661751

Results of a minimally invasive technique for treatment of unicameral bone cysts.

PubMed

Mik, Gökçe; Arkader, Alexandre; Manteghi, Alexander; Dormans, John P

2009-11-01

Unicameral bone cysts are benign bone lesions commonly seen in pediatric patients. Several treatment methods have been described with variable results and high recurrence rates. We previously reported short-term success of a minimally invasive technique that includes combining percutaneous decompression and grafting with medical-grade calcium sulfate pellets. The purpose of this study was to review the additional long-term results with a minimum followup of 24 months (average, 37 months; range, 24-70 months). We identified 55 patients with an average age of 10.8 years (range, 1.3-18 years). Forty-one of 55 lesions occurred in the humerus and femur. Forty-four of 55 (80%) patients had a partial or complete response after initial surgery; of these, seven obtained a partial or complete response after a repeat surgery (cumulative healing rate, 94%). Two patients underwent a third surgery (cumulative healing rate, 98%). One underwent a third repeat surgery (cumulative healing rate, 100%). There were no major complications associated with the procedure. Two patients had a superficial infection that resolved with oral antibiotics. Although some patients required a repeat procedure, complete or partial response at a minimum 24 months' followup was achieved in all patients. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Fears, Uncertainties, and Hopes: Patient-Initiated Actions and Doctors’ Responses During Oncology Interviews*

PubMed Central

Beach, Wayne A.; Dozier, David M.

2015-01-01

New cancer patients frequently raise concerns about fears, uncertainties, and hopes during oncology interviews. This study sought to understand when and how patients raise their concerns, how doctors responded to these patient-initiated actions, and implications for communication satisfaction. A sub-sampling of video recorded and transcribed encounters was investigated involving 44 new patients and 14 oncologists. Patients completed pre-post self-report measures about fears, uncertainties, and hopes as well as post-evaluations of interview satisfaction. Conversation Analysis (CA) was employed to initially identify pairs of patient-initiated and doctor-responsive actions. A coding scheme was subsequently developed, and two independent coding teams, comprised of two coders each, reliably identified patient-initiated and doctor-responsive social actions. Interactional findings reveal that new cancer patients initiate actions much more frequently than previous research had identified, concerns are usually raised indirectly, and with minimal emotion. Doctors tend to respond to these concerns immediately, but with even less affect, and rarely partner with patients. From pre-post results it was determined that the higher patients’ reported fears, the higher their post-visit fears and lower their satisfaction. Patients with high uncertainty were highly proactive (e.g., asked more questions), yet reported even greater uncertainties following encounters. Hopeful patients also exited interviews with high hopes. Overall, new patients were very satisfied: Oncology interviews significantly decreased patients’ fears and uncertainties, while increasing hopes. Discussion raises key issues for improving communication and managing quality cancer care. PMID:26134261

Impact of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography Before and After Definitive Radiation Therapy in Patients With Apparently Solitary Plasmacytoma

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

Kim, Paul J.; Hicks, Rodney J.; Wirth, Andrew

2009-07-01

Purpose: To evaluate the impact of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) on management of patients with apparently isolated plasmacytoma. Methods and Materials: Twenty-one patients with apparently solitary plasmacytoma who underwent FDG-PET for staging or restaging were identified from a central PET database. They were either candidates for or had received definitive radiation therapy (RT). Results: Seventeen patients had initial staging scans for bone (n = 11) or soft tissue (n = 6) plasmacytomas, and 11 had PET scans after RT. Only 1 of 14 known untreated sites of plasmacytoma was not identified on staging PET (lesion sensitivity = 93%).more » Three plasmacytomas were excised before PET. Staging PET influenced management in 6 of 17 patients (35%) by showing multiple myeloma (n = 1), discouraging RT after complete resection (n = 1), excluding plasmacytoma at a second site (n = 1), by increasing RT fields (n = 2), or by suggesting sarcoidosis (n = 1). Fifteen of 17 patients with initial staging PET scans received definitive RT. Restaging PET scans after RT showed complete metabolic response in 8 of 11 cases and progressive disease in 2. Two patients with either no response or partial metabolic response had late responses. Staging sestamibi and PET scans were concordant in five of six occasions (one sestamibi scan was false negative). Conclusions: FDG-PET has value for staging and RT planning in plasmacytoma and potentially could have a role in response-assessment after RT. Slow resolution of FDG uptake posttreatment does not necessarily imply an adverse prognosis.« less

Idiopathic hypersomnia: clinical features and response to treatment.

PubMed

Ali, Mohsin; Auger, R Robert; Slocumb, Nancy L; Morgenthaler, Timothy I

2009-12-15

A recent American Academy of Sleep Medicine publication identified a need for research regarding idiopathic hypersomnia. We describe various clinical and polysomnographic features of patients with idiopathic hypersomnia, with an emphasis on response to pharmacotherapy. A retrospective review of our database initially identified 997 patients, utilizing "idiopathic hypersomnia", "hypersomnia NOS", and "primary hypersomnia" as keywords. The charts of eligible patients were examined in detail, and data were abstracted and analyzed. Response to treatment was graded utilizing an internally developed scale. Eighty-five patients were ultimately identified (65% female). Median (interquartile range) ages of onset and diagnosis were 19.6 (15.5) and 33.7 (15.5), respectively. During a median follow-up duration of 2.4 (4.7) years, 65% of patients demonstrated a "complete response" to pharmacotherapy as assessed by the authors' grading schema. Methylphenidate was most commonly used as a first-line agent prior to December 1998, but subsequently, modafinil became the most common first drug. At the last recorded follow-up visit, 92% of patients were on monotherapy, with greater representation of methylphenidate versus modafinil (51% vs. 32%). Among these patients, methylphenidate produced a higher percentage of "complete" or "partial" responses than modafinil, although statistical significance was not reached (38/40 [95%] vs. 22/25 [88%], respectively, p = 0.291). The majority of patients with idiopathic hypersomnia respond well to treatment. Methylphenidate is chosen more often than modafinil as final monotherapy in the treatment of idiopathic hypersomnia, despite the fact that it is less commonly used initially. Further prospective comparisons of medications should be explored.

Building research capacity in Botswana: a randomized trial comparing training methodologies in the Botswana ethics training initiative.

PubMed

Barchi, Francis H; Kasimatis-Singleton, Megan; Kasule, Mary; Khulumani, Pilate; Merz, Jon F

2013-02-01

Little empirical data are available on the extent to which capacity-building programs in research ethics prepare trainees to apply ethical reasoning skills to the design, conduct, or review of research. A randomized controlled trial was conducted in Botswana in 2010 to assess the effectiveness of a case-based intervention using email to augment in-person seminars. University faculty and current and prospective IRB/REC members took part in a semester-long training program in research ethics. Participants attended two 2-day seminars and were assigned at random to one of two on-line arms of the trial. Participants in both arms completed on-line international modules from the Collaborative Institutional Training Initiative. Between seminars, intervention-arm participants were also emailed a weekly case to analyze in response to set questions; responses and individualized faculty feedback were exchanged via email. Tests assessing ethics knowledge were administered at the start of each seminar. The post-test included an additional section in which participants were asked to identify the ethical issues highlighted in five case studies from a list of multiple-choice responses. Results were analyzed using regression and ANOVA. Of the 71 participants (36 control, 35 intervention) enrolled at the first seminar, 41 (57.7%) attended the second seminar (19 control, 22 intervention). In the intervention arm, 19 (54.3%) participants fully completed and 8 (22.9%) partially completed all six weekly cases. The mean score was higher on the post-test (30.3/40) than on the pre-test (28.0/40), and individual post- and pre-test scores were highly correlated (r = 0.65, p < 0.0001). Group assignment alone did not have an effect on test scores (p > 0.84), but intervention-arm subjects who completed all assigned cases answered an average of 3.2 more questions correctly on the post-test than others, controlling for pre-test scores (p = 0.003). Completion of the case-based intervention improved respondents' test scores, with those who completed all six email cases scoring roughly 10% better than those who failed to complete this task and those in the control arm. There was only suggestive evidence that intensive case work improved ethical issue identification, although there was limited ability to assess this outcome due to a high drop-out rate.

Building research capacity in Botswana: a randomized trial comparing training methodologies in the Botswana ethics training initiative

PubMed Central

2013-01-01

Background Little empirical data are available on the extent to which capacity-building programs in research ethics prepare trainees to apply ethical reasoning skills to the design, conduct, or review of research. A randomized controlled trial was conducted in Botswana in 2010 to assess the effectiveness of a case-based intervention using email to augment in-person seminars. Methods University faculty and current and prospective IRB/REC members took part in a semester-long training program in research ethics. Participants attended two 2-day seminars and were assigned at random to one of two on-line arms of the trial. Participants in both arms completed on-line international modules from the Collaborative Institutional Training Initiative. Between seminars, intervention-arm participants were also emailed a weekly case to analyze in response to set questions; responses and individualized faculty feedback were exchanged via email. Tests assessing ethics knowledge were administered at the start of each seminar. The post-test included an additional section in which participants were asked to identify the ethical issues highlighted in five case studies from a list of multiple-choice responses. Results were analyzed using regression and ANOVA. Results Of the 71 participants (36 control, 35 intervention) enrolled at the first seminar, 41 (57.7%) attended the second seminar (19 control, 22 intervention). In the intervention arm, 19 (54.3%) participants fully completed and 8 (22.9%) partially completed all six weekly cases. The mean score was higher on the post-test (30.3/40) than on the pre-test (28.0/40), and individual post- and pre-test scores were highly correlated (r = 0.65, p < 0.0001). Group assignment alone did not have an effect on test scores (p > 0.84), but intervention-arm subjects who completed all assigned cases answered an average of 3.2 more questions correctly on the post-test than others, controlling for pre-test scores (p = 0.003). Conclusions Completion of the case-based intervention improved respondents’ test scores, with those who completed all six email cases scoring roughly 10% better than those who failed to complete this task and those in the control arm. There was only suggestive evidence that intensive case work improved ethical issue identification, although there was limited ability to assess this outcome due to a high drop-out rate. PMID:23368699

Patterning of physiological and affective responses in older active adults during a maximal graded exercise test and self-selected exercise.

PubMed

Smith, Ashleigh E; Eston, Roger; Tempest, Gavin D; Norton, Belinda; Parfitt, Gaynor

2015-09-01

The American College of Sports Medicine has highlighted the importance of considering the physiological and affective responses to exercise when setting exercise intensity. Here, we examined the relationship between exercise intensity and physiological and affective responses in active older adults. Eighteen participants (60-74 years; 64.4 ± 3.9; 8 women) completed a maximal graded exercise test (GXT) on a treadmill. Since time to exhaustion in the GXT differed between participants, heart rate (HR), oxygen consumption (VO2), affective valence (affect) and rating of perceived exertion (RPE) were expressed relative to the individually determined ventilatory threshold (%atVT). During the GXT, VO2, HR and RPE increased linearly (all P < 0.01). Affect declined initially (but remained positive) (P = 0.03), stabilised around VT (still positive) (P > 0.05) and became negative towards the end of the test (P < 0.01). In a subsequent session, participants completed a 20-min bout of self-selected exercise (at a preferred intensity). Initially, participants chose to exercise below VT (88.2 ± 17.4 %VO2atVT); however, the intensity was adjusted to work at, or above VT (107.7 ± 19.9 %VO2atVT) after 10 min (P < 0.001), whilst affect remained positive. Together, these findings indicate that exercise around VT, whether administered during an exercise test, or self-selected by the participant, is likely to result in positive affective responses in older adults.

Instructors of psychotherapy in M.A. and Ph.D. clinical programs.

PubMed

Stevens, H B

1996-08-01

The present study investigated the characteristics and orientations of the instructors of the initial psychotherapy course of the 44 members and affiliates of the Council of Applied Master's Programs in Psychology. Also examined were the focus of instruction in the course and the teachers' style of instruction. Responses for 26 completed surveys (58%) were compared with responses from instructors of initial psychotherapy courses in 69 of the 170 APA accredited doctoral programs. Five general theoretical orientations were represented by the M.A. instructors with 28% self-identifying as humanistic, 24% as dynamic, 20% as cognitive behavioral, 16% as interpersonal, and 12% as behavioral. No significant differences were found on demographic characteristics, theoretical orientation, focus of instruction, or method of instruction between instructors in M.A. and those in Ph.D. programs.

Initiating/maintaining long-acting injectable antipsychotics in schizophrenia/schizoaffective or bipolar disorder - expert consensus survey part 2.

PubMed

Sajatovic, Martha; Ross, Ruth; Legacy, Susan N; Byerly, Matthew; Kane, John M; DiBiasi, Faith; Fitzgerald, Heather; Correll, Christoph U

2018-01-01

The aim of this study was to provide recommendations on initiating and maintaining long-acting injectable antipsychotics (LAIs) in individuals with schizophrenia/schizoaffective or bipolar disorder. A 50-question survey comprising 916 response options was completed by 34 expert researchers and high prescribers with extensive LAI experience, rating relative appropriateness/importance on a 9-point scale. Consensus was determined using chi-square test of score distributions. Results of 21 questions comprising 339 response options regarding LAI initiation, maintenance treatment, adequate trial definition, identifying treatment nonresponse, and switching are reported. Experts agreed that the most important LAI selection factor was patient response/tolerability to previous antipsychotics. An adequate therapeutic LAI trial was defined as the time to steady state ± 1-2 injection cycles. Experts suggested that oral efficacy and tolerability should be established before switching to an LAI, without consensus on the required time, and that the time for oral supplementation and next injection interval should be determined by the time to attainment of therapeutic LAI levels. Most experts agreed that ≥1 adequate LAI trial is needed to identify the lack of efficacy. There was little agreement about strategies for switching between LAIs. Expert guidance may aid clinicians in their decisions regarding initiating/maintaining LAIs in individuals with schizophrenia/schizoaffective or bipolar disorder.

Longitudinal optical monitoring of blood flow in breast tumors during neoadjuvant chemotherapy

NASA Astrophysics Data System (ADS)

Cochran, J. M.; Chung, S. H.; Leproux, A.; Baker, W. B.; Busch, D. R.; DeMichele, A. M.; Tchou, J.; Tromberg, B. J.; Yodh, A. G.

2017-06-01

We measure tissue blood flow markers in breast tumors during neoadjuvant chemotherapy and investigate their correlation to pathologic complete response in a pilot longitudinal patient study (n  =  4). Tumor blood flow is quantified optically by diffuse correlation spectroscopy (DCS), and tissue optical properties, blood oxygen saturation, and total hemoglobin concentration are derived from concurrent diffuse optical spectroscopic imaging (DOSI). The study represents the first longitudinal DCS measurement of neoadjuvant chemotherapy in humans over the entire course of treatment; it therefore offers a first correlation between DCS flow indices and pathologic complete response. The use of absolute optical properties measured by DOSI facilitates significant improvement of DCS blood flow calculation, which typically assumes optical properties based on literature values. Additionally, the combination of the DCS blood flow index and the tissue oxygen saturation from DOSI permits investigation of tissue oxygen metabolism. Pilot results from four patients suggest that lower blood flow in the lesion-bearing breast is correlated with pathologic complete response. Both absolute lesion blood flow and lesion flow relative to the contralateral breast exhibit potential for characterization of pathological response. This initial demonstration of the combined optical approach for chemotherapy monitoring provides incentive for more comprehensive studies in the future and can help power those investigations.

A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma

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

Hiniker, Susan M., E-mail: shiniker@stanford.edu; Reddy, Sunil A.; Maecker, Holden T.

Purpose: Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte–associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses. Methods and Materials: In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasismore » measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. Results: Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response. Conclusion: This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the potential to be even more effective in combination with RT.« less

Variations in disaster evacuation behavior: public responses versus private sector executive decision-making processes.

PubMed

Drabek, T E

1992-06-01

Data obtained from 65 executives working for tourism firms in three sample communities permitted comparison with the public warning response literature regarding three topics: disaster evacuation planning, initial warning responses, and disaster evacuation behavior. Disaster evacuation planning was reported by nearly all of these business executives, although it was highly variable in content, completeness, and formality. Managerial responses to post-disaster warnings paralleled the type of complex social processes that have been documented within the public response literature, except that warning sources and confirmation behavior were significantly affected by contact with authorities. Five key areas of difference were discovered in disaster evacuation behavior pertaining to: influence of planning, firm versus family priorities, shelter selection, looting concerns, and media contacts.

Electronic surveys: how to maximise success.

PubMed

McPeake, Joanne; Bateson, Meghan; O'Neill, Anna

2014-01-01

To draw on the researchers' experience of developing and distributing a UK-wide electronic survey. The evolution of electronic surveys in healthcare research will be discussed, as well as simple techniques that can be used to improve response rates for this type of data collection. There is an increasing use of electronic survey methods in healthcare research. However, in recent published research, electronic surveys have had lower response rates than traditional survey methods, such as postal and telephone surveys. This is a methodology paper. Electronic surveys have many advantages over traditional surveys, including a reduction in cost and ease of analysis. Drawbacks to this type of data collection include the potential for selection bias and poorer response rates. However, research teams can use a range of simple strategies to boost response rates. These approaches target the different stages of achieving a complete response: initial attraction through personalisation, engagement by having an easily accessible link to the survey, and transparency of survey length and completion though targeting the correct, and thereby interested, population. The fast, efficient and often 'free' electronic survey has many advantages over the traditional postal data collection method, including ease of analysis for what can be vast amounts of data. However, to capitalise on these benefits, researchers must carefully consider techniques to maximise response rates and minimise selection bias for their target population. Researchers can use a range of strategies to improve responses from electronic surveys, including sending up to three reminders, personalising each email, adding the updated response rate to reminder emails, and stating the average time it would take to complete the survey in the title of the email.

A Comparison of Adults' Responses to Collage versus Drawing in an Initial Art-Making Session

ERIC Educational Resources Information Center

Raffaelli, Teresa; Hartzell, Elizabeth

2016-01-01

The goal of this systematic comparison of collage and drawing was to contribute to the sparse body of literature on the way individuals might respond to two materials commonly used in art therapy. Eight graduate and undergraduate university students who identified as non-artists completed two tasks, one using drawing materials and one using…

Students Who Demonstrate Strong Talent and Interest in STEM Are Initially Attracted to STEM through Extracurricular Experiences

ERIC Educational Resources Information Center

VanMeter-Adams, Amy; Frankenfeld, Cara L.; Bases, Jessica; Espina, Virginia; Liotta, Lance A.

2014-01-01

What early experiences attract students to pursue an education and career in science, technology, engineering, and mathematics (STEM)? Does hands-on research influence them to persevere and complete a major course of academic study in STEM? We evaluated survey responses from 149 high school and undergraduate students who gained hands-on research…

Beyond College Eligibility: A New Framework for Promoting College Readiness. College Readiness Indicator Systems Resource Series

ERIC Educational Resources Information Center

Annenberg Institute for School Reform at Brown University, 2014

2014-01-01

The College Readiness Indicator Systems (CRIS) initiative was developed in response to a troubling pattern: More students than ever are enrolling in college after high school, but many of them are not college ready, as evidenced by persistently low rates of college completion. The sense of urgency to close the gap between college eligibility and…

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers.

PubMed

Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J; Brown, Powel H; Dannenberg, Andrew J; Szabo, Eva

2012-09-01

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. Published by Elsevier Inc.

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers

PubMed Central

Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J.; Brown, Powel H.; Dannenberg, Andrew J.; Szabo, Eva

2012-01-01

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. PMID:22771576

Optimization of the photoelectrocatalytic oxidation of landfill leachate using copper and nitrate co-doped TiO2 (Ti) by response surface methodology

PubMed Central

Zhou, Shaoqi; Feng, Xinbin

2017-01-01

In this paper, a statistically-based experimental design with response surface methodology (RSM) was employed to examine the effects of functional conditions on the photoelectrocatalytic oxidation of landfill leachate using a Cu/N co-doped TiO2 (Ti) electrode. The experimental design method was applied to response surface modeling and the optimization of the operational parameters of the photoelectro-catalytic degradation of landfill leachate using TiO2 as a photo-anode. The variables considered were the initial chemical oxygen demand (COD) concentration, pH and the potential bias. Two dependent parameters were either directly measured or calculated as responses: chemical oxygen demand (COD) removal and total organic carbon (TOC) removal. The results of this investigation reveal that the optimum conditions are an initial pH of 10.0, 4377.98mgL-1 initial COD concentration and 25.0 V of potential bias. The model predictions and the test data were in satisfactory agreement. COD and TOC removals of 67% and 82.5%, respectively, were demonstrated. Under the optimal conditions, GC/MS showed 73 organic micro-pollutants in the raw landfill leachate which included hydrocarbons, aromatic compounds and esters. After the landfill leachate treatment processes, 38 organic micro-pollutants disappeared completely in the photoelectrocatalytic process. PMID:28671943

[Axillary pathologic response after neoadjuvant chemotherapy in locally advanced breast cancer with axillary involvement].

PubMed

Jiménez-Ballvé, A; Serrano-Palacio, A; García-Sáenz, J A; Ortega Candil, A; Salsidua-Arroyo, O; Román-Santamaría, J M; Pelayo Alarcón, A; Fuentes Ferrer, M E; Carreras-Delgado, J L

2015-01-01

To compare axillary involvement (N+) at initial staging in locally advanced breast cancer (LABC) with axillary lymphadenectomy histologic results after neoadjuvant chemotherapy treatment (NeoChemo). Retrospective study between November 2011 and September 2013 of LABC cases treated with neoadjuvant chemotherapy based on docetaxel (associated with trastuzumab in HER2 positive cases and carboplatin/adriamycin in HER2 negative cases). Those clinically or radiologically suspected cases of axillary involvement were histologically confirmed. When there was no suspicion of axillary involvement, sentinel lymph node radioguided biopsy (SLNRB) was performed using intradermal injection of (99m)Tc-nanocolloid albumin prior to neoadjuvant treatment. Axillary lymphadenectomy after NeoChemo was undertaken in all cases with positive axilla. Final pathologic response was classified as complete (pCR) when there was no evidence of tumoral disease and as non-pathologic complete response (no pCR) in the opposite case. A total of 346 patients treated with docetaxel were reviewed, identifying 105 LABC. Axillary involvement at initial staging was detected in 70 (67%) before starting NeoChemo. From these 70, 73% (n=51) were N+ (fine needle biopsy and/or biopsy) and the remaining 19 (27%) were occult N+ detected by SLNRB. Axillary lymphadenectomy detected pCR in 56% (39/70), increasing up to 84% pCR when initial N+ status was reached using SNLB. On the other hand, when N+ was detected using fine needle biopsy/lymph biopsy, pCR was only 45%. More than 50% of women affected by locally advanced breast cancer with tumoral axillary involvement at initial diagnosis present free metastatic axilla after therapeutic neoadjuvant chemotherapy effect. This increases up to almost 90% in case of occult metastatic axilla detected with sentinel node biopsy prior starting neoadjuvant chemotherapy. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol: 38 cases (1996-2003).

PubMed

Milner, Rowan J; Peyton, Jamie; Cooke, Kirsten; Fox, Leslie E; Gallagher, Alexander; Gordon, Patti; Hester, Juli

2005-10-01

To determine response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol. Retrospective study. 38 cats with lymphoma. Medical records were reviewed, and information on age, sex, breed, FeLV and FIV infection status, anatomic form, clinical stage, and survival time was obtained. Immunophenotyping was not performed. Mean +/- SD age of the cats was 10.9 +/- 4.4 years. Overall median survival time was 210 days (interquartile range, 90 to 657 days), and overall duration of first remission was 156 days (interquartile range, 87 to 316 days). Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first remission or survival time. Eighteen of the 38 (47%) cats had complete remission, 14 (37%) had partial remission, and 6 (16%) had no response. Duration of first remission was significantly longer for cats with complete remission (654 days) than for cats with partial remission (114 days). Median survival time for cats with complete remission (654 days) was significantly longer than median survival time for cats with partial remission (122 days) and for cats with no response (11 days). Results suggested that a high percentage of cats with lymphoma will respond to treatment with the University of Wisconsin-Madison chemotherapy protocol. Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first response or survival time, but initial response to treatment was.

Value of Surveillance Studies for Patients With Stage I to II Diffuse Large B-Cell Lymphoma in the Rituximab Era

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

Hiniker, Susan M.; Pollom, Erqi L.; Khodadoust, Michael S.

2015-05-01

Background: The role of surveillance studies in limited-stage diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been well defined. We sought to evaluate the use of imaging (computed tomography [CT] and positron emission tomography [PET]-CT) scans and lactate dehydrogenase (LDH) in surveillance of patients with stage I to II DLBCL. Methods: A retrospective analysis was performed of patients who received definitive treatment between 2000 and 2013. Results: One hundred sixty-two consecutive patients with stage I to II DLBCL were treated with chemotherapy +/− rituximab, radiation, or combined modality therapy. The 5-year rates of overall survival (OS) and freedommore » from progression (FFP) were 81.2% and 80.8%, respectively. Of the 162 patients, 124 (77%) were followed up with at least 1 surveillance PET scan beyond end-of-treatment scans; of those, 94 of 124 (76%) achieved a complete metabolic response on PET scan after completion of chemotherapy, and this was associated with superior FFP (P=.01, HR=0.3) and OS (P=.01, HR 0.3). Eighteen patients experienced relapse after initial response to therapy. Nine relapses were initially suspected by surveillance imaging studies (8 PET, 1 CT), and 9 were suspected clinically (5 by patient-reported symptoms and 4 by symptoms and physical examination). No relapses were detected by surveillance LDH. The median duration from initiation of treatment to relapse was 14.3 months among patients with relapses suspected by imaging, and 59.8 months among patients with relapses suspected clinically (P=.077). There was no significant difference in OS from date of first therapy or OS after relapse between patients whose relapse was suspected by imaging versus clinically. Thirteen of 18 patients underwent successful salvage therapy after relapse. Conclusions: A complete response on PET scan immediately after initial chemotherapy is associated with superior FFP and OS in stage I to II DLBCL. The use of PET scans as posttreatment surveillance is not associated with a survival advantage. LDH is not a sensitive marker for relapse. Our results argue for limiting the use of posttreatment surveillance in patients with limited-stage DLBCL.« less

Pedophile types and treatment perspectives.

PubMed

Travin, S; Bluestone, H; Coleman, E; Cullen, K; Melella, J

1986-04-01

Pedophiles constitute a heterogeneous group of sex offenders. Direct physiological assessment of sexual arousal has significantly increased our diagnostic skill and capability of monitoring treatment response. Erectile response studies have indicated that the majority of pedophiles and incest offenders show arousal to other paraphilias and frequently to appropriate adult sexual stimuli. Many sexual offenders deny or minimize their problem during initial interviews, but when confronted with laboratory results indicating deviant sexual arousal, they often acknowledge and elaborate on the paraphilia(s). Complete data and diagnoses are crucial in integrating treatment in the cognitive-behavioral paradigm.

Long-term complete remission of metastatic breast cancer, induced by a steroidal aromatase inhibitor after failure of a non-steroidal aromatase inhibitor

PubMed Central

Shioi, Yoshihiro; Kashiwaba, Masahiro; Inaba, Toru; Komatsu, Hideaki; Sugai, Tamotsu; Wakabayashi, Go

2014-01-01

Patient: Female, 56 Final Diagnosis: Breast cancer Symptoms: Solid mass in the right breast Medication: Exemestane Clinical Procedure: — Specialty: Oncology Objective: Unusual clinical course Background: The efficacy of third-generation aromatase inhibitors for hormone receptor-positive postmenopausal metastatic breast cancer is well established. Although several clinical trials have reported incomplete cross-resistance between different aromatase inhibitors, few cases of complete responses of recurrent metastatic breast cancer occurring after substituting a second aromatase inhibitor have been reported. We here present a rare case of non-steroidal aromatase inhibitor-tolerant metastatic breast cancer with long-term complete remission following substitution of a steroidal aromatase inhibitor. Case Report: We present the case of a 56-year-old Japanese woman who underwent right breast-conserving surgery for breast cancer, TNM staging T1, N0, M0, Stage I. She received adjuvant chemotherapy with 6 cycles of FEC100 and radiation therapy, and then began hormonal therapy with anastrozole. Twelve months postoperatively, computed tomography (CT) revealed multiple lung metastases. Exemestane was substituted for anastrozole. After 3 months of exemestane, CT showed that all lung metastases had completely resolved. Her complete response was maintained for 5 years: she died during a tsunami 6 years after the initial surgery. Conclusions: Substitution of a steroidal for a non-steroidal aromatase inhibitor produced a sustained complete remission in a patient with hormonal receptor-positive postmenopausal recurrent breast cancer. Achieving complete response after switching from a non-steroidal to a steroidal aromatase inhibitor in a hormonal receptor-positive postmenopausal recurrent breast cancer contributed to a higher quality of life for the patient. Further investigation is needed to identify the predictors of long-term remission following such a switch. PMID:24587856

Independent backup mode transfer and mechanism for digital control computers

NASA Technical Reports Server (NTRS)

Tulpule, Bhalchandra R. (Inventor); Oscarson, Edward M. (Inventor)

1992-01-01

An interrupt is provided to a signal processor having a non-maskable interrupt input, in response to the detection of a request for transfer to backup software. The signal processor provides a transfer signal to a transfer mechanism only after completion of the present machine cycle. Transfer to the backup software is initiated by the transfer mechanism only upon reception of the transfer signal.

Human responses to bright light of different durations.

PubMed

Chang, Anne-Marie; Santhi, Nayantara; St Hilaire, Melissa; Gronfier, Claude; Bradstreet, Dayna S; Duffy, Jeanne F; Lockley, Steven W; Kronauer, Richard E; Czeisler, Charles A

2012-07-01

Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying bright light. Thirty-nine young healthy participants (16 female; 22.18±3.62 years) completed a 9-day inpatient study. Following three baseline days, participants underwent an initial circadian phase assessment procedure in dim light (<3 lux), and were then randomized for exposure to a bright light pulse (∼10,000 lux) of 0.2 h, 1.0 h, 2.5 h or 4.0 h duration during a 4.5 h controlled-posture episode centred in a 16 h wake episode. After another 8 h sleep episode, participants completed a second circadian phase assessment. Phase shifts were calculated from the difference in the clock time of the dim light melatonin onset (DLMO) between the initial and final phase assessments. Exposure to varying durations of bright light reset the circadian pacemaker in a dose-dependent, non-linear manner. Per minute of exposure, the 0.2 h duration was over 5 times more effective at phase delaying the circadian pacemaker (1.07±0.36 h) as compared with the 4.0 h duration (2.65±0.24 h). Acute melatonin suppression and subjective sleepiness also had a dose-dependent response to light exposure duration. These results provide strong evidence for a non-linear resetting response of the human circadian pacemaker to light duration.

Feasibility of collecting 24-h urine to monitor sodium intake in the National Health and Nutrition Examination Survey123

PubMed Central

Terry, Ana L; Cogswell, Mary E; Wang, Chia-Yih; Chen, Te-Ching; Loria, Catherine M; Wright, Jacqueline D; Zhang, Xinli; Lacher, David A; Merritt, Robert K; Bowman, Barbara A

2016-01-01

Background: Twenty-four–hour urine sodium excretion is recommended for monitoring population sodium intake. Because of concerns about participation and completion, sodium excretion has not been collected previously in US nationally representative surveys. Objective: We assessed the feasibility of implementing 24-h urine collections as part of a nationally representative survey. Design: We selected a random half sample of nonpregnant US adults aged 20–69 y in 3 geographic locations of the 2013 NHANES. Participants received explicit instructions, started and ended the urine collection in a urine study mobile examination center, and answered questions about their collection. Among those with a complete 24-h urine collection, a random one-half were asked to collect a second 24-h urine sample. Sodium, potassium, chloride, and creatinine excretion were analyzed. Results: The final NHANES examination response rate for adults aged 20–69 y in these 3 study locations was 71%. Of those examined (n = 476), 282 (59%) were randomly selected to participate in the 24-h urine collection. Of these, 212 persons [75% of those selected for 24-h urine collection; 53% (equal to 71% × 75% of those selected for the NHANES)] collected a complete initial 24-h specimen and 92 persons (85% of 108 selected) collected a second complete 24-h urine sample. More men than women completed an initial collection (P = 0.04); otherwise, completion did not vary by sociodemographic characteristics, body mass index, education, or employment status for either collection. Mean 24-h urine volume and sodium excretion were 1964 ± 1228 mL and 3657 ± 2003 mg, respectively, for the first 24-h urine sample, and 2048 ± 1288 mL and 3773 ± 1891 mg, respectively, for the second collection. Conclusion: Given the 53% final component response rate and 75% completion rate, 24-h urine collections were deemed feasible and implemented in the NHANES 2014 on a subsample of adults aged 20–69 y to assess population sodium intake. This study was registered at clinicaltrials.gov as NCT02723682. PMID:27413136

Spatial Discrimination Reversal and Incremental Repeated Acquisition in Adolescent and Adult BALB/c Mice

PubMed Central

Shen, Andrew Nathanael; Pope, Derek A.; Hutsell, Blake A.; Newland, M. Christopher

2015-01-01

Adolescence is characterized by neural and behavior development that includes increases in novel experiences and impulsive choice. Experimental rodent models can characterize behavior phenotypes that typify adolescence. The present experiment was designed to characterize differences between adolescent (post-natal day (PND) 34 - 60) and adult (PND 70 - 96) BALB/c mice using a response-initiated spatial discrimination reversal (SDR) and incremental repeated acquisition of response chains (IRA) procedures. During SDR, adolescents omitted more trials and were slower to initiate trials than adults, but the age groups did not differ on accuracy and perseveration measures. During IRA, adolescents displayed poorer overall performance (measured by progress quotient), lower accuracy at individual chain links, and completed fewer long response chains (>3 links) than adults. In both procedures (SDR and IRA), the poorer performance of adolescents appeared to be related to the use of a response device that was spatially removed from reinforcer delivery. These results indicate that SDR and IRA performance can be established during the brief rodent adolescent period but that these two age groups’ performances differ. We hypothesize that adolescent behavior is more sensitive than adult behavior to the spatiotemporal distance between response device and location of reinforcer delivery. PMID:26051193

Complete response in gallbladder cancer to erlotinib plus gemcitabine does not require mutation of the epidermal growth factor receptor gene: a case report.

PubMed

Mody, Kabir; Strauss, Edward; Lincer, Robert; Frank, Richard C

2010-10-20

Gallbladder cancer typically follows an aggressive course, with chemotherapy the standard of care for advanced disease; complete remissions are rarely encountered. The epidermal growth factor receptor (EGFR) is a promising therapeutic target but the activity of single agent oral EGFR tyrosine kinase inhibitors is low. There have been no previous reports of chemotherapy plus an EGFR-tyrosine kinase inhibitor (TKI) to treat gallbladder cancer or correlations of response with the mutation status of the tyrosine kinase domain of the EGFR gene. A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine (1000 mg/m2) on day 1 and 8 every 21 days as well as daily erlotinib (100 mg). After four cycles of therapy, the CA 19-9 normalized and a PET/CT showed a complete remission; this response was maintained by the end of 12 cycles of therapy. Gemcitabine was then discontinued and single agent erlotinib was continued as maintenance therapy. The disease remains in good control 18 months after initiation of therapy, including 6 months on maintenance erlotinib. The only grade 3 toxicity was a typical EGFR-related skin rash. Because of the remarkable response to erlotinib plus gemcitabine, we performed tumor genotyping of the EGFR gene for response predicting mutations in exons 18, 19 and 21. This disclosed the wild-type genotype with no mutations found. This case report demonstrates a patient with stage IV gallbladder cancer who experienced a rarely encountered complete, prolonged response after treatment with an oral EGFR-TKI plus chemotherapy. This response occurred in the absence of an EGFR gene mutation. These observations should inform the design of clinical trials using EGFR-TKIs to treat gallbladder and other biliary tract cancers; such trials should not select patients based on EGFR mutation status.

Association of O-Antigen Serotype with the Magnitude of Initial Systemic Cytokine Responses and Persistence in the Urinary Tract.

PubMed

Horvath, Dennis J; Patel, Ashay S; Mohamed, Ahmad; Storm, Douglas W; Singh, Chandra; Li, Birong; Zhang, Jingwen; Koff, Stephen A; Jayanthi, Venkata R; Mason, Kevin M; Justice, Sheryl S

2016-01-11

Urinary tract infection (UTI) is one of the most common ailments requiring both short-term and prophylactic antibiotic therapies. Progression of infection from the bladder to the kidney is associated with more severe clinical symptoms (e.g., fever and vomiting) as well as with dangerous disease sequelae (e.g., renal scaring and sepsis). Host-pathogen interactions that promote bacterial ascent to the kidney are not completely understood. Prior studies indicate that the magnitude of proinflammatory cytokine elicitation in vitro by clinical isolates of uropathogenic Escherichia coli (UPEC) inversely correlates with the severity of clinical disease. Therefore, we hypothesize that the magnitude of initial proinflammatory responses during infection defines the course and severity of disease. Clinical UPEC isolates obtained from patients with a nonfebrile UTI elicited high systemic proinflammatory responses early during experimental UTI in a murine model and were attenuated in bladder and kidney persistence. Conversely, UPEC isolates obtained from patients with febrile UTI elicited low systemic proinflammatory responses early during experimental UTI and exhibited prolonged persistence in the bladder and kidney. Soluble factors in the supernatant from saturated cultures as well as the lipopolysaccharide (LPS) serotype correlated with the magnitude of proinflammatory responses in vitro. Our data suggest that the structure of the O-antigen sugar moiety of the LPS may determine the strength of cytokine induction by epithelial cells. Moreover, the course and severity of disease appear to be the consequence of the magnitude of initial cytokines produced by the bladder epithelium during infection. The specific host-pathogen interactions that determine the extent and course of disease are not completely understood. Our studies demonstrate that modest changes in the magnitude of cytokine production observed using in vitro models of infection translate into significant ramifications for bacterial persistence and disease severity. While many studies have demonstrated that modifications of the LPS lipid A moiety modulate the extent of Toll-like receptor 4 (TLR4) activation, our studies implicate the O-antigen sugar moiety as another potential rheostat for the modulation of proinflammatory cytokine production. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Association of O-Antigen Serotype with the Magnitude of Initial Systemic Cytokine Responses and Persistence in the Urinary Tract

PubMed Central

Horvath, Dennis J.; Patel, Ashay S.; Mohamed, Ahmad; Storm, Douglas W.; Singh, Chandra; Li, Birong; Zhang, Jingwen; Koff, Stephen A.; Jayanthi, Venkata R.; Mason, Kevin M.

2016-01-01

ABSTRACT Urinary tract infection (UTI) is one of the most common ailments requiring both short-term and prophylactic antibiotic therapies. Progression of infection from the bladder to the kidney is associated with more severe clinical symptoms (e.g., fever and vomiting) as well as with dangerous disease sequelae (e.g., renal scaring and sepsis). Host-pathogen interactions that promote bacterial ascent to the kidney are not completely understood. Prior studies indicate that the magnitude of proinflammatory cytokine elicitation in vitro by clinical isolates of uropathogenic Escherichia coli (UPEC) inversely correlates with the severity of clinical disease. Therefore, we hypothesize that the magnitude of initial proinflammatory responses during infection defines the course and severity of disease. Clinical UPEC isolates obtained from patients with a nonfebrile UTI elicited high systemic proinflammatory responses early during experimental UTI in a murine model and were attenuated in bladder and kidney persistence. Conversely, UPEC isolates obtained from patients with febrile UTI elicited low systemic proinflammatory responses early during experimental UTI and exhibited prolonged persistence in the bladder and kidney. Soluble factors in the supernatant from saturated cultures as well as the lipopolysaccharide (LPS) serotype correlated with the magnitude of proinflammatory responses in vitro. Our data suggest that the structure of the O-antigen sugar moiety of the LPS may determine the strength of cytokine induction by epithelial cells. Moreover, the course and severity of disease appear to be the consequence of the magnitude of initial cytokines produced by the bladder epithelium during infection. IMPORTANCE The specific host-pathogen interactions that determine the extent and course of disease are not completely understood. Our studies demonstrate that modest changes in the magnitude of cytokine production observed using in vitro models of infection translate into significant ramifications for bacterial persistence and disease severity. While many studies have demonstrated that modifications of the LPS lipid A moiety modulate the extent of Toll-like receptor 4 (TLR4) activation, our studies implicate the O-antigen sugar moiety as another potential rheostat for the modulation of proinflammatory cytokine production. PMID:26755631

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study.

PubMed

Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

2017-02-01

Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200-600 mg) and then monthly rituximab commenced (375 mg/m 2 in month 1 and 500 mg/m 2 in months 2-6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1-2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3-4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66-91) and 89% (95% CI 72-96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax. A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies. AbbVie Inc and Genentech Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study

PubMed Central

Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

2017-01-01

Summary Background Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Methods Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200–600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2–6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Findings Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1–2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3–4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66–91) and 89% (95% CI 72–96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax. Interpretation A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies. PMID:28089635

Outcomes of cervical cancer among HIV-infected and HIV-uninfected women treated at the Brazilian National Institute of Cancer.

PubMed

Ferreira, Mariana P; Coghill, Anna E; Chaves, Claudia B; Bergmann, Anke; Thuler, Luiz C; Soares, Esmeralda A; Pfeiffer, Ruth M; Engels, Eric A; Soares, Marcelo A

2017-02-20

We assessed mortality, treatment response, and relapse among HIV-infected and HIV-uninfected women with cervical cancer in Rio de Janeiro, Brazil. Cohort study of 87 HIV-infected and 336 HIV-uninfected women with cervical cancer. Patients at the Brazilian National Institute of Cancer (2001-2013) were matched on age, calendar year of diagnosis, clinical stage, and tumor histology. Staging and treatment with surgery, radiotherapy, and/or chemotherapy followed international guidelines. We used a Markov model to assess responses to initial therapy, and Cox models for mortality and relapse after complete response (CR). Among 234 deaths, most were from cancer (82% in HIV-infected vs. 93% in HIV-uninfected women); only 9% of HIV-infected women died from AIDS. HIV was not associated with mortality during initial follow-up but was associated more than 1-2 years after diagnosis [overall mortality: stage-adjusted hazard ratio 2.02, 95% confidence interval (CI) 1.27-3.22; cancer-specific mortality: 4.35, 1.86-10.2]. Among 222 patients treated with radiotherapy, HIV-infected had similar response rates to initial cancer therapy as HIV-uninfected women (hazard ratio 0.98, 95% CI 0.58-1.66). However, among women who were treated and had a CR, HIV was associated with elevated risk of subsequent relapse (hazard ratio 3.60, 95% CI 1.86-6.98, adjusted for clinical stage). Among women with cervical cancer, HIV infection was not associated with initial treatment response or early mortality, but relapse after attaining a CR and late mortality were increased in those with HIV. These results point to a role for an intact immune system in control of residual tumor burden among treated cervical cancer patients.

The effectiveness of a monetary incentive offer on survey response rates and response completeness in a longitudinal study.

PubMed

Yu, Shengchao; Alper, Howard E; Nguyen, Angela-Maithy; Brackbill, Robert M; Turner, Lennon; Walker, Deborah J; Maslow, Carey B; Zweig, Kimberly C

2017-04-26

Achieving adequate response rates is an ongoing challenge for longitudinal studies. The World Trade Center Health Registry is a longitudinal health study that periodically surveys a cohort of ~71,000 people exposed to the 9/11 terrorist attacks in New York City. Since Wave 1, the Registry has conducted three follow-up surveys (Waves 2-4) every 3-4 years and utilized various strategies to increase survey participation. A promised monetary incentive was offered for the first time to survey non-respondents in the recent Wave 4 survey, conducted 13-14 years after 9/11. We evaluated the effectiveness of a monetary incentive in improving the response rate five months after survey launch, and assessed whether or not response completeness was compromised due to incentive use. The study compared the likelihood of returning a survey for those who received an incentive offer to those who did not, using logistic regression models. Among those who returned surveys, we also examined whether those receiving an incentive notification had higher rate of response completeness than those who did not, using negative binomial regression models and logistic regression models. We found that a $10 monetary incentive offer was effective in increasing Wave 4 response rates. Specifically, the $10 incentive offer was useful in encouraging initially reluctant participants to respond to the survey. The likelihood of returning a survey increased by 30% for those who received an incentive offer (AOR = 1.3, 95% CI: 1.1, 1.4), and the incentive increased the number of returned surveys by 18%. Moreover, our results did not reveal any significant differences on response completeness between those who received an incentive offer and those who did not. In the face of the growing challenge of maintaining a high response rate for the World Trade Center Health Registry follow-up surveys, this study showed the value of offering a monetary incentive as an additional refusal conversion strategy. Our findings also suggest that an incentive offer could be particularly useful near the end of data collection period when an immediate boost in response rate is needed.

Comparison of Online Survey Recruitment Platforms for Hard-to-Reach Pregnant Smoking Populations: Feasibility Study.

PubMed

Ibarra, Jose Luis; Agas, Jessica Marie; Lee, Melissa; Pan, Julia Lily; Buttenheim, Alison Meredith

2018-04-16

Recruiting hard-to-reach populations for health research is challenging. Web-based platforms offer one way to recruit specific samples for research purposes, but little is known about the feasibility of online recruitment and the representativeness and comparability of samples recruited through different Web-based platforms. The objectives of this study were to determine the feasibility of recruiting a hard-to-reach population (pregnant smokers) using 4 different Web-based platforms and to compare participants recruited through each platform. A screener and survey were distributed online through Qualtrics Panel, Soapbox Sample, Reddit, and Amazon Mechanical Turk (mTurk). Descriptive statistics were used to summarize results of each recruitment platform, including eligibility yield, quality yield, income, race, age, and gestational age. Of the 3847 participants screened for eligibility across all 4 Web-based platforms, 535 were eligible and 308 completed the survey. Amazon mTurk yielded the fewest completed responses (n=9), 100% (9/9) of which passed several quality metrics verifying pregnancy and smoking status. Qualtrics Panel yielded 14 completed responses, 86% (12/14) of which passed the quality screening. Soapbox Sample produced 107 completed surveys, 67% (72/107) of which were found to be quality responses. Advertising through Reddit produced the highest completion rate (n=178), but only 29.2% (52/178) of those surveys passed the quality metrics. We found significant differences in eligibility yield, quality yield, age, number of previous pregnancies, age of smoking initiation, current smokers, race, education, and income (P<.001). Although each platform successfully recruited pregnant smokers, results varied in quality, cost, and percentage of complete responses. Moving forward, investigators should pay careful attention to the percentage yield and cost of online recruitment platforms to maximize internal and external validity. ©Jose Luis Ibarra, Jessica Marie Agas, Melissa Lee, Julia Lily Pan, Alison Meredith Buttenheim. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 16.04.2018.

Emotion suppression affects cardiovascular responses to initial and subsequent laboratory stressors.

PubMed

Quartana, Phillip J; Burns, John W

2010-09-01

The study of anger suppression and risk for cardiovascular disease has relied predominately on inspection of correlations between trait anger-in and cardiovascular risk factors and disease. This approach tells us little about whether inhibitory processes have anything to do with outcomes, and cannot speak to whether suppression of anger per se affects cardiovascular parameters. Drawing on the broader emotion regulation literature, we examined the effects of experimentally induced anger and general negative emotion in the context of expressive and experiential suppression on cardiovascular responses to initial and subsequent laboratory stressors. Of all participants, 201 healthy participants were randomly assigned to one of six conditions formed by crossing emotion (anxiety, anger) and suppression (experiential, expressive, control) conditions. Participants completed a mental arithmetic task with anxiety or anger induction under their respective suppression manipulation instructions, and subsequently were exposed to a cold pressor task. Systolic blood pressure (SBP), diastolic blood pressure, and heart rate values were obtained for each experimental epoch. More robust SBP responses to the initial stressor were evidenced for those in the expressive versus the control condition. In response to the subsequent stressor, those in the experiential suppression condition showed the most pronounced SBP responses, suggesting pronounced delayed effects of this type of suppression. Effects of suppression on SBP reactivity were indistinguishable across anxiety and anger conditions. Effortful suppression of negative emotion has immediate and delayed consequences for stress-induced cardiovascular reactivity. Theoretical and clinical significance of these findings are discussed.

Age-related differences in idiom production in adulthood

PubMed Central

Conner, P. S.; Hyun, J.; O’Connor Wells, B.; Anema, I.; Goral, M.; Monéreau-Merry, M.; Rubino, D.; Kuckuk, R.; Obler, L. K.

2013-01-01

To investigate whether idiom production was vulnerable to age-related difficulties, we asked forty younger (ages 18-30) and forty older healthy adults (ages 60-85) to produce idiomatic expressions in a story-completion task. Younger adults produced significantly more correct idiom responses (73%) than older adults (60%) did. When older adults generated partially correct responses, they were less likely than younger participants to eventually produce the complete target idiom (Old: 32 % / Young: 70%); first-word cues after initial failure to retrieve an idiom resulted in more correct idioms for older (24%) than younger (15%) participants. Correlations between age and idiom correctness were positive for the Young group, and negative for the Older group, suggesting mastery of familiar idioms continues into adulthood. Within each group, scores on the Boston Naming Test correlated with performance on the idiom task. Findings for retrieving idiomatic expressions are thus similar to those for retrieving lexical items. PMID:21728830

[Modern therapy of chronic myeloid leukemia: an example for paradigma shift in hemato-oncology].

PubMed

Leitner, A A; Hehlmann, R

2011-02-01

Chronic myeloid leukemia (CML) is exceptional amongst neoplasias since its underlying pathomechanism has been elucidated, and potent well tolerated targeted drugs, the tyrosine kinase inhibitors (TKI), are available for treatment. They convincingly improve prognosis while retaining good quality of life. Aims of therapy are complete remissions as well as prolongation of life and cure. Imatinib 400 mg per day is current standard therapy. There are hints for a better outcome with a higher initial imatinib dose or with combination therapy. Even after achievement of complete molecular response continuous therapy might be necessary in most cases. In case of imatinib intolerance or failure, the second generation TKI dasatinib and nilotinib and allogeneic stem cell transplantation are available. The use of second generation TKI as first line treatment might further improve prognosis. The therapeutic response should be regularly monitored according to international recommendations.

Long-Term Remission of an Aggressive Sebaceous Carcinoma following Chemotherapy

PubMed Central

Orcurto, Angela; Gay, Béatrice E.; Sozzi, Wendy Jeanneret; Gilliet, Michel; Leyvraz, Serge

2014-01-01

Sebaceous carcinoma (SC) is an uncommon neoplasm manifesting itself either in the eyelid or extraocularly in the head and neck area. Surgery is the standard of care. Irradiation is rarely proposed as monotherapy but is frequently administered as an adjuvant regimen following surgical resection. There is no known strategy concerning chemotherapeutic treatment in highly aggressive recurrent – or metastatic – forms of the disease. Our patient presented with an aggressive SC of the scalp recurring after multiple excisions and local radiotherapy. Chemotherapy with 5-fluorouracil, cisplatin and docetaxel was then initiated; 4 cycles were administered, followed by capecitabine maintenance. Shortly after starting chemotherapy, dermal lesions had completely disappeared and radiological response could be seen. The patient experienced an extended period (>20 months) of complete remission. In this report, we show an excellent response of a highly aggressive SC after a combination of chemotherapy as for head and neck cancers. PMID:24748864

Evaluation of Magnetic Resonance Imaging Responsiveness in Active Psoriatic Arthritis at Multiple Timepoints during the First 12 Weeks of Antitumor Necrosis Factor Therapy.

PubMed

Feletar, Marie; Hall, Stephen; Bird, Paul

2016-01-01

To assess the responsiveness of high- and low-field extremity magnetic resonance imaging (MRI) variables at multiple timepoints in the first 12 weeks post-antitumor necrosis factor (anti-TNF) therapy initiation in patients with psoriatic arthritis (PsA) and active dactylitis. Twelve patients with active PsA and clinical evidence of dactylitis involving at least 1 digit were recruited. Patients underwent sequential high-field conventional (1.5 Tesla) and extremity low-field MRI (0.2 Tesla) of the affected hand or foot, pre- and postgadolinium at baseline (pre-TNF), 2 weeks (post-TNF), 6 weeks, and 12 weeks. A blinded observer scored all images on 2 occasions using the PsA MRI scoring system. Eleven patients completed the study, but only 6 patients completed all high-field and low-field MRI assessments. MRI scores demonstrated rapid response to TNF inhibition with score reduction in tenosynovitis, synovitis, and osteitis at 2 weeks. Intraobserver reliability was good to excellent for all variables. High-field MRI demonstrated greater sensitivity to tenosynovitis, synovitis, and osteitis and greater responsiveness to change posttreatment. Treatment responses were maintained to 12 weeks. This study demonstrates the use of MRI in detecting early response to biologic therapy. MRI variables of tenosynovitis, synovitis, and osteitis demonstrated responsiveness posttherapy with high-field scores more responsive to change than low-field scores.

The impact of comorbid body dysmorphic disorder on the response to sequential pharmacological trials for obsessive-compulsive disorder.

PubMed

Diniz, Juliana B; Costa, Daniel Lc; Cassab, Raony Cc; Pereira, Carlos Ab; Miguel, Euripedes C; Shavitt, Roseli G

2014-06-01

Our aim was to investigate the impact of comorbid body dysmorphic disorder (BDD) on the response to sequential pharmacological trials in adult obsessive-compulsive disorder (OCD) patients. The sequential trial initially involved fluoxetine monotherapy followed by one of three randomized, add-on strategies: placebo, clomipramine or quetiapine. We included 138 patients in the initial phase of fluoxetine, up to 80 mg or the maximum tolerated dosage, for 12 weeks. We invited 70 non-responders to participate in the add-on trial; as 54 accepted, we allocated 18 to each treatment group and followed them for an additional 12 weeks. To evaluate the combined effects of sex, age, age at onset, initial severity, type of augmentation and BDD on the response to sequential treatments, we constructed a model using generalized estimating equations (GEE). Of the 39 patients who completed the study (OCD-BDD, n = 13; OCD-non-BDD, n = 26), the OCD-BDD patients were less likely to be classified as responders than the OCD-non-BDD patients (Pearson Chi-Square = 4.4; p = 0.036). In the GEE model, BDD was not significantly associated with a worse response to sequential treatments (z-robust = 1.77; p = 0.07). The predictive potential of BDD regarding sequential treatment strategies for OCD did not survive when the analyses were controlled for other clinical characteristics. © The Author(s) 2013.

Predictors of HPV vaccine initiation and completion among Hispanic mothers of 11- to 17-year-old daughters living along the Texas-Mexico border

PubMed Central

Parra-Medina, Deborah

2016-01-01

Few Texas Latino girls initiate and complete the HPV vaccine series, but few studies have examined predictors of initiation and completion in this group. Mothers are crucial to vaccine uptake. Using self-reported data from mothers of unvaccinated girls (n=317), we examined the association between predictors (HPV and HPV vaccine knowledge, vaccine self-efficacy) and outcomes (initiation and completion). Despite an increase in HPV and HPV vaccine knowledge from baseline to follow-up (n=195), we found no association between the predictors and the outcomes. Findings showed that health insurance status and study group participation (Entre Madre e Hija program or brochure only) were associated with initiation and completion. PMID:28207677

Updating histological data on crown initiation and crown completion ages in southern Africans.

PubMed

Reid, Donald J; Guatelli-Steinberg, Debbie

2017-04-01

To update histological data on crown initiation and completion ages in southern Africans. To evaluate implications of these data for studies that: (a) rely on these data to time linear enamel hypoplasias (LEHs), or, (b) use these data for comparison to fossil hominins. Initiation ages were calculated on 67 histological sections from southern Africans, with sample sizes ranging from one to 11 per tooth type. Crown completion ages for southern Africans were calculated in two ways. First, actual derived initiation ages were added to crown formation times for each histological section to obtain direct information on the crown completion ages of individuals. Second, average initiation ages from this study were added to average crown formation times of southern Africans from the Reid and coworkers previous studies that were based on larger samples. For earlier-initiating tooth types (all anterior teeth and first molars), there is little difference in ages of initiation and crown completion between this and previous studies. Differences increase as a function of initiation age, such that the greatest differences between this and previous studies for both initiation and crown completion ages are for the second and third molars. This study documents variation in initiation ages, particularly for later-initiating tooth types. It upholds the use of previously published histological aging charts for LEHs on anterior teeth. However, this study finds that ages of crown initiation and completion in second and third molars for this southern African sample are earlier than previously estimated. These earlier ages reduce differences between modern humans and fossil hominins for these developmental events in second and third molars. © 2017 Wiley Periodicals, Inc.

Mod-2 wind turbine system cluster research test program. Volume 1: Initial plan E-1290

NASA Technical Reports Server (NTRS)

Gordon, L. H.

1982-01-01

Upon completion of the design and development of three Mod-2 wind turbines, a series of research experiments are planned to gather data on and evaluate the performance, environmental effects, and operation of a cluster as well as a single, large multimegawatt wind turbine. Information on the program objectives, a Mod-2 system description, a planned schedule, organizational roles, and responsibilities, is included.

Central Visual Prosthesis With Interface at the Lateral Geniculate Nucleus

DTIC Science & Technology

2017-07-01

burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching...currently used in the field to implant Deep Brain Stimulation electrodes. Page 4 We thus limited ourselves to using a ‘4 French’ size split sheath...this program. At this time , several approaches for realizing the complete system have been evaluated. Initially, a very simple mechanical mockup

Dispersion of Droplet Clouds in Turbulence.

PubMed

Bocanegra Evans, Humberto; Dam, Nico; Bertens, Guus; van der Voort, Dennis; van de Water, Willem

2016-10-14

We measure the absolute dispersion of clouds of monodisperse, phosphorescent droplets in turbulent air by means of high-speed image-intensified video recordings. Laser excitation allows the initial preparation of well-defined, pencil-shaped luminous droplet clouds in a completely nonintrusive way. We find that the dispersion of the clouds is faster than the dispersion of fluid elements. We speculate that preferential concentration of inertial droplet clouds is responsible for the enhanced dispersion.

An Examination of the Perceived Importance of Technical Competence in Acquisition Project Management

DTIC Science & Technology

1991-09-01

Develop (First Draft) Instructions Critique (Revision) Answerability Pilot Test (Second Draft) Analysis Response Mode Revision Useability Preparation...appropriate questionnaire items. Initially, the set of questions developed for the study reflected a few shortcomings. A pilot test of the first draft among...resulted. First, feedback from the pilot test indicated a need to reduce the completion time. Because the multiple choice format required several

Retreatment with bortezomib alone or in combination for patients with multiple myeloma following an initial response to bortezomib.

PubMed

Sood, Raman; Carloss, Harry; Kerr, Robert; Lopez, Jose; Lee, Martin; Druck, Mark; Walters, Ian B; Noga, Stephen J

2009-10-01

This clinical trial was conducted to determine the safety and efficacy of bortezomib retreatment in patients with multiple myeloma (MM) who had previously responded to bortezomib. Patients with progressive MM who had previously tolerated bortezomib as a single agent or in combination with other drugs, with a minimum of partial response (PR; >or=50% M-protein reduction) for >or=4 months, who had not received intervening MM therapy, were retreated with bortezomib (days 1, 4, 8, and 11 of a 21-day cycle) with a starting dose being the dose at which the patient ended the initial treatment. Patients were allowed to receive bortezomib on retreatment in combination with dexamethasone, thalidomide, or doxorubicin. Thirty-two patients received bortezomib retreatment (most with added dexamethasone). The median treatment-free interval (last dose of initial bortezomib treatment to first dose of retreatment) was 9.9 (range 2.5-34.0) months. The median duration of retreatment was 2.8 (<1-7.9) months; median total duration of bortezomib treatment was 6.7 (2.5-19.8) months. Based on the investigators' assessment of best response, the overall response rate (complete plus PR) was 50%. The median time from start of retreatment to progressive disease (PD) was 6.6 (95% confidence interval: 5.1-9.6) months. Thirteen patients (41%) experienced PN; bortezomib-related SAEs were reported in four patients. Retreatment with bortezomib alone or in combination is effective and well tolerated in patients with MM who have responded to their initial bortezomib treatment. (c) 2009 Wiley-Liss, Inc.

Improvement in medication education in a pediatric subspecialty practice

PubMed Central

2010-01-01

Background The purpose of this study was to measure the impact of an educational intervention on parents of children taking methotrexate (MTX) for juvenile idiopathic arthritis (JIA). Methods This study was conducted using a pre- and postsurvey design. The parents of 100 children with JIA taking MTX for at least 2 months were surveyed during a routine office visit. The parents completed an initial questionnaire regarding the safe use, adverse effects, and guidelines for monitoring the toxicity of MTX. An educational intervention was then administered, and an identical follow-up questionnaire was given during the next office visit. Statistical analysis using a paired t-test (critical P value < 0.05) was performed on individuals who answered both questionnaires. Results There were 100 responses to the initial questionnaire and 67 responses to the follow-up questionnaire. The mean length of time between surveys was 2.9 ± 0.9 months. In those who completed both questionnaires, the overall correct score increased significantly from 75.8% to 93.4%, respectively (P < 0.0001). Individuals scored the lowest (49%) on the question that addressed MTX's impact on pregnancy and fertility. Conclusions MTX knowledge may be less than expected in the parents of children with JIA. Brief educational interventions in the pediatric subspecialty practice can significantly affect a family's understanding of their child's medications. PMID:20843355

Improvement in medication education in a pediatric subspecialty practice.

PubMed

Patel, Aarat M; Torok, Kathryn S; Rosen, Paul

2010-09-15

The purpose of this study was to measure the impact of an educational intervention on parents of children taking methotrexate (MTX) for juvenile idiopathic arthritis (JIA). This study was conducted using a pre- and postsurvey design. The parents of 100 children with JIA taking MTX for at least 2 months were surveyed during a routine office visit. The parents completed an initial questionnaire regarding the safe use, adverse effects, and guidelines for monitoring the toxicity of MTX. An educational intervention was then administered, and an identical follow-up questionnaire was given during the next office visit. Statistical analysis using a paired t-test (critical P value < 0.05) was performed on individuals who answered both questionnaires. There were 100 responses to the initial questionnaire and 67 responses to the follow-up questionnaire. The mean length of time between surveys was 2.9 ± 0.9 months. In those who completed both questionnaires, the overall correct score increased significantly from 75.8% to 93.4%, respectively (P < 0.0001). Individuals scored the lowest (49%) on the question that addressed MTX's impact on pregnancy and fertility. MTX knowledge may be less than expected in the parents of children with JIA. Brief educational interventions in the pediatric subspecialty practice can significantly affect a family's understanding of their child's medications.

[Initial clinical experience of proton therapy at Shizuoka Cancer Center].

