Comparison of Statistical Approaches Dealing with Time-dependent Confounding in Drug Effectiveness Studies

PubMed Central

Karim, Mohammad Ehsanul; Petkau, John; Gustafson, Paul; Platt, Robert W.; Tremlett, Helen

2017-01-01

In longitudinal studies, if the time-dependent covariates are affected by the past treatment, time-dependent confounding may be present. For a time-to-event response, marginal structural Cox models (MSCMs) are frequently used to deal with such confounding. To avoid some of the problems of fitting MSCM, the sequential Cox approach has been suggested as an alternative. Although the estimation mechanisms are different, both approaches claim to estimate the causal effect of treatment by appropriately adjusting for time-dependent confounding. We carry out simulation studies to assess the suitability of the sequential Cox approach for analyzing time-to-event data in the presence of a time-dependent covariate that may or may not be a time-dependent confounder. Results from these simulations revealed that the sequential Cox approach is not as effective as MSCM in addressing the time-dependent confounding. The sequential Cox approach was also found to be inadequate in the presence of a time-dependent covariate. We propose a modified version of the sequential Cox approach that correctly estimates the treatment effect in both of the above scenarios. All approaches are applied to investigate the impact of beta-interferon treatment in delaying disability progression in the British Columbia Multiple Sclerosis cohort (1995 – 2008). PMID:27659168

Comparison of statistical approaches dealing with time-dependent confounding in drug effectiveness studies.

PubMed

Karim, Mohammad Ehsanul; Petkau, John; Gustafson, Paul; Platt, Robert W; Tremlett, Helen

2018-06-01

In longitudinal studies, if the time-dependent covariates are affected by the past treatment, time-dependent confounding may be present. For a time-to-event response, marginal structural Cox models are frequently used to deal with such confounding. To avoid some of the problems of fitting marginal structural Cox model, the sequential Cox approach has been suggested as an alternative. Although the estimation mechanisms are different, both approaches claim to estimate the causal effect of treatment by appropriately adjusting for time-dependent confounding. We carry out simulation studies to assess the suitability of the sequential Cox approach for analyzing time-to-event data in the presence of a time-dependent covariate that may or may not be a time-dependent confounder. Results from these simulations revealed that the sequential Cox approach is not as effective as marginal structural Cox model in addressing the time-dependent confounding. The sequential Cox approach was also found to be inadequate in the presence of a time-dependent covariate. We propose a modified version of the sequential Cox approach that correctly estimates the treatment effect in both of the above scenarios. All approaches are applied to investigate the impact of beta-interferon treatment in delaying disability progression in the British Columbia Multiple Sclerosis cohort (1995-2008).

Charting Early Trajectories of Executive Control with the Shape School

ERIC Educational Resources Information Center

Clark, Caron A. C.; Sheffield, Tiffany D.; Chevalier, Nicolas; Nelson, Jennifer Mize; Wiebe, Sandra A.; Espy, Kimberly Andrews

2013-01-01

Despite acknowledgement of the importance of executive control for learning and behavior, there is a dearth of research charting its developmental trajectory as it unfolds against the background of children's sociofamilial milieus. Using a prospective, cohort-sequential design, this study describes growth trajectories for inhibitory control…

Depression and Delinquency Covariation in an Accelerated Longitudinal Sample of Adolescents

ERIC Educational Resources Information Center

Kofler, Michael J.; McCart, Michael R.; Zajac, Kristyn; Ruggiero, Kenneth J.; Saunders, Benjamin E.; Kilpatrick, Dean G.

2011-01-01

Objectives: The current study tested opposing predictions stemming from the failure and acting out theories of depression-delinquency covariation. Method: Participants included a nationwide longitudinal sample of adolescents (N = 3,604) ages 12 to 17. Competing models were tested with cohort-sequential latent growth curve modeling to determine…

Coping and Psychological Adjustment among Mothers of Children with ASD: An Accelerated Longitudinal Study

ERIC Educational Resources Information Center

Benson, Paul R.

2014-01-01

Utilizing a cohort sequential design and multilevel modeling on a sample of 113 mothers, the effects of four coping strategies (engagement, disengagement, distraction, and cognitive reframing) on multiple measures of maternal adjustment were assessed over a 7 years period when children with autism spectrum disorders in the study were approximately…

Getting Together: Social Contact Frequency across the Life Span

ERIC Educational Resources Information Center

Sander, Julia; Schupp, Jürgen; Richter, David

2017-01-01

Frequent social interactions are strongly linked to positive affect, longevity, and good health. Although there has been extensive research on changes in the size of social networks over time, little attention has been given to the development of contact frequency across the life span. In this cohort-sequential longitudinal study, we examined…

Cohort Removal Induces Changes in Body Temperature, Pain Sensitivity, and Anxiety-Like Behavior

PubMed Central

Takao, Keizo; Shoji, Hirotaka; Hattori, Satoko; Miyakawa, Tsuyoshi

2016-01-01

Mouse behavior is analyzed to elucidate the effects of various experimental manipulations, including gene mutation and drug administration. When the effect of a factor of interest is assessed, other factors, such as age, sex, temperature, apparatus, and housing, are controlled in experiments by matching, counterbalancing, and/or randomizing. One such factor that has not attracted much attention is the effect of sequential removal of animals from a common cage (cohort removal). Here we evaluated the effects of cohort removal on rectal temperature, pain sensitivity, and anxiety-like behavior by analyzing the combined data of a large number of C57BL/6J mice that we collected using a comprehensive behavioral test battery. Rectal temperature increased in a stepwise manner according to the position of sequential removal from the cage, consistent with previous reports. In the hot plate test, the mice that were removed first from the cage had a significantly longer latency to show the first paw response than the mice removed later. In the elevated plus maze, the mice removed first spent significantly less time on the open arms compared to the mice removed later. The results of the present study demonstrated that cohort removal induces changes in body temperature, pain sensitivity, and anxiety-like behavior in mice. Cohort removal also increased the plasma corticosterone concentration in mice. Thus, the ordinal position in the sequence of removal from the cage should be carefully counterbalanced between groups when the effect of experimental manipulations, including gene manipulation and drug administration, are examined using behavioral tests. PMID:27375443

Normative personality trait development in adulthood: A 6-year cohort-sequential growth model.

PubMed

Milojev, Petar; Sibley, Chris G

2017-03-01

The present study investigated patterns of normative change in personality traits across the adult life span (19 through 74 years of age). We examined change in extraversion, agreeableness, conscientiousness, neuroticism, openness to experience and honesty-humility using data from the first 6 annual waves of the New Zealand Attitudes and Values Study (N = 10,416; 61.1% female, average age = 49.46). We present a cohort-sequential latent growth model assessing patterns of mean-level change due to both aging and cohort effects. Extraversion decreased as people aged, with the most pronounced declines occurring in young adulthood, and then again in old age. Agreeableness, indexed with a measure focusing on empathy, decreased in young adulthood and remained relatively unchanged thereafter. Conscientiousness increased among young adults then leveled off and remained fairly consistent for the rest of the adult life span. Neuroticism and openness to experience decreased as people aged. However, the models suggest that these latter effects may also be partially due to cohort differences, as older people showed lower levels of neuroticism and openness to experience more generally. Honesty-humility showed a pronounced and consistent increase across the adult life span. These analyses of large-scale longitudinal national probability panel data indicate that different dimensions of personality follow distinct developmental processes throughout adulthood. Our findings also highlight the importance of young adulthood (up to about the age of 30) in personality trait development, as well as continuing change throughout the adult life span. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Flynn effects on sub-factors of episodic and semantic memory: parallel gains over time and the same set of determining factors.

PubMed

Rönnlund, Michael; Nilsson, Lars-Göran

2009-09-01

The study examined the extent to which time-related gains in cognitive performance, so-called Flynn effects, generalize across sub-factors of episodic memory (recall and recognition) and semantic memory (knowledge and fluency). We conducted time-sequential analyses of data drawn from the Betula prospective cohort study, involving four age-matched samples (35-80 years; N=2996) tested on the same battery of memory tasks on either of four occasions (1989, 1995, 1999, and 2004). The results demonstrate substantial time-related improvements on recall and recognition as well as on fluency and knowledge, with a trend of larger gains on semantic as compared with episodic memory [Rönnlund, M., & Nilsson, L. -G. (2008). The magnitude, generality, and determinants of Flynn effects on forms of declarative memory: Time-sequential analyses of data from a Swedish cohort study. Intelligence], but highly similar gains across the sub-factors. Finally, the association with markers of environmental change was similar, with evidence that historical increases in quantity of schooling was a main driving force behind the gains, both on the episodic and semantic sub-factors. The results obtained are discussed in terms of brain regions involved.

Psychosocial Development from College through Midlife: A 34-Year Sequential Study

ERIC Educational Resources Information Center

Whitbourne, Susan Krauss; Sneed, Joel R.; Sayer, Aline

2009-01-01

Two cohorts of alumni, leading-edge and trailing-edge baby boomers, first tested in their college years, were followed to ages 43 (N = 136) and 54 (N = 182) on a measure of Erikson's theory of psychosocial development. Hierarchical linear modeling was used to model the trajectory of growth for each psychosocial issue across middle adulthood. As…

Development and Correlates of Alcohol Use from Ages 13-20

ERIC Educational Resources Information Center

Duncan, Susan C.; Gau, Jeff M.; Duncan, Terry E.; Strycker, Lisa A.

2011-01-01

This study examined alcohol use development from ages 13-20 years. The sample comprised 256 youth (50.4% female; 51.2% White, 48.8% African American) assessed annually for 6 years. A cohort-sequential latent growth model was used to model categorical alcohol use (non-use vs. use). Covariates included gender, race, income, parent marital status,…

Trajectories of Social Anxiety during Adolescence and Relations with Cognition, Social Competence, and Temperament

ERIC Educational Resources Information Center

Miers, A. C.; Blote, A. W.; de Rooij, M.; Bokhorst, C. L.; Westenberg, P. M.

2013-01-01

This cohort-sequential study examined developmental trajectories of social anxiety in a nonclinical sample (N = 331, 161 girls) aged 9 to 17 years at initial and 12 to 21 years at final assessment. We tested whether variables assessing cognition, social competence, and temperament discriminated between the trajectories. Variables were collected…

Flynn Effects on Sub-Factors of Episodic and Semantic Memory: Parallel Gains over Time and the Same Set of Determining Factors

ERIC Educational Resources Information Center

Ronnlund, Michael; Nilsson, Lars-Goran.

2009-01-01

The study examined the extent to which time-related gains in cognitive performance, so-called Flynn effects, generalize across sub-factors of episodic memory (recall and recognition) and semantic memory (knowledge and fluency). We conducted time-sequential analyses of data drawn from the Betula prospective cohort study, involving four age-matched…

Postoperative radiotherapy dose requirement in standard combined-modality practice for head and neck squamous cell carcinoma: Analysis of salient surgical and radiotherapy parameters in 2 cohorts.

PubMed

Mohanti, Bidhu K; Thakar, Alok; Kaur, Jaspreet; Bahadur, Sudhir; Malik, Monica; Gandhi, Ajeet K; Bhasker, Suman; Sharma, Atul

2017-09-01

This study compared 2 sequential cohorts to identify the postoperative radiotherapy (PORT) dose requirement for head and neck squamous cell carcinoma (HNSCC). Two distinct PORT dose regimens were prescribed over 11 years; group 1 received 56 Gy or less, and group 2 received 60 Gy or more. The 2D and 3D techniques were used. Two sequential cohorts consisted of 478 patients, with mean and median follow-up for group 1 and 2 as: 37.0 versus 28.5 months and 13.8 versus 13.1 months, respectively. Grades 3-4 mucosal toxicities (11.4% vs 28.3%), hospitalization (3.2% vs 17.4%), and nasogastric feeding (11.9% vs 29.7%) were higher in group 2. The 2-year disease-free survival (DFS) was higher with PORT >60 Gy for the following factors: age ≤ 50 years (P = .041); ≥ 4 positive nodes (P = .029); and overall treatment time (OTT) ≥ 100 days (P = .042). Except for the benefit of doses >60 Gy for limited parameters, a lower PORT dose did not compromise the results and can potentially reduce the morbidities and healthcare costs. © 2017 Wiley Periodicals, Inc.

Validation of Computerized Automatic Calculation of the Sequential Organ Failure Assessment Score

PubMed Central

Harrison, Andrew M.; Pickering, Brian W.; Herasevich, Vitaly

2013-01-01

Purpose. To validate the use of a computer program for the automatic calculation of the sequential organ failure assessment (SOFA) score, as compared to the gold standard of manual chart review. Materials and Methods. Adult admissions (age > 18 years) to the medical ICU with a length of stay greater than 24 hours were studied in the setting of an academic tertiary referral center. A retrospective cross-sectional analysis was performed using a derivation cohort to compare automatic calculation of the SOFA score to the gold standard of manual chart review. After critical appraisal of sources of disagreement, another analysis was performed using an independent validation cohort. Then, a prospective observational analysis was performed using an implementation of this computer program in AWARE Dashboard, which is an existing real-time patient EMR system for use in the ICU. Results. Good agreement between the manual and automatic SOFA calculations was observed for both the derivation (N=94) and validation (N=268) cohorts: 0.02 ± 2.33 and 0.29 ± 1.75 points, respectively. These results were validated in AWARE (N=60). Conclusion. This EMR-based automatic tool accurately calculates SOFA scores and can facilitate ICU decisions without the need for manual data collection. This tool can also be employed in a real-time electronic environment. PMID:23936639

Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses.

PubMed

Wach, Achim; Dembowsky, Klaus; Dale, Glenn E

2018-04-01

Murepavadin is the first in class of the outer membrane protein-targeting antibiotics (OMPTA) and a pathogen-specific peptidomimetic antibacterial with a novel, nonlytic mechanism of action targeting Pseudomonas aeruginosa Murepavadin is being developed for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The pharmacokinetics (PK) and safety of single and multiple doses of murepavadin were investigated in healthy male subjects. Part A of the study was a double-blind, randomized, placebo-controlled, single-ascending-dose investigation in 10 sequential cohorts where each cohort comprised 6 healthy male subjects; 4 subjects were randomized to murepavadin, and 2 subjects were randomized to placebo. Part B was a double-blind, randomized, placebo-controlled, multiple-ascending-dose investigation in 3 sequential cohorts. After a single dose of murepavadin, the geometric mean half-life (2.52 to 5.30 h), the total clearance (80.1 to 114 ml/h/kg), and the volume of distribution (415 to 724 ml/kg) were consistent across dose levels. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Murepavadin was well tolerated, adverse events were transient and generally mild, and no dose-limiting toxicity was identified. Copyright © 2018 American Society for Microbiology.

Safety of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis and Influenza Vaccinations in Pregnancy.

PubMed

Sukumaran, Lakshmi; McCarthy, Natalie L; Kharbanda, Elyse O; Weintraub, Eric S; Vazquez-Benitez, Gabriela; McNeil, Michael M; Li, Rongxia; Klein, Nicola P; Hambidge, Simon J; Naleway, Allison L; Lugg, Marlene M; Jackson, Michael L; King, Jennifer P; DeStefano, Frank; Omer, Saad B; Orenstein, Walter A

2015-11-01

To evaluate the safety of coadministering tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccines during pregnancy by comparing adverse events after concomitant and sequential vaccination. We conducted a retrospective cohort study of pregnant women aged 14-49 years in the Vaccine Safety Datalink from January 1, 2007, to November 15, 2013. We compared medically attended acute events (fever, any acute reaction) and adverse birth outcomes (preterm delivery, low birth weight, small for gestational age) in women receiving concomitant Tdap and influenza vaccination and women receiving sequential vaccination. Among 36,844 pregnancies in which Tdap and influenza vaccines were administered, the vaccines were administered concomitantly in 8,464 (23%) pregnancies and sequentially in 28,380 (77%) pregnancies. Acute adverse events after vaccination were rare. We found no statistically significant increased risk of fever or any medically attended acute adverse event in pregnant women vaccinated concomitantly compared with sequentially. When analyzing women at 20 weeks of gestation or greater during periods of influenza vaccine administration, there were no differences in preterm delivery, low-birth-weight, or small-for-gestational-age neonates between women vaccinated concomitantly compared with sequentially in pregnancy. Concomitant administration of Tdap and influenza vaccines during pregnancy was not associated with a higher risk of medically attended adverse acute outcomes or birth outcomes compared with sequential vaccination. II.

The Impact of an Informal Science Program on Students' Science Knowledge and Interest

ERIC Educational Resources Information Center

Zandstra, Anne Maria

2012-01-01

In this sequential explanatory mixed methods study, quantitative and qualitative data were used to measure the impact of an informal science program on eleventh grade students' science knowledge and interest. The local GEAR UP project has been working for six years with a cohort of students who were in eleventh and twelfth grade during the time of…

Co-Occurring Trajectories of Symptoms of Anxiety, Depression, and Oppositional Defiance from Adolescence to Young Adulthood

ERIC Educational Resources Information Center

Leadbeater, Bonnie; Thompson, Kara; Gruppuso, Vincenza

2012-01-01

This study uses a cohort-sequential longitudinal design to examine the patterns of change and codevelopment of anxiety, depression, and oppositional defiant symptoms (ODS) from late adolescence to young adulthood. Four waves of data were collected biennially by individual interview with a random, community-based sample of 662 youth ages 12 to 18…

Cross-Sectional Analysis of Time-Dependent Data: Mean-Induced Association in Age-Heterogeneous Samples and an Alternative Method Based on Sequential Narrow Age-Cohort Samples

ERIC Educational Resources Information Center

Hofer, Scott M.; Flaherty, Brian P.; Hoffman, Lesa

2006-01-01

The effect of time-related mean differences on estimates of association in cross-sectional studies has not been widely recognized in developmental and aging research. Cross-sectional studies of samples varying in age have found moderate to high levels of shared age-related variance among diverse age-related measures. These findings may be…

Sequential high-content profiling of the IgG-autoantibody repertoire reveals novel antigens in rheumatoid arthritis.

PubMed

Vordenbäumen, Stefan; Lueking, Angelika; Budde, Petra; Zucht, Hans-Dieter; Goehler, Heike; Brinks, Ralph; Fischer-Betz, Rebecca; Richter, Jutta; Bleck, Ellen; Detert, Jacqueline; Langer, Hans-Eckhard; Sörgel, Anne; Burmester, Gerd-Rüdiger; Schulz-Knappe, Peter; Schneider, Matthias

2016-10-12

The aim was to identify novel diagnostic autoantibody candidates for rheumatoid arthritis (RA) by comprehensive screening for autoreactivity. We incubated 5892 recombinant proteins coupled to fluorescent beads, with patients' sera for the detection of IgG-autoantibodies in three independent patient cohorts: A (n = 72 patients with established RA); B/B- (n = 116 patients with early RA (B) and n = 51 CCP-negative patients with early RA from B (B-)); and C (n = 184 patients with early seronegative RA), in comparison to matched healthy controls. Intersects of significantly increased autoantibodies as determined by the Mann-Whitney test were sought. Screening of 5892 antigens in RA cohorts A and B, or the seronegative cohorts B- and C revealed intersects of 23 and 13 significantly increased autoantibodies, respectively. Reactivity to three antigens was increased in all cohorts tested: N-acetylglucosamine-1-phosphate transferase, gamma subunit (GNPTG), heterogeneous nuclear ribonucleoprotein A1-like 2 (HNRNPA1), and insulin-like growth factor binding protein 2 (IGFBP2). Comprehensive sequential screening for autoantibodies reveals novel candidates for diagnostic markers in both seropositive and seronegative RA and suggests new fields of research into the pathogenesis of RA.

Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance

PubMed Central

Roh, Whijae; Chen, Pei-Ling; Reuben, Alexandre; Spencer, Christine N.; Prieto, Peter A.; Miller, John P.; Gopalakrishnan, Vancheswaran; Wang, Feng; Cooper, Zachary A.; Reddy, Sangeetha M.; Gumbs, Curtis; Little, Latasha; Chang, Qing; Chen, Wei-Shen; Wani, Khalida; Petaccia De Macedo, Mariana; Chen, Eveline; Austin-Breneman, Jacob L.; Jiang, Hong; Roszik, Jason; Tetzlaff, Michael T.; Davies, Michael A.; Gershenwald, Jeffrey E.; Tawbi, Hussein; Lazar, Alexander J.; Hwu, Patrick; Hwu, Wen-Jen; Diab, Adi; Glitza, Isabella C.; Patel, Sapna P.; Woodman, Scott E.; Amaria, Rodabe N.; Prieto, Victor G.; Hu, Jianhua; Sharma, Padmanee; Allison, James P.; Chin, Lynda; Zhang, Jianhua; Wargo, Jennifer A.; Futreal, P. Andrew

2018-01-01

Immune checkpoint blockade produces clinical benefit in many patients. However better biomarkers of response are still needed, and mechanisms of resistance remain incompletely understood. To address this, we recently studied a cohort of melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen-4 (CTLA-4) followed by programmed death receptor-1 (PD-1), and identified immune markers of response and resistance. Building on these studies, we performed deep molecular profiling including T-cell receptor sequencing (TCR-seq) and whole exome sequencing (WES) within the same cohort, and demonstrated that a more clonal T cell repertoire was predictive of response to PD-1 but not CTLA-4 blockade. Analysis of copy number alterations identified a higher burden of copy number loss in non-responders to CTLA-4 and PD-1 blockade and found that it was associated with decreased expression of genes in immune-related pathways. The effect of mutational load and burden of copy number loss on response was non-redundant, suggesting the potential utility of a combinatorial biomarker to optimize patient care with checkpoint blockade therapy. PMID:28251903

Implementing a flipped classroom approach in a university numerical methods mathematics course

NASA Astrophysics Data System (ADS)

Johnston, Barbara M.

2017-05-01

This paper describes and analyses the implementation of a 'flipped classroom' approach, in an undergraduate mathematics course on numerical methods. The approach replaced all the lecture contents by instructor-made videos and was implemented in the consecutive years 2014 and 2015. The sequential case study presented here begins with an examination of the attitudes of the 2014 cohort to the approach in general as well as analysing their use of the videos. Based on these responses, the instructor makes a number of changes (for example, the use of 'cloze' summary notes and the introduction of an extra, optional tutorial class) before repeating the 'flipped classroom' approach the following year. The attitudes to the approach and the video usage of the 2015 cohort are then compared with the 2014 cohort and further changes that could be implemented for the next cohort are suggested.

Levobupivacaine vs racemic bupivacaine in spinal anesthesia for sequential bilateral total knee arthroplasty: a retrospective cohort study.

PubMed

Chen, Chee Kean; Lau, Francis C S; Lee, Woo Guan; Phui, Vui Eng

2016-09-01

To compare the anesthetic potency and safety of spinal anesthesia with higher dosages of levobupivacaine and bupivacaine in patients for bilateral sequential for total knee arthroplasty (TKA). Retrospective cohort study. Operation theater with postoperative inpatient follow-up. The medical records of 315 patients who underwent sequential bilateral TKA were reviewed. Patients who received intrathecal levobupicavaine 0.5% were compared with patients who received hyperbaric bupivacaine 0.5% with fentanyl 25 μg for spinal anesthesia. The primary outcome was the use of rescue analgesia (systemic opioids, conversion to general anesthesia) during surgery for both groups. Secondary outcomes included adverse effects of local anesthetics (hypotension and bradycardia) during surgery and morbidity related to spinal anesthesia (postoperative nausea, vomiting, and bleeding) during hospital stay. One hundred fifty patients who received intrathecal levobupivacaine 0.5% (group L) were compared with 90 patients given hyperbaric bupivacaine 0.5% with fentanyl 25 μg (group B). The mean volume of levobupivacaine administered was 5.8 mL (range, 5.0-6.0 mL), and that of bupivacaine was 3.8 mL (range, 3.5-4.0 mL). Both groups achieved similar maximal sensory level of block (T6). The time to maximal height of sensory block was significantly shorter in group B than group L, 18.2 ± 4.5 vs 23.9 ± 3.8 minutes (P< .001). The time to motor block of Bromage 3 was also shorter in group B (8.7 ± 4.1 minutes) than group L (16.0 ± 4.5 minutes) (P< .001). Patients in group B required more anesthetic supplement than group L (P< .001). Hypotension and postoperative bleeding were significantly less common in group L than group B. Levobupivacaine at a higher dosage provided longer duration of spinal anesthesia with better safety profile in sequential bilateral TKA. Copyright © 2016 Elsevier Inc. All rights reserved.

Age, period, and cohort analysis of regular dental care behavior and edentulism: A marginal approach

PubMed Central

2011-01-01

Background To analyze the regular dental care behavior and prevalence of edentulism in adult Danes, reported in sequential cross-sectional oral health surveys by the application of a marginal approach to consider the possible clustering effect of birth cohorts. Methods Data from four sequential cross-sectional surveys of non-institutionalized Danes conducted from 1975-2005 comprising 4330 respondents aged 15+ years in 9 birth cohorts were analyzed. The key study variables were seeking dental care on an annual basis (ADC) and edentulism. For the analysis of ADC, survey year, age, gender, socio-economic status (SES) group, denture-wearing, and school dental care (SDC) during childhood were considered. For the analysis of edentulism, only respondents aged 35+ years were included. Survey year, age, gender, SES group, ADC, and SDC during childhood were considered as the independent factors. To take into account the clustering effect of birth cohorts, marginal logistic regressions with an independent correlation structure in generalized estimating equations (GEE) were carried out, with PROC GENMOD in SAS software. Results The overall proportion of people seeking ADC increased from 58.8% in 1975 to 86.7% in 2005, while for respondents aged 35 years or older, the overall prevalence of edentulism (35+ years) decreased from 36.4% in 1975 to 5.0% in 2005. Females, respondents in the higher SES group, in more recent survey years, with no denture, and receiving SDC in all grades during childhood were associated with higher probability of seeking ADC regularly (P < 0.05). The interaction of SDC and age (P < 0.0001) was significant. The probabilities of seeking ADC were even higher among subjects with SDC in all grades and aged 45 years or older. Females, older age group, respondents in earlier survey years, not seeking ADC, lower SES group, and not receiving SDC in all grades were associated with higher probability of being edentulous (P < 0.05). Conclusions With the use of GEE, the potential clustering effect of birth cohorts in sequential cross-sectional oral health survey data could be appropriately considered. The success of Danish dental health policy was demonstrated by a continued increase of regular dental visiting habits and tooth retention in adults because school dental care was provided to Danes in their childhood. PMID:21410991

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

PubMed

Schiekirka, Sarah; Anders, Sven; Raupach, Tobias

2014-07-21

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

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

PubMed Central

2014-01-01

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

The Longitudinal Effects of Network Characteristics on the Mental Health of Mothers of Children with ASD: The Mediating Role of Parent Cognitions

ERIC Educational Resources Information Center

Benson, Paul R.

2016-01-01

Employing a cohort sequential design, the effects of network characteristics on maternal cognitions (perceived social support and parenting self-efficacy) and mental health (depression and well-being) were assessed over 7 years when children with ASD of mothers in the study were age 7-14. Findings indicated that network size, network emotional…

Costs of achieving live birth from assisted reproductive technology: a comparison of sequential single and double embryo transfer approaches.

PubMed

Crawford, Sara; Boulet, Sheree L; Mneimneh, Allison S; Perkins, Kiran M; Jamieson, Denise J; Zhang, Yujia; Kissin, Dmitry M

2016-02-01

To assess treatment and pregnancy/infant-associated medical costs and birth outcomes for assisted reproductive technology (ART) cycles in a subset of patients using elective double embryo (ET) and to project the difference in costs and outcomes had the cycles instead been sequential single ETs (fresh followed by frozen if the fresh ET did not result in live birth). Retrospective cohort study using 2012 and 2013 data from the National ART Surveillance System. Infertility treatment centers. Fresh, autologous double ETs performed in 2012 among ART patients younger than 35 years of age with no prior ART use who cryopreserved at least one embryo. Sequential single and double ETs. Actual live birth rates and estimated ART treatment and pregnancy/infant-associated medical costs for double ET cycles started in 2012 and projected ART treatment and pregnancy/infant-associated medical costs if the double ET cycles had been performed as sequential single ETs. The estimated total ART treatment and pregnancy/infant-associated medical costs were $580.9 million for 10,001 double ETs started in 2012. If performed as sequential single ETs, estimated costs would have decreased by $195.0 million to $386.0 million, and live birth rates would have increased from 57.7%-68.0%. Sequential single ETs, when clinically appropriate, can reduce total ART treatment and pregnancy/infant-associated medical costs by reducing multiple births without lowering live birth rates. Published by Elsevier Inc.

Long-Term Efficacy and Safety of Cyclosporine in a Cohort of Steroid-Refractory Acute Severe Ulcerative Colitis Patients from the ENEIDA Registry (1989-2013): A Nationwide Multicenter Study.

PubMed

Ordás, I; Domènech, E; Mañosa, M; García-Sánchez, V; Iglesias-Flores, E; Peñalva, M; Cañas-Ventura, A; Merino, O; Fernández-Bañares, F; Gomollón, F; Vera, M; Gutiérrez, A; Garcia-Planella, E; Chaparro, M; Aguas, M; Gento, E; Muñoz, F; Aguirresarobe, M; Muñoz, C; Fernández, L; Calvet, X; Jiménez, C E; Montoro, M A; Mir, A; De Castro, M L; García-Sepulcre, M F; Bermejo, F; Panés, J; Esteve, M

2017-11-01

To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.

Studies on Early Allergic Sensitization in the Lithuanian Birth Cohort

PubMed Central

Dubakiene, Ruta; Rudzeviciene, Odilija; Butiene, Indre; Sezaite, Indre; Petronyte, Malvina; Vaicekauskaite, Dalia; Zvirbliene, Aurelija

2012-01-01

Cohort studies are of great importance in defining the mechanism responsible for the development of allergy-associated diseases, such as atopic dermatitis, allergic asthma, and allergic rhinoconjunctivitis. Although these disorders share genetic and environmental risk factors, it is still under debate whether they are linked or develop sequentially along an atopic pathway. The current study was aimed to determine the pattern of allergy sensitization in the Lithuanian birth cohort “Alergemol” (n = 1558) established as a part of the multicenter European birth cohort “EuroPrevall”. Early sensitization to food allergens in the “Alergemol” birth cohort was analysed. The analysis revealed 1.3% and 2.8% of symptomatic-sensitized subjects at 6 and 12 months of age, respectively. The sensitization pattern in response to different allergens in the group of infants with food allergy symptoms was studied using allergological methods in vivo and in vitro. The impact of maternal and environmental risk factors on the early development of food allergy in at 6 and 12 months of age was evaluated. Our data showed that maternal diet, diseases, the use of antibiotics, and tobacco smoke during pregnancy had no significant impact on the early sensitization to food allergens. However, infants of atopic mothers were significantly more often sensitized to egg as compared to the infants of nonatopic mothers. PMID:22606067

A Latent Transition Analysis of English Learners with Reading Disabilities: Do Measures of Cognition Add to Predictions of Late Emerging Risk Status?