PubMed

Murayama, Shigeyuki; Fuji, Hiroshi; Yamashita, Haruo; Futami, Yasuyuki; Numano, Masumi; Harada, Hideyuki; Kamata, Minoru; Nishimura, Tetsuo

2005-10-01

To present the initial experience and preliminary clinical results of patients treated mainly with proton irradiation at the newly developed proton therapy facility at Shizuoka Cancer Center. We reviewed 125 patients who underwent proton therapy between July 2003 and December 2004. Of these 125 patients, 11 had head and neck malignancies, 15 non-small cell lung cancers, 22 hepatocellular carcinomas, 62 prostate cancers, and 15 other malignant tumors. Most patients experienced Grade 0-1 acute morbidities (NCI-CTC) in skin or mucosa, while a temporary Grade 2-3 reaction was observed in a high dose area. Response rates were 73% for H & N malignancies, 100% for NSCLC, and 77% for HCC. PSA evaluation for patients with prostate cancer revealed a high rate of complete response. The efficacy and safety of proton therapy at Shizuoka Cancer Center was demonstrated for patients with early-stage cancer or locally advanced disease.

Effect of Helicobacter pylori Eradication on Functional Dyspepsia

PubMed Central

Kim, Sung Eun; Park, Young Soo; Kim, Min Soo; Jo, Hyun Jin; Shin, Cheol Min; Lee, Sang Hyub; Hwang, Jin-Hyeok; Kim, Jin-Wook; Jeong, Sook-Hyang; Lee, Dong Ho; Jung, Hyun Chae

2013-01-01

Background/Aims This study evaluated the effect of Helicobacter pylori eradication on functional dyspepsia (FD), and the relationship between the changes of histological gastritis and FD symptom responses. Methods A total of 213 FD patients diagnosed by Rome III criteria were consecutively enrolled. H. pylori tests and gastritis grade by the Sydney system were performed before and 1 year after the proton pump based-eradication therapy for 7 days. Serum levels of pepsinogen, and genetic polymorphisms IL-6, IL-8 and IL-10 were investigated. Results Total of 91 patients completed the 1 year follow-up. When the response rate of dyspepsia was compared at 1 year between the non-eradicated group (n = 24) and eradicated group (n = 67), each group showed complete response of 62.5% and 62.7%; satisfactory response (≥ 50%) of 0.0% and 19.4%; partial response (< 50%) of 12.5% and 11.9%; and refractory response of 25.0% and 6.0%, respectively (P = 0.015). In addition, the responder group (complete + satisfactory response) at 1 year showed improvement of activity and chronic inflammation in both the antrum and corpus (all P < 0.001). Multivariate analysis showed that H. pylori eradication (OR, 5.81; 95% CI, 1.07-31.59) and symptom improvement at 3 month (OR, 28.90; 95% CI, 5.29-157.82) were associated with the improvement of dyspepsia at 1 year. Among the successfully eradicated FD patients (n = 67), male (P = 0.013) and higher initial BMI (P = 0.016) were associated with the improvement of dyspepsia at 1 year. Conclusions H. pylori eradication improved FD symptoms, as well as gastritis at 1 year, suggesting that inflammation mediates FD. PMID:23667755

Three-dimensional power Doppler ultrasound in the early assessment of response to concurrent chemo-radiotherapy for advanced cervical cancer.

PubMed

Xu, Yan; Zhu, Lijing; Ru, Tong; Wang, Huanhuan; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

2017-09-01

Background Three-dimensional power Doppler ultrasound (3D-PDU) imaging has been widely applied to the differentiation of benign and malignant cervical lesions; however, its potential value for predicting response to chemo-radiotherapy has not been fully explored. Purpose To investigate the feasibility of 3D-PDU imaging in predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancer. Material and Methods Fifty-two patients with advanced cervical cancer who received CCRT underwent 3D-PDU examinations at four timepoints: pre-therapy (baseline), 1 week and 2 weeks during, as well as immediately post CCRT. Final tumor response was determined by change in tumor size using magnetic resonance imaging (MRI). Cervical tumor volumes and vascular indices were calculated and compared with the clinical outcome. Results Of the 52 patients, 32 patients who completed all four examinations were included in the analyses: 21 were classified as complete response (CR) and 11 as partial response (PR). During the treatment, the CR group showed that 3D vascular indices (VI and VFI) significantly increased at 1 week ( P = 0.028, P = 0.017, respectively) then decreased at 2 weeks and obviously decreased at therapy completion (both P < 0.001), whereas tumors significantly decreased in volume at 2 weeks after therapy initiation ( P < 0.05). However, no significant differences in 3D vascular indices values were seen in the PR group during the treatment course (all P > 0.05). Conclusion Prospective longitudinal 3D-PDU imaging may have potentials in monitoring early therapeutic response to CCRT in patients with cervical cancer.

Predictors of Human Papillomavirus Vaccine Initiation and Completion Among Latino Mothers of 11- to 17-Year-Old Daughters Living Along the Texas-Mexico Border.

PubMed

Morales-Campos, Daisy Y; Parra-Medina, Deborah

Few Texas Latino girls initiate and complete the human papillomavirus (HPV) vaccine series, but few studies have examined predictors of initiation and completion in this group. Mothers are crucial to vaccine uptake. Using self-reported data from mothers of unvaccinated girls (n = 317), we examined the association between predictors (HPV and HPV vaccine knowledge, vaccine self-efficacy) and outcomes (initiation and completion). Despite an increase in HPV and HPV vaccine knowledge from baseline to follow-up (n = 195), we found no association between the predictors and the outcomes. Findings showed that health insurance status and study group participation (Entre Madre e Hija program or brochure only) were associated with initiation and completion.

Experiences and perceptions of online continuing professional development among clinicians in sub-Saharan Africa.

PubMed

Feldacker, Caryl; Jacob, Sheena; Chung, Michael H; Nartker, Anya; Kim, H Nina

2017-12-29

Limitations in healthcare worker (HCW) capacity compound the burden of dual TB and HIV epidemics in sub-Saharan Africa. To fill gaps in knowledge and skills, effective continuing profession development (CPD) initiatives are needed to support practicing HCWs reach high standards of care. e-learning opportunities can bring expert knowledge to HCWs in the field and provide a flexible learning option adaptable to local settings. Few studies provide insight into HCW experiences with online CPD in the developing country context. An online survey using both close-ended and free response was conducted to HCWs in sub-Saharan Africa who completed the University of Washington (UW) School of Medicine online graduate course, "Clinical Management of HIV." Associations between respondent characteristics (age, gender, rural/urban, job title) and learning preferences, course barriers, and facilitators with an emphasis on online courses were examined using chi-square. Covariates significant at the p < 0.05 were analyzed using multivariable logistic regression. Responses to open-ended comments were analyzed using simplified grounded theory. Of 2,299 former students, 464 (20%) HCWs completed surveys from 13 countries: about half were women. Physicians (33%), nurses (27%), and clinical officers (30%) responded mostly from urban areas (67%) and public institutions (69%). Sixty-two percent accessed the online course from work, noting that slow (55%) or limited (41%) internet as well as lack of time (53%) were barriers to course completion. Women (p < 0.001) and HCWs under age 40 (p = 0.007) were more likely to prefer learning through mentorship than men or older HCWs. Respondents favored group discussion (46%), case studies (42%), and self-paced Internet/computer-based learning (39%) and clinical mentorship (37%) when asked to choose 3 preferred learning modalities. Free-response comments offered additional positive insights into the appeal of online courses by noting the knowledge gains, the flexibility of format, a desire for recognition of course completion, and a request for additional online coursework. Online CPD opportunities were accepted across a diverse group of HCWs from sub-Saharan Africa and should be expanded to provide more flexible opportunities for self-initiated learning; however, these need to be responsive to the limited resources of those who seek these courses.

Hematoma-inspired alginate/platelet releasate/CaPO4 composite: initiation of the inflammatory-mediated response associated with fracture repair in vitro and ex vivo injection delivery.

PubMed

McCanless, Jonathan D; Jennings, Lisa K; Bumgardner, Joel D; Cole, Judith A; Haggard, Warren O

2012-08-01

A clinical need continues for consistent bone remodeling within problematic sites such as those of fracture nonunion, avascular necrosis, or irregular bone formations. In attempt to address such needs, a biomaterial system is proposed to induce early inflammatory responses after implantation and to provide later osteoconductive scaffolding for bone regeneration. Biomaterial-induced inflammation would parallel the early stage of hematoma-induced fracture repair and allow scaffold-promoted remodeling of osseous tissue to a healthy state. Initiation of the wound healing cascade by two human concentrated platelet releasate-containing alginate/β-tricalcium phosphate biocomposites has been studied in vitro using the TIB-71™ RAW264.7 mouse monocyte cell line. Inflammatory responses inherent to the base material were found and could be modulated through incorporation of platelet releasate. Differences in hydrogel wt% (2 vs. 8 %) and/or calcium phosphate granule vol.% (20 vs. 10 %) allowed for tuning the response associated with platelet releasate-associated growth factor elution. Tunability from completely suppressing the inflammatory response to augmenting the response was observed through varied elution profiles of both releasate-derived bioagents and impurities inherent to alginate. A 2.5-fold upregulation of inducible-nitric oxide synthase gene expression followed by a tenfold increase in nitrite media levels was induced by inclusion of releasate within the 8 wt%/10 vol.% formulation and was comparable to an endotoxin positive control. Whereas, near complete elimination of inflammation was seen when releasate was included within the 2 wt%/20 vol.% formulation. These in vitro results suggested tunable interactions between the multiple platelet releasate-derived bioagents and the biocomposites for enhancing hematoma-like fracture repair. Additionally, minimally invasive delivery for in situ curing of the implant system via injection was demonstrated in rat tail vertebrae using microcomputed tomography.

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

Zhang, Fu-Lin, E-mail: flzhang@tju.edu.cn; Chen, Jing-Ling, E-mail: chenjl@nankai.edu.cn; Centre for Quantum Technologies, National University of Singapore, 3 Science Drive 2, Singapore 117543

Recent experimental progress in prolonging the coherence time of a quantum system prompts us to explore the behavior of quantum entanglement at the beginning of the decoherence process. The response of the entanglement under an infinitesimal noise can serve as a signature of the robustness of entangled states. A crucial problem of this topic in multipartite systems is to compute the degree of entanglement in a mixed state. We find a family of global noise in three-qubit systems, which is composed of four W states. Under its influence, the linear response of the tripartite entanglement of a symmetrical three-qubit puremore » state is studied. A lower bound of the linear response is found to depend completely on the initial tripartite and bipartite entanglement. This result shows that the decay of tripartite entanglement is hastened by the bipartite one. - Highlights: • We study a set of W-type noise and its linear effect on symmetric pure states. • Its effect on two-qubit entanglement depends only on the initial concurrence. • A lower bound of the effect on 3-tangle is found in terms of initial entanglements. • We obtain the time of three-tangle sudden death for two families of typical states. • These reveal that the bipartite entanglement speeds up the decay of the tripartite one.« less

Long-Time Asymptotics of a Box-Type Initial Condition in a Viscous Fluid Conduit

NASA Astrophysics Data System (ADS)

Franco, Nevil; Webb, Emily; Maiden, Michelle; Hoefer, Mark; El, Gennady

2017-11-01

The initial value problem for a localized hump disturbance is fundamental to dispersive nonlinear waves, beginning with studies of the celebrated, completely integrable Korteweg-de Vries equation. However, understanding responses to similar disturbances in many realistic dispersive wave systems is more complicated because they lack the mathematical property of complete integrability. This project applies Whitham nonlinear wave modulation theory to estimate how a viscous fluid conduit evolves this classic initial value problem. Comparisons between theory, numerical simulations, and experiments are presented. The conduit system consists of a viscous fluid column (glycerol) and a diluted, dyed version of the same fluid introduced to the column through a nozzle at the bottom. Steady injection and the buoyancy of the injected fluid leads to the eventual formation of a stable fluid conduit. Within this structure, a one hump disturbance is introduced and is observed to break up into a quantifiable number of solitons. This structure's experimental evolution is to Whitham theory and numerical simulations of a long-wave interfacial model equation. The method presented is general and can be applied to other dispersive nonlinear wave systems. Please email me, as I am the submitter.

Utility of the PET-CT in the evaluation of early response to treatment in the diffuse large B-cell lymphoma. Preliminary results.

PubMed

Cortés Romera, M; Gámez Cenzano, C; Caresia Aróztegui, A P; Martín-Comín, J; González-Barca, E; Ricart Brulles, Y; Palacios Abufón, A; Robles Barba, J; Rodríguez-Bel, L; Rossi Seoane, S; Fernández de Sevilla, A

2012-01-01

To assess the role of FDG-PET/CT performed after the first cycles of chemotherapy in the prediction of response to treatment in patients with diffuse large B-cell lymphoma. Twenty patients (mean age: 48 years) were included, 16 initial staging and 4 relapse. All patients underwent PET/CT at 3 times: 1) Baseline, 2) After 1-3 cycles of chemotherapy (early response assessment), and 3) End of treatment (evaluation of final response). Early PET/CT findings were correlated to the end-treatment PET/CT and follow-up. The evaluation of the response was established according to the decrease in uptake of the lesions (SUVmax). In the early assessment, a good response indicator (GRI) was obtained when the lesion disappeared or had more than 50% reduction in SUVmax. At the end of the treatment, a complete metabolic response (CMR) was determined in negative PET scans. Follow-up was superior to 19 months and final outcome was established as progression/relapse or no evidence of disease (NED). At the early treatment evaluation, 16/16 patients of initial staging (100%) and 2/4 of relapse (50%) achieved GRI. At the end of treatment evaluation, 14/16 patients of initial staging with GRI achieved CMR and 1/16 PMR: 14 were alive with NED in the follow-up while 1 relapsed. In the second group, 2/2 patients with GRI achieved CMR (100%): 1 continued with NED in the follow-up and another relapsed. FDG-PET/CT after the first cycles of chemotherapy is useful to monitor treatment due to its high negative predictive value (87.5%), using it to modify treatment early in the non-responders. Copyright © 2011 Elsevier España, S.L. y SEMNIM. All rights reserved.

Delayed-type hypersensitivity (DTH) test anergy does not impact CD4 reconstitution or normalization of DTH responses during antiretroviral therapy.

PubMed

Minidis, Natascha M; Mesner, Octavio; Agan, Brian K; Okulicz, Jason F

2014-01-01

Delayed-type hypersensitivity (DTH) testing is an in vivo assessment of cell-mediated immunity. Although highly active antiretroviral therapy (HAART) improves immunologic parameters, the relationship between DTH responsiveness and CD4 gains on HAART is not completely understood. We investigated CD4 reconstitution and the change in DTH responses from treatment baseline through 24 months of viral load (VL)-suppressive HAART in the U.S. Military HIV Natural History Study. Treatment-naïve subjects with VL <400 copies/mL after ≥24 months on HAART were included (n=302). DTH testing consisted of ≥3 recall antigens, and responses were classified by the number of positive skin tests: anergic (0-1) or non-anergic (≥2). Pre-HAART DTH results were compared for the outcome of CD4 reconstitution at 24 months of HAART. Improvement in DTH responses was also analyzed for those anergic before HAART initiation. Non-anergic responses were observed in 216 (72%) participants, while 86 (28%) individuals were anergic prior to HAART initiation. Demographically there were similar distributions of age at HIV diagnosis and HAART initiation, as well as gender and race or ethnicity. There were no significant differences between non-anergic and anergic participants in pre-HAART CD4 count (409 cells/μL, interquartile range (IQR) 315-517 vs. 373 cells/μL, IQR 228-487; p=0.104) and VL (4.3 log10 copies/mL, IQR 3.4-4.9 vs. 4.4 log10 copies/mL, IQR 3.6-5.0; p=0.292). Median CD4 gains 24 months after HAART initiation were similar between the non-anergic (220 cells/μL, IQR 115-358) and anergic groups (246 cells/μL, IQR 136-358; p=0.498). For individuals anergic before HAART initiation, DTH normalization occurred at 24 months post-HAART in the majority of participants (51 of 86, 59%). Normalization of DTH responses was not associated with CD4 count at HAART initiation (OR 0.73, 95% CI 0.47, 1.09 per 100 cells; p=0.129) nor with AIDS diagnoses prior to HAART (OR 0.34, 95% CI 0.04, 2.51; p=0.283). DTH responsiveness has been shown to predict HIV disease progression independent of CD4 count in untreated individuals. In the setting of HAART, pre-HAART anergy does not appear to impact CD4 gains or the ability to normalize DTH responses after 24 months of VL-suppressive HAART.

Unilateral Laryngoscopic Findings Associated With Response to Gabapentin in Patients With Chronic Cough.

PubMed

Giliberto, John Paul; Dibildox, Daniel; Merati, Albert

2017-11-01

Chronic cough is a debilitating, often multifactorial problem. Vagal neuropathy has been proposed as a cause for a fraction of these cases. There are certain features that support the clinical diagnosis of vagal neuropathy. It is hypothesized that patients with neurogenic cough who have vocal fold motion asymmetry (VFMA) on laryngoscopy will be more likely to respond to gabapentin. To evaluate the association between the history, physical and videostroboscopic examinations, and clinical response to gabapentin. In a retrospective cohort study, patients with chronic cough visiting an academic tertiary laryngology clinic from January 1, 2013, to September 1, 2015, were identified through International Classification of Diseases, Ninth Revision. Of those who had a chronic cough (>8 weeks), 27 patients who received a prescription for gabapentin were included. Patients without videostroboscopy, who did not complete voice therapy, or those without a follow-up examination more than 1 month from the initial evaluation were excluded. Initial history, physical and videostroboscopic examinations, and follow-up evaluations, were performed in a multidisciplinary laryngology clinic including a speech-language pathologist. Documented VFMA by a multidisciplinary team was decided by consensus after review of videostroboscopy recording at the time of the visit. Response to gabapentin was defined by physician-documented subjective patient report of improvement in cough symptoms. Follow-up data were available on 25 of the 27 patients (15 [60%] women; mean [SD] age, 57 [11.8] years). Therapy was initiated in patients with chronic cough with gabapentin, 100 mg twice daily, which was titrated to response or adverse effects. The maximum daily dose was 1800 mg. Partial or complete response to gabapentin was noted in 16 (64%) patients. Vocal fold motion asymmetry was noted in 20 (80%) patients. Fifteen of 16 (94%) responders had VFMA compared with 5 of 9 (56%) nonresponders. The difference in the frequency of VFMA between responders and nonresponders was 38% (95% CI, 18%-58%). Adverse effects limited the gabapentin dose in 4 of 9 (44%) nonresponders and 4 of 16 (25%) responders (odds ratio, 2.5; 95% CI, 0.42-13.6). In patients with chronic cough suspected to be related to vagal neuropathy, the odds of response to gabapentin are higher with the presence of VFMA noted on videostroboscopy.

Heterogeneity of response to antipsychotics from multiple disorders in the schizophrenia spectrum.

PubMed

Garver, D L; Holcomb, J A; Christensen, J D

2000-12-01

Antipsychotic response after the initiation of neuroleptic treatment shows wide variation in schizophrenic patient populations. In this overview, the authors suggest that the variance in antipsychotic drug response within schizophrenia can be reduced by resolving the schizophrenias into several discrete "endophenotypes," each with different etiologic underpinnings. Studies relating differences in the relative speed or completeness of antipsychotic response to differences in distribution of 2 biological markers with possible etiologic significance are reviewed. Such studies had assessed recently hospitalized, neuroleptic-free patients undergoing exacerbation of nonaffective psychotic disorders. Prior to initiation of neuroleptic, the cohort of patients had been assessed for the quantity of the dopamine metabolite homovanillic acid in plasma (pHVA) and had undergone the first of 2 magnetic resonance imaging (MRI) studies for analyses of ventricle volumes. A second MRI was subsequently performed during a period of (partial) remission to determine within-patient stability of ventricular volumes. These selected studies assessed the distribution of pHVA and distribution of rates of ventricular change, with non-normal distributions resolved by K-means clustering. The speed and completeness of neuroleptic-induced antipsychotic response were related to 3 clusters of patients delineated by modal distributions of pHVA and of apparent rates of ventricular change. At least 3 unique "endophenotypes" of the "group of the schizophrenias" can be defined with respect to speed and completeness of antipsychotic response. Each endophenotype appears to show at least one unique biological feature that differentiates it from a normal comparison group. A rapidly responsive psychosis was associated with excessive production of dopamine, as identifiable by elevation of pHVA and a "good-prognosis" course. A delayed-response psychosis had low-to-normal pHVA, clinically demonstrated persistent negative symptoms, and was associated with an excessive rate of change in ventricle volume between exacerbations of psychosis and (partial) remissions. Finally, a nonresponsive psychosis could be characterized as having both low-to-normal pHVA and rate of change of ventricle volumes similar to that of controls. Additional studies revealed that each of the endophenotypes had high rates of the psychoses in family members. The good-prognosis course of the rapidly responsive group of studied patients was also found in their family members who had psychotic disorders. Similarly, the prominent negative symptoms of the delayed-response probands were reflected as a prominent trait in their family members also afflicted with psychosis. The endophenotypes tended to "breed true" in terms of prognosis and negative symptoms. Major differences in antipsychotic response patterns appear to be associated with patient and family characteristics that may be related to differences in the etiology and consequent pathophysiology of illness.

Could Poor Parental Recall of HPV Vaccination Contribute to Low Vaccination Rates?

PubMed

Apte, Gauri; Pierre-Joseph, Natalie; Vercruysse, Jessica L; Perkins, Rebecca B

2015-09-01

Rates of initiation and completion of the human papillomavirus (HPV) vaccine series remain below national goals. Because parents are responsible for ensuring vaccination of their children, we examined the accuracy of parental recall of the number of shots their daughters received. Parents/guardians of girls aged 11 to 17 years were asked to recall the number of HPV doses received by their daughters. Dose number was confirmed using provider-verified medical records. Logistic regression assessed variables associated with correct recall. A total of 79 (63%) parents/guardians correctly identified the number of shots their daughters received. Ninety-one (73%) were aware of whether their daughter started the series at all. The only factor significantly associated with accurate recall in logistic regression models was female gender of parent/guardian. Nearly 40% of parents/guardians inaccurately recalled the number of HPV shots their children received, which may contribute to low rates of vaccine initiation and completion. © The Author(s) 2015.

Internet sexuality research with rural men who have sex with men: can we recruit and retain them?

PubMed

Bowen, Anne

2005-11-01

This study examines the utility of internet banner ads for recruiting rural MSM and identifies correlates of internet HIV risk survey initiation and completion. Banner ads were shown on a popular internet dating site for one month and resulted in 1,045 rural MSM, from 49 States, Canada, Australia/New Zealand, and 5 from other countries initiating the questionnaire. Logistic regression indicated that progression beyond screening questions was negatively related to "expecting pay, but not being paid" and positively related to "using chat rooms to find friends" and identifying as gay. Linear regression indicated that the absolute number of responses by consenting participants was positively correlated with reimbursement, number of sexual partners, motivated by money, and having been HIV tested. Overall, this sample represents one of the largest rural MSM samples; survey completion was high and strengthened by reimbursement and possibly by awareness of HIV risk. Generalizability was limited by low participation of minority and non-gay identified MSM.

Enhancing the far-ultraviolet sensitivity of silicon complementary metal oxide semiconductor imaging arrays

NASA Astrophysics Data System (ADS)

Retherford, Kurt D.; Bai, Yibin; Ryu, Kevin K.; Gregory, James A.; Welander, Paul B.; Davis, Michael W.; Greathouse, Thomas K.; Winters, Gregory S.; Suntharalingam, Vyshnavi; Beletic, James W.

2015-10-01

We report our progress toward optimizing backside-illuminated silicon P-type intrinsic N-type complementary metal oxide semiconductor devices developed by Teledyne Imaging Sensors (TIS) for far-ultraviolet (UV) planetary science applications. This project was motivated by initial measurements at Southwest Research Institute of the far-UV responsivity of backside-illuminated silicon PIN photodiode test structures, which revealed a promising QE in the 100 to 200 nm range. Our effort to advance the capabilities of thinned silicon wafers capitalizes on recent innovations in molecular beam epitaxy (MBE) doping processes. Key achievements to date include the following: (1) representative silicon test wafers were fabricated by TIS, and set up for MBE processing at MIT Lincoln Laboratory; (2) preliminary far-UV detector QE simulation runs were completed to aid MBE layer design; (3) detector fabrication was completed through the pre-MBE step; and (4) initial testing of the MBE doping process was performed on monitoring wafers, with detailed quality assessments.

Accounting for Men's Refusal of Heterosex: A Story-Completion Study with Young Adults.

PubMed

Beres, Melanie Ann; Terry, Gareth; Senn, Charlene Y; Ross, Lily Kay

2017-12-08

In the present study we bring together theory regarding the construction of heterosexuality and masculinities to understand the shifting and changing terrain of heterosexual sex (heterosex). We use inductive qualitative content analysis of story completion data to discover the different ways that heterosex is constructed by the male and female respondents in scenarios where women initiate sex and men, at first, refuse. The stories represented a spectrum of responses that reify and subvert dominant understandings of heterosex. Five major themes were generated from the current data (1) men should initiate sex, (2) he wants to take it slowly, (3) it is natural for men to want sex, (4) it is men's job to look after women, and (5) coercion. We discuss in detail the dominant narratives described by women and men and how they may be shifting. The study thus provides a rich, experience-based representation of heterosexual sexual activity and suggests subtle shifts in how masculinity is managed within heterosexual relationships.

Barriers towards the publication of academic drug trials. Follow-up of trials approved by the Danish Medicines Agency.

PubMed

Berendt, Louise; Petersen, Lene Grejs; Bach, Karin Friis; Poulsen, Henrik Enghusen; Dalhoff, Kim

2017-01-01

To characterize and quantify barriers towards the publication of academic drug trials. We identified academic drug trials approved during a 3-year period (2004-2007) by the Danish Medicines Agency. We conducted a survey among the trial sponsors to describe the rates of initiation, completion, and publication, and the reasons for the failure to reach each of these milestones. Information on size and methodological characteristics of the trials was extracted from the EudraCT database, a prospective register of all approved clinical drug trials submitted to European medicines agencies since 2004. A total of 181 academic drug trials were eligible for inclusion, 139 of which participated in our survey (response rate: 77%). Follow-up time ranged from 5.1 to 7.9 years. Most trials were randomized controlled trials (73%, 95% CI 65-81%). Initiation and completion rates were 92% (95% CI: 88-97%) and 93% (95% CI: 89-97%) respectively. The publication rate of completed trials was 73% (95% CI: 62-79%). RCTs were published faster than non-RCTs (quartile time to publication 2.9 vs. 3.1 years, p = 0.0412). Many academic drug trials are left unpublished. Main barriers towards publication were related to the process from completion to publication. Hence, there is much to gain by facilitating the process from analysis to publication. Research institutions and funders should actively influence this process, e.g. by requiring the publication of trial results within a given time after completion.

14. Implementation, execution, and completion of projects.

PubMed

2014-05-01

Once an intervention has been selected for implementation, it becomes a project. Implementation of a project is a complex process and requires completion of a host of tasks. The implementation process has been deconstructed into its components so that it can be analysed and evaluated. A prerequisite for implementation is an operational plan. The tasks that require completion include: (1) reassessing current status and verifying the needs; (2) activating the operational plan; (3) setting-up and operating an administrative structure; (4) identifying, acquiring, and organising resources (including human resources); (5) assigning roles and responsibilities; (6) educating and training personnel (including mission-specific); (7) briefing staff; (8) preparing/readying resources for transport; (9) assuring project self-sufficiency; (10) arranging for personal necessities; (11) ensuring the safety of personnel and the security of equipment and supplies; (12) insuring personnel; (13) coordinating with other projects/actors; (14) coordinating with other BSF systems (role of the coordination and control centre); (15) communicating with community leaders; (16) initiating the use of standardised progress reports; (17) deploying personnel, equipment, and supplies; (18) initiating the intervention(s); (19) executing the intervention(s); (20) reporting start of interventions; (21) completing the project; and (22) completing and submitting a formal report. This deconstruction is essential in order to study the process and identify critical points of success and failure. It also is recognised that many interventions consist of many components (subfunctions), each of which may be considered a production process.

Photodynamic therapy (PDT) in Barrett's esophagus with dysplasia or early cancer.

PubMed

Foroulis, Christophoros N; Thorpe, James A C

2006-01-01

Esophagectomy is the standard treatment for high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC) arising within Barrett's esophagus. Results of photodynamic therapy (PDT) were retrospectively studied to evaluate the effectiveness of PDT in ablating HGD and/or IMC complicating Barrett's esophagus. Thirty-one patients unfit for or refusing esophagectomy (male: 20, mean age: 73.4+/-9.3 years) underwent Porfimer sodium PDT ablation of their HGD (15 patients), HGD plus IMC (10 patients) or submucosal/limited T2 adenocarcinoma (6 patients). The mean Barrett's length was 5.8+/-2.2 cm. Pre-PDT endoscopic mucosal resection or Nd:YAG laser ablation of mucosal nodularity within Barrett's segment was offered in six patients. The main PDT complications were esophagitis (16.1%), photoreactions (12.9%) and stricture requiring dilatation (6.25%). The median post-PDT follow-up was 14 months. The long-term results were (a) for HGD/IMC: initial complete response (endoscopic and histologic absence of HGD-IMC) to PDT was observed in 80.95% of patients, partial response (no endoscopic abnormality, residual IMC-HGD on biopsy) in 9.52%, no response in 9.52% (the recurrence rate after an initial complete response was 17.64%) and (b) for T1b/limited T2 tumors: two patients died from cancer after 24 and 46 months, no evidence of tumor was found in two patients after 12 and 19 months and tumor recurrence was seen in two after 15 and 17 months. The mean survival was 22.1+/-12.3 months. PDT is effective in ablating HGD/IMC complicating Barrett's esophagus in the majority of cases, while it also seems to be quite effective in treating T1b/limited T2 carcinomas.

Ibrutinib efficacy and tolerability in patients with relapsed chronic lymphocytic leukemia following allogeneic HCT

PubMed Central

Ryan, Christine E.; Sahaf, Bita; Logan, Aaron C.; O’Brien, Susan; Byrd, John C.; Hillmen, Peter; Brown, Jennifer R.; Dyer, Martin J. S.; Mato, Anthony R.; Keating, Michael J.; Jaglowski, Samantha; Clow, Fong; Rezvani, Andrew R.; Styles, Lori; Coutre, Steven E.

2016-01-01

Ibrutinib, a potent and irreversible small-molecule inhibitor of both Bruton’s tyrosine kinase and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival. Here, we present 27 patients with relapsed CLL following allogeneic hematopoietic cell transplant (HCT) who subsequently received ibrutinib salvage therapy. Sixteen of these patients were part of multi-institutional clinical trials and achieved an overall response rate of 87.5%. An additional 11 patients were treated at Stanford University following US Food and Drug Administration approval of ibrutinib; 7 (64%) achieved a complete response, and 3 (27%) achieved a partial response. Of the 9 patients treated at Stanford who had mixed chimerism–associated CLL relapse, 4 (44%) converted to full donor chimerism following ibrutinib initiation, in association with disease response. Four of 11 (36%) patients evaluated by ClonoSeq achieved minimal residual disease negativity with CLL <1/10 000 white blood cells, which persisted even after ibrutinib was discontinued, in 1 case even after 26 months. None of the 27 patients developed graft-versus-host-disease (GVHD) following ibrutinib initiation. We postulate that ibrutinib augments the graft-versus-leukemia (GVL) benefit through a T-cell–mediated effect, most likely due to ITK inhibition. To investigate the immune modulatory effects of ibrutinib, we completed comprehensive immune phenotype characterization of peripheral B and T cells from treated patients. Our results show that ibrutinib selectively targets pre–germinal B cells and depletes Th2 helper cells. Furthermore, these effects persisted after drug discontinuation. In total, our results provide evidence that ibrutinib effectively augments GVL without causing GVHD. PMID:27802969

Ibrutinib efficacy and tolerability in patients with relapsed chronic lymphocytic leukemia following allogeneic HCT.

PubMed

Ryan, Christine E; Sahaf, Bita; Logan, Aaron C; O'Brien, Susan; Byrd, John C; Hillmen, Peter; Brown, Jennifer R; Dyer, Martin J S; Mato, Anthony R; Keating, Michael J; Jaglowski, Samantha; Clow, Fong; Rezvani, Andrew R; Styles, Lori; Coutre, Steven E; Miklos, David B

2016-12-22

Ibrutinib, a potent and irreversible small-molecule inhibitor of both Bruton's tyrosine kinase and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival. Here, we present 27 patients with relapsed CLL following allogeneic hematopoietic cell transplant (HCT) who subsequently received ibrutinib salvage therapy. Sixteen of these patients were part of multi-institutional clinical trials and achieved an overall response rate of 87.5%. An additional 11 patients were treated at Stanford University following US Food and Drug Administration approval of ibrutinib; 7 (64%) achieved a complete response, and 3 (27%) achieved a partial response. Of the 9 patients treated at Stanford who had mixed chimerism-associated CLL relapse, 4 (44%) converted to full donor chimerism following ibrutinib initiation, in association with disease response. Four of 11 (36%) patients evaluated by ClonoSeq achieved minimal residual disease negativity with CLL <1/10 000 white blood cells, which persisted even after ibrutinib was discontinued, in 1 case even after 26 months. None of the 27 patients developed graft-versus-host-disease (GVHD) following ibrutinib initiation. We postulate that ibrutinib augments the graft-versus-leukemia (GVL) benefit through a T-cell-mediated effect, most likely due to ITK inhibition. To investigate the immune modulatory effects of ibrutinib, we completed comprehensive immune phenotype characterization of peripheral B and T cells from treated patients. Our results show that ibrutinib selectively targets pre-germinal B cells and depletes Th2 helper cells. Furthermore, these effects persisted after drug discontinuation. In total, our results provide evidence that ibrutinib effectively augments GVL without causing GVHD. © 2016 by The American Society of Hematology.

Ovipositional response elicited by normal, irradiated, F$sub 1$ male progeny, or castrated male Trichoplusia ni (Lepidoptera: Noctuidae)

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

Karpenko, C.P.; North, D.T.

1973-11-01

The ovipositional response of untreated Trichoplusia ni (Hubner) females that had mated to unirradiated, irradiated, F/sub 1/ male progeny from irradiated males, or castrated males was studied. Females that mated with irradiated males or F/sub 1/ sons of irradiated males oviposited fewer eggs than females that mated with control males, when all females had received a normal quantity of eupyrene and apyrene sperm. Irradiated males and F/sub 1/ sons of irradiated males that transferred an apparently normal sperm complement elicited significantly better oviposition from untreated females than did treated males that transferred mostly apyrene sperm, apyrene sperm only, or nomore » sperm. Males in the latter categories elicited a better ovipositional response from the untreated females than was observed in virgin females. Normal eupyrene sperm and possibly at least 1 accessory fiuid are required to initiate a completely normal ovipositional response in cabbage looper females. The accessory secretion triggers a significant increase in oviposition, but the greatest increase occurs when males contribute normal amounts of eupyrene sperm. The initiation of oviposition and female receptivity may be closely related in this species. (auth)« less

Metastatic pattern and DNA ploidy in stage IV breast cancer at initial diagnosis. Relation to response and survival.

PubMed

De Lena, M; Romero, A; Rabinovich, M; Leone, B; Vallejo, C; Machiavelli, M; Cuevas, M; Rodriguez, R; Lacava, J; Perez, J

1993-06-01

Sixty-nine patients with metastatic breast cancer (MBC) at initial diagnosis were analyzed to verify if metastatic pattern and clinical outcome are related to DNA ploidy determined by flow cytometry (FCM). Characteristics of 55 fully evaluable patients were as follows: median age: 61 years; postmenopausal: 75%; bone-only metastases (BM): 60%; extraosseous-only metastases (EM): 40%. Overall response rates (CR + PR) obtained with different chemotherapies and/or hormonal therapies were 58% and 68% for patients with BM and EM, respectively. Sixty percent of specimens resulted aneuploid, and the mean coefficient of variation of the complete series was 5.1%. In the whole group of patients DNA ploidy of primary tumor did not predict the metastatic pattern and had no influence upon response to treatment, duration of response, time to progression, and overall survival. When analyses were carried out according to metastatic pattern, those patients with BM showed similar results. However, within the group with EM, those with diploid tumors presented a significantly better survival (median 18 vs 13 months, p = .04). FCM-DNA analysis seems to identify a subgroup of patients with poor prognosis constituted by those who had aneuploid primary tumors and metastases to extraosseous sites.

Venetoclax: A novel B-cell lymphoma-2 inhibitor for chronic lymphocytic leukemia and other hematologic malignancies.

PubMed

Olin, Jacqueline L; Griffiths, Carrie L; Smith, Morgan B

2017-01-01

Patients with chronic lymphocytic leukemia with the 17p deletion have a poor prognosis and treatment options are limited. Venetoclax, a novel B-cell lymphoma-2 inhibitor, has been approved for treatment-experienced chronic lymphocytic leukemia patients with the 17p deletion. A phase 1 dose-escalation study to 400 mg daily showed overall response rates across all doses of 79% with a complete response achieved in 20%. A phase 2 multicenter open-label study demonstrated overall response rate of 79.4% of patients (95% confidence interval 70.5-86.6) with median duration of follow-up of 12.1 months (IQR 10.1-14.2). Tumor lysis syndrome has been observed during initiation and titration. Assessing risk of tumor lysis syndrome prior to therapy initiation is essential to provide appropriate prophylactic medications. Neutropenia, potentially warranting dose reduction or discontinuation, has been observed. Venetoclax has demonstrated activity in other leukemias, multiple myeloma, and lymphomas. Venetoclax has shown response, and is well tolerated in patients with highly resistant chronic lymphocytic leukemia. It has the potential to be part of the treatment armamentarium for other malignancies.

Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era

PubMed Central

Ambler, Kimberley L. S.; Vickars, Linda M.; Leger, Chantal S.; Foltz, Lynda M.; Montaner, Julio S. G.; Harris, Marianne; Dias Lima, Viviane; Leitch, Heather A.

2012-01-01

The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 109/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 109/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed. PMID:22693513

Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era.

PubMed

Ambler, Kimberley L S; Vickars, Linda M; Leger, Chantal S; Foltz, Lynda M; Montaner, Julio S G; Harris, Marianne; Dias Lima, Viviane; Leitch, Heather A

2012-01-01

The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 10(9)/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 10(9)/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed.

Assessment of an interactive voice response system for identifying falls in a statewide sample of older adults.

PubMed

Albert, Steven M; King, Jennifer; Keene, Robert M

2015-02-01

Interactive voice response (IVR) systems offer great advantages for data collection in large, geographically dispersed samples involving frequent contact. We assessed the quality of IVR data collected from older respondents participating in a statewide falls prevention program evaluation in Pennsylvania in 2010-12. Participants (n=1834) were followed up monthly for up to 10 months to compare respondents who completed all, some, or no assessments in the IVR system. Validity was assessed by examining IVR-reported falls incidence relative to baseline in-person self-report and performance assessment of balance. While a third of the sample switched from IVR to in-person calls over follow-up, IVR interviews were successfully used to complete 68.1% of completed monthly assessments (10,511/15,430). Switching to in-person interviews was not associated with measures of participant function or cognition. Both self-reported (p<.0001) and performance assessment of balance (p=.05) at baseline were related to falls incidence. IVR is a productive modality for falls research among older adults. Future research should establish what level of initial personal research contact is optimal for boosting IVR completion rates and what research domains are most appropriate for this kind of contact. Copyright © 2014 Elsevier Inc. All rights reserved.

Large Deformation Dynamic Three-Dimensional Coupled Finite Element Analysis of Soft Biological Tissues Treated as Biphasic Porous Media

DTIC Science & Technology

2014-11-01

response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and...over time , when a bipha- sic soft tissue is subjected to dynamic loading. Also, after the initial transient, the variation of solid skeleton stresses...will be naturally calculated as the fluid phase pressure dissipates over time . This is important for developing physiologically- relevant degradation

Countering Radicalization: Refocusing Responses to Violent Extremism Within the United States

DTIC Science & Technology

2011-12-01

obsessed with religion.38 His initial goals were laudable; according to his brother, “He said he just wanted to do good. He wanted to go to heaven...time Samir arrived in North Carolina he was completely obsessed with extremist ideology. A friend, Adam Azad related that during their first...volunteer activities. Efforts can be tailored to specific areas such as university campuses, coffee shops, or community centers. Each effort

Hepatitis A, B, and A/B vaccination series completion among US adults: a claims-based analysis.

PubMed

Ghaswalla, Parinaz K; Patterson, Brandon J; Cheng, Wendy Y; Duchesneau, Emilie; Macheca, Monica; Duh, Mei Sheng

2018-06-20

Hepatitis A and B disease burden persists in the US. We assessed hepatitis A and hepatitis B vaccination series completion rates among 350,240 commercial/Medicare and 12,599 Medicaid enrollees aged ≥19 years. A vaccination series was considered as completed provided that the minimum interval between doses, as defined by the CDC, and the minimum number of doses were reached. We stratified completion rates by vaccine type (i.e. monovalent or bivalent) at initial vaccination for each cohort. In the commercial/Medicare cohort, the series completion rate was 32.0% for hepatitis A and 39.6% for hepatitis B among those who initiated with a monovalent vaccine, and it was 36.2% for hepatitis A and 48.9% for hepatitis B among those who initiated with a bivalent vaccine. In the Medicaid cohort, the series completion rate was 21.0% for hepatitis A and 24.0% for hepatitis B among those who initiated with a monovalent vaccine, and it was 19.0% for hepatitis A and 24.6% for hepatitis B among those who initiated with a bivalent vaccine. In conclusion, hepatitis A and B vaccination series completion rates were low, and appeared to be lower among Medicaid than among commercial/Medicare enrollees. Commercial/Medicare enrollees who initiated with a bivalent vaccine had higher series completion rates than those who initiated with monovalent vaccines - an observation that was not made among Medicaid enrollees.

Nanoscale definition of substrate materials to direct human adult stem cells towards tissue specific populations.

PubMed

Curran, Judith M; Chen, Rui; Stokes, Robert; Irvine, Eleanor; Graham, Duncan; Gubbins, Earl; Delaney, Deany; Amro, Nabil; Sanedrin, Raymond; Jamil, Haris; Hunt, John A

2010-03-01

The development of homogenously nano-patterned chemically modified surfaces that can be used to initiate a cellular response, particularly stem cell differentiation, in a highly controlled manner without the need for exogenous biological factors has never been reported, due to that fact that precisely defined and reproducible systems have not been available that can be used to study cell/material interactions and unlock the potential of a material driven cell response. Until now material driven stem cell (furthermore any cell) responses have been variable due to the limitations in definition and reproducibility of the underlying substrate and the lack of true homogeneity of modifications that can dictate a cellular response at a sub-micron level that can effectively control initial cell interactions of all cells that contact the surface. Here we report the successful design and use of homogenously molecularly nanopatterned surfaces to control initial stem cell adhesion and hence function. The highly specified nano-patterned arrays were compared directly to silane modified bulk coated substrates that have previously been proven to initiate mesenchymal stem cell (MSC) differentiation in a heterogenous manner, the aim of this study was to prove the efficiency of these previously observed cell responses could be enhanced by the incorporation of nano-patterns. Nano-patterned surfaces were prepared by Dip Pen Nanolithography (DPN) to produce arrays of 70 nm sized dots separated by defined spacings of 140, 280 and 1000 nm with terminal functionalities of carboxyl, amino, methyl and hydroxyl and used to control cell growth. These nanopatterned surfaces exhibited unprecedented control of initial cell interactions and will change the capabilities for stem cell definition in vitro and then cell based medical therapies. In addition to highlighting the ability of the materials to control stem cell functionality on an unprecedented scale this research also introduces the successful scale-up of DPN and the novel chemistries and systems to facilitate the production of homogeneously patterned substrates (5 mm2) that are applicable for use in in vitro cell conditions over prolonged periods for complete control of material driven cell responses.

Assessing anesthesiology residents' out-of-the-operating-room (OOOR) emergent airway management.

PubMed

Rochlen, Lauryn R; Housey, Michelle; Gannon, Ian; Mitchell, Shannon; Rooney, Deborah M; Tait, Alan R; Engoren, Milo

2017-07-15

At many academic institutions, anesthesiology residents are responsible for managing emergent intubations outside of the operating room (OOOR), with complications estimated to be as high as 39%. In order to create an OOOR training curriculum, we evaluated residents' familiarity with the content and correct adherence to the American Society of Anesthesiologists' Difficult Airway Algorithm (ASA DAA). Residents completed a pre-simulation multiple-choice survey measuring their understanding and use of the DAA. Residents then managed an emergent, difficult OOOR intubation in the simulation center, where two trained reviewers assessed performance using checklists. Post-simulation, the residents completed a survey rating their behaviors during the simulation. The primary outcome was comprehension and adherence to the DAA as assessed by survey responses and behavior in the simulation. Sixty-three residents completed both surveys and the simulation. Post-survey responses indicated a shift toward decreased self-perceived familiarity with the DAA content compared to pre-survey responses. During the simulation, 22 (35%) residents were unsuccessful with intubation. Of these, 46% placed an LMA and 46% prepared for cricothyroidotomy. Nineteen residents did not attempt intubation. Of these, only 31% considered LMA placement, and 26% initiated cricothyroidotomy. Many anesthesiology residency training programs permit resident autonomy in managing emergent intubations OOOR. Residents self-reported familiarity with the content of and adherence to the DAA was higher than that observed during the simulation. Curriculum focused on comprehension of the DAA, as well as improving communication with higher-level physicians and specialists, may improve outcomes during OOORs.

Inhibition by Siomycin and Thiostrepton of Both Aminoacyl-tRNA and Factor G Binding to Ribosomes

PubMed Central

Ll, Juan Modole; Cabrer, Bartolomé; Parmeggiani, Andrea; Azquez, David V

1971-01-01

Siomycin, a peptide antibiotic that interacts with the 50S ribosomal subunit and inhibits binding of factor G, is shown also to inhibit binding of aminoacyl-tRNA; however, it does not impair binding of fMet-tRNA and completion of the initiation complex. Moreover, unlike other inhibitors of aminoacyl-tRNA binding (tetracycline, sparsomycin, and streptogramin A), siomycin completely abolishes the GTPase activity associated with the binding of aminoacyl-tRNA catalyzed by factor Tu. A single-site interaction of siomycin appears to be responsible for its effect on both the binding of the aminoacyl-tRNA-Tu-GTP complex and that of factor G. PMID:4331558

Transmitting patient and device data via GSM--central management for decentral mobile medical devices.

PubMed

Bachmor, T; Schöchlin, J; Bolz, A

2002-01-01

Equipping medical devices with long range telemetry opens completely new possibilities for emergency response, home care and remote diagnosis. Mobile communications nowadays seem to be a generally accepted part of our modern world, but bridging the gap between new (consumer-) technologies and medical devices still is a challenge today. Providing a telemetry link (GSM) is just the trivial part--ensuring security, reliability and service management are the more critical tasks that need to be addressed. Therefore, a complete system concept consists of an automatic fleet management (e.g. periodic device-initiated service calls) as well as customer relationship management (CRM), including technical service and a trouble-ticket system.

A retrospective review of pain control by a two-step irradiance schedule during topical ALA-photodynamic therapy of non-melanoma skin cancer.

PubMed

Zeitouni, Nathalie C; Paquette, Anne D; Housel, Joseph P; Shi, Yi; Wilding, Gregory E; Foster, Thomas H; Henderson, Barbara W

2013-02-01

Photodynamic therapy (PDT) with topical δ-aminolevulinic acid (ALA) of non-melanoma skin cancers is often associated with treatment-limiting pain. A previous study on basal cell carcinomas (BCCs) at Roswell Park Cancer Institute evaluated a two-step irradiance scheme as a means of minimizing pain, preserving outcomes, and limiting treatment time. We used an initial low irradiance until 90% of the protoporphyrin IX was photobleached, followed by a high irradiance interval until the prescribed fluence was delivered. Success of this pilot investigation motivated integration of the protocol into routine practice. Here, we present a retrospective review of recent clinical experience in a broad patient population. This was a retrospective review of an existing dermatology database. Fourteen caucasion patients-nine men and five women, ages 18-80, with a total of 51 superficial and 73 nodular BCCs, and three Bowen's disease lesions-were included. ALA was applied to each lesion for approximately 4 hours. Lesions received an initial irradiance of 30-50 mW/cm(2) for 20 J/cm(2) , followed by 150 mW/cm(2) for a total fluence of 200-300 J/cm(2) . Pain was assessed using a visual analog scale (VAS). Clinical outcome was determined at 6-12 months. Median VAS scores were 1.0 for both irradiances. Five of 127 lesions required pain control with 1% xylocaine. Pain was strongly influenced by lesion location but not by lesion type, number, or size. Complete responses were achieved in 84.1% of BCCs, which compares favorably with reported results for single ALA-PDT treatments. Two of three Bowen's disease lesions showed a complete response. Complete responses for nodular BCCs were 37%, which are also within the range of reported outcomes. A two-step irradiance protocol in ALA-PDT effectively minimizes pain, maintains excellent clinical outcomes in superficial lesions, and adds minimal treatment time. Copyright © 2013 Wiley Periodicals, Inc.

Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia

PubMed Central

Liebman, Howard A.; Saleh, Mansoor N.; Bussel, James B.; Negrea, O. George; Horne, Heather; Wegener, William A.; Goldenberg, David M.

2016-01-01

We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×109/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues. Forty-seven response-evaluable patients had 23 (49%) objective responses (platelet counts ≥30×109/L and ≥2 × baseline) including 15 (32%) complete responses (platelets ≥100×109/L). Responses (including complete responses) and bleeding reduction occurred in all dose groups and were not dose-dependent. In contrast, response duration increased progressively with total dose, reaching a median of 2.7 years with the four once-weekly 320-mg doses. Among nine responders retreated at relapse, three at higher dose levels responded again, including one patient who was retreated four times. In all dose groups, B-cell depletion occurred after the first dose until recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with dose group according to total dose administered, but terminal half-life and clearance were comparable. Human anti-veltuzumab antibody titers developed without apparent dose dependence in nine patients, of whom six responded including five who had complete responses. Subcutaneous veltuzumab was convenient, well-tolerated, and active, without causing significant safety concerns. Platelet responses and bleeding reduction occurred in all dose groups, and response durability appeared to improve with higher doses. Clinicaltrials.gov identifier: NCT00547066 PMID:27515248

Clinicopathological findings, treatment response and predictors of long-term outcome in a cohort of lupus nephritis patients managed according to the Euro-lupus regime: a retrospective analysis in Sri Lanka.

PubMed

Herath, Nalaka; Ratnatunga, Neelakanthi; Weerakoon, Kosala; Wazil, Abdul; Nanayakkara, Nishantha

2017-02-02

Despite the improvement in survival of patients with lupus nephritis (LN) globally, there is sparse data from Sri Lanka (SL). The current study aims to describe the clinicopathological findings, treatment response and predictors of long-term outcome of patients with WHO class III-IV LN in SL, managed according to the Euro-lupus regime. Of 72 patients, 64 were females. In half of them, LN was diagnosed within the 1st year of the illness. The most common presenting feature was sub-nephrotic proteinuria. Sixteen and twenty patients had nephrotic syndrome and abnormal renal function respectively at the time of diagnosis. Fifty-four patients (75%) responded to the Euro-lupus regimen [CR, 20 (28%); PR, 34(47%)]. Later at 6 months, 65 patients (90%) achieved remission [CR, 31(43%); PR, 34 (47%)]. Seven patients experienced treatment failure. During the total duration of follow up, 54 patients remained in complete or partial remission, 26 developed renal relapses, and 19 suffered severe infective episodes. Renal relapses were more common in people who achieved partial remission than complete remission. The long term renal outcome was not associated with age, sex, severity of proteinuria, class of LN or initial renal function. Patients who achieved remission at 6 months had a good long-term outcome. The demographic and clinical features of WHO class III and IV LN in Sri Lankan patients were similar to that reported in the global literature. 75% of patients responded to the Euro-lupus regimen. Therefore, this regime is a suitable initial regimen for LN patients in SL. Good long-term renal outcome can be predicted by early response to therapy. Further studies are necessary to explore better treatment options for patients who fail to achieve remission during initial therapy.

The discriminant capabilities of stability measures, trunk kinematics, and step kinematics in classifying successful and failed compensatory stepping responses by young adults.

PubMed

Crenshaw, Jeremy R; Rosenblatt, Noah J; Hurt, Christopher P; Grabiner, Mark D

2012-01-03

This study evaluated the discriminant capability of stability measures, trunk kinematics, and step kinematics to classify successful and failed compensatory stepping responses. In addition, the shared variance between stability measures, step kinematics, and trunk kinematics is reported. The stability measures included the anteroposterior distance (d) between the body center of mass and the stepping limb toe, the margin of stability (MOS), as well as time-to-boundary considering velocity (TTB(v)), velocity and acceleration (TTB(a)), and MOS (TTB(MOS)). Kinematic measures included trunk flexion angle and angular velocity, step length, and the time after disturbance onset of recovery step completion. Fourteen young adults stood on a treadmill that delivered surface accelerations necessitating multiple forward compensatory steps. Thirteen subjects fell from an initial disturbance, but recovered from a second, identical disturbance. Trunk flexion velocity at completion of the first recovery step and trunk flexion angle at completion of the second step had the greatest overall classification of all measures (92.3%). TTB(v) and TTB(a) at completion of both steps had the greatest classification accuracy of all stability measures (80.8%). The length of the first recovery step (r ≤ 0.70) and trunk flexion angle at completion of the second recovery step (r ≤ -0.54) had the largest correlations with stability measures. Although TTB(v) and TTB(a) demonstrated somewhat smaller discriminant capabilities than trunk kinematics, the small correlations between these stability measures and trunk kinematics (|r| ≤ 0.52) suggest that they reflect two important, yet different, aspects of a compensatory stepping response. Copyright © 2011 Elsevier Ltd. All rights reserved.

The benchmark aeroelastic models program: Description and highlights of initial results

NASA Technical Reports Server (NTRS)

Bennett, Robert M.; Eckstrom, Clinton V.; Rivera, Jose A., Jr.; Dansberry, Bryan E.; Farmer, Moses G.; Durham, Michael H.

1991-01-01

An experimental effort was implemented in aeroelasticity called the Benchmark Models Program. The primary purpose of this program is to provide the necessary data to evaluate computational fluid dynamic codes for aeroelastic analysis. It also focuses on increasing the understanding of the physics of unsteady flows and providing data for empirical design. An overview is given of this program and some results obtained in the initial tests are highlighted. The tests that were completed include measurement of unsteady pressures during flutter of rigid wing with a NACA 0012 airfoil section and dynamic response measurements of a flexible rectangular wing with a thick circular arc airfoil undergoing shock boundary layer oscillations.

Recruiting Ethnically Diverse General Internal Medicine Patients for a Telephone Survey on Physician-Patient Communication

PubMed Central

Nápoles-Springer, Anna M; Santoyo, Jasmine; Stewart, Anita L

2005-01-01

BACKGROUND Limited evidence exists on the effectiveness of recruitment methods among diverse populations. OBKECTIVE Describe response rates by recruitment stage, ethnic-language group, and type of initial contact letter (for African-American and Latino patients). DESIGN Tracking of response status by recruitment stage and ethnic-language group and a randomized trial of ethnically tailored initial letters nested within a cross-sectional telephone survey on physician-patient communication. PARTICIPANTS Adult general medicine patients with ≥1 visit during the preceding year, stratified by 4 categories: African-American (N= 1,400), English-speaking Latino (N= 894), Spanish-speaking Latino (N= 965), and non-Latino white (N= 1,400). MEASUREMENTS AND RESULTS Ethnically tailored initial letters referred to shortages of African-American (or Latino) physicians and the need to learn about the experiences of African-American (or Latino) patients communicating with physicians. Of 2,482 patients contacted, eligible, and able to participate (identified eligibles), 69.9% completed the survey. Thirty-nine percent of the sampling frame was unable to be contacted, with losses higher among non-Latino whites (46.5%) and African Americans (44.2%) than among English-speaking (32.3%) and Spanish-speaking Latinos (25.1%). For identified eligibles, response rates were highest among Spanish-speaking Latinos (75.2%), lowest for non-Latino whites (66.4%), and intermediate for African Americans (69.7%) and English-speaking Latinos (68.1%). There were no differences in overall response rates between patients receiving ethnically tailored letters (72.2%) and those receiving general letters (70.0%). CONCLUSIONS Household contact and individual response rates differed by ethnic-language group, highlighting the importance of tracking losses by stage and subpopulation. Careful attention to recruitment yielded acceptable response rates among all groups. PMID:15963168

Anti-Ig autoantibody and complement-mediated destruction of neoplastic cells

NASA Technical Reports Server (NTRS)

Towmey, J. J.

1976-01-01

Some immune response are effected through immunoglobulins (Ig), of which five classes have been recognized, namely, IgA, IgD, IgE, IgG, and IgM. Auto-antibodies associated with rheumatoid arthritis, termed rheumatoid factors (RF) react with antigenic determinants on IgG heavy chains. RF has predominant but not complete IgM specificity. This auto-antibody response was not detected in treated patients with primary brain tumors (where tissue is sequestered from the immune system by an intact bloodbrain barrier) or with multiple myeloma where humoral immunity is usually impaired. In addition, the prevalence of RF is not increased with solid tumors prior to initiation of chemotherapy or radiotherapy. It is proposed that RF is related to prior chemotherapy or radiotherapy of tumors anatomically accessible to immunologic tissues capable of antibody responses. A primary IgG response occurs, antigen-antibody complexes form, complexed IgG becomes immunologic, and an RF response results.

Left-handers look before they leap: handedness influences reactivity to novel Tower of Hanoi tasks

PubMed Central

Wright, Lynn; Hardie, Scott M.

2015-01-01

A sample of 203 task naïve left- and right-handed participants were asked to complete a combination of the 3- and 4-disk Towers of Hanoi (ToH), manipulating novelty and complexity. Self-reported state anxiety and latency to respond (initiation time) were recorded before each ToH. Novelty had a major effect on initiation time, particularly for left-handers. Left-handers had a longer latency to start and this was significantly longer on the first trial. Irrespective of hand-preference, initiation time reduced on the second trial, however, this was greatest for left-handers. Condition of task did not systematically influence initiation time for right handers, but did for left-handers. State anxiety was influenced by task novelty and complexity in a more complicated way. During the first trial, there was a significant handedness × number of disks interaction with left-handers having significantly higher state anxiety levels before the 3-disk ToH. This suggests that the initial reaction to this task for left-handers was not simply due to perceived difficulty. On their second trial, participants completing a novel ToH had higher state anxiety scores than those completing a repeated version. Overall, left-handers had a larger reduction in their state anxiety across trials. Relating to this, the expected strong positive correlation between state and trait anxiety was absent for left-handed females in their first tower presentation, but appeared on their second. This was driven by low trait anxiety individuals showing a higher state anxiety response in the first (novel) trial, supporting the idea that left-handed females respond to novelty in a way that is not directly a consequence of their trait anxiety. A possible explanation may be stereotype threat influencing the behavior of left-handed females. PMID:25691878

Factors influencing patient decisions to initiate and discontinue subcutaneous testosterone pellets (Testopel) for treatment of hypogonadism.

PubMed

Smith, Ryan P; Khanna, Abhinav; Coward, Robert M; Rajanahally, Saneal; Kovac, Jason R; Gonzales, Marshall A; Lipshultz, Larry I

2013-09-01

A variety of modalities for testosterone replacement therapy (TRT) are available, including topical gels, injections, and Testopel subcutaneous testosterone pellets (STP). STP are becoming more commonly utilized in the United States; however, patient preferences, expectations, and usage patterns regarding this therapy remain poorly characterized. To identify factors influencing patients' decisions to initiate or discontinue STP. A total of 175 men from an academic urology clinic who were currently using or who had previously used STP for hypogonadism received a 32-item electronic survey. Assessment of the impact of convenience, efficacy, side effects, cost, and symptom relief on initiation and discontinuation of STP. One hundred and thirteen men (64.6% response rate) of mean age 51.4 years who previously underwent a mean of 2.8 STP implant procedures completed the survey. Fifty-nine (52.2%) and 40 (35.4%) men had switched to STP from topical gel and injection therapy, respectively, whereas 14 (12.4%) men initially started TRT with STP. Convenience (68.8%) was the most important factor in patients' decision to start STP, while cost of the previous form of TRT (14.7%) was least important. At the time of the survey, 32 men (28.3%) had discontinued STP therapy. Cost of therapy (50%) was the primary factor in discontinuing STP. There was no difference in serum testosterone levels between men who continued STP and those who discontinued therapy (642.8 vs. 629.0 ng/dL, P = 0.83). Overall, 68.1% of patients continued STP therapy at the time of survey completion. Convenience is the most important factor in a patient's decision to initiate STP; however, physician recommendation also plays a substantial role. Cost was the primary reason for discontinuation. Upon survey completion, greater than two-thirds of respondents elected to continue STP therapy. STP are a viable treatment option for hypogonadal men seeking a convenient and efficacious alternative modality of TRT. © 2013 International Society for Sexual Medicine.

Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy

PubMed Central

Etienne, Gabriel; Dulucq, Stéphanie; Nicolini, Franck-Emmanuel; Morisset, Stéphane; Fort, Marie-Pierre; Schmitt, Anna; Etienne, Madeleine; Hayette, Sandrine; Lippert, Eric; Bureau, Caroline; Tigaud, Isabelle; Adiko, Didier; Marit, Gérald; Reiffers, Josy; Mahon, François-Xavier

2014-01-01

Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR 4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79–10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome. PMID:24362549

Conditional data watchpoint management

DOEpatents

Burdick, Dean Joseph; Vaidyanathan, Basu

2010-08-24

A method, system and computer program product for managing a conditional data watchpoint in a set of instructions being traced is shown in accordance with illustrative embodiments. In one particular embodiment, the method comprises initializing a conditional data watchpoint and determining the watchpoint has been encountered. Upon that determination, examining a current instruction context associated with the encountered watchpoint prior to completion of the current instruction execution, further determining a first action responsive to a positive context examination; otherwise, determining a second action.

Discrete analysis of spatial-sensitivity models

NASA Technical Reports Server (NTRS)

Nielsen, Kenneth R. K.; Wandell, Brian A.

1988-01-01

Procedures for reducing the computational burden of current models of spatial vision are described, the simplifications being consistent with the prediction of the complete model. A method for using pattern-sensitivity measurements to estimate the initial linear transformation is also proposed which is based on the assumption that detection performance is monotonic with the vector length of the sensor responses. It is shown how contrast-threshold data can be used to estimate the linear transformation needed to characterize threshold performance.

Learning and Memory Enhancement by Neuropeptides

DTIC Science & Technology

1987-06-30

learning in an autoshaping task, in which rats learn to touch a lever to obtain food t!-k During the past year we have completed an initial dose...response study of effects of TMT’ý autoshaping and a paper has been accepted for publication (C.A. Cohen, R.B. Messing and S.B. Sparber, Psvchooharmacologv...from specific cognitive effects of the compound. In particular, TMT does not impair performance of easy versions of the autoshaping task with

Does research through Structured Operational Research and Training (SORT IT) courses impact policy and practice?

PubMed Central

Shewade, H. D.; Tripathy, J. P.; Guillerm, N.; Tayler-Smith, K.; Berger, S. Dar; Bissell, K.; Reid, A. J.; Zachariah, R.; Harries, A. D.

2016-01-01

Setting: Structured Operational Research and Training Initiative (SORT IT) courses are well known for their output, with nearly 90% of participants completing the course and publishing in scientific journals. Objective: We assessed the impact of research papers on policy and practice that resulted from six SORT IT courses initiated between July 2012 and March 2013. Design: This was a cross-sectional study involving e-mail-based, self-administered questionnaires and telephone/skype/in-person responses from first and/or senior co-authors of course papers. A descriptive content analysis of the responses was performed and categorised into themes. Results: Of 72 participants, 63 (88%) completed the course. Course output included 81 submitted papers, of which 76 (94%) were published. Of the 81 papers assessed, 45 (55%) contributed to a change in policy and/or practice: 29 contributed to government policy/practice change (20 at national, 4 at subnational and 5 at hospital level), 11 to non-government organisational policy change and 5 to reinforcing existing policy. The changes ranged from modifications of monitoring and evaluation tools, to redrafting of national guidelines, to scaling up existing policies. Conclusion: More than half of the SORT IT course papers contributed to a change in policy and/or practice. Future assessments should include more robust and independent verification of the reported change(s) with all stakeholders. PMID:27051612

Changing Criminal Attitudes Among Incarcerated Offenders: Initial Examination of a Structured Treatment Program.

PubMed

Simourd, David J; Olver, Mark E; Brandenburg, Bryan

2016-09-01

The present study investigated the effect of a criminal attitude treatment program to changes on measured criminal attitudes and postprogram recidivism. The criminal attitude program (CAP) is a standardized therapeutic curriculum consisting of 15 modules offering 44 hr of therapeutic time. It was delivered by trained facilitators to a total of 113 male offenders incarcerated in one of five state correctional institutions. Pretreatment and posttreatment comparisons were made on standardized measures of criminal attitudes, response bias, and motivation for lifestyle changes. Results found statistically significant lower criminal attitudes at posttreatment that were unaffected by response bias. There were also increases in motivation for lifestyle changes, but these did not reach statistical significance. Fifty-seven participants were released into the community following the program and were eligible for recidivism analyses. Comparisons between participants who completed the CAP and those who did not complete the CAP revealed 7% lower rearrest among CAP completers. Although preliminary, these results indicate that the CAP had a positive effect on changes to criminal attitudes and recidivism. The findings are discussed in terms of conceptual and practical considerations in the assessment and treatment of criminal attitudes among offenders. © The Author(s) 2015.

Response-adapted treatment with upfront high-dose chemotherapy followed by autologous stem-cell transplantation rescue or consolidation phase high-dose methotrexate for primary central nervous system lymphoma: a long-term mono-center study.

PubMed

Nakasu, Yoko; Mitsuya, Koichi; Hayashi, Nakamasa; Okamura, Ikue; Mori, Keita; Enami, Terukazu; Tatara, Raine; Nakasu, Satoshi; Ikeda, Takashi

2016-01-01

Treatment regimens for primary central nervous system lymphoma (PCNSL) include high-dose methotrexate (HD-MTX)-based chemotherapy, with or without radiotherapy and are based on studies of selected patient groups. This retrospective study assessed a consistent strategy of response-adapted protocol applied for patients including age >65 years in a cancer center for 10 years longitudinally. Case notes were studied of 61 consecutively treated patients with PCNSL histologically diagnosed between 2003 and 2013. Clinical follow-up during and after treatment included neurologic examination and magnetic resonance imaging. Of the patients studied, 14.8 % (9/61) were clinically unfit for chemotherapy; the remaining 85.2 % (52/61) of patients were treated with HD-MTX. Of these patients, 58 % (30/52) achieved an initial complete response, with a median survival of 100.1 months. Of these response-adapted patients, 33 % (10/30) were <65 years and were treated with upfront high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT). The remaining response-adapted patients included 53 % (16/30) who were ≥65 years underwent consolidation with HD-MTX, and 14 % (4/30) who chose radiotherapy. The median survival of patients with HDC-ASCT had not yet been reached compared with 67.6 months for patients with HD-MTX consolidation treatment (p = 0.26). At the end of the study, 75 % (39/52) of patients had died mainly owing to progression or relapse of PCNSL. Multivariate analysis showed that age younger than 65 years (p = 0.02) and complete response for up-front HD-MTX (p = 0.001) were independent prognostic indicators of overall survival. In conclusion, this single-center retrospective clinical study has shown that treatment of PCNSL with upfront HDC-ASCT and consolidation phase HD-MTX monotherapy may be feasible, even for elderly patients in a routine clinical setting, using the three-step selection by eligibility and response to initial HD-MTX, and age threshold of 65 years for ASCT.

[Management strategies for major depressive episodes as a function of initial response to an SSRI or SNRI antidepressant: results of the ORACLE survey].

PubMed

Spadone, C; Sylvestre, M; Chiarelli, P; Richard-Berthe, C

2005-01-01

The main aim of the major depressive episode treatment is to obtain a complete remission. However, partial remission (persistence of residual symptoms) is a frequent outcome of major depressive episodes, concerning approximately half of the patients who were responders to the treatment. An inadequate treatment response after three weeks of treatment is considered by the ANAES recommendations as a potential reason to modify the treatment regimen. The primary objectives of this survey were to describe the therapeutic strategies implemented in subjects treated as outpatients for a major depressive episode following evaluation of the initial response to an SSRI or an SNRI antidepressant and to assess by a naturalistic way the impact of these strategies on the extent of remission at three months. The secondary objective was to determine, by multivariate analysis, others factors able to influence the remission. This prospective observational survey concerned 2 138 patients treated by community psychiatrists (n=582) and presenting a major depressive episode in the context of a recurrent depressive disorder. Patients were assessed at inclusion and at Weeks 3, at Week 6 and at Week 12. Changes in score on the Hamilton Depression Scale (Ham-D) and CGI severity between inclusion and Week 3 and improvement scores were evaluated. The therapeutic strategies after evaluation were described. Remission was defined as a score of 1 or 2 on the CGI-improvement scale; a treatment response at Week 3 was defined as a decrease of at least 50% in the Ham-D score. The physician also provided an overall rating of satisfaction with the treatment at Week 3. Data from 1 974 patients were analysed. The mean age at inclusion was 42.7 years, 70% of the patients were women; the mean age at first episode was 32.2 years, the average time since the last episode was 3.6 years. The mean Ham-D score at inclusion was 23.6 +/- 5.8. At Week 3, 29.1% of patients were considered treatment responders. The antidepressant dose was subsequently increased in 10.2% of responders compared to 36.3% of non-responders. When the physician rated the treatment response as unsatisfactory, the dose was increased in 56% of cases. At week 12, 83.7% of patients were in remission as defined by the CGI; according to physician judgement, 45.7% were in complete remission and 43.3% in partial remission. According to the literature, the existence of an early response to the treatment predicted a total remission at Week 12 (69.1% of the treatments responders at Week 3 were in complete remission at Week 12, vs 35.7% of the treatments not-responders). These results underline the professional practices in private community psychiatric practice in France. At Week 3, posology increased for only 36.3% of the patients, whereas it is one of the therapeutic strategies recommended by the ANAES. Participating physicians relied on their subjective judgement about initial treatment response when making decisions about treatment strategies rather than by psychometric scores. At Week 3, 29.1% of patients were considered treatment responders according to the change in Ham-D score, compared to 57.3% whose treatment response was considered satisfactory by the physician. The decision to increase the dose was more closely associated with subjective perceptions of satisfaction than with psychometric rating scale scores, despite psychometric evaluation was systematic in the ORACLE survey, what is not the case in usual practice in France, except for clinical research. In addition, this study confirms an important data for the clinician: there is a correlation between early response to the treatment (Week 3) and complete remission at the end of the acute phase of treatment (Week 12).

No evidence of response bias in a population-based childhood cancer survivor questionnaire survey — Results from the Swiss Childhood Cancer Survivor Study

PubMed Central

Gianinazzi, Micòl E.; Michel, Gisela; Zwahlen, Marcel; von der Weid, Nicolas X.; Kuehni, Claudia E.

2017-01-01

Purpose This is the first study to quantify potential nonresponse bias in a childhood cancer survivor questionnaire survey. We describe early and late responders and nonresponders, and estimate nonresponse bias in a nationwide questionnaire survey of survivors. Methods In the Swiss Childhood Cancer Survivor Study, we compared characteristics of early responders (who answered an initial questionnaire), late responders (who answered after ≥1 reminder) and nonresponders. Sociodemographic and cancer-related information was available for the whole population from the Swiss Childhood Cancer Registry. We compared observed prevalence of typical outcomes in responders to the expected prevalence in a complete (100% response) representative population we constructed in order to estimate the effect of nonresponse bias. We constructed the complete population using inverse probability of participation weights. Results Of 2328 survivors, 930 returned the initial questionnaire (40%); 671 returned the questionnaire after ≥1reminder (29%). Compared to early and late responders, we found that the 727 nonresponders (31%) were more likely male, aged <20 years, French or Italian speaking, of foreign nationality, diagnosed with lymphoma or a CNS or germ cell tumor, and treated only with surgery. But observed prevalence of typical estimates (somatic health, medical care, mental health, health behaviors) was similar among the sample of early responders (40%), all responders (69%), and the complete representative population (100%). In this survey, nonresponse bias did not seem to influence observed prevalence estimates. Conclusion Nonresponse bias may play only a minor role in childhood cancer survivor studies, suggesting that results can be generalized to the whole population of such cancer survivors and applied in clinical practice. PMID:28463966

Long-Term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Short Bowel Syndrome.

PubMed

Schwartz, Lauren K; O'Keefe, Stephen J D; Fujioka, Ken; Gabe, Simon M; Lamprecht, Georg; Pape, Ulrich-Frank; Li, Benjamin; Youssef, Nader N; Jeppesen, Palle B

2016-02-04

In the pivotal 24-week, phase III, placebo-controlled trial, teduglutide significantly reduced parenteral support (PS) requirements in patients with short bowel syndrome (SBS). STEPS-2 was a 2-year, open-label extension of that study designed to evaluate long-term safety and efficacy of teduglutide. Enrolled patients had completed 24 weeks of either teduglutide (TED/TED) or placebo (PBO/TED) in the initial placebo-controlled study or qualified for that study, but were not treated (NT/TED) because of full enrollment. Patients received subcutaneous teduglutide 0.05 mg/kg/day for up to 24 months (NT/TED and PBO/TED) or up to 30 months (TED/TED). Clinical response was defined as 20-100% reduction from baseline in weekly PS volume; baseline was considered the beginning of teduglutide treatment in the initial placebo-controlled study (TED/TED) or STEPS-2 (NT/TED and PBO/TED). Descriptive statistics summarized changes in efficacy and safety variables. Of 88 enrolled patients, 65 (74%) completed STEPS-2. The most common treatment-emergent adverse events were abdominal pain (34%), catheter sepsis (28%), and decreased weight (25%). Mean weight, body mass index, and serum albumin remained stable. In patients who completed the study, clinical response was achieved in 28/30 (93%) TED/TED, 16/29 (55%) PBO/TED, and 4/6 (67%) NT/TED patients. Mean PS volume reductions from baseline were 7.6 (66%), 3.1 (28%), and 4.0 (39%) l/week in the TED/TED, PBO/TED, and NT/TED groups, respectively. Thirteen patients achieved full enteral autonomy. In patients with SBS, long-term teduglutide treatment resulted in sustained, continued reductions in PS requirements. Overall health and nutritional status was maintained despite PS reductions.

Long-Term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Short Bowel Syndrome

PubMed Central

Schwartz, Lauren K; O'Keefe, Stephen J D; Fujioka, Ken; Gabe, Simon M; Lamprecht, Georg; Pape, Ulrich-Frank; Li, Benjamin; Youssef, Nader N; Jeppesen, Palle B

2016-01-01

OBJECTIVES: In the pivotal 24-week, phase III, placebo-controlled trial, teduglutide significantly reduced parenteral support (PS) requirements in patients with short bowel syndrome (SBS). STEPS-2 was a 2-year, open-label extension of that study designed to evaluate long-term safety and efficacy of teduglutide. METHODS: Enrolled patients had completed 24 weeks of either teduglutide (TED/TED) or placebo (PBO/TED) in the initial placebo-controlled study or qualified for that study, but were not treated (NT/TED) because of full enrollment. Patients received subcutaneous teduglutide 0.05 mg/kg/day for up to 24 months (NT/TED and PBO/TED) or up to 30 months (TED/TED). Clinical response was defined as 20–100% reduction from baseline in weekly PS volume; baseline was considered the beginning of teduglutide treatment in the initial placebo-controlled study (TED/TED) or STEPS-2 (NT/TED and PBO/TED). Descriptive statistics summarized changes in efficacy and safety variables. RESULTS: Of 88 enrolled patients, 65 (74%) completed STEPS-2. The most common treatment-emergent adverse events were abdominal pain (34%), catheter sepsis (28%), and decreased weight (25%). Mean weight, body mass index, and serum albumin remained stable. In patients who completed the study, clinical response was achieved in 28/30 (93%) TED/TED, 16/29 (55%) PBO/TED, and 4/6 (67%) NT/TED patients. Mean PS volume reductions from baseline were 7.6 (66%), 3.1 (28%), and 4.0 (39%) l/week in the TED/TED, PBO/TED, and NT/TED groups, respectively. Thirteen patients achieved full enteral autonomy. CONCLUSIONS: In patients with SBS, long-term teduglutide treatment resulted in sustained, continued reductions in PS requirements. Overall health and nutritional status was maintained despite PS reductions. PMID:26844839

Genomic organization, complete sequence, and chromosomal location of the gene for human eotaxin (SCYA11), an eosinophil-specific CC chemokine

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

Garcia-Zepeda, E.A.; Sarafi, M.N.; Luster, A.D.

1997-05-01

Eotaxin is a CC chemokine that is a specific chemoattractant for eosinophils and is implicated in the pathogenesis of eosinophilic inflammatory diseases, such as asthma. We describe the genomic organization, complete sequence, including 1354 bp 5{prime} of the RNA initiation site, and chromosomal localization of the human eotaxin gene. Fluorescence in situ hybridization analysis localized eotaxin to human chromosome 17, in the region q21.1-q21.2, and the human gene name SCYA11 was assigned. We also present the 5{prime} flanking sequence of the mouse eotaxin gene and have identified several regulatory elements that are conserved between the murine and the human promoters.more » In particular, the presence of elements such as NF-{Kappa}B, interferon-{gamma} response element, and glucocorticoid response element may explain the observed regulation of the eotaxin gene by cytokines and glucocorticoids. 17 refs., 4 figs., 1 tab.« less

Cardiovascular responses of men and women to lower body negative pressure

NASA Technical Reports Server (NTRS)

Montgomery, L. D.; Kirk, P. J.; Payne, P. A.; Gerber, R. L.; Newton, S. D.; Williams, B. A.

1977-01-01

Changes in blood flow and blood redistribution were measured by impedance plethysmography in the pelvic and leg regions of six male and four female subjects during three 5-min exposures to -20, -40, and -60 mm Hg lower body negative pressure (LBNP). Female subjects demonstrated significantly higher mean heart rate and lower leg blood flow indices than the male subjects during the recumbent control periods. Men had slightly higher mean resting systolic and diastolic blood pressures and higher mean control pelvic blood indices. Women demonstrated significantly less blood pooling in the legs and slightly less in the pelvic region than the men. All of the 18 tests with male subjects at -60 mm Hg were completed without initial signs of syncope, while only two of the tests with women were completed successfully without the subject exhibiting presyncopal conditions. Results indicate that impedance plethysmography can be used to measure segmental cardiovascular responses during LBNP and that females may be less tolerant to -60 mm Hg LBNP than males.

Progress report on the Worldwide Earthquake Risk Management (WWERM) Program

USGS Publications Warehouse

Algermissen, S.T.; Hays, Walter W.; Krumpe, Paul R.

1992-01-01

Considerable progress has been made in the Worldwide Earthquake Risk Management (WWERM) Program since its initiation in late 1989 as a cooperative program of the Agency for International Development (AID), Office of U.S. Foreign Disaster Assistance (OFDA), and the U.S. Geological Survey. Probabilistic peak acceleration and peak Modified Mercalli intensity (MMI) maps have been prepared for Chile and for Sulawesi province in Indonesia. Earthquake risk (loss) studies for dwellings in Gorontalo, North Sulawesi, have been completed and risk studies for dwellings in selected areas of central Chile are underway. A special study of the effect of site response on earthquake ground motion estimation in central Chile has also been completed and indicates that site response may modify the ground shaking by as much as plus or minus two units of MMI. A program for the development of national probabilistic ground motion maps for the Philippines is now underway and pilot studies of earthquake ground motion and risk are being planned for Morocco.

Influence of Self-generated Anchors on the Voice Handicap Index-10 (VHI-10).

PubMed

Canals-Fortuny, Elisabet; Vila-Rovira, Josep

2017-03-01

The aim of this research is to study whether the presentation of the Voice Handicap Index-10 questionnaire administered at the beginning of the treatment impinged on the results of the responses from the end of the treatment. The questionnaire was administered at the beginning of the treatment to a total of 308 patients. After the treatment, a group of 235 patients answered the questionnaire again without any reference to their responses on the initial administration. The other group of participants, consisting of 73 subjects, completed the questionnaire with the answer sheet of their initial self-assessment in sight. The data obtained show that patients who responded to the anchored answer test show less dispersion and a smaller coefficient of variation (0.90) than those who responded to the nonanchored answer test (coefficient of variation = 1.66). The method of administration of the Voice Handicap Index-10 at the end of a treatment influences the dispersion of the results. We recommend that the patient be anchored to the initial answer sheet while responding to the final self-assessment. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

The Australian funding debate on quadrivalent HPV vaccine: a case study for the national pharmaceutical policy.

PubMed

Roughead, Elizabeth Ellen; Gilbert, Andrew L; Vitry, Agnes I

2008-12-01

To analyse the media and political reactions to the initial decision of the Pharmaceutical Benefits Advisory Committee (PBAC) to reject funding of the quadrivalent human papilloma virus (HPV) vaccine in Australia. A case study, informed by media reports and government documents, was utilised to examine the reactions of key stakeholders; PBAC, consumers, consumer organisations, pharmaceutical industry, politicians, health professionals and the media to the initial decision to reject funding of HPV vaccine. The initial decision to reject funding of the HPV vaccine led to unprecedented public response with over 300 newspaper articles and calls by consumers, health professionals and politicians to intervene in the decision making process. Misunderstanding of the decision making process, particularly cost-effectiveness assessments, the need for an independent process, the legislated inability of a timely and transparent response from policy makers and the lack of a risk mitigation strategy all played a role in the public outcry. Despite 15 years of implementation of cost-effectiveness assessments there is still a need for improving stakeholder understanding of the decision making process and for timely transfer of complete information. Risk mitigation strategies should be considered as part of the communication plan for all decisions.

Use of a Geriatric Quality Initiative to Educate Internal Medicine Residents about Delirium and Its Risk Factors.

PubMed

Olveczky, Daniele; Mattison, Melissa L P; Mukamal, Kenneth J

2013-06-01

Delirium is a common and debilitating complication of inpatient care for many older adults, yet internal medicine residents often do not recognize delirium or its risk factors. Integrating geriatric education (eg, delirium recognition) with inpatient quality improvement (QI) is not well tested. We developed an educational pilot program within an ongoing hospital-wide geriatric QI initiative (Global Risk Assessment and Careplan for the Elderly-Acute Care [GRACE-AC]). GRACE-AC modifies the inpatient computerized provider order entry system to meet the needs of vulnerable older adults and uses a bedside care checklist to identify patients with possible delirium and promote delirium prevention by checking on the need for "tethers" (intravenous fluids, Foley catheters, and telemetry). Residents were assessed before and after each inpatient rotation by using anonymous electronic surveys. A total of 167 eligible residents (91%) completed prerotation surveys, and 102 (56%) residents completed postrotation surveys. All but the first rotating resident group received a standardized 2-minute educational in-service orientation. In a comparison of postrotation responses before and after implementation of the in-service, the proportion of residents who reported improvement in their ability to recall which patients had tethers increased from 17% to 52% for intravenous fluids (P  =  .004), 28% to 75% for Foley catheters (P < .001), and 21% to 50% for telemetry (P  =  .02). Comparing pre- and postrotation surveys, the proportion of correct responses to questions on haloperidol dosing and the characteristics of delirium increased from 26% to 76% and 31% to 63%, respectively (both P < .001). Our pilot program demonstrated that inpatient geriatric QI initiatives can be successfully merged with a brief educational curriculum.

Efficacy and Safety of Second-Line 5-Day Dactinomycin in Case of Methotrexate Failure for Gestational Trophoblastic Neoplasia.

PubMed

Prouvot, Catherine; Golfier, François; Massardier, Jérôme; You, Benoit; Lotz, Jean-Pierre; Patrier, Sophie; Devouassoux, Mojgan; Schott, Anne-Marie; Hajri, Touria; Bolze, Pierre-Adrien

2018-06-01

The objective of this study was to evaluate the characteristics and outcomes of patients treated for gestational trophoblastic neoplasia (GTN) with second-line 5-day dactinomycin after failed first-line 8-day methotrexate. From 1999 to 2017, patients with methotrexate resistant GTN treated with second line dactinomycin were identified at the French Trophoblastic Disease Reference Center. Using univariate and multivariate analysis, we identified significant predictive factors of second line dactinomycin failure. A total of 877 GTN patients were treated with first-line 8-day methotrexate, of which 103 required second-line 5-day dactinomycin for methotrexate failure. Complete response was observed in 78 patients (75.7% [95% confidence interval, 66.3-83.6]; P < 0.0001), whereas 25 needed third-line treatment, 13 for dactinomycin resistance and 12 for post-dactinomycin relapse. Overall survival of patients treated with dactinomycin was 100%. An interval of greater than or equal to 7 months between antecedent pregnancy termination and methotrexate initiation was a predictive factor significantly associated with second-line dactinomycin failure in multivariate analysis (exact odds ratio, 9.17 [95% confidence interval, 1.98-50.70]; P = 0.0029). No grades 4 and 5 adverse effects were experienced and the most common toxicity being grade 1 nausea (14.6%). Given a 75.7% complete response rate in methotrexate failed low-risk GTN patients treated with second-line dactinomycin and an overall survival rate of 100% after third-line treatment, the use of dactinomycin should be favored as second-line, regardless of human chorionic gonadotropin level at the time of dactinomycin initiation. However, an interval between the termination of the antecedent pregnancy and methotrexate initiation longer than 6 months should encourage considering alternative therapeutic strategies.

A pan-Canadian web-based education program to support screening for distress: evaluation of outcomes.

PubMed

McLeod, Deborah L; Morck, Angela C; Curran, Janet A

2014-02-01

Cancer-related distress has been endorsed as the sixth vital sign by many international cancer organizations, and some countries such as Canada have implemented national screening for distress programs. The completion of a screening tool is an important first step in improving responsiveness to cancer-related distress, but screening must be followed with skilled supportive care to make a difference in patient-reported outcomes. Our objective was to create a web-based education program to support nurses and other frontline staff in providing an initial response to screening results. To address screening and supportive care learning needs, the Canadian Association of Psychosocial Oncology (CAPO), with support from the Canadian Partnership Against Cancer, created a web-based education program as one component of the national screening for distress agenda. The program provides clinically grounded and interactive learning through the use of PowerPoint presentations, video clips of clinical interactions with patients and family members, and test questions. Presentation topics include, for example, strategies for dealing with screening results, managing referrals, and supportive counseling. We employed a matched pairs, pre-post survey design to assess the effect of the education program on confidence in screening and in providing initial supportive care. Our analysis of the first 147 matched pairs to complete the course suggests that satisfaction with the course was high. Statistically significant increases in confidence in relation to screening for distress and assessing distress, and in providing initial supportive care, were evident. Our ongoing experience with CAPO's Interprofessional Psychosocial Oncology Distance Education (IPODE) project (www.ipode.ca) project suggests that healthcare professionals value web-based learning for its accessibility and convenience. Such programs appear to offer excellent opportunities for cost-effective education that supports practice change.

Night Blood Pressure Responses to Atenolol and Hydrochlorothiazide in Black and White Patients With Essential Hypertension

PubMed Central

2014-01-01

BACKGROUND Night blood pressure (BP) predicts patient outcomes. Variables associated with night BP response to antihypertensive agents have not been fully evaluated in essential hypertension. METHODS We sought to measure night BP responses to hydrochlorothiazide (HCTZ), atenolol (ATEN), and combined therapy using ambulatory blood pressure (ABP) monitoring in 204 black and 281 white essential hypertensive patients. Initial therapy was randomized; HCTZ and ATEN once daily doses were doubled after 3 weeks and continued for 6 more weeks with the alternate medication added for combined therapy arms. ABP was measured at baseline and after completion of each drug. Night, day, and night/day BP ratio responses (treatment − baseline) were compared in race/sex subgroups. RESULTS Baseline night systolic BP and diastolic BP, and night/day ratios were greater in blacks than whites (P < 0.01, all comparisons). Night BP responses to ATEN were absent and night/day ratios increased significantly in blacks (P < 0.05). At the end of combined therapy, women, blacks, and those starting with HCTZ as opposed to ATEN had significantly greater night BP responses (P < 0.01). Variables that significantly associated with ATEN response differed from those that associated with HCTZ response and those that associated with night BP response differed from those that associated with day BP response. CONCLUSIONS In summary, after completion of HCTZ and ATEN therapy, women, blacks, and those who started with HCTZ had greater night BP responses. Reduced night BP response and increased night/day BP ratios occured with ATEN in blacks. Given the prognostic significance of night BP, strategies for optimizing night BP antihypertensive therapy should be considered. CLINICAL TRIAL REGISTRATION Clinicaltrials.gov identifier NCT00246519 PMID:23886594

Crawler Acquisition and Testing Demonstration Project Management Plan

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

DEFIGH-PRICE, C.

2000-10-23

If the crawler based retrieval system is selected, this project management plan identifies the path forward for acquiring a crawler/track pump waste retrieval system, and completing sufficient testing to support deploying the crawler for as part of a retrieval technology demonstration for Tank 241-C-104. In the balance of the document, these activities will be referred to as the Crawler Acquisition and Testing Demonstration. During recent Tri-Party Agreement negotiations, TPA milestones were proposed for a sludge/hard heel waste retrieval demonstration in tank C-104. Specifically one of the proposed milestones requires completion of a cold demonstration of sufficient scale to support finalmore » design and testing of the equipment (M-45-03G) by 6/30/2004. A crawler-based retrieval system was one of the two options evaluated during the pre-conceptual engineering for C-104 retrieval (RPP-6843 Rev. 0). The alternative technology procurement initiated by the Hanford Tanks Initiative (HTI) project, combined with the pre-conceptual engineering for C-104 retrieval provide an opportunity to achieve compliance with the proposed TPA milestone M-45-03H. This Crawler Acquisition and Testing Demonstration project management plan identifies the plans, organizational interfaces and responsibilities, management control systems, reporting systems, timeline and requirements for the acquisition and testing of the crawler based retrieval system. This project management plan is complimentary to and supportive of the Project Management Plan for Retrieval of C-104 (RPP-6557). This project management plan focuses on utilizing and completing the efforts initiated under the Hanford Tanks Initiative (HTI) to acquire and cold test a commercial crawler based retrieval system. The crawler-based retrieval system will be purchased on a schedule to support design of the waste retrieval from tank C-104 (project W-523) and to meet the requirement of proposed TPA milestone M-45-03H. This Crawler Acquisition and Testing Demonstration project management plan includes the following: (1) Identification of acquisition strategy and plan to obtain a crawler based retrieval system; (2) Plan for sufficient cold testing to make a decision for W-523 and to comply with TPA Milestone M-45-03H; (3) Cost and schedule for path forward; (4) Responsibilities of the participants; and (5) The plan is supported by updated Level 1 logics, a Relative Order of Magnitude cost estimate and preliminary project schedule.« less

Graft-versus-Host Disease Treatment: Predictors of Survival

PubMed Central

Levine, John E.; Logan, Brent; Wu, Juan; Alousi, Amin M.; Ho, Vincent; Bolaños-Meade, Javier; Weisdorf, Daniel

2010-01-01

Acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplant (HCT) is the major reason for non-relapse mortality and thus is a major determinant of long term survival. Clinical trials of new aGVHD treatments are needed in order to identify approaches that will ultimately improve upon HCT survival. At present it is not clear how quickly response to GVHD treatment needs to be established in order to reliably categorize patients at high risk for death or to promptly identify those who might benefit from alternate treatment. Therefore, we analyzed time to response from onset of aGVHD treatment in 180 patients who were enrolled on a national, randomized, phase II aGVHD treatment clinical trial whose initial treatment of GVHD consisted of high dose steroids plus a second immunosuppressive agent. The aim of this analysis was to determine whether time to aGVHD treatment response predicts patient outcomes, especially survival. We used response at 14, 28 and 56 days from initiation of aGVHD treatment to categorize patients for non-relapse mortality and survival. Multivariate analyses and specificity/sensitivity analyses identified that day 28 response (complete or partial response) best categorized patients by non-relapse mortality and survival at 9 months from start of aGVHD treatment. If verified as a reliable predictor of late outcomes following other aGVHD treatment approaches, day 28 response should serve as a standard early endpoint for future trials of aGVHD therapy. PMID:20541024

Seasonal Predictions with the GEOS GCM

NASA Technical Reports Server (NTRS)

Schubert, Siegfried; Chang, Yehui; Suarez, Max

1999-01-01

A number of ensembles of seasonal forecasts have recently been completed as part of NASA's Seasonal to Interannual Prediction Project (NSIPP). The focus is on the extratropical response of the atmosphere to observed Surface Sea Temperature (SST) anomalies during boreal winter. The prediction experiments consist of nine forecasts starting from slightly different initial conditions for each year of the 15 year period 1981-95, employing version 2 of the Goddard Earth Observing System (GEOS) atmospheric Global Circulation Models (GCM). The initial conditions are obtained from the NASA GEOS-1 reanalysis data. Comparisons with a companion set of six long-term simulations with observed SST (starting in 1978, so they have no memory of the initial conditions for the periods of interest) are used to assess the relative contributions of the initial conditions and SST anomalies to forecast skill ranging from daily to seasonal time scales. The ensembles are used to isolate the signal, and to assess the nature of the inherent variability (noise) of the forecasts.

Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy

PubMed Central

Wyluda, Edward J; Cheng, Jihua; Schell, Todd D; Haley, Jeremy S; Mallon, Carol; Neves, Rogerio I; Robertson, Gavin; Sivik, Jeffrey; Mackley, Heath; Talamo, Giampaolo; Drabick, Joseph J

2015-01-01

We report 3 cases of durable complete response (CR) in patients with BRAF-mutated metastatic melanoma who were initially treated unsuccessfully with sequential immunotherapies (high dose interleukin 2 followed by ipilimumab with or without concurrent radiation therapy). After progression during or post immunotherapy, these patients were given BRAF inhibitor therapy and developed rapid CRs. Based on the concomitant presence of autoimmune manifestations (including vitiligo and hypophysitis), we postulated that there was a synergistic effect between the prior immune therapy and the BRAF targeting agents. Accordingly, the inhibitors were gradually weaned off beginning at 3 months and were stopped completely at 9–12 months. The three patients remain well and in CR off of all therapy at up to 15 months radiographic follow-up. The institution of the BRAF therapy was associated with development of severe rheumatoid-like arthritis in 2 patients which persisted for months after discontinuation of therapy, suggesting it was not merely a known toxicity of BRAF inhibitors (arthralgias). On immunologic analysis, these patients had high levels of non-T-regulatory, CD4 positive effector phenotype T-cells, which persisted after completion of therapy. Of note, we had previously reported a similar phenomenon in patients with metastatic melanoma who failed high dose interleukin-2 and were then placed on a finite course of temozolomide with rapid complete responses that have remained durable for many years after discontinuation of temozolomide. We postulate that a finite course of cytotoxic or targeted therapy specific for melanoma given after apparent failure of prior immunotherapy can result in complete and durable remissions that may persist long after the specific cytotoxic or targeted agents have been discontinued suggesting the existence of sequence specific synergism between immunotherapy and these agents. Here, we discuss these cases in the context of the literature on synergy between conventional or targeted cytotoxic therapy and immunotherapy in cancer treatment. PMID:25806780

Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy.

PubMed

Wyluda, Edward J; Cheng, Jihua; Schell, Todd D; Haley, Jeremy S; Mallon, Carol; Neves, Rogerio I; Robertson, Gavin; Sivik, Jeffrey; Mackley, Heath; Talamo, Giampaolo; Drabick, Joseph J

2015-01-01

We report 3 cases of durable complete response (CR) in patients with BRAF-mutated metastatic melanoma who were initially treated unsuccessfully with sequential immunotherapies (high dose interleukin 2 followed by ipilimumab with or without concurrent radiation therapy). After progression during or post immunotherapy, these patients were given BRAF inhibitor therapy and developed rapid CRs. Based on the concomitant presence of autoimmune manifestations (including vitiligo and hypophysitis), we postulated that there was a synergistic effect between the prior immune therapy and the BRAF targeting agents. Accordingly, the inhibitors were gradually weaned off beginning at 3 months and were stopped completely at 9-12 months. The three patients remain well and in CR off of all therapy at up to 15 months radiographic follow-up. The institution of the BRAF therapy was associated with development of severe rheumatoid-like arthritis in 2 patients which persisted for months after discontinuation of therapy, suggesting it was not merely a known toxicity of BRAF inhibitors (arthralgias). On immunologic analysis, these patients had high levels of non-T-regulatory, CD4 positive effector phenotype T-cells, which persisted after completion of therapy. Of note, we had previously reported a similar phenomenon in patients with metastatic melanoma who failed high dose interleukin-2 and were then placed on a finite course of temozolomide with rapid complete responses that have remained durable for many years after discontinuation of temozolomide. We postulate that a finite course of cytotoxic or targeted therapy specific for melanoma given after apparent failure of prior immunotherapy can result in complete and durable remissions that may persist long after the specific cytotoxic or targeted agents have been discontinued suggesting the existence of sequence specific synergism between immunotherapy and these agents. Here, we discuss these cases in the context of the literature on synergy between conventional or targeted cytotoxic therapy and immunotherapy in cancer treatment.

Simulation of Top Quark Pair Production as a Background for Higgs Events at the Compact Muon Solenoid

NASA Astrophysics Data System (ADS)

Justus, Christopher

2005-04-01

In this study, we simulated top-antitop (tt-bar) quark events at the Compact Muon Solenoid (CMS), an experiment presently being constructed at the Large Hadron Collider in Geneva, Switzerland. The tt-bar process is an important background for Higgs events. We used a chain of software to simulate and reconstruct processes that will occur inside the detector. CMKIN was used to generate and store Monte Carlo Events. OSCAR, a GEANT4 based CMS detector simulator, was used to simulate the CMS detector and how particles would interact with the detector. Next, we used ORCA to simulate the response of the readout electronics at CMS. Last, we used the Jet/MET Root maker to create root files of jets and missing energy. We are now using this software analysis chain to complete a systematic study of initial state radiation at hadron colliders. This study is essential because tt-bar is the main background for the Higgs boson and these processes are extremely sensitive to initial state radiation. Results of our initial state radiation study will be presented. We started this study at the new LHC Physics Center (LPC) located at Fermi National Accelerator Laboratory, and we are now completing the study at the University of Rochester.

Dam Failure Inundation Map Project

NASA Technical Reports Server (NTRS)

Johnson, Carl; Iokepa, Judy; Dahlman, Jill; Michaud, Jene; Paylor, Earnest (Technical Monitor)

2000-01-01

At the end of the first year, we remain on schedule. Property owners were identified and contacted for land access purposes. A prototype software package has been completed and was demonstrated to the Division of Land and Natural Resources (DLNR), National Weather Service (NWS) and Pacific Disaster Center (PDC). A field crew gathered data and surveyed the areas surrounding two dams in Waimea. (A field report is included in the annual report.) Data sensitivity analysis was initiated and completed. A user's manual has been completed. Beta testing of the software was initiated, but not completed. The initial TNK and property owner data collection for the additional test sites on Oahu and Kauai have been initiated.

Style preference survey: a report on the psychometric properties and a cross-validation experiment.

PubMed

Smith, Sherri L; Ricketts, Todd; McArdle, Rachel A; Chisolm, Theresa H; Alexander, Genevieve; Bratt, Gene

2013-02-01

Several self-report measures exist that target different aspects of outcomes for hearing aid use. Currently, no comprehensive questionnaire specifically assesses factors that may be important for differentiating outcomes pertaining to hearing aid style. The goal of this work was to develop the Style Preference Survey (SPS), a questionnaire aimed at outcomes associated with hearing aid style differences. Two experiments were conducted. After initial item development, Experiment 1 was conducted to refine the items and to determine its psychometric properties. Experiment 2 was designed to cross-validate the findings from the initial experiment. An observational design was used in both experiments. Participants who wore traditional, custom-fitted (TC) or open-canal (OC) style hearing aids from 3 mo to 3 yr completed the initial experiment. One-hundred and eighty-four binaural hearing aid users (120 of whom wore TC hearing aids and 64 of whom wore OC hearing aids) participated. A new sample of TC and OC users (n = 185) participated in the cross-validation experiment. Currently available self-report measures were reviewed to identify items that might differentiate between hearing aid styles, particularly preference for OC versus TC hearing aid styles. A total of 15 items were selected and modified from available self-report measures. An additional 55 items were developed through consensus of six audiologists for the initial version of the SPS. In the first experiment, the initial SPS version was mailed to 550 veterans who met the inclusion criteria. A total of 184 completed the SPS. Approximately three weeks later, a subset of participants (n = 83) completed the SPS a second time. Basic analyses were conducted to evaluate the psychometric properties of the SPS including subscale structure, internal consistency, test-retest reliability, and responsiveness. Based on the results of Experiment 1, the SPS was revised. A cross-validation experiment was then conducted using the revised version of the SPS to confirm the subscale structure, internal consistency, and responsiveness of the questionnaire in a new sample of participants. The final factor analysis led to the ultimate version of the SPS, which had a total of 35 items encompassing five subscales: (1) Feedback, (2) Occlusion/Own Voice Effects, (3) Localization, (4) Fit, Comfort, and Cosmetics, and (5) Ease of Use. The internal consistency of the total SPS (Cronbach's α = .92) and of the subscales (each Cronbach's α > .75) was high. Intraclass correlations (ICCs) showed that the test-retest reliability of the total SPS (ICC = .93) and of the subscales (each ICC > .80) also was high. TC hearing aid users had significantly poorer outcomes than OC hearing aid users on 4 of the 5 subscales, suggesting that the SPS largely is responsive to factors related to style-specific differences. The results suggest that the SPS has good psychometric properties and is a valid and reliable measure of outcomes related to style-specific, hearing aid preference. American Academy of Audiology.

Case finding and mental health services for children in the aftermath of the Oklahoma City bombing.

PubMed

Pfefferbaum, Betty; Sconzo, Guy M; Flynn, Brian W; Kearns, Lauri J; Doughty, Debby E; Gurwitch, Robin H; Nixon, Sara Jo; Nawaz, Shajitha

2003-01-01

The 1995 Oklahoma City bombing killed 168 people, including 19 children, and injured hundreds more. Children were a major focus of concern in the mental health response. Most services for them were delivered in the Oklahoma City Public Schools where approximately 40,000 students were enrolled at the time of the explosion. Middle and high school students in the Oklahoma City Public Schools completed a clinical assessment 7 weeks after the explosion. The responses of 2720 students were analyzed to explore predictors of posttraumatic stress symptomatology, functioning, and treatment contact. Posttraumatic stress symptomatology was associated with initial reaction to the incident and to bomb-related television exposure. Functional difficulty was associated with initial reaction and posttraumatic stress symptomatology. Only 5% of the students surveyed had received counseling. There was no relationship between posttraumatic stress symptomatology and counseling contact for students with the highest levels of posttraumatic stress. Implications for school-based services are discussed.

Predicting Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer with Textural Features Derived from Pretreatment 18F-FDG PET/CT Imaging.

PubMed

Beukinga, Roelof J; Hulshoff, Jan B; van Dijk, Lisanne V; Muijs, Christina T; Burgerhof, Johannes G M; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Slump, Cornelis H; Mul, Véronique E M; Plukker, John Th M

2017-05-01

Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUV max in 18 F-FDG PET/CT imaging. To improve the prediction of response, we constructed a model to predict complete response to nCRT in EC based on pretreatment clinical parameters and 18 F-FDG PET/CT-derived textural features. Methods: From a prospectively maintained single-institution database, we reviewed 97 consecutive patients with locally advanced EC and a pretreatment 18 F-FDG PET/CT scan between 2009 and 2015. All patients were treated with nCRT (carboplatin/paclitaxel/41.4 Gy) followed by esophagectomy. We analyzed clinical, geometric, and pretreatment textural features extracted from both 18 F-FDG PET and CT. The current most accurate prediction model with SUV max as a predictor variable was compared with 6 different response prediction models constructed using least absolute shrinkage and selection operator regularized logistic regression. Internal validation was performed to estimate the model's performances. Pathologic response was defined as complete versus incomplete response (Mandard tumor regression grade system 1 vs. 2-5). Results: Pathologic examination revealed 19 (19.6%) complete and 78 (80.4%) incomplete responders. Least absolute shrinkage and selection operator regularization selected the clinical parameters: histologic type and clinical T stage, the 18 F-FDG PET-derived textural feature long run low gray level emphasis, and the CT-derived textural feature run percentage. Introducing these variables to a logistic regression analysis showed areas under the receiver-operating-characteristic curve (AUCs) of 0.78 compared with 0.58 in the SUV max model. The discrimination slopes were 0.17 compared with 0.01, respectively. After internal validation, the AUCs decreased to 0.74 and 0.54, respectively. Conclusion: The predictive values of the constructed models were superior to the standard method (SUV max ). These results can be considered as an initial step in predicting tumor response to nCRT in locally advanced EC. Further research in refining the predictive value of these models is needed to justify omission of surgery. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: clinical and histologic outcomes.

PubMed

Serra-Guillén, Carlos; Nagore, Eduardo; Hueso, Luis; Traves, Victor; Messeguer, Francesc; Sanmartín, Onofre; Llombart, Beatriz; Requena, Celia; Botella-Estrada, Rafael; Guillén, Carlos

2012-04-01

Photodynamic therapy (PDT) and imiquimod are the treatments of choice for actinic keratosis (AK). As they have different mechanisms of action, it seems reasonable to assume that applying both treatments sequentially would be efficacious. We sought to determine which of these therapeutic modalities provides a better clinical and histologic response in patients with AK and whether sequential use of both was more efficacious than each separately. Patients were randomly assigned to one treatment group: group 1, PDT only; group 2, imiquimod only; or group 3, sequential use of PDT and imiquimod. The primary outcome measure was complete clinical response. Partial clinical response was defined as a reduction of more than 75% in the initial number of lesions. A complete clinicopathologic response was defined as lack of evidence of AK in the biopsy specimen. In all, 105 patients completed the study (group 1, 40 patients; group 2, 33 patients; group 3, 32 patients). Sequential application of PDT and imiquimod was more efficacious in all the outcome measures. More patients were satisfied with PDT than with the other two modalities (P = .003). No significant differences were observed among the 3 modalities and tolerance to treatment. Only one cycle of imiquimod was administered. The follow-up period was brief. Sequential application of PDT and imiquimod provides a significantly better clinical and histologic response in the treatment of AK than PDT or imiquimod monotherapy. It also produces less intense local reactions and better tolerance and satisfaction than imiquimod monotherapy. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry

PubMed Central

Maccari, Maria Elena; Abolhassani, Hassan; Aghamohammadi, Asghar; Aiuti, Alessandro; Aleinikova, Olga; Bangs, Catherine; Baris, Safa; Barzaghi, Federica; Baxendale, Helen; Buckland, Matthew; Burns, Siobhan O.; Cancrini, Caterina; Cant, Andrew; Cathébras, Pascal; Cavazzana, Marina; Chandra, Anita; Conti, Francesca; Coulter, Tanya; Devlin, Lisa A.; Edgar, J. David M.; Faust, Saul; Fischer, Alain; Garcia-Prat, Marina; Hammarström, Lennart; Heeg, Maximilian; Jolles, Stephen; Karakoc-Aydiner, Elif; Kindle, Gerhard; Kiykim, Ayca; Kumararatne, Dinakantha; Grimbacher, Bodo; Longhurst, Hilary; Mahlaoui, Nizar; Milota, Tomas; Moreira, Fernando; Moshous, Despina; Mukhina, Anna; Neth, Olaf; Neven, Benedicte; Nieters, Alexandra; Olbrich, Peter; Ozen, Ahmet; Schmid, Jana Pachlopnik; Picard, Capucine; Prader, Seraina; Rae, William; Reichenbach, Janine; Rusch, Stephan; Savic, Sinisa; Scarselli, Alessia; Scheible, Raphael; Sediva, Anna; Sharapova, Svetlana O.; Shcherbina, Anna; Slatter, Mary; Soler-Palacin, Pere; Stanislas, Aurelie; Suarez, Felipe; Tucci, Francesca; Uhlmann, Annette; van Montfrans, Joris; Warnatz, Klaus; Williams, Anthony Peter; Wood, Phil; Kracker, Sven; Condliffe, Alison Mary; Ehl, Stephan

2018-01-01

Activated phosphoinositide 3-kinase (PI3K) δ Syndrome (APDS), caused by autosomal dominant mutations in PIK3CD (APDS1) or PIK3R1 (APDS2), is a heterogeneous primary immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical and immunological manifestations, questions about long-term disease evolution and response to therapy remain. The prospective European Society for Immunodeficiencies (ESID)-APDS registry aims to characterize the disease course, identify outcome predictors, and evaluate treatment responses. So far, 77 patients have been recruited (51 APDS1, 26 APDS2). Analysis of disease evolution in the first 68 patients pinpoints the early occurrence of recurrent respiratory infections followed by chronic lymphoproliferation, gastrointestinal manifestations, and cytopenias. Although most manifestations occur by age 15, adult-onset and asymptomatic courses were documented. Bronchiectasis was observed in 24/40 APDS1 patients who received a CT-scan compared with 4/15 APDS2 patients. By age 20, half of the patients had received at least one immunosuppressant, but 2–3 lines of immunosuppressive therapy were not unusual before age 10. Response to rapamycin was rated by physician visual analog scale as good in 10, moderate in 9, and poor in 7. Lymphoproliferation showed the best response (8 complete, 11 partial, 6 no remission), while bowel inflammation (3 complete, 3 partial, 9 no remission) and cytopenia (3 complete, 2 partial, 9 no remission) responded less well. Hence, non-lymphoproliferative manifestations should be a key target for novel therapies. This report from the ESID-APDS registry provides comprehensive baseline documentation for a growing cohort that will be followed prospectively to establish prognostic factors and identify patients for treatment studies. PMID:29599784

Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry.

PubMed

Maccari, Maria Elena; Abolhassani, Hassan; Aghamohammadi, Asghar; Aiuti, Alessandro; Aleinikova, Olga; Bangs, Catherine; Baris, Safa; Barzaghi, Federica; Baxendale, Helen; Buckland, Matthew; Burns, Siobhan O; Cancrini, Caterina; Cant, Andrew; Cathébras, Pascal; Cavazzana, Marina; Chandra, Anita; Conti, Francesca; Coulter, Tanya; Devlin, Lisa A; Edgar, J David M; Faust, Saul; Fischer, Alain; Garcia-Prat, Marina; Hammarström, Lennart; Heeg, Maximilian; Jolles, Stephen; Karakoc-Aydiner, Elif; Kindle, Gerhard; Kiykim, Ayca; Kumararatne, Dinakantha; Grimbacher, Bodo; Longhurst, Hilary; Mahlaoui, Nizar; Milota, Tomas; Moreira, Fernando; Moshous, Despina; Mukhina, Anna; Neth, Olaf; Neven, Benedicte; Nieters, Alexandra; Olbrich, Peter; Ozen, Ahmet; Schmid, Jana Pachlopnik; Picard, Capucine; Prader, Seraina; Rae, William; Reichenbach, Janine; Rusch, Stephan; Savic, Sinisa; Scarselli, Alessia; Scheible, Raphael; Sediva, Anna; Sharapova, Svetlana O; Shcherbina, Anna; Slatter, Mary; Soler-Palacin, Pere; Stanislas, Aurelie; Suarez, Felipe; Tucci, Francesca; Uhlmann, Annette; van Montfrans, Joris; Warnatz, Klaus; Williams, Anthony Peter; Wood, Phil; Kracker, Sven; Condliffe, Alison Mary; Ehl, Stephan

2018-01-01

Activated phosphoinositide 3-kinase (PI3K) δ Syndrome (APDS), caused by autosomal dominant mutations in PIK3CD (APDS1) or PIK3R1 (APDS2), is a heterogeneous primary immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical and immunological manifestations, questions about long-term disease evolution and response to therapy remain. The prospective European Society for Immunodeficiencies (ESID)-APDS registry aims to characterize the disease course, identify outcome predictors, and evaluate treatment responses. So far, 77 patients have been recruited (51 APDS1, 26 APDS2). Analysis of disease evolution in the first 68 patients pinpoints the early occurrence of recurrent respiratory infections followed by chronic lymphoproliferation, gastrointestinal manifestations, and cytopenias. Although most manifestations occur by age 15, adult-onset and asymptomatic courses were documented. Bronchiectasis was observed in 24/40 APDS1 patients who received a CT-scan compared with 4/15 APDS2 patients. By age 20, half of the patients had received at least one immunosuppressant, but 2-3 lines of immunosuppressive therapy were not unusual before age 10. Response to rapamycin was rated by physician visual analog scale as good in 10, moderate in 9, and poor in 7. Lymphoproliferation showed the best response (8 complete, 11 partial, 6 no remission), while bowel inflammation (3 complete, 3 partial, 9 no remission) and cytopenia (3 complete, 2 partial, 9 no remission) responded less well. Hence, non-lymphoproliferative manifestations should be a key target for novel therapies. This report from the ESID-APDS registry provides comprehensive baseline documentation for a growing cohort that will be followed prospectively to establish prognostic factors and identify patients for treatment studies.

Phase II Trial of Full-Dose Gemcitabine and Bevacizumab in Combination With Attenuated Three-Dimensional Conformal Radiotherapy in Patients With Localized Pancreatic Cancer

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

Small, William, E-mail: wsmall@nmff.or; Mulcahy, Mary F.; Rademaker, Alfred

Purpose: To evaluate response rate, survival, and toxicity in patients with nonmetastatic pancreatic cancer treated with gemcitabine, bevacizumab, and radiotherapy. Methods and Materials: Patients received three cycles of therapy over 10 weeks. In total, treatment consisted of intravenous (IV) gemcitabine, 1,000 mg/m{sup 2}, every 1 to 2 weeks (7 doses), IV bevacizumab, 10 mg/kg every 2 weeks (5 doses), and 36 Gy of radiotherapy (2.4-Gy fractions during cycle two). Response was assessed by cross-sectional imaging and carbohydrate antigen 19-9 (CA 19-9) levels. Patients with resectable tumors underwent surgery 6 to 8 weeks after the last dose of bevacizumab. Maintenance gemcitabinemore » and bevacizumab doses were delivered to patients who had unresected tumors and no progression. Results: Twenty-eight of the 32 enrolled patients completed all three cycles. The median follow-up was 11.07 months. Most grade 3 or 4 toxicities occurred in the initial treatment phase; the most frequent toxicities were leukopenia (21%), neutropenia (17%), and nausea (17%). At week 10, 1 patient (4%) had a complete response, 2 patients (7%) had partial responses, 21 patients (75%) had stable disease, and 4 patients (14%) had progressive disease. The median pretreatment and posttreatment CA 19-9 levels (25 patients) were 184.3 and 57.9 U/ml, respectively (p = 0.0006). One of 10 patients proceeding to surgery experienced a major complication. Two of 6 patients undergoing resection had complete pathologic responses. The median progression-free and overall survival durations were 9.9 months and 11.8 months, respectively. Conclusions: The combination of full-dose gemcitabine, bevacizumab, and radiotherapy was active and was not associated with a high rate of major surgical complications.« less

Imaging the Spatio-Temporal Dynamics of Supragranular Activity in the Rat Somatosensory Cortex in Response to Stimulation of the Paws

PubMed Central

Morales-Botello, M. L.; Aguilar, J.; Foffani, G.

2012-01-01

We employed voltage-sensitive dye (VSD) imaging to investigate the spatio-temporal dynamics of the responses of the supragranular somatosensory cortex to stimulation of the four paws in urethane-anesthetized rats. We obtained the following main results. (1) Stimulation of the contralateral forepaw evoked VSD responses with greater amplitude and smaller latency than stimulation of the contralateral hindpaw, and ipsilateral VSD responses had a lower amplitude and greater latency than contralateral responses. (2) While the contralateral stimulation initially activated only one focus, the ipsilateral stimulation initially activated two foci: one focus was typically medial to the focus activated by contralateral stimulation and was stereotaxically localized in the motor cortex; the other focus was typically posterior to the focus activated by contralateral stimulation and was stereotaxically localized in the somatosensory cortex. (3) Forepaw and hindpaw somatosensory stimuli activated large areas of the sensorimotor cortex, well beyond the forepaw and hindpaw somatosensory areas of classical somatotopic maps, and forepaw stimuli activated larger cortical areas with greater activation velocity than hindpaw stimuli. (4) Stimulation of the forepaw and hindpaw evoked different cortical activation dynamics: forepaw responses displayed a clear medial directionality, whereas hindpaw responses were much more uniform in all directions. In conclusion, this work offers a complete spatio-temporal map of the supragranular VSD cortical activation in response to stimulation of the paws, showing important somatotopic differences between contralateral and ipsilateral maps as well as differences in the spatio-temporal activation dynamics in response to forepaw and hindpaw stimuli. PMID:22829873

Circulating endothelial cells and their progenitors in acute myeloid leukemia

PubMed Central

Zahran, Asmaa Mohammed; Aly, Sanaa Shaker; Altayeb, Hanan Ahmed; Ali, Arwa Mohammed

2016-01-01

Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by the accumulation of immature myeloid progenitor cells in the bone marrow. Studies are required to investigate the prognostic and predictive value of surrogate biomarkers. Given the importance of angiogenesis in oncology in terms of pathogenesis as well as being a target for treatment, circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) are promising candidates to serve as such markers. The aim of the present study was to quantify CECs and EPCs in patients with AML at initial diagnosis and following induction chemotherapy, and to correlate these findings with the response to treatment in AML patients. The present study included 40 patients with de novo AML and 20 age- and gender-matched healthy controls. CECs and EPCs were evaluated by flow cytometry at initial diagnosis and after induction chemotherapy (3+7 protocol for AML other than M3 and all-trans-retinoic acid plus anthracycline for M3 disease). CECs and EPCs were significantly higher in AML patients at diagnosis and after induction chemotherapy than in controls. After induction chemotherapy, CECs and EPCs were significantly decreased compared with the levels at initial diagnosis. Patients who achieved complete response (n=28) had lower initial CEC and EPC levels compared with patients who did not respond to treatment. These results suggest that CEC levels are higher in AML patients and may correlate with disease status and treatment response. Further investigations are required to better determine the predictive value and implication of these cells in AML management. PMID:27602121

EDTA a novel inducer of pisatin, a phytoalexin indicator of the non-host resistance in peas.

PubMed

Hadwiger, Lee A; Tanaka, Kiwamu

2014-12-23

Pea pod endocarp suppresses the growth of an inappropriate fungus or non-pathogen by generating a "non-host resistance response" that completely suppresses growth of the challenging fungus within 6 h. Most of the components of this resistance response including pisatin production can be elicited by an extensive number of both biotic and abiotic inducers. Thus this phytoalexin serves as an indicator to be used in evaluating the chemical properties of inducers that can initiate the resistance response. Many of the pisatin inducers are reported to interact with DNA and potentially cause DNA damage. Here we propose that EDTA (ethylenediaminetetraacetic acid) is an elicitor to evoke non-host resistance in plants. EDTA is manufactured as a chelating agent, however at low concentration it is a strong elicitor, inducing the phytoalexin pisatin, cellular DNA damage and defense-responsive genes. It is capable of activating complete resistance in peas against a pea pathogen. Since there is also an accompanying fragmentation of pea DNA and alteration in the size of pea nuclei, the potential biochemical insult as a metal chelator may not be its primary action. The potential effects of EDTA on the structure of DNA within pea chromatin may assist the transcription of plant defense genes.

In vivo quantification of response to treatment in patients with multiple myeloma by 1H magnetic resonance spectroscopy of bone marrow.

PubMed

Oriol, Albert; Valverde, Daniel; Capellades, Jaume; Cabañas, Miquel E; Ribera, Josep-Maria; Arús, Carles

2007-04-01

Magnetic resonance imaging (MRI) is the gold standard non-invasive technique to detect malignant disease in the bone marrow. Proton magnetic resonance spectroscopy (MRS) can be performed as a quick adjunct to routine spinal MRI. We performed proton MRS to patients with multiple myeloma (MM) at diagnosis and after treatment to investigate the possible correlation of MRS data with response to therapy. Twenty-one patients with newly diagnosed MM underwent combined MRI/MRS explorations of a transverse center section in the fifth lumbar vertebral body. MRS was acquired with STEAM and 40 ms TE. Areas of unsuppressed water and lipid resonances were used to calculate the lipid-to-water ratio (LWR). No association was detected between initial LWRs and the clinical characteristics of patients. Post treatment MRS was available in 16 patients of whom 11 (69%) presented an LWR increase, this included all complete responders (8/8, 100%, P = 0.012). A post-treatment LWR value equal to or larger than one is proposed as a non-invasive marker of complete response to treatment. Only patients responding to treatment presented a significant increase in bone marrow LWR after therapy. MRS may provide an adequate quantification of response to chemotherapy in patients with MM.

Group hypnotherapy for irritable bowel syndrome with long-term follow-up.

PubMed

Gerson, Charles D; Gerson, Jessica; Gerson, Mary-Joan

2013-01-01

This study tested whether group gut-focused hypnotherapy would improve irritable bowel syndrome (IBS). Several possible outcome predictors were also studied. Before treatment, 75 patients completed a Symptom Severity Scale, a Mind-Body attribution questionnaire, and a Quality of Relationship Inventory (QRI). The symptom scale was completed posttreatment, 3, 6, and 12 months later. There was significant symptom reduction at each data point (p < .001). Sixty percent had a reduction of more than 50 points, indicative of clinical improvement. Initial severity score (p = .0004) and QRI conflict (p = .057) were directly correlated with a response to hypnotherapy, while attribution of symptoms to mind (emotional) causation was inversely correlated (p = .0056). The authors conclude that group hypnotherapy is effective in patients with IBS.

Catheter-Directed Thrombolysis of Lower Limb Thrombosis

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

Pianta, Marcus J.; Thomson, Kenneth R., E-mail: k.thomson@alfred.org.au

2011-02-15

Late complications of thrombosis of the deep veins in the region between the popliteal vein termination and the confluence of the common iliac veins and inferior vena cava (suprapopliteal deep-vein thrombosis) are common and often unrecognized by those responsible for the initial management. Pharmacomechanical-assisted clearance of the thrombus at the time of first presentation provides the best opportunity for complete recovery with preservation of normal venous valve function and avoidance of recurrent deep-vein thrombosis and postthrombotic syndrome. Recent interventional radiology methods provide for rapid and complete thrombolysis even in some patients in whom thrombolysis was previously considered contraindicated. This reviewmore » describes the methods, safety, and efficacy of acute interventional treatment of suprapopliteal deep-vein thrombosis.« less

Plasma sterilization of Geobacillus Stearothermophilus by O{mathsf2}:N{mathsf2} RF inductively coupled plasma

NASA Astrophysics Data System (ADS)

Kylián, O.; Sasaki, T.; Rossi, F.

2006-05-01

The aim of this work is to identify the main process responsible for sterilization of Geobacillus Stearothermophilus spores in O{2}:N{2} RF inductively coupled plasma. In order to meet this objective the sterilization efficiencies of discharges in mixtures differing in the initial O{2}/N{2} ratios are compared with plasma properties and with scanning electron microscopy images of treated spores. According to the obtained results it can be concluded that under our experimental conditions the time needed to reach complete sterilization is more related to O atom density than UV radiation intensity, i.e. complete sterilization is not related only to DNA damage as in UV sterilization but more likely to the etching of the spore.

A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged

PubMed Central

Nacionales, Dina C.; Szpila, Benjamin; Ungaro, Ricardo; Lopez, M. Cecilia; Zhang, Jianyi; Gentile, Lori F.; Cuenca, Angela L.; Vanzant, Erin; Mathias, Brittany; Jyot, Jeevan; Westerveld, Donevan; Bihorac, Azra; Joseph, Anna; Mohr, Alicia; Duckworth, Lizette V.; Moore, Frederick A.; Baker, Henry V.; Leeuwenburgh, Christiaan; Moldawer, Lyle L.; Brakenridge, Scott; Efron, Philip A.

2015-01-01

The elderly are particularly susceptible to trauma, and their outcomes are frequently dismal. Such patients often have complicated clinical courses and ultimately die from infection and sepsis. Recent research has revealed that although elderly subjects have increased baseline inflammation as compared to their younger counterparts, the elderly do not respond to severe infection/injury with an exaggerated inflammatory response. Initial retrospective analysis of clinical data from the Glue Grant trauma database demonstrated that despite a similar frequency, elderly trauma patients have worse outcomes to pneumonia than younger subjects. Subsequent analysis with a murine trauma model also demonstrated that elderly mice had increased mortality after post-trauma Pseudomonas pneumonia. Blood, bone marrow, and bronchoalveolar lavage sample analyses from juvenile and 20–24 month old mice showed that increased mortality to trauma combined with secondary infection in the aged are not due to an exaggerated inflammatory response. Rather, they are due to a failure of bone marrow progenitors, blood neutrophils, and bronchoalveolar lavage cells to initiate and complete an ‘emergency myelopoietic’ response, engendering myeloid cells that fail to clear secondary infection. In addition, the elderly appeared unable to effectively resolve their inflammatory response to severe injury. PMID:26246141

Thoracic Epidural Anesthesia Can Be Effective for the Short-Term Management of Ventricular Tachycardia Storm.