ERIC Educational Resources Information Center

Swanson, H. Lee

2017-01-01

The purpose of this cohort sequential study was to extend previously reported latent transition analyses conducted by Swanson, Kudo, and Guzman-Orth (2016) by determining the role of cognitive measures in identifying English learners (EL) at risk for late emerging reading disabilities (LERD). To this end, EL students (N = 450) in Grades 1, 2, and…

Does Growth in the Executive System of Working Memory Underlie Growth in Literacy for Bilingual Children with and without Reading Disabilities?

ERIC Educational Resources Information Center

Swanson, H. Lee; Orosco, Michael J.; Kudo, Milagros

2017-01-01

This cohort-sequential study explored the components of working memory (WM) that underlie second language (L2) reading growth in 450 children at risk and not at risk for reading disabilities (RD) whose first language is Spanish. English language learners designated as balanced and nonbalanced bilinguals with and without risk for RD in Grades 1, 2,…

Recombinant human interleukin-3 (rhIL-3) enhances the mobilization of peripheral blood progenitor cells by recombinant human granulocyte colony-stimulating factor (rhG-CSF) in normal volunteers.

PubMed

Huhn, R D; Yurkow, E J; Tushinski, R; Clarke, L; Sturgill, M G; Hoffman, R; Sheay, W; Cody, R; Philipp, C; Resta, D; George, M

1996-06-01

To identify a precisely timed and safe protocol for progenitor cell mobilization, we studied the effects of rhIL-3 and rhG-CSF administration to normal volunteers. rhG-CSF 5 micrograms/kg/d was administered subcutaneously (s.c.) for 7 consecutive days either alone or preceded by rhIL-3 5 micrograms/kg/d s.c. for 4 consecutive days in sequential or partially overlapping schedules. The combined cytokines were well-tolerated--adverse effects were similar to those of the individual agents. Total white blood cell (WBC) and neutrophil counts rose briskly in response to rhG-CSF, and peak mean values were similar between treatment cohorts. Mean platelet counts were modestly elevated during rhG-CSF treatment only in the cohorts receiving rhIL-3 and rhG-CSF. Mean circulating CD34+ cells peaked on day 5 in the rhG-CSF group (38.9+/-14.3/microliter), day 6 in the sequential rhIL-3/rhG-CSF group (56.4+/-12.4/microliter), and day 6 in the partial overlap group (46.1+/-10.9/microliter). On day 3, mean CD34+ cell counts of the subjects who received sequential treatment were markedly higher than observed in the other groups (p<0.05) and were estimated to have been sufficient for collection of adequate grafts by single 10-L leukapheresis procedures in 60% of subjects. Circulating clonogenic cells (CFU-GM and/or BFU-E) were substantially higher in the sequential group than the rhG-CSF group on days 3-6 but were only minimally elevated above baseline in the partial overlap group. The numbers of circulating CD34+/Lin-/Thy-1+ cells (putative stem cells) were increased substantially, especially in the sequential group. On the basis of this pilot trial, we conclude that priming with rhIL-3 is a safe and well-tolerated method for enhancing the mobilization of human blood progenitors and stem cells by rhG-CSF.

Age- and cohort-related variance of type-A behavior over 24 years: the Young Finns Study.

PubMed

Hintsa, Taina; Jokela, Markus; Pulkki-Råback, Laura; Keltikangas-Järvinen, Liisa

2014-12-01

Over the recent decades, the incidence of cardiovascular and heart diseases has decreased while levels of type-A behavior, i.e., a potential risk factor, appear to have increased. However, the long-term developmental patterns of type-A behavior is poorly understood. Both age- and cohort-related changes may be involved in these developments. The purpose of this study was to examine an age- and cohort-related changes of Hunter-Wolf type-A behavior from adolescence to adulthood. Type-A behavior and its components (aggressiveness, leadership, hard driving, and eagerness energy) were assessed using the Hunter-Wolf A-B rating scale at five time points (1983, 1986, 1989, 2001, and 2007) in a population-based sample consisting of six birth cohorts born between 1962 and 1977 (n = 3,341, a total of 10,506 person observations). Development of type-A behavior and its components was examined with cohort-sequential multilevel modeling. Aggressiveness decreased with age, eagerness energy, hard driving, and global type-A behavior increased, and leadership exhibited no mean level changes. Younger cohorts had higher aggressiveness, lower hard driving, and global type-A behavior. The findings suggest that in order to understand the health consequences of type-A behavior, both life span and societal changes should be considered.

Speech detection in noise and spatial unmasking in children with simultaneous versus sequential bilateral cochlear implants.

PubMed

Chadha, Neil K; Papsin, Blake C; Jiwani, Salima; Gordon, Karen A

2011-09-01

To measure speech detection in noise performance for children with bilateral cochlear implants (BiCI), to compare performance in children with simultaneous implant versus those with sequential implant, and to compare performance to normal-hearing children. Prospective cohort study. Tertiary academic pediatric center. Children with early-onset bilateral deafness and 2-year BiCI experience, comprising the "sequential" group (>2 yr interimplantation delay, n = 12) and "simultaneous group" (no interimplantation delay, n = 10) and normal-hearing controls (n = 8). Thresholds to speech detection (at 0-degree azimuth) were measured with noise at 0-degree azimuth or ± 90-degree azimuth. Spatial unmasking (SU) as the noise condition changed from 0-degree azimuth to ± 90-degree azimuth and binaural summation advantage (BSA) of 2 over 1 CI. Speech detection in noise was significantly poorer than controls for both BiCI groups (p < 0.0001). However, the SU in the simultaneous group approached levels found in normal controls (7.2 ± 0.6 versus 8.6 ± 0.6 dB, p > 0.05) and was significantly better than that in the sequential group (3.9 ± 0.4 dB, p < 0.05). Spatial unmasking was unaffected by the side of noise presentation in the simultaneous group but, in the sequential group, was significantly better when noise was moved to the second rather than the first implanted ear (4.8 ± 0.5 versus 3.0 ± 0.4 dB, p < 0.05). This was consistent with a larger BSA from the sequential group's second rather than first CI. Children with simultaneously implanted BiCI demonstrated an advantage over children with sequential implant by using spatial cues to improve speech detection in noise.

Sequential cyclophosphamide-bortezomib-dexamethasone unmasks the harmful cardiac effect of dexamethasone in primary light-chain cardiac amyloidosis.

PubMed

Le Bras, Fabien; Molinier-Frenkel, Valerie; Guellich, Aziz; Dupuis, Jehan; Belhadj, Karim; Guendouz, Soulef; Ayad, Karima; Colombat, Magali; Benhaiem, Nicole; Tissot, Claire Marie; Hulin, Anne; Jaccard, Arnaud; Damy, Thibaud

2017-05-01

Chemotherapy combining cyclophosphamide, bortezomib and dexamethasone is widely used in light-chain amyloidosis. The benefit is limited in patients with cardiac amyloidosis mainly because of adverse cardiac events. Retrospective analysis of our cohort showed that 39 patients died with 42% during the first month. A new escalation-sequential regimen was set to improve the outcomes. Nine newly-diagnosed patients were prospectively treated with close monitoring of serum N-terminal pro-brain natriuretic peptide, troponin-T and free light chains. The results show that corticoids may destabilise the heart through fluid retention. Thus, a sequential protocol may be a promising approach to treat these patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Decision-Making Involvement and Prediction of Adherence in Youth With Type 1 Diabetes: A Cohort Sequential Study.

PubMed

Miller, Victoria A; Jawad, Abbas F

2018-05-17

To assess developmental trajectories of decision-making involvement (DMI), defined as the ways in which parents and children engage each other in decision-making about illness management, in youth with type 1 diabetes (T1D) and examine the effects of DMI on levels of and changes in adherence with age. Participants included 117 youth with T1D, enrolled at ages 8-16 years and assessed five times over 2 years. The cohort sequential design allowed for the approximation of the longitudinal curve from age 8 to 19 from overlapping cohort segments. Children and parents completed the Decision-Making Involvement Scale, which yields subscales for different aspects of DMI, and a self-report adherence questionnaire. Mixed-effects growth curve modeling was used for analysis, with longitudinal measures nested within participant and participants nested within cohort. Most aspects of DMI (Parent Express, Parent Seek, Child Express, and Joint) increased with child age; scores on some child report subscales (Parent Express, Child Seek, and Joint) decreased after age 12-14 years. After accounting for age, Child Seek, Child Express, and Joint were associated with overall higher levels of adherence in both child (estimates = 0.08-0.13, p < .001) and parent (estimates = 0.07- 0.13, p < .01) report models, but they did not predict changes in adherence with age. These data suggest that helping children to be more proactive in T1D discussions, by encouraging them to express their opinions, share information, and solicit guidance from parents, is a potential target for interventions to enhance effective self-management.

Association of the Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) Score With Excess Hospital Mortality in Adults With Suspected Infection in Low- and Middle-Income Countries.

PubMed

Rudd, Kristina E; Seymour, Christopher W; Aluisio, Adam R; Augustin, Marc E; Bagenda, Danstan S; Beane, Abi; Byiringiro, Jean Claude; Chang, Chung-Chou H; Colas, L Nathalie; Day, Nicholas P J; De Silva, A Pubudu; Dondorp, Arjen M; Dünser, Martin W; Faiz, M Abul; Grant, Donald S; Haniffa, Rashan; Van Hao, Nguyen; Kennedy, Jason N; Levine, Adam C; Limmathurotsakul, Direk; Mohanty, Sanjib; Nosten, François; Papali, Alfred; Patterson, Andrew J; Schieffelin, John S; Shaffer, Jeffrey G; Thuy, Duong Bich; Thwaites, C Louise; Urayeneza, Olivier; White, Nicholas J; West, T Eoin; Angus, Derek C

2018-05-20

The quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score has not been well-evaluated in low- and middle-income countries (LMICs). To assess the association of qSOFA with excess hospital death among patients with suspected infection in LMICs and to compare qSOFA with the systemic inflammatory response syndrome (SIRS) criteria. Retrospective secondary analysis of 8 cohort studies and 1 randomized clinical trial from 2003 to 2017. This study included 6569 hospitalized adults with suspected infection in emergency departments, inpatient wards, and intensive care units of 17 hospitals in 10 LMICs across sub-Saharan Africa, Asia, and the Americas. Low (0), moderate (1), or high (≥2) qSOFA score (range, 0 [best] to 3 [worst]) or SIRS criteria (range, 0 [best] to 4 [worst]) within 24 hours of presentation to study hospital. Predictive validity (measured as incremental hospital mortality beyond that predicted by baseline risk factors, as a marker of sepsis or analogous severe infectious course) of the qSOFA score (primary) and SIRS criteria (secondary). The cohorts were diverse in enrollment criteria, demographics (median ages, 29-54 years; males range, 36%-76%), HIV prevalence (range, 2%-43%), cause of infection, and hospital mortality (range, 1%-39%). Among 6218 patients with nonmissing outcome status in the combined cohort, 643 (10%) died. Compared with a low or moderate score, a high qSOFA score was associated with increased risk of death overall (19% vs 6%; difference, 13% [95% CI, 11%-14%]; odds ratio, 3.6 [95% CI, 3.0-4.2]) and across cohorts (P < .05 for 8 of 9 cohorts). Compared with a low qSOFA score, a moderate qSOFA score was also associated with increased risk of death overall (8% vs 3%; difference, 5% [95% CI, 4%-6%]; odds ratio, 2.8 [95% CI, 2.0-3.9]), but not in every cohort (P < .05 in 2 of 7 cohorts). High, vs low or moderate, SIRS criteria were associated with a smaller increase in risk of death overall (13% vs 8%; difference, 5% [95% CI, 3%-6%]; odds ratio, 1.7 [95% CI, 1.4-2.0]) and across cohorts (P < .05 for 4 of 9 cohorts). qSOFA discrimination (area under the receiver operating characteristic curve [AUROC], 0.70 [95% CI, 0.68-0.72]) was superior to that of both the baseline model (AUROC, 0.56 [95% CI, 0.53-0.58; P < .001) and SIRS (AUROC, 0.59 [95% CI, 0.57-0.62]; P < .001). When assessed among hospitalized adults with suspected infection in 9 LMIC cohorts, the qSOFA score identified infected patients at risk of death beyond that explained by baseline factors. However, the predictive validity varied among cohorts and settings, and further research is needed to better understand potential generalizability.

The Doctrine of Original Antigenic Sin: Separating Good From Evil.

PubMed

Monto, Arnold S; Malosh, Ryan E; Petrie, Joshua G; Martin, Emily T

2017-06-15

The term "original antigenic sin" was coined approximately 60 years ago to describe the imprinting by the initial first influenza A virus infection on the antibody response to subsequent vaccination. These studies did not suggest a reduction in the response to current antigens but instead suggested anamnestic recall of antibody to earlier influenza virus strains. Then, approximately 40 years ago, it was observed that sequential influenza vaccination might lead to reduced vaccine effectiveness (VE). This conclusion was largely dismissed after an experimental study involving sequential administration of then-standard influenza vaccines. Recent observations have provided convincing evidence that reduced VE after sequential influenza vaccination is a real phenomenon. We propose that such reduction in VE be termed "negative antigenic interaction," given that there is no age cohort effect. In contrast, the potentially positive protective effect of early influenza virus infection later in life continues to be observed. It is essential that we understand better the immunologic factors underlying both original antigenic sin and negative antigenic interaction, to support development of improved influenza vaccines and vaccination strategies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Brief Assessment of Parental Perception (BAPP): Development and validation of a new measure for assessing paediatric outcomes after bilateral cochlear implantation.

PubMed

Samuel, V; Gamble, C; Cullington, H; Bathgate, F; Bennett, E; Coop, N; Cropper, J; Emond, A; Kentish, R; Edwards, L

2016-11-01

In contrast to previous clinical practice, current guidelines recommend bilateral cochlear implantation in children, resulting in a cohort of children who initially received one implant, but have subsequently had a second, contralateral implant. This study aimed to explore satisfaction and quality of life in children implanted simultaneously or sequentially. A novel measure of satisfaction and quality of life following paediatric bilateral cochlear implantation (the Brief Assessment of Parental Perception; BAPP) was developed and preliminary validation undertaken as part of a large, national project of bilateral implantation. Children's parents completed the measure yearly for up to three years following implantation. Children from 14 UK implant centres were recruited into the study; data were available for 410 children one year post-implantation. The BAPP was found to have good face and convergent validity, and internal consistency. Results indicated very high levels of satisfaction with the devices, and improvements in quality of life. However there was evidence that children implanted sequentially were less willing to wear their second implant in the first two years than those children receiving simultaneous implants. Simultaneous and sequential cochlear implants have a positive impact on the quality of life of deaf children.

Validation of a motion-robust 2D sequential technique for quantification of hepatic proton density fat fraction during free breathing.

PubMed

Pooler, B Dustin; Hernando, Diego; Ruby, Jeannine A; Ishii, Hiroshi; Shimakawa, Ann; Reeder, Scott B

2018-04-17

Current chemical-shift-encoded (CSE) MRI techniques for measuring hepatic proton density fat fraction (PDFF) are sensitive to motion artifacts. Initial validation of a motion-robust 2D-sequential CSE-MRI technique for quantification of hepatic PDFF. Phantom study and prospective in vivo cohort. Fifty adult patients (27 women, 23 men, mean age 57.2 years). 3D, 2D-interleaved, and 2D-sequential CSE-MRI acquisitions at 1.5T. Three CSE-MRI techniques (3D, 2D-interleaved, 2D-sequential) were performed in a PDFF phantom and in vivo. Reference standards were 3D CSE-MRI PDFF measurements for the phantom study and single-voxel MR spectroscopy hepatic PDFF measurements (MRS-PDFF) in vivo. In vivo hepatic MRI-PDFF measurements were performed during a single breath-hold (BH) and free breathing (FB), and were repeated by a second reader for the FB 2D-sequential sequence to assess interreader variability. Correlation plots to validate the 2D-sequential CSE-MRI against the phantom and in vivo reference standards. Bland-Altman analysis of FB versus BH CSE-MRI acquisitions to evaluate robustness to motion. Bland-Altman analysis to assess interreader variability. Phantom 2D-sequential CSE-MRI PDFF measurements demonstrated excellent agreement and correlation (R 2 > 0.99) with 3D CSE-MRI. In vivo, the mean (±SD) hepatic PDFF was 8.8 ± 8.7% (range 0.6-28.5%). Compared with BH acquisitions, FB hepatic PDFF measurements demonstrated bias of +0.15% for 2D-sequential compared with + 0.53% for 3D and +0.94% for 2D-interleaved. 95% limits of agreement (LOA) were narrower for 2D-sequential (±0.99%), compared with 3D (±3.72%) and 2D-interleaved (±3.10%). All CSE-MRI techniques had excellent correlation with MRS (R 2 > 0.97). The FB 2D-sequential acquisition demonstrated little interreader variability, with mean bias of +0.07% and 95% LOA of ± 1.53%. This motion-robust 2D-sequential CSE-MRI can accurately measure hepatic PDFF during free breathing in a patient population with a range of PDFF values of 0.6-28.5%, permitting accurate quantification of liver fat content without the need for suspended respiration. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

The Impact of Child and Family Stressors on the Self-Rated Health of Mothers of Children with Autism Spectrum Disorder: Associations with Depressed Mood over a 12-Year Period

ERIC Educational Resources Information Center

Benson, Paul R.

2018-01-01

Employing a cohort sequential design and multilevel modeling, the effects of child and family stressors and maternal depressed mood on the self-rated health of 110 mothers of children with autism spectrum disorder were assessed over a 12-year period when children in the study were 7-19 years old. Findings indicate a significant decline in…

Mexican-Origin Youth's Risk Behavior from Adolescence to Young Adulthood: The Role of Familism Values

PubMed Central

Wheeler, Lorey A.; Zeiders, Katharine H.; Updegraff, Kimberly A.; Umaña-Taylor, Adriana J.; Rodríguez de Jesús, Sue A.; Perez-Brena, Norma J.

2016-01-01

Engagement in risk behavior has implications for individuals' academic achievement, health, and well-being, yet there is a paucity of developmental research on the role of culturally-relevant strengths in individual and family differences in risk behavior involvement among ethnic minority youth. In this study, we used a longitudinal cohort-sequential design to chart intraindividual trajectories of risk behavior and test variation by gender and familism values in 492 youth from 12 to 22 years of age. Participants were older and younger siblings from 246 Mexican-origin families who reported on their risk behaviors in interviews spaced over eight years. Multilevel cohort-sequential growth models revealed that youth reported an increase in risk behavior from 12 to 18 years of age, and then a decline to age 22. Male youth reported greater overall levels and a steeper increase in risk behavior from ages 12 to 18, compared to female youth. For familism values, on occasions when youth reported higher levels, they also reported lower levels of risk behavior (i.e., within-person effect). For sibling dyads characterized by higher average levels of familism values, youth reported lower average levels of risk behavior (i.e., between-family effect). Findings provide unique insights into risk behavior from adolescence to young adulthood among Mexican-origin youth. PMID:28026193

Genome-wide association study of suicide attempts in mood disorder patients.

PubMed

Perlis, Roy H; Huang, Jie; Purcell, Shaun; Fava, Maurizio; Rush, A John; Sullivan, Patrick F; Hamilton, Steven P; McMahon, Francis J; Schulze, Thomas G; Schulze, Thomas; Potash, James B; Zandi, Peter P; Willour, Virginia L; Penninx, Brenda W; Boomsma, Dorret I; Vogelzangs, Nicole; Middeldorp, Christel M; Rietschel, Marcella; Nöthen, Markus; Cichon, Sven; Gurling, Hugh; Bass, Nick; McQuillin, Andrew; Hamshere, Marian; Craddock, Nick; Sklar, Pamela; Smoller, Jordan W

2010-12-01

Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.

Genome-Wide Association Study of Suicide Attempts in Mood Disorder Patients

PubMed Central

Perlis, Roy H.; Huang, Jie; Purcell, Shaun; Fava, Maurizio; Rush, A. John; Sullivan, Patrick F.; Hamilton, Steven P.; McMahon, Francis J.; Schulze, Thomas; Potash, James B.; Zandi, Peter P.; Willour, Virginia L.; Penninx, Brenda W.; Boomsma, Dorret I.; Vogelzangs, Nicole; Middeldorp, Christel M.; Rietschel, Marcella; Nöthen, Markus; Cichon, Sven; Gurling, Hugh; Bass, Nick; McQuillin, Andrew; Hamshere, Marian; Craddock, Nick; Sklar, Pamela; Smoller, Jordan W.

2013-01-01

Objective Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. Method The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Results Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. Conclusions The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation. PMID:21041247

Simultaneous Versus Sequential Side-by-Side Bilateral Metal Stent Placement for Malignant Hilar Biliary Obstructions.

PubMed

Inoue, Tadahisa; Ishii, Norimitsu; Kobayashi, Yuji; Kitano, Rena; Sakamoto, Kazumasa; Ohashi, Tomohiko; Nakade, Yukiomi; Sumida, Yoshio; Ito, Kiyoaki; Nakao, Haruhisa; Yoneda, Masashi

2017-09-01

Endoscopic bilateral self-expandable metallic stent (SEMS) placement for malignant hilar biliary obstructions (MHBOs) is technically demanding, and a second SEMS insertion is particularly challenging. A simultaneous side-by-side (SBS) placement technique using a thinner delivery system may mitigate these issues. We aimed to examine the feasibility and efficacy of simultaneous SBS SEMS placement for treating MHBOs using a novel SEMS that has a 5.7-Fr ultra-thin delivery system. Thirty-four patients with MHBOs underwent SBS SEMS placement between 2010 and 2016. We divided the patient cohort into those who underwent sequential (conventional) SBS placement between 2010 and 2014 (sequential group) and those who underwent simultaneous SBS placement between 2015 and 2016 (simultaneous group), and compared the groups with respect to the clinical outcomes. The technical success rates were 71% (12/17) and 100% (17/17) in the sequential and simultaneous groups, respectively, a difference that was significant (P = .045). The median procedure time was significantly shorter in the simultaneous group (22 min) than in the sequential group (52 min) (P = .017). There were no significant group differences in the time to recurrent biliary obstruction (sequential group: 113 days; simultaneous group: 140 days) or other adverse event rates (sequential group: 12%; simultaneous group: 12%). Simultaneous SBS placement using the novel 5.7-Fr SEMS delivery system may be more straightforward and have a higher success rate compared to that with sequential SBS placement. This new method may be useful for bilateral stenting to treat MHBOs.

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

PubMed Central

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

2013-01-01

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

Sequential analysis as a tool for detection of amikacin ototoxicity in the treatment of multidrug-resistant tuberculosis.

PubMed

Vasconcelos, Karla Anacleto de; Frota, Silvana Maria Monte Coelho; Ruffino-Netto, Antonio; Kritski, Afrânio Lineu

2018-04-01

To investigate early detection of amikacin-induced ototoxicity in a population treated for multidrug-resistant tuberculosis (MDR-TB), by means of three different tests: pure-tone audiometry (PTA); high-frequency audiometry (HFA); and distortion-product otoacoustic emission (DPOAE) testing. This was a longitudinal prospective cohort study involving patients aged 18-69 years with a diagnosis of MDR-TB who had to receive amikacin for six months as part of their antituberculosis drug regimen for the first time. Hearing was assessed before treatment initiation and at two and six months after treatment initiation. Sequential statistics were used to analyze the results. We included 61 patients, but the final population consisted of 10 patients (7 men and 3 women) because of sequential analysis. Comparison of the test results obtained at two and six months after treatment initiation with those obtained at baseline revealed that HFA at two months and PTA at six months detected hearing threshold shifts consistent with ototoxicity. However, DPOAE testing did not detect such shifts. The statistical method used in this study makes it possible to conclude that, over the six-month period, amikacin-associated hearing threshold shifts were detected by HFA and PTA, and that DPOAE testing was not efficient in detecting such shifts.

The Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination with Febuxostat When Treating Hyperuricemia Associated with Gout.

PubMed

Steinberg, Alexandra S; Vince, Bradley D; Choi, Yun-Jung; Martin, Robert L; McWherter, Charles A; Boudes, Pol F

2017-03-01

Arhalofenate (ARH), in development for gout, has uricosuric and anti-flare activities. ARH plus febuxostat (FBX) were evaluated in subjects with gout for serum uric acid (SUA) lowering, drug interaction, and safety. Open phase II trial in gout volunteers (NCT02252835). Cohort 1 received ARH 600 mg for 2 weeks, followed by sequential 1-week co-administration of FBX 80 mg followed by 40 mg. FBX 40 mg was continued alone for 2 weeks. Cohort 2 received ARH 800 mg for 2 weeks, followed by sequential 1-week co-administration of FBX 40 mg followed by 80 mg. FBX 80 mg was continued alone for 2 weeks. SUA, its fractional excretion (FEUA), and plasma oxypurines were assessed. Pharmacokinetics of FBX and ARH were determined alone and in combination for cohort 2. Baseline mean SUA was 9.4 mg/dl for cohort 1 (n = 16) and 9.2 mg/dl for cohort 2 (n = 16). The largest SUA decrease (63%) was observed with ARH 800 mg + FBX 80 mg, with all subjects reaching SUA < 6 mg/dl and 93% < 5 mg/dl. The area under the curve (AUC) (0-t) of ARH acid + FBX/ARH acid was 108%. The AUC (0-t) of FBX + ARH acid/FBX was 87%. As expected, FBX increased oxypurines and increases were unaffected by ARH co-administration. Baseline FEUA were low (3.5%-4.6%) and ARH increased them toward normal without overexcretion of UA. ARH was well tolerated and appeared safe. ARH and FBX lowered SUA by complementary mechanisms. The combination provided greater decreases than each drug alone. The combination was well tolerated and appeared safe. NCT02252835.

Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients.

PubMed

Gligorov, J; Ataseven, B; Verrill, M; De Laurentiis, M; Jung, K H; Azim, H A; Al-Sakaff, N; Lauer, S; Shing, M; Pivot, X

2017-09-01

To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sequential imaging of asymptomatic carotid atheroma using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging: a feasibility study.

PubMed

Sadat, Umar; Howarth, Simon P S; Usman, Ammara; Tang, Tjun Y; Graves, Martin J; Gillard, Jonathan H

2013-11-01

Inflammation within atheromatous plaques is a known risk factor for plaque vulnerability. This can be detected in vivo on high-resolution magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxide (USPIO) contrast medium. The purpose of this study was to assess the feasibility of performing sequential USPIO studies over a 1-year period. Ten patients with moderate asymptomatic carotid stenosis underwent carotid MRI imaging both before and 36 hours after USPIO infusion at 0, 6, and 12 months. Images were manually segmented into quadrants, and the signal change per quadrant was calculated at these time points. A mixed repeated measures statistical model was used to determine signal change attributable to USPIO uptake over time. All patients remained asymptomatic during the study. The mixed model revealed no statistical difference in USPIO uptake between the 3 time points. Intraclass correlation coefficients revealed a good agreement of quadrant signal pre-USPIO infusion between 0 and 6 months (0.70) and 0 and 12 months (0.70). Good agreement of quadrant signal after USPIO infusion was shown between 0 and 6 months (0.68) and moderate agreement was shown between 0 and 12 months (0.33). USPIO-enhanced sequential MRI of atheromatous carotid plaques is clinically feasible. This may have important implications for future longitudinal studies involving pharmacologic intervention in large patient cohorts. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The Impact of Adjuvant Postoperative Radiation Therapy and Chemotherapy on Survival After Esophagectomy for Esophageal Carcinoma.

PubMed

Wong, Andrew T; Shao, Meng; Rineer, Justin; Lee, Anna; Schwartz, David; Schreiber, David

2017-06-01

The objective of this study was to analyze the impact on overall survival (OS) from the addition of postoperative radiation with or without chemotherapy after esophagectomy, using a large, hospital-based dataset. Previous retrospective studies have suggested an OS advantage for postoperative chemoradiation over surgery alone, although prospective data are lacking. The National Cancer Data Base was queried to select patients diagnosed with stage pT3-4Nx-0M0 or pT1-4N1-3M0 esophageal carcinoma (squamous cell or adenocarcinoma) from 1998 to 2011 treated with definitive esophagectomy ± postoperative radiation and/or chemotherapy. OS was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with OS. There were 4893 patients selected, of whom 1153 (23.6%) received postoperative radiation. Most patients receiving radiation also received sequential/concomitant chemotherapy (89.9%). For the entire cohort, postoperative radiation was associated with a statistically significant but modest absolute improvement in survival (hazard ratio 0.77; 95% CI, 0.71-0.83; P < 0.001). On subgroup analysis, postoperative radiation was associated with improved OS for patients with node-positive disease (3-yr OS 34.3 % vs 27.8%, P < 0.001) or positive margins (3-yr OS 36.4% vs 18.0%, P < 0.001). When chemotherapy usage was incorporated, sequential chemotherapy was associated with the best survival (P < 0.001). Multivariate analysis revealed that the addition of chemotherapy to radiation therapy, whether sequentially or concurrently, was a strong prognostic factor for OS. In this hospital-based study, the addition of postoperative chemoradiation (either sequentially or concomitantly) after esophagectomy was associated with improved OS for patients with node-positive disease or positive margins.

Ovary Apical Abortion under Water Deficit Is Caused by Changes in Sequential Development of Ovaries and in Silk Growth Rate in Maize.

PubMed

Oury, Vincent; Tardieu, François; Turc, Olivier

2016-06-01

Grain abortion allows the production of at least a few viable seeds under water deficit but causes major yield loss. It is maximum for water deficits occurring during flowering in maize (Zea mays). We have tested the hypothesis that abortion is linked to the differential development of ovary cohorts along the ear and to the timing of silk emergence. Ovary volume and silk growth were followed over 25 to 30 d under four levels of water deficit and in four hybrids in two experiments. A position-time model allowed characterizing the development of ovary cohorts and their silk emergence. Silk growth rate decreased in water deficit and stopped 2 to 3 d after first silk emergence, simultaneously for all ovary cohorts, versus 7 to 8 d in well-watered plants. Abortion rate in different treatments and positions on the ear was not associated with ovary growth rate. It was accounted for by the superposition of (1) the sequential emergence of silks originating from ovaries of different cohorts along the ear with (2) one event occurring on a single day, the simultaneous silk growth arrest. Abortion occurred in the youngest ovaries whose silks did not emerge 2 d before silk arrest. This mechanism accounted for more than 90% of drought-related abortion in our experiments. It resembles the control of abortion in a large range of species and inflorescence architectures. This finding has large consequences for breeding drought-tolerant maize and for modeling grain yields in water deficit. © 2016 American Society of Plant Biologists. All Rights Reserved.