PubMed

Do, Duc H; Bradfield, Jason; Ajijola, Olujimi A; Vaseghi, Marmar; Le, John; Rahman, Siamak; Mahajan, Aman; Nogami, Akihiko; Boyle, Noel G; Shivkumar, Kalyanam

2017-10-27

Novel therapies aimed at modulating the autonomic nervous system, including thoracic epidural anesthesia (TEA), have been shown in small case series to be beneficial in treating medically refractory ventricular tachycardia (VT) storm. However, it is not clear when these options should be considered. We reviewed a multicenter experience with TEA in the management of VT storm to determine its optimal therapeutic use. Data for 11 patients in whom TEA was instituted for VT storm between July 2005 and March 2016 were reviewed to determine the clinical characteristics, outcomes, and role in management. The clinical presentation was incessant VT in 7 (64%), with polymorphic VT in 3 (27%) and monomorphic VT in 8 (73%). The underlying conditions were nonischemic cardiomyopathy in 5 (45%), ischemic cardiomyopathy in 3 (27%), and hypertrophic cardiomyopathy, Brugada syndrome, and cardiac lipoma in 1 (9%) each. Five (45%) had a complete and 1 (9%) had a partial response to TEA; 4 of the complete responders had incessant VT. All 4 patients with a documented response to deep sedation demonstrated a complete response to TEA. More than half of the patients with VT storm in our series responded to TEA. TEA may be effective and should be considered as a therapeutic option in patients with VT storm, especially incessant VT, who are refractory to initial management. Improvement in VT burden with deep sedation may suggest that sympathoexcitation plays a key role in perpetuating VT and predict a positive response to TEA. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The Efficacy of Radiotherapy in the Treatment of Orbital Pseudotumor

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

Matthiesen, Chance, E-mail: chance-matthiesen@ouhsc.ed; Bogardus, Carl; Thompson, J. Spencer

Purpose: To review institutional outcomes for patients treated with external-beam radiotherapy (EBRT) for orbital pseudotumor. Methods and Materials: This is a single-institution retrospective review of 20 orbits in 16 patients diagnosed with orbital pseudotumor that received EBRT at the University of Oklahoma, Department of Radiation Oncology. Treated patients had a median follow-up of 16.5 months. Results: Fifteen patients (93.7%) were initially treated with corticosteroids. Eight had recurrence after steroid cessation, six were unable to taper corticosteroids completely or partially, and one experienced progression of symptoms despite corticosteroid therapy. Fourteen patients (87.5%) initially responded to radiotherapy indicated by clinical improvement ofmore » preradiation symptoms and/or tapering of corticosteroid dose. Mean EBRT dose was 20 Gy (range, 14-30 Gy). Thirteen patients (81.2%) continued to improve after radiation therapy. Patient outcomes were complete cessation of corticosteroid therapy in nine patients (56.3%) and reduced corticosteroid dose in four patients (25%). Radiotherapy did not achieve long-term control for three patients (18.7%), who still required preradiation corticosteroid dosages. Three patients received retreatment(s) of four orbits, of which two patients achieved long-term symptom control without corticosteroid dependence. One patient received retreatment to an orbit three times, achieving long-term control without corticosteroid dependence. No significant late effects have been observed in retreated patients. Conclusions: Radiotherapy is an effective treatment for acute symptomatic improvement and long-term control of orbital pseudotumor. Orbital retreatment can be of clinical benefit, without apparent increase in morbidity, when initial irradiation fails to achieve complete response.« less

Predictors of Human Papillomavirus Vaccine Completion Among Female and Male Vaccine Initiators in Family Planning Centers.

PubMed

Simons, Hannah R; Unger, Zoe D; Lopez, Priscilla M; Kohn, Julia E

2015-12-01

We estimated human papillomavirus (HPV) vaccine series completion and examined predictors of completion among adolescents and young adults in a large family planning network. Our retrospective cohort study of vaccine completion within 12 months and time to completion used electronic health record data from 119 Planned Parenthood health centers in 11 US states for 9648 patients who initiated HPV vaccination between January 2011 and January 2013. Among vaccine initiators, 29% completed the series within 12 months. Patients who were male, younger than 22 years, or non-Hispanic Black or who had public insurance were less likely to complete within 12 months and completed more slowly than their counterparts. Gender appeared to modify the effect of public versus private insurance on completion (adjusted hazard ratio = 0.76 for women and 0.95 for men; relative excess risk due to interaction = 0.41; 95% confidence interval = 0.09, 0.73). Completion was low yet similar to previous studies conducted in safety net settings.

Pediatric Dentistry in Primary Healthcare: Creation, Development, and Evaluation of a Distance Education Course.

PubMed

Bavaresco, Caren Serra; Bragança, Silvana Gonçalves; D'Avila, Otávio Pereira; Umpierre, Roberto; Harzheim, Erno; Rodrigues, Jonas Almeida

2018-01-02

Oral health in childhood is a major problem for global public health. In Brazil, the prevalence of childhood tooth decay varies from 12% to 46%. Dental care treatment in Brazil is almost the exclusive responsibility of primary healthcare (PHC). Therefore, it is essential these professionals are prepared to conduct restorative, endodontic, and exodontic treatments and preventive care in children. Children make up a large proportion of the population in territories requiring advanced dental care provided by PHC in Brazil. To care for these patients, it is necessary to have both manual dexterity and technical knowledge of pediatric dentistry. Accordingly, this study aimed to develop a distance course on pediatric dentistry. A pretest questionnaire consisting of 15 questions was used to assess initial dental knowledge of participants. After completion of a five-module course, participants retook the same initial dental knowledge questionnaire (post-test). Descriptive statistic and paired t test, one-way analysis of variance, and Pearson and Spearman correlation were used, and a significance level of 5% was set. The majority of participants completing the five-module course were women who earned specialty degrees beyond undergraduate studies and currently worked in PHC (>5 years). Participant performance on the dental knowledge questionnaire after completion of the five-module course improved pre- to post-test. These data suggest that completion of a distance course on pediatric dentistry can be an effective tool for improving knowledge of pediatric dentistry in PHC professionals.

Assuring dental hygiene clinical competence for licensure: a national survey of dental hygiene program directors.

PubMed

Fleckner, Lucinda M; Rowe, Dorothy J

2015-02-01

To conduct a national survey of dental hygiene program directors to gain their opinions of alternative assessments of clinical competency, as qualifications for initial dental hygiene licensure. A 22 question survey, comprised of statements eliciting Likert-scale responses, was developed and distributed electronically to 341 U.S. dental hygiene program directors. Responses were tabulated and analyzed using University of California, San Francisco Qualtrics® computer software. Data were summarized as frequencies of responses to each item on the survey. The response rate was 42% (n=143). The majority of respondents (65%) agreed that graduating from a Commission on Dental Accreditation (CODA)-approved dental hygiene program and passing the national board examination was the best measure to assure competence for initial licensure. The addition of "successfully completing all program's competency evaluations" to the above core qualifications yielded a similar percentage of agreement. Most (73%) agreed that "the variability of live patients as test subjects is a barrier to standardizing the state and regional examinations," while only 29% agreed that the "use of live patients as test subjects is essential to assure competence for initial licensure." The statement that the one-time state and regional examinations have "low validity in reflecting the complex responsibilities of the dental hygienist in practice" had a high (77%) level of agreement. Most dental hygiene program directors agree that graduating from a CODA-approved dental hygiene program and passing the national board examination would ensure that a graduate has achieved clinical competence and readiness to provide comprehensive patient-centered care as a licensed dental hygienist. Copyright © 2015 The American Dental Hygienists’ Association.

Development of NRC inspection procedure 38703: Commercial-grade dedication

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

Potapovs, U.; Pettis, R.L. Jr.

1994-12-31

The purpose of this paper is to present an overview of the recently completed U.S. Nuclear Regulatory Commission (NRC) inspection procedure 38703, {open_quotes}Commercial Grade Dedication,{close_quotes} which was issued on November 8, 1993. This procedure embodies the information gained from the NRC`s inspections and assessments of licensee procurement practices, a public workshop, industry feedback and public comments, and the NRC`s perspective of the industry`s response to the Nuclear Management and Resource Council (NUMARC) procurement initiatives.

Design of a modular digital computer system DRL 4 and 5. [design of airborne/spaceborne computer system

NASA Technical Reports Server (NTRS)

1973-01-01

Design and development efforts for a spaceborne modular computer system are reported. An initial baseline description is followed by an interface design that includes definition of the overall system response to all classes of failure. Final versions for the register level designs for all module types were completed. Packaging, support and control executive software, including memory utilization estimates and design verification plan, were formalized to insure a soundly integrated design of the digital computer system.

Tailoring the Systems Engineering Technical Review Implementation Within Naval Acquisition

DTIC Science & Technology

2017-09-01

additional feedback regarding SETR implementations. Free Text N/A 40 B. SURVEY DATA (1) Question 1 Figure 12 provides the results to the initial...instruction. The complete set of responses provided in the free text field—”Other (please specify)”—are included in Appendix B. Figure 13. Question 2...provided in the free text field— ”Other (please specify)”—are included in Appendix B. Figure 14. Question 3 Survey Results 43 (4) Question 4

Army Needs to Improve the Reliability of the Spare Parts Forecasts It Submits to the Defense Logistics Agency

DTIC Science & Technology

2014-09-29

In response to this finding, AMC is initiating a Depot Material Requirements Planning ( MRP ) Integrated Process Team (IPT) from which one objective...methodologies for DOF reviews and corrective actions by AMC and its component organizations. The target completion date for the Depot MRP IPT is June...implemented a matrix for MRP SOW where the aviation programs were updated in Production LMP 1QFY14. Army Materiel Command (cont’d) Management

Dynamic stability and handling qualities tests on a highly augmented, statically unstable airplane

NASA Technical Reports Server (NTRS)

Gera, Joseph; Bosworth, John T.

1987-01-01

Initial envelope clearance and subsequent flight testing of a new, fully augmented airplane with an extremely high degree of static instability can place unusual demands on the flight test approach. Previous flight test experience with these kinds of airplanes is very limited or nonexistent. The safe and efficient flight testing may be further complicated by a multiplicity of control effectors that may be present on this class of airplanes. This paper describes some novel flight test and analysis techniques in the flight dynamics and handling qualities area. These techniques were utilized during the initial flight envelope clearance of the X-29A aircraft and were largely responsible for the completion of the flight controls clearance program without any incidents or significant delays.

Equipment. [for testing human space perception

NASA Technical Reports Server (NTRS)

1974-01-01

A discussion is presented on the problems encountered in designing and constructing a simulator to determine human vestibular response to a range of linear accelerations from 0 to 0.3 g's. Starting with a set of initial performance specifications, the designers combined an array of commercially available components into a system which, altough requiring further refinement before completion, shows considerable promise of fulfilling the initial requirements. The resulting system consists of a wheeled vehicle driven by a cable and drum arrangement, powered by a hydraulic-electric servo-valve. Technical design considerations are presented along with a discussion of the trade-offs between various component options. A description of the system characteristics as well as an analysis of preliminary test results and recommendations for future system improvements are included.

Performance characteristics and statistics of a laser initiated microdetonator

NASA Technical Reports Server (NTRS)

Yang, L. C.

1979-01-01

The test results of 320 units of the laser initiated microdetonator are summarized. The commercially fabricated units used a lead styphnate/lead azide/HMX (1 mg/17.5 mg/13.5 mg) explosive train design contained in a miniature aluminum can and completed with a glass-metal seal window. The test parameters were the high and low laser energy, high and low temperature, laser pulse duration, laser wavelength and nuclear radiation (5 x 10 to the 6th rads of 1 MeV gamma ray). The performance parameters were the laser energy for ignition and the actuation response time. Included also is a description of the development of a flexible, continuously advanced train of explosive devices by using the units, miniature optics and fiber optics.

NPY/AgRP neurons are not essential for feeding responses to glucoprivation.

PubMed

Luquet, Serge; Phillips, Colin T; Palmiter, Richard D

2007-02-01

Animals respond to hypoglycemia by eating and by stimulating gluconeogenesis. These responses to glucose deprivation are initiated by glucose-sensing neurons in the brain, but the neural circuits that control feeding behavior are not well established. Neurons in the arcuate region of the hypothalamus that express neuropeptide Y (NPY) and agouti-related protein (AgRP) have been implicated in mediating the feeding response to glucoprivation. We devised a method to selectively ablate these neurons in neonatal mice and then tested adult mice for their feeding responses to fasting, mild hypoglycemia, 2-deoxy-d-glucose and a ghrelin receptor agonist. Whereas the feeding response to the ghrelin receptor agonist was completely abrogated, the feeding response to glucoprivation was normal. The feeding response after a fast was attenuated when standard chow was available but normal with more palatable solid or liquid diet. We conclude that NPY/AgRP neurons are not necessary for generating or mediating the orexigenic response to glucose deficiency, but they are essential for the feeding response to ghrelin and refeeding on standard chow after a fast.

Infectious Disease Surveillance in the 21st Century: An Integrated Web-Based Surveillance and Case Management System

PubMed Central

Haney, Gillian; Cocoros, Noelle; Cranston, Kevin; DeMaria, Alfred

2014-01-01

The Massachusetts Virtual Epidemiologic Network (MAVEN) was deployed in 2006 by the Massachusetts Department of Public Health, Bureau of Infectious Disease to serve as an integrated, Web-based disease surveillance and case management system. MAVEN replaced program-specific, siloed databases, which were inaccessible to local public health and unable to integrate electronic reporting. Disease events are automatically created without human intervention when a case or laboratory report is received and triaged in real time to state and local public health personnel. Events move through workflows for initial notification, case investigation, and case management. Initial development was completed within 12 months and recent state regulations mandate the use of MAVEN by all 351 jurisdictions. More than 300 local boards of health are using MAVEN, there are approximately one million events, and 70 laboratories report electronically. MAVEN has demonstrated responsiveness and flexibility to emerging diseases while also streamlining routine surveillance processes and improving timeliness of notifications and data completeness, although the long-term resource requirements are significant. PMID:24587547

L1C signal design options

USGS Publications Warehouse

Betz, J.W.; Cahn, C.R.; Dafesh, P.A.; Hegarty, C.J.; Hudnut, K.W.; Jones, A.J.; Keegan, R.; Kovach, K.; Lenahan, L.S.; Ma, H.H.; Rushanan, J.J.; Stansell, T.A.; Wang, C.C.; Yi, S.K.

2006-01-01

Design activities for a new civil signal centered at 1575.42 MHz, called L1C, began in 2003, and the Phase 1 effort was completed in 2004. The L1C signal design has evolved and matured during a Phase 2 design activity that began in 2005. Phase 2 has built on the initial design activity, guided by responses to international user surveys conducted during Phase 1. A common core of signal characteristics has been developed to provide advances in robustness and performance. The Phase 2 activity produced five design options, all drawing upon the core signal characteristics, while representing different blends of characteristics and capabilities. A second round of international user surveys was completed to solicit advice concerning these design options. This paper provides an update of the L1C design process, and describes the current L1C design options. Initial performance estimates are presented for each design option, displaying trades between signal tracking robustness, the speed and robustness of clock and ephemeris data, and the rate and robustness of other data message contents. Planned remaining activities are summarized, leading to optimization of the L1C design.

Anti-myelin antibodies play an important role in the susceptibility to develop proteolipid protein-induced experimental autoimmune encephalomyelitis

PubMed Central

Marín, N; Eixarch, H; Mansilla, M J; Rodríguez-Martín, E; Mecha, M; Guaza, C; Álvarez-Cermeño, J C; Montalban, X; Villar, L M; Espejo, C

2014-01-01

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is an autoimmune disorder in which activated T cells cross the blood–brain barrier (BBB) to initiate an inflammatory response that leads to demyelination and axonal damage. The key mechanisms responsible for disease initiation are still unknown. We addressed this issue in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. It is widely known that EAE manifests only in certain strains when immunized with myelin proteins or peptides. We studied the differential immune responses induced in two mouse strains that are susceptible or resistant to EAE induction when they are immunized with the 139–151 peptide of proteolipid protein, an encephalitogenic peptide capable of inducing EAE in the susceptible strain. The adequate combination of major histocompatibility complex alleles and myelin peptides triggered in susceptible mice a T helper type 17 (Th17) response capable of inducing the production of high-affinity anti-myelin immunoglobulin (Ig)G antibodies. These were not detected in resistant mice, despite immunization with the encephalitogenic peptide in junction with complete Freund's adjuvant and pertussis toxin, which mediate BBB disruption. These data show the pivotal role of Th17 responses and of high-affinity anti-myelin antibodies in EAE induction and that mechanisms that prevent their appearance can contribute to resistance to EAE. PMID:24188195

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

Stoiber, Marcus; Celniker, Susan; Cherbas, Lucy

Steroid hormones induce cascades of gene activation and repression with transformative effects on cell fate . Steroid transduction plays a major role in the development and physiology of nearly all metazoan species, and in the progression of the most common forms of cancer. Despite the paramount importance of steroids in developmental and translational biology, a complete map of transcriptional response has not been developed for any hormone . In the case of 20-hydroxyecdysone (ecdysone) in Drosophila melanogaster, these trajectories range from apoptosis to immortalization. We mapped the ecdysone transduction network in a cohort of 41 cell lines, the largest suchmore » atlas yet assembled. We found that the early transcriptional response mirrors the distinctiveness of physiological origins: genes respond in restricted patterns, conditional on the expression levels of dozens of transcription factors. Only a small cohort of genes is constitutively modulated independent of initial cell state. Ecdysone-responsive genes tend to organize into directional same-stranded units, with consecutive genes induced from the same strand. Here, we identify half of the ecdysone receptor heterodimer as the primary rate-limiting step in the response, and find that initial receptor isoform levels modulate the activated cohort of target transcription factors. In conclusion, this atlas of steroid response reveals organizing principles of gene regulation by a model type II nuclear receptor and lays the foundation for comprehensive and predictive understanding of the ecdysone transduction network in the fruit fly.« less

A two-phase sampling survey for nonresponse and its paradata to correct nonresponse bias in a health surveillance survey.

PubMed

Santin, G; Bénézet, L; Geoffroy-Perez, B; Bouyer, J; Guéguen, A

2017-02-01

The decline in participation rates in surveys, including epidemiological surveillance surveys, has become a real concern since it may increase nonresponse bias. The aim of this study is to estimate the contribution of a complementary survey among a subsample of nonrespondents, and the additional contribution of paradata in correcting for nonresponse bias in an occupational health surveillance survey. In 2010, 10,000 workers were randomly selected and sent a postal questionnaire. Sociodemographic data were available for the whole sample. After data collection of the questionnaires, a complementary survey among a random subsample of 500 nonrespondents was performed using a questionnaire administered by an interviewer. Paradata were collected for the complete subsample of the complementary survey. Nonresponse bias in the initial sample and in the combined samples were assessed using variables from administrative databases available for the whole sample, not subject to differential measurement errors. Corrected prevalences by reweighting technique were estimated by first using the initial survey alone and then the initial and complementary surveys combined, under several assumptions regarding the missing data process. Results were compared by computing relative errors. The response rates of the initial and complementary surveys were 23.6% and 62.6%, respectively. For the initial and the combined surveys, the relative errors decreased after correction for nonresponse on sociodemographic variables. For the combined surveys without paradata, relative errors decreased compared with the initial survey. The contribution of the paradata was weak. When a complex descriptive survey has a low response rate, a short complementary survey among nonrespondents with a protocol which aims to maximize the response rates, is useful. The contribution of sociodemographic variables in correcting for nonresponse bias is important whereas the additional contribution of paradata in correcting for nonresponse bias is questionable. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Second-order schedules: discrimination of components1

PubMed Central

Squires, Nancy; Norborg, James; Fantino, Edmund

1975-01-01

Pigeons were exposed to a series of second-order schedules in which the completion of a fixed number of fixed-interval components produced food. In Experiment 1, brief (2 sec) stimulus presentations occurred as each fixed-interval component was completed. During the brief-stimulus presentation terminating the last fixed-interval component, a response was required on a second key, the brief-stimulus key, to produce food. Responses on the brief-stimulus key before the last brief-stimulus presentation had no scheduled consequences, but served as a measure of the extent to which the final component was discriminated from preceding components. Whether there were one, two, four, or eight fixed-interval components, responses on the brief-stimulus key occurred during virtually every brief-stimulus presentation. In Experiment 2, an attempt was made to punish unnecessary responses on the brief-stimulus key, i.e., responses on the brief-stimulus key that occurred before the last component. None of the pigeons learned to withhold these responses, even though they produced a 15-sec timeout and loss of primary reinforcement. In Experiment 3, different key colors were associated with each component of a second-order schedule (a chain schedule). In contrast to Experiment 1, brief-stimulus key responses were confined to the last component. It was concluded that pigeons do not discriminate well between components of second-order schedules unless a unique exteroceptive cue is provided for each component. The relative discriminability of the components may account for the observed differences in initial-component response rates between comparable brief-stimulus, tandem, and chain schedules. PMID:16811868

Managing an Online Survey about Influenza Vaccination in Primary Healthcare Workers

PubMed Central

Toledo, Diana; Aerny, Nicole; Soldevila, Núria; Baricot, Maretva; Godoy, Pere; Castilla, Jesús; García-Gutierrez, Susana; Torner, Núria; Astray, Jenaro; Mayoral, José María; Tamames, Sonia; González-Candelas, Fernando; Martín, Vicente; Díaz, José; Domíguez, Angela

2015-01-01

Online surveys are increasingly used due to their speed and efficiency. The aim of this study was to analyze factors that may have contributed to the quality and speed of response of an online survey on influenza vaccination in primary healthcare workers. A multicenter study including family physicians, nurses and pediatricians from primary healthcare teams from seven Spanish Autonomous Communities was designed. The centers were selected by simple random sampling. The survey remained active and accessible for 56 days and four reminders were sent. The odds ratios (OR) and their 95% confidence intervals (CI) were calculated to assess the association of sociodemographic variables and responding to the survey before the second reminder. Complete, validated information was obtained from 1965 primary healthcare workers. The total response rate was 36.2%. More nurses (46.3%) responded before the second reminder and more family physicians (52.8%) after the second reminder. The adjusted OR shows that family physicians responded later (AOR 1.46, 95% CI 1.2–1.8) than nurses. The responses obtained in the first 24 h after the initial sending and the reminders accounted for 41.7% of the completed surveys, indicating the importance of reminders. PMID:25584421

Transient inflammatory response mediated by interleukin-1β is required for proper regeneration in zebrafish fin fold.

PubMed

Hasegawa, Tomoya; Hall, Christopher J; Crosier, Philip S; Abe, Gembu; Kawakami, Koichi; Kudo, Akira; Kawakami, Atsushi

2017-02-23

Cellular responses to injury are crucial for complete tissue regeneration, but their underlying processes remain incompletely elucidated. We have previously reported that myeloid-defective zebrafish mutants display apoptosis of regenerative cells during fin fold regeneration. Here, we found that the apoptosis phenotype is induced by prolonged expression of interleukin 1 beta ( il1b ). Myeloid cells are considered to be the principal source of Il1b, but we show that epithelial cells express il1b in response to tissue injury and initiate the inflammatory response, and that its resolution by macrophages is necessary for survival of regenerative cells. We further show that Il1b plays an essential role in normal fin fold regeneration by regulating expression of regeneration-induced genes. Our study reveals that proper levels of Il1b signaling and tissue inflammation, which are tuned by macrophages, play a crucial role in tissue regeneration.

Dental care as a vital service response for disaster victims.

PubMed

Mosca, Nicholas G; Finn, Emanuel; Joskow, Renée

2007-05-01

Hurricane Katrina's impact on the infrastructure of public health and the health care system in the affected areas was unprecedented in the United States. Many dental offices were flood-bound in New Orleans and over 60% of dental practices were partially or completely damaged in affected counties in Mississippi. Most needs assessments conducted during the initial recovery operations did not include questions about access to oral health care. However, the extent of the destruction of the health care infrastructure demonstrated the need for significant state and federal support to make dental treatment accessible to survivors and evacuees. The Katrina response is one of the few times that state and federal government agencies responded to provide dental services to victims as part of disaster response and recovery. The purpose of this paper is to share our experiences in Mississippi and the District of Columbia providing urgent dental care to disaster victims as part of a crisis response.

Probabilistic Structural Analysis of SSME Turbopump Blades: Probabilistic Geometry Effects

NASA Technical Reports Server (NTRS)

Nagpal, V. K.

1985-01-01

A probabilistic study was initiated to evaluate the precisions of the geometric and material properties tolerances on the structural response of turbopump blades. To complete this study, a number of important probabilistic variables were identified which are conceived to affect the structural response of the blade. In addition, a methodology was developed to statistically quantify the influence of these probabilistic variables in an optimized way. The identified variables include random geometric and material properties perturbations, different loadings and a probabilistic combination of these loadings. Influences of these probabilistic variables are planned to be quantified by evaluating the blade structural response. Studies of the geometric perturbations were conducted for a flat plate geometry as well as for a space shuttle main engine blade geometry using a special purpose code which uses the finite element approach. Analyses indicate that the variances of the perturbations about given mean values have significant influence on the response.

Chemotherapy for neuroendocrine tumors: the Beatson Oncology Centre experience.

PubMed

Hatton, M Q; Reed, N S

1997-01-01

The role of chemotherapy in malignant neuroendocrine tumours is difficult to assess because of their rarity and variation in biological behaviour. We present a retrospective review of chemotherapy given to 18 patients with metastatic and one with locally advanced neuroendocrine tumours. There were eight poorly differentiated neuroendocrine tumours, six thyroid medullary carcinomas, two phaeochromocytomas, two pancreatic islet cell tumours and one undifferentiated neuroblastoma. Four patients were given 3-weekly dacarbazine, vincristine and cyclophosphamide (DOC) chemotherapy. In eight patients, this regimen was modified by substituting the dacarbazine and cisplatin and etoposide (OPEC). A further six patients were treated with dacarbazine reintroduced into the 3-weekly regimen (DOPEC). The remaining patient received cisplatin and etoposide. There were two complete responses (both with OPEC) and eight partial responses (two with DOC, three with OPEC and three with DOPEC). Five patients had stable disease and four progressed. Four received further chemotherapy on relapse, producing one complete and one partial response. The median response duration to initial chemotherapy was 10 months (range 3-34). The median survival was 12 months (range 1-42). The main toxicity was haematological, with grade 3-4 neutropenia in 12 patients; eight suffered episodes of sepsis. One death was treatment related. Other toxicity was mild although three patients discontinued vincristine with grade 2 neurotoxicity. The response rate and side effects of these three regimens appear comparable. We conclude that, although these patient numbers are small, combination chemotherapy produces an encouraging response rate (53%; 95% CI 30-75) in malignant neuroendocrine tumours, with acceptable toxicity.

Fate of protocols submitted to a French national funding scheme: a cohort study.

PubMed

Decullier, Evelyne; Huot, Laure; Chapuis, François R

2014-01-01

The fate of clinical research projects funded by a grant has been investigated, but there is no information on the projects which did not receive funding. The fate of these projects is not known: do they apply for and/or receive funding from other sources or are they carried out without specific funding? The aim of the study was to describe all clinical research projects submitted to a French national funding scheme (PHRC 2000) and to assess project initiation, completion and publication status taking into account whether or not they received funding. This study is a retrospective cohort. The initial project characteristics were retrieved from the submission files and follow-up information was collected from the primary investigator. The percentages of projects started, completed and published were studied. A total of 481 projects were studied. Follow-up information was obtained for 366. Overall, 185 projects were initiated (51%); 139 of them were funded by the PHRC 2000 or other sources. The most commonly cited reason for not initiating a project was a lack of funding. Subsequently, 121 of the projects initiated were completed (65%). Accrual difficulties were the main reason cited to explain why studies were stopped prematurely or were still ongoing. Finally, 88 of the completed projects were published (73%). Amongst the completed projects, the only factor explaining publication was the statistical significance of the results. Obtainment of funding was a determining factor for project initiation. However, once initiated, the funding did not influence completion or publication.

The requirement for prior consent to participate on survey response rates: a population-based survey in Grampian

PubMed Central

Angus, Val C; Entwistle, Vikki A; Emslie, Margaret J; Walker, Kim A; Andrew, Jane E

2003-01-01

Background A survey was carried out in the Grampian region of Scotland with a random sample of 10,000 adults registered with a General Practitioner in Grampian. The study complied with new legislation requiring a two-stage approach to identify and recruit participants, and examined the implications of this for response rates, non-response bias and speed of response. Methods A two-stage survey was carried out consistent with new confidentiality guidelines. Individuals were contacted by post and asked by the Director of Public Health to consent to receive a postal or electronic questionnaire about communicating their views to the NHS. Those who consented were then sent questionnaires. Response rates at both stages were measured. Results 25% of people returned signed consent forms and were invited to complete questionnaires. Respondents at the consent stage were more likely to be female (odds ratio (OR) response rate of women compared to men = 1.5, 95% CI 1.4, 1.7), less likely to live in deprived postal areas (OR = 0.59, 95% CI 0.45, 0.78) and more likely to be older (OR for people born in 1930–39 compared to people born in 1970–79 = 2.82, 95% CI 2.36, 3.37). 80% of people who were invited to complete questionnaires returned them. Response rates were higher among older age groups. The overall response rate to the survey was 20%, relative to the original number approached for consent (1951/10000). Conclusion The requirement of a separate, prior consent stage may significantly reduce overall survey response rates and necessitate the use of substantially larger initial samples for population surveys. It may also exacerbate non-response bias with respect to demographic variables. PMID:14622444

High-intensity compared to moderate-intensity training for exercise initiation, enjoyment, adherence, and intentions: an intervention study.

PubMed

Heinrich, Katie M; Patel, Pratik M; O'Neal, Joshua L; Heinrich, Bryan S

2014-08-03

Understanding exercise participation for overweight and obese adults is critical for preventing comorbid conditions. Group-based high-intensity functional training (HIFT) provides time-efficient aerobic and resistance exercise at self-selected intensity levels which can increase adherence; behavioral responses to HIFT are unknown. This study examined effects of HIFT as compared to moderate-intensity aerobic and resistance training (ART) on exercise initiation, enjoyment, adherence, and intentions. A stratified, randomized two-group pre-test posttest intervention was conducted for eight weeks in 2012 with analysis in 2013. Participants (n = 23) were stratified by median age (< or ≥ 28) and body mass index (BMI; < or ≥ 30.5). Participants were physically inactive with an average BMI of 31.1 ± 3.5 kg/m2, body fat percentage of 42.0 ± 7.4%, weight of 89.5 ± 14.2 kg, and ages 26.8 ± 5.9 years. Most participants were white, college educated, female, and married/engaged. Both groups completed 3 training sessions per week. The ART group completed 50 minutes of moderate aerobic exercise each session and full-body resistance training on two sessions per week. The HIFT group completed 60-minute sessions of CrossFit™ with actual workouts ranging from 5-30 minutes. Participants completed baseline and posttest questionnaires indicating reasons for exercise initiation (baseline), exercise enjoyment, and exercise intentions (posttest). Adherence was defined as completing 90% of exercise sessions. Daily workout times were recorded. Participants provided mostly intrinsic reasons for exercise initiation. Eighteen participants adhered (ART = 9, 81.8%; HIFT = 9, 75%). HIFT dropouts (p = .012) and ART participants (p = .009) reported lower baseline exercise enjoyment than HIFT participants, although ART participants improved enjoyment at posttest (p = .005). More HIFT participants planned to continue the same exercise than ART participants (p = .002). No significant changes in BMI or body composition were found. Workouts were shorter for HIFT than ART (p < .001). HIFT participants spent significantly less time exercising per week, yet were able to maintain exercise enjoyment and were more likely to intend to continue. High-intensity exercise options should be included in public health interventions. ClinicalTrials.gov Identifier: http://NCT02185872. Registered 9 July 2014.

User's guide to computer programs JET 5A and CIVM-JET 5B to calculate the large elastic-plastic dynamically-induced deformations of multilayer partial and/or complete structural rings

NASA Technical Reports Server (NTRS)

Wu, R. W. H.; Stagliano, T. R.; Witmer, E. A.; Spilker, R. L.

1978-01-01

These structural ring deflections lie essentially in one plane and, hence, are called two-dimensional (2-d). The structural rings may be complete or partial; the former may be regarded as representing a fragment containment ring while the latter may be viewed as a 2-d fragment-deflector structure. These two types of rings may be either free or supported in various ways (pinned-fixed, locally clamped, elastic-foundation supported, mounting-bracket supported, etc.). The initial geometry of each ring may be circular or arbitrarily curved; uniform-thickness or variable-thickness rings may be analyzed. Strain-hardening and strain-rate effects of initially-isotropic material are taken into account. An approximate analysis utilizing kinetic energy and momentum conservation relations is used to predict the after-impact velocities of each fragment and of the impact-affected region of the ring; this procedure is termed the collision-imparted velocity method (CIVM) and is used in the CIVM-JET 5 B program. This imparted-velocity information is used in conjunction with a finite-element structural response computation code to predict the transient, large-deflection, elastic-plastic responses of the ring. Similarly, the equations of motion of each fragment are solved in small steps in time. Provisions are made in the CIVM-JET 5B code to analyze structural ring response to impact attack by from 1 to 3 fragments, each with its own size, mass, translational velocity components, and rotational velocity. The effects of friction between each fragment and the impacted ring are included.

Real world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States.

PubMed

Mato, Anthony R; Thompson, Meghan; Allan, John N; Brander, Danielle M; Pagel, John M; Ujjani, Chaitra S; Hill, Brian T; Lamanna, Nicole; Lansigan, Frederick; Jacobs, Ryan; Shadman, Mazyar; Skarbnik, Alan P; Pu, Jeffrey J; Barr, Paul M; Sehgal, Alison R; Cheson, Bruce D; Zent, Clive S; Tuncer, Hande H; Schuster, Stephen J; Pickens, Peter V; Shah, Nirav N; Goy, Andre; Winter, Allison M; Garcia, Christine; Kennard, Kaitlin; Isaac, Krista; Dorsey, Colleen; Gashonia, Lisa M; Singavi, Arun K; Roeker, Lindsey E; Zelenetz, Andrew; Williams, Annalynn; Howlett, Christina; Weissbrot, Hanna; Ali, Naveed; Khajavian, Sirin; Sitlinger, Andrea; Tranchito, Eve; Rhodes, Joanna; Felsenfeld, Joshua; Bailey, Neil; Patel, Bhavisha; Burns, Timothy F; Yacur, Melissa; Malhotra, Mansi; Svoboda, Jakub; Furman, Richard R; Nabhan, Chadi

2018-06-07

Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with CLL treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26.8% complex karyotype (≥ 3 abnormalities). Prior to venetoclax initiation, 89% received a B-cell receptor antagonist. For tumor lysis syndrome prophylaxis, 93% received allopurinol, 92% normal saline, and 45% rasburicase. Dose escalation to the maximum recommended dose of 400 mg daily was achieved in 85% of patients. Adverse events of interest included neutropenia in 47.4%, thrombocytopenia in 36%, tumor lysis syndrome in 13.4%, neutropenic fever in 11.6%, and diarrhea in 7.3%. The overall response rate to venetoclax was 72% (19.4% complete remission). With a median follow up of 7 months, median progression free survival and overall survival for the entire cohort have not been reached. To date, 41 venetoclax treated patients have discontinued therapy and 24 have received a subsequent therapy, most commonly ibrutinib. In the largest clinical experience of venetoclax-treated chronic lymphocytic leukemia patients , the majority successfully completed and maintained a maximum recommended dose. Response rates and duration of response appear comparable to clinical trial data. Venetoclax was active in patients with mutations known to confer ibrutinib resistance. Optimal sequencing of newer chronic lymphocytic leukemia therapies requires further study. Copyright © 2018, Ferrata Storti Foundation.

Patterns of relapse in primary central nervous system lymphoma: inferences regarding the role of the neuro-vascular unit and monoclonal antibodies in treating occult CNS disease.

PubMed

Ambady, Prakash; Fu, Rongwei; Netto, Joao Prola; Kersch, Cymon; Firkins, Jenny; Doolittle, Nancy D; Neuwelt, Edward A

2017-06-02

The radiologic features and patterns of primary central nervous system lymphoma (PCNSL) at initial presentation are well described. High response rates can be achieved with first-line high-dose methotrexate (HD-MTX) based regimens, yet many relapse within 2 years of diagnosis. We describe the pattern of relapse and review the potential mechanisms involved in relapse. We identified 78 consecutive patients who attained complete radiographic response (CR) during or after first-line treatment for newly diagnosed PCNSL (CD20+, diffuse large B cell type). Patients were treated with HD-MTX based regimen in conjunction with blood-brain barrier disruption (HD-MTX/BBBD); 44 subsequently relapsed. Images and medical records of these 44 consecutive patients were retrospectively reviewed. The anatomical location of enhancing lesions at initial diagnosis and at the time of relapse were identified and compared. 37/44 patients fulfilled inclusion criteria and had new measureable enhancing lesions at relapse; the pattern and location of relapse of these 37 patients were identified. At relapse, the new enhancement was at a spatially distinct site in 30 of 37 patients. Local relapse was found only in seven patients. Unlike gliomas, the majority of PCNSL had radiographic relapse at spatially distinct anatomical locations within the brain behind a previously intact neurovascular unit (NVU), and in few cases outside, the central nervous system (CNS). This may suggest either (1) reactivation of occult reservoirs behind an intact NVU in the CNS (or ocular) or (2) seeding from bone marrow or other extra CNS sites. Recognizing patterns of relapse is key for early detection and may provide insight into potential mechanisms of relapse as well as help develop strategies to extend duration of complete response.

Experimental results on mechanisms of action of electrical neuromodulation in chronic urinary retention.

PubMed

Schultz-Lampel, D; Jiang, C; Lindström, S; Thüroff, J W

1998-01-01

Sacral foramen neuromodulation--initially applied for the treatment of urinary incontinence--has proved to be effective in patients with chronic urinary retention. Thus far, the underlying neurophysiological mechanisms have not been elucidated. In an experimental study on the neurophysiological basis of sacral neurostimulation, one objective was to investigate the mechanisms responsible for initiation of micturition in chronic urinary retention. In ten female cats anesthetized with alpha-chloralose the clinical situation of sacral foramen stimulation was experimentally reproduced by isolated S2 nerve stimulation after L6-S3 laminectomy. Stimulation responses were recorded from the bladder, peripheral nerves, and striated muscles of the foot and pelvic floor. The effect of sudden cessation of prolonged S2 stimulation, during which the bladder was completely inhibited, was evaluated in 70 stimulation sequences in 5 cats. Sacral nerve stimulation induced excitatory and inhibitory effects on the bladder, depending on the frequency and intensity of stimulation. With unilateral S2 stimulation, bladder excitation was best at frequencies of 2-5 Hz and at intensities ranging between 0.8 and 1.4 times the threshold for the M-response of the foot muscle. Inhibition was the dominating effect at frequencies of 7-10 Hz and at intensities exceeding 1.4 times the threshold. Prolonged S2 stimulation above the threshold produced complete bladder inhibition during stimulation but induced strong bladder contractions after sudden interruption of stimulation, with amplitudes being significantly higher than that of spontaneous contractions preceding the stimulation. These results confirm the hypothesis of a "rebound" phenomenon as the mechanism of action for induction of spontaneous voiding in patients with chronic urinary retention.

Consumer participation in quality improvements for chronic disease care: development and evaluation of an interactive patient-centered survey to identify preferred service initiatives.

PubMed

Fradgley, Elizabeth A; Paul, Christine L; Bryant, Jamie; Roos, Ian A; Henskens, Frans A; Paul, David J

2014-12-19

With increasing attention given to the quality of chronic disease care, a measurement approach that empowers consumers to participate in improving quality of care and enables health services to systematically introduce patient-centered initiatives is needed. A Web-based survey with complex adaptive questioning and interactive survey items would allow consumers to easily identify and prioritize detailed service initiatives. The aim was to develop and test a Web-based survey capable of identifying and prioritizing patient-centered initiatives in chronic disease outpatient services. Testing included (1) test-retest reliability, (2) patient-perceived acceptability of the survey content and delivery mode, and (3) average completion time, completion rates, and Flesch-Kincaid reading score. In Phase I, the Web-based Consumer Preferences Survey was developed based on a structured literature review and iterative feedback from expert groups of service providers and consumers. The touchscreen survey contained 23 general initiatives, 110 specific initiatives available through adaptive questioning, and a relative prioritization exercise. In Phase II, a pilot study was conducted within 4 outpatient clinics to evaluate the reliability properties, patient-perceived acceptability, and feasibility of the survey. Eligible participants were approached to complete the survey while waiting for an appointment or receiving intravenous therapy. The age and gender of nonconsenters was estimated to ascertain consent bias. Participants with a subsequent appointment within 14 days were asked to complete the survey for a second time. A total of 741 of 1042 individuals consented to participate (71.11% consent), 529 of 741 completed all survey content (78.9% completion), and 39 of 68 completed the test-retest component. Substantial or moderate reliability (Cohen's kappa>0.4) was reported for 16 of 20 general initiatives with observed percentage agreement ranging from 82.1%-100.0%. The majority of participants indicated the Web-based survey was easy to complete (97.9%, 531/543) and comprehensive (93.1%, 505/543). Participants also reported the interactive relative prioritization exercise was easy to complete (97.0%, 189/195) and helped them to decide which initiatives were of most importance (84.6%, 165/195). Average completion time was 8.54 minutes (SD 3.91) and the Flesch-Kincaid reading level was 6.8. Overall, 84.6% (447/529) of participants indicated a willingness to complete a similar survey again. The Web-based Consumer Preferences Survey is sufficiently reliable and highly acceptable to patients. Based on completion times and reading level, this tool could be integrated in routine clinical practice and allows consumers to easily participate in quality evaluation. Results provide a comprehensive list of patient-prioritized initiatives for patients with major chronic conditions and delivers practice-ready evidence to guide improvements in patient-centered care.

Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma

PubMed Central

Piekarz, Richard L.; Frye, Robin; Turner, Maria; Wright, John J.; Allen, Steven L.; Kirschbaum, Mark H.; Zain, Jasmine; Prince, H. Miles; Leonard, John P.; Geskin, Larisa J.; Reeder, Craig; Joske, David; Figg, William D.; Gardner, Erin R.; Steinberg, Seth M.; Jaffe, Elaine S.; Stetler-Stevenson, Maryalice; Lade, Stephen; Fojo, A. Tito; Bates, Susan E.

2009-01-01

Purpose Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. Patients and Methods The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sézary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease (stage IIB, n = 15; stage III, n= 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months. Conclusion The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL. PMID:19826128

Diverse Hormone Response Networks in 41 Independent Drosophila Cell Lines

DOE PAGES

Stoiber, Marcus; Celniker, Susan; Cherbas, Lucy; ...

2016-01-15

Steroid hormones induce cascades of gene activation and repression with transformative effects on cell fate . Steroid transduction plays a major role in the development and physiology of nearly all metazoan species, and in the progression of the most common forms of cancer. Despite the paramount importance of steroids in developmental and translational biology, a complete map of transcriptional response has not been developed for any hormone . In the case of 20-hydroxyecdysone (ecdysone) in Drosophila melanogaster, these trajectories range from apoptosis to immortalization. We mapped the ecdysone transduction network in a cohort of 41 cell lines, the largest suchmore » atlas yet assembled. We found that the early transcriptional response mirrors the distinctiveness of physiological origins: genes respond in restricted patterns, conditional on the expression levels of dozens of transcription factors. Only a small cohort of genes is constitutively modulated independent of initial cell state. Ecdysone-responsive genes tend to organize into directional same-stranded units, with consecutive genes induced from the same strand. Here, we identify half of the ecdysone receptor heterodimer as the primary rate-limiting step in the response, and find that initial receptor isoform levels modulate the activated cohort of target transcription factors. In conclusion, this atlas of steroid response reveals organizing principles of gene regulation by a model type II nuclear receptor and lays the foundation for comprehensive and predictive understanding of the ecdysone transduction network in the fruit fly.« less

A refined risk score for acute GVHD that predicts response to initial therapy, survival and transplant-related mortality

PubMed Central

MacMillan, Margaret L.; Robin, Marie; Harris, Andrew C.; DeFor, Todd E.; Martin, Paul J.; Alousi, Amin; Ho, Vincent T.; Bolaños-Meade, Javier; Ferrara, James L.M.; Jones, Richard; Arora, Mukta; Blazar, Bruce R.; Holtan, Shernan G.; Jacobsohn, David; Pasquini, Marcelo; Socie, Gerard; Antin, Joseph H.; Levine, John E.; Weisdorf, Daniel J.

2015-01-01

To develop a novel acute graft-versus-host disease (GVHD) Risk Score, we examined the GVHD clinical stage and grade of 1723 patients at the onset of treatment with systemic steroids. Using clinical grouping, descriptive statistics and recursive partitioning, we identified poorly responsive, high-risk (HR) acute GVHD by the number of involved organs and severity of GVHD at onset. The overall response [(complete response/partial response (CR/PR)] rate 28 days after initiation of steroid therapy for acute GVHD was lower in the 269 patients with HR-GVHD than in the 1454 patients with standard risk (SR)-GVHD [44% (95% CI 38–50%) vs. 68% (95% CI 66–70%), p<0.001. Patients with HR-GVHD were less likely to respond at day 28 [odds ratio (OR), 0.3, 95% CI 0.2–0.4, p<0.001], and had higher risks of mortality [relative risk (RR) 2.1, 95% CI 1.7–2.6, P<0.001] and transplant-related mortality (RR 2.5, 95% CI 2.0–3.2%, p<0.001) compared to patients with SR-GVHD. This refined definition of acute GVHD risk is a better predictor of response, survival and transplant-related mortality than other published acute GVHD risk scores. Patients with HR-GVHD are candidates for studies investigating new treatment approaches. Likewise, patients with SR-GVHD are candidates for studies investigating less toxic therapy. PMID:25585275

Health responsibility and workplace health promotion among women: early detection of cancer.

PubMed

Kushnir, T; Rabinowitz, S; Melamed, S; Weisberg, E; Ribak, J

1995-01-01

The importance of health responsibility as one aspect of a health-promoting lifestyle has been emphasized repeatedly. Yet there are only a few empirical studies of its role in preventive behavior. We examined the relationship between health responsibility and early-detection practices for breast and cervical cancer. A group of 253 women employees of a large industrial company participated in a cancer screening program subsidized by the employer. They completed questionnaires assessing health responsibility and reported early-detection practices: frequency of breast self-examination and physician breast examinations, frequency of Pap tests, and time lapsed since last Pap test and breast examinations. Health responsibility was a significant independent predictor of breast examination indicators but not of Pap tests. Education level was an important predictor for Pap tests, and age predicted most early-detection practices. The findings lend some support to the role of health responsibility in initiating breast examinations. Better prediction of early-detection practices could be achieved by adding cognitive and emotional components to the existing responsibility scale and by distinguishing between retrospective and prospective responsibility.

Linkage and retention in HCV care for HIV-infected populations: early data from the DAA era.

PubMed

Sacks-Davis, Rachel; Doyle, Joseph S; Rauch, Andri; Beguelin, Charles; Pedrana, Alisa E; Matthews, Gail V; Prins, Maria; van der Valk, Marc; Klein, Marina B; Saeed, Sahar; Lacombe, Karine; Chkhartishvili, Nikoloz; Altice, Frederick L; Hellard, Margaret E

2018-04-01

There is currently no published data on the effectiveness of DAA treatment for elimination of HCV infection in HIV-infected populations at a population level. However, a number of relevant studies and initiatives are emerging. This research aims to report cascade of care data for emerging HCV elimination initiatives and studies that are currently being evaluated in HIV/HCV co-infected populations in the context of implementation science theory. HCV elimination initiatives and studies in HIV co-infected populations that are currently underway were identified. Context, intervention characteristics and cascade of care data were synthesized in the context of implementation science frameworks. Seven HCV elimination initiatives and studies were identified in HIV co-infected populations, mainly operating in high-income countries. Four were focused mainly on HCV elimination in HIV-infected gay and bisexual men (GBM), and three included a combination of people who inject drugs (PWID), GBM and other HIV-infected populations. None were evaluating treatment delivery in incarcerated populations. Overall, HCV RNA was detected in 4894 HIV-infected participants (range within studies: 297 to 994): 48% of these initiated HCV treatment (range: 21% to 85%; within studies from a period where DAAs were broadly available the total is 57%, range: 36% to 74%). Among studies with treatment completion data, 96% of 1109 initiating treatment completed treatment (range: 94% to 99%). Among those who could be assessed for sustained virological response at 12 weeks (SVR12), 1631 of 1757 attained SVR12 (93%, range: 86% to 98%). Early results from emerging research on HCV elimination in HIV-infected populations suggest that HCV treatment uptake is higher than reported levels prior to DAA treatment availability, but approximately half of patients remain untreated. These results are among diagnosed populations and additional effort is required to increase diagnosis rates. Among those who have initiated treatment, completion and SVR rates are promising. More data are required in order to evaluate the effectiveness of these elimination programmes in the long term, assess which intervention components are effective, and whether they need to be tailored to particular population groups. © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

HPV literacy and its link to initiation and completion of HPV vaccine among young adults in Minnesota.

PubMed

Lee, H Y; Lee, J; Henning-Smith, C; Choi, J

2017-11-01

This study identifies whether, and how, human papillomavirus (HPV) literacy and predisposing, enabling, and need factors are associated with HPV vaccine initiation and completion among young adults in Minnesota. Cross-sectional survey design. Using a sample of 170 young adults (aged 18-26 years), we used logistic regression models to identify factors associated with HPV vaccination initiation and completion, including HPV literacy, adjusting for relevant predisposing, enabling, and need factors. Consistent with national estimates, we found relatively low rates of HPV vaccination initiation (46%) and completion (36%). Better HPV literacy was significantly associated with higher rates of both initiation and completion, as was being female and having an annual check-up. Being married/partnered was significantly associated with lower odds of HPV vaccination. Public health programs, policy-makers, and healthcare providers can use these results to increase HPV vaccination rates by making concerted efforts to improve HPV vaccination literacy through individual and public education campaigns and by improving access to annual check-ups. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Two nights of sleep deprivation with or without energy restriction does not impair the thermal response to cold.

PubMed

Oliver, Samuel J; Harper Smith, Adam D; Costa, Ricardo J S; Maassen, Norbert; Bilzon, James L J; Walsh, Neil P

2015-10-01

In persons completing exhaustive daily exercise, sleep and energy restriction have been highlighted as risk factors for hypothermia in cold environments. The present study therefore sought to determine the effect of sleep deprivation (SDEP), with and without energy restriction, on the thermal response to cold. In a random order, ten recreationally active men (mean ± SD: age 25 ± 6 years, body fat 17 ± 5 %) completed three 53 h trials: a control (CON: 436 min/night sleep), SDEP (0 min sleep), and sleep deprivation and energy restriction (SDEP + ER: 0 min sleep and 10% daily energy requirements). Exhaustive exercise was completed after 5 and 29 h. After 53 h participants completed a semi-nude seated cold air test (CAT, 0 °C), for 4 h or until rectal core temperature (T re) reached 36 °C. Two nights of sleep and energy restriction did not impair the thermal response to cold (T re, CON 36.15 ± 0.20 °C, SDEP 36.30 ± 0.15 °C, SDEP + ER 36.25 ± 0.20 °C, P = 0.25). Rewarming was also similar as indicated by 1 h post-CAT T re (P = 0.78). In contrast, perceived thermal discomfort during the initial hour of the CAT tended to be greater after SDEP and SDEP + ER (P ≤ 0.1). Sleep and energy restriction, at least as evaluated within this experiment, should be considered minimal risk factors for hypothermia. The greater perception of cold discomfort at the same body temperature suggests that sleep and energy restriction may actually reduce cold injury risk, as people are likely to engage earlier in normal behavioral cold adaptation.

Analysis of outcomes achieved with squamous cell carcinomas of the anus in a single university hospital over the last two decades: Clinical response rate, relapse and survival of 190 patients.

PubMed

Gravante, Gianpiero; Stephenson, James Andrew; Elshaer, Mohamed; Osman, Ahmed; Vasanthan, Subramaniam; Mullineux, Joseph H; Gani, Mohamed Akil Dilawar; Sharpe, David; Yeung, Justin; Norwood, Michael; Miller, Andrew; Boyle, Kirsten; Hemingway, David

2018-02-01

We reviewed our series of anal squamous cell carcinomas (ASCC) treated over the last two decades. ASCC patients undergoing treatment at the Leicester Royal Infirmary between 1998 and 2016 were selected. Age, gender, pathological tumor characteristics, treatment adopted, the overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) at 5-year follow-up were recorded and calculated. A total of 190 ASCC were reviewed, of these 64.2% (n = 122) received primary radical chemoradiotherapy. Complete response rate was 92.6% (n = 113) and four patients with residual disease underwent a salvage APER. Twenty-eight patients experienced recurrent disease (23.0%) either systemic (n = 8), local (n = 14), or both (n = 6); six had a salvage APER. Complete follow-up data are available for 63.1% patients (77/122). Overall, the locoregional failure rate of primary chemoradiotherapy (residual + recurrent disease) was present in 29 patients (29/122; 23.8%). OS was 41.6% CSS was 69.2% and DFS 60.0% at 5 years follow-up. In our series of ASCC primary chemoradiotherapy had achieved significant initial complete response rates, however, long term-follow ups still present systemic and local recurrences. APR is able to treat 30% of the pelvic recurrences (6/20), the others are either associated with systemic disease or locally inoperable masses. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2018-02-01

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

Who sends the email? Using electronic surveys in violence research.

PubMed

Sutherland, Melissa A; Amar, Angela F; Laughon, Kathryn

2013-08-01

Students aged 16-24 years are at greatest risk for interpersonal violence and the resulting short and long-term health consequences. Electronic survey methodology is well suited for research related to interpersonal violence. Yet methodological questions remain about best practices in using electronic surveys. While researchers often indicate that potential participants receive multiple emails as reminders to complete the survey, little mention is made of the sender of the recruitment email. The purpose of this analysis is to describe the response rates from three violence-focused research studies when the recruitment emails are sent from a campus office, researcher or survey sampling firm. Three violence-focused studies were conducted about interpersonal violence among college students in the United States. Seven universities and a survey sampling firm were used to recruit potential participants to complete an electronic survey. The sender of the recruitment emails varied within and across the each of the studies depending on institutional review boards and university protocols. An overall response rate of 30% was noted for the 3 studies. Universities in which researcher-initiated recruitment emails were used had higher response rates compared to universities where campus officials sent the recruitment emails. Researchers found lower response rates to electronic surveys at Historically Black Colleges or Universities and that other methods were needed to improve response rates. The sender of recruitment emails for electronic surveys may be an important factor in response rates for violence-focused research. For researchers identification of best practices for survey methodology is needed to promote accurate disclosure and increase response rates.

Correlates of human papillomavirus vaccination rates in low-income, minority adolescents: a multicenter study.

PubMed

Perkins, Rebecca B; Brogly, Susan B; Adams, William G; Freund, Karen M

2012-08-01

Low rates of human papillomavirus (HPV) vaccination in low-income, minority adolescents may exacerbate racial disparities in cervical cancer incidence. Using electronic medical record data and chart abstraction, we examined correlates of HPV vaccine series initiation and completion among 7702 low-income and minority adolescents aged 11-21 receiving primary care at one of seven medical centers between May 1, 2007, and June 30, 2009. Our population included 61% African Americans, 13% Caucasians, 15% Latinas, and 11% other races; 90% receive public insurance (e.g., Medicaid). We used logistic regression to estimate the associations between vaccine initiation and completion and age, race/ethnicity, number of contacts with the healthcare system, provider documentation, and clinical site of care. Of the 41% of adolescent girls who initiated HPV vaccination, 20% completed the series. A higher proportion of girls aged 11-<13 (46%) and 13-<18 (47%) initiated vaccination than those aged 18-21 (28%). In adjusted analyses, receipt of other recommended adolescent vaccines was associated with vaccine initiation, and increased contact with the medical system was associated with both initiation and completion of the series. Conversely, provider failure to document risky health behaviors predicted nonvaccination. Manual review of a subset of unvaccinated patients' charts revealed no documentation of vaccine discussions in 67% of cases. Fewer than half of low-income and minority adolescents receiving health maintenance services initiated HPV vaccination, and only 20% completed the series. Provider failure to discuss vaccination with their patients appears to be an important contributor to nonvaccination. Future research should focus on improving both initiation and completion of HPV vaccination in high-risk adolescents.

An education initiative modifies opinions of hemodialysis nurses towards home dialysis.

PubMed

Phillips, Matthew; Wile, Colleen; Bartol, Carolyn; Stockman, Cynthia; Dhir, Minakshi; Soroka, Steven D; Hingwala, Jay; Bargman, Joanne M; Chan, Christopher T; Tennankore, Karthik K

2015-01-01

It has been shown that in-center hemodialysis (HD) nurses prefer in-center HD for patients with certain characteristics; however it is not known if their opinions can be changed. To determine if an education initiative modified the perceptions of in-center HD nurses towards home dialysis. Cross-sectional survey of in-center HD nurses before and after a three hour continuing nursing education (CNE) initiative. Content of the CNE initiative included a didactic review of benefits of home dialysis, common misconceptions about patient eligibility, cost comparisons of different modalities and a home dialysis patient testimonial video. All in-center HD nurses (including those working in satellite dialysis units) affiliated with a single academic institution. Survey themes included perceived barriers to home dialysis, preferred modality (home versus in-center HD), ideal modality distribution in the local program, awareness of home dialysis and patient education about home modalities. Paired comparisons of responses before and after the CNE initiative. Of the 115 in-center HD nurses, 100 registered for the CNE initiative and 89 completed pre and post surveys (89% response rate). At baseline, in-center HD nurses perceived that impaired cognition, poor motor strength and poor visual acuity were barriers to peritoneal dialysis and home HD. In-center HD was preferred for availability of multidisciplinary care and medical personnel in case of catastrophic events. After the initiative, perceptions were more in favor of home dialysis for all patient characteristics, and most patient/system factors. Home dialysis was perceived to be underutilized both at baseline and after the initiative. Finally, in-center HD nurses were more aware of home dialysis, felt better informed about its benefits and were more comfortable teaching in-center HD patients about home modalities after the CNE session. Single-center study. CNE initiatives can modify the opinions of in-center HD nurses towards home modalities and should complement the multitude of strategies aimed at promoting home dialysis.

Adjuvant effects of saponins on animal immune responses*

PubMed Central

Rajput, Zahid Iqbal; Hu, Song-hua; Xiao, Chen-wen; Arijo, Abdullah G.

2007-01-01

Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines, ISCOMs (immunostimulating complexes), Freund’s complete adjuvant, Freund’s incomplete adjuvant, alums, bacterial toxins etc., are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed. PMID:17323426

Central nervous system involvement in AIDS-related lymphomas.

PubMed

Barta, Stefan K; Joshi, Jitesh; Mounier, Nicolas; Xue, Xiaonan; Wang, Dan; Ribera, Josep-Maria; Navarro, Jose-Tomas; Hoffmann, Christian; Dunleavy, Kieron; Little, Richard F; Wilson, Wyndham H; Spina, Michele; Galicier, Lionel; Noy, Ariela; Sparano, Joseph A

2016-06-01

Central nervous system (CNS) involvement is reportedly more common in acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARL). We describe factors and outcomes associated with CNS involvement at baseline (CNS(B) ) and relapse (CNS(R) ) in 886 patients with newly diagnosed ARL. Of 886 patients, 800 received either intrathecal (IT) therapy for CNS(B) or IT prophylaxis. CNS(B) was found in 13%. CNS(B) was not associated with reduced overall survival (OS). There was no difference in the prevalence of CNS(B) between the pre-combination antiretroviral therapy (cART) and cART eras. 5·3% of patients experienced CNS(R) at a median of 4·2 months after diagnosis (12% if CNS(B) ; 4% if not). Median OS after CNS(R) was 1·6 months. On multivariate analysis, only CNS(B) [hazard ratio (HR) 3·68, P = 0·005] and complete response to initial therapy (HR 0·14, P < 0·0001) were significantly associated with CNS(R) . When restricted to patients without CNS(B) , IT CNS prophylaxis with 3 vs. 1 agent did not significantly impact the risk of CNS(R) . Despite IT CNS prophylaxis, 5% of patients experienced CNS(R) . Our data confirms that CNS(R) in ARL occurs early and has a poor outcome. Complete response to initial therapy was associated with a reduced frequency of CNS(R) . Although CNS(B) conferred an increased risk for CNS(R) , it did not impact OS. © 2016 John Wiley & Sons Ltd.

A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia

PubMed Central

Lamanna, Nicole; Kipps, Thomas J.; Flinn, Ian; Zelenetz, Andrew D.; Burger, Jan A.; Keating, Michael; Mitra, Siddhartha; Holes, Leanne; Yu, Albert S.; Johnson, David M.; Miller, Langdon L.; Kim, Yeonhee; Dansey, Roger D.; Dubowy, Ronald L.; Coutre, Steven E.

2015-01-01

Idelalisib is a first-in-class oral inhibitor of PI3Kδ that has shown substantial activity in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as initial therapy, 64 treatment-naïve older patients with CLL or small lymphocytic leukemia (median age, 71 years; range, 65-90) were treated with rituximab 375 mg/m2 weekly ×8 and idelalisib 150 mg twice daily continuously for 48 weeks. Patients completing 48 weeks without progression could continue to receive idelalisib on an extension study. The median time on treatment was 22.4 months (range, 0.8-45.8+). The overall response rate (ORR) was 97%, including 19% complete responses. The ORR was 100% in patients with del(17p)/TP53 mutations and 97% in those with unmutated IGHV. Progression-free survival was 83% at 36 months. The most frequent (>30%) adverse events (any grade) were diarrhea (including colitis) (64%), rash (58%), pyrexia (42%), nausea (38%), chills (36%), cough (33%), and fatigue (31%). Elevated alanine transaminase/aspartate transaminase was seen in 67% of patients (23% grade ≥3). The combination of idelalisib and rituximab was highly active, resulting in durable disease control in treatment-naïve older patients with CLL. These results support the further development of idelalisib as initial treatment of CLL. This study is registered at ClinicalTrials.gov as #NCT01203930. PMID:26472751

HPV vaccination among lesbian and bisexual women: Findings from a national survey of young adults

PubMed Central

McRee, Annie-Laurie; Katz, Mira L.; Paskett, Electra D.; Reiter, Paul L.

2014-01-01

Background Human papillomavirus (HPV) infection and associated cervical disease are common among all women, regardless of sexual identity, yet limited research has examined HPV vaccination among lesbian and bisexual women. Methods A national sample of lesbian and bisexual women ages 18-26 (n=543) completed our online survey during Fall 2013. We used multivariable logistic regression to identify correlates of HPV vaccine initiation (receipt of at least 1 dose) and completion (receipt of all 3 recommended doses among initiators). Results Overall, 45% of respondents had initiated HPV vaccine, and 70% of initiators reported completing the series. HPV vaccine initiation was higher among respondents who: were students, had received a healthcare provider's recommendation, perceived greater positive social vaccination norms, or anticipated greater regret if they did not get vaccinated and later got HPV. Initiation was lower among those who perceived greater HPV vaccine harms or greater barriers to getting the vaccine (all p<.05). HPV vaccine completion was higher among initiators who had a college degree while it was lower among those who perceived a greater likelihood of acquiring HPV or who anticipated greater regret if they got the vaccine and fainted (all p<.05). Among HPV vaccine initiators who had not yet completed the series, about half (47%) intended to get the remaining doses. Conclusions Many lesbian and bisexual women are not getting vaccinated against HPV. Healthcare provider recommendations and women's health beliefs may be important leverage points for increasing vaccination among this population. PMID:25038312

From non school-based, co-payment to school-based, free Human Papillomavirus vaccination in Flanders (Belgium): a retrospective cohort study describing vaccination coverage, age-specific coverage and socio-economic inequalities.