Ovary Apical Abortion under Water Deficit Is Caused by Changes in Sequential Development of Ovaries and in Silk Growth Rate in Maize1[OPEN

PubMed Central

Tardieu, François

2016-01-01

Grain abortion allows the production of at least a few viable seeds under water deficit but causes major yield loss. It is maximum for water deficits occurring during flowering in maize (Zea mays). We have tested the hypothesis that abortion is linked to the differential development of ovary cohorts along the ear and to the timing of silk emergence. Ovary volume and silk growth were followed over 25 to 30 d under four levels of water deficit and in four hybrids in two experiments. A position-time model allowed characterizing the development of ovary cohorts and their silk emergence. Silk growth rate decreased in water deficit and stopped 2 to 3 d after first silk emergence, simultaneously for all ovary cohorts, versus 7 to 8 d in well-watered plants. Abortion rate in different treatments and positions on the ear was not associated with ovary growth rate. It was accounted for by the superposition of (1) the sequential emergence of silks originating from ovaries of different cohorts along the ear with (2) one event occurring on a single day, the simultaneous silk growth arrest. Abortion occurred in the youngest ovaries whose silks did not emerge 2 d before silk arrest. This mechanism accounted for more than 90% of drought-related abortion in our experiments. It resembles the control of abortion in a large range of species and inflorescence architectures. This finding has large consequences for breeding drought-tolerant maize and for modeling grain yields in water deficit. PMID:26598464

A 2-step penalized regression method for family-based next-generation sequencing association studies.

PubMed

Ding, Xiuhua; Su, Shaoyong; Nandakumar, Kannabiran; Wang, Xiaoling; Fardo, David W

2014-01-01

Large-scale genetic studies are often composed of related participants, and utilizing familial relationships can be cumbersome and computationally challenging. We present an approach to efficiently handle sequencing data from complex pedigrees that incorporates information from rare variants as well as common variants. Our method employs a 2-step procedure that sequentially regresses out correlation from familial relatedness and then uses the resulting phenotypic residuals in a penalized regression framework to test for associations with variants within genetic units. The operating characteristics of this approach are detailed using simulation data based on a large, multigenerational cohort.

Mexican-origin youth's risk behavior from adolescence to young adulthood: The role of familism values.

PubMed

Wheeler, Lorey A; Zeiders, Katharine H; Updegraff, Kimberly A; Umaña-Taylor, Adriana J; Rodríguez de Jesús, Sue A; Perez-Brena, Norma J

2017-01-01

Engagement in risk behavior has implications for individuals' academic achievement, health, and well-being, yet there is a paucity of developmental research on the role of culturally relevant strengths in individual and family differences in risk behavior involvement among ethnic minority youth. In this study, we used a longitudinal cohort-sequential design to chart intraindividual trajectories of risk behavior and test variation by gender and familism values in 492 youth from 12 to 22 years of age. Participants were older and younger siblings from 246 Mexican-origin families who reported on their risk behaviors in interviews spaced over 8 years. Multilevel cohort-sequential growth models revealed that youth reported an increase in risk behavior from 12 to 18 years of age, and then a decline to age 22. Male youth reported greater overall levels and a steeper increase in risk behavior from ages 12 to 18, compared to female youth. For familism values, on occasions when youth reported higher levels, they also reported lower levels of risk behavior (i.e., within-person effect). For sibling dyads characterized by higher average levels of familism values, youth reported lower average levels of risk behavior (i.e., between-family effect). Findings provide unique insights into risk behavior from adolescence to young adulthood among Mexican-origin youth. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The Relationship between Victimization at School and Achievement: The Cusp Catastrophe Model for Reading Performance

ERIC Educational Resources Information Center

Sideridis, Georgios D.; Antoniou, Faye; Stamovlasis, Dimitrios; Morgan, Paul L.

2013-01-01

We evaluated the relationship between victimization and academic achievement from a nonlinear perspective using a cusp catastrophe model. Participants were 62 students with identified learning disabilities (LD) using statewide criteria in Greece. Students participated in a 2-year cohort-sequential design. Reading assessments involved measures of…

Ghrelin and obestatin plasma levels and ghrelin/obestatin prepropeptide gene polymorphisms in small for gestational age infants.

PubMed

Zhang, Shulian; Zhai, Guanpeng; Zhang, Jinping; Zhou, Jianguo; Chen, Chao

2014-12-01

To investigate plasma ghrelin and obestatin levels, and ghrelin/obestatin prepropeptide gene polymorphisms, in sequentially enrolled small for gestational age (SGA) infants. Neonates were sequentially enrolled into this study and were then subdivided into different groups, according to different study aims and availability of study materials. Consequently, plasma ghrelin and obestatin levels were measured in term SGA, term appropriate for gestational age (AGA), term large for gestational age (LGA), preterm SGA and preterm AGA neonates. Levels of both peptides were also measured in AGA infants of different gestational ages, and in term AGA neonates at different days following birth. Three ghrelin/obestatin prepropeptide gene single nucleotide polymorphisms (SNPs), Arg51Gln, Leu72Met, and Gln90Leu, were measured in neonates. The study involved a total cohort of 581 neonates. Out of 150 neonates (30 term AGA, 30 term SGA, 30 term LGA, 30 preterm AGA, and 30 preterm SGA), plasma obestatin levels were significantly higher in term SGA versus term LGA neonates (0.21 ± 0.02 ng/ml versus 0.17 ± 0.01 ng/ml, respectively). Out of a wider cohort, there were no significant differences in genotypes and allele frequencies of Arg51Gln, Leu72Met, and Gln90Leu SNPs between term SGA and AGA neonates, or between preterm SGA and AGA neonates. Ghrelin/obestatin prepropeptide polymorphisms were not found to be associated with SGA status in neonates; however, ghrelin and obestatin levels may be involved in growth and development. Further studies are required to understand the relationship between ghrelin, obestatin and prenatal development. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Spinal cord ischemia after simultaneous and sequential treatment of multilevel aortic disease.

PubMed

Piffaretti, Gabriele; Bonardelli, Stefano; Bellosta, Raffaello; Mariscalco, Giovanni; Lomazzi, Chiara; Tolenaar, Jip L; Zanotti, Camilla; Guadrini, Cristina; Sarcina, Antonio; Castelli, Patrizio; Trimarchi, Santi

2014-10-01

The aim of the present study is to report a risk analysis for spinal cord injury in a recent cohort of patients with simultaneous and sequential treatment of multilevel aortic disease. We performed a multicenter study with a retrospective data analysis. Simultaneous treatment refers to descending thoracic and infrarenal aortic lesions treated during the same operation, and sequential treatment refers to separate operations. All descending replacements were managed with endovascular repair. Of 4320 patients, multilevel aortic disease was detected in 77 (1.8%). Simultaneous repair was performed in 32 patients (41.5%), and a sequential repair was performed in 45 patients (58.4%). Postoperative spinal cord injury developed in 6 patients (7.8%). At multivariable analysis, the distance of the distal aortic neck from the celiac trunk was the only independent predictor of postoperative spinal cord injury (odds ratio, 0.75; 95% confidence interval, 0.56-0.99; P=.046); open surgical repair of the abdominal aortic disease was associated with a higher risk of spinal cord injury but did not reach statistical significance (odds ratio, 0.16; 95% confidence interval, 0.02-1.06; P=.057). Actuarial survival estimates at 1, 2, and 5 years after the procedure were 80%±5%, 68%±6%, and 63%±7%, respectively. Spinal cord injury did not impair survival (P=.885). In our experience, the risk of spinal cord injury is still substantial at 8% in patients with multilevel aortic disease. The distance of the distal landing zone from the celiac trunk is a significant predictor of spinal cord ischemia. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Comparing Quick Sequential Organ Failure Assessment Scores to End-tidal Carbon Dioxide as Mortality Predictors in Prehospital Patients with Suspected Sepsis.

PubMed

Hunter, Christopher L; Silvestri, Salvatore; Ralls, George; Stone, Amanda; Walker, Ayanna; Mangalat, Neal; Papa, Linda

2018-05-01

Early identification of sepsis significantly improves outcomes, suggesting a role for prehospital screening. An end-tidal carbon dioxide (ETCO 2 ) value ≤ 25 mmHg predicts mortality and severe sepsis when used as part of a prehospital screening tool. Recently, the Quick Sequential Organ Failure Assessment (qSOFA) score was also derived as a tool for predicting poor outcomes in potentially septic patients. We conducted a retrospective cohort study among patients transported by emergency medical services to compare the use of ETCO 2 ≤ 25 mmHg with qSOFA score of ≥ 2 as a predictor of mortality or diagnosis of severe sepsis in prehospital patients with suspected sepsis. By comparison of receiver operator characteristic curves, ETCO 2 had a higher discriminatory power to predict mortality, sepsis, and severe sepsis than qSOFA. Both non-invasive measures were easily obtainable by prehospital personnel, with ETCO 2 performing slightly better as an outcome predictor.

Dysphagia after sequential chemoradiation therapy for advanced head and neck cancer.

PubMed

Goguen, Laura A; Posner, Marshall R; Norris, Charles M; Tishler, Roy B; Wirth, Lori J; Annino, Donald J; Gagne, Adele; Sullivan, Christopher A; Sammartino, Daniel E; Haddad, Robert I

2006-06-01

Assess impact of sequential chemoradiation therapy (SCRT) for advanced head and neck cancer (HNCA) on swallowing, nutrition, and quality of life. Prospective cohort study of 59 patients undergoing SCRT for advanced head and neck cancer. Follow-up median was 47.5 months. Regional Cancer Center. Median time to gastrostomy tube removal was 21 weeks. Eighteen of 23 patients who underwent modified barium swallow demonstrated aspiration; none developed pneumonia. Six of 7 with pharyngoesophageal stricture underwent successful dilatation. Functional Assessment of Cancer Therapy-Head and Neck Scale questionnaires at median 6 months after treatment revealed "somewhat" satisfaction with swallowing. At the time of analysis, 97% have the gastronomy tube removed and take soft/regular diet. Early after treatment dysphagia adversely affected weight, modified barium swallow results, and quality of life. Diligent swallow therapy, and dilation as needed, allowed nearly all patients to have their gastronomy tubes removed and return to a soft/regular diet. Dysphagia is significant after SCRT but generally slowly recovers 6 to 12 months after SCRT. C-4.

Adjuvant Chemotherapy and Trastuzumab Is Safe and Effective in Older Women With Small, Node-Negative, HER2-Positive Early-Stage Breast Cancer.

PubMed

Cadoo, Karen A; Morris, Patrick G; Cowell, Elizabeth P; Patil, Sujata; Hudis, Clifford A; McArthur, Heather L

2016-12-01

The benefit of adjuvant trastuzumab with chemotherapy is well established for women with higher risk human epidermal growth factor receptor 2-positive (HER2 + ) breast cancer. However, its role in older patients with smaller, node-negative tumors is less clear. We conducted a retrospective, sequential cohort study of this population to describe the impact of trastuzumab on breast cancer outcomes and cardiac safety. Women ≥ 55 years with ≤ 2 cm, node-negative, HER2 + breast cancer were identified and electronic medical records reviewed. A no-trastuzumab cohort of 116 women diagnosed between January 1, 1999 and May 14, 2004 and a trastuzumab cohort of 128 women diagnosed between May 16, 2006 and December 31, 2010 were identified. Overall survival and distant relapse-free survival were estimated by Kaplan-Meier methods. The median ages of the trastuzumab and no-trastuzumab cohorts were 62 and 64 years, respectively. More patients in the trastuzumab cohort had grade III (P = .001), lymphovascular invasion (P = .001), or estrogen receptor-negative (P < .001) cancers. The majority of the trastuzumab cohort received chemotherapy versus one-half of the no-trastuzumab cohort (98% vs. 53%; P < .0001). The median follow-up was 4 versus 9 years in the trastuzumab versus no-trastuzumab cohorts; therefore, outcomes at 4 years are reported. Despite the higher-risk tumor features in the trastuzumab group, the 4-year overall survival was 99% in both cohorts; the distant relapse-free survival was 99% versus 97% in the trastuzumab versus no-trastuzumab cohorts. Four (3.1%; 95% confidence interval, 1.0%-7.8%) women in the trastuzumab cohort and 1 in the no-trastuzumab cohort developed symptomatic heart failure. There were no cardiac-related deaths in either arm. Following adjuvant trastuzumab with chemotherapy, selected older women with small, node-negative, HER2 + breast cancers have excellent disease control. The rate of cardiac events is low. Copyright © 2016 Elsevier Inc. All rights reserved.

Developmental personality types from childhood to adolescence: associations with parenting and adjustment.

PubMed

de Haan, Amaranta D; Deković, Maja; van den Akker, Alithe L; Stoltz, Sabine E M J; Prinzie, Peter

2013-01-01

This study examined whether changes in children's self-reported Big Five dimensions are represented by (developmental) personality types, using a cohort-sequential design with three measurement occasions across 5 years (four cohorts, 9-12 years at T1; N = 523). Correlates of, and gender differences in, type membership were examined. Latent class growth modeling yielded three personality types: Resilients (highest initial levels on all Big Five), Overcontrollers (lowest Extraversion, Emotional Stability, Imagination), and Undercontrollers (lowest Benevolence, Conscientiousness). Gender differences in type membership were small. Warm parenting, but not overreactive discipline, in childhood was associated with type membership. The types differed in adjustment problems by the end of middle adolescence. Personality change more likely occurs at the level of dimensions within types than in type membership. © 2013 The Authors. Child Development © 2013 Society for Research in Child Development, Inc.

Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure.

PubMed

Jalan, Rajiv; Saliba, Faouzi; Pavesi, Marco; Amoros, Alex; Moreau, Richard; Ginès, Pere; Levesque, Eric; Durand, Francois; Angeli, Paolo; Caraceni, Paolo; Hopf, Corinna; Alessandria, Carlo; Rodriguez, Ezequiel; Solis-Muñoz, Pablo; Laleman, Wim; Trebicka, Jonel; Zeuzem, Stefan; Gustot, Thierry; Mookerjee, Rajeshwar; Elkrief, Laure; Soriano, German; Cordoba, Joan; Morando, Filippo; Gerbes, Alexander; Agarwal, Banwari; Samuel, Didier; Bernardi, Mauro; Arroyo, Vicente

2014-11-01

Acute-on-chronic liver failure (ACLF) is a frequent syndrome (30% prevalence), characterized by acute decompensation of cirrhosis, organ failure(s) and high short-term mortality. This study develops and validates a specific prognostic score for ACLF patients. Data from 1349 patients included in the CANONIC study were used. First, a simplified organ function scoring system (CLIF Consortium Organ Failure score, CLIF-C OFs) was developed to diagnose ACLF using data from all patients. Subsequently, in 275 patients with ACLF, CLIF-C OFs and two other independent predictors of mortality (age and white blood cell count) were combined to develop a specific prognostic score for ACLF (CLIF Consortium ACLF score [CLIF-C ACLFs]). A concordance index (C-index) was used to compare the discrimination abilities of CLIF-C ACLF, MELD, MELD-sodium (MELD-Na), and Child-Pugh (CPs) scores. The CLIF-C ACLFs was validated in an external cohort and assessed for sequential use. The CLIF-C ACLFs showed a significantly higher predictive accuracy than MELDs, MELD-Nas, and CPs, reducing (19-28%) the corresponding prediction error rates at all main time points after ACLF diagnosis (28, 90, 180, and 365 days) in both the CANONIC and the external validation cohort. CLIF-C ACLFs computed at 48 h, 3-7 days, and 8-15 days after ACLF diagnosis predicted the 28-day mortality significantly better than at diagnosis. The CLIF-C ACLFs at ACLF diagnosis is superior to the MELDs and MELD-Nas in predicting mortality. The CLIF-C ACLFs is a clinically relevant, validated scoring system that can be used sequentially to stratify the risk of mortality in ACLF patients. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Academic Growth Expectations for Students with Emotional and Behavior Disorders

ERIC Educational Resources Information Center

Ysseldyke, Jim; Scerra, Carmine; Stickney, Eric; Beckler, Amanda; Dituri, Joan; Ellis, Karen

2017-01-01

Computer adaptive assessments were used to monitor the academic status and growth of students with emotional behavior disorders (EBD) in reading (N = 321) and math (N = 322) in a regional service center serving 56 school districts. A cohort sequential model was used to compare that performance to the status and growth of a national user base of…

Association of autoimmune Addison's disease with alleles of STAT4 and GATA3 in European cohorts.

PubMed

Mitchell, Anna L; Macarthur, Katie D R; Gan, Earn H; Baggott, Lucy E; Wolff, Anette S B; Skinningsrud, Beate; Platt, Hazel; Short, Andrea; Lobell, Anna; Kämpe, Olle; Bensing, Sophie; Betterle, Corrado; Kasperlik-Zaluska, Anna; Zurawek, Magdalena; Fichna, Marta; Kockum, Ingrid; Nordling Eriksson, Gabriel; Ekwall, Olov; Wahlberg, Jeanette; Dahlqvist, Per; Hulting, Anna-Lena; Penna-Martinez, Marissa; Meyer, Gesine; Kahles, Heinrich; Badenhoop, Klaus; Hahner, Stephanie; Quinkler, Marcus; Falorni, Alberto; Phipps-Green, Amanda; Merriman, Tony R; Ollier, William; Cordell, Heather J; Undlien, Dag; Czarnocka, Barbara; Husebye, Eystein; Pearce, Simon H S

2014-01-01

Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for. To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts. A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity. We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-κB1 and IL23A genes in the UK and Italian cohorts respectively. Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.

Radiographic and Clinical Outcomes of the Treatment of Immature Permanent Teeth by Revascularization or Apexification: A Pilot Retrospective Cohort Study

PubMed Central

Alobaid, Adel S.; Cortes, Lina M.; Lo, Jeffery; Nguyen, Thuan T.; Albert, Jeffery; Abu-Melha, Abdulaziz S; Lin, Louis M.; Gibbs, Jennifer L.

2014-01-01

Introduction This retrospective cohort study compared clinical and radiographic outcomes of endodontic treatment performed in immature non-vital permanent teeth, by apexification (calcium hydroxide or apical barrier with Mineral Trioxide Aggregate (MTA)), versus revascularization. Methods A comprehensive chart review was performed to obtain a cohort of sequential previously completed cases with recalls. Clinical and radiographic data were collected for 31 treated teeth (19 revascularization and 12 apexification) with an average follow up time of 17 months and a recall rate of 63%. Tooth survival, success rate, and adverse events were analyzed. Changes in radiographic root length, width and area were quantified. Results The majority of treated teeth survived throughout the study period with 30/31 (97%) teeth surviving (18/19 (95%) revascularization, 12/12 apexification). Most cases were also clinically successful with 27/31 (87%) meeting criteria for success, (15/19 (78%) revascularization and 12/12 apexification; non-significant difference). A greater incidence of adverse events was observed in the revascularization group (8/19 (42%) versus 1/12 (11%) in apexification (Risk Ratio= 5.1, p=0.04, 95%CI (0.719, 35.48)). Although more revascularization cases than apexification cases demonstrated an increase in radiographic root area and width, the effect was not statistically significant. Conclusion In this study, revascularization was not superior to other apexification techniques in either clinical or radiographic outcomes. Studies with large subject cohorts, and long follow up periods are needed to evaluate outcomes of revascularization and apexification, while accounting for important co-variants relevant to clinical success. PMID:25069909

Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria: A meta-analysis and trial sequential analysis

NASA Astrophysics Data System (ADS)

Sun, Fengmei; Zhang, Juan; Pu, Yuepu

2017-10-01

This study is designed to perform a meta-analysis and trial sequential analysis (TSA) to investigate whether people with G6PD deficiency suffered less malarial infection. We searched from PubMed, Science Direct, Springer Link, CNKI, and Wan Fang databases for case-control study, cohort study or cross section study until April 2017. TSA was used to determine the state of evidence and calculate the required sample size. Eight case-control studies and five cross-sectional studies (30,683participants) were included in this meta-analysis. Compared with normal control group, we found significant protection from severe malaria (OR 0.644, 95% CI [0.493-0.842]; P=0.001) among people with decreasing G6PD activity. People with variations of G6PD gene at nucleotide 202(G6PD A-) were also found to be associated with resistance on severe malaria pooled (OR 0.851, 95% CI [0.779-0.930]; P =0.0001). Sex-stratified test suggested that protection of severe malaria is conferred to both G6PD A-males and heterozygous females (with a single copy of the variant). In conclusion, our study found a significant protection from severe malaria among G6PD deficient people compared to the

A prospective cohort study of the morbidity associated with operative vaginal deliveries performed by day and at night.

PubMed

Butler, Katherine; Ramphul, Meenakshi; Dunney, Clare; Farren, Maria; McSweeney, Aoife; McNamara, Karen; Murphy, Deirdre J

2014-10-29

To evaluate maternal and neonatal outcomes associated with operative vaginal deliveries (OVDs) performed by day and at night. Prospective cohort study. Urban maternity unit in Ireland with off-site consultant staff at night. All nulliparous women requiring an OVD with a term singleton fetus in a cephalic presentation from February to November 2013. Delivery outcomes were compared for women who delivered by day (08:00-19:59) or at night (20:00-07:59). The main outcomes included postpartum haemorrhage (PPH), anal sphincter tear and neonatal unit admission. Procedural factors included operator grade, sequential use of instruments and caesarean section. Of the 597 women who required an OVD, 296 (50%) delivered at night. Choice of instrument, place of delivery, sequential use of instruments and caesarean section did not differ significantly in relation to time of birth. Mid-grade operators performed less OVDs by day than at night, OR 0.60 (95% CI 0.43 to 0.83), and a consultant supervisor was more frequently present by day, OR 2.26 (95% CI 1.05 to 4.83). Shoulder dystocia occurred more commonly by day, OR 2.57 (95% CI 1.05 to 6.28). The incidence of PPH, anal sphincter tears, neonatal unit admission, fetal acidosis and neonatal trauma was similar by day and at night. The mean decision to delivery intervals were 12.0 and 12.6 min, respectively. There was no evidence of an association between time of OVD and adverse perinatal outcomes despite off-site consultant obstetric support at night. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Association of the tumor necrosis factor-alpha promoter polymorphism with change in triacylglycerol response to sequential meals.

PubMed

Jackson, Kim G; Li, Yue; Ryan, Miriam F; Gibney, Eileen R; Brennan, Lorraine; Roche, Helen M; Williams, Christine M; Lovegrove, Julie A; Vimaleswaran, Karani S

2016-07-25

Reported associations between Tumor Necrosis Factor-alpha (TNFA) and the postprandial triacylglycerol (TAG) response have been inconsistent, which could be due to variations in the TNFA gene, meal fat composition or participant's body weight. Hence, we investigated the association of TNFA polymorphism (-308G → A) with body mass index (BMI) and postprandial lipaemia and also determined the impact of BMI on the association of the polymorphism with postprandial lipaemia. The study participants (n = 230) underwent a sequential meal postprandial study. Blood samples were taken at regular intervals after a test breakfast (t = 0, 49 g fat) and lunch (t =330 min, 29 g fat) to measure fasting and postprandial lipids, glucose and insulin. The Metabolic Challenge Study (MECHE) comprising 67 Irish participants who underwent a 54 g fat oral lipid tolerance test was used as a replication cohort. The impact of genotype on postprandial responses was determined using general linear model with adjustment for potential confounders. The -308G → A polymorphism showed a significant association with BMI (P = 0.03) and fasting glucose (P = 0.006), where the polymorphism explained 13 % of the variation in the fasting glucose. A 30 % higher incremental area under the curve (IAUC) was observed for the postprandial TAG response in the GG homozygotes than A-allele carriers (P = 0.004) and the genotype explained 19 % of the variation in the IAUC. There was a non-significant trend in the impact of BMI on the association of the genotype with TAG IAUC (P = 0.09). These results were not statistically significant in the MECHE cohort, which could be due to the differences in the sample size, meal composition, baseline lipid profile, allelic diversity and postprandial characterisation of participants across the two cohorts. Our findings suggest that TNFA -308G → A polymorphism may be an important candidate for BMI, fasting glucose and postprandial TAG response. Further studies are required to investigate the mechanistic effects of the polymorphism on glucose and TAG metabolism, and determine whether BMI is an important variable which should be considered in the design of future studies. NCT01172951 .

Cost-effectiveness of the sequential application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

PubMed

Rochau, Ursula; Sroczynski, Gaby; Wolf, Dominik; Schmidt, Stefan; Jahn, Beate; Kluibenschaedl, Martina; Conrads-Frank, Annette; Stenehjem, David; Brixner, Diana; Radich, Jerald; Gastl, Günther; Siebert, Uwe

2015-01-01

Several tyrosine kinase inhibitors (TKIs) are approved for chronic myeloid leukemia (CML) therapy. We evaluated the long-term cost-effectiveness of seven sequential therapy regimens for CML in Austria. A cost-effectiveness analysis was performed using a state-transition Markov model. As model parameters, we used published trial data, clinical, epidemiological and economic data from the Austrian CML registry and national databases. We performed a cohort simulation over a life-long time-horizon from a societal perspective. Nilotinib without second-line TKI yielded an incremental cost-utility ratio of 121,400 €/quality-adjusted life year (QALY) compared to imatinib without second-line TKI after imatinib failure. Imatinib followed by nilotinib after failure resulted in 131,100 €/QALY compared to nilotinib without second-line TKI. Nilotinib followed by dasatinib yielded 152,400 €/QALY compared to imatinib followed by nilotinib after failure. Remaining strategies were dominated. The sequential application of TKIs is standard-of-care, and thus, our analysis points toward imatinib followed by nilotinib as the most cost-effective strategy.

Impact of a Sequential Intervention on Albumin Utilization in Critical Care.

PubMed

Lyu, Peter F; Hockenberry, Jason M; Gaydos, Laura M; Howard, David H; Buchman, Timothy G; Murphy, David J

2016-07-01

Literature generally finds no advantages in mortality risk for albumin over cheaper alternatives in many settings. Few studies have combined financial and nonfinancial strategies to reduce albumin overuse. We evaluated the effect of a sequential multifaceted intervention on decreasing albumin use in ICU and explore the effects of different strategies. Prospective prepost cohort study. Eight ICUs at two hospitals in an academic healthcare system. Adult patients admitted to study ICUs from September 2011 to August 2014 (n = 22,004). Over 2 years, providers in study ICUs participated in an intervention to reduce albumin use involving monthly feedback and explicit financial incentives in the first year and internal guidelines and order process changes in the second year. Outcomes measured were albumin orders per ICU admission, direct albumin costs, and mortality. Mean (SD) utilization decreased 37% from 2.7 orders (6.8) per admission during the baseline to 1.7 orders (4.6) during the intervention (p < 0.001). Regression analysis revealed that the intervention was independently associated with 0.9 fewer orders per admission, a 42% relative decrease. This adjusted effect consisted of an 18% reduction in the probability of using any albumin (p < 0.001) and a 29% reduction in the number of orders per admission among patients receiving any (p < 0.001). Secondary analysis revealed that probability reductions were concurrent with internal guidelines and order process modification while reductions in quantity occurred largely during the financial incentives and feedback period. Estimated cost savings totaled $2.5M during the 2-year intervention. There was no significant difference in ICU or hospital mortality between baseline and intervention. A sequential intervention achieved significant reductions in ICU albumin use and cost savings without changes in patient outcomes, supporting the combination of financial and nonfinancial strategies to align providers with evidence-based practices.

A placebo-controlled, double-blind, dose-escalation study to assess the safety, tolerability and pharmacokinetics/pharmacodynamics of single and multiple intravenous infusions of AZD9773 in patients with severe sepsis and septic shock

PubMed Central

2012-01-01

Introduction Tumor necrosis factor-alpha (TNF-α), an early mediator in the systemic inflammatory response to infection, is a potential therapeutic target in sepsis. The primary objective of this study was to determine the safety and tolerability of AZD9773, an ovine, polyclonal, anti-human TNF-α Fab preparation, in patients with severe sepsis. Secondary outcomes related to pharmacokinetic (PK) and pharmacodynamic (PD) parameters. Methods In this double-blind, placebo-controlled, multicenter Phase IIa study, patients were sequentially enrolled into five escalating-dose cohorts (single doses of 50 or 250 units/kg; multiple doses of 250 units/kg loading and 50 units/kg maintenance, 500 units/kg loading and 100 units/kg maintenance, or 750 units/kg loading and 250 units/kg maintenance). In each cohort, patients were randomized 2:1 to receive AZD9773 or placebo. Results Seventy patients received AZD9773 (n = 47) or placebo (n = 23). Baseline characteristics were similar across cohorts. Mean baseline APACHE score was 25.9. PK data demonstrated an approximately proportional increase in concentration with increasing dose and a terminal half-life of 20 hours. For the multiple-dose cohorts, serum TNF-α concentrations decreased to near-undetectable levels within two hours of commencing AZD9773 infusion. This suppression was maintained in most patients for the duration of treatment. AZD9773 was well tolerated. Most adverse events were of mild-to-moderate intensity and considered by the reporting investigator as unrelated to study treatment. Conclusions The safety, PK and PD data support the continued evaluation of AZD9773 in larger Phase IIb/III studies. PMID:22340283

MODUL-a multicenter randomized clinical trial of biomarker-driven maintenance therapy following first-line standard induction treatment of metastatic colorectal cancer: an adaptable signal-seeking approach.

PubMed

Schmoll, Hans-Joachim; Arnold, Dirk; de Gramont, Aimery; Ducreux, Michel; Grothey, Axel; O'Dwyer, Peter J; Van Cutsem, Eric; Hermann, Frank; Bosanac, Ivan; Bendahmane, Belguendouz; Mancao, Christoph; Tabernero, Josep

2018-06-01

The old approach of one therapeutic for all patients with mCRC is evolving with a need to target specific molecular aberrations or cell-signalling pathways. Molecular screening approaches and new biomarkers are required to fully characterize tumours, identify patients most likely to benefit, and predict treatment response. MODUL is a signal-seeking trial with a design that is highly adaptable, permitting modification of different treatment cohorts and inclusion of further additional cohorts based on novel evidence on new compounds/combinations that emerge during the study. MODUL is ongoing and its adaptable nature permits timely and efficient recruitment of patients into the most appropriate cohort. Recruitment will take place over approximately 5 years in Europe, Asia, Africa, and South America. The design of MODUL with ongoing parallel/sequential treatment cohorts means that the overall size and duration of the trial can be modified/prolonged based on accumulation of new data. The early success of the current trial suggests that the design may provide definitive leads in a patient-friendly and relatively economical trial structure. Along with other biomarker-driven trials that are currently underway, it is hoped that MODUL will contribute to the continuing evolution of clinical trial design and permit a more 'tailored' approach to the treatment of patients with mCRC.

Making of epistemologically sophisticated physics teachers: A cross-sequential study of epistemological progression from preservice to in-service teachers

NASA Astrophysics Data System (ADS)

Ding, Lin; Zhang, Ping

2016-12-01

Previous literature on learners' epistemological beliefs about physics has almost exclusively focused on analysis of university classroom instruction and its effects on students' views. However, little is known about other populations or factors other than classroom instruction on learners' epistemologies. In this study, we used a cross-sequential method, combining both longitudinal and cross-sectional designs, to investigate an epistemological progression trend from preservice to in-service teachers. Six cohorts of participants were studied, who either were then attending or had completed an undergraduate teacher preparation program in physics at a major Chinese university. These cohorts were incoming freshmen, end-of-year freshmen, end-of-year sophomores, end-of-year juniors, end-of-year seniors, and 1st-year high school physics teachers who were about to enter the 2nd year of teaching. We used the Colorado Learning Attitudes about Science Survey (CLASS) as both a pretest and a post-test to gauge the changes in the participants' epistemological views over an entire academic year. Follow-up interviews were also conducted to explore factors responsible for such changes. Results showed that the epistemological trend as measured by CLASS did not increase monotonically. Instead, there was a decrease in the epistemological trend among the incoming freshmen in their first year undergraduate studies, followed by a long stasis until the end of the senior year. Then, there was a rebound for the end-of-year seniors in their 1st year of teaching, followed by another plateau. Interviews revealed that the competitive learning environment, increased content difficulty, and unfamiliar pedagogies in college were major factors that negatively influenced incoming freshmen's views about physics. Conversely, a role change from student to teacher and relatively easy content in high school positively impacted end-of-year seniors' views about physics and learning.