PubMed

Lefevere, Eva; Theeten, Heidi; Hens, Niel; De Smet, Frank; Top, Geert; Van Damme, Pierre

2015-09-22

School-based, free HPV vaccination for girls in the first year of secondary school was introduced in Flanders (Belgium) in 2010. Before that, non school-based, co-payment vaccination for girls aged 12-18 was in place. We compared vaccination coverage, age-specific coverage and socio-economic inequalities in coverage - 3 important parameters contributing to the effectiveness of the vaccination programs - under both vaccination systems. We used retrospective administrative data from different sources. Our sample consisted of all female members of the National Alliance of Christian Mutualities born in 1995, 1996, 1998 or 1999 (N=66,664). For each vaccination system we described the cumulative proportion HPV vaccination initiation and completion over time. We used life table analysis to calculate age-specific rates of HPV vaccination initiation and completion. Analyses were done separately for higher income and low income groups. Under non school-based, co-payment vaccination the proportions HPV vaccination initiation and completion slowly rose over time. By age 17, the proportion HPV vaccination initiation/completion was 0.75 (95% CI 0.74-076)/0.66 (95% CI 0.65-0.67). The median age at vaccination initiation/completion was 14.4 years (95% CI 14.4-14.5)/15.4 years (95% CI 15.3-15.4). Socio-economic inequalities in coverage widened over time and with age. Under school-based, free vaccination rates of HPV vaccination initiation were substantially higher. By age 14,the proportion HPV vaccination initiation/completion was 0.90 (95% CI 0.90-0.90)/0.87 (95% CI 0.87-0.88). The median age at vaccination initiation/completion was 12.7 years (95% CI 12.7-12.7)/13.3 years (95% CI 13.3-13.3). Socio-economic inequalities in coverage and in age-specific coverage were substantially smaller. Copyright © 2015. Published by Elsevier Ltd.

Ontogeny of flight initiation in the fly Drosophila melanogaster: implications for the giant fibre system.

PubMed

Hammond, Sarah; O'Shea, Michael

2007-11-01

There are two modes of flight initiation in Drosophila melanogaster-escape and voluntary. Although the circuitry underlying escape is accounted for by the Giant fibre (GF) system, the system underlying voluntary flight initiation is unknown. The GF system is functionally complete before the adult fly ecloses, but immature adults initially fail to react to a stimulus known to reliably evoke escape in mature adults. This suggests that escape in early adulthood, approximately 2-h post-eclosion, is not automatically triggered by the hard-wired GF system. Indeed, we reveal that escape behaviour displays a staged emergence during the first hour post-eclosion, suggesting that the GF system is subject to declining levels of suppression. Voluntary flight initiations are not observed at all during the period when the GF system is released from its suppression, nor indeed for some time after. We addressed the question whether voluntary flight initiation requires the GF system by observing take-off in Shak-B ( 2 ) mutant flies, in which the GF system is defunct. While the escape response is severely impaired in these mutants, they displayed normal voluntary flight initiation. Thus, the escape mechanism is subject to developmental modulation following eclosion and the GF system does not underlie voluntary flight.

A locally initiated and executed measles outbreak response immunization campaign in the nylon health district, Douala Cameroon 2011.

PubMed

Sume, Gerald Etapelong; Fouda, André Arsène Bita; Kobela, Marie; Nguelé, Salomé; Emah, Irène; Atem, Peter

2013-03-16

The Cameroon health system is divided into central, intermediate and peripheral levels. Of the 43 health districts with a measles outbreak in Cameroon in 2011, only the Nylon Health District organized a documented outbreak response immunization. We present the methods and results of the response campaign solely shouldered by the district and intermediate level. The risk group, targets and neighborhoods to be vaccinated were identified after a detailed analysis of initial cases. The intermediate level defined strategies, provided logistics, capacity building and 41% of the operational budget while 59% was completed by the peripheral level. Microsoft Office Excel 2007 was used to estimate coverage rates and to draw an epidemic curve. The response immunization campaign was organized on the 14th epidemiological week, 10 weeks after the onset of the outbreak which ended 11 weeks thereafter. A total of 15867(108.5%) children aged 9-59 months were vaccinated in five health areas at a direct cost (vaccines excluded) of 71.34FCFA ($0.143) per vaccinated child. An additional 824 children aged 9-59 months were vaccinated around the residence of notified cases in neighborhoods which were not involved in the response campaign. The number of cases after the response campaign was lower than before. Once vaccines are available, prompt outbreak response campaigns can be organized at operational level to obtain commendable results instead of depending solely on international organizations or central levels. Decision makers at the intermediate and operational levels should redeploy available funds during emergencies to prevent the development of extreme public health conditions.

Community nurse-led initiation of antiviral therapy for chronic hepatitis C in people who inject drugs does not increase uptake of or adherence to treatment.

PubMed

Lewis, Heather; Kunkel, Jan; Axten, David; Dalton, Jane; Gardner, Hayley; Tippett, Andrew; Wynne, Stephanie; Wilkinson, Mandie; Foster, Graham R

2016-11-01

Chronic hepatitis C is common in people who inject drugs (PWID) and this population serves as a reservoir for infection. Treatment levels are low among this group, ranging from 1 to 19%. We explored whether a nurse-initiated community treatment model increased uptake of and adherence to interferon-based therapies. This was a cluster randomized trial of nurse-initiated versus physician-initiated antiviral therapy with pegylated interferon and ribavirin for hepatitis C virus in community clinics (trial registration: ISRCTN07774040). The proportion of participants initiating treatment during follow-up was 10% with nurse-initiated (6/62) and 9% with physician-initiated (6/76) therapy. Adherence was similar in both groups, with only one patient in each arm not adhering to therapy. There were no serious adverse events, but interferon-related side effects were common. Drug and alcohol use did not change during therapy. Despite easy access to antiviral therapy, uptake of treatment was poor, with no significant difference between the groups. Nurse-led initiation of interferon-based antiviral therapy in PWID did not lead to increased uptake of, response to or adherence with treatment. Further service improvement is unlikely to increase the proportion of PWID undergoing antiviral therapy for hepatitis C virus and early adoption of interferon-free regimens may increase the proportion initiating and completing treatment.

Induction of Attachment-Independent Biofilm Formation and Repression of hfq Expression by Low-Fluid-Shear Culture of Staphylococcus aureus ▿

PubMed Central

Castro, Sarah L.; Nelman-Gonzalez, Mayra; Nickerson, Cheryl A.; Ott, C. Mark

2011-01-01

The opportunistic pathogen Staphylococcus aureus encounters a wide variety of fluid shear levels within the human host, and they may play a key role in dictating whether this organism adopts a commensal interaction with the host or transitions to cause disease. By using rotating-wall vessel bioreactors to create a physiologically relevant, low-fluid-shear environment, S. aureus was evaluated for cellular responses that could impact its colonization and virulence. S. aureus cells grown in a low-fluid-shear environment initiated a novel attachment-independent biofilm phenotype and were completely encased in extracellular polymeric substances. Compared to controls, low-shear-cultured cells displayed slower growth and repressed virulence characteristics, including decreased carotenoid production, increased susceptibility to oxidative stress, and reduced survival in whole blood. Transcriptional whole-genome microarray profiling suggested alterations in metabolic pathways. Further genetic expression analysis revealed downregulation of the RNA chaperone Hfq, which parallels low-fluid-shear responses of certain Gram-negative organisms. This is the first study to report an Hfq association with fluid shear in a Gram-positive organism, suggesting an evolutionarily conserved response to fluid shear among structurally diverse prokaryotes. Collectively, our results suggest S. aureus responds to a low-fluid-shear environment by initiating a biofilm/colonization phenotype with diminished virulence characteristics, which could lead to insight into key factors influencing the divergence between infection and colonization during the initial host-pathogen interaction. PMID:21803898

Utility of bortezomib retreatment in relapsed or refractory multiple myeloma patients: a multicenter case series.

PubMed

Wolf, Jeffrey; Richardson, Paul G; Schuster, Michael; LeBlanc, Annette; Walters, Ian B; Battleman, David S

2008-10-01

Bortezomib therapy has become an important part of the standard of care for patients with relapsed multiple myeloma, and preliminary clinical evidence suggests that bortezomib retreatment in patients previously treated with the drug may prolong disease control. This retrospective study was designed to clarify the utility of bortezomib as a repeat therapy. We reviewed records from 3 major cancer centers that had participated in the phase II (SUMMIT or CREST) or phase III (APEX) registration studies to identify patients who were subsequently retreated off protocol with bortezomib-based therapy. We found 22 patients who received bortezomib retreatment following a 60 or more day gap between bortezomib treatments. Twelve patients had intervening therapy between initial bortezomib treatment and bortezomib retreatment. During retreatment, 14 of 22 patients received bortezomib in combination with another antineoplastic agent. The overall response rate for bortezomib retreatment was 50% (9% complete responses). The median length of retreatment was 5.1 months in responding patients and 2.4 months in nonresponding patients. Therapy was terminated due to unmanageable toxicity in 2 patients during retreatment, compared with 6 patients during initial treatment. During retreatment, no patients required dose reduction due to peripheral neuropathy, compared to 4 patients during their initial treatment. Thus, bortezomib retreatment appears to be safe and effective. Favorable observed response rates with bortezomib retreatment suggest that it may be a viable option for relapsed or refractory multiple myeloma, even in patients previously exposed to bortezomib.

An assessment of pharmacists’ readiness for paperless labeling: a national survey

PubMed Central

Ho, Yun-Xian; Chen, Qingxia; Nian, Hui; Johnson, Kevin B

2014-01-01

Objective To assess the state of readiness for the adoption of paperless labeling among a nationally representative sample of pharmacies, including chain pharmacies, independent retail pharmacies, hospitals, and other rural or urban dispensing sites. Methods Both quantitative and qualitative analyses were used to analyze responses to a cross-sectional survey disseminated to American Pharmacists Association pharmacists nationwide. The survey assessed factors related to pharmacists’ attitudinal readiness (ie, perceptions of impact) and pharmacies’ structural readiness (eg, availability of electronic resources, internet access) for the paperless labeling initiative. Results We received a total of 436 survey responses (6% response rate) from pharmacists representing 44 US states and territories. Across the spectrum of settings we studied, pharmacists had work access to computers, printers, fax machines and access to the internet or intranet. Approximately 79% of respondents believed that the initiative would improve the adequacy of drug information available in their work site and 95% believed it would either not change (33%) or would improve (62%) communication to patients. Overall, respondents’ comments supported advancing the initiative; however, some comments revealed reservations regarding corporate or pharmacy buy-in, success of implementation, and ease of adoption. Conclusions This is the first nationwide study to report about pharmacists’ perspectives on paperless labeling. In general, pharmacists believe they are ready and that their pharmacies are well equipped for the transition to paperless labeling. Further exploration of perspectives from product label manufacturers and corporate pharmacy offices is needed to understand fully what will be necessary to complete this transition. PMID:23523874

An assessment of pharmacists' readiness for paperless labeling: a national survey.

PubMed

Ho, Yun-Xian; Chen, Qingxia; Nian, Hui; Johnson, Kevin B

2014-01-01

To assess the state of readiness for the adoption of paperless labeling among a nationally representative sample of pharmacies, including chain pharmacies, independent retail pharmacies, hospitals, and other rural or urban dispensing sites. Both quantitative and qualitative analyses were used to analyze responses to a cross-sectional survey disseminated to American Pharmacists Association pharmacists nationwide. The survey assessed factors related to pharmacists' attitudinal readiness (ie, perceptions of impact) and pharmacies' structural readiness (eg, availability of electronic resources, internet access) for the paperless labeling initiative. We received a total of 436 survey responses (6% response rate) from pharmacists representing 44 US states and territories. Across the spectrum of settings we studied, pharmacists had work access to computers, printers, fax machines and access to the internet or intranet. Approximately 79% of respondents believed that the initiative would improve the adequacy of drug information available in their work site and 95% believed it would either not change (33%) or would improve (62%) communication to patients. Overall, respondents' comments supported advancing the initiative; however, some comments revealed reservations regarding corporate or pharmacy buy-in, success of implementation, and ease of adoption. This is the first nationwide study to report about pharmacists' perspectives on paperless labeling. In general, pharmacists believe they are ready and that their pharmacies are well equipped for the transition to paperless labeling. Further exploration of perspectives from product label manufacturers and corporate pharmacy offices is needed to understand fully what will be necessary to complete this transition.

Improving response rate and quality of survey data with a scratch lottery ticket incentive

PubMed Central

2012-01-01

Background The quality of data collected in survey research is usually indicated by the response rate; the representativeness of the sample, and; the rate of completed questions (item-response). In attempting to improve a generally declining response rate in surveys considerable efforts are being made through follow-up mailings and various types of incentives. This study examines effects of including a scratch lottery ticket in the invitation letter to a survey. Method Questionnaires concerning oral health were mailed to a random sample of 2,400 adults. A systematically selected half of the sample (1,200 adults) received a questionnaire including a scratch lottery ticket. One reminder without the incentive was sent. Results The incentive increased the response rate and improved representativeness by reaching more respondents with lower education. Furthermore, it reduced item nonresponse. The initial incentive had no effect on the propensity to respond after the reminder. Conclusion When attempting to improve survey data, three issues become important: response rate, representativeness, and item-response. This study shows that including a scratch lottery ticket in the invitation letter performs well on all the three. PMID:22515335

Personalized Medicine-Based Approach to Model Patterns of Chemoresistance and Tumor Recurrence Using Ovarian Cancer Stem Cell Spheroids.

PubMed

Raghavan, Shreya; Mehta, Pooja; Ward, Maria R; Bregenzer, Michael E; Fleck, Elyse M A; Tan, Lijun; McLean, Karen; Buckanovich, Ronald J; Mehta, Geeta

2017-11-15

Purpose: Chemoresistant ovarian cancers grow in suspension within the ascites fluid. To screen the effect of chemotherapeutics and biologics on resistant ovarian cancers with a personalized basis, we developed a 3D hanging drop spheroid platform. Experimental Design: We initiated spheroids with primary aldehyde dehydrogenase-positive (ALDH + ) CD133 + ovarian cancer stem cells (OvCSC) from different patient samples and demonstrated that stem cell progeny from harvested spheroids was similar to the primary tumor. OvCSC spheroids were utilized to initiate tumors in immunodeficient mice. Drug responses to cisplatin and ALDH-targeting compound or JAK2 inhibitor determined whether the OvCSC population within the spheroids could be targeted. Cells that escaped therapy were isolated and used to initiate new spheroids and model tumor reemergence in a personalized manner. Results: OvCSC spheroids from different patients exhibited varying and personalized responses to chemotherapeutics. Xenografts were established from OvCSC spheroids, even with a single spheroid. Distinct responses to therapy were observed in distinct primary tumor xenografts similar to those observed in spheroids. Spheroids resistant to cisplatin/ALDH inhibitor therapy had persistent, albeit lower ALDH expression and complete loss of CD133 expression, whereas those resistant to cisplatin/JAK2 inhibitor therapy were enriched for ALDH + cells. Conclusions: Our 3D hanging drop suspension platform can be used to propagate primary OvCSCs that represent individual patient tumors effectively by differentiating in vitro and initiating tumors in mice. Therefore, our platform can be used to study cancer stem cell biology and model tumor reemergence to identify new targeted therapeutics from an effective personalized medicine standpoint. Clin Cancer Res; 23(22); 6934-45. ©2017 AACR . ©2017 American Association for Cancer Research.

A Retrospective Review of Pain Control by a Two-Step Irradiance Schedule During Topical ALA-Photodynamic Therapy of Non-melanoma Skin Cancer

PubMed Central

Zeitouni, Nathalie C.; Paquette, Anne D.; Housel, Joseph P.; Shi, Yi; Wilding, Gregory; Foster, Thomas H.; Henderson, Barbara W.

2013-01-01

Background and Objective Photodynamic therapy (PDT) with topical δ-aminolevulinic acid (ALA) of non-melanoma skin cancers is often associated with treatment-limiting pain. A previous study on basal cell carcinomas (BCCs) at Roswell Park Cancer Institute evaluated a two-step irradiance scheme as a means of minimizing pain, preserving outcomes, and limiting treatment time. We used an initial low irradiance until 90% of the protoporphyrin IX was photobleached, followed by a high irradiance interval until the prescribed fluence was delivered. Success of this pilot investigation motivated integration of the protocol into routine practice. Here we present a retrospective review of recent clinical experience in a broad patient population. Study Design/Materials and Methods This was a retrospective review of an existing dermatology data base. Fourteen caucasion patients - 9 men and 5 women, ages 18 to 80, with a total of 51 superficial and 73 nodular BCCs, and three Bowen's disease lesions – were included. ALA was applied to each lesion for approximately 4h. Lesions received an initial irradiance of 30 - 50 mW/cm2 for 20 J/cm2, followed by 150 mW/cm2 for a total fluence of 200-300 J/cm2. Pain was assessed using a visual analog scale (VAS). Clinical outcome was determined at 6-12 months. Results Median VAS scores were 1.0 for both irradiances. Five of 127 lesions required pain control with 1% xylocaine. Pain was strongly influenced by lesion location but not by lesion type, number, or size. Complete responses were achieved in 84.1% of BCCs, which compares favorably with reported results for single ALA-PDT treatments. Two of three Bowen's disease lesions showed a complete response. Complete responses for nodular BCCs were 37%, which are also within the range of reported outcomes. Conclusions A two-step irradiance protocol in ALA-PDT effectively minimizes pain, maintains excellent clinical outcomes in superficial lesions, and adds minimal treatment time. PMID:23390058

Family homework and school-based sex education: delaying early adolescents' sexual behavior.

PubMed

Grossman, Jennifer M; Frye, Alice; Charmaraman, Linda; Erkut, Sumru

2013-11-01

Early sexual activity can undermine adolescents' future school success and health outcomes. The purpose of this study was to assess the role of a family homework component of a comprehensive sex education intervention in delaying sexual initiation for early adolescents and to explore what social and contextual factors prevent adolescents from completing these family homework activities. This mixed methods study included 6th- and 7th-grade survey responses from 706 students at 11 middle school schools receiving a sex education intervention, as well as interviews from a subset of 33, 7th-grade students from the larger sample. Adolescents who completed more family homework assignments were less likely to have vaginal intercourse in 7th grade than those who completed fewer assignments, after controlling for self-reports of having had vaginal intercourse in 6th grade and demographic variables. Participants' explanations for not completing assignments included personal, curriculum, and family-based reasons. Family homework activities designed to increase family communication about sexual issues can delay sex among early adolescents and contribute to school-based sex education programs. Successful sex education programs must identify and address barriers to family homework completion. © 2013, American School Health Association.

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

Improving the reliability of verbal communication between primary care physicians and pediatric hospitalists at hospital discharge.

PubMed

Mussman, Grant M; Vossmeyer, Michael T; Brady, Patrick W; Warrick, Denise M; Simmons, Jeffrey M; White, Christine M

2015-09-01

Timely and reliable verbal communication between hospitalists and primary care physicians (PCPs) is critical for prevention of medical adverse events but difficult in practice. Our aim was to increase the proportion of completed verbal handoffs from on-call residents or attendings to PCPs within 24 hours of patient discharge from a hospital medicine service to ≥90% within 18 months. A multidisciplinary team collaborated to redesign the process by which PCPs were contacted following patient discharge. Interventions focused on the key drivers of obtaining stakeholder buy-in, standardization of the communication process, including assigning primary responsibility for discharge communication to a single resident on each team and batching calls during times of maximum resident availability, reliable automated process initiation through leveraging the electronic health record (EHR), and transparency of data. A run chart assessed the impact of interventions over time. The percentage of calls initiated within 24 hours of discharge improved from 52% to 97%, and the percentage of calls completed improved to 93%. Results were sustained for 18 months. Standardization of the communication process through hospital telephone operators, use of the discharge order to ensure initiation of discharge communication, and batching of phone calls were associated with improvements in our measures. Reliable verbal discharge communication can be achieved through the use of a standardized discharge communication process coupled with the EHR. © 2015 Society of Hospital Medicine.

Effects of diabetes mellitus on the clinical presentation and treatment response in tuberculosis.

PubMed

Leung, Chi C; Yew, Wing W; Mok, Thomas Y W; Lau, Kam S; Wong, Chi F; Chau, Chi H; Chan, Chi K; Chang, Kwok C; Tam, Greta; Tam, Cheuk M

2017-08-01

With the colliding global epidemics of diabetes mellitus (DM) and tuberculosis (TB), we studied the effects of DM on the presentation of TB and its response to treatment. Consecutive TB patients from 2006 to 2010 in a territory-wide treatment programme offering 9-month extended treatment for TB patients with DM were examined and followed up prospectively to assess their treatment response. Successful treatment completers were tracked through the TB registry and death registry for relapse, death or till 31 December 2014, whichever was the earliest. DM was independently associated with more chest symptoms (adjusted OR (AOR): 1.13) and systemic symptoms (AOR: 1.30) but less with other site-specific symptoms (AOR: 0.58) at TB presentation. There was more frequent pulmonary involvement (AOR: 1.69), with more extensive lung lesion (AOR: 1.25), lung cavity (AOR: 2.00) and positive sputum smear (AOR: 1.83) and culture (AOR: 1.38), but no difference in the proportion of retreatment cases or isoniazid and/or rifampicin resistance. After treatment initiation, there was higher overall incidence (AOR: 1.38) of adverse effects (mainly gastrointestinal symptoms, renal impairment and peripheral neuropathy but less fever and skin hypersensitivity reactions), more smear non-conversion (AOR: 1.59) and culture non-conversion (AOR: 1.40) at 2 months, and lower combined cure/treatment completion rate at 12 months (AOR: 0.79), but no difference in the relapse rate after having successfully completed treatment. DM adversely affected the clinical presentation and treatment response of TB, but there was no difference in the drug resistance and relapse rates. © 2017 Asian Pacific Society of Respirology.

Consumer Participation in Quality Improvements for Chronic Disease Care: Development and Evaluation of an Interactive Patient-Centered Survey to Identify Preferred Service Initiatives

PubMed Central

Paul, Christine L; Bryant, Jamie; Roos, Ian A; Henskens, Frans A; Paul, David J

2014-01-01

Background With increasing attention given to the quality of chronic disease care, a measurement approach that empowers consumers to participate in improving quality of care and enables health services to systematically introduce patient-centered initiatives is needed. A Web-based survey with complex adaptive questioning and interactive survey items would allow consumers to easily identify and prioritize detailed service initiatives. Objective The aim was to develop and test a Web-based survey capable of identifying and prioritizing patient-centered initiatives in chronic disease outpatient services. Testing included (1) test-retest reliability, (2) patient-perceived acceptability of the survey content and delivery mode, and (3) average completion time, completion rates, and Flesch-Kincaid reading score. Methods In Phase I, the Web-based Consumer Preferences Survey was developed based on a structured literature review and iterative feedback from expert groups of service providers and consumers. The touchscreen survey contained 23 general initiatives, 110 specific initiatives available through adaptive questioning, and a relative prioritization exercise. In Phase II, a pilot study was conducted within 4 outpatient clinics to evaluate the reliability properties, patient-perceived acceptability, and feasibility of the survey. Eligible participants were approached to complete the survey while waiting for an appointment or receiving intravenous therapy. The age and gender of nonconsenters was estimated to ascertain consent bias. Participants with a subsequent appointment within 14 days were asked to complete the survey for a second time. Results A total of 741 of 1042 individuals consented to participate (71.11% consent), 529 of 741 completed all survey content (78.9% completion), and 39 of 68 completed the test-retest component. Substantial or moderate reliability (Cohen’s kappa>0.4) was reported for 16 of 20 general initiatives with observed percentage agreement ranging from 82.1%-100.0%. The majority of participants indicated the Web-based survey was easy to complete (97.9%, 531/543) and comprehensive (93.1%, 505/543). Participants also reported the interactive relative prioritization exercise was easy to complete (97.0%, 189/195) and helped them to decide which initiatives were of most importance (84.6%, 165/195). Average completion time was 8.54 minutes (SD 3.91) and the Flesch-Kincaid reading level was 6.8. Overall, 84.6% (447/529) of participants indicated a willingness to complete a similar survey again. Conclusions The Web-based Consumer Preferences Survey is sufficiently reliable and highly acceptable to patients. Based on completion times and reading level, this tool could be integrated in routine clinical practice and allows consumers to easily participate in quality evaluation. Results provide a comprehensive list of patient-prioritized initiatives for patients with major chronic conditions and delivers practice-ready evidence to guide improvements in patient-centered care. PMID:25532217

Trough concentration and ABCG2 polymorphism are better to predict imatinib response in chronic myeloid leukemia: a meta-analysis.

PubMed

Jiang, Zhi-Ping; Zhao, Xie-Lan; Takahashi, Naoto; Angelini, Sabrina; Dubashi, Biswajit; Sun, Li; Xu, Ping

2017-01-01

The present study aimed to conduct a series of meta-analyses to investigate the influence of imatinib trough concentration (C 0 ), as well as ABCB1 and ABCG2 polymorphisms, on the clinical response in patients with chronic myeloid leukemia (CML). A literature search was conducted using the PubMed and Cochrane electronic databases to locate relevant papers from 2003 onward. Then, an initial meta-analysis of 14 studies involving 2184 patients was conducted to understand the effect of imatinib mesylate (IM) C 0 on clinical outcome in CML patients. Subsequently, a series of meta-analyses were performed, including up to 23 studies with 2577 patients, on the effect of genetic polymorphisms of ABCB1 and ABCG2 on the clinical response to IM. Meta-analysis revealed that patients who achieved a major molecular response (MMR) have a significantly higher IM C 0 than those who failed to achieve an MMR. We also found that the patients who achieved a complete cytogenic response (CCyR) have a significantly higher IM C 0 than those who did not achieve a CCyR. However, no significant difference in IM C 0 was found between the complete molecular response and non-complete molecular response groups. Additional analysis showed that ABCG2 421 variant A allele was significantly associated with a higher rate of MMR and overall response, especially in Asian patients. Meta-analysis did not reveal a correlation between ABCB1 C3435T and C1236T polymorphisms with any clinical response to IM. However, the G2677T/A polymorphism could play a role in IM response in the recessive model. This meta-analysis demonstrates that there was a significant correlation between the IM trough concentration and clinical responses, especially MMR and CCyR, in CML patients. Furthermore, we found that the probability of successful treatment was correlated with the ABCG2 C421A polymorphism, at least within the Asian population. We failed to determine an association between ABCB1 polymorphisms and IM response, although the G2677T/A polymorphism might be involved. However, further large-scale investigations using more sensitive genotyping methods would be required to confirm this.

Use of a Self-Instructional Radiographic Anatomy Module for Dental Hygiene Faculty Calibration.

PubMed

Brame, Jennifer L; AlGheithy, Demah Salem; Platin, Enrique; Mitchell, Shannon H

2017-06-01

Purpose: Dental hygiene educators often provide inconsistent instruction in clinical settings and various attempts to address the lack of consistency have been reported in the literature. The purpose of this pilot study was to determine if the use of a use of a self-instructional, radiographic anatomy (SIRA) module improved DH faculty calibration regarding the identifica-tion of normal intraoral and extraoral radiographic anatomy and whether its effect could be sustained over a period of four months. Methods: A convenience sample consisting of all dental hygiene faculty members involved in clinical instruction (N=23) at the University of North Carolina (UNC) was invited to complete the four parts of this online pilot study: a pre-test, review of the SIRA module, an immediate post-test, and a four-month follow-up post-test. Descriptive analyses, the Friedman's ANOVA, and the exact form of the Wilcoxon-Signed-Rank test were used to an-alyze the data. Level of significance was set at 0.05. Participants who did not complete all parts of the study were omitted from data analysis comparing the pre to post-test performance. Results: The pre-test response rate was 73.9% (N=17), and 88.2% (N=15) of those initial participants completed both the immediate and follow-up post-tests. Faculty completing all parts of the study consisted of: 5 full-time faculty, 5 part-time faculty, and 5 graduate teaching assistants. The Friedman's ANOVA revealed no statistically significant difference (P=0.179) in percentages of correct responses between the three tests (pre, post and follow-up). The exact form of the Wilcoxon-Signed-Rank test revealed marginal significance when comparing percent of correct responses at pre-test and immediate post-test (P=0.054), and no statistically significant difference when comparing percent of correct responses at immediate post-test and the follow-up post-test four months later (P=0.106). Conclusions: Use of a SIRA module did not significantly affect DH faculty test performance. Lack of statistical significance in the percentages of correct responses between the three tests may have been affected by the small number of participants completing all four parts of the study (N=15). Additional research is needed to identify and improve methods for faculty calibration. Copyright © 2017 The American Dental Hygienists’ Association.

Challenges of metal recycling and an international covenant as possible instrument of a globally extended producer responsibility.

PubMed

Wilts, Hennning; Bringezu, Stefan; Bleischwitz, Raimund; Lucas, Rainer; Wittmer, Dominic

2011-09-01

As illustrated by the case studies of end-of-life vehicles and waste electric and electronic equipment, the approach of an extended producer responsibility is undermined by the exports of used and waste products. This fact causes severe deficits regarding circular flows, especially of critical raw materials such as platinum group metals. With regard to global recycling there seems to be a responsibility gap which leads somehow to open ends of waste flows and a loss or down-cycling of potential secondary resources. Existing product-orientated extended producer responsibility (EPR) approaches with mass-based recycling quotas do not create adequate incentives to supply waste materials containing precious metals to a high-quality recycling and should be amended by aspects of a material stewardship. The paper analyses incentive effects on EPR for the mentioned product groups and metals, resulting from existing regulations in Germany. It develops a proposal for an international covenant on metal recycling as a policy instrument for a governance-oriented framework to initiate systemic innovations along the complete value chain taking into account product group- and resource group-specific aspects on different spatial levels. It aims at the effective implementation of a central idea of EPR, the transition of a waste regime still focusing on safe disposal towards a sustainable management of resources for the complete lifecycle of products.

Changes in metabolism in response to fasting and food restriction in the Steller sea lion (Eumetopias jubatus).

PubMed

Rosen, David A S; Trites, Andrew W

2002-06-01

Many animals lower their resting metabolism (metabolic depression) when fasting or consuming inadequate food. We sought to document this response by subjecting five Steller sea lions to periods of: (1) complete fasting; or (2) restricting them to 50% of their normal herring diet. The sea lions lost an average of 1.5% of their initial body mass per day (2.30 kg/d) during the 9-14-day fast, and their resting metabolic rates decreased 31%, which is typical of a "fasting response". However, metabolic depression did not occur during the 28-day food restriction trials, despite the loss of 0.30% of body mass per day (0.42 kg/d). This difference in response suggests that undernutrition caused by reduced food intake may stimulate a "hunger response", which in turn might lead to increased foraging effort. The progressive changes in metabolism we observed during the fasts were related to, but were not directly caused by, changes in body mass from control levels. Combining these results with data collected from experiments when Steller sea lions were losing mass on low energy squid and pollock diets reveals a strong relationship between relative changes in body mass and relative changes in resting metabolism across experimental conditions. While metabolic depression caused by fasting or consuming large amounts of low energy food reduced the direct costs from resting metabolism, it was insufficient to completely overcome the incurred energy deficit.

Laboratory-Induced Stress and Craving among Individuals with Prescription Opioid Dependence

PubMed Central

Back, Sudie E.; Gros, Daniel F.; Price, Matthew; LaRowe, Steve; Flanagan, Julianne; Brady, Kathleen T.; Davis, Charles; Jaconis, Maryanne; McCauley, Jenna L.

2015-01-01

Background Stress and conditioned drug cues have been implicated in the initiation, maintenance and relapse to substances of abuse. Although stress and drug cues are often encountered together, little research exists on whether stress potentiates the response to drug cues. Method Participants (N = 75) were 39 community recruited individuals with current prescription opioid (PO) dependence and 36 healthy controls. Participants stayed overnight in the hospital for one night and then completed laboratory testing the following morning. During laboratory testing, participants were randomly assigned to a stress task (Trier Social Stress Task; TSST) or a no-stress condition. Following the stress manipulation, all participants completed a PO cue paradigm. Immediately before and after the stress and cue tasks, the following were assessed: subjective (stress, craving, anger, sadness, happiness), physiological (heart rate, blood pressure, galvanic skin response), and neuroendocrine responses (cortisol and dehydroepiandrosterone). Results Internal validity of the stress task was demonstrated, as evidenced by significantly higher subjective stress, as well as cortisol, heart rate and blood pressure in the TSST compared to the no-stress group. Individuals with PO dependence evidenced significantly greater reactivity to the stress task than controls. Craving increased significantly in response to the drug cue task among PO participants. No stress × cue interaction was observed. Conclusions In this study, heightened stress reactivity was observed among individuals with PO dependence. Exposure to acute stress, however, did not potentiate craving in response to conditioned drug cues. PMID:26342626

Habituation of the metabolic and ventilatory responses to cold-water immersion in humans.

PubMed

Tipton, Michael J; Wakabayashi, Hitoshi; Barwood, Martin J; Eglin, Clare M; Mekjavic, Igor B; Taylor, Nigel A S

2013-01-01

An experiment was undertaken to answer long-standing questions concerning the nature of metabolic habituation in repeatedly cooled humans. It was hypothesised that repeated skin and deep-body cooling would produce such a habituation that would be specific to the magnitude of the cooling experienced, and that skin cooling alone would dampen the cold-shock but not the metabolic response to cold-water immersion. Twenty-one male participants were divided into three groups, each of which completed two experimental immersions in 12°C water, lasting until either rectal temperature fell to 35°C or 90min had elapsed. Between these two immersions, the control group avoided cold exposures, whilst two experimental groups completed five additional immersions (12°C). One experimental group repeatedly immersed for 45min in average, resulting in deep-body (1.18°C) and skin temperature reductions. The immersions in the second experimental group were designed to result only in skin temperature reductions, and lasted only 5min. Only the deep-body cooling group displayed a significantly blunted metabolic response during the second experimental immersion until rectal temperature decreased by 1.18°C, but no habituation was observed when they were cooled further. The skin cooling group showed a significant habituation in the ventilatory response during the initial 5min of the second experimental immersion, but no alteration in the metabolic response. It is concluded that repeated falls of skin and deep-body temperature can habituate the metabolic response, which shows tissue temperature specificity. However, skin temperature cooling only will lower the cold-shock response, but appears not to elicit an alteration in the metabolic response. Copyright © 2012 Elsevier Ltd. All rights reserved.

Patterns of relapse from a phase 3 Study of response-based therapy for intermediate-risk Hodgkin lymphoma (AHOD0031): a report from the Children's Oncology Group.

PubMed

Dharmarajan, Kavita V; Friedman, Debra L; Schwartz, Cindy L; Chen, Lu; FitzGerald, T J; McCarten, Kathleen M; Kessel, Sandy K; Iandoli, Matt; Constine, Louis S; Wolden, Suzanne L

2015-05-01

The study was designed to determine whether response-based therapy improves outcomes in intermediate-risk Hodgkin lymphoma. We examined patterns of first relapse in the study. From September 2002 to July 2010, 1712 patients <22 years old with stage I-IIA with bulk, I-IIAE, I-IIB, and IIIA-IVA with or without doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide were enrolled. Patients were categorized as rapid (RER) or slow early responders (SER) after 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). The SER patients were randomized to 2 additional ABVE-PC cycles or augmented chemotherapy with 21 Gy involved field radiation therapy (IFRT). RER patients were stipulated to undergo 2 additional ABVE-PC cycles and were then randomized to 21 Gy IFRT or no further treatment if complete response (CR) was achieved. RER without CR patients were non-randomly assigned to 21 Gy IFRT. Relapses were characterized without respect to site (initial, new, or both; and initial bulk or initial nonbulk), and involved field radiation therapy field (in-field, out-of-field, or both). Patients were grouped by treatment assignment (SER; RER/no CR; RER/CR/IFRT; and RER/CR/no IFRT). Summary statistics were reported. At 4-year median follow-up, 244 patients had experienced relapse, 198 of whom were fully evaluable for review. Those who progressed during treatment (n=30) or lacked relapse imaging (n=16) were excluded. The median time to relapse was 12.8 months. Of the 198 evaluable patients, 30% were RER/no CR, 26% were SER, 26% were RER/CR/no IFRT, 16% were RER/CR/IFRT, and 2% remained uncategorized. The 74% and 75% relapses involved initially bulky and nonbulky sites, respectively. First relapses rarely occurred at exclusively new or out-of-field sites. By contrast, relapses usually occurred at nodal sites of initial bulky and nonbulky disease. Although response-based therapy has helped define treatment for selected RER patients, it has not improved outcome for SER patients or facilitated refinement of IFRT volumes or doses. Copyright © 2015 Elsevier Inc. All rights reserved.

Partial maintenance of auditory-based cognitive training benefits in older adults

PubMed Central

Anderson, Samira; White-Schwoch, Travis; Choi, Hee Jae; Kraus, Nina

2014-01-01

The potential for short-term training to improve cognitive and sensory function in older adults has captured the public’s interest. Initial results have been promising. For example, eight weeks of auditory-based cognitive training decreases peak latencies and peak variability in neural responses to speech presented in a background of noise and instills gains in speed of processing, speech-in-noise recognition, and short-term memory in older adults. But while previous studies have demonstrated short-term plasticity in older adults, we must consider the long-term maintenance of training gains. To evaluate training maintenance, we invited participants from an earlier training study to return for follow-up testing six months after the completion of training. We found that improvements in response peak timing to speech in noise and speed of processing were maintained, but the participants did not maintain speech-in-noise recognition or memory gains. Future studies should consider factors that are important for training maintenance, including the nature of the training, compliance with the training schedule, and the need for booster sessions after the completion of primary training. PMID:25111032

Performance feedback, self-esteem, and cardiovascular adaptation to recurring stressors.

PubMed

Brown, Eoin G; Creaven, Ann-Marie

2017-05-01

This study sought to examine the effects of performance feedback and individual differences in self-esteem on cardiovascular habituation to repeat stress exposure. Sixty-six university students (n = 39 female) completed a self-esteem measure and completed a cardiovascular stress-testing protocol involving repeated exposure to a mental arithmetic task. Cardiovascular functioning was sampled across four phases: resting baseline, initial stress exposure, a recovery period, and repeated stress exposure. Participants were randomly assigned to receive fictional positive feedback, negative feedback, or no feedback following the recovery period. Negative feedback was associated with a sensitized blood pressure response to a second exposure of the stress task. Positive feedback was associated with decreased cardiovascular and psychological responses to a second exposure. Self-esteem was also found to predict reactivity and this interacted with the type of feedback received. These findings suggest that negative performance feedback sensitizes cardiovascular reactivity to stress, whereas positive performance feedback increases both cardiovascular and psychological habituation to repeat exposure to stressors. Furthermore, an individual's self-esteem also appears to influence this process.

Building toward Completion: Five Years into President Obama's 2020 Completion Initiative, Some Community Colleges Find Ways to Move the Needle on Student Success

ERIC Educational Resources Information Center

Pierce, Dennis

2015-01-01

In 2009, President Barack Obama announced the 2020 College Completion initiative. The goal: By 2020, the United States will have the greatest proportion of citizens who are college graduates, compared with the rest of the world. On a national level, however, the average six-year completion rate hasn't changed much in the more than five years since…

Dynamic gene expression response to altered gravity in human T cells.

PubMed

Thiel, Cora S; Hauschild, Swantje; Huge, Andreas; Tauber, Svantje; Lauber, Beatrice A; Polzer, Jennifer; Paulsen, Katrin; Lier, Hartwin; Engelmann, Frank; Schmitz, Burkhard; Schütte, Andreas; Layer, Liliana E; Ullrich, Oliver

2017-07-12

We investigated the dynamics of immediate and initial gene expression response to different gravitational environments in human Jurkat T lymphocytic cells and compared expression profiles to identify potential gravity-regulated genes and adaptation processes. We used the Affymetrix GeneChip® Human Transcriptome Array 2.0 containing 44,699 protein coding genes and 22,829 non-protein coding genes and performed the experiments during a parabolic flight and a suborbital ballistic rocket mission to cross-validate gravity-regulated gene expression through independent research platforms and different sets of control experiments to exclude other factors than alteration of gravity. We found that gene expression in human T cells rapidly responded to altered gravity in the time frame of 20 s and 5 min. The initial response to microgravity involved mostly regulatory RNAs. We identified three gravity-regulated genes which could be cross-validated in both completely independent experiment missions: ATP6V1A/D, a vacuolar H + -ATPase (V-ATPase) responsible for acidification during bone resorption, IGHD3-3/IGHD3-10, diversity genes of the immunoglobulin heavy-chain locus participating in V(D)J recombination, and LINC00837, a long intergenic non-protein coding RNA. Due to the extensive and rapid alteration of gene expression associated with regulatory RNAs, we conclude that human cells are equipped with a robust and efficient adaptation potential when challenged with altered gravitational environments.

Pharmacogenetics of steroid-responsive acute graft-versus-host disease.

PubMed

Arora, Mukta; Weisdorf, Daniel J; Shanley, Ryan M; Thyagarajan, Bharat

2017-05-01

Glucocorticoids are central to effective therapy of acute graft-versus-host disease (GVHD). However, only about half of the patients respond to steroids in initial therapy. Based on postulated mechanisms for anti-inflammatory effectiveness, we explored genetic variations in glucocorticoid receptor, co-chaperone proteins, membrane transporters, inflammatory mediators, and variants in the T-cell receptor complex in hematopoietic cell transplant recipients with acute GVHD requiring treatment with steroids and their donors toward response at day 28 after initiation of therapy. A total of 300 recipient and donor samples were analyzed. Twenty-three SNPs in 17 genes affecting glucocorticoid pathways were included in the analysis. In multiple regression analysis, donor SNP rs3192177 in the ZAP70 gene (O.R. 2.8, 95% CI: 1.3-6.0, P=.008) and donor SNP rs34471628 in the DUSPI gene (O.R. 0.3, 95% CI: 0.1-1.0, P=.048) were significantly associated with complete or partial response. However, after adjustment for multiple testing, these SNPs did not remain statistically significant. Our results, on this small, exploratory, hypothesis generating analysis suggest that common genetic variation in glucocorticoid pathways may help identify subjects with differential response to glucocorticoids. This needs further assessment in larger datasets and if validated could help identify subjects for alternative treatments and design targeted treatments to overcome steroid resistance. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Characterization of the photosynthetic induction response in a Populus species with stomata barely responding to light changes.

PubMed

Tang, Y; Liang, N

2000-08-01

The photosynthetic induction response is constrained by stomatal and biochemical limitations. However, leaves in some plants like Populus koreana x trichocarpa cv. Peace (a hybrid clone) may have little stomatal limitation because their stomata barely respond to changes in photon flux density (PFD). We examined the induction responses of leaves of well-watered and dehydrated P. koreana x trichocarpa plants grown in a high-light or a low-light regime. With an increase in PFD from 50 to 500 micromol m(-2) s(-1), steady-state stomatal conductance (g(s)) increased by only 0.25-8.2%, regardless of the initial g(s), but steady-state assimilation rate (A) increased by 550-1810%. Photosynthetic induction times required to reach 50% (IT50) and 90% (IT90) of A at high PFD were 60-90 s and 210-360 s, respectively. Examination of the dynamic relationships between A and g(s), and between A and intercellular CO2 concentration, indicated that the induction limitation was imposed completely by the biochemical components within 30-40 s after the PFD increase. Values of IT50 and IT90 were significantly higher in low-light leaves than in high-light leaves, whereas the induction state at 60 s and the induction efficiency at 60 and 120 s after the increase in PFD were lower in low-light leaves than in high-light leaves. Dehydration reduced leaf water potential (psi) significantly, resulting in a significantly decreased initial g(s). Leaf water potential had no significant effects on induction time in high-light leaves, but a low psi significantly reduced the induction time in low-light leaves. We conclude that the photosynthetic induction response was limited almost completely by biochemical components because the stomata barely responded to light changes. The biochemical limitation appeared to be higher in low-light leaves than in high-light leaves. Mild water stress may have reduced steady-state A and g(s), but it had little effect on the photosynthetic induction response in high-light leaves.

Protection against methanol-induced retinal toxicity by LED photostimulation

NASA Astrophysics Data System (ADS)

Whelan, Harry T.; Wong-Riley, Margaret T. T.; Eells, Janis T.

2002-06-01

We have initiated experiments designed to test the hypothesis that 670-nm Light-Emitting Diode (LED) exposure will attenuate formate-induced retinal dysfunction in a rodent model of methanol toxicity. Methanol intoxication produces toxic injury to the retina. The toxic metabolite formed in methanol intoxication is formic acid, a mitochondrial toxin known to inhibit cytochrome oxidase activity. 670-nm LED light has been hypothesized to act by stimulating cytochrome oxidase activity. To test this hypothesis, one group of animals was intoxicated with methanol, a second group was intoxicated with methanol and LED-treated and a third group was untreated. LED treatment (670 nm for 1 min 45 seconds equals 50 mW/cm2, 4 joules/cm2) was administered at 5, 25, and 50 hours after the initial dose of methanol. At 72 hours of methanol intoxication, retinal function was assessed by measurement of ERG responses and retinas were prepared for histologic analysis. ERG responses recorded in methanol-intoxicated animals revealed profound attenuation of both rod-dominated and UV-cone mediated responses. In contrast, methanol- intoxicated animals exposed to LED treatment exhibited a nearly complete recovery of rod-dominated ERG responses and a slight improvement of UV-cone mediated ERG responses. LED treatment also protected the retina against the histopathologic changes produced by formate in methanol intoxication. These data provide evidence that LED phototherapy protects the retina against the cytotoxic actions of formate and are consistent with the hypothesis that LED photostimulation improves mitochondrial respiratory chain function.

Evaluating the nondrug costs of formulary coverage restrictions.

PubMed

Abourjaily, Paul; Gouveia, William A; Selker, Harry P; Zucker, Deborah R

2005-08-01

Clinicians often are required to switch prescribed therapy for their patients in response to health plan initiatives for controlling drug expenditures. To explore the effect of these initiatives, we sought clinicians' feedback regarding their practices and processes for switching patients' medications to accommodate insurance coverage. Self-administered Intranet-based survey of clinicians at an urban, tertiary-care hospital. Using survey responses, we calculate nondrug costs induced by formulary cost-saving measures. A total of 91 responses were received from 569 providers who were sent a request to complete the questionnaire via electronic mail (18 percent response rate). It took an average of 11.1, 18.9, and 16.4 minutes for physicians, nurses, and nurse practitioners/physician assistants, respectively, to make the medication switch. The mean number of switches per month ranged from 10.6 to 36.9. More than half the time spent on these switches is not directly reimbursed. Specific switch-induced intervention costs differed for different drug types. The effect on clinician workload tended to be an inconvenience. While the majority of physicians and nurse practitioners/physician assistants did not feel this process damaged patient-provider relations, most nurses did. In response to formulary restrictions, other costs are induced and incurred by providers and patients. The extent of patient costs, including those from adverse drug reactions, needs further study. More research is needed to elucidate costs and burden shifts as all parties involved evaluate and modify plans to moderate prescription drug expenditures.

Kinematics of self-initiated and reactive karate punches.

PubMed

Martinez de Quel, Oscar; Bennett, Simon J

2014-03-01

This study investigated whether within-task expertise affects the reported asymmetry in execution time exhibited in reactive and self-initiated movements. Karate practitioners and no-karate practitioners were compared performing a reverse punch in reaction to an external stimulus or following the intention to produce a response (self-initiated). The task was completed following the presentation of a specific (i.e., life-size image of opponent) or general stimulus and in the presence of click trains or white noise. Kinematic analyses indicated reactive movement had shorter time to peak velocity and movement time, as well as greater accuracy than self-initiated movement. These differences were independent of participant skill level although peak velocity was higher in the karate practice group than in the no-karate practice group. Reaction time (RT) of skilled participants was facilitated by a specific stimulus. There was no effect on RT or kinematic variables of the different type of auditory cues. The results of this study indicate that asymmetry in execution time of reactive and self-initiated movement holds irrespective of within-task expertise and stimulus specificity. This could have implications for training of sports and/or relearning of tasks that require rapid and accurate movements to intercept/contact a target.

Predictors of outcome of an Internet-based cognitive-behavioural therapy for post-traumatic stress disorder in older adults.

PubMed

Böttche, Maria; Kuwert, Philipp; Pietrzak, Robert H; Knaevelsrud, Christine

2016-03-01

The aim of this study was to evaluate the role of resource-oriented variables such as self-efficacy, locus of control (LOC) and post-traumatic growth (PTG) in predicting treatment response in older adults with post-traumatic stress. Fifty-eight older adults with subsyndromal or greater severity of war-associated post-traumatic stress disorder (PTSD) symptoms completed a randomized controlled Internet-based cognitive-behavioural therapy (CBT) with immediate and delayed treatment groups. Assessments of PTSD severity and resource-oriented variables of self-efficacy, LOC and PTG were conducted at baseline, post-treatment and at a 6-month follow-up. Results revealed that pre-treatment scores on measures of internal LOC and PTG predicted PTSD symptom severity at post-treatment, even after controlling for initial PTSD. At a 6-month follow-up, internal LOC continued to predict PTSD symptom severity. In addition, repeated-measures analyses of variance revealed that, relative to older adults with low internal LOC and PTG, older adults with high internal LOC and PTG, respectively, did not differ with respect to initial PTSD severity, but they showed a more pronounced response to treatment. These findings suggest that greater locus of control and post-traumatic growth is associated with greater improvement in PTSD symptoms following Internet-based CBT. Assessment of these constructs may be useful in identifying trauma survivors who are most likely to respond to CBT. Greater internal locus of control and post-traumatic growth is associated with greater improvement in PTSD symptoms following Internet-based CBT. Older adults with initial high internal locus of control and post-traumatic growth, respectively, did not differ with respect to initial PTSD severity, but they showed a more pronounced response to treatment. It could be assumed that patients with initial functional appraisals could benefit easier and faster from a trauma-focused cognitive-behavioural therapy compared to individuals with lower internal locus of control and post-traumatic growth. © 2015 The British Psychological Society.

Cisplatin, Gemcitabine, and Lapatinib as Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer.

PubMed

Narayan, Vivek; Mamtani, Ronac; Keefe, Stephen; Guzzo, Thomas; Malkowicz, S Bruce; Vaughn, David J

2016-07-01

We sought to investigate the safety and efficacy of gemcitabine, cisplatin, and lapatinib (GCL) as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) planned for radical cystectomy. Four cycles of GCL were administered as neoadjuvant therapy for patients with MIBC. Although initially designed as a phase II efficacy study with a primary endpoint of pathologic complete response at the time of radical cystectomy, the dose selected for investigation proved excessively toxic. A total of six patients were enrolled. The initial four patients received gemcitabine 1,000 mg/m(2) intravenously on days 1 and 8 and cisplatin 70 mg/m(2) intravenously on day 1 of each 21-day treatment cycle. Lapatinib was administered as 1,000 mg orally daily starting one week prior to the initiation of cycle 1 of gemcitabine and cisplatin (GC) and continuing until the completion of cycle 4 of GC. These initial doses were poorly tolerated, and the final two enrolled patients received a reduced lapatinib dose of 750 mg orally daily. However, reduction of the lapatinib dose did not result in improved tolerance or drug-delivery, and the trial was terminated early due to excessive toxicity. Grade 3/4 toxicities included diarrhea (33%), nausea/vomiting (33%), and thrombocytopenia (33%). The addition of lapatinib to GC as neoadjuvant therapy for MIBC was limited by excessive treatment-related toxicity. These findings highlight the importance of thorough dose-escalation investigation of combination therapies prior to evaluation in the neoadjuvant setting, as well as the limitations of determination of maximum tolerated dose for novel targeted combination regimens.

Geoscientific Site Evaluation Approach for Canada's Deep Geological Repository for Used Nuclear Fuel

NASA Astrophysics Data System (ADS)

Sanchez-Rico Castejon, M.; Hirschorn, S.; Ben Belfadhel, M.

2015-12-01

The Nuclear Waste Management Organization (NWMO) is responsible for implementing Adaptive Phased Management, the approach selected by the Government of Canada for long-term management of used nuclear fuel generated by Canadian nuclear reactors. The ultimate objective of APM is the centralized containment and isolation of Canada's used nuclear fuel in a Deep Geological Repository in a suitable crystalline or sedimentary rock formation. In May 2010, the NWMO published and initiated a nine-step site selection process to find an informed and willing community to host a deep geological repository for Canada's used nuclear fuel. The site selection process is designed to address a broad range of technical and social, economic and cultural factors. The site evaluation process includes three main technical evaluation steps: Initial Screenings; Preliminary Assessments; and Detailed Site Characterizations, to assess the suitability of candidate areas in a stepwise manner over a period of many years. By the end of 2012, twenty two communities had expressed interest in learning more about the project. As of July 2015, nine communities remain in the site selection process. To date (July 2015), NWMO has completed Initial Screenings for the 22 communities that expressed interest, and has completed the first phase of Preliminary Assessments (desktop) for 20 of the communities. Phase 2 of the Preliminary Assessments has been initiated in a number of communities, with field activities such as high-resolution airborne geophysical surveys and geological mapping. This paper describes the approach, methods and criteria being used to assess the geoscientific suitability of communities currently involved in the site selection process.

Incorporating Variational Local Analysis and Prediction System (vLAPS) Analyses with Nudging Data Assimilation: Methodology and Initial Results

DTIC Science & Technology

2017-09-01

Robert E Dumais Jr  Computational and  Information  Sciences Directorate, ARL    Yuanfu Xie  National Oceanic and Atmospheric Administration, Boulder, CO...No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for...reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection information

White Sands Missile Range 2007 Urban Study (W07US): Data Analysis, Volume DA-1 (Analysis of Disaster Response Drills and Concurrent Atmospheric Data)

DTIC Science & Technology

2011-10-01

situational awareness resource that would automatically transmit this timely information to the mobilized workforce and rescuer professionals. AUTHOR...To the east were a small, tailored grassy area; a four-row parking lot with a dividing walkway between rows two and three; and a four- lane road...the west side of the subject building was an impediment and was moved . Once completed, the PI and Fire Chief initiated the fire alarm. The subject

Healthcare professionals' perceptions on the emotional impact of having an inadequate response to antidepressant medications: survey and prospective patient audit.

PubMed

Mago, Rajnish; Fagiolini, Andrea; Weiller, Emmanuelle; Weiss, Catherine

2018-01-01

Despite the availability of effective antidepressants, about half of patients with major depressive disorder (MDD) display an inadequate response to their initial treatment. A large patient survey recently reported that 29.8% of MDD patients experiencing an inadequate treatment response felt frustrated about their medication and 19.2% were frustrated with their healthcare provider. This survey and chart audit evaluated healthcare professionals' (HCP) views on the emotional impact of having an inadequate response to antidepressant medication. HCPs who frequently treat patients with MDD completed a survey and chart audit of their MDD patients currently experiencing an inadequate response to antidepressant treatment. 287 HCPs completed 1336 chart audits. HCPs reported that 38% of their patients were trusting/accepting of their MDD medications and 41% of their patients trusted/felt confident with their healthcare provision. Conversely, HCPs reported that 11% of their patients were frustrated with their medication and 5% with their healthcare benefits. HCPs cited impact on daily life (53%) and treatment issues (lack of efficacy and side effects; 50%) as the main drivers for their patients' feelings of frustration. When HCPs recognized patients' feelings of frustration, the top concerns of the HCPs were worsening of symptoms (43%) and non-compliance (41%). This survey and chart audit highlights the emotional burden associated with inadequate responses to MDD treatment in addition to persistent symptoms. Differences between the views of the HCPs and patients are highlighted and suggest that HCPs may underestimate the full impact that having to try numerous medications has on their patients.

Correlates of adherence to a telephone-based multiple health behavior change cancer preventive intervention for teens: the Healthy for Life Program (HELP).

PubMed

Mays, Darren; Peshkin, Beth N; Sharff, McKane E; Walker, Leslie R; Abraham, Anisha A; Hawkins, Kirsten B; Tercyak, Kenneth P

2012-02-01

This study examined factors associated with teens' adherence to a multiple health behavior cancer preventive intervention. Analyses identified predictors of trial enrollment, run-in completion, and adherence (intervention initiation, number of sessions completed). Of 104 teens screened, 73% (n = 76) were trial eligible. White teens were more likely to enroll than non-Whites (χ(2)[1] df = 4.49, p = .04). Among enrolled teens, 76% (n = 50) completed the run-in; there were no differences between run-in completers and noncompleters. A majority of run-in completers (70%, n = 35) initiated the intervention, though teens who initiated the intervention were significantly younger than those who did not (p < .05). The mean number of sessions completed was 5.7 (SD = 2.6; maximum = 8). After adjusting for age, teens with poorer session engagement (e.g., less cooperative) completed fewer sessions (B = -1.97, p = .003, R (2) = .24). Implications for adolescent cancer prevention research are discussed.

Male sexuality.

PubMed

Ginsberg, Terrie B

2010-05-01

It should be recognized that sexuality in the aging male is of such import that a complete sexual history must be performed. By taking a complete sexual history, facts can be obtained that will allow for appropriate focus relating to a holistic evaluation and will enable us to dispel antiquated sexual myths pertaining to the aging male. If initiated by the history taker, questions concerning sexuality may be discussed more comfortably by the patient. Erectile dysfunction, male sexual response cycle, testosterone, sexually transmitted diseases, human immunodeficiency virus, long-term illness, along with religion and culture are explored in this article with the aim of improving one's knowledge base, self reflection, and awareness of the importance of male sexuality. A complete understanding and appreciation of the aging male's medical history, surgical history, social history, and emotional history as well as his sexual, cultural, and religious concepts will allow the health care provider to better analyze information, and to recommend and provide appropriate advice and treatment to the aging male patient. Copyright 2010 Elsevier Inc. All rights reserved.

Structural features of the rice chromosome 4 centromere.

PubMed

Zhang, Yu; Huang, Yuchen; Zhang, Lei; Li, Ying; Lu, Tingting; Lu, Yiqi; Feng, Qi; Zhao, Qiang; Cheng, Zhukuan; Xue, Yongbiao; Wing, Rod A; Han, Bin

2004-01-01

A complete sequence of a chromosome centromere is necessary for fully understanding centromere function. We reported the sequence structures of the first complete rice chromosome centromere through sequencing a large insert bacterial artificial chromosome clone-based contig, which covered the rice chromosome 4 centromere. Complete sequencing of the 124-kb rice chromosome 4 centromere revealed that it consisted of 18 tracts of 379 tandemly arrayed repeats known as CentO and a total of 19 centromeric retroelements (CRs) but no unique sequences were detected. Four tracts, composed of 65 CentO repeats, were located in the opposite orientation, and 18 CentO tracts were flanked by 19 retroelements. The CRs were classified into four types, and the type I retroelements appeared to be more specific to rice centromeres. The preferential insert of the CRs among CentO repeats indicated that the centromere-specific retroelements may contribute to centromere expansion during evolution. The presence of three intact retrotransposons in the centromere suggests that they may be responsible for functional centromere initiation through a transcription-mediated mechanism.

The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5-RNA interaction and filament assembly

PubMed Central

Bruns, Annie M.; Leser, George P.; Lamb, Robert A.; Horvath, Curt M.

2014-01-01

SUMMARY Cytoplasmic pattern recognition receptors detect non-self RNAs during virus infections and initiate antiviral signaling. One receptor, MDA5, possesses essential signaling domains, but weak RNA binding. A second receptor, LGP2, rapidly detects diverse dsRNA species, but lacks signaling domains. Accumulating evidence suggests LGP2 and MDA5 work together to detect viral RNA and generate a complete antiviral response, but the basis for their cooperation has been elusive. Experiments presented here address this gap in antiviral signaling, revealing that LGP2 assists MDA5-RNA interactions leading to enhanced MDA5-mediated antiviral signaling. LGP2 increases the initial rate of MDA5-RNA interaction and regulates MDA5 filament assembly, resulting in the formation of more numerous, shorter MDA5 filaments that are shown to generate equivalent or greater signaling activity in vivo than the longer filaments containing only MDA5. These findings provide a mechanism for LGP2 co-activation of MDA5 and a biological context for MDA5-RNA filaments in antiviral responses. PMID:25127512

Long-term survival in an adolescent with widely metastatic renal cell carcinoma with rhabdoid features.

PubMed

Ettinger, L J; Goodell, L A; Javidian, P; Hsieh, Y; Amenta, P

2000-01-01

Renal cell carcinoma is rarely seen in children and adolescents. Patients with widespread disease at diagnosis have a particularly poor survival rate. Currently, all known chemotherapy has been ineffective in improving the median survival in patients with advanced disease. A 13-year-old black boy with stage IV renal cell carcinoma with rhabdoid features is a long-term disease-free survivor after aggressive multiagent chemotherapy. After the initial evaluation and histologic diagnosis of renal cell carcinoma, the patient received three courses of an aggressive chemotherapy regimen consisting of vincristine, doxorubicin, cyclophosphamide with mesna uroprotection, granulocyte colony-stimulating factor and erythropoietin (Epogen). After an almost complete response, a radical nephrectomy was performed and results demonstrated a solitary small nodule with viable tumor. After surgery, he received floxuridine infusion for 14 days by circadian schedule at 28-day intervals for a total of 1 year. The patient is well and free of disease 5 years after initial presentation. The dramatic response to treatment and long-term disease-free survival of this patient suggest this chemotherapeutic approach warrants additional investigation.

Recent Advances in Chemotherapy and Surgery for Colorectal Liver Metastases

PubMed Central

Passot, Guillaume; Soubrane, Olivier; Giuliante, Felice; Zimmitti, Giuseppe; Goéré, Diane; Yamashita, Suguru; Vauthey, Jean-Nicolas

2016-01-01

Background The liver is the most common site of metastases for colorectal cancer, and combined resection with systemic chemotherapy is the most effective strategy for survival. The aim of this article is to provide a comprehensive summary on four hot topics related to chemotherapy and surgery for colorectal liver metastases (CLM), namely: (1) chemotherapy-related liver injuries: prediction and impact, (2) surgery for initially unresectable CLM, (3) the emerging role of RAS mutations, and (4) the role of hepatic arterial infusion of chemotherapy (HAIC). Summary and Key Messages (1) The use of chemotherapy before liver resection for CLM leads to drug-specific hepatic toxicity, which negatively impacts posthepatectomy outcomes. (2) Curative liver resection of initially unresectable CLM following conversion chemotherapy should be attempted whenever possible, provided that a safe future liver remnant volume is achieved. (3) For CLM, RAS mutation status is needed to guide the use of targeted chemotherapy with anti-epithelial growth factor receptor (EGFR) agents, and is a major prognostic factor that may contribute to optimize surgical strategy. (4) HAIC agents increase the rate of objective response and the rate of complete pathological response. PMID:27995091

Recent Advances in Chemotherapy and Surgery for Colorectal Liver Metastases.