Trajectories of impairment in amyotrophic lateral sclerosis: Insights from the Pooled Resource Open-Access ALS Clinical Trials cohort.

PubMed

Thakore, Nimish J; Lapin, Brittany R; Pioro, Erik P

2018-06-01

Rate of decline of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score is a common outcome measure and a powerful predictor of mortality in ALS. Observed rate of decline (postslope) of ALSFRS-R, its linearity, and its relationship to decline at first visit (preslope) were examined in the Pooled Resource Open-Access ALS Clinical Trials cohort by using longitudinal mixed effects models. Mean ALSFRS-R postslope in 3,367 patients was -0.99 points/month. Preslope and postslope were correlated and had powerful effects on survival. ALSFRS-R trajectories were slightly accelerated overall, but slope and direction/degree of curvature varied. Subscore decline was sequential by site of onset. Respiratory subscore decline was the least steep. Variable curvilinearity of ALSFRS-R trajectories confounds interpretation in clinical studies that assume linear decline. Subscore trajectories recapitulate phenotypic diversity and topographical progression of ALS. ALSFRS-R is better used as a multidimensional measure. Muscle Nerve 57: 937-945, 2018. © 2017 Wiley Periodicals, Inc.

The peroxisome proliferator-activated receptor agonist pioglitazone and 5-lipoxygenase inhibitor zileuton have no effect on lung inflammation in healthy volunteers by positron emission tomography in a single-blind placebo-controlled cohort study.

PubMed

Chen, Delphine L; Huang, Howard J; Byers, Derek E; Shifren, Adrian; Belikoff, Bryan; Engle, Jacquelyn T; Arentson, Elizabeth; Kemp, Debra; Phillips, Sharon; Scherrer, David E; Fujiwara, Hideji; Spayd, Katherine J; Brooks, Frank J; Pierce, Richard A; Castro, Mario; Isakow, Warren

2018-01-01

Anti-inflammatory drug development efforts for lung disease have been hampered in part by the lack of noninvasive inflammation biomarkers and the limited ability of animal models to predict efficacy in humans. We used 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in a human model of lung inflammation to assess whether pioglitazone, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, and zileuton, a 5-lipoxygenase inhibitor, reduce lung inflammation. For this single center, single-blind, placebo-controlled cohort study, we enrolled healthy volunteers sequentially into the following treatment cohorts (N = 6 per cohort): pioglitazone plus placebo, zileuton plus placebo, or dual placebo prior to bronchoscopic endotoxin instillation. 18F-FDG uptake pre- and post-endotoxin was quantified as the Patlak graphical analysis-determined Ki (primary outcome measure). Secondary outcome measures included the mean standard uptake value (SUVmean), post-endotoxin bronchoalveolar lavage (BAL) cell counts and differentials and blood adiponectin and urinary leukotriene E4 (LTE4) levels, determined by enzyme-linked immunosorbent assay, to verify treatment compliance. One- or two-way analysis of variance assessed for differences among cohorts in the outcome measures (expressed as mean ± standard deviation). Ten females and eight males (29±6 years of age) completed all study procedures except for one volunteer who did not complete the post-endotoxin BAL. Ki and SUVmean increased in all cohorts after endotoxin instillation (Ki increased by 0.0021±0.0019, 0.0023±0.0017, and 0.0024±0.0020 and SUVmean by 0.47±0.14, 0.55±0.15, and 0.54±0.38 in placebo, pioglitazone, and zileuton cohorts, respectively, p<0.001) with no differences among treatment cohorts (p = 0.933). Adiponectin levels increased as expected with pioglitazone treatment but not urinary LTE4 levels as expected with zileuton treatment. BAL cell counts (p = 0.442) and neutrophil percentage (p = 0.773) were similar among the treatment cohorts. Endotoxin-induced lung inflammation in humans is not responsive to pioglitazone or zileuton, highlighting the challenge in translating anti-inflammatory drug efficacy results from murine models to humans. ClinicalTrials.gov NCT01174056.

The peroxisome proliferator-activated receptor agonist pioglitazone and 5-lipoxygenase inhibitor zileuton have no effect on lung inflammation in healthy volunteers by positron emission tomography in a single-blind placebo-controlled cohort study

PubMed Central

Huang, Howard J.; Byers, Derek E.; Shifren, Adrian; Belikoff, Bryan; Engle, Jacquelyn T.; Arentson, Elizabeth; Kemp, Debra; Phillips, Sharon; Scherrer, David E.; Fujiwara, Hideji; Spayd, Katherine J.; Brooks, Frank J.; Pierce, Richard A.; Castro, Mario; Isakow, Warren

2018-01-01

Background Anti-inflammatory drug development efforts for lung disease have been hampered in part by the lack of noninvasive inflammation biomarkers and the limited ability of animal models to predict efficacy in humans. We used 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in a human model of lung inflammation to assess whether pioglitazone, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, and zileuton, a 5-lipoxygenase inhibitor, reduce lung inflammation. Methods For this single center, single-blind, placebo-controlled cohort study, we enrolled healthy volunteers sequentially into the following treatment cohorts (N = 6 per cohort): pioglitazone plus placebo, zileuton plus placebo, or dual placebo prior to bronchoscopic endotoxin instillation. 18F-FDG uptake pre- and post-endotoxin was quantified as the Patlak graphical analysis-determined Ki (primary outcome measure). Secondary outcome measures included the mean standard uptake value (SUVmean), post-endotoxin bronchoalveolar lavage (BAL) cell counts and differentials and blood adiponectin and urinary leukotriene E4 (LTE4) levels, determined by enzyme-linked immunosorbent assay, to verify treatment compliance. One- or two-way analysis of variance assessed for differences among cohorts in the outcome measures (expressed as mean ± standard deviation). Results Ten females and eight males (29±6 years of age) completed all study procedures except for one volunteer who did not complete the post-endotoxin BAL. Ki and SUVmean increased in all cohorts after endotoxin instillation (Ki increased by 0.0021±0.0019, 0.0023±0.0017, and 0.0024±0.0020 and SUVmean by 0.47±0.14, 0.55±0.15, and 0.54±0.38 in placebo, pioglitazone, and zileuton cohorts, respectively, p<0.001) with no differences among treatment cohorts (p = 0.933). Adiponectin levels increased as expected with pioglitazone treatment but not urinary LTE4 levels as expected with zileuton treatment. BAL cell counts (p = 0.442) and neutrophil percentage (p = 0.773) were similar among the treatment cohorts. Conclusions Endotoxin-induced lung inflammation in humans is not responsive to pioglitazone or zileuton, highlighting the challenge in translating anti-inflammatory drug efficacy results from murine models to humans. Trial registration ClinicalTrials.gov NCT01174056. PMID:29414995

Sleep-disordered breathing and the risk of cognitive decline: a meta-analysis of 19,940 participants.

PubMed

Zhu, Xiaoxia; Zhao, Yanli

2018-03-01

Sleep-disordered breathing (SDB) is related to the incidence of cognitive decline. However, results of cohort studies were inconsistent. We performed a meta-analysis of cohort studies to evaluate the sequential association between SDB and cognitive decline. Cohort studies were identified by the searching of PubMed and Embase databases. A random effect model was applied to combine the results. Nineteen thousand nine hundred forty participants from six cohort studies were included. Participants with SDB at baseline had significantly higher risk of cognitive decline, as indicated by a combined outcome of mild cognitive impairment (MCI) or dementia (RR = 1.69, p < 0.001; I 2  = 60%). The association between SDB and the subsequent risk of cognitive decline remains in older people (RR = 1.70, p < 0.001; I 2  = 66%). Results of subgroup analyses indicated consistent results regardless of whether SDB was confirmed by PSG or whether the apolipoprotein E4 allele was adjusted. However, participants with SDB at baseline were with higher risk for developing MCI (RR = 2.44, p < 0.001) than dementia (RR = 1.61, p < 0.001; p for subgroup difference = 0.04). Moreover, SDB was associated with a significantly higher risk of cognitive decline in female participants (RR = 2.06, p < 0.001), but not in the males (RR = 1.18, p = 0.19; p for subgroup difference = 0.03). SDB may be an independent risk factor for the developing of cognitive decline, and gender difference may exist regarding this association.

Early development of language by hand: composing, reading, listening, and speaking connections; three letter-writing modes; and fast mapping in spelling.

PubMed

Berninger, Virginia W; Abbott, Robert D; Jones, Janine; Wolf, Beverly J; Gould, Laura; Anderson-Youngstrom, Marci; Shimada, Shirley; Apel, Kenn

2006-01-01

The first findings from a 5-year, overlapping-cohorts longitudinal study of typical language development are reported for (a) the interrelationships among Language by Ear (listening), Mouth (speaking), Eye (reading), and Hand (writing) in Cohort 1 in 1st and 3rd grade and Cohort 2 in 3rd and 5th grade; (b) the interrelationships among three modes of Language by Hand (writing manuscript letters with pen and keyboard and cursive letters with pen) in each cohort in the same grade levels as (a); and (c) the ability of the 1st graders in Cohort 1 and the 3rd graders in Cohort 2 to apply fast mapping in learning to spell pseudowords. Results showed that individual differences in Listening Comprehension, Oral Expression, Reading Comprehension, and Written Expression are stable developmentally, but each functional language system is only moderately correlated with the others. Likewise, manuscript writing, cursive writing, and keyboarding are only moderately correlated, and each has a different set of unique neuropsychological predictors depending on outcome measure and grade level. Results support the use of the following neuropsychological measures in assessing handwriting modes: orthographic coding, rapid automatic naming, finger succession (grapho-motor planning for sequential finger movements), inhibition, inhibition/switching, and phonemes skills (which may facilitate transfer of abstract letter identities across letter formats and modes of production). Both 1st and 3rd graders showed evidence of fast mapping of novel spoken word forms onto written word forms over 3 brief sessions (2 of which involved teaching) embedded in the assessment battery; and this fast mapping explained unique variance in their spelling achievement over and beyond their orthographic and phonological coding abilities and correlated significantly with current and next-year spelling achievement.

A prediction model for early death in non-small cell lung cancer patients following curative-intent chemoradiotherapy.

PubMed

Jochems, Arthur; El-Naqa, Issam; Kessler, Marc; Mayo, Charles S; Jolly, Shruti; Matuszak, Martha; Faivre-Finn, Corinne; Price, Gareth; Holloway, Lois; Vinod, Shalini; Field, Matthew; Barakat, Mohamed Samir; Thwaites, David; de Ruysscher, Dirk; Dekker, Andre; Lambin, Philippe

2018-02-01

Early death after a treatment can be seen as a therapeutic failure. Accurate prediction of patients at risk for early mortality is crucial to avoid unnecessary harm and reducing costs. The goal of our work is two-fold: first, to evaluate the performance of a previously published model for early death in our cohorts. Second, to develop a prognostic model for early death prediction following radiotherapy. Patients with NSCLC treated with chemoradiotherapy or radiotherapy alone were included in this study. Four different cohorts from different countries were available for this work (N = 1540). The previous model used age, gender, performance status, tumor stage, income deprivation, no previous treatment given (yes/no) and body mass index to make predictions. A random forest model was developed by learning on the Maastro cohort (N = 698). The new model used performance status, age, gender, T and N stage, total tumor volume (cc), total tumor dose (Gy) and chemotherapy timing (none, sequential, concurrent) to make predictions. Death within 4 months of receiving the first radiotherapy fraction was used as the outcome. Early death rates ranged from 6 to 11% within the four cohorts. The previous model performed with AUC values ranging from 0.54 to 0.64 on the validation cohorts. Our newly developed model had improved AUC values ranging from 0.62 to 0.71 on the validation cohorts. Using advanced machine learning methods and informative variables, prognostic models for early mortality can be developed. Development of accurate prognostic tools for early mortality is important to inform patients about treatment options and optimize care.

Adjuvant trastuzumab with chemotherapy is effective in women with small, node-negative, HER2-positive breast cancer.

PubMed

McArthur, Heather L; Mahoney, Kathleen M; Morris, Patrick G; Patil, Sujata; Jacks, Lindsay M; Howard, Jane; Norton, Larry; Hudis, Clifford A

2011-12-15

Several large, randomized trials established the benefits of adjuvant trastuzumab with chemotherapy. However, the benefit for women with small, node-negative HER2-positive (HER2+) disease is unknown, as these patients were largely excluded from these trials. Therefore, a retrospective, single-institution, sequential cohort study of women with small, node-negative, HER2+ breast cancer who did or did not receive adjuvant trastuzumab was conducted. Women with ≤ 2 cm, node-negative, HER2+ (immunohistochemistry 3+ or fluorescence in situ hybridization ≥ 2) breast cancer were identified through an institutional database. A "no-trastuzumab" cohort of 106 trastuzumab-untreated women diagnosed between January 1, 2002 and May 14, 2004 and a "trastuzumab" cohort of 155 trastuzumab-treated women diagnosed between May 16, 2005 and December 31, 2008 were described. Survival and recurrence outcomes were estimated by Kaplan-Meier methods. The cohorts were similar in age, median tumor size, histology, hormone receptor status, hormone therapy, and locoregional therapy. Chemotherapy was administered in 66% and 100% of the "no trastuzumab" and "trastuzumab" cohorts, respectively. The median recurrence-free and survival follow-up was: 6.5 years (0.7-8.5) and 6.8 years (0.7-8.5), respectively, for the "no trastuzumab" cohort and 3.0 years (0.5-5.2) and 3.0 years (0.6-5.2), respectively, for the "trastuzumab" cohort. The 3-year locoregional invasive recurrence-free, distant recurrence-free, invasive disease-free, and overall survival were 92% versus 98% (P = .0137), 95% versus 100% (P = .0072), 82% versus 97% (P < .0001), and 97% versus 99% (P = .18) for the "no trastuzumab" and "trastuzumab" cohorts, respectively. Women with small, node-negative, HER2+ primary breast cancers likely derive significant benefit from adjuvant trastuzumab with chemotherapy. Copyright © 2011 American Cancer Society.

Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy.

PubMed

Akdim, Fatima; Stroes, Erik S G; Sijbrands, Eric J G; Tribble, Diane L; Trip, Mieke D; Jukema, J Wouter; Flaim, Joann D; Su, John; Yu, Rosie; Baker, Brenda F; Wedel, Mark K; Kastelein, John J P

2010-04-13

The aim of this study was to evaluate the efficacy and safety of mipomersen in hypercholesterolemic subjects taking stable statin therapy. Mipomersen is an apolipoprotein (apo) B synthesis inhibitor that has demonstrated significant reductions in apo B and low-density lipoprotein (LDL) cholesterol in Phase 1 clinical trials in healthy volunteers. A randomized, placebo-controlled, dose-escalation Phase 2 study was designed to evaluate the effects of mipomersen in hypercholesterolemic subjects taking stable statin therapy. Seventy-four subjects were enrolled sequentially into 1 of 6 dose cohorts at a 4:1 (active/placebo) ratio. Subjects received 7 doses of 30 to 400 mg over 5 weeks in the first 5 cohorts and 15 doses of 200 mg over 13 weeks in the sixth cohort. Pre-specified end points included percentage change from baseline in apo B and LDL cholesterol. Safety was assessed with laboratory test results and by the incidence and severity of adverse events. The apo B and LDL cholesterol were reduced by 19% to 54% and 21% to 52%, respectively, at doses of 100 mg/week mipomersen and higher in the 5-week treatment cohorts. Efficacy seemed to increase upon treatment for 13 weeks at a dose of 200 mg/week. Injection site reactions (mild to moderate erythema [90%]) and hepatic transaminase increases (17%) were the most common adverse events, leading to discontinuation in 2 subjects and 1 subject, respectively. In the 13-week treatment cohort, 5 of 10 subjects (50%) had elevations >or=3x the upper limit of normal, 4 of which persisted on 2 consecutive occasions. Mipomersen might hold promise for treatment of patients not reaching target LDL cholesterol levels on stable statin therapy. Further studies are needed to address the mechanisms and clinical relevance of transaminase changes after mipomersen administration. (Dose-Escalating Safety Study in Subjects on Stable Statin Therapy; NCT00231569). Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Parenting and trajectories of children's maladaptive behaviors: a 12-year prospective community study.

PubMed

Luyckx, Koen; Tildesley, Elizabeth A; Soenens, Bart; Andrews, Judy A; Hampson, Sarah E; Peterson, Missy; Duriez, Bart

2011-01-01

This study investigated how parenting accounted for interindividual differences in developmental trajectories of different child behaviors across childhood and adolescence. In a cohort sequential community sample of 1,049 children, latent class growth analysis was applied to three parent-reported dimensions (monitoring, positive parenting, inconsistent discipline) across 12 annual assessments (ages 6-18). Four longitudinal parenting styles (authoritative, authoritarian, indulgent, uninvolved) were differentiated on the basis of levels and rates of change in the constituent parenting dimensions. Multigroup analyses demonstrated that these parenting styles were differentially related to changes in parent- and child-reported measures of children's alcohol and cigarette use, antisocial behavior, and internalizing symptoms, with the authoritative parenting class being related to the most optimal long-term development.

Shifting patterns of variance in adolescent alcohol use: Testing consumption as a developing trait-state.

PubMed

Nealis, Logan J; Thompson, Kara D; Krank, Marvin D; Stewart, Sherry H

2016-04-01

While average rates of change in adolescent alcohol consumption are frequently studied, variability arising from situational and dispositional influences on alcohol use has been comparatively neglected. We used variance decomposition to test differences in variability resulting from year-to-year fluctuations in use (i.e., state-like) and from stable individual differences (i.e., trait-like) using data from the Project on Adolescent Trajectories and Health (PATH), a cohort-sequential study spanning grades 7 to 11 using three cohorts starting in grades seven, eight, and nine, respectively. We tested variance components for alcohol volume, frequency, and quantity in the overall sample, and changes in components over time within each cohort. Sex differences were tested. Most variability in alcohol use reflected state-like variation (47-76%), with a relatively smaller proportion of trait-like variation (19-36%). These proportions shifted across cohorts as youth got older, with increases in trait-like variance from early adolescence (14-30%) to later adolescence (30-50%). Trends were similar for males and females, although females showed higher trait-like variance in alcohol frequency than males throughout development (26-43% vs. 11-25%). For alcohol volume and frequency, males showed the greatest increase in trait-like variance earlier in development (i.e., grades 8-10) compared to females (i.e., grades 9-11). The relative strength of situational and dispositional influences on adolescent alcohol use has important implications for preventative interventions. Interventions should ideally target problematic alcohol use before it becomes more ingrained and trait-like. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rare Copy Number Variation in Treatment-Resistant Major Depressive Disorder

PubMed Central

O’Dushlaine, Colm; Ripke, Stephan; Ruderfer, Douglas M.; Hamilton, Steven P.; Fava, Maurizio; Iosifescu, Dan V.; Kohane, Isaac S.; Churchill, Susanne E.; Castro, Victor M.; Clements, Caitlin C.; Blumenthal, Sarah R.; Murphy, Shawn N.; Smoller, Jordan W.; Perlis, Roy H.

2014-01-01

Background While antidepressant treatment response appears to be partially heritable, no consistent genetic associations have been identified. Large, rare copy number variants (CNVs) play a role in other neuropsychiatric diseases, so we assessed their association with treatment-resistant depression (TRD). Methods We analyzed data from two genome-wide association studies comprising 1263 Caucasian patients with major depressive disorder. One was drawn from a large health system by applying natural language processing to electronic health records (i2b2 cohort). The second consisted of a multicenter study of sequential antidepressant treatments, Sequenced Treatment Alternatives to Relieve Depression. The Birdsuite package was used to identify rare deletions and duplications. Individuals without symptomatic remission, despite two antidepressant treatment trials, were contrasted with those who remitted with a first treatment trial. Results CNV data were derived for 778 subjects in the i2b2 cohort, including 300 subjects (37%) with TRD, and 485 subjects in Sequenced Treatment Alternatives to Relieve Depression cohort, including 152 (31%) with TRD. CNV burden analyses identified modest enrichment of duplications in cases (empirical p = .04 for duplications of 100–200 kilobase) and a particular deletion region spanning gene PABPC4L (empirical p = .02, 6 cases: 0 controls). Pathway analysis suggested enrichment of CNVs intersecting genes regulating actin cytoskeleton. However, none of these associations survived genome-wide correction. Conclusions Contribution of rare CNVs to TRD appears to be modest, individually or in aggregate. The electronic health record-based methodology demonstrated here should facilitate collection of larger TRD cohorts necessary to further characterize these effects. PMID:24529801

Single Dose and Repeat Once-Daily Dose Safety, Tolerability and Pharmacokinetics of Valbenazine in Healthy Male Subjects.

PubMed

Luo, Rosa; Bozigian, Haig; Jimenez, Roland; Loewen, Gordon; O'Brien, Christopher F

2017-08-01

Valbenazine (VBZ) is a vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia. The safety, tolerability and pharmacokinetics of VBZ following single and repeat once-daily (QD) dosing were evaluated in 2 randomized, single-center, double-blind studies in healthy male subjects. In the first study, 2 cohorts of 8 subjects were administered single doses (SD) of placebo (PBO; N = 2/period) or VBZ (N = 6/period; 1, 2, 5, or 12.5 mg for Cohort 1 and 12.5, 25, 50, or 75 mg for Cohort 2) using a sequential escalation scheme. The second study consisted of 2 phases. In the initial phase, subjects were administered SD PBO (N = 2/period) or VBZ (N = 6/period; 75, 100, 125 or 150 mg) with sequential escalation. In the second phase, subjects received PBO, or 50 or 100 mg VBZ (N = 4:8:8) QD for 8 days (Cohort 1) or PBO or 50 mg VBZ (N = 6:6) QD for 8 days (Cohort 2). For both studies, plasma concentrations of VBZ and its active metabolite, NBI-98782, were determined. Safety was assessed throughout the studies. PK parameters were determined using noncompartmental methods. In both studies, VBZ was rapidly absorbed with peak concentrations typically observed within 1.5 hours. Peak NBI-98782 concentrations were typically observed at 4.0 to 9.0 hours. Terminal elimination half-life for both VBZ and NBI-98782 was ~20 hours. Across the 1 to 150 mg SD range evaluated across the studies, VBZ and NBI-98782 C max and AUC increased dose-proportionally from 50 to 150 mg and more than dose-proportionally from 1 to 50 mg. QD VBZ and NBI-98782 C max and AUC parameters were also dose-proportional between the 50 and 100 mg doses. Steady-state for both analytes appeared to be achieved by Day 8. The accumulation index was ~1.5 for VBZ and ~2.5 for NBI-98782. Peak to trough fluctuation was approximately 250% for VBZ and 70% for NBI-98782. Across both studies, NBI-98782 exposure was approximately 20%-30% that of VBZ based on molar ratios. In the first study, the maximum-tolerated dose was not achieved; headache (2 events) was the only treatment-emergent adverse event (TEAE) reported by more than one subject. In the second study, fatigue (4 events) was the only TEAE reported by more than one subject following SD VBZ. Following QD VBZ, the TEAEs of fatigue, insomnia, disturbance in attention, and nervousness were dose-dependent; the latter three TEAEs were considered dose-limiting. Subject withdrawals due to TEAEs were 1 each for PBO and 50 mg VBZ QD, and 3 for 100 mg VBZ QD. Clinically relevant effects on laboratory parameters, vital signs or ECGs were limited to increased CPK (SD: 1 each for 5 mg VBZ and PBO), ALT (QD: 1 each for 50 and 100 mg VBZ and PBO), and triglycerides (QD: 1 each for 50 mg VBZ and PBO). VBZ has an acceptable safety profile and predictable pharmacokinetics that result in stable concentrations of active compounds with low peak-to-trough fluctuation following once-daily dosing.

Single Dose and Repeat Once-Daily Dose Safety, Tolerability and Pharmacokinetics of Valbenazine in Healthy Male Subjects

PubMed Central

Luo, Rosa; Bozigian, Haig; Jimenez, Roland; Loewen, Gordon; O’Brien, Christopher F.

2017-01-01

Valbenazine (VBZ) is a vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia. The safety, tolerability and pharmacokinetics of VBZ following single and repeat once-daily (QD) dosing were evaluated in 2 randomized, single-center, double-blind studies in healthy male subjects. In the first study, 2 cohorts of 8 subjects were administered single doses (SD) of placebo (PBO; N = 2/period) or VBZ (N = 6/period; 1, 2, 5, or 12.5 mg for Cohort 1 and 12.5, 25, 50, or 75 mg for Cohort 2) using a sequential escalation scheme. The second study consisted of 2 phases. In the initial phase, subjects were administered SD PBO (N = 2/period) or VBZ (N = 6/period; 75, 100, 125 or 150 mg) with sequential escalation. In the second phase, subjects received PBO, or 50 or 100 mg VBZ (N = 4:8:8) QD for 8 days (Cohort 1) or PBO or 50 mg VBZ (N = 6:6) QD for 8 days (Cohort 2). For both studies, plasma concentrations of VBZ and its active metabolite, NBI-98782, were determined. Safety was assessed throughout the studies. PK parameters were determined using noncompartmental methods. In both studies, VBZ was rapidly absorbed with peak concentrations typically observed within 1.5 hours. Peak NBI-98782 concentrations were typically observed at 4.0 to 9.0 hours. Terminal elimination half-life for both VBZ and NBI-98782 was ~20 hours. Across the 1 to 150 mg SD range evaluated across the studies, VBZ and NBI-98782 Cmax and AUC increased dose-proportionally from 50 to 150 mg and more than dose-proportionally from 1 to 50 mg. QD VBZ and NBI-98782 Cmax and AUC parameters were also dose-proportional between the 50 and 100 mg doses. Steady-state for both analytes appeared to be achieved by Day 8. The accumulation index was ~1.5 for VBZ and ~2.5 for NBI-98782. Peak to trough fluctuation was approximately 250% for VBZ and 70% for NBI-98782. Across both studies, NBI-98782 exposure was approximately 20%–30% that of VBZ based on molar ratios. In the first study, the maximum-tolerated dose was not achieved; headache (2 events) was the only treatment-emergent adverse event (TEAE) reported by more than one subject. In the second study, fatigue (4 events) was the only TEAE reported by more than one subject following SD VBZ. Following QD VBZ, the TEAEs of fatigue, insomnia, disturbance in attention, and nervousness were dose-dependent; the latter three TEAEs were considered dose-limiting. Subject withdrawals due to TEAEs were 1 each for PBO and 50 mg VBZ QD, and 3 for 100 mg VBZ QD. Clinically relevant effects on laboratory parameters, vital signs or ECGs were limited to increased CPK (SD: 1 each for 5 mg VBZ and PBO), ALT (QD: 1 each for 50 and 100 mg VBZ and PBO), and triglycerides (QD: 1 each for 50 mg VBZ and PBO). VBZ has an acceptable safety profile and predictable pharmacokinetics that result in stable concentrations of active compounds with low peak-to-trough fluctuation following once-daily dosing. PMID:28839339

Negative transfer effects between reference memory and working memory training in the water maze in C57BL/6 mice.

PubMed

Serrano Sponton, Lucas Ezequiel; Soria, Gonzalo Jose; Dubroqua, Sylvain; Singer, Philipp; Feldon, Joram; Gargiulo, Pascual A; Yee, Benjamin K

2018-02-26

The water maze is one of the most widely employed spatial learning paradigms in the cognitive profiling of genetically modified mice. Oftentimes, tests of reference memory (RM) and working memory (WM) in the water maze are sequentially evaluated in the same animals. However, critical difference in the rules governing efficient escape from the water between WM and RM tests is expected to promote the adoption of incompatible mnemonic or navigational strategies. Hence, performance in a given test is likely poorer if it follows the other test instead of being conducted first. Yet, the presence of such negative transfer effects (or proactive interference) between WM and RM training in the water maze is often overlooked in the literature. To gauge whether this constitutes a serious concern, the present study determined empirically the magnitude, persistence, and directionality of the transfer effect in wild-type C57BL/6 mice. We contrasted the order of tests between two cohorts of mice. Performance between the two cohorts in the WM and RM tests were then separately compared. We showed that prior training of either test significantly reduced performance in the subsequent one. The statistical effect sizes in both directions were moderate to large. Although extended training could overcome the deficit, it could re-emerge later albeit in a more transient fashion. Whenever RM and WM water maze tests are conducted sequentially in the same animals - regardless of the test order, extra caution is necessary when interpreting the outcomes in the second test. Counterbalancing test orders between animals is recommended. Copyright © 2017 Elsevier B.V. All rights reserved.

Colorectal cancer mortality trends in Córdoba, Argentina.

PubMed

Pou, Sonia Alejandra; Osella, Alberto Rubén; Eynard, Aldo Renato; Niclis, Camila; Diaz, María del Pilar

2009-12-01

Colorectal cancer is a leading cause of death worldwide for men and women, and one of the most commonly diagnosed in Córdoba, Argentina. The aim of this work was to provide an up-to-date approach to descriptive epidemiology of colorectal cancer in Córdoba throughout the estimation of mortality trends in the period 1986-2006, using Joinpoint and age-period-cohort (APC) models. Age-standardized (world population) mortality rates (ASMR), overall and truncated (35-64 years), were calculated and Joinpoint regression performed to compute the estimated annual percentage changes (EAPC). Poisson sequential models were fitted to estimate the effect of age (11 age groups), period (1986-1990, 1991-1995, 1996-2000 or 2001-2006) and cohort (13 ten-years cohorts overlapping each other by five-years) on colorectal cancer mortality rates. ASMR showed an overall significant decrease (EAPC -0.9 95%CI: -1.7, -0.2) for women, being more noticeable from 1996 onwards (EAPC -2.1 95%CI: -4.0, -0.1). Age-effect showed an important rise in both sexes, but more evident in males. Birth cohort- and period effects reflected increasing and decreasing tendencies for men and women, respectively. Differences in mortality rates were found according to sex and could be related to age-period-cohort effects linked to the ageing process, health care and lifestyle. Further research is needed to elucidate the specific age-, period- and cohort-related factors.

TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets

PubMed Central

Yeung, David T.; Osborn, Michael P.; White, Deborah L.; Branford, Susan; Braley, Jodi; Herschtal, Alan; Kornhauser, Michael; Issa, Samar; Hiwase, Devendra K.; Hertzberg, Mark; Schwarer, Anthony P.; Filshie, Robin; Arthur, Christopher K.; Kwan, Yiu Lam; Trotman, Judith; Forsyth, Cecily J.; Taper, John; Ross, David M.; Beresford, Jennifer; Tam, Constantine; Mills, Anthony K.; Grigg, Andrew P.