PubMed

Passot, Guillaume; Soubrane, Olivier; Giuliante, Felice; Zimmitti, Giuseppe; Goéré, Diane; Yamashita, Suguru; Vauthey, Jean-Nicolas

2016-11-01

The liver is the most common site of metastases for colorectal cancer, and combined resection with systemic chemotherapy is the most effective strategy for survival. The aim of this article is to provide a comprehensive summary on four hot topics related to chemotherapy and surgery for colorectal liver metastases (CLM), namely: (1) chemotherapy-related liver injuries: prediction and impact, (2) surgery for initially unresectable CLM, (3) the emerging role of RAS mutations, and (4) the role of hepatic arterial infusion of chemotherapy (HAIC). (1) The use of chemotherapy before liver resection for CLM leads to drug-specific hepatic toxicity, which negatively impacts posthepatectomy outcomes. (2) Curative liver resection of initially unresectable CLM following conversion chemotherapy should be attempted whenever possible, provided that a safe future liver remnant volume is achieved. (3) For CLM, RAS mutation status is needed to guide the use of targeted chemotherapy with anti-epithelial growth factor receptor (EGFR) agents, and is a major prognostic factor that may contribute to optimize surgical strategy. (4) HAIC agents increase the rate of objective response and the rate of complete pathological response.

Exploring parental behavior and child interactive engagement: A study on children with a significant cognitive and motor developmental delay.

PubMed

Van Keer, Ines; Colla, Stephy; Van Leeuwen, Karla; Vlaskamp, Carla; Ceulemans, Eva; Hoppenbrouwers, Karel; Desoete, Annemie; Maes, Bea

2017-05-01

Parenting factors are one of the most striking gaps in the current scientific literature on the development of young children with significant cognitive and motor disabilities. We aim to explore the characteristics of, and the association between, parental behavior and children's interactive engagement within this target group. Twenty-five parent-child dyads (with children aged 6-59 months) were video-taped during a 15-min unstructured play situation. Parents were also asked to complete the Parental Behavior Scale for toddlers. The video-taped observations were scored using the Child and Maternal Behavior Rating Scales. Low levels of parental discipline and child initiation were found. Parental responsivity was positively related to child attention and initiation. Compared to children with no or other levels of disabilities, this target group exhibits large differences in frequency levels and, to a lesser extent, the concrete operationalization of parenting domains. Further, this study confirms the importance of sensitive responsivity as the primary variable in parenting research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Correlates of human papillomavirus (HPV) vaccination initiation and completion among 18-26 year olds in the United States.

PubMed

Adjei Boakye, Eric; Lew, Daphne; Muthukrishnan, Meera; Tobo, Betelihem B; Rohde, Rebecca L; Varvares, Mark A; Osazuwa-Peters, Nosayaba

2018-04-30

To examine correlates of HPV vaccination uptake in a nationally representative sample of 18-26-year-old adults. Young adults aged 18-26 years were identified from the 2014 and 2015 National Health Interview Survey (n = 7588). Survey-weighted multivariable logistic regression models estimated sociodemographic factors associated with HPV vaccine initiation (≥1 dose) and completion (≥3 doses). Approximately 27% of study participants had initiated the HPV vaccine and 16% had completed the HPV vaccine. Participants were less likely to initiate the vaccine if they were men [(adjusted odds ratio) 0.19; (95% confidence interval) 0.16-0.23], had a high school diploma (0.40; 0.31-0.52) or less (0.46; 0.32-0.64) vs. college graduates, and were born outside the United States (0.52; 0.40-0.69). But, participants were more likely to initiate the HPV vaccine if they visited the doctor's office 1-5 times (2.09; 1.56-2.81), or ≥ 6 times (1.86; 1.48-2.34) within the last 12 months vs. no visits. Odds of completing HPV vaccine uptake followed the same pattern as initiation. And after stratifying the study population by gender and foreign-born status, these variables remained statistically significant. In our nationally representative study, only one out of six 18-26 year olds completed the required vaccine doses. Men, individuals with high school or less education, and those born outside the United States were less likely to initiate and complete the HPV vaccination. Our findings suggest that it may be useful to develop targeted interventions to promote HPV vaccination among those in the catch-up age range.

Administering an epoch initiated for remote memory access

DOEpatents

Blocksome, Michael A; Miller, Douglas R

2014-03-18

Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

Administering an epoch initiated for remote memory access

DOEpatents

Blocksome, Michael A; Miller, Douglas R

2012-10-23

Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

Administering an epoch initiated for remote memory access

DOEpatents

Blocksome, Michael A.; Miller, Douglas R.

2013-01-01

Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

Excellent response to chemotherapy post immunotherapy

PubMed Central

Dwary, Ashish D.; Master, Samip; Patel, Abhishek; Cole, Constance; Mansour, Richard; Mills, Glenn; Koshy, Nebu; Peddi, Prakash; Burton, Gary; Hammoud, Dalia; Beedupalli, Kavitha

2017-01-01

Introduction Immunotherapy in the form of immune checkpoint inhibitors has changed the landscape of cancer treatment. Newer monoclonal antibodies are coming up and are being tested in various cancers during different stages of treatment. With the increasing use of immune checkpoint inhibitors in the management of various types of cancers, the question is raised as to what next can be offered to a patient who has progressed on this newer treatment. Does Sequence matter? There have been reports of improved responses to chemotherapy after immunotherapy in the form of vaccines. Here we present a case series of 6 patients who progressed on immunotherapy with immune checkpoint inhibitors after initial modality of treatment (chemotherapy/radiation), subsequently received chemotherapy with excellent response. Methods We have a cohort of six patients who had disease progression on second line Immunotherapy for solid or hematological malignancies and had ECOG < 2. All these patients received third line salvage chemotherapy. Three patients had metastatic head and neck cancer, 2 had non-small cell lung cancer (NSCLC), and one had T -cell rich B- cell lymphoma. Prior review and approval were obtained from our institutional review board. Results All patients had an excellent response to chemotherapy in third line setting, after immune checkpoint inhibitors and most of them achieved a complete response. Conclusion Targeting cancer with chemotherapy after failure of immunotherapy is a valid option and can lead to better response rates and PFS which may lead to OS. This effect may be secondary to immunotherapy removing the inhibition exerted by tumor cells or other immune cells initially followed by cytotoxic chemotherapy mediated killing of tumor cells. PMID:29207685

Conditional survival in patients with chronic myeloid leukemia in chronic phase in the era of tyrosine kinase inhibitors.

PubMed

Sasaki, Koji; Kantarjian, Hagop M; Jain, Preetesh; Jabbour, Elias J; Ravandi, Farhad; Konopleva, Marina; Borthakur, Gautam; Takahashi, Koichi; Pemmaraju, Naveen; Daver, Naval; Pierce, Sherry A; O'Brien, Susan M; Cortes, Jorge E

2016-01-15

Tyrosine kinase inhibitors (TKIs) significantly improve survival in patients with chronic myeloid leukemia in chronic phase (CML-CP). Conditional probability provides survival information in patients who have already survived for a specific period of time after treatment. Cumulative response and survival data from 6 consecutive frontline TKI clinical trials were analyzed. Conditional probability was calculated for failure-free survival (FFS), transformation-free survival (TFS), event-free survival (EFS), and overall survival (OS) according to depth of response within 1 year of the initiation of TKIs, including complete cytogenetic response, major molecular response, and molecular response with a 4-log or 4.5-log reduction. A total of 483 patients with a median follow-up of 99.4 months from the initiation of treatment with TKIs were analyzed. Conditional probabilities of FFS, TFS, EFS, and OS for 1 additional year for patients alive after 12 months of therapy ranged from 92.0% to 99.1%, 98.5% to 100%, 96.2% to 99.6%, and 96.8% to 99.7%, respectively. Conditional FFS for 1 additional year did not improve with a deeper response each year. Conditional probabilities of TFS, EFS, and OS for 1 additional year were maintained at >95% during the period. In the era of TKIs, patients with chronic myeloid leukemia in chronic phase who survived for a certain number of years maintained excellent clinical outcomes in each age group. Cancer 2016;122:238-248. © 2015 American Cancer Society. © 2015 American Cancer Society.

Social media methods for studying rare diseases.

PubMed

Schumacher, Kurt R; Stringer, Kathleen A; Donohue, Janet E; Yu, Sunkyung; Shaver, Ashley; Caruthers, Regine L; Zikmund-Fisher, Brian J; Fifer, Carlen; Goldberg, Caren; Russell, Mark W

2014-05-01

For pediatric rare diseases, the number of patients available to support traditional research methods is often inadequate. However, patients who have similar diseases cluster "virtually" online via social media. This study aimed to (1) determine whether patients who have the rare diseases Fontan-associated protein losing enteropathy (PLE) and plastic bronchitis (PB) would participate in online research, and (2) explore response patterns to examine social media's role in participation compared with other referral modalities. A novel, internet-based survey querying details of potential pathogenesis, course, and treatment of PLE and PB was created. The study was available online via web and Facebook portals for 1 year. Apart from 2 study-initiated posts on patient-run Facebook pages at the study initiation, all recruitment was driven by study respondents only. Response patterns and referral sources were tracked. A total of 671 respondents with a Fontan palliation completed a valid survey, including 76 who had PLE and 46 who had PB. Responses over time demonstrated periodic, marked increases as new online populations of Fontan patients were reached. Of the responses, 574 (86%) were from the United States and 97 (14%) were international. The leading referral sources were Facebook, internet forums, and traditional websites. Overall, social media outlets referred 84% of all responses, making it the dominant modality for recruiting the largest reported contemporary cohort of Fontan patients and patients who have PLE and PB. The methodology and response patterns from this study can be used to design research applications for other rare diseases. Copyright © 2014 by the American Academy of Pediatrics.

Initiating undergraduate medical students into communities of research practise: what do supervisors recommend?

PubMed Central

2010-01-01

Background Much has been written in the educational literature on the value of communities of practise in enhancing student learning. Here, we take the experience of senior undergraduate medical students involved in short-term research as a member of a team as a paradigm for learning in a community of practise. Based on feedback from experienced supervisors, we offer recommendations for initiating students into the research culture of their team. In so doing, we endeavour to create a bridge between theory and practise through disseminating advice on good supervisory practise, where the supervisor is perceived as an educator responsible for designing the research process to optimize student learning. Methods Using the questionnaire design tool SurveyMonkey and comprehensive lists of contact details of staff who had supervised research projects at the University of Edinburgh during 1995 - 2008, current and previous supervisors were invited to recommend procedures which they had found successful in initiating students into the research culture of a team. Text responses were then coded in the form of derivative recommendations and categorized under general themes and sub-themes. Results Using the chi-square tests of linear trend and association, evidence was found for a positive trend towards more experienced supervisors offering responses (χ2 = 16.833, p < 0.0005, n = 215) while there was a lack of evidence of bias in the gender distribution of respondents (χ2 = 0.482, p = 0.487, n = 203), respectively. A total of 126 codes were extracted from the text responses of 65 respondents. These codes were simplified to form a complete list of 52 recommendations, which were in turn categorized under seven derivative overarching themes, the most highly represented themes being Connecting the student with others and Cultivating self-efficacy in research competence. Conclusions Through the design of a coding frame for supervisor responses, a wealth of ideas has been captured to make communities of research practise effective mediums for undergraduate student learning. The majority of these recommendations are underpinned by educational theory and have the potential to take the learner beyond the stage of initiation to that of integration within their community of research practise. PMID:21092088

An Examination of Stress and Coping among Adults Diagnosed with Severe Mental Illness

PubMed Central

Robilotta, Stephanie; Cueto, Ecena; Yanos, Philip T.

2011-01-01

The present study explored the types of major life and chronic stressors that people with severe mental illness experience, and the coping strategies that are used in response to them. Twenty-eight adults with severe mental illness completed qualitative interviews focused on stress and coping in the prior six months. Participants reported experiencing disruptive major life events including the sudden death of a loved one, loss of housing, and criminal victimization, as well as chronic stressors such as psychiatric symptoms and substance abuse issues, substandard living conditions, legal problems, and health concerns. Results suggested that persons with severe mental illness frequently use problem-centered coping strategies in response to most types of stressors, including major life events, although this occurred after the initial application of avoidant coping strategies. Future research should explore whether or not the identified stressors and the coping strategies used in response to them are unique to this population. PMID:21149987

Memory self-efficacy predicts responsiveness to inductive reasoning training in older adults.

PubMed

Payne, Brennan R; Jackson, Joshua J; Hill, Patrick L; Gao, Xuefei; Roberts, Brent W; Stine-Morrow, Elizabeth A L

2012-01-01

In the current study, we assessed the relationship between memory self-efficacy at pretest and responsiveness to inductive reasoning training in a sample of older adults. Participants completed a measure of self-efficacy assessing beliefs about memory capacity. Participants were then randomly assigned to a waitlist control group or an inductive reasoning training intervention. Latent change score models were used to examine the moderators of change in inductive reasoning. Inductive reasoning showed clear improvements in the training group compared with the control. Within the training group, initial memory capacity beliefs significantly predicted change in inductive reasoning such that those with higher levels of capacity beliefs showed greater responsiveness to the intervention. Further analyses revealed that self-efficacy had effects on how trainees allocated time to the training materials over the course of the intervention. Results indicate that self-referential beliefs about cognitive potential may be an important factor contributing to plasticity in adulthood.

Experiences with Extra-Vehicular Activities in Response to Critical ISS Contingencies

NASA Technical Reports Server (NTRS)

Van Cise, Edward A.; Kelly, Brian J.; Radigan, Jeffery P.; Cranmer, Curtis W.

2016-01-01

Initial "Big 14" work was put to the test for the first time in 2010. Deficiencies were found in some of the planning and approaches to that work; Failure Response Assessment Team created in 2010 to address deficiencies -Identify and perform engineering analysis in operations products prior to failure; incorporate results into operations products -Identify actions for protecting ISS against a Next Worse Failure after the first failure occurs -Better document not only EVA products but also planning products, assumptions, and open actions; Pre-failure investments against critical failures best postures ISS for swift response and recovery -A type of insurance policy -Has proven effective in a number of contingency EVA cases since 2010. Planning for MBSU R&R in 2012, Second PM R&R in 2013, EXT MDM R&R in 2014; Current FRAT schedule projects completion of all analysis in 2018

Mechanistic Insights in Ethylene Perception and Signal Transduction1

PubMed Central

Ju, Chuanli; Chang, Caren

2015-01-01

The gaseous hormone ethylene profoundly affects plant growth, development, and stress responses. Ethylene perception occurs at the endoplasmic reticulum membrane, and signal transduction leads to a transcriptional cascade that initiates diverse responses, often in conjunction with other signals. Recent findings provide a more complete picture of the components and mechanisms in ethylene signaling, now rendering a more dynamic view of this conserved pathway. This includes newly identified protein-protein interactions at the endoplasmic reticulum membrane, as well as the major discoveries that the central regulator ETHYLENE INSENSITIVE2 (EIN2) is the long-sought phosphorylation substrate for the CONSTITUTIVE RESPONSE1 protein kinase, and that cleavage of EIN2 transmits the signal to the nucleus. In the nucleus, hundreds of potential gene targets of the EIN3 master transcription factor have been identified and found to be induced in transcriptional waves, and transcriptional coregulation has been shown to be a mechanism of ethylene cross talk. PMID:26246449

Model correlation and damage location for large space truss structures: Secant method development and evaluation

NASA Technical Reports Server (NTRS)

Smith, Suzanne Weaver; Beattie, Christopher A.

1991-01-01

On-orbit testing of a large space structure will be required to complete the certification of any mathematical model for the structure dynamic response. The process of establishing a mathematical model that matches measured structure response is referred to as model correlation. Most model correlation approaches have an identification technique to determine structural characteristics from the measurements of the structure response. This problem is approached with one particular class of identification techniques - matrix adjustment methods - which use measured data to produce an optimal update of the structure property matrix, often the stiffness matrix. New methods were developed for identification to handle problems of the size and complexity expected for large space structures. Further development and refinement of these secant-method identification algorithms were undertaken. Also, evaluation of these techniques is an approach for model correlation and damage location was initiated.

The Impact of Educational Interventions on Organizational Culture at an Urban Federal Agency. Ph.D. Thesis - Old Dominion Univ.

NASA Technical Reports Server (NTRS)

Mckenzie, Janet Myrick

1994-01-01

This study on the impact of educational interventions on organizational culture is an evaluation of a major educational initiative undertaken by an urban federal agency, namely the National Aeronautics and Space Administration's Langley Research Center (NASA-LaRC). The design of this educational evaluation captures the essence of NASA-LaRC's efforts to continue its distinguished and international stature in the aeronautical research community following the Challenger tragedy. More specifically, this study is an evaluation of the educational initiative designed to ameliorate organizational culture via educational interventions, with emphasis on communications, rewards and recognition, and career development. After completing a review of the related literature, chronicling the educational initiative, interviewing senior managers and employees, and critically examining thousands of free responses on employee perceptions of organizational culture, it is found that previous definitions of organizational culture are more accurately classified as manifestations of organizational culture. This research has endeared to redefine 'organizational culture' by offering a more accurate and diagnostic perspective.

How do associative and phonemic overlap interact to boost illusory recollection?

PubMed

Hutchison, Keith A; Meade, Michelle L; Williams, Nikolas S; Manley, Krista D; McNabb, Jaimie C

2018-05-01

This project investigated the underlying mechanisms that boost false remember responses when participants receive study words that are both semantically and phonologically similar to a critical lure. Participants completed a memory task in which they were presented with a list of words all associated with a critical lure. Included within the list of semantic associates was a target that was either semantically associated (e.g., yawn) to the critical lure (e.g., sleep) or shared the initial (e.g., slam) or final (e.g., beep) phoneme(s) with the critical lure. After hearing the list, participants recalled each list item and indicated whether they just knew it was on the list or if they instead recollected specific contextual details of that item's presentation. We found that inserting an initial phonemic overlap target boosted experiences of recollection, but only when semantically related associates were presented beforehand. The results are consistent with models of spoken word recognition and show that established semantic context plus initial phonemic overlap play important roles in boosting false recollection.

Initial testing of an instrument to measure teacher identity in physicians.

PubMed

Starr, Susan; Haley, Heather-Lyn; Mazor, Kathleen M; Ferguson, Warren; Philbin, Mary; Quirk, Mark

2006-01-01

A previous study described 7 elements of teacher identity: intrinsic satisfaction from teaching, knowledge and skill about teaching, belonging to a community of teachers, receiving rewards for teaching, believing that being a doctor means being a teacher, feeling a responsibility to teach, and sharing clinical expertise. To conduct the initial testing of an instrument to measure the 7 elements of teacher identity in clinical educators and to consider the potential applications of such an instrument. A 37-item questionnaire was mailed to 153 preceptors of preclinical students. Categories reflected the elements of teacher identity listed here. Demographic data were collected. Means, alphas, ANOVAs, and paired t tests were calculated. Of 153 preceptors, 127 (83%) completed the questionnaire. Cronbach's alpha for the overall scale and several subscales were high. Salaried physicians and those who had completed a faculty development program scored significantly higher on several subscales than physicians who volunteered to teach or who did not have faculty development. This study provides preliminary evidence that teacher identity can be measured and that preceptors do not respond as a homogeneous group. Assessing teacher identity may be helpful to medical schools looking to identify and support physicians who teach.

Responses to salinity stress in bivalves: Evidence of ontogenetic changes in energetic physiology on Cerastoderma edule.

PubMed

Peteiro, Laura G; Woodin, Sarah A; Wethey, David S; Costas-Costas, Damian; Martínez-Casal, Arantxa; Olabarria, Celia; Vázquez, Elsa

2018-05-29

Estuarine bivalves are especially susceptible to salinity fluctuations. Stage-specific sensibilities may influence the structure and spatial distribution of the populations. Here we investigate differences on the energetic strategy of thread drifters (3-4 mm) and sedentary settlers (9-10 mm) of Cerastoderma edule over a wide range of salinities. Several physiological indicators (clearance, respiration and excretion rates, O:N) were measured during acute (2 days) and acclimated responses (7 days of exposure) for both size classes. Our results revealed a common lethal limit for both developmental stages (Salinity 15) but a larger physiological plasticity of thread drifters than sedentary settlers. Acclimation processes in drifters were initiated after 2 days of exposure and they achieved complete acclimation by day 7. Sedentary settlers delay acclimation and at day 7 feeding activity had not resumed and energetic losses through respiration and excretion were higher at the lowest salinity treatment. Different responses facing salinity stress might be related to differences in habitat of each stage. For sedentary settlers which occupy relatively stable niches, energy optimisation include delaying the initiation of the energetically expensive acclimation processes while drifters which occupy less stable environments require a more flexible process which allow them to optimize energy acquisition as fast as possible.

A metabolomics and mouse models approach to study inflammatory and immune responses to radiation

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

Fornace, Albert J.; Li, Henghong

2013-12-02

The three-year project entitled "A Metabolomics and Mouse Models Approach to Study Inflammatory and Immune Responses to Radiation" was initiated in September 2009. The overall objectives of this project were to investigate the acute and persistent effects of low dose radiation on T cell lymphocyte function and physiology, as well the contributions of these cells to radiation-induced inflammatory responses. Inflammation after ionizing radiation (IR), even at low doses, may impact a variety of disease processes, including infectious disease, cardiovascular disease, cancer, and other potentially inflammatory disorders. There were three overall specific aims: 1. To investigate acute and persistent effects ofmore » low dose radiation on T cell subsets and function; 2. A genetic approach with mouse models to investigate p38 MAPK pathways that are involved in radiation-induced inflammatory signaling; 3. To investigate the effect of radiation quality on the inflammatory response. We have completed the work proposed in these aims.« less

Transient inflammatory response mediated by interleukin-1β is required for proper regeneration in zebrafish fin fold

PubMed Central

Hasegawa, Tomoya; Hall, Christopher J; Crosier, Philip S; Abe, Gembu; Kawakami, Koichi; Kudo, Akira; Kawakami, Atsushi

2017-01-01

Cellular responses to injury are crucial for complete tissue regeneration, but their underlying processes remain incompletely elucidated. We have previously reported that myeloid-defective zebrafish mutants display apoptosis of regenerative cells during fin fold regeneration. Here, we found that the apoptosis phenotype is induced by prolonged expression of interleukin 1 beta (il1b). Myeloid cells are considered to be the principal source of Il1b, but we show that epithelial cells express il1b in response to tissue injury and initiate the inflammatory response, and that its resolution by macrophages is necessary for survival of regenerative cells. We further show that Il1b plays an essential role in normal fin fold regeneration by regulating expression of regeneration-induced genes. Our study reveals that proper levels of Il1b signaling and tissue inflammation, which are tuned by macrophages, play a crucial role in tissue regeneration. DOI: http://dx.doi.org/10.7554/eLife.22716.001 PMID:28229859

Public Perceptions of Self-Harm: Perceived Motivations of (and Willingness to Help in Response to) Adolescent Self-Harm.

PubMed

Nielsen, Emma; Townsend, Ellen

2018-01-01

We investigated public perceptions of, and responses to, adolescent self-harm-an under-researched topic, given that the majority of self-harm in this group is not disclosed to formal support services. Participants (N = 355, aged 18-67 years) were presented with 1 of 10 vignettes and completed self-report measures assessing perceived motivations for self-harm and helping/rejecting responses. Vignettes were manipulated across conditions for stated motivation, controllability of stated cause, and presentation format. Results indicate that stated motivation for self-harm, controllability of stated cause, and presentation format affect perceived motivations. Further, participants demonstrate an understanding of the complex nature of self-harm, indicating an appreciation that an individual may hold multiple motivations simultaneously. Perceived motivations for self-harm are associated with the endorsement of helping/rejecting behaviors. These relationships are important to explore, given the critical importance of initial responses to self-harm on subsequent disclosures and help-seeking.

[Intramuscular depot steroids : Possible treatment of postsurgical cystoid macula edema with steroid response?

PubMed

Seuthe, A-M; Szurman, P; Boden, K T

2017-11-01

We report on a patient with postsurgical cystoid macular edema (CME) after phacoemulsification and multifocal intraocular lens (MIOL) implantation. At first, there was a very good reaction to intravitreal triamcinolone, inducing complete regression of the edema without increasing intraocular pressure (IOP). One year later the patient suffered from retinal detachment and was treated with vitrectomy, laser, and gas tamponade. Afterward, he developed macular pucker with edema. After surgical treatment with pucker peeling and intravitreal triamcinolone, the patient showed a steroid response and an increase IOP. Postoperatively, there was a recurrence of CME. A coincidental administration of a steroid injection intramuscularly by the general practitioner achieved a prompt reduction of the CME without increasing IOP. This case shows that an initially good reaction to triamcinolone without increasing IOP does not rule out a future steroid response, and that a potential treatment option for CME in patients with a known steroid response could consist of intramuscularly injected steroids.

Modeling retrospective attribution of responsibility to hazard-managing institutions: an example involving a food contamination incident.

PubMed

Johnson, Branden B; Hallman, William K; Cuite, Cara L

2015-03-01

Perceptions of institutions that manage hazards are important because they can affect how the public responds to hazard events. Antecedents of trust judgments have received far more attention than antecedents of attributions of responsibility for hazard events. We build upon a model of retrospective attribution of responsibility to individuals to examine these relationships regarding five classes of institutions that bear responsibility for food safety: producers (e.g., farmers), processors (e.g., packaging firms), watchdogs (e.g., government agencies), sellers (e.g., supermarkets), and preparers (e.g., restaurants). A nationally representative sample of 1,200 American adults completed an Internet-based survey in which a hypothetical scenario involving contamination of diverse foods with Salmonella served as the stimulus event. Perceived competence and good intentions of the institution moderately decreased attributions of responsibility. A stronger factor was whether an institution was deemed (potentially) aware of the contamination and free to act to prevent or mitigate it. Responsibility was rated higher the more aware and free the institution. This initial model for attributions of responsibility to impersonal institutions (as opposed to individual responsibility) merits further development. © 2014 Society for Risk Analysis.

[A case of a geriatric patient with stage IV anal canal cancer showing complete response to chemoradiation therapy].

PubMed

Kuroda, Masatoshi; Hirai, Ryuji; Ikeda, Eiji; Tsuji, Hisashi; Takagi, Shoji; Yamano, Toshihisa; Yoshitomi, Seiji

2012-11-01

We present a case in which chemoradiation therapy was effective in a geriatric patient with Stage IV anal canal cancer. The patient is an 81-year-old woman who complained of proctorrhagia and anal pain. She was referred to us by her family doctor who suspected rectal cancer. Tumors as large as 6.5 cm in diameter mainly on the right side of the rectum as well as 2 palpable enlarged lymph nodes on the right inguinal area, were found during the initial physical examination. Squamous cell carcinoma was elevated to 16 ng/mL. A CT scan revealed that irregularly shaped masses as large as 7 cm in diameter were externally exposed on the right side of the rectum along with enlarged lymph nodes on the right inguinal area and metastasis at S7 lesion in the liver. Squamous cell carcinoma was diagnosed from biopsy results. Due to her age, the chemotherapy regimen was S-1+CDDP with radiation therapy and 4-port irradiation (50.4 Gy) of the primary tumor, interior of the pelvis, and inguinal lymph nodes. Partial response was observed upon completion of treatment, and complete response was obtained after 6 months. She is currently an outpatient taking S-1: 60 mg/day orally. There is no indication of cancer recurrence after 1 year and 3 months, and she continues to visit an outpatient clinic for regular follow-ups. These results demonstrate the effectiveness of chemoradiation therapy for geriatric patients with Stage IV anal canal cancer.

Examination of the equivalence of self-report survey-based paper-and-pencil and internet data collection methods.

PubMed

Weigold, Arne; Weigold, Ingrid K; Russell, Elizabeth J

2013-03-01

Self-report survey-based data collection is increasingly carried out using the Internet, as opposed to the traditional paper-and-pencil method. However, previous research on the equivalence of these methods has yielded inconsistent findings. This may be due to methodological and statistical issues present in much of the literature, such as nonequivalent samples in different conditions due to recruitment, participant self-selection to conditions, and data collection procedures, as well as incomplete or inappropriate statistical procedures for examining equivalence. We conducted 2 studies examining the equivalence of paper-and-pencil and Internet data collection that accounted for these issues. In both studies, we used measures of personality, social desirability, and computer self-efficacy, and, in Study 2, we used personal growth initiative to assess quantitative equivalence (i.e., mean equivalence), qualitative equivalence (i.e., internal consistency and intercorrelations), and auxiliary equivalence (i.e., response rates, missing data, completion time, and comfort completing questionnaires using paper-and-pencil and the Internet). Study 1 investigated the effects of completing surveys via paper-and-pencil or the Internet in both traditional (i.e., lab) and natural (i.e., take-home) settings. Results indicated equivalence across conditions, except for auxiliary equivalence aspects of missing data and completion time. Study 2 examined mailed paper-and-pencil and Internet surveys without contact between experimenter and participants. Results indicated equivalence between conditions, except for auxiliary equivalence aspects of response rate for providing an address and completion time. Overall, the findings show that paper-and-pencil and Internet data collection methods are generally equivalent, particularly for quantitative and qualitative equivalence, with nonequivalence only for some aspects of auxiliary equivalence. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Translational signaling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans

PubMed Central

Mayhew, David L.; Kim, Jeong-su; Cross, James M.; Ferrando, Arny A.

2009-01-01

While skeletal muscle protein accretion during resistance training (RT)-mediated myofiber hypertrophy is thought to result from upregulated translation initiation signaling, this concept is based on responses to a single bout of unaccustomed resistance exercise (RE) with no measure of hypertrophy across RT. Further, aging appears to affect acute responses to RE, but whether age differences in responsiveness persist during RT leading to impaired RT adaptation is unclear. We therefore tested whether muscle protein fractional synthesis rate (FSR) and Akt/mammalian target of rapamycin (mTOR) signaling in response to unaccustomed RE differed in old vs. young adults, and whether age differences in acute responsiveness were associated with differences in muscle hypertrophy after 16 wk of RT. Fifteen old and 21 young adult subjects completed the 16-wk study. The phosphorylation states of Akt, S6K1, ribosomal protein S6 (RPS6), eukaryotic initiation factor 4E (eIF4E) binding protein (4EBP1), eIF4E, and eIF4G were all elevated (23–199%) 24 h after a bout of unaccustomed RE. A concomitant 62% increase in FSR was found in a subset (6 old, 8 young). Age × time interaction was found only for RPS6 phosphorylation (+335% in old subjects only), while there was an interaction trend (P = 0.084) for FSR (+96% in young subjects only). After 16 wk of RT, gains in muscle mass, type II myofiber size, and voluntary strength were similar in young and old subjects. In conclusion, at the level of translational signaling, we found no evidence of impaired responsiveness among older adults, and for the first time, we show that changes in translational signaling after unaccustomed RE were associated with substantial muscle protein accretion (hypertrophy) during continued RT. PMID:19589955

A locally initiated and executed measles outbreak response immunization campaign in the nylon health district, Douala Cameroon 2011

PubMed Central

2013-01-01

The Cameroon health system is divided into central, intermediate and peripheral levels. Of the 43 health districts with a measles outbreak in Cameroon in 2011, only the Nylon Health District organized a documented outbreak response immunization. We present the methods and results of the response campaign solely shouldered by the district and intermediate level. The risk group, targets and neighborhoods to be vaccinated were identified after a detailed analysis of initial cases. The intermediate level defined strategies, provided logistics, capacity building and 41% of the operational budget while 59% was completed by the peripheral level. Microsoft Office Excel 2007 was used to estimate coverage rates and to draw an epidemic curve. The response immunization campaign was organized on the 14th epidemiological week, 10 weeks after the onset of the outbreak which ended 11 weeks thereafter. A total of 15867(108.5%) children aged 9-59 months were vaccinated in five health areas at a direct cost (vaccines excluded) of 71.34FCFA ($0.143) per vaccinated child. An additional 824 children aged 9-59 months were vaccinated around the residence of notified cases in neighborhoods which were not involved in the response campaign. The number of cases after the response campaign was lower than before. Once vaccines are available, prompt outbreak response campaigns can be organized at operational level to obtain commendable results instead of depending solely on international organizations or central levels. Decision makers at the intermediate and operational levels should redeploy available funds during emergencies to prevent the development of extreme public health conditions. PMID:23497712

Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

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

Habr-Gama, Angelita, E-mail: gamange@uol.com.br; University of São Paulo School of Medicine, São Paulo; Gama-Rodrigues, Joaquim

Purpose: To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials: Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results: 90 of 183 patients experienced cCR at initial assessment after CRT (49%). Whenmore » early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions: Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation.« less

Cardiac Screening Prior to Stimulant Treatment of ADHD: A Survey of US-Based Pediatricians

PubMed Central

Rodday, Angie Mae; Saunders, Tully S.; Cohen, Joshua T.; Wong, John B.; Parsons, Susan K.

2012-01-01

OBJECTIVES: To determine pediatricians’ attitudes, barriers, and practices regarding cardiac screening before initiating treatment with stimulants for attention-deficit/hyperactivity disorder. METHODS: A survey of 1600 randomly selected, practicing US pediatricians with American Academy of Pediatrics membership was conducted. Multivariate models were created for 3 screening practices: (1) performing an in-depth cardiac history and physical (H & P) examination, (2) discussing potential stimulant-related cardiac risks, and (3) ordering an electrocardiogram (ECG). RESULTS: Of 817 respondents (51%), 525 (64%) met eligibility criteria. Regarding attitudes, pediatricians agreed that both the risk for sudden cardiac death (SCD) (24%) and legal liability (30%) were sufficiently high to warrant cardiac assessment; 75% agreed that physicians were responsible for informing families about SCD risk. When identifying cardiac disorders, few (18%) recognized performing an in-depth cardiac H & P as a barrier; in contrast, 71% recognized interpreting a pediatric ECG as a barrier. When asked about cardiac screening practices before initiating stimulant treatment for a recent patient, 93% completed a routine H & P, 48% completed an in-depth cardiac H & P, and 15% ordered an ECG. Almost half (46%) reported discussing stimulant-related cardiac risks. Multivariate modeling indicated that ≥1 of these screening practices were associated with physicians’ attitudes about SCD risk, legal liability, their responsibility to inform about risk, their ability to perform an in-depth cardiac H & P, and family concerns about risk. CONCLUSIONS: Variable pediatrician attitudes and cardiac screening practices reflect the limited evidence base and conflicting guidelines regarding cardiac screening. Barriers to identifying cardiac disorders influence practice. PMID:22250023

Assessing university students' sexual risk behaviors as predictors of human papillomavirus (HPV) vaccine uptake behavior.

PubMed

Rohde, Rebecca L; Adjei Boakye, Eric; Christopher, Kara M; Geneus, Christian J; Walker, Ronald J; Varvares, Mark A; Osazuwa-Peters, Nosayaba

2018-06-14

There exists a significant gap in vaccine coverage of the human papillomavirus (HPV) among college-aged students. This study assessed sexual risk-taking behavior among university students and analyzed predictors of HPV vaccine initiation and completion in this population. Data (n = 746) were from an anonymous online, cross-sectional survey distributed to university students, between the ages of 19-26 years, at a private Midwestern university. Both chi-square and multivariable logistics regression models estimated the association between sociodemographic characteristics and sexual risk factors (including number of vaginal sexual partners, number of oral sexual partners, initiation of oral sex, and initiation of vaginal sex), with HPV vaccine initiation and completion. A significant number of participants (40%) had not received a single dose of the HPV vaccine series. Of those who initiated the series, more than half (51%) did not achieve completion. Additionally, a greater number of participants have had multiple (4 or more) oral sexual partners than vaginal sexual partners (25.7% vs. 20.3%). After adjusting for covariates, it was found that sexual risk factors were not significantly associated with HPV vaccine initiation or completion. HPV vaccine initiation and completion rates are suboptimal among university students. High levels of sexual-risk taking behaviors associated with HPV infection persist, yet are not significant predictors of HPV vaccine behaviors in this age group. To increase uptake among 18-26-year-old students, future public health interventions should focus on HPV vaccine education and uptake across the entire population, irrespective of sexual risk profile. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tinea profunda of the genital area. Successful treatment of a rare skin disease.

PubMed

Bakardzhiev, Ilko; Chokoeva, Anastasiya; Tchernev, Georgi; Wollina, Uwe; Lotti, Torello

2016-05-01

We present a rare case of 36-year-old female patient, who developed a severe Majocchi granuloma in the pubis after waxing, with isolated causative agent Trichophyton mentagrophytes. The condition was initially misdiagnosed as a bacterial folliculitis and treated unsuccessfully with topical corticosteroids and antibiotics. After the adequate diagnose was confirmed by mycological examination, followed by histopathological verification, complete remission of the symptoms was achieved at the 4th week after initiating 6 weeks course of antifungal therapy with Terbinafine 250 mg/daily dose, while good therapeutic response was observed even in the 10th day. The etiopathogenesis of the disease, as well as its current treatment options are considered, in respect to the rare occurrence of this condition in the pubic area and its frequent misdiagnosis. © 2015 Wiley Periodicals, Inc.

Learning procedures from interactive natural language instructions

NASA Technical Reports Server (NTRS)

Huffman, Scott B.; Laird, John E.

1994-01-01

Despite its ubiquity in human learning, very little work has been done in artificial intelligence on agents that learn from interactive natural language instructions. In this paper, the problem of learning procedures from interactive, situated instruction is examined in which the student is attempting to perform tasks within the instructional domain, and asks for instruction when it is needed. Presented is Instructo-Soar, a system that behaves and learns in response to interactive natural language instructions. Instructo-Soar learns completely new procedures from sequences of instruction, and also learns how to extend its knowledge of previously known procedures to new situations. These learning tasks require both inductive and analytic learning. Instructo-Soar exhibits a multiple execution learning process in which initial learning has a rote, episodic flavor, and later executions allow the initially learned knowledge to be generalized properly.

Imitating the Great Imitator The Intersection of Sarcoidosis and Hodgkin's Lymphoma A Report of Two Cases.

PubMed

Outlaw, Darryl; Mehta, Amitkumar; Dalvi, Sam R

2018-06-01

Sarcoidosis and Hodgkin's lymphoma represent two distinct diseases with different pathogenic mechanisms, therapeutic interventions, and prognoses. Nevertheless, both diseases can have overlapping presentations, thus blurring the line between successful identification and treatment. A propensity to develop one of these diseases following diagnosis of the other has long been appreciated. Here we review two cases of presumed sarcoidosis that were ultimately diagnosed as Hodgkin's lymphoma. Both patients initially presented with non-specific symptoms and underwent a thorough workup, including histological evaluation demonstrating non-caseating granulomas without evidence of malignancy. Both patients started sarcoid-directed therapies with relapse of symptoms. Repeat imaging and tissue biopsy eventually led to the diagnosis of stage IVB Hodgkin's lymphoma. After the initiation of Hodgkin's-directed therapies, both patients showed marked clinical responses, and entered complete remission.

Treatment patterns and prognostic indicators of response to therapy among patients with chronic myeloid leukemia in Australia, Canada, and South Korea.

PubMed

Whiteley, Jennifer; Iyer, Shrividya; Candrilli, Sean D; Kaye, James A

2015-02-01

Given the multiple options for treatment of chronic-phase chronic myeloid leukemia (CML) with tyrosine kinase inhibitors, our objective was to understand treatment patterns in routine practice and prognostic indicators of response. We conducted a retrospective medical record review of 681 patients with CML in Australia, Canada, and South Korea. Eligible patients had a diagnosis of chronic-phase CML, were Philadelphia chromosome and/or BCR-ABL positive, were aged 18 years or older, and had been treated with first-line imatinib therapy between January 2005 and September 2010. Data on patient demographics, medical history (e.g., comorbidities, Sokal score), and treatment characteristics (e.g., time to initiation, therapy duration) were abstracted. Descriptive analyses were stratified by country and therapy line. Prognostic indicators of response to imatinib were evaluated using multivariable logistic regression, adjusting for country, patient demographics, medical history, treatment characteristics, and side effects. Hematologic, cytogenetic, and molecular responses at 3, 6, 12, and 18 months following initiation of each therapy line. Patients' average age was 57 years, and 59% were male. Overall, imatinib was initiated approximately 4 months following CML diagnosis. Complete or major molecular response (C/MMR) at 6 months following imatinib initiation was 54% in Australia, 22% in Canada, and 38% in South Korea. At 18 months, over 60% of patients achieved C/MMR. Approximately 30% of patients discontinued imatinib primarily due to intolerance and lack of response. Among patients who received second-line treatment, dasatinib was used more frequently than nilotinib. Multivariable regression results indicated Sokal score was identified as a prognostic indicator of response to imatinib therapy at several time points. There are several limitations to this study. First, we selected a convenience sample of patients and physicians and therefore results may not be representative of the true population of patients with chronic-phase CML. Second, data were entered by the selected physician and could be subject to data entry errors or inaccuracies. Third, limited information was collected from the patient records, and it is possible that we did not capture additional prognostic or confounding factors related to the measured outcomes. Next, because this was an analysis of previously documented data (i.e., retrospective), we were unable to provide a priori definitions of response. Finally, multivariable analyses were limited to imatinib-related outcomes. Treatment patterns and prognostic indicators differed by country. Health care providers, payers, and patients can utilize these results to inform treatment and policies aimed at improving the effectiveness of care for patients with chronic-phase CML.

Re-Staging Following Long-Course Chemoradiotherapy For Rectal Cancer: Does It Influence Management?

PubMed

McBrearty, A; McCallion, K; Moorehead, R J; McAllister, I; Mulholland, K; Gilliland, R; Campbell, W J

2016-09-01

In patients with locally advanced or low rectal cancers, long-course chemoradiotherapy (LCCRT) is recommended prior to surgical management. 1 The need for restaging afterwards has been questioned as it may be difficult to interpret imaging due to local tissue effects of chemoradiotherapy. The purpose of this study was to determine if restaging affected the management of patients receiving long-course chemoradiotherapy for rectal cancer. A retrospective review of patients with rectal cancer discussed at the South Eastern Health and Social Care Trust Lower Gastrointestinal Multi-Disciplinary Team Meeting (LGIMDT) in 2013 who had received long-course chemoradiotherapy was performed. Patients were identified from the Trust Audit Department, LGIMDT notes and patient records. Imaging results and outcomes from meetings were obtained through the Northern Ireland Picture Archiving and Communications System ® (NIPACS) and Electronic Care Record ® (ECR). Data including patient demographics, initial radiological staging and LGIMDT discussion, restaging modality and result, outcome from post-treatment LGIMDT discussion and recorded changes in management plans were documented using a proforma. Seventy-one patients with rectal cancer were identified as having LCCRT in 2013 (M:F 36:35; age range 31 - 85 years). Fifty-nine patients were restaged following long-course treatment with computed tomography (CT) and magnetic resonance imaging (MRI). Twelve patients did not undergo restaging. Data was not available for 6 patients, one patient underwent emergency surgery, two patients were not fit for treatment, one failed to attend for restaging and two patients died prior to completion of treatment. Of the 59 patients restaged, 19 patients (32%) had their management plan altered from that which had been proposed at the initial LGIMDT discussion. The most common change in plan was not to operate. Ten patients had a complete clinical and radiological response to treatment and have undergone intensive follow-up. Nine patients had disease progression, with 3 requiring palliative surgery and 6 referred for palliative care. Of those patients who were restaged, 32% had their management plan altered from that recorded at the initial LGIMDT discussion. Seventeen per cent of patients in this group had a complete clinical and radiological response to treatment. Fifteen percent demonstrated disease progression. We recommend, therefore, that patients with rectal cancer be restaged with CT and MRI following long-course chemoradiotherapy as surgery may be avoided in up to 27% of cases.

Use of Sirolimus (Rapamycin) for Treatment of Cytopenias and Lymphoproliferation Linked to Autoimmune Lymphoproliferative Syndrome (ALPS). Two Case Reports.

PubMed

Cayrol, Julie; Garrido Colino, Carmen

2017-05-01

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte apoptosis. Children present with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and autoimmune cytopenias. Recent advances show efficacy of treatment with immunosuppressive drugs. Sirolimus, an mammalian target of rapamycin inhibitor, improves autoimmune cytopenias and lymphoproliferation, with a safe profile. We present 2 patients, a 5-year-old girl and 15-year-old boy, diagnosed with ALPS with initial partial response to steroid treatment. Autoimmune cytopenias and lymphoproliferation then became refractory to treatment, with recurrence of symptoms. In both cases, treatment with sirolimus was started, with a rapid response, complete remission of cytopenias, and resolution of lymphoproliferation, with no significant adverse effects. sirolimus is an effective and safe drug for controlling children with cytopenias and lymphoproliferation linked to ALPS.

Crystal Structures of the E. coli Transcription Initiation Complexes with a Complete Bubble

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

Zuo, Yuhong; Steitz, Thomas A.

2015-05-01

During transcription initiation, RNA polymerase binds to promoter DNA to form an initiation complex containing a DNA bubble and enters into abortive cycles of RNA synthesis before escaping the promoter to transit into the elongation phase for processive RNA synthesis. Here we present the crystal structures of E. coli transcription initiation complexes containing a complete transcription bubble and de novo synthesized RNA oligonucleotides at about 6-Å resolution. The structures show how RNA polymerase recognizes DNA promoters that contain spacers of different lengths and reveal a bridging interaction between the 5'-triphosphate of the nascent RNA and the σ factor that maymore » function to stabilize the short RNA-DNA hybrids during the early stage of transcription initiation. The conformation of the RNA oligonucleotides and the paths of the DNA strands in the complete initiation complexes provide insights into the mechanism that controls both the abortive and productive RNA synthesis.« less

The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

PubMed

Gills, Jessie; Parker, William P; Pate, Scott; Niu, Sida; Van Veldhuizen, Peter; Mirza, Moben; Holzbeierlein, Jeffery M; Lee, Eugene K

2017-09-01

We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Hypersonic and Unsteady Flow Science Issues for Explosively Formed Penetrators

DTIC Science & Technology

2006-08-01

under going real- time dynamic deformation. ACCOMPLISHMENTS/RESULTS • Completed initial assessment of flow chemistry • Completed initial stability... flow chemistry during rapid deformation •Cannot use static boundary conditions in CFD codes •Interfaces one approach to coupling with hydrocodes

Implementation of Cognitive-Behavioral Substance Abuse Treatment in Sub-Saharan Africa: Treatment Engagement and Abstinence at Treatment Exit.

PubMed

Gouse, Hetta; Magidson, Jessica F; Burnhams, Warren; Remmert, Jocelyn E; Myers, Bronwyn; Joska, John A; Carrico, Adam W

2016-01-01

This study documented the treatment cascade for engagement in care and abstinence at treatment exit as well as examined correlates of these outcomes for the first certified Matrix Model® substance abuse treatment site in Sub-Saharan Africa. This retrospective chart review conducted at a resource-limited community clinic in Cape Town, South Africa, assessed treatment readiness and substance use severity at treatment entry as correlates of the number of sessions attended and biologically confirmed abstinence at treatment exit among 986 clients who initiated treatment from 2009-2014. Sociodemographic and clinical correlates of treatment outcomes were examined using logistic regression, modeling treatment completion and abstinence at treatment exit separately. Of the 2,233 clients who completed screening, approximately 44% (n = 986) initiated treatment. Among those who initiated treatment, 45% completed at least four group sessions, 30% completed early recovery skills training (i.e., at least eight group sessions), and 13% completed the full 16-week program. Approximately half (54%) of clients who provided a urine sample had negative urine toxicology results for any substance at treatment exit. Higher motivation at treatment entry was independently associated with greater odds of treatment completion and negative urine toxicology results at treatment exit. Findings provide initial support for the successful implementation the Matrix Model in a resource-limited setting. Motivational enhancement interventions could support treatment initiation, promote sustained engagement in treatment, and achieve better treatment outcomes.

Role of Cyclic Nucleotide-Dependent Actin Cytoskeletal Dynamics: [Ca2+]i and Force Suppression in Forskolin-Pretreated Porcine Coronary Arteries

PubMed Central

Hocking, Kyle M.; Baudenbacher, Franz J.; Putumbaka, Gowthami; Venkatraman, Sneha; Cheung-Flynn, Joyce; Brophy, Colleen M.; Komalavilas, Padmini

2013-01-01

Initiation of force generation during vascular smooth muscle contraction involves a rise in intracellular calcium ([Ca2+]i) and phosphorylation of myosin light chains (MLC). However, reversal of these two processes alone does not account for the force inhibition that occurs during relaxation or inhibition of contraction, implicating that other mechanisms, such as actin cytoskeletal rearrangement, play a role in the suppression of force. In this study, we hypothesize that forskolin-induced force suppression is dependent upon changes in actin cytoskeletal dynamics. To focus on the actin cytoskeletal changes, a physiological model was developed in which forskolin treatment of intact porcine coronary arteries (PCA) prior to treatment with a contractile agonist resulted in complete suppression of force. Pretreatment of PCA with forskolin suppressed histamine-induced force generation but did not abolish [Ca2+]i rise or MLC phosphorylation. Additionally, forskolin pretreatment reduced filamentous actin in histamine-treated tissues, and prevented histamine-induced changes in the phosphorylation of the actin-regulatory proteins HSP20, VASP, cofilin, and paxillin. Taken together, these results suggest that forskolin-induced complete force suppression is dependent upon the actin cytoskeletal regulation initiated by the phosphorylation changes of the actin regulatory proteins and not on the MLC dephosphorylation. This model of complete force suppression can be employed to further elucidate the mechanisms responsible for smooth muscle tone, and may offer cues to pathological situations, such as hypertension and vasospasm. PMID:23593369

Role of cyclic nucleotide-dependent actin cytoskeletal dynamics:Ca(2+)](i) and force suppression in forskolin-pretreated porcine coronary arteries.

PubMed

Hocking, Kyle M; Baudenbacher, Franz J; Putumbaka, Gowthami; Venkatraman, Sneha; Cheung-Flynn, Joyce; Brophy, Colleen M; Komalavilas, Padmini

2013-01-01

Initiation of force generation during vascular smooth muscle contraction involves a rise in intracellular calcium ([Ca(2+)]i) and phosphorylation of myosin light chains (MLC). However, reversal of these two processes alone does not account for the force inhibition that occurs during relaxation or inhibition of contraction, implicating that other mechanisms, such as actin cytoskeletal rearrangement, play a role in the suppression of force. In this study, we hypothesize that forskolin-induced force suppression is dependent upon changes in actin cytoskeletal dynamics. To focus on the actin cytoskeletal changes, a physiological model was developed in which forskolin treatment of intact porcine coronary arteries (PCA) prior to treatment with a contractile agonist resulted in complete suppression of force. Pretreatment of PCA with forskolin suppressed histamine-induced force generation but did not abolish [Ca(2+)]i rise or MLC phosphorylation. Additionally, forskolin pretreatment reduced filamentous actin in histamine-treated tissues, and prevented histamine-induced changes in the phosphorylation of the actin-regulatory proteins HSP20, VASP, cofilin, and paxillin. Taken together, these results suggest that forskolin-induced complete force suppression is dependent upon the actin cytoskeletal regulation initiated by the phosphorylation changes of the actin regulatory proteins and not on the MLC dephosphorylation. This model of complete force suppression can be employed to further elucidate the mechanisms responsible for smooth muscle tone, and may offer cues to pathological situations, such as hypertension and vasospasm.

Effects of mecamylamine on responses of carotid body chemoreceptors in vivo to physiological and pharmacological stimuli

PubMed Central

Sampson, S. R.

1971-01-01

1. Effects of mecamylamine on the spontaneous discharge rate of afferent fibres of carotid body chemoreceptors in vivo and their responses to ACh, NaCN, HCl and hypoxia were studied in sixteen cats. 2. Cats were anaesthetized with sodium pentobarbitone, paralysed with gallamine triethiodide and artificially ventilated. Chemoreceptor excitants were injected into the common carotid artery; mecamylamine was given intravenously. 3. Mecamylamine, 230 μg/kg or greater, failed to diminish either the rate of spontaneous discharge of carotid body chemoreceptors at high arterial oxygen tensions (greater than 130 mm Hg), or the responses of these receptors to NaCN (0·5-25 μg), HCl or hypoxic blood. 4. Responses of chemoreceptor afferent fibres to ACh (1·0-50 μg) in the same preparations were either completely abolished or considerably reduced by mecamylamine. 5. These data do not support the hypothesis of a cholinergic mechanism for the initiation of chemosensory discharges in the carotid body, either at rest or in response to stimuli such as NaCN, acid or hypoxia. PMID:5557066

Decision-making, sensitivity to reward, and attrition in weight-management

PubMed Central

Koritzky, Gilly; Dieterle, Camille; Rice, Chantelle; Jordan, Katie; Bechara, Antoine

2014-01-01

Objective Attrition is a common problem in weight-management. Understanding the risk factors for attrition should enhance professionals’ ability to increase completion rates and improve health outcomes for more individuals. We propose a model that draws upon neuropsychological knowledge on reward-sensitivity in obesity and overeating to predict attrition. Design & Methods 52 participants in a weight-management program completed a complex decision-making task.Decision-making characteristics – including sensitivity to reward – were further estimated using a quantitative model. Impulsivity and risk-taking measures were also administered. Results Consistent with the hypothesis that sensitivity to reward predicted attrition, program dropouts had higher sensitivity to reward than completers (p < 0.03). No differences were observed between completers and dropouts in initial BMI, age, employment status, or the number of prior weight-loss attempts (p ≥ 0.07). Completers had a slightly higher education level than dropouts, but its inclusion in the model did not increase predictive power. Impulsivity, delay of gratification, and risk-taking did not predict attrition, either. Conclusions Findings link attrition in weight-management to the neural mechanisms associated with reward-seeking and related influences on decision-making. Individual differences in the magnitude of response elicited by rewards may account for the relative difficulty experienced by dieters in adhering to treatment. PMID:24771588

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

Shim, Su Jung; Yang, Woo-Ick; Shin, Eunah

Purpose: To determine whether there are any differences in therapeutic response, patterns of systemic recurrence, and prognosis of patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type, by the cyclooxygenase-2 (COX-2) expression. Patients and Methods: Thirty-four patients with Ann Arbor Stage I and II extranodal NK/T-cell lymphoma who underwent chemotherapy or radiotherapy, or both, were retrospectively reviewed. These patients were divided into two groups according to their immunohistochemical staining for COX-2 expressions: a COX-2-negative group (n = 10 patients) and a COX-2-positive group (n = 24 patients). The treatment response, patterns of treatment failure, and survival data for the patientsmore » were compared between the COX-2-positive and negative groups. Results: There was no significant difference in the clinical profiles between the COX-2-negative and COX-2-positive groups. All patients (100%) in the COX-2-negative group achieved complete response after initial treatment, whereas only 14 patients (58%) in the COX-2-positive group achieved complete response (p = 0.03). Compared with the patients in the COX-2-negative group, those in the COX-2-positive group had a significantly lower 2-year systemic recurrence-free survival rate (100% for the COX-2-negative group vs. 54% for the COX-2-positive group) (p = 0.02) and a decreased 5-year overall survival rate (70% for the COX-2-negative group vs. 32% for the COX-2-positive group) (p = 0.06). Conclusion: Cyclooxygenase-2 expression can serve as a predictive factor for poor treatment response, higher systemic recurrence, and unfavorable prognosis in patients with extranodal NK/T-cell lymphoma, nasal type.« less

Fluoxetine maintains a state of heightened responsiveness to motor training early after stroke in a mouse model

PubMed Central

Ng, Kwan; Gibson, Ellen M.; Hubbard, Robert; Yang, Juemin; Caffo, Brian; O’Brien, Richard; Krakauer, John W.; Zeiler, Steven R.

2016-01-01

Background and purpose Data from both humans and animal models suggest that most recovery from motor impairment occurs in a sensitive period that lasts only weeks after stroke and is mediated in part by an increased responsiveness to training. Here we used a mouse model of focal cortical stroke to test two hypotheses. First we investigated if responsiveness to training decreases over time after stroke. Second, we tested whether fluoxetine, which can influence synaptic plasticity and stroke recovery, can prolong the period over which large training-related gains can be elicited after stroke. Methods Mice were trained to perform a skilled prehension task to an asymptotic level of performance after which they underwent stroke induction in the caudal forelimb area (CFA). The mice were then retrained after a 1-day or 7-day delay with and without fluoxetine. Results Recovery of prehension after a CFA stroke was complete if training was initiated one day after stroke but incomplete if it was delayed by 7 days. In contrast, if fluoxetine was administered at 24 hours after stroke, then complete recovery of prehension was observed even with the 7-day training delay. Fluoxetine appeared to mediate its beneficial effect by reducing inhibitory interneuron expression in intact premotor cortex rather than through effects on infarct volume or cell death. Conclusions There is a gradient of diminishing responsiveness to motor training over the first week after stroke. Fluoxetine can overcome this gradient and maintain maximal levels of responsiveness to training even 7 days after stroke. PMID:26294676

Fluoxetine Maintains a State of Heightened Responsiveness to Motor Training Early After Stroke in a Mouse Model.

PubMed

Ng, Kwan L; Gibson, Ellen M; Hubbard, Robert; Yang, Juemin; Caffo, Brian; O'Brien, Richard J; Krakauer, John W; Zeiler, Steven R

2015-10-01

Data from both humans and animal models suggest that most recovery from motor impairment after stroke occurs in a sensitive period that lasts only weeks and is mediated, in part, by an increased responsiveness to training. Here, we used a mouse model of focal cortical stroke to test 2 hypotheses. First, we investigated whether responsiveness to training decreases over time after stroke. Second, we tested whether fluoxetine, which can influence synaptic plasticity and stroke recovery, can prolong the period over which large training-related gains can be elicited after stroke. Mice were trained to perform a skilled prehension task to an asymptotic level of performance after which they underwent stroke induction in the caudal forelimb area. The mice were then retrained after a 1- or 7-day delay with and without fluoxetine. Recovery of prehension after a caudal forelimb area stroke was complete if training was initiated 1 day after stroke but incomplete if it was delayed by 7 days. In contrast, if fluoxetine was administered at 24 hours after stroke, then complete recovery of prehension was observed even with the 7-day training delay. Fluoxetine seemed to mediate its beneficial effect by reducing inhibitory interneuron expression in intact premotor cortex rather than through effects on infarct volume or cell death. There is a gradient of diminishing responsiveness to motor training over the first week after stroke. Fluoxetine can overcome this gradient and maintain maximal levels of responsiveness to training even 7 days after stroke. © 2015 American Heart Association, Inc.

Numbering questionnaires had no impact on the response rate and only a slight influence on the response content of a patient safety culture survey: a randomized trial.

PubMed

Kundig, François; Staines, Anthony; Kinge, Thompson; Perneger, Thomas V

2011-11-01

In self-completed surveys, anonymous questionnaires are sometimes numbered so as to avoid sending reminders to initial nonrespondents. This number may be perceived as a threat to confidentiality by some respondents, which may reduce the response rate, or cause social desirability bias. In this study, we evaluated whether using nonnumbered vs. numbered questionnaires influenced the response rate and the response content. During a patient safety culture survey, we randomized participants into two groups: one received an anonymous nonnumbered questionnaire and the other a numbered questionnaire. We compared the survey response rates and distributions of the responses for the 42-questionnaire items across the two groups. Response rates were similar in the two groups (nonnumbered, 75.2%; numbered, 72.8%; difference, 2.4%; P=0.28). Five of the 42 questions had statistically significant differences in distributions, but these differences were small. Unexpectedly, in all five instances, the patient safety culture ratings were more favorable in the nonnumbered group. Numbering of mailed questionnaires had no impact on the response rate. Numbering influenced significantly the response content of several items, but these differences were small and ran against the hypothesis of social desirability bias. Copyright © 2011 Elsevier Inc. All rights reserved.

NASA’s Wallops Flight Facility Completes Initial Assessment after Orbital Launch Mishap

NASA Image and Video Library

2017-12-08

An aerial view of the Wallops Island launch facilities taken by the Wallops Incident Response Team Oct. 29 following the failed launch attempt of Orbital Science Corp.'s Antares rocket Oct. 28. Credit: NASA/Terry Zaperach --- The Wallops Incident Response Team completed today an initial assessment of Wallops Island, Virginia, following the catastrophic failure of Orbital Science Corp.’s Antares rocket shortly after liftoff at 6:22 p.m. EDT Tuesday, Oct. 28, from Pad 0A of the Mid-Atlantic Regional Spaceport at NASA’s Wallops Flight Facility in Virginia. “I want to praise the launch team, range safety, all of our emergency responders and those who provided mutual aid and support on a highly-professional response that ensured the safety of our most important resource -- our people,” said Bill Wrobel, Wallops director. “In the coming days and weeks ahead, we'll continue to assess the damage on the island and begin the process of moving forward to restore our space launch capabilities. There's no doubt in my mind that we will rebound stronger than ever.” The initial assessment is a cursory look; it will take many more weeks to further understand and analyze the full extent of the effects of the event. A number of support buildings in the immediate area have broken windows and imploded doors. A sounding rocket launcher adjacent to the pad, and buildings nearest the pad, suffered the most severe damage. At Pad 0A the initial assessment showed damage to the transporter erector launcher and lightning suppression rods, as well as debris around the pad. The Wallops team also met with a group of state and local officials, including the Virginia Department of Environmental Quality, the Virginia Department of Emergency Management, the Virginia Marine Police, and the U.S. Coast Guard. The Wallops environmental team also is conducting assessments at the site. Preliminary observations are that the environmental effects of the launch failure were largely contained within the southern third of Wallops Island, in the area immediately adjacent to the pad. Immediately after the incident, the Wallops’ industrial hygienist collected air samples at the Wallops mainland area, the Highway 175 causeway, and on Chincoteague Island. No hazardous substances were detected at the sampled locations. Additional air, soil and water samples will be collected from the incident area as well as at control sites for comparative analysis. The Coast Guard and Virginia Marine Resources Commission reported today they have not observed any obvious signs of water pollution, such as oil sheens. Furthermore, initial assessments have not revealed any obvious impacts to fish or wildlife resources. The Incident Response Team continues to monitor and assess. Following the initial assessment, the response team will open the area of Wallops Island, north of the island flagpole opposite of the launch pad location, to allow the U.S. Navy to return back to work. Anyone who finds debris or damage to their property in the vicinity of the launch mishap is cautioned to stay away from it and call the Incident Response Team at 757-824-1295. Further updates on the situation and the progress of the ongoing investigation will be available at: www.orbital.com and www.nasa.gov/orbital NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Outcomes of a hospital-based employee lactation program.

PubMed

Spatz, Diane L; Kim, Gabriella S; Froh, Elizabeth B

2014-12-01

Little has been published about employee lactation support in hospitals and other healthcare facilities. The Children's Hospital of Philadelphia (CHOP), Philadelphia, PA, has a comprehensive employee lactation program. The objective of this study was to describe the breastfeeding practices of our employees and compare these results with national Centers for Disease Control and Prevention (CDC) data. The human resources department generated a list of all employees who filed for maternity leave between 2007 and 2011. These employees were contacted confidentially via e-mail to complete an electronic-based (SurveyMonkey.com) questionnaire. An initial message and three reminder messages were sent over a 3-month period during the last quarter of 2012, with 545 women completing the survey (response rate, 40%). Women who responded to the survey had significantly higher breastfeeding initiation rates compared with national CDC data (94.5% vs. 76.9%; p<0.0001). At 6 months, significantly more CHOP employees were breastfeeding (78.6% vs. 47.2%; p<0.0001). At 12 months 32.4% of CHOP employees were still breastfeeding compared with CDC data of 25.5% (p=0.0003). Additionally, over 20% of CHOP employees breastfed their infants for over 12 months (no national data for comparison). Within CHOP's comprehensive employee lactation program, women achieved breastfeeding milestones that well exceeded national data and the Healthy People 2020 targets for breastfeeding initiation and duration. CHOP's employee lactation program can serve as a model for other institutions.

Apremilast and Narrowband Ultraviolet-B Combination Therapy for Treating Moderate-to-Severe Plaque Psoriasis.

PubMed

Bagel, Jerry; Nelson, Elise; Keegan, Brian R

2017-10-01

Combining narrowband UVB (NB-UVB) phototherapy with biologics has been shown to enhance the therapeutic response of plaque psoriasis patients. The objective of this study was to evaluate the effectiveness of apremilast combined with NB-UVB in patients with moderate to severe plaque psoriasis. This was a 12-week, open-label study of 29 patients diagnosed with moderate to severe psoriasis. Patients received apremilast 30 mg twice daily, and increasing doses of NB-UVB (310-312 nm) 3 times per week for 12 weeks. Twenty-two of 29 patients (76%) completed the 12-week apremilast and NB-UVB combination therapy; 73% (16 of 22 completers) achieved a PASI 75 response at week 12. Mean scores for PASI, VAS pain, VAS itch, DLQI, and PGA improved by 77%, 77%, 69%, 70%, and 67%, respectively, at week 12. The most commonly reported adverse events (AEs) were mild and moderate first-degree burns related to NB-UVB (n=11 [38%] patients). A second-degree NB-UVB burn was reported (likely due to an underlying photosensitivity) and was considered a serious AE. The combination of apremilast with NB-UVB was effective for the treatment of moderate to severe plaque psoriasis, without any unexpected safety signals. Apremilast combined with NB-UVB provided a high treatment response in patients with moderate to severe plaque psoriasis, and may be an option for patients to enhance a patient's initial therapeutic response.

J Drugs Dermatol. 2017;16(10):957-962.

Canakinumab: in patients with cryopyrin-associated periodic syndromes.

PubMed

Curran, Monique P

2012-02-01

Canakinumab is a recombinant, fully human, monoclonal, anti-human interleukin-1β (IL-1β) antibody that binds with high affinity and specificity to human IL-1β, preventing its interaction with IL-1 receptors. Canakinumab (150 mg in patients weighing >40 kg or 2 mg/kg in those weighing 15-40 kg) administered once every 8 weeks as a single dose via subcutaneous injection provided a rapid and sustained response in patients with cryopyrin-associated periodic syndromes (CAPS). During the initial 8-week phase of a three-part, phase III trial, a complete response to a single dose of canakinumab occurred in 97% of the 35 patients with CAPS, with 71% of responses occurring within 8 days. After 8 weeks, 31 responders entered a 24-week, randomized, double-blind, withdrawal phase; there was a significant between-group difference in this phase in that none of the canakinumab recipients relapsed compared with 81% of placebo recipients. All patients from the second phase of the trial entered a third, 16-week phase of open-label treatment with canakinumab once every 8 weeks; clinical and biochemical remission was maintained in 28 of 29 patients who completed the trial. In a 2-year, open-label, phase III trial, subcutaneous canakinumab once every 8 weeks provided sustained disease control in the majority of patients with CAPS. Canakinumab was generally well tolerated in all trials, with the predominant adverse events being mild to moderate infections that were responsive to standard treatment.

Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia

PubMed Central

Porter, David L.; Hwang, Wei-Ting; Frey, Noelle V.; Lacey, Simon F.; Shaw, Pamela A.; Loren, Alison W.; Bagg, Adam; Marcucci, Katherine T.; Shen, Angela; Gonzalez, Vanessa; Ambrose, David; Grupp, Stephan A.; Chew, Anne; Zheng, Zhaohui; Milone, Michael C.; Levine, Bruce L.; Melenhorst, Jan J.; June, Carl H.

2018-01-01

Patients with multiply relapsed or refractory chronic lymphocytic leukemia (CLL) have a poor prognosis. Chimeric antigen receptor (CAR)–modified T cells targeting CD19 have the potential to improve on the low complete response rates with conventional therapies by inducing sustained remissions in patients with refractory B cell malignancies. We previously reported preliminary results on three patients with refractory CLL. We report the mature results from our initial trial using CAR-modified T cells to treat 14 patients with relapsed and refractory CLL. Autologous T cells transduced with a CD19-directed CAR (CTL019) lentiviral vector were infused into patients with relapsed/refractory CLL at doses of 0.14 × 108 to 11 × 108 CTL019 cells (median, 1.6 × 108 cells). Patients were monitored for toxicity, response, expansion, and persistence of circulating CTL019 T cells. The overall response rate in these heavily pretreated CLL patients was 8 of 14 (57%), with 4 complete remissions (CR) and 4 partial remissions (PR). The in vivo expansion of the CAR T cells correlated with clinical responses, and the CAR T cells persisted and remained functional beyond 4 years in the first two patients achieving CR. No patient in CR has relapsed. All responding patients developed B cell aplasia and experienced cytokine release syndrome, coincident with T cell proliferation. Minimal residual disease was not detectable in patients who achieved CR, suggesting that disease eradication may be possible in some patients with advanced CLL. PMID:26333935

An Excel tool for deriving key photosynthetic parameters from combined gas exchange and chlorophyll fluorescence: theory and practice.

PubMed

Bellasio, Chandra; Beerling, David J; Griffiths, Howard

2016-06-01

Combined photosynthetic gas exchange and modulated fluorometres are widely used to evaluate physiological characteristics associated with phenotypic and genotypic variation, whether in response to genetic manipulation or resource limitation in natural vegetation or crops. After describing relatively simple experimental procedures, we present the theoretical background to the derivation of photosynthetic parameters, and provide a freely available Excel-based fitting tool (EFT) that will be of use to specialists and non-specialists alike. We use data acquired in concurrent variable fluorescence-gas exchange experiments, where A/Ci and light-response curves have been measured under ambient and low oxygen. From these data, the EFT derives light respiration, initial PSII (photosystem II) photochemical yield, initial quantum yield for CO2 fixation, fraction of incident light harvested by PSII, initial quantum yield for electron transport, electron transport rate, rate of photorespiration, stomatal limitation, Rubisco (ribulose 1·5-bisphosphate carboxylase/oxygenase) rate of carboxylation and oxygenation, Rubisco specificity factor, mesophyll conductance to CO2 diffusion, light and CO2 compensation point, Rubisco apparent Michaelis-Menten constant, and Rubisco CO2 -saturated carboxylation rate. As an example, a complete analysis of gas exchange data on tobacco plants is provided. We also discuss potential measurement problems and pitfalls, and suggest how such empirical data could subsequently be used to parameterize predictive photosynthetic models. © 2015 John Wiley & Sons Ltd.

Polishing of treated palm oil mill effluent (POME) from ponding system by electrocoagulation process.

PubMed

Bashir, Mohammed J K; Mau Han, Tham; Jun Wei, Lim; Choon Aun, Ng; Abu Amr, Salem S

2016-01-01

As the ponding system used to treat palm oil mill effluent (POME) frequently fails to satisfy the discharge standard in Malaysia, the present study aimed to resolve this problem using an optimized electrocoagulation process. Thus, a central composite design (CCD) module in response surface methodology was employed to optimize the interactions of process variables, namely current density, contact time and initial pH targeted on maximum removal of chemical oxygen demand (COD), colour and turbidity with satisfactory pH of discharge POME. The batch study was initially designed by CCD and statistical models of responses were subsequently derived to indicate the significant terms of interactive process variables. All models were verified by analysis of variance showing model significances with Prob > F < 0.01. The optimum performance was obtained at the current density of 56 mA/cm(2), contact time of 65 min and initial pH of 4.5, rendering complete removal of colour and turbidity with COD removal of 75.4%. The pH of post-treated POME of 7.6 was achieved, which is suitable for direct discharge. These predicted outputs were subsequently confirmed by insignificant standard deviation readings between predicted and actual values. This optimum condition also permitted the simultaneous removal of NH3-N, and various metal ions, signifying the superiority of the electrocoagulation process optimized by CCD.

Introduction of Virtual Patient Software to Enhance Physician Assistant Student Knowledge in Palliative Medicine.

PubMed

Prazak, Kristine A

2017-01-01

The purpose of this project was to infuse palliative medicine and end-of-life care creatively into physician assistant (PA) education. Nine second-year PA students volunteered to participate in this quasi-experimental, pretest-posttest pilot study. Students initially completed an anonymous survey evaluating seven domains of knowledge in palliative medicine coupled with a self-assessment in competence. Virtual patient software was then used to simulate clinical encounters that addressed major palliative care domains. Upon completion of these cases, the same survey, with the addition of three questions about their own personal feelings, was administered. Overall response was positive in regard to improved knowledge and the virtual patient experience. After completion of the cases, students rated their self-assessed skills higher in all domains than prior to completing the cases. Factual knowledge scores showed a slight but not significant improvement, with an average pre-survey score of 4.56 and post-survey score of 4.67. Using virtual patient software can be a way of infusing palliative medicine and end-of-life care into PA education. These encounters can then be modified to include interprofessional encounters within the health professions.

Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial.

PubMed

Masarova, Lucia; Patel, Keyur P; Newberry, Kate J; Cortes, Jorge; Borthakur, Gautam; Konopleva, Marina; Estrov, Zeev; Kantarjian, Hagop; Verstovsek, Srdan

2017-04-01

Pegylated interferon alfa-2a is an immunomodulatory agent used to treat polycythemia vera. The durability of responses and long-term safety of this drug in patients with polycythaemia vera and essential thrombocythaemia have not been reported. Here, we present long-term efficacy and safety data from a single-centre, open-label, phase 2 trial, after a median of 83 months follow up. Patients older than 18 years who were diagnosed with essential thrombocythaemia or polycythaemia vera according to 2001 WHO criteria were eligible to enrol in our study. The initial starting dose of pegylated interferon alfa-2a was 450 μg subcutaneously once per week, but was decreased in a stepwise manner due to toxic effects to a final starting dose of 90 mg per week: three patients were started at a dose of 450 mg per week, three at 360 mg per week, 19 at 270 mg per week, 26 at 180 mg per week, and 32 at 90 mg per week. Treatment was continued for as long as the patients derived clinical benefit with reductions in dose and frequency of administration allowed at the discretion of the treating physician. Haematological responses were assessed every 3-6 months on the basis of blood counts as defined by the European LeukemiaNet critieria. The primary endpoint of the initial study was the proportion of patients with a haematological response. Complete haematological response was defined as normalisation of blood counts (for patients with essential thrombocythaemia, platelets ≤440 × 10 9 per L; for patients with polycythaemia vera, haemoglobin <15·0 g/L without phlebotomy) with complete resolution of palpable splenomegaly or symptoms in the absence of a thrombotic event. Data were analysed with descriptive statistics and in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00452023 and is ongoing but not enrolling new patients. Between May 21, 2005, and Dec 1, 2015, patients were followed up for a median of 83 months (IQR 69-94 months). Pegylated interferon alfa-2a induced haematological (66 [80%] of 83 patients) and molecular responses (35 [63%] of 55 patients) in 40 patients with essential thrombocythaemia and 43 patients with polycythaemia vera, with median durations of 66 months (IQR 35-83) and 53 months (24-70), respectively. 26 (39%) of 66 haematological responders and 25 (71%) of 35 molecular responders (with the JAK2 Val617Phe mutation) have maintained some response during follow-up: 49% maintained their best molecular response (nine of ten patients who had a complete response, five of 20 who had a partial response, and three of five who had a minor response). The incidence of major venous-thrombotic events during the study was 1·22 per 100 person-years. Overall, 18 (22%) of 83 patients discontinued therapy due to treatment-related toxicity. Although toxicity rates decreased over time, five patients had treatment-limiting grade 3 or 4 toxicities after 60 months on therapy. 32 patients are still enrolled on the study. Pegylated interferon alfa-2a can induce durable haematological and molecular responses in patients with essential thrombocythaemia and polycythaemia vera. This drug alone and in combination with other drugs could be explored further in clinical trials. US National Cancer Institute. Copyright © 2017 Elsevier Ltd. All rights reserved.

Responsiveness of Self-Report Measures in Individuals with Vertigo, Dizziness and Unsteadiness

PubMed Central

Friscia, Lauren A.; Morgan, Michael T.; Sparto, Patrick J.; Furman, Joseph M.; Whitney, Susan L.

2018-01-01

Objective The responsiveness (sensitivity to change) of many self-report measures commonly used with individuals who have balance and vestibular dysfunction has not been assessed. The purpose of this study was to determine the responsiveness of four self-report measures including the Activities-specific Balance Confidence (ABC) scale, the Dizziness Handicap Inventory (DHI), the Falls Efficacy Scale-International (FES-I), and the Vestibular Activities and Participation (VAP) scale in people seeking treatment for vertigo, dizziness, and unsteadiness. Study design A prospective descriptive study. Patients Forty-five patients (mean age 56 y, range 18–79 y) with vertigo, dizziness, and unsteadiness were included. Main outcome measures Participants completed the measures at their initial physician examination and four to six weeks later. The follow-up visit included a Global Rating of Change Scale (GROC). The change in total scores for each self-report measure from initial visit to follow-up visit were recorded and compared against the GROC. A Spearman correlation was performed to determine the relationship between all four self-report measures and the GROC. A Receiver Operating Characteristic (ROC) curve was also used to evaluate responsiveness. Results Significant correlations were found between the GROC and ABC (ρ = 0.50), DHI (ρ = 0.61), and FES-I (ρ = 0.36), but not the VAP (ρ = 0.27). The ROC curve analysis showed that the area under the curve was significantly greater than 0.5 for the ABC, DHI and FES-I. Conclusion The DHI demonstrated the greatest responsiveness, with an optimal cutoff of a change in 3 points related to significant change. PMID:24829039

[Measurement of 75Se-SeHCAT abdominal retention in the initial diagnosis of Bile Acid Absorption (BAM)].

PubMed

Notta, P C; Ramal, D; Maisterra, S; Rodríguez Gasen, A; Maymó, S; Sabaté, A; Girbau, A; Guardiola, J; Martín-Comín, J

2011-01-01

To evaluate the usefulness of the (75)SeHCAT abdominal retention (AR) measurement in the early diagnosis of diarrhea syndrome (DS). Thirty-seven patients with diarrhea syndrome within the first month of evolution were prospectively evaluated. The (75)Se-SeHCAT abdominal retention was measured 4 and 7 days post-administration of 0.01 mCi of (75)SeHCAT. The test was performed prior to treatment and at 3 months when the baseline study was positive. The test was considered positive if the RA was <25% at 4(th) and <10% on the 7th day. The patients were visited at 3 months. Depending on the response, 3 groups were established: a) complete response: normalization of stool frequency, b) partial response, decrease of frequency or c) no response. Group A: The AR of (75)Se-SEHCAT was normal in 21 patients. Six were diagnosed of colonic diverticulosis, 8 of irritable bowel syndrome, 1 of lymphocytic colitis, 1 of post-gastroenteritis syndrome, 1 of celiac disease and 1 of stenosis of the cardia. Four are still under study. Group B: The AR of (75)Se-SEHCAT decreased in 16 patients. All showed abnormal AR at day 7 and all but 1 at day 4. Following administration of cholestyramine resin, 8 (50%) presented partial response and 8 (50%) complete response. At 3 months, AR had increased at day 4 and 9 at day 7. The measurement of (75)SEHCAT abdominal retention allows the early diagnosis of bile acid malabsorption in 43% of the patients with DS. Measurement at 7 days seems more accurate than that at 4 days. Copyright © 2010 Elsevier España, S.L. y SEMNIM. All rights reserved.

Familial Risk for Insomnia Is Associated With Abnormal Cortisol Response to Stress.

PubMed

Drake, Christopher L; Cheng, Philip; Almeida, David M; Roth, Thomas

2017-10-01

Abnormalities in the stress system have been implicated in insomnia. However, studies examining physiological stress regulation in insomnia have not consistently detected differences in the hypothalamic-pituitary-adrenal (HPA)-axis response to stress. One explanation may be that deficits in the stress system are associated specifically with a biological vulnerability to insomnia rather than the phenotypic expression of insomnia. To examine stress response as a function of vulnerability to insomnia, this study tested response to the Trier Social Stress Test in a sample of healthy sleepers with varying familial risks for insomnia. Thirty-five healthy individuals with and without familial risk for insomnia were recruited to complete a laboratory stressor. Participants with one or both biological parents with insomnia were categorized as positive for familial risk, whereas those without biological parents with insomnia were categorized as negative for familial risk. Participants completed the Trier Social Stress Test in the laboratory, and psychological and physiological (autonomic and HPA-axis) responses were compared. Despite self-reported increases in anxiety, those positive for familial risk exhibited a blunted cortisol response relative to those without familial risk for insomnia. Individuals with blunted cortisol also reported heightened reactivity to personal life stressors, including increased sleep disturbances, elevated cognitive intrusions, and more behavioral avoidance. Findings from this study provide initial evidence that abnormal stress regulation may be a biological predisposing factor conferred via familial risk for insomnia. This deficit may also predict negative consequences over time, including insomnia and the associated psychiatric comorbidities. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Naltrexone moderates the relationship between cue-induced craving and subjective response to methamphetamine in individuals with methamphetamine use disorder.

PubMed

Roche, Daniel J O; Worley, Matthew J; Courtney, Kelly E; Bujarski, Spencer; London, Edythe D; Shoptaw, Steven; Ray, Lara A

2017-07-01

Reductions in cue-induced craving and subjective response to drugs of abuse are commonly used as initial outcome measures when testing novel medications for the treatment of addiction. Yet neither the relationship between these two measures at the individual level nor the moderating effects of pharmacotherapies on this relationship has been examined. This secondary data analysis sought to examine (1) the predictive relationship between cue-induced craving and subsequent acute subjective response to methamphetamine (MA) and (2) whether the opioid-receptor antagonist naltrexone moderated this association in a sample of non-treatment-seeking individuals who met DSM-IV criteria for MA use disorder (abuse or dependence). Participants (n = 30) completed two 4-day medication regimens (oral naltrexone 50 mg or placebo, in a randomized, counterbalanced, and double-blind fashion). On day 4 of each medication regimen, participants completed a cue-reactivity paradigm followed by intravenous MA administration. Methamphetamine craving was assessed after the cue-reactivity paradigm, and subjective response to MA was assessed during MA infusion. Cue-induced craving for MA was positively associated with post-infusion subjective MA effects, including positive (i.e., stimulation, good effects, feel drug, high), negative (i.e., anxious and depressed), and craving-related (i.e., want more, would like access to drug, crave) responses. Naltrexone, vs. placebo, significantly reduced the association between cue-induced craving and positive subjective response to MA. The findings indicate that naltrexone moderates the predictive relationship between cue-induced craving and positive subjective effects of MA, thereby suggesting a behavioral mechanism by which naltrexone may be efficacious in treating MA use disorder.

Initiation & completion rates of hepatitis A vaccination among US pediatric populations born between 2005 and 2009.

PubMed

Weiss, Thomas; Zhang, Dongmu; Borse, Nagesh N; Walter, Emmanuel B

2015-11-27

To estimate hepatitis A vaccine series initiation and completion rates, assess time to vaccination, identify missed opportunities for the hepatitis A vaccine series, and examine factors associated with hepatitis A vaccine series initiation and completion. We conducted a retrospective, observational study using three healthcare claims databases separately. The study population was comprised of children born between years 2005 and 2009 that were continuously enrolled for at least three and a half years from the date of birth. Every child was followed from date of birth for three and a half years for hepatitis A vaccination. There were 93,735 eligible children from Clinformatics Data Mart, 202,513 from MarketScan Commercial, and 207,545 from MarketScan Medicaid. The overall hepatitis A vaccine series initiation rate was 63.8-79.4% and completion rate was 45.1-66.8% across the three databases. About 62.8-90.1% of the children who never initiated hepatitis A vaccine had at least one well visit from 1 year to three and a half years old. Children were more likely to initiate and complete the hepatitis A vaccine series if they were from more recent birth cohorts, from states with a hepatitis A vaccination recommendation prior to the ACIP universal recommendation, from states with daycare/school entry requirements, were enrolled in an HMO health plan, had pediatricians as primary providers, had more doctor's office/well visits and received MMR/Varicella vaccines. In this study, approximately one in every three to five children remained unvaccinated against hepatitis A. Although the hepatitis A vaccine series initiation and completion improved from 2005 to 2009, vaccine coverage has stabilized in recent years. It is important for providers to identify every opportunity for hepatitis A vaccination and to assure that children get protection from this vaccine-preventable disease. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Rotavirus vaccine coverage and factors associated with uptake using linked data: Ontario, Canada

PubMed Central

Chung, Hannah; Schwartz, Kevin L.; Guttmann, Astrid; Deeks, Shelley L.; Kwong, Jeffrey C.; Crowcroft, Natasha S.; Wing, Laura; Tu, Karen

2018-01-01

Background In August 2011, Ontario, Canada introduced a rotavirus immunization program using Rotarix™ vaccine. No assessments of rotavirus vaccine coverage have been previously conducted in Ontario. Methods We assessed vaccine coverage (series initiation and completion) and factors associated with uptake using the Electronic Medical Record Administrative data Linked Database (EMRALD), a collection of family physician electronic medical records (EMR) linked to health administrative data. Series initiation (1 dose) and series completion (2 doses) before and after the program’s introduction were calculated. To identify factors associated with series initiation and completion, adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) were calculated using logistic regression. Results A total of 12,525 children were included. Series completion increased each year of the program (73%, 79% and 84%, respectively). Factors associated with series initiation included high continuity of care (aOR = 2.15; 95%CI, 1.61–2.87), maternal influenza vaccination (aOR = 1.55; 95%CI,1.24–1.93), maternal immmigration to Canada in the last five years (aOR = 1.47; 95% CI, 1.05–2.04), and having no siblings (aOR = 1.62; 95%CI,1.30–2.03). Relative to the first program year, infants were more likely to initiate the series in the second year (aOR = 1.71; 95% CI 1.39–2.10) and third year (aOR = 2.02; 95% CI 1.56–2.61) of the program. Infants receiving care from physicians with large practices were less likely to initiate the series (aOR 0.91; 95%CI, 0.88–0.94, per 100 patients rostered) and less likely to complete the series (aOR 0.94; 95%CI, 0.91–0.97, per 100 patients rostered). Additional associations were identified for series completion. Conclusions Family physician delivery achieved moderately high coverage in the program’s first three years. This assessment demonstrates the usefulness of EMR data for evaluating vaccine coverage. Important insights into factors associated with initiation or completion (i.e. high continuity of care, smaller roster sizes, rural practice location) suggest areas for research and potential program supports. PMID:29444167

Ketogenic diet in adolescents and adults with epilepsy.

PubMed

Nei, Maromi; Ngo, Ly; Sirven, Joseph I; Sperling, Michael R

2014-06-01

The ketogenic diet is an alternative treatment for patients with refractory epilepsy. Most studies to date report dietary response in children. There are limited data evaluating the efficacy of the ketogenic diet in adults. This is a report of the long-term outcome in a largely adult population of patients treated with the ketogenic diet for epilepsy. Twenty-nine adult and adolescent patients (mean age 32 years, range 11-51) were initiated on the ketogenic diet and followed until diet discontinuation. Clinical response and adverse effects were noted during the duration of the diet. Fifty-two percent of patients had a significant reduction in seizure frequency on the ketogenic diet, including 45% with ≥50% reduction in seizure frequency. Thirty-one percent had no improvement, seven percent were unable to successfully initiate the diet, and 10% had a >50% increase in seizure frequency. The diet was continued for a mean of 9 months (range 0.13-35 months), with five patients completing ≥23 months. There was a trend toward better response and better tolerability/longer duration in patients with symptomatic generalized epilepsy. The diet was generally well-tolerated, but undesired weight loss and constipation were the most frequent adverse effects. The ketogenic diet can be used safely in the adult and adolescent population, with a response rate similar to those seen in children. Patient with symptomatic generalized epilepsy may be particularly good candidates for this type of dietary treatment. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Circulatory Responses to Asphyxia Differ if the Asphyxia Occurs In Utero or Ex Utero in Near-Term Lambs

PubMed Central

Sobotka, Kristina S.; Morley, Colin; Ong, Tracey; Polglase, Graeme R.; Aridas, James D. S.; Miller, Suzanne L.; Schmölzer, Georg M.; Klingenberg, Claus; Moss, Timothy J. M.; Jenkin, Graham; Hooper, Stuart B.

2014-01-01

Background A cornerstone of neonatal resuscitation teaching suggests that a rapid vagal-mediated bradycardia is one of the first signs of perinatal compromise. As this understanding is based primarily on fetal studies, we investigated whether the heart rate and blood pressure response to total asphyxia is influenced by whether the animal is in utero or ex utero. Methods Fetal sheep were instrumented at ∼139 days of gestation and then asphyxiated by umbilical cord occlusion until mean arterial blood pressure decreased to ∼20 mmHg. Lambs were either completely submerged in amniotic fluid (in utero; n = 8) throughout the asphyxia or were delivered and then remained ex utero (ex utero; n = 8) throughout the asphyxia. Heart rate and arterial blood pressure were continuously recorded. Results Heart rate was higher in ex utero lambs than in utero lambs. Heart rates in in utero lambs rapidly decreased, while heart rates in ex utero lambs initially increased following cord occlusion (for ∼1.5 min) before they started to decrease. Mean arterial pressure initially increased then decreased in both groups. Conclusions Heart rate response to asphyxia was markedly different depending upon whether the lamb was in utero or ex utero. This indicates that the cardiovascular responses to perinatal asphyxia are significantly influenced by the newborn's local environment. As such, based solely on heart rate, the stage and severity of a perinatal asphyxic event may not be as accurate as previously assumed. PMID:25393411

Circulatory responses to asphyxia differ if the asphyxia occurs in utero or ex utero in near-term lambs.

PubMed

Sobotka, Kristina S; Morley, Colin; Ong, Tracey; Polglase, Graeme R; Aridas, James D S; Miller, Suzanne L; Schmölzer, Georg M; Klingenberg, Claus; Moss, Timothy J M; Jenkin, Graham; Hooper, Stuart B

2014-01-01

A cornerstone of neonatal resuscitation teaching suggests that a rapid vagal-mediated bradycardia is one of the first signs of perinatal compromise. As this understanding is based primarily on fetal studies, we investigated whether the heart rate and blood pressure response to total asphyxia is influenced by whether the animal is in utero or ex utero. Fetal sheep were instrumented at ∼ 139 days of gestation and then asphyxiated by umbilical cord occlusion until mean arterial blood pressure decreased to ∼ 20 mmHg. Lambs were either completely submerged in amniotic fluid (in utero; n = 8) throughout the asphyxia or were delivered and then remained ex utero (ex utero; n = 8) throughout the asphyxia. Heart rate and arterial blood pressure were continuously recorded. Heart rate was higher in ex utero lambs than in utero lambs. Heart rates in in utero lambs rapidly decreased, while heart rates in ex utero lambs initially increased following cord occlusion (for ∼ 1.5 min) before they started to decrease. Mean arterial pressure initially increased then decreased in both groups. Heart rate response to asphyxia was markedly different depending upon whether the lamb was in utero or ex utero. This indicates that the cardiovascular responses to perinatal asphyxia are significantly influenced by the newborn's local environment. As such, based solely on heart rate, the stage and severity of a perinatal asphyxic event may not be as accurate as previously assumed.

Light colour and intensity alters reproductive/seasonal responses in Japanese quail.

PubMed

Yadav, Suneeta; Chaturvedi, Chandra Mohini

2015-08-01

An extensive literature is available on the photoperiodic responses of avian species but studies on light colour and wavelength from light emitting diode (LED) sources on reproduction are limited. Hence, an experiment was designed to study the effect of different colours and intensities of light on the reproductive responses of Japanese quail. Three-week old quail were exposed to five different light conditions with a long photoperiod (LD 16:8): WT (white fluorescent light 100 lux as control), W LED (white light emitting diode, 30 lux), B LED (blue LED, 30 lux), G LED (green LED, 30 lux) and R-LED (red LED, 30 lux). The cloacal gland size, an indicator of androgenic activity, was monitored weekly. The results indicated an early initiation of gonadal growth in WT quail which continued and maintained a plateau throughout the period of study. On the other hand, in general low intensity light, there was a decreased amplitude of the reproductive cycle and the quail exposed to different colour lights (green, red and blue lights) used different incubation times to initiate their gonadal growth and exhibited a gonadal cycle of a different duration up to 15.5 weeks. Thereafter, the gonad of quail of all the LED groups started developing again (including the blue LED exposed quail which remained undeveloped until this age) and attained the increased degree of growth until 26.5 weeks of age. During the second cycle, gonads of green and red light exposed quail continued to increase and maintained a plateau of development similar to WT exposed control while white and blue LED exposed quail exhibited spontaneous regression and attained complete sexual quiescence. Based on our study, it is suggested that long term exposure to blue LED light of low intensity may induce gonadal regression even under long-day conditions (LD 16:8), while exposure to green and red lights appears to maintain a constant photosensitivity after one complete gonadal cycle. Copyright © 2015 Elsevier Inc. All rights reserved.

Granulocytic sarcoma of the ovary in a nonleukemic patient.

PubMed

Aguiar, R C; Pozzi, D H; Chamone, D A

1993-01-01

We report a case of granulocytic sarcoma of the ovary preceding acute myeloid leukemia by twelve months, with no evidence of any hematological involvement at the time of first diagnosis. The patient was initially treated with surgery and chemotherapy for undifferentiated lymphoma and, although this aggressive protocol resulted in a complete response, granulocytic sarcoma recurred as extramedullary disease, followed by the appearance of acute myeloid leukemia. We discuss the clinical, histopathological and immunohistochemical features of the disease, the differential diagnosis and, in particular, the role of early aggressive treatment on the outcome of the patient.

[Effect of alcohol intake on the ability to pilot aircraft].

PubMed

Ushakov, I B; Egorov, S V

1996-01-01

During the initial 4 hours after alcohol intake at a dose of 1.9 g/kg aircraft operators displayed disturbances in the psychic processes and functions responsible for each (from information reception and processing up to decision-making and building-up the controlling actions) structural elements in their activity resulting in considerable limitation or a complete failure to pilot aircraft. Main disorders included inability to correctly analyse flight situation and loss of skills to automatically control simulator, a sudden depletion of psychophysiological reserves and deterioration of operator's reliability. Less elaborated professional skills appear to be the most vulnerable.

Effect of stress concentrations in composite structures

NASA Technical Reports Server (NTRS)

Babcock, C. D.; Waas, A. M.

1985-01-01

Composite structures have found wide use in many engineering fields and a sound understanding of their response under load is important to their utilization. An experimental program is being carried out to gain a fundamental understanding of the failure mechanics of multilayered composite structures at GALCIT. As a part of this continuing study, the performance of laminated composite plates in the presence of a stress gradient and the failure of composite structures at points of thickness discontinuity is assessed. In particular, the questions of initiation of failure and its subsequent growth to complete failure of the structure are addressed.

Lunar surface magnetometer experiment

NASA Technical Reports Server (NTRS)

Dyal, P.; Parkin, C. W.; Colburn, D. S.; Schubert, G.

1972-01-01

The Apollo 16 lunar surface magnetometer (LSM) activation completed the network installation of magnetic observatories on the lunar surface and initiated simultaneous measurements of the global response of the moon to large-scale solar and terrestrial magnetic fields. Fossil remanent magnetic fields have been measured at nine locations on the lunar surface, including the Apollo 16 LSM site in the Descartes highlands area. This fossil record indicates the possible existence of an ancient lunar dynamo or a solar or terrestrial field much stronger than exists at present. The experimental technique and operation of the LSM are described and the results obtained are discussed.

Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis.

PubMed

Lanternier, F; Poiree, S; Elie, C; Garcia-Hermoso, D; Bakouboula, P; Sitbon, K; Herbrecht, R; Wolff, M; Ribaud, P; Lortholary, O

2015-11-01

Mucormycosis incidence is increasing and is associated with a high rate of mortality. Although lipid-based formulations of amphotericin B are the recommended first-line treatment, only one prospective trial in a limited number of patients has been performed to evaluate this regimen. Patients with proven or probable mucormycosis were included between June 2007 and March 2011. Patients were scheduled to receive 10 mg/kg/day liposomal amphotericin B (L-AMB) monotherapy for 1 month and surgery was performed when appropriate. The primary outcome was response rate at week 4 or at the end of treatment (EOT) if before week 4, evaluated by an independent committee. ClinicalTrials.gov Identifier: NCT00467883. Forty patients were enrolled. Response was analysed in 33 patients at week 4. Most patients had a haematological malignancy as their primary underlying disease (53%). Seventy-one percent of patients underwent therapeutic surgery. The response rate at week 4 or at EOT was 36%, with 18% partial responses and 18% complete responses. The response rate at week 12 was 45%, with 13% partial responses and 32% complete responses. Overall mortality was 38% at week 12 and 53% at week 24. Serum creatinine doubled in 16 (40%) patients and returned to normal levels within 12 weeks in 10/16 (63%). High-dose L-AMB for mucormycosis, in combination with surgery in 71% of cases, was associated with an overall response rate of 36% at week 4 and 45% at week 12 and creatinine level doubling in 40% of patients (transient in 63%). These results may serve as the basis for future clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2.

PubMed

Coste, S C; Kesterson, R A; Heldwein, K A; Stevens, S L; Heard, A D; Hollis, J H; Murray, S E; Hill, J K; Pantely, G A; Hohimer, A R; Hatton, D C; Phillips, T J; Finn, D A; Low, M J; Rittenberg, M B; Stenzel, P; Stenzel-Poore, M P

2000-04-01

The actions of corticotropin-releasing hormone (Crh), a mediator of endocrine and behavioural responses to stress, and the related hormone urocortin (Ucn) are coordinated by two receptors, Crhr1 (encoded by Crhr) and Crhr2. These receptors may exhibit distinct functions due to unique tissue distribution and pharmacology. Crhr-null mice have defined central functions for Crhr1 in anxiety and neuroendocrine stress responses. Here we generate Crhr2-/- mice and show that Crhr2 supplies regulatory features to the hypothalamic-pituitary-adrenal axis (HPA) stress response. Although initiation of the stress response appears to be normal, Crhr2-/- mice show early termination of adrenocorticotropic hormone (Acth) release, suggesting that Crhr2 is involved in maintaining HPA drive. Crhr2 also appears to modify the recovery phase of the HPA response, as corticosterone levels remain elevated 90 minutes after stress in Crhr2-/- mice. In addition, stress-coping behaviours associated with dearousal are reduced in Crhr2-/- mice. We also demonstrate that Crhr2 is essential for sustained feeding suppression (hypophagia) induced by Ucn. Feeding is initially suppressed in Crhr2-/- mice following Ucn, but Crhr2-/- mice recover more rapidly and completely than do wild-type mice. In addition to central nervous system effects, we found that, in contrast to wild-type mice, Crhr2-/- mice fail to show the enhanced cardiac performance or reduced blood pressure associated with systemic Ucn, suggesting that Crhr2 mediates these peripheral haemodynamic effects. Moreover, Crhr2-/- mice have elevated basal blood pressure, demonstrating that Crhr2 participates in cardiovascular homeostasis. Our results identify specific responses in the brain and periphery that involve Crhr2.

An Initial evaluation of law enforcement overdose training in Rhode Island.

PubMed

Saucier, Cory D; Zaller, Nickolas; Macmadu, Alexandria; Green, Traci C

2016-05-01

To assess initial change in knowledge, self-efficacy, and anticipated behaviors among Rhode Island law enforcement officers on drug overdose response and prevention. Law enforcement officers (N=316) voluntarily completed a pre-post evaluation immediately before and after taking part in overdose prevention and response trainings. Assessment items included measures of knowledge (Brief Overdose Recognition and Response Assessment (BORRA)), self-efficacy, attitudes toward drugs and overdose prevention, awareness of the Good Samaritan Law, and open-ended items pertaining to overdose knowledge and response behaviors. Non-parametric tests measured within-group and between-group differences. Wilcoxon Signed Rank tests and Kruskal-Wallis tests evaluated changes in BORRA scores and self-efficacy items. McNemar's tests assessed changes regarding the Good Samaritan law and open-ended items. Wilcoxon Signed Rank tests measured post-training change in attitudes. Law enforcement officers demonstrated statistically significant improvements in self-efficacy (identifying signs of opioid overdose, naloxone indication, counseling witnesses in overdose prevention, and referring witnesses for more information), overdose identification knowledge (BORRA mean increased from 7.00 to 10.39), naloxone administration knowledge (BORRA mean increased from 10.15 to 12.59), Good Samaritan Law awareness (17.9% increase after training), and anticipated behaviors in response to future observed overdose (65.7% changed from passive to active response post training). Harm reduction programs can provide law enforcement officers with the knowledge and skills necessary to intervene and reduce overdose mortality. Given the statistically significant improvements in self-efficacy, attitudinal changes, and Good Samaritan law awareness, law enforcement officers are more prepared to actively interact with drug users during a drug-involved emergency. Copyright © 2016. Published by Elsevier Ireland Ltd.

Neoadjuvant Sandwich Treatment With Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial

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

Gao, Yuan-Hong; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou; Lin, Jun-Zhong

Purpose: Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications. Methods and Materials: Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consistingmore » of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded. Results: All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively. Conclusions: Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen as induction, concomitant, and consolidation chemotherapy to the conventional radiation is well tolerated. The strategy is highly effective in terms of pCR and major regression, which warrants further investigation.« less

Comparison of curative surgery and definitive chemoradiotherapy as initial treatment for patients with cervical esophageal cancer.

PubMed

Takebayashi, Katsushi; Tsubosa, Yasuhiro; Matsuda, Satoru; Kawamorita, Keisuke; Niihara, Masahiro; Tsushima, Takahiro; Yokota, Tomoya; Sato, Hiroshi; Onozawa, Yusuke; Ogawa, Hirofumi; Kamijo, Tomoyuki; Onitsuka, Tetsuro; Nakagawa, Masahiro; Yasui, Hirofumi

2017-02-01

Esophagectomy and definitive chemoradiotherapy are recognized standard initial treatment modalities for cervical esophageal cancer. The goal of this study was to compare the treatment outcomes of curative surgery with those of chemoradiotherapy in patients who had potentially resectable tumor and who were candidates for surgery. We evaluated the data from 49 consecutive patients who were diagnosed with potentially resectable cervical esophageal cancer and who were deemed candidates for surgery. Thirteen patients were included in the surgery group, and 36 patients were included in chemoradiotherapy group. Baseline characteristics were balanced between the two groups. In the chemoradiotherapy group, the complete response rate was 58.3%. There was no significant difference in 5-year overall survival when comparing the surgery group and the chemoradiotherapy group (surgery, 60.6%; chemoradiotherapy, 51.4%; P = 0.89). In the chemoradiotherapy group, of the 15 patients who failed to respond to initial treatment, 11 patients subsequently underwent salvage surgery. In conclusion, curative surgery and chemoradiotherapy as initial treatment for cervical esophageal cancer have comparable survival outcomes. Chemoradiotherapy should be selected as the initial larynx-preserving treatment for patients with cervical esophageal cancer although chemoradiotherapy non-responders require additional treatment, including salvage surgery. © 2016 International Society for Diseases of the Esophagus.

Regulation of anxiety and initiation of sexual behavior by CREB in the nucleus accumbens

PubMed Central

Barrot, Michel; Wallace, Deanna L.; Bolaños, Carlos A.; Graham, Danielle L.; Perrotti, Linda I.; Neve, Rachael L.; Chambliss, Heather; Yin, Jerry C.; Nestler, Eric J.

2005-01-01

Sexual deficits and other behavioral disturbances such as anxiety-like behaviors can be observed in animals that have undergone social isolation, especially in species having important social interactions. Using a model of protracted social isolation in adult rats, we observed increased anxiety-like behavior and deficits in both the latency to initiate sexual behavior and the latency to ejaculate. We show, using transgenic cAMP response element (CRE)-LacZ reporter mice, that protracted social isolation also reduces CRE-dependent transcription within the nucleus accumbens. This decrease in CRE-dependent transcription can be mimicked in nonisolated animals by local viral gene transfer of a dominant negative mutant of CRE-binding protein (CREB). We previously showed that this manipulation increases anxiety-like behavior. We show here that it also impairs initiation of sexual behavior in nonisolated animals, a deficit that can be corrected by anxiolytic drug treatment. This local reduction in CREB activity, however, has no influence on ejaculation parameters. Reciprocally, we used the viral transgenic approach to overexpress CREB in the nucleus accumbens of isolated animals. We show that this local increase in CREB activity completely rescued the anxiety phenotype of the isolated animals, as well as their deficit in initiating sexual behavior, but failed to rescue the deficit in ejaculation. Our data suggest a role for the nucleus accumbens in anxiety responses and in specific aspects of sexual behavior. The results also provide insight into the molecular mechanisms by which social interactions affect brain plasticity and behavior. PMID:15923261

Free range users and one hit wonders: community users of an Internet-based cognitive behaviour therapy program.

PubMed

Christensen, Helen; Griffiths, Kathy; Groves, Chloe; Korten, Ailsa

2006-01-01

Little is known about the predictors of symptom change or the methods that might increase user 'compliance' on websites designed to improve mental health outcomes. The present paper: (i) examines predictors of expected final depression and anxiety scores on the MoodGYM website as a function of user characteristics; and (ii) compares the compliance rates of the original site with the new public version of the site (MoodGYM Mark II). The latter site requires compulsory completion of 'core' online assessments and may increase completion of site questionnaires. MoodGYM Mark I participants were 19,607 visitors (public registrants) between April 2001 and September 2003 plus 182 participants who had been randomly assigned to MoodGYM in an earlier trial (The BlueMood Trial). MoodGYM Mark II participants were 38,791 public registrants of the MoodGYM Mark II site collected between September 2003 and October 2004. Symptom assessments are repeated within the website intervention to allow the examination of change in symptoms. Outcome variables were gender, initial depression severity scores, number of assessments completed and final anxiety and depression scores. Men are predicted to be 0.19 units (SE=0.095) higher than women on depression, controlling for the initial depression level and number of modules completed. For initial depression scores above 2, it is predicted that the final score will indicate improvement relative to the initial score, the magnitude of the improvement increasing as a function of the number of modules attempted. For initial anxiety scores above 2, it is predicted that the final score will indicate improvement relative to the initial score, the magnitude of the improvement increasing as a function of the number of modules attempted. Mark II registrants were more likely than to Mark I registrants to complete onsite assessments. Visitors to the MoodGYM site are likely to have better psychological outcomes if they complete more of the site material. Compulsory completion of core sections increases assessment completion. There is a need to examine further the significance of attrition from online interventions, to develop methods of handling missing data, and to investigate strategies to improve visitor dropout.

Summary of the land-use inventory for the nonpoint-source evaluation monitoring watersheds in Wisconsin

USGS Publications Warehouse

Wierl, J.A.; Rappold, K.F.; Amerson, F.U.

1996-01-01

In 1992, the Wisconsin Department of Natural Resources (WDNR) in cooperation with the U.S. Geological Survey initiated a land-use inventory to identify sources of pollutants and track the land-management changes for eight evaluation monitoring watersheds established as part of the WDNR's Nonpoint Source Program. Each evaluation monitoring watershed is within a WDNR priority watershed. The U.S. Geological Survey is responsible for collection of water-quality data in the evaluation monitoring watersheds. An initial inventory was completed for each of the WDNR priority watersheds before nonpoint-source plans were developed for the control of nonpoint pollution. The land-use inventory described in this report expands upon the initial inventory by including nonpoint pollution sources that were not identified and also by updating changes in landuse and land-management practices. New sources of nonpoint pollution, not identified in the initial inventory, could prove to be important when monitored and modeled data are analyzed. This effort to inventory the evaluation monitoring watersheds will help with the interpretation of future land-use and water-quality data. This report describes landuse inventory methods, presents results of the inventory, and lists proposed future activities.

Initial Assessments of E-Learning Modules in Cytotechnology Education.

PubMed

Mukherjee, Maheswari S; Donnelly, Amber D

2018-01-01

Nine E-learning modules (ELMs) were developed in our program using Articulate software. This study assessed our cytotechnology (CT) students' perceptions on the content of the ELMs, and the perceived influence of the ELMs on students' performance during clinical rotations. All CT students watched nine ELMs before the related classroom lecture and group discussion. Following that, students completed nine preclinical rotation surveys. After their clinical rotations, students completed nine postclinical rotation surveys. Statements on the content of the ELMs regarding the quality of the video and audio, duration, navigation, and the materials presented, received positive responses from the majority of the students. While there were a few disagreements and neutral responses, most of the students responded positively saying that the ELMs better prepared them for their role, as well as helped them to better perform their roles during the clinical rotation. The majority of the students recommended developing more EMLs for cytology courses in the future. This study has given hope that the ELMs have potential to enhance our online curriculum and benefit students, within the United States and internationally, who have no easy access to cytology clinical laboratories for hands-on training.

Hierarchical protein export mechanism of the bacterial flagellar type III protein export apparatus.

PubMed

Minamino, Tohru

2018-06-01

The bacterial flagellum is supramolecular motility machinery consisting of the basal body, the hook and the filament. Flagellar proteins are translocated across the cytoplasmic membrane via a type III protein export apparatus, diffuse down the central channel of the growing structure and assemble at the distal end. Flagellar assembly begins with the basal body, followed by the hook and finally the filament. The completion of hook assembly is the most important morphological checkpoint of the sequential flagellar assembly process. When the hook reaches its mature length of about 55 nm in Salmonella enterica, the type III protein export apparatus switches export specificity from proteins required for the structure and assembly of the hook to those responsible for filament assembly, thereby terminating hook assembly and initiating filament assembly. Three flagellar proteins, namely FliK, FlhB and FlhA, are responsible for this substrate specificity switching. Upon completion of the switching event, interactions among FlhA, the cytoplasmic ATPase complex and flagellar type III export chaperones establish the assembly order of the filament at the hook tip. Here, we describe our current understanding of a hierarchical protein export mechanism used in flagellar type III protein export.

Mechanisms of palatal epithelial seam disintegration by Transforming Growth Factor (TGF)-β3

PubMed Central

Ahmed, Shaheen; Liu, Chang-Chih; Nawshad, Ali

2007-01-01

TGFβ3 signaling initiates and completes sequential phases of cellular differentiation that is required for complete disintegration of the palatal medial edge seam, that progresses between 14 to 17 embryonic days in the murine system, which is necessary in establishing confluence of the palatal stroma. Understanding the cellular mechanism of palatal MES disintegration in response to TGFβ3 signaling will result in new approaches to defining the causes of cleft palate and other facial clefts that may result from failure of seam disintegration. We have isolated MES primary cells to study the details of MES disintegration mechanism by TGFβ3 during palate development using several biochemical and genetic approaches. Our results demonstrate a novel mechanism of MES disintegration where MES, independently yet sequentially, undergoes cell cycle arrest, cell migration and apoptosis to generate immaculate palatal confluency during palatogenesis in response to robust TGFβ3 signaling. The results contribute to a missing fundamental element to our base knowledge of the diverse roles of TGFβ3 in functional and morphological changes that MES undergo during palatal seam disintegration. We believe that our findings will lead to more effective treatment of facial clefting. PMID:17698055

NPS alternate techsat satellite, design project for AE-4871

NASA Technical Reports Server (NTRS)

1993-01-01

This project was completed as part of AE-4871, Advanced Spacecraft Design. The intent of the course is to provide experience in the design of all the major components in a spacecraft system. Team members were given responsibility for the design of one of the six primary subsystems: power, structures, propulsion, attitude control, telemetry, tracking and control (TT&C), and thermal control. In addition, a single member worked on configuration control, launch vehicle integration, and a spacecraft test plan. Given an eleven week time constraint, a preliminary design of each subsystem was completed. Where possible, possible component selections were also made. Assistance for this project came principally from the Naval Research Laboratory's Spacecraft Technology Branch. Specific information on components was solicited from representatives in industry. The design project centers on a general purpose satellite bus that is currently being sought by the Strategic Defense Initiative.

Maturation of the MOUTh Intervention

PubMed Central

Jablonski-Jaudon, Rita A.; Kolanowski, Ann M.; Winstead, Vicki; Jones-Townsend, Corteza; Azuero, Andres

2016-01-01

The purpose of the current article is to describe a personalized practice originally conceived as a way to prevent and minimize care-resistant behavior to provide mouth care to older adult with dementia. The original intervention, Managing Oral Hygiene Using Threat Reduction Strategies (MOUTh), matured during the clinical trial study into a relationship-centered intervention with emphasis on developing strategies that support residents behavioral health and staff involved in care. Relationships that were initially pragmatic (i.e., focused on the task of completing mouth care) developed into more personal and responsive relationships that involved deeper engagement between mouth care providers and nursing home (NH) residents. Mouth care was accomplished and completed in a manner enjoyable to NH residents and mouth care providers. The MOUTh intervention may also concurrently affirm the dignity and personhood of the care recipient because of its emphasis on connecting with older adults. PMID:26934969

Studies with a reconstituted muscle glycolytic system. The anaerobic glycolytic response to simulated tetanic contraction

PubMed Central

Scopes, Robert K.

1974-01-01

By using a reconstituted glycolytic system and a highly active adenosine triphosphatase (ATPase), the metabolism during muscular tetanic contraction was simulated and observed. With an ATPase activity somewhat greater than can be maintained in muscle tissue, phosphocreatine was rapidly and completely utilized, lactate production commenced about 5s after the ATPase was added and after 15s adenine nucleotides were lost through deamination to IMP. By 40s, all metabolism ceased because of complete loss of adenine mononucleotides. With a lower ATPase activity, glycolytic regeneration of ATP was capable of maintaining the ATP concentration at its initial value and even by 80s, only one-half of the phosphocreatine had been utilized. No deamination occurred in this time. It is suggested that the metabolic events observed in the simulated system are basically the same as occur in muscle doing heavy work. PMID:4275706

Introduction of a quality improvement curriculum in the Department of Internal Medicine, Lincoln Medical Center.

PubMed

Venugopal, Usha; Kasubhai, Moiz; Paruchuri, Vikram

2017-01-01

Community hospitals with limited resources struggle to engage physicians in Quality improvement initiatives. We introduced Quality Improvement (QI) curriculum for residents in response to ACGME requirements and surveyed the residents understanding of QI and their involvement in QI projects before and after the introduction of the curriculum. The current article describes our experiences with the process, the challenges and possible solutions to have a successful resident led QI initiative in a community hospital. Methods: A formal QI curriculum was introduced in the Department of Internal Medicine from September to October 2015 using the Model for Improvement from Institute for Health care Improvement (IHI). Learners were expected to read the online modules, discuss in small group sessions and later encouraged to draft their QI projects using the Charter form and PDSA form available on the HI website. Online surveys were conducted a week prior and 3 months after completion of the curriculum Results: 80% (100/117) of residents completed the pre-curriculum survey and 52% (61/117) completed the survey post curriculum. 96.7% of residents report that physicians should lead QI projects and training rather than the hospital administrators. Residents had 20% increase in understanding and confidence in leading quality improvement projects post curriculum once initiated. Most Residents (72%) feel QI should be taught during residency. Active involvement of residents with interest was seen after the initiation of Open School Institute of health improvement (IHI) curriculum as compared to Institutional led QI's. The resident interventions, pitfalls with change processes with an example of PDSA cycle are discussed. Conclusion: A Dedicated QI curriculum is necessary to prepare the physicians deliver quality care in an increasing complex health care delivery system. The strength of the curriculum is the ease of understanding the material, easily available to all, and can be easily replicated in a Community Hospital program with limited resources. Participation in QI by residents may promote constructive competitiveness among related hospitals in public system to improve delivery of safe care. Abbreviations: ACGME: Accreditation Council for Graduate Medical Education; IHI: Institute of Healthcare Improvement; PDSA: Plan-Do-Study-Act; PGY: QI: Quality improvement.

30 CFR 764.15 - Initial processing, recordkeeping, and notification requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Initial processing, recordkeeping, and notification requirements. 764.15 Section 764.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND... petitioner by certified mail whether the petition is complete under § 764.13 (b) or (c). Complete, for a...

30 CFR 764.15 - Initial processing, recordkeeping, and notification requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Initial processing, recordkeeping, and notification requirements. 764.15 Section 764.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND... petitioner by certified mail whether the petition is complete under § 764.13 (b) or (c). Complete, for a...

30 CFR 764.15 - Initial processing, recordkeeping, and notification requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Initial processing, recordkeeping, and notification requirements. 764.15 Section 764.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND... petitioner by certified mail whether the petition is complete under § 764.13 (b) or (c). Complete, for a...

30 CFR 764.15 - Initial processing, recordkeeping, and notification requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Initial processing, recordkeeping, and notification requirements. 764.15 Section 764.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND... petitioner by certified mail whether the petition is complete under § 764.13 (b) or (c). Complete, for a...

30 CFR 764.15 - Initial processing, recordkeeping, and notification requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Initial processing, recordkeeping, and notification requirements. 764.15 Section 764.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND... petitioner by certified mail whether the petition is complete under § 764.13 (b) or (c). Complete, for a...

The effect of glutathione as chain transfer agent in PNIPAAm-based thermo-responsive hydrogels for controlled release of proteins.

PubMed

Drapala, Pawel W; Jiang, Bin; Chiu, Yu-Chieh; Mieler, William F; Brey, Eric M; Kang-Mieler, Jennifer J; Pérez-Luna, Victor H

2014-03-01

To control degradation and protein release using thermo-responsive hydrogels for localized delivery of anti-angiogenic proteins. Thermo-responsive hydrogels derived from N-isopropylacrylamide (NIPAAm) and crosslinked with poly(ethylene glycol)-co-(L-lactic acid) diacrylate (Acry-PLLA-b-PEG-b-PLLA-Acry) were synthesized via free radical polymerization in the presence of glutathione, a chain transfer agent (CTA) added to modulate their degradation and release properties. Immunoglobulin G (IgG) and the recombinant proteins Avastin® and Lucentis® were encapsulated in these hydrogels and their release was studied. The encapsulation efficiency of IgG was high (75-87%) and decreased with CTA concentration. The transition temperature of these hydrogels was below physiological temperature, which is important for minimally invasive therapies involving these materials. The toxicity from unreacted monomers and free radical initiators was eliminated with a minimum of three buffer extractions. Addition of CTA accelerated degradation and resulted in complete protein release. Glutathione caused the degradation products to become solubilized even at 37°C. Hydrogels prepared without glutathione did not disintegrate nor released protein completely after 3 weeks at 37°C. PEGylation of IgG postponed the burst release effect. Avastin® and Lucentis® released from degraded hydrogels retained their biological activity. These systems offer a promising platform for the localized delivery of proteins.

Perceptions of Barriers to Effective Obesity Care: Results from the National ACTION Study.

PubMed

Kaplan, Lee M; Golden, Angela; Jinnett, Kimberly; Kolotkin, Ronette L; Kyle, Theodore K; Look, Michelle; Nadglowski, Joseph; O'Neil, Patrick M; Parry, Thomas; Tomaszewski, Kenneth J; Stevenin, Boris; Lilleøre, Søren Kruse; Dhurandhar, Nikhil V

2018-01-01

ACTION (Awareness, Care, and Treatment in Obesity maNagement) examined obesity-related perceptions, attitudes, and behaviors among people with obesity (PwO), health care providers (HCPs), and employer representatives (ERs). A total of 3,008 adult PwO (BMI ≥ 30 by self-reported height and weight), 606 HCPs, and 153 ERs completed surveys in a cross-sectional design. Despite several weight loss (WL) attempts, only 23% of PwO reported 10% WL during the previous 3 years. Many PwO (65%) recognized obesity as a disease, but only 54% worried their weight may affect future health. Most PwO (82%) felt "completely" responsible for WL; 72% of HCPs felt responsible for contributing to WL efforts; few ERs (18%) felt even partially responsible. Only 50% of PwO saw themselves as "obese," and 55% reported receiving a formal diagnosis of obesity. Despite HCPs' reported comfort with weight-related conversations, time constraints deprioritized these efforts. Only 24% of PwO had a scheduled follow-up to initial weight-related conversations. Few PwO (17%) perceived employer-sponsored wellness offerings as helpful in supporting WL. Although generally perceived as a disease, obesity is not commonly treated as such. Divergence in perceptions and attitudes potentially hinders better management. This study highlights inconsistent understanding of the impact of obesity and need for both self-directed and medical management. © 2017 The Obesity Society.

Outcomes and predictors of survival in blast phase myeloproliferative neoplasms.

PubMed

Lancman, Guido; Brunner, Andrew; Hoffman, Ronald; Mascarenhas, John; Hobbs, Gabriela

2018-05-21

We retrospectively reviewed treatment outcomes for 57 patients with myeloproliferative neoplasms in blast phase (MPN-BP). The median overall survival (OS) of the entire cohort was 5.8 months. For patients receiving induction therapy, 67% achieved a complete response (CR) and 75% received stem cell transplantation (SCT). Median OS for all transplanted patients (n = 19) was not reached after a median follow-up of 19.2 months compared with 3.8 months in non-transplanted patients (p < 0.0001); patients who did not receive SCT after induction chemotherapy survived a median of 4.9 months. OS was not improved in patients transplanted after CR (OS not reached after median follow-up of 26.7 months) compared with those transplanted upfront or after suboptimal response to initial therapy (9.0 months; p = .097). Those who were transfusion-dependent during their MPN course and received SCT had a median OS of 4.4 months, with all patients dying from SCT complications. Patients receiving hypomethylating agents (HMA) survived 6.7 months, while those receiving supportive care survived 1.1 months. Although outcomes for MPN-BP remain poor, long-term survival can be achieved in appropriately selected patients utilizing SCT, optimally after attaining a complete response with induction therapy. For patients ineligible for SCT, HMAs can offer similar survival to induction chemotherapy with less toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Muenster Parental Programme empowers parents in communicating with their infant with hearing loss.

PubMed

Glanemann, Reinhild; Reichmuth, Karen; Matulat, Peter; Zehnhoff-Dinnesen, Antoinette Am

2013-12-01

With the implementation of the Universal Newborn Hearing Screening (UNHS), the age of diagnosis of children with hearing loss (HL) has been steadily declining in the past years. Consequently, there is a need for early educational intervention methods that are suitable for infants at the preverbal level. To meet this need we have developed and evaluated the Muenster Parental Programme (MPP), a responsive parenting programme for parents of children with HL aged 3-18 months. It aims at enhancing the parents' communicative skills towards their child. The MPP is introduced following confirmation of a HL. Flanked by two individual counselling sessions, the programme comprises six group sessions and two single training sessions with video feedback. The focus of the programme lies in enhancing parents' responsive behaviour and in reducing inappropriate initiative behaviour. The present study involved 29 parents of 24 children aged 6.6 (mean, range: 3-12) months at the outset of the MPP. The children's degree of HL ranged from moderate to profound. Parents of children with unilateral HL and/or risk for an additional developmental delay were included. The prospective study compared parent communication skills of a trained (N = 15) versus a control group (N = 14) before and after the MPP. For this purpose, instances of responsive behaviour to the signals of the child and total time of initiative behaviour within a 4-min video-sample were measured before and after completion of the study in both groups. Trained parents could enhance their responsiveness to vocal and preverbal signals of the child (Wilcoxon test, p = .002) and also their responsiveness to non-verbal signals (Wilcoxon test, p < .001). Moreover, parents reduced their inappropriate initiative behaviour (related t-test, p < .001). Pre-post comparisons in the control group were non-significant. The increased parental responsiveness to infants with HL is of great importance as these early behaviours underlie later acquisition of speech, language, hearing and social communication skills. The MPP constitutes the first evaluated group concept for parents of infants with HL in the German-speaking countries and equally meets the needs of parents and professionals. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Value of Surgery for Retroperitoneal Sarcoma

PubMed Central

Gholami, Sepideh; Jacobs, Charlotte D.; Kapp, Daniel S.; Parast, Layla M.; Norton, Jeffrey A.

2009-01-01

Introduction. Retroperitoneal sarcomas are uncommon large malignant tumors. Methods. Forty-one consecutive patients with localized retroperitoneal sarcoma were retrospectively studied. Results. Median age was 58 years (range 20–91 years). Median tumor size was 17.5 cm (range 4–41 cm). Only 2 tumors were <5 cm. Most were liposarcoma (44%) and high-grade (59%). 59% were stage 3 and the rest was stage 1. Median followup was 10 months (range 1–106 months). Thirty-eight patients had an initial complete resection; 15 (37%) developed recurrent sarcoma and 12 (80%) had a second complete resection. Patients with an initial complete resection had a 5-year survival of 46%. For all patients, tumor grade affected overall survival (P = .006). Complete surgical resection improved overall survival for high-grade tumors (P = .03). Conclusions. Tumor grade/stage and complete surgical resection for high-grade tumors are important prognostic variables. Radiation therapy or chemotherapy had no significant impact on overall or recurrence-free survival. Complete surgical resection is the treatment of choice for patients with initial and locally recurrent retroperitoneal sarcoma. PMID:19826633

Patterns of Relapse From a Phase 3 Study of Response-Based Therapy for Intermediate-Risk Hodgkin Lymphoma (AHOD0031): A Report From the Children's Oncology Group

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

Dharmarajan, Kavita V.; Friedman, Debra L.; Schwartz, Cindy L.