2015-01-01

The Therapeutic Intensification in De Novo Leukaemia (TIDEL)-II study enrolled 210 patients with chronic phase chronic myeloid leukemia (CML) in two equal, sequential cohorts. All started treatment with imatinib 600 mg/day. Imatinib plasma trough level was performed at day 22 and if <1000 ng/mL, imatinib 800 mg/day was given. Patients were then assessed against molecular targets: BCR-ABL1 ≤10%, ≤1%, and ≤0.1% at 3, 6, and 12 months, respectively. Cohort 1 patients failing any target escalated to imatinib 800 mg/day, and subsequently switched to nilotinib 400 mg twice daily for failing the same target 3 months later. Cohort 2 patients failing any target switched to nilotinib directly, as did patients with intolerance or loss of response in either cohort. At 2 years, 55% of patients remained on imatinib, and 30% on nilotinib. Only 12% were >10% BCR-ABL1 at 3 months. Confirmed major molecular response was achieved in 64% at 12 months and 73% at 24 months. MR4.5 (BCR-ABL1 ≤0.0032%) at 24 months was 34%. Overall survival was 96% and transformation-free survival was 95% at 3 years. This trial supports the feasibility and efficacy of an imatinib-based approach with selective, early switching to nilotinib. This trial was registered at www.anzctr.org.au as #12607000325404. PMID:25519749

Progression-Free and Overall Survival in ALK-Positive NSCLC Patients Treated with Sequential Crizotinib and Ceritinib.

PubMed

Gainor, Justin F; Tan, Daniel S W; De Pas, Tomasso; Solomon, Benjamin J; Ahmad, Aziah; Lazzari, Chiara; de Marinis, Filippo; Spitaleri, Gianluca; Schultz, Katherine; Friboulet, Luc; Yeap, Beow Y; Engelman, Jeffrey A; Shaw, Alice T

2015-06-15

Anaplastic lymphoma kinase (ALK) rearrangements are important therapeutic targets in non-small cell lung cancer (NSCLC) that confer sensitivity to the ALK inhibitors crizotinib and ceritinib. To determine the outcome of sequential treatment with crizotinb and ceritinib, we retrospectively evaluated a cohort of ALK-positive patients treated with both agents. We identified 73 ALK-positive NSCLC patients treated with crizotinib followed by ceritinib at four institutions. Medical records were reviewed to determine overall survival (OS) and progression-free survival (PFS) on crizotinib and ceritinib. Among 73 ALK-positive patients, the median PFS (mPFS) on crizotinib was 8.2 months [95% confidence interval (CI), 7.4-10.6]. The median interval from crizotinib discontinuation to initiation of ceritinib was 25 days (range, 1-694). The mPFS on ceritinib was 7.8 months (6.5-9.1). Among 53 patients with no interval therapies between crizotinib and ceritinib, the mPFS on ceritinib was similar at 7.8 months (5.4-9.8). The median combined PFS for sequential treatment with crizotinib and ceritinib was 17.4 months (15.5-19.4). Among 23 patients who underwent post-crizotinib/pre-ceritinib biopsies, there was no difference in PFS on ceritinib between patients with or without ALK resistance mutations (mPFS 5.8 vs. 6.5 months, respectively; P = 0.510). In the overall study population, median OS was 49.4 months (35.5-63.1). Ceritinib has significant antitumor activity in ALK-positive NSCLC-even when crizotinib immediately precedes treatment with ceritinib (median combined PFS 17.0 months). Additional studies are necessary to further define the impact of specific ALK resistance mutations on duration of response to ceritinib. ©2015 American Association for Cancer Research.

Relevant factors for the optimal duration of extended endocrine therapy in early breast cancer.

PubMed

Blok, Erik J; Kroep, Judith R; Meershoek-Klein Kranenbarg, Elma; Duijm-de Carpentier, Marjolijn; Putter, Hein; Liefers, Gerrit-Jan; Nortier, Johan W R; Rutgers, Emiel J Th; Seynaeve, Caroline M; van de Velde, Cornelis J H

2018-04-01

For postmenopausal patients with hormone receptor-positive early breast cancer, the optimal subgroup and duration of extended endocrine therapy is not clear yet. The aim of this study using the IDEAL patient cohort was to identify a subgroup for which longer (5 years) extended therapy is beneficial over shorter (2.5 years) extended endocrine therapy. In the IDEAL trial, 1824 patients who completed 5 years of adjuvant endocrine therapy (either 5 years of tamoxifen (12%), 5 years of an AI (29%), or a sequential strategy of both (59%)) were randomized between either 2.5 or 5 years of extended letrozole. For each prior therapy subgroup, the value of longer therapy was assessed for both node-negative and node-positive patients using Kaplan Meier and Cox regression survival analyses. In node-positive patients, there was a significant benefit of 5 years (over 2.5 years) of extended therapy (disease-free survival (DFS) HR 0.67, p = 0.03, 95% CI 0.47-0.96). This effect was only observed in patients who were treated initially with a sequential scheme (DFS HR 0.60, p = 0.03, 95% CI 0.38-0.95). In all other subgroups, there was no significant benefit of longer extended therapy. Similar results were found in patients who were randomized for their initial adjuvant therapy in the TEAM trial (DFS HR 0.37, p = 0.07, 95% CI 0.13-1.06), although this additional analysis was underpowered for definite conclusions. This study suggests that node-positive patients could benefit from longer extended endocrine therapy, although this effect appears isolated to patients treated with sequential endocrine therapy during the first 5 years and needs validation and long-term follow-up.

Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: A promising treatment approach

PubMed Central

Fischer, Monika; Phelps, Emmalee; Rogers, Nicholas; Sagi, Sashidhar; Bohm, Matthew; Xu, Huiping; Kassam, Zain

2017-01-01

ABSTRACT Severe and severe-complicated Clostridium difficile infection (CDI) is associated with high morbidity and mortality. Colectomy is standard of care; however, post-surgical mortality rates approach 50%. Case reports suggest fecal microbiota transplant (FMT) is a promising treatment of severe and severe-complicated disease but there is a paucity of data. Here, we present a single center experience with a novel sequential FMT protocol for patients refractory to maximal medical therapy. This approach consists of at least one FMT delivered via colonoscopy with criteria for repeat FMT and continued vancomycin therapy based on clinical response and pseudomembranes. Our cohort included 57 consecutive inpatients diagnosed with severe or severe-complicated CDI and treated with FMT. Overall, 91% (52/57) experienced clinical cure at 1 month with a 100% cure rate among severe CDI (n = 19) patients and an 87% cure rate for severe-complicated CDI (n = 33) patients. For the cohort, the survival rate was 94.7% at 1 month and 78.6% at 3 months. There were no serious adverse events related to FMT including no procedure-related complications or perforation. There was no difference in outcome between fresh or frozen fecal material. Sequential FMT for inpatients with severe or severe-complicated CDI is promising and may be preferred over colectomy in certain patients. PMID:28001467

Real view radiology-impact on search patterns and confidence in radiology education.

PubMed

Bailey, Jared H; Roth, Trenton D; Kohli, Mark D; Heitkamp, Darel E

2014-07-01

Search patterns are important for radiologists because they enable systematic case review. Because radiology residents are exposed to so many imaging modalities and anatomic regions, and they rotate on-and-off service so frequently, they may have difficulty establishing effective search patterns. We developed Real View Radiology (RVR), an educational system founded on guided magnetic resonance imaging (MRI) case review and evaluated its impact on search patterns and interpretative confidence of junior radiology residents. RVR guides learners through unknown examinations by sequentially prompting learners to certain aspects of a case via a comprehensive question set and then providing immediate feedback. Junior residents first completed a brief evaluation regarding their level of confidence when interpreting certain joint MRI cases and frequency of search pattern use. They spent four half-days interpreting cases using RVR. Once finished, they repeated the evaluations. The junior resident results were compared to third-year residents who had not used RVR. The data were analyzed for change in confidence, use of search patterns, and number of cases completed. Twelve first-year and thirteen second-year residents (trained cohort) were enrolled in the study. During their 4-week musculoskeletal rotations, they completed on average 29.3 MRI knee (standard deviation [SD], 1.6) and 17.4 shoulder (SD, 1.2) cases using RVR. Overall search pattern scores of the trained cohort increased significantly both from pretraining to posttraining (knee P < .01, shoulder P < .01) and compared to the untrained third-year residents (knee (P < .01, and shoulder P < .01). The trained cohort confidence scores also increased significantly from pre to post for all joints (knee P < .01, shoulder P < .01, pelvis P < .01, and ankle P < .01). Radiology residents can increase their MRI case interpretation confidence and improve the consistency of search pattern use by training with a question-based sequential reveal educational program. RVR could be used to supplement training and assist with search pattern creation in areas in which residents often do not acquire adequate clinical exposure. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Safety, Tolerability, and Pharmacokinetics of Therapeutic and Supratherapeutic Doses of Tramadol Hydrochloride in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Multiple-Ascending-Dose Study.

PubMed

DeLemos, Byron; Richards, Henry M; Vandenbossche, Joris; Ariyawansa, Jay; Natarajan, Jaya; Alexander, Binu; Ramakrishna, Tage; Murtaugh, Thomas; Stahlberg, Hans-Jürgen

2017-11-01

This randomized, double-blind, parallel-group multiple-ascending-dose study evaluated the safety, tolerability, and pharmacokinetics of tramadol hydrochloride in healthy adults to inform dosage and design for a subsequent QT/QTc study. Healthy men and women, 18 to 45 years old (inclusive), were sequentially assigned to the tramadol 200, 400, or 600 mg/day treatment cohort and within each cohort, randomized (4:1) to either tramadol or placebo every 6 hours for 9 oral doses. Of the 24 participants randomized to tramadol (n = 8/cohort), 22 (91.7%) completed the study. The AUC tau,ss of tramadol increased approximately 2.2- and 3.6-fold for the (+) enantiomer and 2.0- and 3.5-fold for the (-) enantiomer with increasing dose from 200 to 400  and 600 mg/day, whereas the C max,ss increased 2.1- and 3.3-fold for the (+) enantiomer and 2.0- and 3.2-fold for the (-) enantiomer. Overall, 21 participants (87.5%) participants reported ≥1 treatment-emergent adverse event; most frequent were nausea (17 of 24, 70.8%) and vomiting (7 of 24, 29.2%). Vomiting (affected participants and events) increased with increasing dose from 200 to 600 mg/day but was mild (5 of 24) or moderate (2 of 24) in severity. All tested dosage regimens of tramadol showed acceptable safety and tolerability profile for further investigation in a thorough QT/QTc study. © 2017, The American College of Clinical Pharmacology.

A risk-adapted protocol for delayed administration of filgrastim after high-dose chemotherapy and autologous stem cell transplantation.

PubMed

Khot, Amit; Dickinson, Michael; Stokes, Kerrie; Harrison, Simon; Burbury, Kate; Fleming, Shaun; Wall, Dominic; Gambell, Peter; Prince, H Miles; Seymour, John F; Ritchie, David

2013-02-01

The routine use of recombinant human granulocyte-colony stimulating factor (rhG-CSF) after high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) is associated with increased costs. We prospectively explored a strategy that used prophylactic delayed filgrastim only in patients with risk factors. This sequential cohort analysis compared the outcomes of consecutive patients, treated on the risk-adapted protocol (RAP) (risk factors: prior febrile neutropenia; age >60 years; and CD34+ cell infused dose of <2 × 10(6/)/kg), who received filgrastim from day +6 after auto-SCT with a historical cohort (historical day-1 cohort [HD1]), who received filgrastim from day +1. Eighty-two patients were treated in the RAP cohort and compared with 115 patients in the HD1 cohort. There were no differences in median age (55 years) or median CD34+ cell dose (5.21 × 10(6)/kg [range, 2-62.2 × 10(6)/kg] vs. 5.24 × 10(6)/kg [range, 2.4-29.8 × 10(6)/kg]). Filgrastim was used for 6 fewer days in the RAP cohort (median 5 days [range, 0-11 days] vs. 11 days [range, 9-47 days]). There was a small absolute but significant difference in median time to neutrophil recovery in the HD1 cohort for the whole group, 10 days (range, 8-46 days) vs. 11 days (range, 9-22 days) (P = .03) and in patients with myeloma; 10 days (range, 9-14 days) vs. 11 days (range, 9-18 days) (P < .0001) as compared to the RAP cohort. There was no difference in median inpatient duration, 13 days (range, 10-26 days) vs. 12 days (range, 1-38 days) (P = .22) and 3-year survival (79% vs. 83% [P = .43]) between HD1 and RAP cohorts respectively. The use of a RAP to identify patients likely to benefit from prophylactic filgrastim is safe and results in cost savings. Patients with myeloma benefit from earlier introduction of filgrastim in terms of neutrophil recovery; this disease-specific observation is an important consideration for future studies. Copyright © 2013 Elsevier Inc. All rights reserved.

A dose-finding and safety study of novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia in patients receiving multicycle chemotherapy

PubMed Central

Glaspy, J; Jadeja, J Singh; Justice, G; Kessler, J; Richards, D; Schwartzberg, L; Rigas, J; Kuter, D; Harmon, D; Prow, D; Demetri, G; Gordon, D; Arseneau, J; Saven, A; Hynes, H; Boccia, R; O'Byrne, J; Colowick, A B

2001-01-01

Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from rHuEPO, due to its increased sialic acid content. NESP has an approximately 3-fold greater half-life. rHuEPO has been shown to be safe and effective for the treatment of chemotherapy-induced anaemia. This study assessed the safety and efficacy of NESP administered once per week, under the supervision of a physician, to patients with solid tumours who were receiving multicycle chemotherapy for up to 12 weeks. Three dose cohorts are presented in this sequential, unblinded and dose-escalating study. Thirteen to 59 patients received NESP (0.5, 1.5 or 2.25 mcg kg−1wk−1) in each cohort. Patients were monitored for adverse events, including antibody formation to NESP and for effects on haemoglobin. NESP appeared to be well tolerated. Adverse events were similar across all cohorts and were consistent with the population being studied. No antibody formation was detected over the 16-week study period and follow-up. A dose–response relationship was evident for NESP and multiple measures of efficacy, including proportion of patients responding to NESP and the mean change in haemoglobin by week 4 and end of treatment for NESP 0.5, 1.5 and 2.25 mcg kg−1wk−1cohorts (mean change in haemoglobin at end of treatment was 1.24, 1.73 and 2.15 g dl−1respectively). Controlled studies of this agent at higher doses and less frequent schedules of administration are ongoing. © 2001 Cance Cancer Research Campaign PMID:11308270

Pharmacokinetics of surotomycin from phase 1 single and multiple ascending dose studies in healthy volunteers.

PubMed

Chandorkar, Gurudatt; Zhan, Qiao; Donovan, Julie; Rege, Shruta; Patino, Hernando

2017-03-28

Surotomycin, a novel, orally administered, cyclic, lipopeptide antibacterial in development for the treatment of Clostridium difficile-associated diarrhea, has demonstrated minimal intestinal absorption in animal models. Safety, tolerability, and plasma pharmacokinetics of single and multiple ascending oral doses (SAD/MAD) of surotomycin in healthy volunteers were characterized in two randomized, double-blind, placebo-controlled, phase 1 studies. Participants were sequentially enrolled into one of four SAD (500, 1000, 2000, 4000 mg surotomycin) or three MAD (250, 500, 1000 mg surotomycin twice/day for 14 days) cohorts. Ten subjects were randomized 4:1 into each cohort to receive surotomycin or placebo. Surotomycin plasma concentrations rose as dose increased (maximum plasma concentration [C max ]: 10.5, 21.5, 66.6, and 86.7 ng/mL). Systemic levels were generally low, with peak median surotomycin plasma concentrations observed 6-12 h after the first dose. In the MAD study, surotomycin plasma concentrations were higher on day 14 (C max : 25.5, 37.6, and 93.5 ng/mL) than on day 1 (C max : 6.8, 11.0, and 21.1 ng/mL for increasing doses), indicating accumulation. In the SAD study, <0.01% of the administered dose was recovered in urine. Mean surotomycin stool concentration from the 1000 mg MAD cohort was 6394 μg/g on day 5. Both cohorts were well tolerated with all adverse events reported as mild to moderate. Both SAD and MAD studies of surotomycin demonstrated minimal systemic exposure, with feces the primary route of elimination following oral administration; consistent with observations with similar compounds, such as fidaxomicin. Results of these phase 1 studies support the continued clinical development of surotomycin for the treatment of Clostridium difficile-associated diarrhea. NCT02835118 and NCT02835105 . Retrospectively registered, July 13 2016.

Cardiovascular mortality sex differentials in selected East Asian and Western populations.

PubMed

Zhao, Jiaying; Booth, Heather; Dear, Keith; Tu, Edward Jow-Ching

2016-10-01

Explaining patterns in the sex ratio (male/female) of cardiovascular disease (CVD) mortality would improve understanding of mortality transitions under modernisation. Little research has examined secular trends in this ratio across populations, taking age and cohort into account. We examine cohort effects in the ratios of CVD mortality (including ischaemic heart disease and cerebrovascular disease) among 4 East Asian populations that vary in the timing of their modernisation, and assess the effect of smoking on these patterns in comparison with Western populations. The sequential method for log-linear models is applied to analyse age, period and cohort effects for sex ratios. Age and cohort effects are fitted first, with population as offset; period effects are fitted in a second model using the fitted values from the first model as the offset. Lung cancer mortality serves as a proxy for smoking. Increases in sex ratios of CVD mortality began in earlier cohorts in Western than in East Asian populations. Once begun, increases were more rapid in East Asia. The cohort effect for the sex ratio of CVD mortality differs from that for lung cancer mortality. Trends in sex ratios of CVD mortality by cohort are similar before and after adjustment for lung cancer mortality in East Asia; the increasing trend across 1900-1945 cohorts is maintained in Western populations after adjustment. The sex ratio of CVD mortality has increased across successive cohorts living in increasingly modernised environments. There is scant evidence that this increase is attributable to changing sex-specific rates of smoking. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

NY-ESO-1 Protein Cancer Vaccine With Poly-ICLC and OK-432: Rapid and Strong Induction of NY-ESO-1-specific Immune Responses by Poly-ICLC.

PubMed

Takeoka, Tomohira; Nagase, Hirotsugu; Kurose, Koji; Ohue, Yoshihiro; Yamasaki, Makoto; Takiguchi, Shuji; Sato, Eiichi; Isobe, Midori; Kanazawa, Takayuki; Matsumoto, Mitsunobu; Iwahori, Kota; Kawashima, Atsunari; Morimoto-Okazawa, Akiko; Nishikawa, Hiroyoshi; Oka, Mikio; Pan, Linda; Venhaus, Ralph; Nakayama, Eiichi; Mori, Masaki; Doki, Yuichiro; Wada, Hisashi

2017-03-23

We conducted a clinical trial of a cancer vaccine using NY-ESO-1 protein with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) and/or OK-432 against solid tumors. A total of 15 patients were sequentially enrolled in 4 cohorts. Patients in cohort 1 received NY-ESO-1 protein; cohort 2a received NY-ESO-1 protein+OK-432; cohort 2b received NY-ESO-1 protein+poly-ICLC; cohort 3 received NY-ESO-1 protein+OK-432+poly-ICLC with Montanide ISA-51. The endpoints of this trial were safety, NY-ESO-1 immune responses, and clinical response. Vaccine-related adverse events observed were fever and injection-site reaction (grade 1). Two patients showed stable disease after vaccination. NY-ESO-1 antibodies were observed in 4 patients at the baseline (sero-positive) and augmented in all patients after vaccination. Eleven patients showed a conversion of negative antibody responses at baseline to positive after vaccination (seroconversion). The seroconversions were observed in all 11 sero-negative patients by the fourth immunization; in particular, it was observed by the second immunization in patients with poly-ICLC, and these induced antibody responses were stronger than those in patients immunized without poly-ICLC. The number of NY-ESO-1-specific interferon (IFN)γ-producing T cells was increased in patients immunized with poly-ICLC and/or OK-432, and furthermore, the increase of IFNγ-producing CD8 T cells in patients immunized with poly-ICLC was significantly higher than that in patients without poly-ICLC. Nonspecific activations of T-cell or antigen presenting cells were not observed. Our present study showed that poly-ICLC is a promising adjuvant for cancer vaccines.

Does Everyone's Motivational Beliefs about Physical Science Decline in Secondary School?: Heterogeneity of Adolescents' Achievement Motivation Trajectories in Physics and Chemistry.

PubMed

Wang, Ming-Te; Chow, Angela; Degol, Jessica Lauren; Eccles, Jacquelynne Sue

2017-08-01

Students' motivational beliefs about learning physical science are critical for achieving positive educational outcomes. In this study, we incorporated expectancy-value theory to capture the heterogeneity of adolescents' motivational trajectories in physics and chemistry from seventh to twelfth grade and linked these trajectories to science-related outcomes. We used a cross-sequential design based on three different cohorts of adolescents (N = 699; 51.5 % female; 95 % European American; M ages for youngest, middle, and oldest cohorts at the first wave = 13.2, 14.1, and 15.3 years) coming from ten public secondary schools. Although many studies claim that physical science motivation declines on average over time, we identified seven differential motivational trajectories of ability self-concept and task values, and found associations of these trajectories with science achievement, advanced science course taking, and science career aspirations. Adolescents' ability self-concept and task values in physics and chemistry were also positively related and interlinked over time. Examining how students' motivational beliefs about physical science develop in secondary school offers insight into the capacity of different groups of students to successfully adapt to their changing educational environments.

Who Wants to Play? Sport Motivation Trajectories, Sport Participation, and the Development of Depressive Symptoms.

PubMed

Wang, Ming-Te; Chow, Angela; Amemiya, Jamie

2017-09-01

Although sport involvement has the potential to enhance psychological wellbeing, studies have suggested that motivation to participate in sports activities declines across childhood and adolescence. This study incorporated expectancy-value theory to model children's sport ability self-concept and subjective task values trajectories from first to twelfth grade. Additionally, it examined if sport motivation trajectories predicted individual and team-based sport participation and whether sport participation in turn reduced the development of depressive symptoms. Data were drawn from the Childhood and Beyond Study, a cross-sequential longitudinal study comprised of three cohorts (N = 1065; 49% male; 92% European American; M ages for youngest, middle, and oldest cohorts at the first wave were 6.42, 7.39, and 9.36 years, respectively). Results revealed four trajectories of students' co-development of sport self-concept and task values: congruent stable high, incongruent stable high, middle school decreasing, and decreasing. Trajectory membership predicted individual and team-based sports participation, but only team-based sport participation predicted faster declines in depressive symptoms. The use of a person-centered approach enabled us to identify heterogeneity in trajectories of sport motivation that can aid in the development of nuanced strategies to increase students' motivation to participate in sports.

Comparison of Statistical Approaches for Dealing With Immortal Time Bias in Drug Effectiveness Studies

PubMed Central

Karim, Mohammad Ehsanul; Gustafson, Paul; Petkau, John; Tremlett, Helen

2016-01-01

In time-to-event analyses of observational studies of drug effectiveness, incorrect handling of the period between cohort entry and first treatment exposure during follow-up may result in immortal time bias. This bias can be eliminated by acknowledging a change in treatment exposure status with time-dependent analyses, such as fitting a time-dependent Cox model. The prescription time-distribution matching (PTDM) method has been proposed as a simpler approach for controlling immortal time bias. Using simulation studies and theoretical quantification of bias, we compared the performance of the PTDM approach with that of the time-dependent Cox model in the presence of immortal time. Both assessments revealed that the PTDM approach did not adequately address immortal time bias. Based on our simulation results, another recently proposed observational data analysis technique, the sequential Cox approach, was found to be more useful than the PTDM approach (Cox: bias = −0.002, mean squared error = 0.025; PTDM: bias = −1.411, mean squared error = 2.011). We applied these approaches to investigate the association of β-interferon treatment with delaying disability progression in a multiple sclerosis cohort in British Columbia, Canada (Long-Term Benefits and Adverse Effects of Beta-Interferon for Multiple Sclerosis (BeAMS) Study, 1995–2008). PMID:27455963

Sequential organ failure assessment (SOFA) scores differ between genders in a sepsis cohort: cause or effect?

PubMed

Jacobson, Sofie; Liedgren, Eva; Johansson, Göran; Ferm, Martin; Winsö, Ola

2012-11-01

Controversy exists regarding the influence of gender on sepsis events and outcome. Epidemiological data from other countries may not always apply to local circumstances. The aim of this study was to identify gender differences in patient characteristics, treatment, and outcome related to the occurrence of sepsis at admission to the ICU. A prospective observational cohort study on patients admitted to the ICU over a 3-year period fulfilling sepsis criteria during the first 24 hours. Demographic data, APACHE II score, SOFA score, TISS 76, aetiology, length of stay (LOS), mortality rate, and aspects of treatment were collected and then analysed with respect to gender differences. There were no gender-related differences in mortality or length of stay. Early organ dysfunction assessed as SOFA score at admission was a stronger risk factor for hospital mortality for women than for men. This discrepancy was mainly associated with the coagulation sub-score. CRP levels differed between genders in relation to hospital mortality. Infection from the abdominopelvic region was more common among women, whereas infection from skin or skin structures were more common in men. In this cohort, gender was not associated with increased mortality during a 2-year follow-up period. SOFA score at ICU admission was a stronger risk factor for hospital mortality for women than for men. The discrepancy was mainly related to the coagulation SOFA sub-score. Together with differences in CRP levels this may suggest differences in inflammatory response patterns between genders.

Derivation and Validation of a Biomarker-Based Clinical Algorithm to Rule Out Sepsis From Noninfectious Systemic Inflammatory Response Syndrome at Emergency Department Admission: A Multicenter Prospective Study.

PubMed

Mearelli, Filippo; Fiotti, Nicola; Giansante, Carlo; Casarsa, Chiara; Orso, Daniele; De Helmersen, Marco; Altamura, Nicola; Ruscio, Maurizio; Castello, Luigi Mario; Colonetti, Efrem; Marino, Rossella; Barbati, Giulia; Bregnocchi, Andrea; Ronco, Claudio; Lupia, Enrico; Montrucchio, Giuseppe; Muiesan, Maria Lorenza; Di Somma, Salvatore; Avanzi, Gian Carlo; Biolo, Gianni

2018-05-07

To derive and validate a predictive algorithm integrating a nomogram-based prediction of the pretest probability of infection with a panel of serum biomarkers, which could robustly differentiate sepsis/septic shock from noninfectious systemic inflammatory response syndrome. Multicenter prospective study. At emergency department admission in five University hospitals. Nine-hundred forty-seven adults in inception cohort and 185 adults in validation cohort. None. A nomogram, including age, Sequential Organ Failure Assessment score, recent antimicrobial therapy, hyperthermia, leukocytosis, and high C-reactive protein values, was built in order to take data from 716 infected patients and 120 patients with noninfectious systemic inflammatory response syndrome to predict pretest probability of infection. Then, the best combination of procalcitonin, soluble phospholypase A2 group IIA, presepsin, soluble interleukin-2 receptor α, and soluble triggering receptor expressed on myeloid cell-1 was applied in order to categorize patients as "likely" or "unlikely" to be infected. The predictive algorithm required only procalcitonin backed up with soluble phospholypase A2 group IIA determined in 29% of the patients to rule out sepsis/septic shock with a negative predictive value of 93%. In a validation cohort of 158 patients, predictive algorithm reached 100% of negative predictive value requiring biomarker measurements in 18% of the population. We have developed and validated a high-performing, reproducible, and parsimonious algorithm to assist emergency department physicians in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome.

Development of a novel score for the prediction of hospital mortality in patients with severe sepsis: the use of electronic healthcare records with LASSO regression.

PubMed

Zhang, Zhongheng; Hong, Yucai

2017-07-25

There are several disease severity scores being used for the prediction of mortality in critically ill patients. However, none of them was developed and validated specifically for patients with severe sepsis. The present study aimed to develop a novel prediction score for severe sepsis. A total of 3206 patients with severe sepsis were enrolled, including 1054 non-survivors and 2152 survivors. The LASSO score showed the best discrimination (area under curve: 0.772; 95% confidence interval: 0.735-0.810) in the validation cohort as compared with other scores such as simplified acute physiology score II, acute physiological score III, Logistic organ dysfunction system, sequential organ failure assessment score, and Oxford Acute Severity of Illness Score. The calibration slope was 0.889 and Brier value was 0.173. The study employed a single center database called Medical Information Mart for Intensive Care-III) MIMIC-III for analysis. Severe sepsis was defined as infection and acute organ dysfunction. Clinical and laboratory variables used in clinical routines were included for screening. Subjects without missing values were included, and the whole dataset was split into training and validation cohorts. The score was coined LASSO score because variable selection was performed using the least absolute shrinkage and selection operator (LASSO) technique. Finally, the LASSO score was evaluated for its discrimination and calibration in the validation cohort. The study developed the LASSO score for mortality prediction in patients with severe sepsis. Although the score had good discrimination and calibration in a randomly selected subsample, external validations are still required.

Reliability of semiautomated computational methods for estimating tibiofemoral contact stress in the Multicenter Osteoarthritis Study.

PubMed

Anderson, Donald D; Segal, Neil A; Kern, Andrew M; Nevitt, Michael C; Torner, James C; Lynch, John A

2012-01-01

Recent findings suggest that contact stress is a potent predictor of subsequent symptomatic osteoarthritis development in the knee. However, much larger numbers of knees (likely on the order of hundreds, if not thousands) need to be reliably analyzed to achieve the statistical power necessary to clarify this relationship. This study assessed the reliability of new semiautomated computational methods for estimating contact stress in knees from large population-based cohorts. Ten knees of subjects from the Multicenter Osteoarthritis Study were included. Bone surfaces were manually segmented from sequential 1.0 Tesla magnetic resonance imaging slices by three individuals on two nonconsecutive days. Four individuals then registered the resulting bone surfaces to corresponding bone edges on weight-bearing radiographs, using a semi-automated algorithm. Discrete element analysis methods were used to estimate contact stress distributions for each knee. Segmentation and registration reliabilities (day-to-day and interrater) for peak and mean medial and lateral tibiofemoral contact stress were assessed with Shrout-Fleiss intraclass correlation coefficients (ICCs). The segmentation and registration steps of the modeling approach were found to have excellent day-to-day (ICC 0.93-0.99) and good inter-rater reliability (0.84-0.97). This approach for estimating compartment-specific tibiofemoral contact stress appears to be sufficiently reliable for use in large population-based cohorts.

Bipolar polygenic loading and bipolar spectrum features in major depressive disorder

PubMed Central

Wiste, Anna; Robinson, Elise B; Milaneschi, Yuri; Meier, Sandra; Ripke, Stephan; Clements, Caitlin C; Fitzmaurice, Garrett M; Rietschel, Marcella; Penninx, Brenda W; Smoller, Jordan W; Perlis, Roy H

2014-01-01

Objectives Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of this study was to determine whether this shared genetic liability influences clinical presentation. Methods A polygenic risk score for bipolar disorder, derived from a large genome-wide association meta-analysis, was generated for each subject of European–American ancestry (n = 1,274) in the Sequential Treatment Alternatives to Relieve Depression study (STAR*D) outpatient major depressive disorder cohort. A hypothesis-driven approach was used to test for association between bipolar disorder risk score and features of depression associated with bipolar disorder in the literature. Follow-up analyses were performed in two additional cohorts. Results A generalized linear mixed model including seven features hypothesized to be associated with bipolar spectrum illness was significantly associated with bipolar polygenic risk score [F = 2.07, degrees of freedom (df) = 7, p = 0.04). Features included early onset, suicide attempt, recurrent depression, atypical depression, subclinical mania, subclinical psychosis, and severity. Post-hoc univariate analyses demonstrated that the major contributors to this omnibus association were onset of illness at age ≤ 18 years [odds ratio (OR) = 1.2, p = 0.003], history of suicide attempt (OR = 1.21, p = 0.03), and presence of at least one manic symptom (OR = 1.16, p = 0.02). The maximal variance in these traits explained by polygenic score ranged from 0.8–1.1%. However, analyses in two replication cohorts testing a five feature model did not support this association. Conclusions Bipolar genetic loading appeared to be associated with bipolar-like presentation in major depressive disorder in the primary analysis. However, results are at most inconclusive because of lack of replication. Replication efforts are challenged by different ascertainment and assessment strategies in the different cohorts. The methodological approach described here may prove useful in applying genetic data to clarify psychiatric nosology in future studies. PMID:24725193

Predicting the Necessity for Extracorporeal Circulation During Lung Transplantation: A Feasibility Study.

PubMed

Hinske, Ludwig Christian; Hoechter, Dominik Johannes; Schröeer, Eva; Kneidinger, Nikolaus; Schramm, René; Preissler, Gerhard; Tomasi, Roland; Sisic, Alma; Frey, Lorenz; von Dossow, Vera; Scheiermann, Patrick

2017-06-01

The factors leading to the implementation of unplanned extracorporeal circulation during lung transplantation are poorly defined. Consequently, the authors aimed to identify patients at risk for unplanned extracorporeal circulation during lung transplantation. Retrospective data analysis. Single-center university hospital. A development data set of 170 consecutive patients and an independent validation cohort of 52 patients undergoing lung transplantation. The authors investigated a cohort of 170 consecutive patients undergoing single or sequential bilateral lung transplantation without a priori indication for extracorporeal circulation and evaluated the predictive capability of distinct preoperative and intraoperative variables by using automated model building techniques at three clinically relevant time points (preoperatively, after endotracheal intubation, and after establishing single-lung ventilation). Preoperative mean pulmonary arterial pressure was the strongest predictor for unplanned extracorporeal circulation. A logistic regression model based on preoperative mean pulmonary arterial pressure and lung allocation score achieved an area under the receiver operating characteristic curve of 0.85. Consequently, the authors developed a novel 3-point scoring system based on preoperative mean pulmonary arterial pressure and lung allocation score, which identified patients at risk for unplanned extracorporeal circulation and validated this score in an independent cohort of 52 patients undergoing lung transplantation. The authors showed that patients at risk for unplanned extracorporeal circulation during lung transplantation could be identified by their novel 3-point score. Copyright © 2017 Elsevier Inc. All rights reserved.

Students' attitudes and perceptions of teaching and assessment of evidence-based practice in an occupational therapy professional Master's curriculum: a mixed methods study.

PubMed

Thomas, Aliki; Han, Lu; Osler, Brittony P; Turnbull, Emily A; Douglas, Erin

2017-03-27

Most health professions, including occupational therapy, have made the application of evidence-based practice a desired competency and professional responsibility. Despite the increasing emphasis on evidence-based practice for improving patient outcomes, there are numerous research-practice gaps in the health professions. In addition to efforts aimed at promoting evidence-based practice with clinicians, there is a strong impetus for university programs to design curricula that will support the development of the knowledge, attitudes, skills and behaviours associated with evidence-based practice. Though occupational therapy curricula in North America are becoming increasingly focused on evidence-based practice, research on students' attitudes towards evidence-based practice, their perceptions regarding the integration and impact of this content within the curricula, and the impact of the curriculum on their readiness for evidence-based practice is scarce. The present study examined occupational therapy students' perceptions towards the teaching and assessment of evidence-based practice within a professional master's curriculum and their self-efficacy for evidence-based practice. The study used a mixed methods explanatory sequential design. The quantitative phase included a cross-sectional questionnaire exploring attitudes towards evidence-based practice, perceptions of the teaching and assessment of evidence-based practice and evidence-based practice self-efficacy for four cohorts of students enrolled in the program and a cohort of new graduates. The questionnaire was followed by a focus group of senior students aimed at further exploring the quantitative findings. All student cohorts held favourable attitudes towards evidence-based practice; there was no difference across cohorts. There were significant differences with regards to perceptions of the teaching and assessment of evidence-based practice within the curriculum; junior cohorts and students with previous education had less favourable perceptions. Students' self-efficacy for evidence-based practice was significantly higher across cohorts. Four main themes emerged from the focus group data: (a) Having mixed feelings about the value of evidence-based practice (b) Barriers to the application of evidence-based practice; (c) Opposing worlds and (d) Vital and imperfect role of the curriculum. This study provides important data to support the design and revision of evidence-based practice curricula within professional rehabilitation programs.

Parenting and Trajectories of Children’s Maladaptive Behaviors: A 12-year Prospective Community Study

PubMed Central

Luyckx, Koen; Tildesley, Elizabeth A.; Soenens, Bart; Andrews, Judy A.; Hampson, Sarah E.; Peterson, Missy; Duriez, Bart

2011-01-01

This study investigated how parenting accounted for inter-individual differences in developmental trajectories of different child behaviors across childhood and adolescence. In a cohort sequential community sample of 1,049 children, latent class growth analysis was applied to three parent-reported dimensions (monitoring, positive parenting, inconsistent discipline) across 12 annual assessments (ages 6–18). Four longitudinal parenting styles (authoritative, authoritarian, indulgent, uninvolved) were differentiated on the basis of levels and rates of change in the constituent parenting dimensions. Multi-group analyses demonstrated that these parenting styles were differentially related to changes in parent- and child-reported measures of children’s alcohol and cigarette use, antisocial behavior, and internalizing symptoms, with the authoritative parenting class being related to the most optimal long-term development. Practical implications and future research suggestions are discussed. PMID:21534057

Lung Volume Measured during Sequential Swallowing in Healthy Young Adults

ERIC Educational Resources Information Center

Hegland, Karen Wheeler; Huber, Jessica E.; Pitts, Teresa; Davenport, Paul W.; Sapienza, Christine M.

2011-01-01

Purpose: Outcomes from studying the coordinative relationship between respiratory and swallow subsystems are inconsistent for sequential swallows, and the lung volume at the initiation of sequential swallowing remains undefined. The first goal of this study was to quantify the lung volume at initiation of sequential swallowing ingestion cycles and…

Improving Outcomes in Colorectal Surgery by Sequential Implementation of Multiple Standardized Care Programs.

PubMed

Keenan, Jeffrey E; Speicher, Paul J; Nussbaum, Daniel P; Adam, Mohamed Abdelgadir; Miller, Timothy E; Mantyh, Christopher R; Thacker, Julie K M

2015-08-01

The purpose of this study was to examine the impact of the sequential implementation of the enhanced recovery program (ERP) and surgical site infection bundle (SSIB) on short-term outcomes in colorectal surgery (CRS) to determine if the presence of multiple standardized care programs provides additive benefit. Institutional ACS-NSQIP data were used to identify patients who underwent elective CRS from September 2006 to March 2013. The cohort was stratified into 3 groups relative to implementation of the ERP (February 1, 2010) and SSIB (July 1, 2011). Unadjusted characteristics and 30-day outcomes were assessed, and inverse proportional weighting was then used to determine the adjusted effect of these programs. There were 787 patients included: 337, 165, and 285 in the pre-ERP/SSIB, post-ERP/pre-SSIB, and post-ERP/SSIB periods, respectively. After inverse probability weighting (IPW) adjustment, groups were balanced with respect to patient and procedural characteristics considered. Compared with the pre-ERP/SSIB group, the post-ERP/pre-SSIB group had significantly reduced length of hospitalization (8.3 vs 6.6 days, p = 0.01) but did not differ with respect to postoperative wound complications and sepsis. Subsequent introduction of the SSIB then resulted in a significant decrease in superficial SSI (16.1% vs 6.3%, p < 0.01) and postoperative sepsis (11.2% vs 1.8%, p < 0.01). Finally, inflation-adjusted mean hospital cost for a CRS admission fell from $31,926 in 2008 to $22,044 in 2013 (p < 0.01). Sequential implementation of the ERP and SSIB provided incremental improvements in CRS outcomes while controlling hospital costs, supporting their combined use as an effective strategy toward improving the quality of patient care. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Sequential Organ Failure Assessment (SOFA) scores differ between genders in a sepsis cohort: Cause or effect?

PubMed Central

Liedgren, Eva; Johansson, Göran; Ferm, Martin; Winsö, Ola

2012-01-01

Background. Controversy exists regarding the influence of gender on sepsis events and outcome. Epidemiological data from other countries may not always apply to local circumstances. The aim of this study was to identify gender differences in patient characteristics, treatment, and outcome related to the occurrence of sepsis at admission to the ICU. Methods. A prospective observational cohort study on patients admitted to the ICU over a 3-year period fulfilling sepsis criteria during the first 24 hours. Demographic data, APACHE II score, SOFA score, TISS 76, aetiology, length of stay (LOS), mortality rate, and aspects of treatment were collected and then analysed with respect to gender differences. Results. There were no gender-related differences in mortality or length of stay. Early organ dysfunction assessed as SOFA score at admission was a stronger risk factor for hospital mortality for women than for men. This discrepancy was mainly associated with the coagulation sub-score. CRP levels differed between genders in relation to hospital mortality. Infection from the abdominopelvic region was more common among women, whereas infection from skin or skin structures were more common in men. Conclusion. In this cohort, gender was not associated with increased mortality during a 2-year follow-up period. SOFA score at ICU admission was a stronger risk factor for hospital mortality for women than for men. The discrepancy was mainly related to the coagulation SOFA sub-score. Together with differences in CRP levels this may suggest differences in inflammatory response patterns between genders. PMID:22793786

Protocol for a prospective longitudinal study investigating the participation and educational trajectories of Australian students with autism

PubMed Central

Roberts, Jacqueline Margaret Anne; Adams, Dawn; Heussler, Helen; Keen, Deborah; Paynter, Jessica; Trembath, David; Westerveld, Marleen; Williams, Katrina

2018-01-01

Introduction Autism is associated with high cost to individuals, families, communities and government. Understanding educational and participation trajectories during the school years, and factors influencing these, is fundamental to reducing financial and personal costs. The primary aim of this study is to document the trajectories of Australian students with autism during their education. The secondary aim is to examine personal (eg, student skills) and environmental (eg, school setting) factors associated with differing trajectories and outcomes. Methods and analysis The cross-sequential longitudinal study will recruit two cohorts of 120 parents/caregivers of children with autism. Cohort 1 aged between 4 and 5 years and cohort 2 between 9 and 10 years to start the study. Information will be gathered from parents, teachers and school principals at six annual time points (T1 to T6). Parents will be emailed a link to an online initial questionnaire (T1) and then contacted annually and asked to complete either an extended questionnaire (T3, T5 and T6) or an abbreviated questionnaire (T2, T4). Where consent is given, the child’s current school will be contacted annually (T1 to T6) and teacher and school principal asked to complete questionnaires about the child and school. Parent and school questionnaires are comprised of questions about demographic and school factors that could influence trajectories and a battery of developmental and behavioural assessment tools designed to assess educational and participation trajectories and outcomes. Surveys will provide longitudinal data on educational and participation trajectories for children and adolescents with autism. In addition cross-sectional comparisons (within or between age groups) at each time point and cohort effects will be explored. Ethics and dissemination Ethics approvals have been granted for this study by all recruiting sites and universities in the project. Study findings will inform policy and practice to promote successful inclusion and participation of children with autism in education. Results will be disseminated through journal publication, conference and seminar presentation. PMID:29362247

Lack of financial barriers to pediatric cochlear implantation: impact of socioeconomic status on access and outcomes.

PubMed

Chang, David T; Ko, Alvin B; Murray, Gail S; Arnold, James E; Megerian, Cliff A

2010-07-01

(1) To analyze if socioeconomic status influences access to cochlear implantation in an environment with adequate Medicaid reimbursement. (2) To determine the impact of socioeconomic status on outcomes after unilateral cochlear implantation. Retrospective cohort study. University Hospitals Case Medical Center and Rainbow Babies and Children's Hospital (tertiary referral center), Cleveland, Ohio. Pediatric patients (age range, newborn to 18 years) who received unilateral cochlear implantation during the period 1996 to 2008. Access to cochlear implantation after referral to a cochlear implant center, postoperative complications, compliance with follow-up appointments, and access to sequential bilateral cochlear implantation. A total of 133 pediatric patients were included in this study; 64 were Medicaid-insured patients and 69 were privately insured patients. There was no statistical difference in the odds of initial cochlear implantation, age at referral, or age at implantation between the 2 groups. The odds of prelingual Medicaid-insured patients receiving sequential bilateral cochlear implantation was less than half that of the privately insured group (odds ratio [OR], 0.43; P = .03). The odds of complications in Medicaid-insured children were almost 5-fold greater than the odds for privately insured children (OR, 4.6; P = .03). There were 10 complications in 51 Medicaid-insured patients (19.6%) as opposed to 3 in 61 privately insured patients (4.9%). Medicaid-insured patients missed substantially more follow-up appointments overall (35% vs 23%) and more consecutive visits (1.9 vs 1.1) compared with privately insured patients. In an environment with adequate Medicaid reimbursement, eligible children have equal access to cochlear implantation, regardless of socioeconomic background. However, lower socioeconomic background is associated with higher rates of postoperative complications, worse follow-up compliance, and lower rates of sequential bilateral implantation, observed herein in Medicaid-insured patients. These findings present opportunities for cochlear implant centers to create programs to address such downstream disparities.

Serum antibodies in mares and foals to Actinobacillus equuli whole cells, outer membrane proteins, and Aqx toxin.

PubMed

Holyoak, G R; Smith, C M; Boyette, R; Montelongo, M; Wray, J H; Ayalew, S; Duggan, V E; Confer, A W

2007-08-15

Actinobacillus equuli is carried in the alimentary tract of mares and can cause severe septicemia of neonatal foals. A hemolytic subspecies, A. equuli subsp. haemolyticus, and a non-hemolytic subspecies, A. equuli subsp. equuli, have been identified. Hemolytic strains produce the RTX toxin Aqx. The purpose of this study was to demonstrate sequentially in two sets of mare-foal pairs antibodies to A. equuli whole bacterial cells, outer membrane proteins, and recombinant Aqx and to compare the transfer of antibodies to these antigens between mares and their foals. Two mare/foal sets of sera were evaluated. Cohort A consisted of 18 mare-foal pairs obtained in the spring of 2005. Cohort B consisted of 10 mare-foal pairs obtained in the spring of 2006. For both sets, mare and foal sera were obtained immediately after foaling and prior to nursing (time 0) as well as at 12 and 24h and daily thereafter for 7 days. For Cohort B, sera were also obtained 30 days after birth. At parturition all mares had detectable antibodies to A. equuli whole cells and outer membranes; however, of those mares, two in Cohort A had undetectable antibodies to Aqx and their foals likewise had undetectable anti-Aqx antibodies. Antibodies against whole cells, outer membrane proteins, and Aqx were readily transferred from mares to foals. In most cases, there were significant correlations (p<0.05) between antibodies against whole cells, outer membrane proteins, and Aqx in mares' sera at the time of parturition and foal sera 24 after birth. Antibodies against the three antigen preparations had declined insignificantly (p>0.05) by day 30.

A Molecular Host Response Assay to Discriminate Between Sepsis and Infection-Negative Systemic Inflammation in Critically Ill Patients: Discovery and Validation in Independent Cohorts

PubMed Central

McHugh, Leo; Seldon, Therese A.; Brandon, Roslyn A.; Kirk, James T.; Rapisarda, Antony; Sutherland, Allison J.; Presneill, Jeffrey J.; Venter, Deon J.; Lipman, Jeffrey; Thomas, Mervyn R.; Klein Klouwenberg, Peter M. C.; van Vught, Lonneke; Scicluna, Brendon; Bonten, Marc; Cremer, Olaf L.; Schultz, Marcus J.; van der Poll, Tom; Yager, Thomas D.; Brandon, Richard B.

2015-01-01

Background Systemic inflammation is a whole body reaction having an infection-positive (i.e., sepsis) or infection-negative origin. It is important to distinguish between these two etiologies early and accurately because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on peripheral blood RNAs could be discovered that would (1) determine which patients with systemic inflammation had sepsis, (2) be robust across independent patient cohorts, (3) be insensitive to disease severity, and (4) provide diagnostic utility. The goal of this study was to identify and validate such a molecular classifier. Methods and Findings We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICUs). Biomarker discovery utilized an Australian cohort (n = 105) consisting of 74 cases (sepsis patients) and 31 controls (post-surgical patients with infection-negative systemic inflammation) recruited at five tertiary care settings in Brisbane, Australia, from June 3, 2008, to December 22, 2011. A four-gene classifier combining CEACAM4, LAMP1, PLA2G7, and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte Lab, was validated using reverse transcription quantitative PCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Patients for validation were selected from the Molecular Diagnosis and Risk Stratification of Sepsis study (ClinicalTrials.gov, NCT01905033), which recruited ICU patients from the Academic Medical Center in Amsterdam and the University Medical Center Utrecht. Patients recruited from November 30, 2012, to August 5, 2013, were eligible for inclusion in the present study. Validation cohort 1 (n = 59) consisted entirely of unambiguous cases and controls; SeptiCyte Lab gave an area under curve (AUC) of 0.95 (95% CI 0.91–1.00) in this cohort. ROC curve analysis of an independent, more heterogeneous group of patients (validation cohorts 2–5; 249 patients after excluding 37 patients with an infection likelihood of “possible”) gave an AUC of 0.89 (95% CI 0.85–0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility of SeptiCyte Lab was evaluated by comparison to various clinical and laboratory parameters available to a clinician within 24 h of ICU admission. SeptiCyte Lab was significantly better at differentiating cases from controls than all tested parameters, both singly and in various logistic combinations, and more than halved the diagnostic error rate compared to procalcitonin in all tested cohorts and cohort combinations. Limitations of this study relate to (1) cohort compositions that do not perfectly reflect the composition of the intended use population, (2) potential biases that could be introduced as a result of the current lack of a gold standard for diagnosing sepsis, and (3) lack of a complete, unbiased comparison to C-reactive protein. Conclusions SeptiCyte Lab is a rapid molecular assay that may be clinically useful in managing ICU patients with systemic inflammation. Further study in population-based cohorts is needed to validate this assay for clinical use. PMID:26645559

Group Sequential Testing of the Predictive Accuracy of a Continuous Biomarker with Unknown Prevalence

PubMed Central

Koopmeiners, Joseph S.; Feng, Ziding

2015-01-01

Group sequential testing procedures have been proposed as an approach to conserving resources in biomarker validation studies. Previously, Koopmeiners and Feng (2011) derived the asymptotic properties of the sequential empirical positive predictive value (PPV) and negative predictive value curves, which summarize the predictive accuracy of a continuous marker, under case-control sampling. A limitation of their approach is that the prevalence can not be estimated from a case-control study and must be assumed known. In this manuscript, we consider group sequential testing of the predictive accuracy of a continuous biomarker with unknown prevalence. First, we develop asymptotic theory for the sequential empirical PPV and NPV curves when the prevalence must be estimated, rather than assumed known in a case-control study. We then discuss how our results can be combined with standard group sequential methods to develop group sequential testing procedures and bias-adjusted estimators for the PPV and NPV curve. The small sample properties of the proposed group sequential testing procedures and estimators are evaluated by simulation and we illustrate our approach in the context of a study to validate a novel biomarker for prostate cancer. PMID:26537180

Effect of prior chemotherapy regimens on the efficacy of endocrine therapy within a German cohort of the TEAM trial.

PubMed

Bossart, Michaela; Hadji, Peyman; Klar, Maximilian; Kieback, Dirk G; Hasenburg, Annette

2014-01-01

Prior chemotherapy may affect the efficacy of endocrine therapy. The tamoxifen exemestane adjuvant multinational (TEAM) trial compared 5 years of adjuvant exemestane with the sequence of tamoxifen followed by exemestane in postmenopausal women with hormone-receptor-positive breast cancer. A total of 1,502 patients were enrolled in Germany (739 received tamoxifen followed by exemestan and 610 exemestan alone). A retrospective analysis of the German cohort of TEAM was conducted to determine whether prior chemotherapy affected clinical outcome of endocrine therapy. Overall survival, disease-free survival and distant recurrence were similar between patients who received sequential therapy and those who received exemestane monotherapy, irrespective of prior chemotherapy. Overall survival was not significantly different between patients who had received prior chemotherapy and those who had not (P = 0.2836). Disease-free survival and distant recurrence were significantly better in patients who had not received prior chemotherapy versus those who had (P = 0.0308 and P = 0.0001). In patients receiving sequential therapy, there were no significant differences in overall survival according to prior chemotherapy use (P = 0.1812). However, disease-free survival and distant recurrence were significantly different dependent on prior chemotherapy (P = 0.0143 and P = 0.0053). In conclusion, there was no difference in overall survival between breast cancer patients who did receive prior chemotherapy before endocrine therapy and those who had not. Patients who had not received prior chemotherapy had significantly improved disease-free survival and less distant recurrence versus those who had received chemotherapy.

Clinical experiences derived from implementation of an easy to use concept for treatment of wound healing by secondary intention and guidance in selection of appropriate dressings.

PubMed

Braumann, Chris; Guenther, Nina; Menenakos, Charalambos; Muenzberg, Helga; Pirlich, Matthias; Lochs, Herbert; Mueller, Joachim M

2011-06-01

The main objective of this case-cohort-type observational study conducted at different Surgical Departments of the Charité-Universitätsmedizin in Berlin was to evaluate the sequential use concept first described by Systagenix Wound Management in 2007. Fifty-two patients with different wound healing by secondary intention were treated for 7 weeks at the Charité-Universitätsmedizin in Berlin. A multidisciplinary team worked together to reach consensus in wound assessment; in classification of infection status according to the criteria described by European Wound Management Association (EWMA); in treatment protocol and on dressings to be used to 'cover' wounds. Before dressing application, all wounds were cleaned from debris. Following the sequential use concept, wounds classified as stages 2 and 3 were dressed with SILVERCEL(®) and TIELLE(®) or TIELLE PLUS(®) to 'clean' the wounds. After 2-3 weeks, treatment was changed to PROMOGRAN PRISMA(®) and TIELLE(®) to 'close and cover' wounds, thus providing optimal wound healing. Wounds classified as non infected were dressed with PROMOGRAN PRISMA(®) and TIELLE(®) during the complete treatment period. Patients were asked to evaluate the treatment using a simplified questionnaire developed at the Charité-Universitätsmedizin in Berlin. Wounds comprised 37 surgical procedures, 8 chronic mixed ulcer, 4 pressure sores, 1 diabetic foot ulcer, 1 venous leg ulcer, and 1 mixed arterial/venous ulcer. At baseline, 12 wounds were classified as stage 3, 38 wounds as stage 2 and 2 wounds as stage 1. After 7 weeks of treatment, all patients showed a positive clinical response to the sequential use treatment. Results of wound size showed a high significant progression of wound healing expressed with a profound reduction of wound area (P in all measurements <0·001, chi-square test) and improved granulation. This study summarises the clinical experiences derived from the evaluation of the sequential use concept in the daily clinical practice of wound treatment. On the basis of the wound healing results, patients' evaluation of treatment and the clinicians' and staff experiences, this concept was implemented at different Surgical Departments of the Charité-Universitätsmedizin in Berlin. © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Early Self-Regulation, Early Self-Regulatory Change, and Their Longitudinal Relations to Adolescents' Academic, Health, and Mental Well-Being Outcomes.

PubMed

Howard, Steven J; Williams, Kate E

2018-05-16

To evaluate the extent to which early self-regulation and early changes in self-regulation are associated with adolescents' academic, health, and mental well-being outcomes. Data were collected from 1 of the cohorts in a large dual-cohort cross-sequential study of Australian children. This cohort consisted of a nationally representative data set of 4983 Australian children assessed at 4 to 5 years of age, who were followed longitudinally to 14 to 15 years of age. Using regression within a path analysis framework, we first sought to investigate associations of early self-regulation (at 4-5 years and 6-7 years of age) with a broad range of academic, health, and mental well-being outcomes in adolescence (at 14-15 years). We next investigated the extent to which an early change in self-regulation (from 4 to 7 years of age) predicted these adolescents' outcomes. Early self-regulation predicted the full range of adolescents' outcomes considered such that a 1-SD increase in self-regulation problems was associated with a 1.5- to 2.5-times greater risk of more-negative outcomes. An early positive change in self-regulation was associated with a reduced risk of these negative outcomes for 11 of the 13 outcomes considered. These results suggest the potential of early self-regulation interventions, in particular, in influencing long-term academic, health, and well-being trajectories.

Levels of Urinary Metabolites of Organophosphate Flame Retardants, TDCIPP, and TPHP, in Pregnant Women in Shanghai

PubMed Central

Ouyang, Fengxiu; Liu, Liangpo; Wang, Xu; Wang, Xia; Li, Yi-Ju; Murtha, Amy; Shen, Heqing; Zhang, Junfeng; Zhang, Jun Jim

2016-01-01

Flame retardants are widely used in consumer products to reduce their flammability. Previously used flame retardants have been sequentially banned due to their environmental and human toxicity. Currently, tris(1,3-dichloropropyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) are among the most commonly used flame retardants. TDCIPP and TPHP are reproductive toxins and have carcinogenic, neurotoxic, and endocrine-disrupting properties. Although high levels of TDCIPP and TPHP have been found in drinking water, seawater, and office air in China, data regarding human exposure are lacking. In this study, we assessed the level of urinary TPHP and TDCIPP metabolites (DPHP and BDCIPP, resp.) in a cohort of pregnant women (N = 23) from Shanghai, China, using liquid chromatography-tandem mass spectrometry. DPHP were detected in 100% urine samples, while only four urine samples had detectable level of BDCIPP in this cohort (17% detected). Geometric means of DPHP and BDCIPP concentrations were 1.1 ng/mL (interquartile range [IQR]: 0.6, 1.5 ng/mL) and 1.2 ng/mL (IQR: 0.6, 2.2 ng/mL), respectively. In this small cohort, urinary DPHP and BDCIPP levels were not significantly correlated with miscarriages, neonatal birthweight, gestational diabetes, or maternal age. These data suggest that exposure to TPHP is widespread, and they demonstrate the feasibility of using urinary biomarkers to measure exposures to modern flame-retardant chemicals. PMID:28115951

Development of exploration of spatial-relational object properties in the second and third years of life.

PubMed

Oudgenoeg-Paz, Ora; Boom, Jan; Volman, M Chiel J M; Leseman, Paul P M

2016-06-01

Within a perception-action framework, exploration is seen as a driving force in young children's development. Through exploration, children become skilled in perceiving the affordances in their environment and acting on them. Using a perception-action framework, the current study examined the development of children's exploration of the spatial-relational properties of objects such as the possibility of containing or stacking. A total of 61 children, belonging to two age cohorts, were followed from 9 to 24 months and from 20 to 36 months of age, respectively. Exploration of a standard set of objects was observed in five home visits in each cohort conducted every 4 months. A cohort-sequential augmented growth model for categorical data, incorporating assumptions of item response theory, was constructed that fitted the data well, showing that the development of exploration of spatial-relational object properties follows an overlapping waves pattern. This is in line with Siegler's model (Emerging Minds, 1996), which suggested that skill development can be seen as ebbing and flowing of alternative (simple and advanced) behaviors. Although the probability of observing the more complex forms of exploration increased with age, the simpler forms did not disappear altogether but only became less probable. Findings support a perception-action view on development. Individual differences in observed exploration and their relations with other variables, as well as future directions for research, are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Continuity of the sequential product of sequential quantum effect algebras

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

Lei, Qiang, E-mail: leiqiang@hit.edu.cn; Su, Xiaochao, E-mail: hitswh@163.com; Wu, Junde, E-mail: wjd@zju.edu.cn

In order to study quantum measurement theory, sequential product defined by A∘B = A{sup 1/2}BA{sup 1/2} for any two quantum effects A, B has been introduced. Physically motivated conditions ask the sequential product to be continuous with respect to the strong operator topology. In this paper, we study the continuity problems of the sequential product A∘B = A{sup 1/2}BA{sup 1/2} with respect to other important topologies, such as norm topology, weak operator topology, order topology, and interval topology.

Maternal and neonatal morbidity in relation to the instrument used for mid-cavity rotational operative vaginal delivery: a prospective cohort study.

PubMed

Bahl, R; Van de Venne, M; Macleod, M; Strachan, B; Murphy, D J

2013-11-01

To compare the maternal and neonatal morbidity associated with alternative instruments used to perform a mid-cavity rotational delivery. A prospective cohort study. Two university teaching hospitals in Scotland and England. Three hundred and eighty-one nulliparous women who had a mid-cavity rotational operative vaginal delivery. A data collection sheet was completed by the research team following delivery. Postpartum haemorrhage, third- and fourth-degree perineal tears, low cord pH, neonatal trauma, and failed or sequential operative vaginal delivery. One hundred and sixty-three women (42.8%) underwent manual rotation followed by non-rotational forceps delivery, 73 (19.1%) had a rotational vacuum delivery, and 145 (38.1%) delivered with the assistance of rotational (Kielland) forceps. The rates of postpartum haemorrhage were similar when comparing manual rotation with rotational vacuum (adjusted OR 1.42, 95% CI 0.66-3.98), and when comparing manual rotation with Kielland forceps (adjusted OR 1.22, 95% CI 0.71-2.88). The results were comparable for third- and fourth-degree perineal tears (adjusted OR 0.85, 95% CI 0.13-1.89; adjusted OR 0.94, 95% CI 0.39-1.82), low cord pH (adjusted OR 1.76, 95% CI 0.44-6.91; adjusted OR 1.12, 95% CI 0.44-2.83), neonatal trauma (adjusted OR 0.50, 95% CI 0.16-1.55; adjusted OR 3.25, 95% CI 0.65-16.17), and admission to the neonatal intensive care unit (adjusted OR 1.47, 95% CI 0.45-4.81; adjusted OR 1.04, 95% CI 0.49-2.19). The sequential use of instruments was less likely with manual rotation and forceps than with rotational vacuum delivery (0.6 versus 36.9%, OR 0.01, 95% CI 0.002-0.090). Maternal and perinatal outcomes are comparable with Kielland forceps, vacuum extraction, and manual rotation, with few serious adverse outcomes. With appropriate training mid-cavity rotational delivery can be practiced safely, including the use of Kielland forceps. © 2013 RCOG.