2015-05-01

Purpose: The study was designed to determine whether response-based therapy improves outcomes in intermediate-risk Hodgkin lymphoma. We examined patterns of first relapse in the study. Patients and Methods: From September 2002 to July 2010, 1712 patients <22 years old with stage I-IIA with bulk, I-IIAE, I-IIB, and IIIA-IVA with or without doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide were enrolled. Patients were categorized as rapid (RER) or slow early responders (SER) after 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). The SER patients were randomized to 2 additional ABVE-PC cycles or augmented chemotherapy with 21 Gy involved field radiationmore » therapy (IFRT). RER patients were stipulated to undergo 2 additional ABVE-PC cycles and were then randomized to 21 Gy IFRT or no further treatment if complete response (CR) was achieved. RER without CR patients were non-randomly assigned to 21 Gy IFRT. Relapses were characterized without respect to site (initial, new, or both; and initial bulk or initial nonbulk), and involved field radiation therapy field (in-field, out-of-field, or both). Patients were grouped by treatment assignment (SER; RER/no CR; RER/CR/IFRT; and RER/CR/no IFRT). Summary statistics were reported. Results: At 4-year median follow-up, 244 patients had experienced relapse, 198 of whom were fully evaluable for review. Those who progressed during treatment (n=30) or lacked relapse imaging (n=16) were excluded. The median time to relapse was 12.8 months. Of the 198 evaluable patients, 30% were RER/no CR, 26% were SER, 26% were RER/CR/no IFRT, 16% were RER/CR/IFRT, and 2% remained uncategorized. The 74% and 75% relapses involved initially bulky and nonbulky sites, respectively. First relapses rarely occurred at exclusively new or out-of-field sites. By contrast, relapses usually occurred at nodal sites of initial bulky and nonbulky disease. Conclusion: Although response-based therapy has helped define treatment for selected RER patients, it has not improved outcome for SER patients or facilitated refinement of IFRT volumes or doses.« less

Web-Based Recruitment and Survey Methodology to Maximize Response Rates from Followers of Popular Diets: the Adhering to Dietary Approaches for Personal Taste (ADAPT) Feasibility Survey

PubMed Central

Karlsen, Micaela C; Lichtenstein, Alice H; Economos, Christina D; Folta, Sara C; Rogers, Gail; Jacques, Paul F; Livingston, Kara A; Rancaño, Katherine M; McKeown, Nicola M

2018-01-01

Abstract Background Although there is interest in popular diets such as vegan and vegetarian, Paleo, and other “whole food” diets, existing cohort studies lack data for these subgroups. The use of electronic data capture and Web-based surveys in nutrition research may be valuable for future studies by allowing targeting of specific dietary subgroups. Objective The aim was to perform a Feasibility Survey (FS) to assess the practicality of Web-based research methods to gather data and to maximize response rates among followers of popular diets. Methods The FS was an open, voluntary, 15-min survey conducted over 8 wk in the summer of 2015. Recruitment targeted self-identified followers of popular diets from a convenience sample, offering no incentives, via social media and e-newsletters shared by recruitment partners. Feasibility was assessed by number of responses, survey completion rate, distribution of diets, geographic location, and willingness to participate in future research. Results A total of 14,003 surveys were initiated; 13,787 individuals consented, and 9726 completed the survey (71% of consented). The numbers of unique visitors to the questionnaire site, view rate, and participation rate were not captured. Among respondents with complete demographic data, 83% were female and 93% were white. Diet designations were collapsed into the following groups: whole-food, plant-based (25%); vegan and raw vegan (19%); Paleo (14%); try to eat healthy (11%); vegetarian and pescatarian (9%); whole food (8%); Weston A Price (5%); and low-carbohydrate (low-carb) (4%). Forced-response, multiple-choice questions produced the highest response rates (0–2% selected “prefer not to answer”). The percentage who were willing to complete future online questionnaires was 86%, diet recall was 93%, and food diary was 75%; the percentages willing to provide a finger-stick blood sample, venipuncture blood sample, urine sample, and stool sample were 60%, 44%, 58%, and 42%, respectively. Conclusions This survey suggests that recruiting followers of popular diets is feasible with the use of Web-based methods. The unbalanced sample with respect to sex and race/ethnicity could be corrected with specific recruitment strategies using targeted online marketing techniques. PMID:29955724

Description and Evaluation of an Educational Intervention on Health Care Costs and Value.

PubMed

Jonas, Jennifer A; Ronan, Jeanine C; Petrie, Ian; Fieldston, Evan S

2016-02-01

There is growing consensus that to ensure that health care dollars are spent efficiently, physicians need more training in how to provide high-value, cost-conscious care. Thus, in fiscal year 2014, The Children's Hospital of Philadelphia piloted a 9-part curriculum on health care costs and value for faculty in the Division of General Pediatrics. This study uses baseline and postintervention surveys to gauge knowledge, perceptions, and views on these issues and to assess the efficacy of the pilot curriculum. Faculty completed surveys about their knowledge and perceptions about health care costs and value and their views on the role physicians should play in containing costs and promoting value. Baseline and postintervention responses were compared and analyzed on the basis of how many of the sessions respondents attended. Sixty-two faculty members completed the baseline survey (71% response rate), and 45 faculty members completed the postintervention survey (63% response rate). Reported knowledge of health care costs and value increased significantly in the postintervention survey (P=.04 and P<.001). Odds of being knowledgeable about costs and value were 2.42 (confidence interval: 1.05-5.58) and 6.22 times greater (confidence interval: 2.29-16.90), respectively, postintervention. Reported knowledge of health care costs and value increased with number of sessions attended (P=.01 and P<.001). The pilot curriculum appeared to successfully introduce physicians to concepts around health care costs and value and initiated important discussions about the role physicians can play in containing costs and promoting value. Additional education, increased cost transparency, and more decision support tools are needed to help physicians translate knowledge into practice. Copyright © 2016 by the American Academy of Pediatrics.

Clinical results of definitive-dose (50 Gy/25 fractions) preoperative chemoradiotherapy for unresectable esophageal cancer.

PubMed

Ishikawa, Kazuki; Nakamatsu, Kiyoshi; Shiraishi, Osamu; Yasuda, Takushi; Nishimura, Yasumasa

2015-06-01

The clinical results of definitive-dose preoperative chemoradiotherapy (CRT) of 50 Gy/25 fractions/5 weeks for unresectable esophageal cancer were analyzed. Inclusion criteria were unresectable esophageal squamous cell carcinoma with T4b or mediastinal lymph nodes invading to the trachea or aorta. Radiation therapy of 50 Gy/25 fractions/5 weeks was combined concurrently with two courses of FP therapy (CDDP 70 mg/m(2) + 5-FU 700 mg/m(2)/d × 5 days: day 1-5, day 29-33). Tumor response was evaluated 4 weeks after completion of RT. Subtotal esophagectomy was planned 6-8 weeks after RT. Thirty patients (26 male and 4 female) aged from 50-78 years (median 66) were enrolled between 2008 and 2011. The clinical stages according to the 7th edition of UICC were stages II/III/IV, 1/23/6; T1/2/3/4, 1/1/4/24; and N0/1/2/3, 3/25/1/1. All 30 patients completed RT of 50 Gy/25 fractions. Initial tumor responses were 21 patients with resectable disease, 7 with unresectable disease, and 2 with progressive disease. Subtotal esophagectomy was performed in 18 (60%) of the 30 patients. Pathological complete response was obtained in five (28%) patients. There were two patients with hospitalization death after surgery (11%). Six of the 7 patients who still had unresectable disease were treated with 1-3 courses of docetaxel, CDDP and 5-FU. Three patients treated without surgery showed long-term survival. The 3-year loco-regional control rate and the 3-year overall survival rate for the 30 patients were 70 and 49%, respectively. Definitive-dose preoperative CRT was feasible, and is a promising treatment strategy for unresectable esophageal cancer.

Favre-Racouchot syndrome: a novel two-step treatment approach using the carbon dioxide laser.

PubMed

Rai, S; Madan, V; August, P J; Ferguson, J E

2014-03-01

Favre-Racouchot syndrome (FRS) is both disfiguring and difficult to treat. Available medical and surgical therapies are of variable efficacy. Most treatments do not achieve complete resolution and do not show maintenance of therapeutic response. To assess the response to a novel two-step treatment using the CO2 laser in patients with FRS. Seven patients with FRS were treated with the CO2 laser in resurfacing mode with manual expression of comedones under infiltrative local anaesthesia. The procedure was completed in one treatment session lasting 30 min and the wound was left to heal by secondary intention. A topical antibiotic was applied to treated areas, which were covered with a nonadherent dressing. All patients were assessed 3 months postoperatively by the operating laser surgeon and a visual assessment of clinical response to treatment in comparison with pretreatment photographs was made. Patient satisfaction was also recorded. All patients achieved complete resolution of FRS. The follow-up duration for our cohort ranged from 8 months to 3 years. Two patients required further treatment within a 2-3-year period from initial treatment. Disease relapse was noted over 1 year after the primary treatment; both these cases were smokers and repeat treatment with similar laser parameters maintained reproducible results. Our longest disease-free follow-up duration was 3 years postprimary treatment. The laser surgeons and patients reported high levels of therapeutic benefit and satisfaction with the results. This two-step treatment of FRS (CO2 laser resurfacing and manual pressure-induced expression of comedones) is an effective and durable treatment for FRS with an excellent cosmetic outcome. Long-term follow-up beyond 3 years is planned to determine whether later recurrence occurs with this technique. © 2013 British Association of Dermatologists.

Twenty-five years after Chernobyl: outcome of radioiodine treatment in children and adolescents with very high-risk radiation-induced differentiated thyroid carcinoma.

PubMed

Reiners, Christoph; Biko, Johannes; Haenscheid, Heribert; Hebestreit, Helge; Kirinjuk, Stalina; Baranowski, Oleg; Marlowe, Robert J; Demidchik, Ewgeni; Drozd, Valentina; Demidchik, Yuri

2013-07-01

After severe reactor emergencies with release of radioactive iodine, elevated thyroid cancer risk in children and adolescents is considered the main health consequence for the population exposed. We studied thyroid cancer outcome after 11.3 years' median follow-up in a selected, very high-risk cohort, 234 Chernobyl-exposed Belarusian children and adolescents undergoing postsurgical radioiodine therapy (RIT) in Germany. Cumulatively 100 children with or (without; n = 134) distant metastasis received a median 4 (2) RITs and 16.9 (6.6) GBq, corresponding to 368 (141) MBq/kg iodine-131. Outcomes were response to therapy and disease status, mortality, and treatment toxicity. Of 229 patients evaluable for outcome, 147 (64.2%) attained complete remission [negative iodine-131 whole-body scan and TSH-stimulated serum thyroglobulin (Tg) < 1 μg /L], 69 (30.1%) showed nearly complete remission (complete response, except stimulated Tg 1-10 μg/L), and 11 (4.8%) had partial remission (Tg > 10 μg/L, decrease from baseline in radioiodine uptake intensity in ≥ 1 focus, in tumor volume or in Tg). Except for 2 recurrences (0.9%) after partial remission, no recurrences, progression, or disease-specific mortality were noted. One patient died of lung fibrosis 17.5 years after therapy, 2 of apparently thyroid cancer-unrelated causes. The only RIT side effect observed was pulmonary fibrosis in 5 of 69 patients (7.2%) with disseminated lung metastases undergoing intensive pulmonary surveillance. Experience of a large, very high-risk pediatric cohort with radiation-induced differentiated thyroid carcinoma suggests that even when such disease is advanced and initially suboptimally treated, response to subsequent RIT and final outcomes are mostly favorable.

Systematic review with meta-analysis: recurrence of hepatocellular carcinoma following direct-acting antiviral therapy.

PubMed

Saraiya, N; Yopp, A C; Rich, N E; Odewole, M; Parikh, N D; Singal, A G

2018-05-30

Although studies suggest decreased incident hepatocellular carcinoma (HCC) after direct-acting antivirals (DAA), data are conflicting regarding HCC recurrence and aggressiveness in patients who have a history of HCC with complete response. Characterize HCC recurrence patterns after DAA therapy. Two reviewers searched MEDLINE and SCOPUS from January 2015 to December 2017 and identified studies evaluating HCC recurrence patterns following DAA therapy. A pooled estimate was calculated using the DerSimonian and Laird method for a random effects model. The study was conducted in accordance with PRISMA guidelines. Among 24 studies (n = 1820 patients), the proportion of patients with HCC recurrence following DAA therapy ranged from 0% to 59% (pooled estimate 24.4%; 95% CI: 18.4%-30.4%). Among 11 full text manuscripts, pooled HCC recurrence was 21.9% (95% CI: 16.2%-28.3%). Factors associated with recurrence included history of prior HCC recurrence and a shorter interval between HCC complete response and DAA initiation. Nine studies comparing DAA-treated and interferon-treated or untreated patients found similar recurrence among DAA-treated patients. Most (77.8%) patients with HCC recurrence were detected at an early tumour stage, of whom 64.7% received curative treatment. Study limitations included heterogeneous cohorts, potential misclassification of HCC absence prior to DAA, ascertainment bias for recurrence, and short durations of follow-up. Current data suggest acceptable HCC recurrence rates after DAA therapy, particularly if DAA therapy is delayed at least 6 months after HCC complete response. However, data characterising HCC recurrence after DAA therapy are of limited quality, highlighting the need for high quality prospective studies. © 2018 John Wiley & Sons Ltd.

The Management of Synchronous Bilateral Wilms Tumor: A Report from the National Wilms Tumor Study Group

PubMed Central

Hamilton, Thomas E.; Ritchey, Michael L.; Haase, Gerald M.; Argani, Pedram; Peterson, Susan M.; Anderson, James R.; Green, Daniel M.; Shamberger, Robert C.

2013-01-01

Objective To provide guidelines for future trials, we reviewed the outcomes of children with synchronous bilateral Wilms tumors (BWT) treated on National Wilms Tumor Study-4 (NWTS-4). Methods NWTS-4 enrolled 3,335 patients (pts) including 188 pts with BWT (5.6%). Treatment and outcome data were collected. Results Among 188 BWT pts registered with NWTS-4, 195 kidneys in 123 patients had initial open biopsy, 44 kidneys in 31 pts had needle biopsies. Although pre-resection chemotherapy was recommended, 87 kidneys in 83 pts were managed with primary resection: Complete nephrectomy 48 in 48 pts, 31 partial/wedge nephrectomies in 27 pts, enucleations 8 in 8 pts. No initial surgery was performed in 45 kidneys in 43 pts, 5 kidneys in 3 pts not coded. Anaplasia was diagnosed after completion of the initial course of chemotherapy in 14 pts (initial surgical procedure: 9 open biopsies, 4 needle biopsies, 1 partial nephrectomy). The average number of days from the start of chemotherapy to diagnosis of anaplasia was 390 (range 44–1,925 days). Relapse or progression of disease occurred in 54 children. End stage renal failure occurred in 23 children, 6 of whom had bilateral nephrectomies. The 8 year event free survival (EFS) for BWT with favorable histology was 74%, and overall survival (OS) was 89%; while the EFS for BWT with unfavorable histology was 40%, OS was 45%. Conclusion The current analysis of patients with BWT treated on NWTS-4 shows that preservation of renal parenchyma is possible in many pts following initial preoperative chemotherapy. The incidence of end-stage renal disease remains significantly higher in children with BWT. Future studies are warranted to address the need for earlier biopsy in non-responsive tumors and earlier definitive surgery to recognize unfavorable histology in these high risk patients. PMID:21394016

Data analyst technician: an innovative role for the pharmacy technician.

PubMed

Ervin, K C; Skledar, S; Hess, M M; Ryan, M

2001-10-01

The development of an innovative role for the pharmacy technician is described. The role of the pharmacy technician was based on a needs assessment and the expertise of the pharmacy technician selected. Initial responsibilities of the technician included chart reviews, benchmarking surveys, monthly financial impact analysis, initiative assessment, and quality improvement reporting. As the drug-use and disease-state management (DUDSM) program expanded, pharmacist activities increased, requiring the expansion of data analyst technician (DAT) duties. These new responsibilities included participation in patient assessment, data collection and interpretation, and formulary enforcement. Most recently, technicians' expanded duties include maintenance of a physician compliance profiling database, quality improvement reporting and graphing, active role in patient risk assessment and database management for adult vaccination, and support of financial impact monitoring for other institutions within the health system. This pharmacist-technician collaboration resulted a threefold increase in patient assessments completed per day. In addition, as the DUDSM program continues to expand across the health system, an increase in DAT resources from 0.5 to 1.0 full-time equivalent was obtained. The role of the DAT has increased the efficiency of the DUDSM program and has provided an innovative role for the pharmacy technician.

Use of Neural Response Telemetry for Pediatric Cochlear Implants: Current Practice.

PubMed

Almosnino, Galit; Anne, Samantha; Schwartz, Seth R

2018-06-01

Evaluate usage trends of neural response telemetry (NRT) in cochlear implant centers across the nation and assess reported benefits of intraoperative NRT for pediatric cochlear implant recipients. Survey. All US cochlear implant centers (n = 110). A 15-question multiple-choice survey was distributed electronically to all centers. The survey captured demographic information of all centers, practice patterns surrounding the use of NRT, and the extent to which intraoperative NRT is of benefit. Thirty-two invited participants (29%) completed the survey. A majority of participants reported practicing in an academic center (66%), followed by a hospital setting (19%) and private practice (16%). Seventy-two percent of survey participants reported using NRT for pediatric cochlear implant recipients. Sixty-three percent felt it improved the ability to program at initial activation, and 50% of participants felt that NRT improves satisfaction at initial activation. This study suggests that a majority of surgeons use intraoperative NRT for pediatric cochlear implantation as an additional measure to ensure appropriate electrode placement and improve device activation. Larger studies are needed to better establish the relationship between intraoperative NRT and postoperative outcomes and justify the additional costs associated with intraoperative NRT.

Constitutive activation of a plasma membrane H(+)-ATPase prevents abscisic acid-mediated stomatal closure.

PubMed

Merlot, Sylvain; Leonhardt, Nathalie; Fenzi, Francesca; Valon, Christiane; Costa, Miguel; Piette, Laurie; Vavasseur, Alain; Genty, Bernard; Boivin, Karine; Müller, Axel; Giraudat, Jérôme; Leung, Jeffrey

2007-07-11

Light activates proton (H(+))-ATPases in guard cells, to drive hyperpolarization of the plasma membrane to initiate stomatal opening, allowing diffusion of ambient CO(2) to photosynthetic tissues. Light to darkness transition, high CO(2) levels and the stress hormone abscisic acid (ABA) promote stomatal closing. The overall H(+)-ATPase activity is diminished by ABA treatments, but the significance of this phenomenon in relationship to stomatal closure is still debated. We report two dominant mutations in the OPEN STOMATA2 (OST2) locus of Arabidopsis that completely abolish stomatal response to ABA, but importantly, to a much lesser extent the responses to CO(2) and darkness. The OST2 gene encodes the major plasma membrane H(+)-ATPase AHA1, and both mutations cause constitutive activity of this pump, leading to necrotic lesions. H(+)-ATPases have been traditionally assumed to be general endpoints of all signaling pathways affecting membrane polarization and transport. Our results provide evidence that AHA1 is a distinct component of an ABA-directed signaling pathway, and that dynamic downregulation of this pump during drought is an essential step in membrane depolarization to initiate stomatal closure.

Delayed auditory pathway maturation and prematurity.

PubMed

Koenighofer, Martin; Parzefall, Thomas; Ramsebner, Reinhard; Lucas, Trevor; Frei, Klemens

2015-06-01

Hearing loss is the most common sensory disorder in developed countries and leads to a severe reduction in quality of life. In this uncontrolled case series, we evaluated the auditory development in patients suffering from congenital nonsyndromic hearing impairment related to preterm birth. Six patients delivered preterm (25th-35th gestational weeks) suffering from mild to profound congenital nonsyndromic hearing impairment, descending from healthy, nonconsanguineous parents and were evaluated by otoacoustic emissions, tympanometry, brainstem-evoked response audiometry, and genetic testing. All patients were treated with hearing aids, and one patient required cochlear implantation. One preterm infant (32nd gestational week) initially presented with a 70 dB hearing loss, accompanied by negative otoacoustic emissions and normal tympanometric findings. The patient was treated with hearing aids and displayed a gradual improvement in bilateral hearing that completely normalized by 14 months of age accompanied by the development of otoacoustic emission responses. Conclusions We present here for the first time a fully documented preterm patient with delayed auditory pathway maturation and normalization of hearing within 14 months of birth. Although rare, postpartum development of the auditory system should, therefore, be considered in the initial stages for treating preterm hearing impaired patients.

The Catalonian Expert Patient Programme for Chagas Disease: An Approach to Comprehensive Care Involving Affected Individuals.

PubMed

Claveria Guiu, Isabel; Caro Mendivelso, Johanna; Ouaarab Essadek, Hakima; González Mestre, Maria Asunción; Albajar-Viñas, Pedro; Gómez I Prat, Jordi

2017-02-01

The Catalonian Expert Patient Programme on Chagas disease is a initiative, which is part of the Chronic Disease Programme. It aims to boost responsibility of patients for their own health and to promote self-care. The programme is based on nine sessions conducted by an expert patient. Evaluation was focusing in: habits and lifestyle/self-care, knowledge of disease, perception of health, self-esteem, participant satisfaction, and compliance with medical follow-up visits. Eighteen participants initiated the programme and 15 completed it. The participants were Bolivians. The 66.7 % of them had been diagnosed with chagas disease in Spain. The 100 % mentioned that they would participate in this activity again and would recommend it to family and friends. The knowledge about disease improve after sessions. The method used in the programme could serve as a key strategy in the field of comprehensive care for individuals with this disease.

Patient initiated aggression - prevalence and impact for general practice staff.

PubMed

Herath, Pushpani; Forrest, Laura; McRae, Ian; Parker, Rhian

2011-06-01

Patient initiated aggression toward general practice staff can cause distress among staff, however, it is unknown how frequently practice staff experience patient aggression in the workplace. The aim of this study is to determine the national prevalence of patient aggression toward general practice staff. A clustered cross sectional survey involving general practice staff working in Australia. A questionnaire was posted to 1109 general practices nationally and 217 questionnaires were completed and returned (19.6% response rate). It was found that verbal aggression is commonly experienced by practice staff, particularly receptionists, whereas physical aggression is infrequent. Staff working in larger practices experience more verbal aggression and property damage or theft and it was reported that verbal aggression has a greater impact on staff wellbeing than physical aggression. This study provides some national evidence of the prevalence of patient aggression toward general practice staff. This may inform the development of policy and procedures.

Tug of War between Survival and Death: Exploring ATM Function in Cancer

PubMed Central

Stagni, Venturina; Oropallo, Veronica; Fianco, Giulia; Antonelli, Martina; Cinà, Irene; Barilà, Daniela

2014-01-01

Ataxia-telangiectasia mutated (ATM) kinase is a one of the main guardian of genome stability and plays a central role in the DNA damage response (DDR). The deregulation of these pathways is strongly linked to cancer initiation and progression as well as to the development of therapeutic approaches. These observations, along with reports that identify ATM loss of function as an event that may promote tumor initiation and progression, point to ATM as a bona fide tumor suppressor. The identification of ATM as a positive modulator of several signalling networks that sustain tumorigenesis, including oxidative stress, hypoxia, receptor tyrosine kinase and AKT serine-threonine kinase activation, raise the question of whether ATM function in cancer may be more complex. This review aims to give a complete overview on the work of several labs that links ATM to the control of the balance between cell survival, proliferation and death in cancer. PMID:24681585

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

Boyack, B.E.; Steiner, J.L.; Harmony, S.C.

The PIUS Advanced Reactor is a 640-MW(e) pressurized-water reactor developed by Asea Brown Boveri. A unique feature of the PIUS concept is the absence of mechanical control and shutdown rods. Reactivity normally is controlled by the boron concentration in the coolant and the temperature of the moderator coolant. Analyses of five initiating events have been completed on the basis of calculations performed with the system neutronic and thermal-hydraulic analysis code TRAC-PF1/MOD2. The initiating events analyzed are (1) reactor scram, (2) loss of off-site power (3) main steam-line break, (4) small-break loss of coolant, and (5) large-break loss of coolant. Inmore » addition to the baseline calculation for each sequence, sensitivity studies were performed to explore the response of the PIUS reactor to severe off-normal conditions having a very low probability of occurrence. The sensitivity studies provide insights into the robustness of the design.« less

Responsible Translation of Stem Cell Research: An Assessment of Clinical Trial Registration and Publications.

PubMed

Fung, Moses; Yuan, Yan; Atkins, Harold; Shi, Qian; Bubela, Tania

2017-05-09

We assessed the extent to which the publication of clinical trial results of innovative cell-based interventions reflects International Society for Stem Cell Research best practice guidelines. We assessed: (1) characteristics and time to publication of completed trials; (2) quality of reported trials; and (3) results of published trials. We identified and analyzed publications from 1,052 novel stem cell clinical trials: 179 (45.4%) of 393 completed trials had published results; 48 trials were registered by known stem cell tourism clinics, none of which reported results. Completed non-industry-sponsored trials initially published more rapidly, but differences with industry-sponsored trials decreased over time. Most publications reported safety, and 67.3% (mainly early-stage trials) reported positive outcomes. A higher proportion of industry trials reported positive efficacy. Heightened patient expectations for stem cell therapies give rise to ethical obligations for the transparent conduct of clinical trials. Reporting guidelines need to be developed that are specific to early-phase clinical trials. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Adolescent parenting: outcomes and maternal perceptions.

PubMed

Thompson, P J; Powell, M J; Patterson, R J; Ellerbee, S M

1995-10-01

To describe selected outcomes and maternal perceptions of adolescent parenting. Qualitative and quantitative methods, interview, and two standardized instruments were combined in this follow-up study of adolescents who received perinatal services between 1985 and 1988. Data were collected in the mothers' homes. Mothers who were randomly selected for an earlier chart outcome audit (N = 98) and could be located (n = 19). Subsequent pregnancies; school completion; children's development, indicated by the Developmental Profile II (DPII); parental attitudes, indicated by the Adult-Adolescent Parenting Inventory (AAPI); and maternal perceptions. Responses revealed irregular use of contraceptives as one reason for the initial pregnancy and for subsequent unplanned pregnancies. Sixteen mothers completed high school, and 18 intend to complete postsecondary programs. The DPII indicated age-appropriate development of the children. AAPI scores for 84% of the mothers indicated nonnurturing attitudes. Mothers described family support, motherhood, and their children. Research is needed with larger samples and to test interventions to promote regular use of contraception. Findings support the need for research-based programs to educate and promote the development of adolescent mothers and their children.

Complete remission of recalcitrant genital warts with a combination approach of surgical debulking and oral isotretinoin in a patient with systemic lupus erythematosus.

PubMed

Yew, Yik Weng; Pan, Jiun Yit

2014-01-01

Genital warts in immunocompromised patients can be extensive and recalcitrant to treatment. We report a case of recalcitrant genital warts in a female patient with systemic lupus erythematosus (SLE), who achieved complete remission with a combination approach of surgical debulking and oral isotretinoin at an initial dose of 20 mg/day with a gradual taper of dose over 8 months. She had previously been treated with a combination of topical imiquimod cream and regular fortnightly liquid nitrogen. Although there was partial response, there was no complete clearance. Her condition worsened after topical imiquimod cream was stopped because of her pregnancy. She underwent a combination approach of surgical debulking and oral isotretinoin after her delivery and achieved full clearance for more than 2 years duration. Oral isotretinoin, especially in the treatment of recalcitrant genital warts, is a valuable and feasible option when other more conventional treatment methods have failed or are not possible. It can be used alone or in combination with other local or physical treatment methods. © 2013 Wiley Periodicals, Inc.

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.

Engineering a responsive, low cost, tactical satellite, TACSAT-1

NASA Astrophysics Data System (ADS)

Hurley, M.; Duffey, T.; Huffine, Christopher; Weldy, Ken; Clevland, Jeff; Hauser, Joe

2004-11-01

The Secretary of Defense's Office of Force Transformation (OFT) is currently undertaking an initiative to develop a low-cost, responsive, operationally relevant space capability using small satellites. The Naval Research Laboratory (NRL) is tasked to be program manger for this initiative, which seeks to make space assets and capabilities available to operational users. TacSat-1 is the first in a series of small satellites that will result in rapid, tailored, and operationally relevant experimental space capabilities for tactical forces. Components of the resulting tactical architecture include a highly automated small satellite bus, modular payloads, common launch and payload interfaces, tasking and data dissemination using the SIPRNET (Secret Internet Protocol Routing Network), and low cost, rapid response launches. The overall goal of TacSat-1 is to demonstrate the utility of a broader complementary business model and provide a catalyst for energizing DoD and industry in the operational space area. This paper first provides a brief overview of the TacSat- 1 experiment and then discusses the engineering designs and practices used to achieve the aggressive cost and schedule goals. Non-standard approaches and engineering philosophies that allowed the TacSat-1 spacecraft to be finished in twelve months are detailed and compared with "normal" satellite programs where applicable. Specific subsystem design, integration and test techniques, which contributed to the successful completion of the TacSat-1 spacecraft, are reviewed. Finally, lessons learned are discussed.

Response surface method optimization of ectoine fermentation medium with moderate halophilic bacteria Halomonas sp. H02

NASA Astrophysics Data System (ADS)

Li, T. T.; Qu, A.; Yuan, X. N.; Tan, F. X.; Li, X. W.; Wang, T.; Zhang, L. H.

2017-07-01

Moderate halophilic bacteria are of halophilic bacteria whose suitable growth of NaCl is 5-10%. When the moderate halophilic bacteria response to high osmotic stress, the intracellular will synthesize small organic molecule compatible solutes. Ectoine, which is the major synthetic osmotic compatible solutes for moderate halophilic bacteria, can help microbial enzymes, nucleic acids and the whole cell resist to hypertonic, high temperature, freezing and other inverse environment. In order to increase the Ectoine production of Moderate halophilic bacteria Halomonas sp. H02, the Ectoine fermentation medium component was optimized by Plackett-Burman (PB) and Response Surface Methodology (RSM) based on the principle of non-complete equilibrium The results of PB experiments showed that the three main influencing factors of Moderate halophilic bacteria Halomonas sp. H02 synthesis Ectoine culture medium were C5H8NNaO4 concentration, NaCl concentration and initial pH. According to the center point of the steepest climbing experiment, the central combination design experiment was used to show that the model is consistent with the actual situation. The optimum combination of three influencing factors were C5H8NNaO4 41 g/L, NaCl 87.2 g/L and initial pH 5.9, and the predicted amount of Ectoine was 1835.8 mg/L, increased by 41.6%.

Enhancing the far-UV sensitivity of silicon CMOS imaging arrays

NASA Astrophysics Data System (ADS)

Retherford, K. D.; Bai, Yibin; Ryu, Kevin K.; Gregory, J. A.; Welander, Paul B.; Davis, Michael W.; Greathouse, Thomas K.; Winter, Gregory S.; Suntharalingam, Vyshnavi; Beletic, James W.

2014-07-01

We report our progress toward optimizing backside-illuminated silicon PIN CMOS devices developed by Teledyne Imaging Sensors (TIS) for far-UV planetary science applications. This project was motivated by initial measurements at Southwest Research Institute (SwRI) of the far-UV responsivity of backside-illuminated silicon PIN photodiode test structures described in Bai et al., SPIE, 2008, which revealed a promising QE in the 100-200 nm range as reported in Davis et al., SPIE, 2012. Our effort to advance the capabilities of thinned silicon wafers capitalizes on recent innovations in molecular beam epitaxy (MBE) doping processes. Key achievements to date include: 1) Representative silicon test wafers were fabricated by TIS, and set up for MBE processing at MIT Lincoln Laboratory (LL); 2) Preliminary far-UV detector QE simulation runs were completed to aid MBE layer design; 3) Detector fabrication was completed through the pre-MBE step; and 4) Initial testing of the MBE doping process was performed on monitoring wafers, with detailed quality assessments. Early results suggest that potential challenges in optimizing the UV-sensitivity of silicon PIN type CMOS devices, compared with similar UV enhancement methods established for CCDs, have been mitigated through our newly developed methods. We will discuss the potential advantages of our approach and briefly describe future development steps.

Retention of Implicit Sequence Learning in Persons who Stutter and Persons with Parkinson's Disease

PubMed Central

Smits-Bandstra, Sarah; Gracco, Vincent

2014-01-01

This study investigated the retention of implicit sequence learning in 14 persons with Parkinson's disease (PPD), 14 persons who stutter (PWS) and 14 control participants. Participants completed a nonsense syllable serial reaction time task in a 120-minute session. Participants named aloud four syllables in response to four visual stimuli. The syllables formed a repeating 8-item sequence not made known to participants. After one week, participants completed a 60-minute retention session that included an explicit learning questionnaire and a sequence generation task. PPD showed retention of general learning equivalent to controls but PWS's reaction times were significantly slower on early trials of the retention test relative to other groups. Controls showed implicit learning during the initial session that was retained on the retention test. In contrast, PPD and PWS did not demonstrate significant implicit learning until the retention test suggesting intact, but delayed, learning and retention of implicit sequencing skills. All groups demonstrated similar limited explicit sequence knowledge. Performance differences between PWS and PPD relative to controls during the initial session and on early retention trials indicated possible dysfunction of the cortico-striato-thalamo-cortical loop. The etiological implications for stuttering, and clinical implications for both populations, of this dysfunction are discussed. PMID:23844763

Complete atrioventricular block as initial manifestation of systemic lupus erythematosus.

PubMed

Arce-Salinas, C A; Carmona-Escamilla, M A; Rodríguez-García, F

2009-01-01

Only a few cases of complete atrioventricular block (AVB) in adult lupus patients have been previously described, but only one as the initial manifestation. A 19-year-old woman who presented with seizures and loss of consciousness, was diagnosed with complete ABV and underwent pacemaker placement. Over the next weeks she developed serositis, joint, cutaneous, and renal involvement; positive antinuclear antibodies and high anti-SSA/Ro titers. This is the second case with AVB as a feature of SLE at onset. A review of previous complete AVB cases of adult SLE patients is presented.

Growth responses of young Douglas-fir and tanoak 11 years after various levels of hardwood removal and understory suppression in southwestern Oregon, USA

USGS Publications Warehouse

Harrington, T.B.; Tappeiner, John C.

1997-01-01

At two sites in southwestern Oregon, height, diameter, and crown width of young Douglas-fir (Pseudotsuga menziesii) and sprout-origin tanoak (Lithocarpus densiflorus) were measured 1–11 years after reducing the density of a 2-year-old tanoak stand to 0%, 25%, 50%, and 100% of its initial cover. Some plots also included suppression of understory vegetation. Tanoak cover developed linearly with time, with steepness of the growth trajectory increasing at a diminishing rate with increasing percentage of initial tanoak cover. Fifth-year cover of understory vegetation declined linearly with increasing percentage of initial tanoak cover (R2 = 0.29). Survival of Douglas-fir (96–100%) differed little among initial abundances of tanoak, while growth trajectories for its size became increasingly exponential with decreasing percentage of initial tanoak cover. Eleventh-year heights of Douglas-fir were similar for 0%, 25%, and 50% of initial tanoak cover; however, diameter increased linearly with decreasing percentage of initial tanoak cover (R2 = 0.73), and the slope of the relationship steepened with understory suppression. Our results indicate that young stands exhibiting a wide range of stand compositions and productivities can be established by early manipulations of tanoak and understory abundance. Complete removal of tanoak plus understory suppression are necessary to maximize Douglas-fir growth, while productive, mixed stands can be achieved by removing 50% or more of tanoak cover.

Integrating Climate and Ecosystem-Response Sciences in Temperate Western North American Mountains: The CIRMOUNT Initiative

NASA Astrophysics Data System (ADS)

Millar, C. I.; Fagre, D. B.

2004-12-01

Mountain regions are uniquely sensitive to changes in climate, vulnerable to climate effects on biotic and physical factors of intense social concern, and serve as critical early-warning systems of climate impacts. Escalating demands on western North American (WNA) mountain ecosystems increasingly stress both natural resources and rural community capacities; changes in mountain systems cascade to issues of national concern. Although WNA has long been a focus for climate- and climate-related environmental research, these efforts remain disciplinary and poorly integrated, hindering interpretation into policy and management. Knowledge is further hampered by lack of standardized climate monitoring stations at high-elevations in WNA. An initiative is emerging as the Consortium for Integrated Climate Research in Western Mountains (CIRMOUNT) whose primary goal is to improve knowledge of high-elevation climate systems and to better integrate physical, ecological, and social sciences relevant to climate change, ecosystem response, and natural-resource policy in WNA. CIRMOUNT seeks to focus research on climate variability and ecosystem response (progress in understanding synoptic scale processes) that improves interpretation of linkages between ecosystem functions and human processing (progress in understanding human-environment integration), which in turn would yield applicable information and understanding on key societal issues such as mountains as water towers, biodiversity, carbon forest sinks, and wildland hazards such as fire and forest dieback (progress in understanding ecosystem services and key thresholds). Achieving such integration depends first on implementing a network of high-elevation climate-monitoring stations, and linking these with integrated ecosystem-response studies. Achievements since 2003 include convening the 2004 Mountain Climate Sciences Symposium (1, 2) and several special sessions at technical conferences; initiating a biennial mountain climate research symposium (MTNCLIM), the first to be held in spring 2005; developing a strategy for climate-monitoring in WNA; installing and networking high-elevation (>3000m) climate-monitoring stations; and completing three target regions (Glacier National Park, MT; Sierra Nevada and White Mountains, CA) of the international GLORIA (Global Observation Research Initiative in Alpine Environments) plant-monitoring project, the first in WNA. CIRMOUNT emphasizes integration at the regional scale in WNA, collaborating with and complementing projects such as the Western Mountain Initiative, whose mandate is more targeted than CIRMOUNT's, and global programs such as GLORIA and the international Mountain Research Initiative. Achievement of continuing success in WNA hinges on the capacity to secure long-term funding and institutional investment. (1) See associated URL for paper and poster pdfs (2) Discussing the future of western U.S. mountains, climate change, and ecosystems. EOS 31 August 2004, 85(35), p. 329

Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Fludarabine and Cytarabine, in Pediatric Relapsed or Refractory Acute Leukemia.

PubMed

Alexander, Thomas B; Lacayo, Norman J; Choi, John K; Ribeiro, Raul C; Pui, Ching-Hon; Rubnitz, Jeffrey E

2016-12-01

Purpose To characterize the toxicity, pharmacokinetics, and pharmacodynamics of selinexor, a selective inhibitor of nuclear export, when combined with fludarabine and cytarabine, in children with relapsed or refractory leukemia. Patients and Methods Eighteen patients with relapsed or refractory acute leukemia were enrolled in the SELHEM (Selinexor With Fludarabine and Cytarabine for Treatment of Refractory or Relapsed Leukemia or Myelodysplastic Syndrome) clinical trial (NCT02212561). Selinexor, initially at 30 mg/m 2 per dose, was given orally on days 1, 3, 8, 10, 22, and 24 and was escalated according to a rolling-six design. Fludarabine 30 mg/m 2 and cytarabine 2 g/m 2 were administered on days 15 to 19. Pharmacokinetic and pharmacodynamic studies were performed on days 1 and 22. Response evaluations were performed on day 15 and at the completion of course 1. Results Among the 17 patients who were evaluable for toxicity, three were treated at 30 mg/m 2 , three at 40 mg/m 2 , six at 55 mg/m 2 , and five at 70 mg/m 2 . The most common grade 3 nonhematologic toxicity was asymptomatic hyponatremia. Two patients who were treated at 70 mg/m 2 experienced reversible cerebellar toxicity, thereby defining the dose-limiting toxicity. Pharmacokinetic parameters demonstrated that plasma exposure was dose proportional. Fifteen of 16 patients demonstrated at least a twofold increase of XPO1 mRNA, indicating inhibition of the XPO1 protein. In this group of heavily pretreated, relapsed, and refractory patients, seven of 15 evaluable patients (47%) achieved complete response or complete response with incomplete count recovery. Conclusion Selinexor, in combination with fludarabine and cytarabine, is tolerable at doses up to 55 mg/m 2 in pediatric patients with relapsed or refractory leukemia. All patients who received selinexor at ≥ 40 mg/m 2 demonstrated XPO1 target inhibition. Response rates are promising and will be further explored in a phase II trial.

Pharmaceutical policies in Canada: another example of federal-provincial discord

PubMed Central

Anis, A H

2000-01-01

Pharmaceutical policy in Canada is set at both the federal and provincial levels of government. The federal government is responsible for intellectual property rights of manufacturers (patents) and the initial approval and labelling of prescription drugs and for ensuring overall market competitiveness. The provincial government has responsibility and jurisdiction over the funding of all health care services, including pharmaceuticals. Various interactions between the pharmaceutical industry, the federal and provincial governments and consumers have shaped the current landscape for prescription drugs in Canada. One key failing of the system is that the federal government is almost completely insulated from the impact of its policies because, although it regulates drug prices, it does not buy any drugs. In contrast, provincial governments have no jurisdiction over market competitiveness or pricing, yet end up paying for most of the drug expenditures incurred. PMID:10701389

Mitogen-activated protein kinase cascades in signaling plant growth and development.

PubMed

Xu, Juan; Zhang, Shuqun

2015-01-01

Mitogen-activated protein kinase (MAPK) cascades are ubiquitous signaling modules in eukaryotes. Early research of plant MAPKs has been focused on their functions in immunity and stress responses. Recent studies reveal that they also play essential roles in plant growth and development downstream of receptor-like protein kinases (RLKs). With only a limited number of MAPK components, multiple functional pathways initiated from different receptors often share the same MAPK components or even a complete MAPK cascade. In this review, we discuss how MAPK cascades function as molecular switches in response to spatiotemporal-specific ligand-receptor interactions and the availability of downstream substrates. In addition, we discuss other possible mechanisms governing the functional specificity of plant MAPK cascades, a question central to our understanding of MAPK functions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tissue healing response following hyperthermic vapor ablation in the porcine longissimus muscle

NASA Astrophysics Data System (ADS)

Grantham, John T.; Grisez, Brian T.; Famoso, Justin; Hoey, Michael; Dixon, Chris; Coad, James E.

2015-03-01

As the use of hyperthermic ablation technologies has increased, so too has the need to understand their effects on tissue and their healing responses. This study was designed to characterize tissue injury and healing following hyperthermic vapor ablation in the in vivo porcine longissimus muscle model. The individual ablations were performed using the NxThera Vapor Delivery System (NxThera Inc., Minneapolis, MN). To assess the vapor ablation's evolution, the swine were euthanized post-treatment on Day 0, Day 3, Day 7, Day 14, Day 28, Day 45 and Day 90. Triphenyltetrazolium chloride viability staining (TTC staining) was used to macroscopically assess the extent of each vapor ablation within the tissue. The ablation associated healing responses were then histologically evaluated for acute inflammation, chronic inflammation, foreign body reaction and fibrosis. Two zones of tissue injury were initially identified in the ablations: 1) a central zone of complete coagulative necrosis and 2) an outer "transition zone" of viable and non-viable cells. The ablations initially increased in size from Day 0 to Day 7 and then progressively decreased in size though Day 45. The initial Day 3 healing changes originated in the transition zone with minimal acute and chronic inflammation. As time progressed, granulation tissue began to form by Day 7 and peaked around Day 14. Collagen formation, deposition and remodeling began in the adjacent healthy tissue by Day 28, replaced the ablation site by Day 45 and reorganized by Day 90. In conclusion, this vapor ablation technology provided a non-desiccating form of hyperthermic ablation that resulted in coagulative necrosis without a central thermally/heat-fixed tissue component, followed a classical wound healing pathway, and healed with minimal associated inflammation.

Local Failure in Parameningeal Rhabdomyosarcoma Correlates With Poor Response to Induction Chemotherapy

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

Ladra, Matthew M.; Mandeville, Henry C.; Niemierko, Andrzej

2015-06-01

Background: Local control remains a challenge in pediatric parameningeal rhabdomyosarcoma (PM-RMS), and survival after local failure (LF) is poor. Identifying patients with a high risk of LF is of great interest to clinicians. In this study, we examined whether tumor response to induction chemotherapy (CT) could predict LF in embryonal PM-RMS. Methods: We identified 24 patients with embryonal PM-RMS, age 2 to 18 years, with complete magnetic resonance imaging and gross residual disease after surgical resection. All patients received proton radiation therapy (RT), median dose 50.4 Gy{sub RBE} (50.4-55.8 Gy{sub RBE}). Tumor size was measured before initial CT and before RT. Results:more » With a median follow-up time of 4.1 years for survivors, LF was seen in 9 patients (37.5%). The median time from the initiation of CT to the start of RT was 4.8 weeks. Patients with LF had a similar initial (pre-CT) tumor volume compared with patients with local controlled (LC) (54 cm{sup 3} vs 43 cm{sup 3}, P=.9) but a greater median volume before RT (pre-RT) (40 cm{sup 3} vs 7 cm{sup 3}, P=.009) and a smaller median relative percent volume reduction (RPVR) in tumor size (0.4% vs 78%, P<.001). Older age (P=.05), larger pre-RT tumor volume (P=.03), and smaller RPVR (P=.003) were significantly associated with actuarial LF on univariate Cox analysis. Conclusions: Poor response to induction CT appears to be associated with an increased risk of LF in pediatric embryonal PM-RMS.« less

Measles, mumps, and rubella antibody status and response to immunization in children after therapy for acute lymphoblastic leukemia.

PubMed

Aytac, Selin; Yalcin, S Songul; Cetin, Mualla; Yetgin, Sevgi; Gumruk, Fatma; Tuncer, Murat; Yurdakok, Kadriye; Gurgey, Aytemiz

2010-08-01

Seventy-seven patients with acute lymphoblastic leukemia (ALL) who were in complete remission and whose therapies had been stopped for at least 6 months before enrollment in this study were retrospectively analyzed regarding their antibody status for measles, mumps, and rubella, with the aim to demonstrate the seropositivity rate after treatment in the authors' group. Each patient's serum samples were analyzed by enzyme-linked immunosorbent assay (ELISA) method to determine the antibody titers before and after immunization. Measles serology was available in 77 children; 45 (58%) were seronegative. Initial ages of measle-seronegative patients were statistically lower than those of seropositive cases (median 3.29 versus 4.91 years, respectively). Mumps serology was available in 76 children; 36 (47%) were seronegative. Mumps-seropositive cases tended to have more frequent previous history of infection than seronegative cases (55.0% versus 28.6%, respectively, P = .05). Rubella serology was available in 76 children, and 20 (26.3%) were seronegative. It was determined that initial ages of rubella-seronegative patients were statistically lower than those of seropositive cases (median 3.03 versus 4.32 years, respectively). The authors concluded based on the results of their study that at a median of 3.31 years after completion of chemotherapy for ALL, the majority of cases had antibody levels lower than protective values for measles (58.4%); however, these values were 47.3% for mumps and 26.3% for rubella. Seroconversion rates after measles (55%) and mumps vaccination (57.1%) were still low. However, in the available cases, relatively adequate response to rubella vaccination (92.3%) was observed.

A multicenter phase II study of carboplatin in advanced ovarian carcinoma: final report.

PubMed

Kjorstad, K; Harris, A; Bertelsen, K; Slevin, M; Schultz, H; Hellman, K; Janssens, N; Martin, A; Canetta, R

1992-03-01

A phase II trial of single-agent carboplatin in advanced ovarian cancer was performed by 19 institutions from 10 European countries. A total of 260 patients were treated, with a median age of 55 (range: 20-79) years. Karnofsky performance status was 80-100 in about two-thirds of the patients. Prior therapy consisted of surgery only in 31 patients, irradiation in 9, chemotherapy without cisplatin in 45, and with cisplatin in 175. Carboplatin was administered as second-line therapy in about one-half and as third-line or more in one additional third of the study population. Initial dose was 400 mg/m2 in 90, 360 mg/m2 in 152, and 320 mg/m2 or less in 18 patients. A total of 971 courses (mean 3.7, median 2, range: 1-13) of therapy were administered. A total of 16 complete and 46 partial responses were observed in 226 evaluable patients, for an objective response rate of 27%. Efficacy was greater in chemotherapy-untreated patients (51% vs. 23%, p = 0.002). In cisplatin-pretreated patients activity was significantly higher in non-refractory patients (26% vs. 4%, p = 0.015). Myelosuppression was the most significant side effect. However, low hematologic counts seldom translated into clinically significant complications. Patients with impaired baseline creatinine clearance and poor performance status were at higher risk of developing severe myelosuppression during the initial course of treatment. Non hematologic side effects were rare and mild, except for emesis. Carboplatin has a definite role in the treatment of ovarian cancer, but almost complete cross-resistance with the parent compound was observed clinically.

Design principles for engaging and retaining virtual citizen scientists.

PubMed

Wald, Dara M; Longo, Justin; Dobell, A R

2016-06-01

Citizen science initiatives encourage volunteer participants to collect and interpret data and contribute to formal scientific projects. The growth of virtual citizen science (VCS), facilitated through websites and mobile applications since the mid-2000s, has been driven by a combination of software innovations and mobile technologies, growing scientific data flows without commensurate increases in resources to handle them, and the desire of internet-connected participants to contribute to collective outputs. However, the increasing availability of internet-based activities requires individual VCS projects to compete for the attention of volunteers and promote their long-term retention. We examined program and platform design principles that might allow VCS initiatives to compete more effectively for volunteers, increase productivity of project participants, and retain contributors over time. We surveyed key personnel engaged in managing a sample of VCS projects to identify the principles and practices they pursued for these purposes and led a team in a heuristic evaluation of volunteer engagement, website or application usability, and participant retention. We received 40 completed survey responses (33% response rate) and completed a heuristic evaluation of 20 VCS program sites. The majority of the VCS programs focused on scientific outcomes, whereas the educational and social benefits of program participation, variables that are consistently ranked as important for volunteer engagement and retention, were incidental. Evaluators indicated usability, across most of the VCS program sites, was higher and less variable than the ratings for participant engagement and retention. In the context of growing competition for the attention of internet volunteers, increased attention to the motivations of virtual citizen scientists may help VCS programs sustain the necessary engagement and retention of their volunteers. © 2016 Society for Conservation Biology.

Receptor revision in CD4 T cells is influenced by follicular helper T cell formation and germinal-center interactions.

PubMed

Higdon, Lauren E; Deets, Katherine A; Friesen, Travis J; Sze, Kai-Yin; Fink, Pamela J

2014-04-15

Peripheral CD4 T cells in Vβ5 transgenic (Tg) C57BL/6J mice undergo tolerance to an endogenous superantigen encoded by mouse mammary tumor virus 8 (Mtv-8) by either deletion or T-cell receptor (TCR) revision. Revision is a process by which surface expression of the Vβ5(+) TCR is down-regulated in response to Mtv-8 and recombination activating genes are expressed to drive rearrangement of the endogenous TCRβ locus, effecting cell rescue through the expression of a newly generated, non-self-reactive TCR. In an effort to identify the microenvironment in which revision takes place, we show here that the proportion of T follicular helper cells (Tfh) and production of high-affinity antibody during a primary response are increased in Vβ5 Tg mice in an Mtv-8-dependent manner. Revising T cells have a Tfh-like surface phenotype and transcription factor profile, with elevated expression of B-cell leukemia/lymphoma 6 (Bcl-6), CXC chemokine receptor 5, programmed death-1, and other Tfh-associated markers. Efficient revision requires Bcl-6 and is inhibited by B lymphocyte-induced maturation protein-1. Revision completes less efficiently in the absence of signaling lymphocytic activation molecule-associated protein although initiation proceeds normally. These data indicate that Tfh formation is required for the initiation of revision and germinal-center interactions for its completion. The germinal center is known to provide a confined space in which B-cell antigen receptors undergo selection. Our data extend the impact of this selective microenvironment into the arena of T cells, suggesting that this fluid structure also provides a regulatory environment in which TCR revision can safely take place.

The Veterans Metrics Initiative study of US veterans' experiences during their transition from military service.

PubMed

Vogt, Dawne; Perkins, Daniel F; Copeland, Laurel A; Finley, Erin P; Jamieson, Christopher S; Booth, Bradford; Lederer, Suzanne; Gilman, Cynthia L

2018-06-11

Efforts to promote the health and well-being of military veterans have been criticised for being inadequately informed of veterans' most pressing needs as they separate from military service, as well as the programmes that are most likely to meet these needs. The current article summarises limitations of the current literature and introduces The Veterans Metrics Initiative (TVMI) study, a longitudinal assessment of US veterans' well-being and programme use in the first three years after they separate from military service. Veterans were assessed within 3 months of military separation and will complete five additional assessments at 6-month intervals during the subsequent period. The TVMI study cohort consists of a national sample of 9566 newly separated US veterans that were recruited in the fall of 2016. The TVMI sample includes representation from all branches of service, men and women, and officers and enlisted personnel. Although representative of the larger population on many characteristics, differential response rates were observed for some subgroups, necessitating the development of non-response bias weights. Comparisons between unweighed and weighted results suggest that the weighting procedure adequately adjusts for observed differences. Analyses are under way to examine veterans' well-being and programme use in the period following separation after military service, as well as factors associated with poor outcomes. We have also begun to decompose programmes into their core components to facilitate examination of how these components relate to well-being. Once our third data collection is complete, we will examine factors related to different patterns of readjustment over time. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evaluation of the Technical Feasibility and Effective Cost of Various Wafer Thicknesses for the Manufacture of Solar Cells

NASA Technical Reports Server (NTRS)

1979-01-01

Fourteen wafering characterization runs were completed on a wire saw. Wafer thickness/taper uniformity was excellent. Several alternations and design adjustments were made, facilitating saw operation. A wafering characterization cycle was initiated, and is close to completion. A cell characterization cycle was initiated.

77 FR 60124 - Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1010] Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical... certain drug master files, namely, Type II active pharmaceutical ingredient (API) drug master files (DMFs...

Conformal symmetries of Einstein's field equations and initial data

NASA Astrophysics Data System (ADS)

Sharma, Ramesh

2005-04-01

This paper examines the initial data for the evolution of the space-time solution of Einstein's equations admitting a conformal symmetry. Under certain conditions on the extrinsic curvature of the initial complete spacelike hypersurface and sectional curvature of the space-time with respect to sections containing the normal vector field, we have shown that the initial hypersurface is conformally diffeomorphic to a sphere or a flat space or a hyperbolic space or the product of an open real interval and a complete 2-manifold. It has been further shown that if the initial hypersurface is compact, then it is conformally diffeomorphic to a sphere. Finally, the conformal symmetries of a generalized Robertson-Walker space-time have been described.

Chemical decontamination technical resources at Los Alamos National Laboratory (2008)

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

Moore, Murray E

This document supplies information resources for a person seeking to create planning or pre-planning documents for chemical decontamination operations. A building decontamination plan can be separated into four different sections: Pre-planning, Characterization, Decontamination (Initial response and also complete cleanup), and Clearance. Of the identified Los Alamos resources, they can be matched with these four sections: Pre-planning -- Dave Seidel, EO-EPP, Emergency Planning and Preparedness; David DeCroix and Bruce Letellier, D-3, Computational fluids modeling of structures; Murray E. Moore, RP-2, Aerosol sampling and ventilation engineering. Characterization (this can include development projects) -- Beth Perry, IAT-3, Nuclear Counterterrorism Response (SNIPER database); Fernandomore » Garzon, MPA-11, Sensors and Electrochemical Devices (development); George Havrilla, C-CDE, Chemical Diagnostics and Engineering; Kristen McCabe, B-7, Biosecurity and Public Health. Decontamination -- Adam Stively, EO-ER, Emergency Response; Dina Matz, IHS-IP, Industrial hygiene; Don Hickmott, EES-6, Chemical cleanup. Clearance (validation) -- Larry Ticknor, CCS-6, Statistical Sciences.« less

A Full Dynamic Compound Inverse Method for output-only element-level system identification and input estimation from earthquake response signals

NASA Astrophysics Data System (ADS)

Pioldi, Fabio; Rizzi, Egidio

2016-08-01

This paper proposes a new output-only element-level system identification and input estimation technique, towards the simultaneous identification of modal parameters, input excitation time history and structural features at the element-level by adopting earthquake-induced structural response signals. The method, named Full Dynamic Compound Inverse Method (FDCIM), releases strong assumptions of earlier element-level techniques, by working with a two-stage iterative algorithm. Jointly, a Statistical Average technique, a modification process and a parameter projection strategy are adopted at each stage to achieve stronger convergence for the identified estimates. The proposed method works in a deterministic way and is completely developed in State-Space form. Further, it does not require continuous- to discrete-time transformations and does not depend on initialization conditions. Synthetic earthquake-induced response signals from different shear-type buildings are generated to validate the implemented procedure, also with noise-corrupted cases. The achieved results provide a necessary condition to demonstrate the effectiveness of the proposed identification method.

Memory Self-Efficacy Predicts Responsiveness to Inductive Reasoning Training in Older Adults

PubMed Central

Jackson, Joshua J.; Hill, Patrick L.; Gao, Xuefei; Roberts, Brent W.; Stine-Morrow, Elizabeth A. L.

2012-01-01

Objectives. In the current study, we assessed the relationship between memory self-efficacy at pretest and responsiveness to inductive reasoning training in a sample of older adults. Methods. Participants completed a measure of self-efficacy assessing beliefs about memory capacity. Participants were then randomly assigned to a waitlist control group or an inductive reasoning training intervention. Latent change score models were used to examine the moderators of change in inductive reasoning. Results. Inductive reasoning showed clear improvements in the training group compared with the control. Within the training group, initial memory capacity beliefs significantly predicted change in inductive reasoning such that those with higher levels of capacity beliefs showed greater responsiveness to the intervention. Further analyses revealed that self-efficacy had effects on how trainees allocated time to the training materials over the course of the intervention. Discussion. Results indicate that self-referential beliefs about cognitive potential may be an important factor contributing to plasticity in adulthood. PMID:21743037

Larval cannibalism and pupal defense against cannibalism in two species of tenebrionid beetles.

PubMed

Ichikawa, Toshio; Kurauchi, Toshiaki

2009-08-01

Cannibalism of pupae by larvae has been documented In many species of Insects, but the features of larval cannibalism and pupal defensive mechanisms against larval cannibalism have been largely Ignored. Pupae of tenebrionld beetles rotate their abdominal segments in a circular motion in response to the tactile stimulation of appendages, including legs, antennae, maxillary pulps, and wings. When the pupal abdominal rotation responses of Tenebrio molitor and Zophobas atratus were completely blocked by transecting the ventral nerve cord (VNC) of the pupae, the appendages of the paralytic pupae became initial, major targets for attack by larval cannibals. The majority of 20 paralytic pupae was cannibalized by 100 larvae within 6 h, and almost all the pupae were killed within 2-3 days. In contrast, only a few pupae of Z. atratus and several pupae of T. molitor were cannibalized when the VNC was Intact. The abdominal rotation response of the pupae thus functions as an effective defense against larval cannibalism.

FDG-PET/CT Imaging Predicts Histopathologic Treatment Responses after Neoadjuvant Therapy in Adult Primary Bone Sarcomas

DOE PAGES

Benz, Matthias R.; Czernin, Johannes; Tap, William D.; ...

2010-01-01

Purpose . Tmore » he aim of this study was to prospectively evaluate whether FDG-PET allows an accurate assessment of histopathologic response to neoadjuvant treatment in adult patients with primary bone sarcomas. Methods . Twelve consecutive patients with resectable, primary high grade bone sarcomas were enrolled prospectively. FDG-PET/CT imaging was performed prior to the initiation and after completion of neoadjuvant treatment. Imaging findings were correlated with histopathologic response. Results . Histopathologic responders showed significantly more pronounced decreases in tumor FDG-SUVmax from baseline to late follow up than non-responders ( 64 ± 19 % versus 29 ± 30 %, resp.; P = .03 ). Using a 60% decrease in tumor FDG-uptake as a threshold for metabolic response correctly classified 3 of 4 histopathologic responders and 7 of 8 histopathologic non-responders as metabolic responders and non-responders, respectively (sensitivity, 75%; specificity, 88%). Conclusion . These results suggest that changes in FDG-SUVmax at the end of neoadjuvant treatment can identify histopathologic responders and non-responders in adult primary bone sarcoma patients.« less

Effect of educational intervention on attitudes toward the concept of criminal responsibility.

PubMed

Shiina, Akihiro; Niitsu, Tomihisa; Sato, Aiko; Omiya, Soichiro; Nagata, Takako; Tomoto, Aika; Watanabe, Hiroyuki; Igarashi, Yoshito; Iyo, Masaomi

2017-12-22

To evaluate the effect of educational intervention on individuals' knowledge of and attitudes toward forensic mental health. We conducted a questionnaire regarding attitudes toward various ideas about forensic mental health. The respondents attended a 1-h seminar regarding forensic mental health after answering the questionnaire. On completion of the seminar, the respondents answered another questionnaire containing many of the same questions as contained in the pre-seminar questionnaire. A total of 86 individuals attended the seminar, and 78 responded to the questionnaire. Only 13 (18.8%) participants were supportive of the concept of criminal responsibility initially, and there was a statistically significant increase in those who became more supportive after the seminar, with 22 (33%) being supportive after the seminar (Wilcoxon signed-rank test, P < 0.001). Logistic regression analysis revealed that participants who were skeptical about forensic mental systems and those with fewer opportunities to see media reports regarding psychiatry were likely to become supportive of criminal responsibility after the intervention. These results suggest that public attitudes toward criminal responsibility and mental health can be influenced via educational interventions.

Invertibility of retarded response functions for Laplace transformable potentials: Application to one-body reduced density matrix functional theory.

PubMed

Giesbertz, K J H

2015-08-07

A theorem for the invertibility of arbitrary response functions is presented under the following conditions: the time dependence of the potentials should be Laplace transformable and the initial state should be a ground state, though it might be degenerate. This theorem provides a rigorous foundation for all density-functional-like theories in the time-dependent linear response regime. Especially for time-dependent one-body reduced density matrix (1RDM) functional theory, this is an important step forward, since a solid foundation has currently been lacking. The theorem is equally valid for static response functions in the non-degenerate case, so can be used to characterize the uniqueness of the potential in the ground state version of the corresponding density-functional-like theory. Such a classification of the uniqueness of the non-local potential in ground state 1RDM functional theory has been lacking for decades. With the aid of presented invertibility theorem presented here, a complete classification of the non-uniqueness of the non-local potential in 1RDM functional theory can be given for the first time.

The Neural Response to Maternal Stimuli: An ERP Study

PubMed Central

Wu, Lili; Gu, Ruolei; Cai, Huajian; Luo, Yu L. L.; Zhang, Jianxin

2014-01-01

Mothers are important to all humans. Research has established that maternal information affects individuals' cognition, emotion, and behavior. We measured event-related potentials (ERPs) to examine attentional and evaluative processing of maternal stimuli while participants completed a Go/No-go Association Task that paired mother or others words with good or bad evaluative words. Behavioral data showed that participants responded faster to mother words paired with good than the mother words paired with bad but showed no difference in response to these others across conditions, reflecting a positive evaluation of mother. ERPs showed larger P200 and N200 in response to mother than in response to others, suggesting that mother attracted more attention than others. In the subsequent time window, mother in the mother + bad condition elicited a later and larger late positive potential (LPP) than it did in the mother + good condition, but this was not true for others, also suggesting a positive evaluation of mother. These results suggest that people differentiate mother from others during initial attentional stage, and evaluative mother positively during later stage. PMID:25375157

The modified Memorial Symptom Assessment Scale Short Form: a modified response format and rational scoring rules.

PubMed

Sharp, J L; Gough, K; Pascoe, M C; Drosdowsky, A; Chang, V T; Schofield, P

2018-07-01

The Memorial Symptom Assessment Scale Short Form (MSAS-SF) is a widely used symptom assessment instrument. Patients who self-complete the MSAS-SF have difficulty following the two-part response format, resulting in incorrectly completed responses. We describe modifications to the response format to improve useability, and rational scoring rules for incorrectly completed items. The modified MSAS-SF was completed by 311 women in our Peer and Nurse support Trial to Assist women in Gynaecological Oncology; the PeNTAGOn study. Descriptive statistics were used to summarise completion of the modified MSAS-SF, and provide symptom statistics before and after applying the rational scoring rules. Spearman's correlations with the Functional Assessment for Cancer Therapy-General (FACT-G) and Hospital Anxiety and Depression Scale (HADS) were assessed. Correct completion of the modified MSAS-SF items ranged from 91.5 to 98.7%. The rational scoring rules increased the percentage of useable responses on average 4% across all symptoms. MSAS-SF item statistics were similar with and without the scoring rules. The pattern of correlations with FACT-G and HADS was compatible with prior research. The modified MSAS-SF was useable for self-completion and responses demonstrated validity. The rational scoring rules can minimise loss of data from incorrectly completed responses. Further investigation is recommended.