Initial Results of a Phase I Dose-Escalation Trial of Concurrent and Maintenance Erlotinib and Reirradiation for Recurrent and New Primary Head-and-Neck Cancer

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

Rusthoven, Kyle E.; Feigenberg, Steven J.; Raben, David

2010-11-15

Purpose: To present the first report of a Phase I trial evaluating concurrent and maintenance erlotinib and reirradiation in patients with recurrent or secondary primary head-and-neck cancer (HNC). Methods and Materials: Patients with recurrent or new primary HNC with an interval of at least 6 months since prior radiation were eligible. Patients were treated in 3 sequential cohorts: Cohort I, 100 mg of erlotinib daily with reirradiation at 61.6 Gy in 28 fractions; Cohort II, 150 mg of erlotinib with 61.6 Gy in 28 fractions; and Cohort III, 150 mg of erlotinib with 66 Gy in 30 fractions. Maintenance erlotinibmore » started immediately after reirradiation at 150 mg daily and was continued for 2 years or until disease progression or dose-limiting toxicity. Dose-limiting toxicities were defined as any Grade 4 or 5 toxicity or a toxicity-related delay in radiation therapy of greater than 7 days. Results: Fourteen patients were accrued, 3 to Cohort I, 4 to Cohort II, and 7 to Cohort III. Thirteen patients were evaluable for toxicity. Median follow-up was 8.4 months overall and 15.1 months for surviving patients. One patient had a dose-limiting toxicity in Cohort III. This patient declined initial percutaneous endoscopic gastrostomy tube placement, was hospitalized with Grade 3 dysphagia and aspiration, and required a delay in radiation therapy of greater than 7 days. No Grade 4 acute toxicity was observed. Acute Grade 3 toxicity occurred in 9 of 13 patients. No erlotinib-related toxicity of Grade 3 or greater was observed during maintenance therapy. One patient had Grade 5 carotid hemorrhage 6 months after reirradiation, and another patient had Grade 3 osteoradionecrosis. Conclusions: Reirradiation (66 Gy in 2.2 Gy fractions) with concurrent and maintenance erlotinib (150 mg daily) for recurrent or new primary HNC is feasible.« less

Asymptotic Properties of the Sequential Empirical ROC, PPV and NPV Curves Under Case-Control Sampling.

PubMed

Koopmeiners, Joseph S; Feng, Ziding

2011-01-01

The receiver operating characteristic (ROC) curve, the positive predictive value (PPV) curve and the negative predictive value (NPV) curve are three measures of performance for a continuous diagnostic biomarker. The ROC, PPV and NPV curves are often estimated empirically to avoid assumptions about the distributional form of the biomarkers. Recently, there has been a push to incorporate group sequential methods into the design of diagnostic biomarker studies. A thorough understanding of the asymptotic properties of the sequential empirical ROC, PPV and NPV curves will provide more flexibility when designing group sequential diagnostic biomarker studies. In this paper we derive asymptotic theory for the sequential empirical ROC, PPV and NPV curves under case-control sampling using sequential empirical process theory. We show that the sequential empirical ROC, PPV and NPV curves converge to the sum of independent Kiefer processes and show how these results can be used to derive asymptotic results for summaries of the sequential empirical ROC, PPV and NPV curves.

Asymptotic Properties of the Sequential Empirical ROC, PPV and NPV Curves Under Case-Control Sampling

PubMed Central

Koopmeiners, Joseph S.; Feng, Ziding

2013-01-01

The receiver operating characteristic (ROC) curve, the positive predictive value (PPV) curve and the negative predictive value (NPV) curve are three measures of performance for a continuous diagnostic biomarker. The ROC, PPV and NPV curves are often estimated empirically to avoid assumptions about the distributional form of the biomarkers. Recently, there has been a push to incorporate group sequential methods into the design of diagnostic biomarker studies. A thorough understanding of the asymptotic properties of the sequential empirical ROC, PPV and NPV curves will provide more flexibility when designing group sequential diagnostic biomarker studies. In this paper we derive asymptotic theory for the sequential empirical ROC, PPV and NPV curves under case-control sampling using sequential empirical process theory. We show that the sequential empirical ROC, PPV and NPV curves converge to the sum of independent Kiefer processes and show how these results can be used to derive asymptotic results for summaries of the sequential empirical ROC, PPV and NPV curves. PMID:24039313

Prospective cohort studies of newly marketed medications: using covariate data to inform the design of large-scale studies.

PubMed

Franklin, Jessica M; Rassen, Jeremy A; Bartels, Dorothee B; Schneeweiss, Sebastian

2014-01-01

Nonrandomized safety and effectiveness studies are often initiated immediately after the approval of a new medication, but patients prescribed the new medication during this period may be substantially different from those receiving an existing comparator treatment. Restricting the study to comparable patients after data have been collected is inefficient in prospective studies with primary collection of outcomes. We discuss design and methods for evaluating covariate data to assess the comparability of treatment groups, identify patient subgroups that are not comparable, and decide when to transition to a large-scale comparative study. We demonstrate methods in an example study comparing Cox-2 inhibitors during their postmarketing period (1999-2005) with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). Graphical checks of propensity score distributions in each treatment group showed substantial problems with overlap in the initial cohorts. In the first half of 1999, >40% of patients were in the region of nonoverlap on the propensity score, and across the study period this fraction never dropped below 10% (the a priori decision threshold for transitioning to the large-scale study). After restricting to patients with no prior NSAID use, <1% of patients were in the region of nonoverlap, indicating that a large-scale study could be initiated in this subgroup and few patients would need to be trimmed from analysis. A sequential study design that uses pilot data to evaluate treatment selection can guide the efficient design of large-scale outcome studies with primary data collection by focusing on comparable patients.

Robustness of the Sequential Lineup Advantage

ERIC Educational Resources Information Center

Gronlund, Scott D.; Carlson, Curt A.; Dailey, Sarah B.; Goodsell, Charles A.

2009-01-01

A growing movement in the United States and around the world involves promoting the advantages of conducting an eyewitness lineup in a sequential manner. We conducted a large study (N = 2,529) that included 24 comparisons of sequential versus simultaneous lineups. A liberal statistical criterion revealed only 2 significant sequential lineup…

Phase II Study of First‐Line Trebananib Plus Sorafenib in Patients with Advanced Hepatocellular Carcinoma

PubMed Central

Blanc, Jean‐Frederic; Miles, Steven; Ganten, Tom; Trojan, Jörg; Cebon, Jonathan; Liem, Andre K.; Lipton, Lara; Gupta, Charu; Wu, Benjamin; Bass, Michael; Hollywood, Ellen; Ma, Jennifer; Bradley, Margaret; Litten, Jason; Saltz, Leonard B.

2017-01-01

Abstract Lessons Learned. Trebananib leveraging anti‐angiogenic mechanism that is distinct from the classic sorafenib anti‐vascular endothelial growth factor inhibition did not demonstrate improved progression‐free survival at 4 months in patients with advanced hepatocellular carcinoma (HCC).In support of previously reported high Ang‐2 levels’ association with poor outcome in HCC for patients, trebananib treatment with lower baseline Ang‐2 at study entry was associated with improved overall survival to 22 months and may suggest future studies to be performed within the context of low baseline Ang‐2. Background. Ang‐1 and Ang‐2 are angiopoietins thought to promote neovascularization via activation of the Tie‐2 angiopoietin receptor. Trebananib sequesters Ang‐1 and Ang‐2, preventing interaction with the Tie‐2 receptor. Trebananib plus sorafenib combination has acceptable toxicity. Elevated Ang‐2 levels are associated with poor prognosis in hepatocellular carcinoma (HCC). Methods. Patients with HCC, Eastern Cooperative Oncology Group ≤2, and Childs‐Pugh A received IV trebananib at 10 mg/kg or 15 mg/kg weekly plus sorafenib 400 mg orally twice daily. The study was planned for ≥78% progression‐free survival (PFS) rate at 4 months relative to 62% for sorafenib historical control (power = 80% α = 0.20). Secondary endpoints included safety, tolerability, overall survival (OS), and multiple biomarkers, including serum Ang‐2. Results. Thirty patients were enrolled sequentially in each of the two nonrandomized cohorts. Demographics were comparable between the two arms and the historical controls. PFS rates at 4 months were 57% and 54% on the 10 mg/kg and 15 mg/kg trebananib cohorts, respectively. Median OS was 17 and 11 months, respectively. Grade 3 and above events noted in ≥10% of patients included fatigue, hypertension, diarrhea, liver failure, palmar‐plantar erythrodysesthesia syndrome, dyspnea, and hypophosphatemia. One death was due to hepatic failure. Serum Ang‐2 dichotomized at the median was associated with improved OS in both cohorts. Conclusion. There was no improvement in PFS rate at 4 months in either cohort, when compared with sorafenib historical control. PMID:28592620

Negative Stereotypes of Ethnic Out-groups: A Longitudinal Examination Among Palestinian, Israeli Jewish, and Israeli Arab Youth.

PubMed

Niwa, Erika Y; Boxer, Paul; Dubow, Eric F; Huesmann, L Rowell; Landau, Simha; Shikaki, Khalil; Gvirsman, Shira Dvir

2016-03-01

Ethno-political conflict impacts thousands of youth globally and has been associated with a number of negative psychological outcomes. Extant literature has mostly addressed the adverse emotional and behavioral outcomes of exposure while failing to examine change over time in social-cognitive factors in contexts of ethno-political conflict. Using cohort-sequential longitudinal data, the present study examines ethnic variation in the development of negative stereotypes about ethnic out-groups among Palestinian ( n =600), Israeli Jewish ( n =451), and Israeli Arab ( n =450) youth over three years. Age and exposure to ethno-political violence were included as covariates for these trajectories. Findings indicate important ethnic differences in trajectories of negative stereotypes about ethnic out-groups, as well as variation in how such trajectories are shaped by prolonged ethno-political conflict.

Negative Stereotypes of Ethnic Out-groups: A Longitudinal Examination Among Palestinian, Israeli Jewish, and Israeli Arab Youth

PubMed Central

Niwa, Erika Y.; Boxer, Paul; Dubow, Eric F.; Huesmann, L. Rowell; Landau, Simha; Shikaki, Khalil; Gvirsman, Shira Dvir

2014-01-01

Ethno-political conflict impacts thousands of youth globally and has been associated with a number of negative psychological outcomes. Extant literature has mostly addressed the adverse emotional and behavioral outcomes of exposure while failing to examine change over time in social-cognitive factors in contexts of ethno-political conflict. Using cohort-sequential longitudinal data, the present study examines ethnic variation in the development of negative stereotypes about ethnic out-groups among Palestinian (n=600), Israeli Jewish (n=451), and Israeli Arab (n=450) youth over three years. Age and exposure to ethno-political violence were included as covariates for these trajectories. Findings indicate important ethnic differences in trajectories of negative stereotypes about ethnic out-groups, as well as variation in how such trajectories are shaped by prolonged ethno-political conflict. PMID:27019573

Clinical risk factors for venous thrombosis associated with air travel.

PubMed

Kesteven, P J; Robinson, B J

2001-02-01

Recent reports have linked air travel with venous thrombo-embolism (VTE). Risk factors and associated features of this link are poorly understood. We have accumulated clinical data from a relatively large cohort of patients with traveler's thrombosis. A total of 86 patients who developed venous thromboembolism within 28 d of flying were questioned concerning traveling habits, medical history (including risk factors for VTE) and characteristics of the index flight. Of the patients, 72% had at least one risk factor for VTE (excluding thrombophilia) prior to their flight. Of interest, 87% of VTE cases occurred following either a return trip or after an outward journey involving long trips made up of sequential flights. In only two cases could no identifiable risk factor or earlier journey be found. Duration of flights ranged from 2 to 30 h. Of responders, 38% presented with chest symptoms; 92% with VTE developed symptoms within 96 h of their flight. We conclude that the majority of VTE associated with air travel occur in those with identifiable risk factors prior to their flight, and that sequential flights may increase this risk.

Phase 1b Study of New Posaconazole Tablet for Prevention of Invasive Fungal Infections in High-Risk Patients with Neutropenia

PubMed Central

López-Jiménez, Javier; Cornely, Oliver A.; Laverdiere, Michel; Helfgott, David; Haider, Shariq; Chandrasekar, Pranatharthi; Langston, Amelia; Perfect, John; Ma, Lei; van Iersel, Marlou L. P. S.; Connelly, Nancy; Kartsonis, Nicholas; Waskin, Hetty

2014-01-01

Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.) PMID:25049247

Comparison of Statistical Approaches for Dealing With Immortal Time Bias in Drug Effectiveness Studies.

PubMed

Karim, Mohammad Ehsanul; Gustafson, Paul; Petkau, John; Tremlett, Helen

2016-08-15

In time-to-event analyses of observational studies of drug effectiveness, incorrect handling of the period between cohort entry and first treatment exposure during follow-up may result in immortal time bias. This bias can be eliminated by acknowledging a change in treatment exposure status with time-dependent analyses, such as fitting a time-dependent Cox model. The prescription time-distribution matching (PTDM) method has been proposed as a simpler approach for controlling immortal time bias. Using simulation studies and theoretical quantification of bias, we compared the performance of the PTDM approach with that of the time-dependent Cox model in the presence of immortal time. Both assessments revealed that the PTDM approach did not adequately address immortal time bias. Based on our simulation results, another recently proposed observational data analysis technique, the sequential Cox approach, was found to be more useful than the PTDM approach (Cox: bias = -0.002, mean squared error = 0.025; PTDM: bias = -1.411, mean squared error = 2.011). We applied these approaches to investigate the association of β-interferon treatment with delaying disability progression in a multiple sclerosis cohort in British Columbia, Canada (Long-Term Benefits and Adverse Effects of Beta-Interferon for Multiple Sclerosis (BeAMS) Study, 1995-2008). © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

NTCP reduction for advanced head and neck cancer patients using proton therapy for complete or sequential boost treatment versus photon therapy.

PubMed

Jakobi, Annika; Stützer, Kristin; Bandurska-Luque, Anna; Löck, Steffen; Haase, Robert; Wack, Linda-Jacqueline; Mönnich, David; Thorwarth, Daniel; Perez, Damien; Lühr, Armin; Zips, Daniel; Krause, Mechthild; Baumann, Michael; Perrin, Rosalind; Richter, Christian

2015-01-01

To determine by treatment plan comparison differences in toxicity risk reduction for patients with head and neck squamous cell carcinoma (HNSCC) from proton therapy either used for complete treatment or sequential boost treatment only. For 45 HNSCC patients, intensity-modulated photon (IMXT) and proton (IMPT) treatment plans were created including a dose escalation via simultaneous integrated boost with a one-step adaptation strategy after 25 fractions for sequential boost treatment. Dose accumulation was performed for pure IMXT treatment, pure IMPT treatment and for a mixed modality treatment with IMXT for the elective target followed by a sequential boost with IMPT. Treatment plan evaluation was based on modern normal tissue complication probability (NTCP) models for mucositis, xerostomia, aspiration, dysphagia, larynx edema and trismus. Individual NTCP differences between IMXT and IMPT (∆NTCPIMXT-IMPT) as well as between IMXT and the mixed modality treatment (∆NTCPIMXT-Mix) were calculated. Target coverage was similar in all three scenarios. NTCP values could be reduced in all patients using IMPT treatment. However, ∆NTCPIMXT-Mix values were a factor 2-10 smaller than ∆NTCPIMXT-IMPT. Assuming a threshold of ≥ 10% NTCP reduction in xerostomia or dysphagia risk as criterion for patient assignment to IMPT, less than 15% of the patients would be selected for a proton boost, while about 50% would be assigned to pure IMPT treatment. For mucositis and trismus, ∆NTCP ≥ 10% occurred in six and four patients, respectively, with pure IMPT treatment, while no such difference was identified with the proton boost. The use of IMPT generally reduces the expected toxicity risk while maintaining good tumor coverage in the examined HNSCC patients. A mixed modality treatment using IMPT solely for a sequential boost reduces the risk by 10% only in rare cases. In contrast, pure IMPT treatment may be reasonable for about half of the examined patient cohort considering the toxicities xerostomia and dysphagia, if a feasible strategy for patient anatomy changes is implemented.

The association between the combined oral contraceptive pill and insulin resistance, dysglycemia and dyslipidemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of observational studies.

PubMed

Halperin, Ilana J; Kumar, Shoba Sujana; Stroup, Donna F; Laredo, Sheila E

2011-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of young women. First-line treatment is often the oral contraceptive pill (OC), but evidence suggests that OC may worsen metabolic outcomes in this population. We undertook this meta-analysis of observational studies and cohorts from within randomized controlled studies to investigate the association between OC use and dysglycemia, dyslipidemia and insulin resistance (IR) in women with PCOS. We searched MEDLINE (1966-April 2010), EMBASE (1980-April 2010) and All EBM Reviews. We included prospective cohorts and RCTs that treated women, aged 13-44, with PCOS with OC for at least 3 months. Blinded quality assessment and data extraction were conducted on 35 included studies by two independent reviewers. We used random effects methods to calculate weighted mean differences as the effect size. We investigated heterogeneity using sequential removal of studies, subgroup analysis and meta-regression. OC use was significantly associated with an increase in high-density lipoprotein cholesterol (HDL-C) (P = 0.004) and triglycerides (P = 0.004). Significant heterogeneity was found in glucose, cholesterol, HDL-C, low-density lipoprotein cholesterol triglycerides, fasting glucose to insulin ratios and homeostatic model assessments-IR. Study characteristics such as mean BMI, mean age and duration of study could explain some of the heterogeneity. Use of OC was not associated with clinically significant adverse metabolic consequences. Because of limitations of the underlying studies, further research including rigorously designed randomized trials would more definitively confirm our findings.

Is the HAS-BLED score useful in predicting post-extraction bleeding in patients taking warfarin? A retrospective cohort study

PubMed Central

Kataoka, Toshiyuki; Hoshi, Keika; Ando, Tomohiro

2016-01-01

Objective Unexpected post-extraction bleeding is often experienced in clinical practice. Therefore, determining the risk of post-extraction bleeding in patients receiving anticoagulant therapy prior to surgery is beneficial. This study aimed to verify whether the HAS-BLED score was useful in predicting post-extraction bleeding in patients taking warfarin. Design Retrospective cohort study. Setting Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University. Participants Participants included 258 sequential cases (462 teeth) who had undergone tooth extraction between 1 January 2010 and 31 December 2012 while continuing warfarin therapy. Main outcome measure Post-extraction risk factors for bleeding. The following data were collected as the predicting variables for multivariate logistic analysis: the HAS-BLED score, extraction site, tooth type, stability of teeth, extraction procedure, prothrombin time-international normalised ratio value, platelet count and the use of concomitant antiplatelet agents. Results Post-extraction bleeding was noted in 21 (8.1%) of the 258 cases. Haemostasis was achieved with localised haemostatic procedures in all the cases of post-extraction bleeding. The HAS-BLED score was found to be insufficient in predicting post-extraction bleeding (area under the curve=0.548, p=0.867, multivariate analysis). The risk of post-extraction bleeding was approximately three times greater in patients taking concomitant oral antiplatelet agents (risk ratio=2.881, p=0.035, multivariate analysis). Conclusions The HAS-BLED score alone could not predict post-extraction bleeding. The concomitant use of oral antiplatelet agents was a risk factor for post-extraction bleeding. No episodes of post-extraction bleeding required more than local measures for haemostasis. However, because this was a retrospective study conducted at a single institution, large-scale prospective cohort studies, which include cases of outpatient tooth extraction, will be necessary in the future. PMID:26936909

Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

PubMed

Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E

2017-11-01

Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.

Sequential biases in accumulating evidence

PubMed Central

Huggins, Richard; Dogo, Samson Henry

2015-01-01

Whilst it is common in clinical trials to use the results of tests at one phase to decide whether to continue to the next phase and to subsequently design the next phase, we show that this can lead to biased results in evidence synthesis. Two new kinds of bias associated with accumulating evidence, termed ‘sequential decision bias’ and ‘sequential design bias’, are identified. Both kinds of bias are the result of making decisions on the usefulness of a new study, or its design, based on the previous studies. Sequential decision bias is determined by the correlation between the value of the current estimated effect and the probability of conducting an additional study. Sequential design bias arises from using the estimated value instead of the clinically relevant value of an effect in sample size calculations. We considered both the fixed‐effect and the random‐effects models of meta‐analysis and demonstrated analytically and by simulations that in both settings the problems due to sequential biases are apparent. According to our simulations, the sequential biases increase with increased heterogeneity. Minimisation of sequential biases arises as a new and important research area necessary for successful evidence‐based approaches to the development of science. © 2015 The Authors. Research Synthesis Methods Published by John Wiley & Sons Ltd. PMID:26626562

Patterns of C-reactive protein ratio response to antibiotics in pediatric sepsis: A prospective cohort study.

PubMed

Lanziotti, Vanessa Soares; Póvoa, Pedro; Prata-Barbosa, Arnaldo; Pulcheri, Lucas Berbet; Rabello, Ligia S C F; Lapa E Silva, José Roberto; Soares, Marcio; Salluh, Jorge I F

2018-04-01

Evaluate sequential C-reactive protein (CRP) measurements and patterns of CRP-ratio response to antibiotic therapy during first 7days in Pediatric Intensive Care Unit (PICU) of septic children. Prospective, cohort study of children (1month-12years) admitted at 3 PICUs, with diagnosis of sepsis with <72h course. CRP-ratio was calculated in relation to D0_CRP value. Children were classified according to an individual pattern of CRP-ratio response: fast - CRP_D4 of therapy was <0.4 of D0_CRP; slow - continuous but slow decrease of CRP; non - CRP remained ≥0.8 of D0_CRP; biphasic - initial CRP decrease to levels <0.8 of D0_CRP followed by secondary rise ≥0.8. 103 septic children (age-median: 2yrs; 54% male) were prospectively included (infection focus: 65% respiratory, 12.5% central nervous system). Overall PICU mortality was 11.7%. 102 children could be classified according to a predefined CRP-ratio response pattern. Time-dependent analysis of CRP-ratio and CRP course of the different patterns were significantly different. Besides, PICU mortality rate was significantly different according CRP-ratio response patterns: fast response 4.5%; slow response 5.8%; non-response 29.4%; biphasic response 42.8%. In pediatric sepsis, CRP-ratio serial evaluation was useful in early identification of patients with poor outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

A prospective cohort study examining the preferred learning styles of acute care registered nurses.

PubMed

McCrow, Judy; Yevchak, Andrea; Lewis, Peter

2014-03-01

This paper reports on the preferred learning styles of Registered Nurses practicing in acute care environments and relationships between gender, age, post-graduate experience and the identified preferred learning styles. A prospective cohort study design was used. Participants completed a demographic questionnaire and the Felder-Silverman Index of Learning Styles (ILS) questionnaire to determine preferred learning styles. Most of the Registered Nurse participants were balanced across the Active-Reflective (n = 77, 54%), and Sequential-Global (n = 96, 68%) scales. Across the other scales, sensing (n = 97, 68%) and visual (n = 76, 53%) were the most common preferred learning style. There were only a small proportion who had a preferred learning style of reflective (n = 21, 15%), intuitive (n = 5, 4%), verbal (n = 11, 8%) or global learning (n = 15, 11%). Results indicated that gender, age and years since undergraduate education were not related to the identified preferred learning styles. The identification of Registered Nurses' learning style provides information that nurse educators and others can use to make informed choices about modification, development and strengthening of professional hospital-based educational programs. The use of the Index of Learning Styles questionnaire and its ability to identify 'balanced' learning style preferences may potentially yield additional preferred learning style information for other health-related disciplines. Copyright © 2013 Elsevier Ltd. All rights reserved.

Welding, longitudinal lung function decline and chronic respiratory symptoms: a systematic review of cohort studies.

PubMed

Szram, Joanna; Schofield, Susie J; Cosgrove, Martin P; Cullinan, Paul

2013-11-01

While the acute respiratory risks of welding are well characterised, more chronic effects, including those on lung function, are less clear. We carried out a systematic review of published longitudinal studies of lung function decline in welders. Original cohort studies documenting two or more sequential measurements of lung function were reviewed. Meta-analysis was carried out on studies with suitable data on forced expiratory volume in 1 s (FEV1). Seven studies were included; their quality (measured on the Newcastle-Ottawa scale) was good, although exposure assessment was limited and the studies showed significant heterogeneity. Five had data suitable for meta-analysis; the pooled estimate of the difference in FEV1 decline between welders and nonwelders was -9.0 mL · year(-1) (95% CI -22.5-4.5; p=0.193). The pooled estimates of difference in annual FEV1 decline between welders and referents who smoked was -13.7 mL · year(-1) (95% CI -33.6-6.3; p=0.179). For welders and referents who did not smoke the estimated difference was -3.8 mL · year(-1) (95% CI -20.2-12.6; p=0.650). Symptom prevalence data were mainly narrative; smoking appeared to have the greatest effect on symptom evolution. Collectively, available longitudinal data on decline of lung function in welders and respiratory symptoms suggest a greater effect in those who smoke, supporting a focus on smoking cessation as well as control of fume exposure in this trade. Further prospective studies are required to confirm these findings.

Associations between maternal long-chain polyunsaturated fatty acid concentrations and child cognition at 7 years of age: The MEFAB birth cohort.

PubMed

Brouwer-Brolsma, E M; van de Rest, O; Godschalk, R; Zeegers, M P A; Gielen, M; de Groot, R H M

2017-11-01

Concentrations of the fish fatty acids EPA and DHA are low among Dutch women of reproductive age. As the human brain incorporates high concentrations of these fatty acids in utero, particularly during third trimester of gestation, these low EPA and DHA concentrations may have adverse consequences for fetal brain development and functioning. Analyses were conducted using longitudinal observational data of 292 mother-child pairs participating in the MEFAB cohort. Maternal AA, DHA, and EPA were determined in plasma phospholipids - obtained in three trimesters - by gas-liquid chromatography. Cognitive function was assessed at 7 years of age, using the Kaufman Assessment Battery for Children, resulting in three main outcome parameters: sequential processing (short-term memory), simultaneous processing (problem-solving skills), and the mental processing composite score. Spline regression and linear regression analyses were used to analyse the data, while adjusting for potential relevant covariates. Only 2% of the children performed more than one SD below the mental processing composite norm score. Children with lower test scores (<25%) were more likely to have a younger mother with a higher pre-gestational BMI, less likely to be breastfed, and more likely to be born with a lower birth weight, compared to children with higher test scores (≥25%). Fully-adjusted linear regression models did not show associations of maternal AA, DHA, or EPA status during any of the pregnancy trimesters with childhood sequential and simultaneous processing. Maternal fatty acid status during pregnancy was not associated with cognitive performance in Dutch children at age 7. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nail gun injuries in residential carpentry: lessons from active injury surveillance.

PubMed

Lipscomb, H J; Dement, J M; Nolan, J; Patterson, D; Li, L

2003-03-01

To describe circumstances surrounding injuries involving nail guns among carpenters, calculate injury rates, identify high risk groups and preventive measures. and setting: Active injury surveillance was used to identify causes of injury among a large cohort of union residential and drywall carpenters. Injured carpenters were interviewed by experienced journeymen; enumeration of workers and hourworked were provided by the union. The combined data allowed definition of a cohort of carpenters, their hours worked, detailed information on the circumstances surrounding injuries, and identification of preventive measures from the perspectives of the injured worker and an experienced investigator. Nail guns were involved in 14% of injuries investigated. Ninety percent of these injuries were the result of the carpenter being struck, most commonly by a nail puncturing a hand or fingers. The injury rate among apprentices was 3.7 per 200 000 hours worked (95% confidence interval (CI) 2.7 to 4.9) compared with a rate of 1.2 among journeymen (95% CI 0.80 to 1.7). While not always the sole contributing factor, a sequential trigger would have likely prevented 65% of the injuries from tools with contact trip triggers. Training, engineering, and policy changes in the workplace and manufacturing arena are all appropriate targets for prevention of these injuries. Use of sequential triggers would likely decrease acute injury rates markedly. Over 70% of injuries among residential carpenters were associated with through nailing tasks (such as nailing studs or blocks, trusses or joists) or toe nailing (angled, corner nailing) as opposed to flat nailing used for sheathing activities; this provides some indication that contact trip tools could be used solely for flat nailing.

Nail gun injuries in residential carpentry: lessons from active injury surveillance

PubMed Central

Lipscomb, H; Dement, J; Nolan, J; Patterson, D; Li, L

2003-01-01

Objective: To describe circumstances surrounding injuries involving nail guns among carpenters, calculate injury rates, identify high risk groups and preventive measures. Methods and setting: Active injury surveillance was used to identify causes of injury among a large cohort of union residential and drywall carpenters. Injured carpenters were interviewed by experienced journeymen; enumeration of workers and hourworked were provided by the union. The combined data allowed definition of a cohort of carpenters, their hours worked, detailed information on the circumstances surrounding injuries, and identification of preventive measures from the perspectives of the injured worker and an experienced investigator. Results: Nail guns were involved in 14% of injuries investigated. Ninety percent of these injuries were the result of the carpenter being struck, most commonly by a nail puncturing a hand or fingers. The injury rate among apprentices was 3.7 per 200 000 hours worked (95% confidence interval (CI) 2.7 to 4.9) compared with a rate of 1.2 among journeymen (95% CI 0.80 to 1.7). While not always the sole contributing factor, a sequential trigger would have likely prevented 65% of the injuries from tools with contact trip triggers. Conclusions: Training, engineering, and policy changes in the workplace and manufacturing arena are all appropriate targets for prevention of these injuries. Use of sequential triggers would likely decrease acute injury rates markedly. Over 70% of injuries among residential carpenters were associated with through nailing tasks (such as nailing studs or blocks, trusses or joists) or toe nailing (angled, corner nailing) as opposed to flat nailing used for sheathing activities; this provides some indication that contact trip tools could be used solely for flat nailing. PMID:12642553

Predicting pneumonitis risk: a dosimetric alternative to mean lung dose.

PubMed

Tucker, Susan L; Mohan, Radhe; Liengsawangwong, Raweewan; Martel, Mary K; Liao, Zhongxing

2013-02-01

To determine whether the association between mean lung dose (MLD) and risk of severe (grade ≥3) radiation pneumonitis (RP) depends on the dose distribution pattern to normal lung among patients receiving 3-dimensional conformal radiation therapy for non-small-cell lung cancer. Three cohorts treated with different beam arrangements were identified. One cohort (2-field boost [2FB]) received 2 parallel-opposed (anteroposterior-posteroanterior) fields per fraction initially, followed by a sequential boost delivered using 2 oblique beams. The other 2 cohorts received 3 or 4 straight fields (3FS and 4FS, respectively), ie, all fields were irradiated every day. The incidence of severe RP was plotted against MLD in each cohort, and data were analyzed using the Lyman-Kutcher-Burman (LKB) model. The incidence of grade ≥3 RP rose more steeply as a function of MLD in the 2FB cohort (N=120) than in the 4FS cohort (N=138), with an intermediate slope for the 3FS group (N=99). The estimated volume parameter from the LKB model was n=0.41 (95% confidence interval, 0.15-1.0) and led to a significant improvement in fit (P=.05) compared to a fit with volume parameter fixed at n=1 (the MLD model). Unlike the MLD model, the LKB model with n=0.41 provided a consistent description of the risk of severe RP in all three cohorts (2FB, 3FS, 4FS) simultaneously. When predicting risk of grade ≥3 RP, the mean lung dose does not adequately take into account the effects of high doses. Instead, the effective dose, computed from the LKB model using volume parameter n=0.41, may provide a better dosimetric parameter for predicting RP risk. If confirmed, these findings support the conclusion that for the same MLD, high doses to small lung volumes ("a lot to a little") are worse than low doses to large volumes ("a little to a lot"). Copyright © 2013 Elsevier Inc. All rights reserved.

A hybrid classroom-online curriculum format for RN-BSN students: cohort support and curriculum structure improve graduation rates.

PubMed

Davidson, Susan C; Metzger, Richard; Lindgren, Katherine S

2011-05-01

As more registered nurses (RNs) return to school to obtain a bachelor of science in nursing (BSN), innovative ways must be found to support them in this endeavor. Barriers for RNs who return to school include scheduling of coursework and fear of failure. One school of nursing with a traditional BSN program reviewed its RN-BSN track, with its low retention and graduation rates. With input from nursing leaders and nurses in the community, the school applied for and was awarded a 3-year Health Resources and Services Administration grant to redesign the RN-BSN program. A hybrid classroom-online curriculum is offered in a structured, sequential format so that the RNs are admitted once a year and must complete the courses as a group, in a cohort. Data collected from evaluations showed that program support, technology support, and social support from peers encouraged the RNs to "stay the course," and 100% completed the requirements to graduate. Copyright 2011, SLACK Incorporated.

Self-Debriefing vs Instructor Debriefing in a Pre-Internship Simulation Curriculum: Night on Call.

PubMed

Oikawa, Sayaka; Berg, Benjamin; Turban, Joseph; Vincent, Dale; Mandai, Yasuhiro; Birkmire-Peters, Deborah

2016-05-01

This study sought to determine if learner self-performance assessment (SPA) and team-performance assessment (TPA) were different when simulation based education (SBE) was supported by self-debriefing (S-DB), compared to traditional facilitator-led debriefing (F-DB). "One-Night-On-Call," an internship preparation curriculum, was selected to provide SBE. Participants worked as team members in 4 sequential bedside acute care problem-solving scenarios. Fifty-seven learners were randomized to 9 F-DB and 10 S-DB Teams. Participants completed SPA and TPA assessment checklist questionnaires immediately following the first and fourth (final) scenarios. Learner SPA and TPA scores improved overall from the first to the fourth scenarios (P <.05). F-DB versus S-DB cohorts did not differ in overall SPA scores. The F-DB average TPA score was 12.8 (SD±2.1) compared to a S-DB score of 14.1 (SD±2.1) (P =.001). F-DB participants' increase in TPA was due to increases in the Patient Assessment and Treatment sub-domains that exceeded corresponding improvements in the S-DB cohort. Self- debriefing strategies are equivalent to facilitator-led debriefing in some situations. Self-debriefing offers opportunities to enable simulation-based education by decreasing the number of required faculty debriefers, and may be uniquely well matched to simulation-based teamwork training.

Correlation of treatment-emergent adverse events and clinical response to endocrine therapy in early breast cancer: a retrospective analysis of the German cohort of TEAM.

PubMed

Hadji, P; Kieback, D G; Tams, J; Hasenburg, A; Ziller, M

2012-10-01

Previous studies have suggested a correlation between the occurrence of vasomotor or joint symptoms during tamoxifen or aromatase inhibitor treatment and improved clinical response. A retrospective analysis of the German cohort of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial was carried out to assess disease-free survival (DFS) and overall survival (OS) in patients with and without arthralgia/myalgia and/or menopausal symptoms during adjuvant endocrine treatment. A total of 1502 patients were included; 739 patients received tamoxifen followed by exemestane and 763 received exemestane. Patients reporting arthralgia/myalgia and patients reporting menopausal symptoms during endocrine treatment had significantly longer OS and DFS than those not reporting these events. The effect on OS was irrespective of treatment. DFS was significantly improved in exemestane-treated patients reporting arthralgia/myalgia or those reporting menopausal symptoms versus those not reporting these events. This effect on DFS was not observed in patients receiving sequential treatment. A combined analysis of patients reporting either menopausal symptoms or arthralgia/myalgia showed that OS and DFS were significantly improved in patients reporting one of these symptoms versus those not reporting either symptom. The occurrence of arthralgia/myalgia or menopausal symptoms during endocrine treatment is associated with significantly improved OS.

Robustness of the sequential lineup advantage.

PubMed

Gronlund, Scott D; Carlson, Curt A; Dailey, Sarah B; Goodsell, Charles A

2009-06-01

A growing movement in the United States and around the world involves promoting the advantages of conducting an eyewitness lineup in a sequential manner. We conducted a large study (N = 2,529) that included 24 comparisons of sequential versus simultaneous lineups. A liberal statistical criterion revealed only 2 significant sequential lineup advantages and 3 significant simultaneous advantages. Both sequential advantages occurred when the good photograph of the guilty suspect or either innocent suspect was in the fifth position in the sequential lineup; all 3 simultaneous advantages occurred when the poorer quality photograph of the guilty suspect or either innocent suspect was in the second position. Adjusting the statistical criterion to control for the multiple tests (.05/24) revealed no significant sequential advantages. Moreover, despite finding more conservative overall choosing for the sequential lineup, no support was found for the proposal that a sequential advantage was due to that conservative criterion shift. Unless lineups with particular characteristics predominate in the real world, there appears to be no strong preference for conducting lineups in either a sequential or a simultaneous manner. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

Youth participation in organized and informal sports activities across childhood and adolescence: exploring the relationships of motivational beliefs, developmental stage and gender.

PubMed

Dawes, Nickki Pearce; Vest, Andrea; Simpkins, Sandra

2014-08-01

Involvement in physically active pursuits, such as sports, contributes to achieving and maintaining good emotional and physical health. The central goal of this article was to examine the longitudinal relationships between participation (i.e., time spent in the activities) in organized and informal sports contexts and motivational beliefs, and factors that might impact these relationships, such as developmental stage and gender. The data for the current study were drawn from the childhood and beyond longitudinal study, which utilized a cohort sequential design with data collected on three cohorts across four waves. The current study sample included 986 European American youth (51 % female), who t were mostly from working- and middle-class families. Self-report questionnaires were used to collect data from the youth about their participation in sports and their motivational beliefs (i.e., value and perceptions of competence) about this activity. Structural equation modeling was used to examine the relationships between participation and motivational beliefs across childhood and adolescence. The results provide some support for a model of reciprocal relationships between participation and motivational beliefs in organized and informal sports activities. These relationships between participation and motivational beliefs did not vary significantly based on developmental stage or by gender. Overall, the findings suggest that participation in organized and informal sports contexts may be fostered by supporting the development of positive motivational beliefs about the activities across developmental periods.

Characteristics of sequential swallowing of liquids in young and elderly adults: an integrative review.

PubMed

Veiga, Helena Perrut; Bianchini, Esther Mandelbaum Gonçalves

2012-01-01

To perform an integrative review of studies on liquid sequential swallowing, by characterizing the methodology of the studies and the most important findings in young and elderly adults. Review of the literature written in English and Portuguese on PubMed, LILACS, SciELO and MEDLINE databases, within the past twenty years, available fully, using the following uniterms: sequential swallowing, swallowing, dysphagia, cup, straw, in various combinations. Research articles with a methodological approach on the characterization of liquid sequential swallowing by young and/or elderly adults, regardless of health condition, excluding studies involving only the esophageal phase. The following research indicators were applied: objectives, number and gender of participants; age group; amount of liquid offered; intake instruction; utensil used, methods and main findings. 18 studies met the established criteria. The articles were categorized according to the sample characterization and the methodology on volume intake, utensil used and types of exams. Most studies investigated only healthy individuals, with no swallowing complaints. Subjects were given different instructions as to the intake of all the volume: usual manner, continually, as rapidly as possible. The findings about the characterization of sequential swallowing were varied and described in accordance with the objectives of each study. It found great variability in the methodology employed to characterize the sequential swallowing. Some findings are not comparable, and sequential swallowing is not studied in most swallowing protocols, without consensus on the influence of the utensil.

Safety and tolerability of adjunctive lacosamide intravenous loading dose in lacosamide-naive patients with partial-onset seizures.

PubMed

Fountain, Nathan B; Krauss, Gregory; Isojarvi, Jouko; Dilley, Deanne; Doty, Pamela; Rudd, G David

2013-01-01

To examine the safety and tolerability of rapidly initiating adjunctive lacosamide via a single intravenous loading dose followed by twice-daily oral lacosamide in lacosamide-naive adults with partial-onset seizures. This open-label, multicenter trial, enrolled patients with epilepsy who were taking 1-2 antiepileptic drugs (AEDs) in one of four sequential cohorts containing 25 subjects each. An intravenous lacosamide loading dose (200, 300, or 400 mg) was administered over 15 min followed 12 h later by initiation of oral dosing consisting of one-half of the loading dose administered twice daily for 6.5 days. The first cohort was administered lacosamide 200 mg/day, followed by a cohort at 300 mg/day, and then a cohort at 400 mg/day. The results from each cohort were evaluated before enrolling the next highest dose level. The fourth cohort enrolled patients at the highest dose with clinically acceptable safety and tolerability results. Safety evaluations included treatment-emergent adverse events (TEAEs), patient withdrawals due to TEAEs, and changes in vital signs, 12-lead electrocardiography (ECG) studies, laboratory parameters, and clinical examinations. Postinfusion lacosamide plasma concentrations were also evaluated. A total of 100 patients were enrolled, 25 in each cohort. The loading dose for the repeat cohort was 300 mg; therefore, 25 patients were enrolled at 200 mg/day, 50 at 300 mg/day, and 25 at 400 mg/day. Most TEAEs occurred within the first 4 h following infusion; dose-related TEAEs (incidence ≥10%) during this timeframe included dizziness, somnolence, and nausea. Seven patients withdrew, all due to TEAEs: three (6%) from the combined 300 mg group and four (16%) from the 400 mg group; four of these patients discontinued within 4 h following infusion. The most common TEAEs leading to discontinuation (overall incidence >1%) were dizziness (6%), nausea (5%), and vomiting (3%). No clinically relevant pattern of changes from baseline ECG, clinical laboratory parameters, or vital signs were observed. Trough plasma concentrations suggested that near steady-state lacosamide concentrations were achieved with a single intravenous loading dose. Intravenous loading doses of 200 and 300 mg lacosamide administered over 15 min followed by oral lacosamide were well tolerated in lacosamide-naive patients. The 400-mg loading dose was less well tolerated due to a higher frequency of dose-related TEAEs. These results support the feasibility of rapid initiation of adjunctive lacosamide treatment. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Effects of Training Auditory Sequential Memory and Attention on Reading.

ERIC Educational Resources Information Center

Klein, Pnina S.; Schwartz, Allen A.

To determine if auditory sequential memory (ASM) in young children can be improved through training and to discover the effects of such training on the reading scores of children with reading problems, a study was conducted involving 92 second and third graders. For purposes of this study, auditory sequential memory was defined as the ability to…

Cost-effectiveness of simultaneous versus sequential surgery in head and neck reconstruction.

PubMed

Wong, Kevin K; Enepekides, Danny J; Higgins, Kevin M

2011-02-01

To determine whether simultaneous (ablation and reconstruction overlaps by two teams) head and neck reconstruction is cost effective compared to sequentially (ablation followed by reconstruction) performed surgery. Case-controlled study. Tertiary care hospital. Oncology patients undergoing free flap reconstruction of the head and neck. A match paired comparison study was performed with a retrospective chart review examining the total time of surgery for sequential and simultaneous surgery. Nine patients were selected for both the sequential and simultaneous groups. Sequential head and neck reconstruction patients were pair matched with patients who had undergone similar oncologic ablative or reconstructive procedures performed in a simultaneous fashion. A detailed cost analysis using the microcosting method was then undertaken looking at the direct costs of the surgeons, anesthesiologist, operating room, and nursing. On average, simultaneous surgery required 3 hours 15 minutes less operating time, leading to a cost savings of approximately $1200/case when compared to sequential surgery. This represents approximately a 15% reduction in the cost of the entire operation. Simultaneous head and neck reconstruction is more cost effective when compared to sequential surgery.

The effect of a sequential structure of practice for the training of perceptual-cognitive skills in tennis

PubMed Central

2017-01-01

Objective Anticipation of opponent actions, through the use of advanced (i.e., pre-event) kinematic information, can be trained using video-based temporal occlusion. Typically, this involves isolated opponent skills/shots presented as trials in a random order. However, two different areas of research concerning representative task design and contextual (non-kinematic) information, suggest this structure of practice restricts expert performance. The aim of this study was to examine the effect of a sequential structure of practice during video-based training of anticipatory behavior in tennis, as well as the transfer of these skills to the performance environment. Methods In a pre-practice-retention-transfer design, participants viewed life-sized video of tennis rallies across practice in either a sequential order (sequential group), in which participants were exposed to opponent skills/shots in the order they occur in the sport, or a non-sequential (non-sequential group) random order. Results In the video-based retention test, the sequential group was significantly more accurate in their anticipatory judgments when the retention condition replicated the sequential structure compared to the non-sequential group. In the non-sequential retention condition, the non-sequential group was more accurate than the sequential group. In the field-based transfer test, overall decision time was significantly faster in the sequential group compared to the non-sequential group. Conclusion Findings highlight the benefits of a sequential structure of practice for the transfer of anticipatory behavior in tennis. We discuss the role of contextual information, and the importance of representative task design, for the testing and training of perceptual-cognitive skills in sport. PMID:28355263

Lineup composition, suspect position, and the sequential lineup advantage.

PubMed

Carlson, Curt A; Gronlund, Scott D; Clark, Steven E

2008-06-01

N. M. Steblay, J. Dysart, S. Fulero, and R. C. L. Lindsay (2001) argued that sequential lineups reduce the likelihood of mistaken eyewitness identification. Experiment 1 replicated the design of R. C. L. Lindsay and G. L. Wells (1985), the first study to show the sequential lineup advantage. However, the innocent suspect was chosen at a lower rate in the simultaneous lineup, and no sequential lineup advantage was found. This led the authors to hypothesize that protection from a sequential lineup might emerge only when an innocent suspect stands out from the other lineup members. In Experiment 2, participants viewed a simultaneous or sequential lineup with either the guilty suspect or 1 of 3 innocent suspects. Lineup fairness was varied to influence the degree to which a suspect stood out. A sequential lineup advantage was found only for the unfair lineups. Additional analyses of suspect position in the sequential lineups showed an increase in the diagnosticity of suspect identifications as the suspect was placed later in the sequential lineup. These results suggest that the sequential lineup advantage is dependent on lineup composition and suspect position. (c) 2008 APA, all rights reserved

Differential impact of five coronary devices on plaque size: insights from the ABSORB and SPIRIT trials.

PubMed

García-García, Héctor M; Serruys, Patrick W; Campos, Carlos M; Onuma, Yoshinobu

2014-08-20

Coronary plaque size modification, by either local (device) or systemic treatments, has been the target for many years. From ABSORB Cohort A (Absorb BVS 1.0), ABSORB Cohort B (Absorb BVS 1.1), SPIRIT FIRST (Multi-Link Vision vs. Xience V) & SPIRIT II (Xience V vs. Taxus), we calculated the total plaque area (vessel minus lumen area - thus it comprises both compartments - the plaque behind struts and the neointima.) changes by IVUS. A total of 313 patients were included. Comparison-at-6-month follow-up: All devices induced an increase in the total plaque area. The largest increase occurred with Vision and Taxus stents as compared to other devices [Absorb BVS (1.0 and 1.1) and Xience V], (p=0.0002). Comparison-at-2-year follow-up: Absorb BVS 1.1 had a larger increase from post procedure in total plaque compared to Absorb BVS 1.0, Xience V and Taxus (p=0.0499). However, in Absorb BVS 1.1 total plaque showed a reduction of 2.2% from 1 to 3 years. Specifically, the total plaque in the sequential cohorts of Absorb BVS 1.1 increased 16.2% from baseline to 2 years (Cohort B1) while at 3 years this increase is only 5% compared to baseline (Cohort B2). Local devices affect coronary plaque size differently and it depends on the platform (metallic vs. polymeric) and on whether it is a bare - or drug eluting stent. Coronary scaffolds appear to be a promising alternative to metallic stents since they allow plaque regression at long-term follow-up. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Improving medication titration in heart failure by embedding a structured medication titration plan.

PubMed

Hickey, Annabel; Suna, Jessica; Marquart, Louise; Denaro, Charles; Javorsky, George; Munns, Andrew; Mudge, Alison; Atherton, John J

2016-12-01

To improve up-titration of medications to target dose in heart failure patients by improving communication from hospital to primary care. This quality improvement project was undertaken within three heart failure disease management (HFDM) services in Queensland, Australia. A structured medication plan was collaboratively designed and implemented in an iterative manner, using methods including awareness raising and education, audit and feedback, integration into existing work practice, and incentive payments. Evaluation was undertaken using sequential audits, and included process measures (use of the titration plan, assignment of responsibility) and outcome measures (proportion of patients achieving target dose) in HFDM service patients with reduced left ventricular ejection fraction. Comparison of the three patient cohorts (pre-intervention cohort A n=96, intervention cohort B n=95, intervention cohort C n=89) showed increase use of the titration plan, a shift to greater primary care responsibility for titration, and an increase in the proportion of patients achieving target doses of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) (A 37% vs B 48% vs C 55%, p=0.051) and beta-blockers (A 38% vs B 33% vs C 51%, p=0.045). Combining all three cohorts, patients not on target doses when discharged from hospital were more likely to achieve target doses of ACEI/ARB (p<0.0001) and beta blockers (p<0.0001) within six months if they received a medication titration plan. A medication titration plan was successfully implemented in three HFDM services and improved transitional communication and achievement of target doses of evidence-based therapies within six months of hospital discharge. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Non-invasive imaging of atherosclerosis regression with magnetic resonance to guide drug development.

PubMed

Raggi, Paolo; Baldassarre, Damiano; Day, Simon; de Groot, Eric; Fayad, Z A

2016-08-01

Slowing of progression and inducing the regression of atherosclerosis with medical therapy have been shown to be associated with an extensive reduction in risk of cardiovascular events. This proof of concept was obtained with invasive angiographic studies but these are, for obvious reasons, impractical for sequential investigations. Non-invasive imaging has henceforth replaced the more cumbersome invasive studies and has proven extremely valuable in numerous occasions. Because of excellent reproducibility and no radiation exposure, magnetic resonance imaging (MRI) has become the non-invasive method of choice to assess the efficacy of anti-atherosclerotic drugs. The high accuracy of this technology is particularly helpful in rare diseases where the small number of affected patients makes the conduct of outcome-trials in large cohorts impractical. With MRI it is possible to assess the extent, as well as the composition, of atherosclerotic plaques and this further enhances the utility of this technology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Parental Knowledge is a Contextual Amplifier of Associations of Pubertal Maturation and Substance Use.

PubMed

Marceau, Kristine; Abar, Caitlin C; Jackson, Kristina M

2015-09-01

Earlier pubertal development and less parental knowledge have been linked to more substance use during adolescence. The present study examines interactions between pubertal timing and tempo and parental knowledge (children's disclosure, parental control, and parental solicitation) for adolescent substance initiation. Data are from a northeastern US-based cohort-sequential study examining 1023 youth (52 % female) semiannually for up to 6 assessments (ages 10.5-19 years). The findings supported the hypothesis that lower knowledge is a contextual amplifier of early timing-substance use associations in girls and later timing/slower tempo-substance use associations in boys, though results varied based on source of knowledge. The findings suggest that prevention efforts may have the greatest impact when targeting families of early developing girls, and later developing boys, and that incorporating a focus on specific sources of knowledge depending on the pubertal maturation profile of the adolescent may prove valuable in prevention/intervention efforts.

Simultaneous dual contrast weighting using double echo rapid acquisition with relaxation enhancement (RARE) imaging.

PubMed

Fuchs, Katharina; Hezel, Fabian; Klix, Sabrina; Mekle, Ralf; Wuerfel, Jens; Niendorf, Thoralf

2014-12-01

This work proposes a dual contrast rapid acquisition with relaxation enhancement (RARE) variant (2in1-RARE), which provides simultaneous proton density (PD) and T2 * contrast in a single acquisition. The underlying concept of 2in1-RARE is the strict separation of spin echoes and stimulated echoes. This approach offers independent weighting of spin echoes and stimulated echoes. 2in1-RARE was evaluated in phantoms including signal-to-noise ratio (SNR) and point spread function assessment. 2in1-RARE was benchmarked versus coherent RARE and a split-echo RARE variant. The applicability of 2in1-RARE for brain imaging was demonstrated in a small cohort of healthy subjects (n = 10) and, exemplary, a multiple sclerosis patient at 3 Tesla as a precursor to a broader clinical study. 2in1-RARE enables the simultaneous acquisition of dual contrast weighted images without any significant image degradation and without sacrificing SNR versus split-echo RARE. This translates into a factor of two speed gain over multi-contrast, sequential split-echo RARE. A 15% broadening of the point spread function was observed in 2in1-RARE. T1 relaxation effects during the mixing time can be neglected for brain tissue. 2in1-RARE offers simultaneous acquisition of images of anatomical (PD) and functional (T2 *) contrast. It presents an alternative to address scan time constraints frequently encountered during sequential acquisition of T2 * or PD-weighted RARE. © 2013 Wiley Periodicals, Inc.

Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses

NASA Astrophysics Data System (ADS)

Bansal, Sandeep Kumar; Jaiswal, Deepika; Gupta, Nishi; Singh, Kiran; Dada, Rima; Sankhwar, Satya Narayan; Gupta, Gopal; Rajender, Singh

2016-02-01

We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 ± 57.45 million/ml) in comparison to those without deletions (72.49 ± 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39-2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations.

Spatial versus sequential correlations for random access coding

NASA Astrophysics Data System (ADS)

Tavakoli, Armin; Marques, Breno; Pawłowski, Marcin; Bourennane, Mohamed

2016-03-01

Random access codes are important for a wide range of applications in quantum information. However, their implementation with quantum theory can be made in two very different ways: (i) by distributing data with strong spatial correlations violating a Bell inequality or (ii) using quantum communication channels to create stronger-than-classical sequential correlations between state preparation and measurement outcome. Here we study this duality of the quantum realization. We present a family of Bell inequalities tailored to the task at hand and study their quantum violations. Remarkably, we show that the use of spatial and sequential quantum correlations imposes different limitations on the performance of quantum random access codes: Sequential correlations can outperform spatial correlations. We discuss the physics behind the observed discrepancy between spatial and sequential quantum correlations.

Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized study.

PubMed

Nasa, Mukesh; Choksey, Ajay; Phadke, Aniruddha; Sawant, Prabha

2013-11-01

Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. A sequential treatment schedule has been reported to be effective, but studies published to date were performed in Italy. We undertook this study to determine whether these results could be replicated in India. A randomized, open-labeled, prospective controlled trial comparing sequential vs. standard triple-drug therapy was carried out at Lokmanya Tilak Municipal General Hospital, Mumbai. Two hundred and thirty-one patients with dyspepsia were randomized to a 10-day sequential regimen (40 mg of pantoprazole, 1 g of amoxicillin, each administered twice daily for the first 5 days, followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days) or to standard 14-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily). The eradication rate achieved with the sequential regimen was significantly greater than that obtained with the triple therapy. Per-protocol eradication rate of sequential therapy was 92.4% (95% CI 85.8-96.1%) vs. 81.8% (95% CI 73.9-87.8%) (p = 0.027) for standard drug therapy. Intention-to-treat eradication rates were 88.2% (95% CI 80.9-93.0%) vs. 79.1% (95% CI 71.1-85.4%), p = 0.029, respectively. The incidence of major and minor side effects between therapy groups was not significantly different (14.6% in the triple therapy group vs. 23.5% in sequential group, p = 0.12). Follow up was incomplete in 3.3% and 4.7% patients in standard and sequential therapy groups, respectively. Sequential therapy includes one additional antibiotic (tinidazole) that is not contained in standard therapy. Sequential therapy was significantly better than standard therapy for eradicating H. pylori infection.

Proteomic signatures in plasma during early acute renal allograft rejection.

PubMed

Freue, Gabriela V Cohen; Sasaki, Mayu; Meredith, Anna; Günther, Oliver P; Bergman, Axel; Takhar, Mandeep; Mui, Alice; Balshaw, Robert F; Ng, Raymond T; Opushneva, Nina; Hollander, Zsuzsanna; Li, Guiyun; Borchers, Christoph H; Wilson-McManus, Janet; McManus, Bruce M; Keown, Paul A; McMaster, W Robert

2010-09-01

Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change >or=1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and beta(2)-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and controls throughout the period of quiescent follow-up. Results were validated using ELISA where possible, and initial cross-validation estimated a sensitivity of 80% and specificity of 90% for classification of BCAR based on a four-protein ELISA classifier. This study provides evidence that protein concentrations in plasma may provide a relevant measure for the occurrence of BCAR and offers a potential tool for immunologic monitoring.

Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection*

PubMed Central

Freue, Gabriela V. Cohen; Sasaki, Mayu; Meredith, Anna; Günther, Oliver P.; Bergman, Axel; Takhar, Mandeep; Mui, Alice; Balshaw, Robert F.; Ng, Raymond T.; Opushneva, Nina; Hollander, Zsuzsanna; Li, Guiyun; Borchers, Christoph H.; Wilson-McManus, Janet; McManus, Bruce M.; Keown, Paul A.; McMaster, W. Robert

2010-01-01

Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change ≥1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and β2-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and controls throughout the period of quiescent follow-up. Results were validated using ELISA where possible, and initial cross-validation estimated a sensitivity of 80% and specificity of 90% for classification of BCAR based on a four-protein ELISA classifier. This study provides evidence that protein concentrations in plasma may provide a relevant measure for the occurrence of BCAR and offers a potential tool for immunologic monitoring. PMID:20501940

Discrimination between sequential and simultaneous virtual channels with electrical hearing

PubMed Central

Landsberger, David; Galvin, John J.

2011-01-01

In cochlear implants (CIs), simultaneous or sequential stimulation of adjacent electrodes can produce intermediate pitch percepts between those of the component electrodes. However, it is unclear whether simultaneous and sequential virtual channels (VCs) can be discriminated. In this study, CI users were asked to discriminate simultaneous and sequential VCs; discrimination was measured for monopolar (MP) and bipolar + 1 stimulation (BP + 1), i.e., relatively broad and focused stimulation modes. For sequential VCs, the interpulse interval (IPI) varied between 0.0 and 1.8 ms. All stimuli were presented at comfortably loud, loudness-balanced levels at a 250 pulse per second per electrode (ppse) stimulation rate. On average, CI subjects were able to reliably discriminate between sequential and simultaneous VCs. While there was no significant effect of IPI or stimulation mode on VC discrimination, some subjects exhibited better VC discrimination with BP + 1 stimulation. Subjects’ discrimination between sequential and simultaneous VCs was correlated with electrode discrimination, suggesting that spatial selectivity may influence perception of sequential VCs. To maintain equal loudness, sequential VC amplitudes were nearly double those of simultaneous VCs, presumably resulting in a broader spread of excitation. These results suggest that perceptual differences between simultaneous and sequential VCs might be explained by differences in the spread of excitation. PMID:21895094

Discrimination between sequential and simultaneous virtual channels with electrical hearing.

PubMed

Landsberger, David; Galvin, John J

2011-09-01

In cochlear implants (CIs), simultaneous or sequential stimulation of adjacent electrodes can produce intermediate pitch percepts between those of the component electrodes. However, it is unclear whether simultaneous and sequential virtual channels (VCs) can be discriminated. In this study, CI users were asked to discriminate simultaneous and sequential VCs; discrimination was measured for monopolar (MP) and bipolar + 1 stimulation (BP + 1), i.e., relatively broad and focused stimulation modes. For sequential VCs, the interpulse interval (IPI) varied between 0.0 and 1.8 ms. All stimuli were presented at comfortably loud, loudness-balanced levels at a 250 pulse per second per electrode (ppse) stimulation rate. On average, CI subjects were able to reliably discriminate between sequential and simultaneous VCs. While there was no significant effect of IPI or stimulation mode on VC discrimination, some subjects exhibited better VC discrimination with BP + 1 stimulation. Subjects' discrimination between sequential and simultaneous VCs was correlated with electrode discrimination, suggesting that spatial selectivity may influence perception of sequential VCs. To maintain equal loudness, sequential VC amplitudes were nearly double those of simultaneous VCs, presumably resulting in a broader spread of excitation. These results suggest that perceptual differences between simultaneous and sequential VCs might be explained by differences in the spread of excitation. © 2011 Acoustical Society of America

Sequential acquisition of human papillomavirus (HPV) infection of the anus and cervix: the Hawaii HPV Cohort Study.

PubMed

Goodman, Marc T; Shvetsov, Yurii B; McDuffie, Katharine; Wilkens, Lynne R; Zhu, Xuemei; Thompson, Pamela J; Ning, Lily; Killeen, Jeffrey; Kamemoto, Lori; Hernandez, Brenda Y

2010-05-01

Relatively little is known about the epidemiology of anal human papillomavirus (HPV) infection in healthy women and its association with cervical HPV infection. he association of an incident cervical (or anal) HPV infection with the subsequent risk of a genotype-concordant incident anal (or cervical) HPV infection was examined in a longitudinal cohort study of 751 sexually active women. Age-adjusted hazard ratios, obtained using Cox regression, served as measurements of relative risk (RR). Among women, the RR of acquiring an anal HPV infection after a cervical infection with HPV of the same genotype was 20.5 (95% confidence interval, 16.3-25.7), and the RR of acquiring a cervical HPV infection after an anal infection with HPV of the same genotype was 8.8 (95% confidence interval, 6.4-12.2), compared with women without a previous anal/cervical infection with HPV of a concordant genotype. RRs varied by phylogenetic species, with HPV alpha3/alpha15 and alpha1/alpha8/alpha10 types having a greater likelihood than other types of HPV infecting the anus among women with a previous infection at the cervix with HPV of the same genotype. It appears common for anal and cervical HPV infections to occur consecutively. The high degree of genotype-specific concordance suggests that the cervix (vagina) and anus may serve as reservoirs for HPV infection at the other anatomical site.

Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype

PubMed Central

Wei, Caimiao; Gould, Rebekah; Yu, Xian; Zhang, Ya; Liu, Mei; Walls, Andrew; Bousamra, Alex; Ramineni, Maheshwari; Sinn, Bruno; Hunt, Kelly; Buchholz, Thomas A.; Valero, Vicente; Buzdar, Aman U.; Yang, Wei; Brewster, Abenaa M.; Moulder, Stacy; Pusztai, Lajos; Hatzis, Christos; Hortobagyi, Gabriel N.

2017-01-01

Purpose To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)–targeted treatment. Methods We conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor–negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor–negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. Conclusion RCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated. PMID:28135148

Combining qualitative and quantitative evidence to determine factors leading to late presentation for antiretroviral therapy in Malawi.

PubMed

Parrott, Fiona R; Mwafulirwa, Charles; Ngwira, Bagrey; Nkhwazi, Sothini; Floyd, Sian; Houben, Rein M G J; Glynn, Judith R; Crampin, Amelia C; French, Neil

2011-01-01

Treatment seeking delays among people living with HIV have adverse consequences for outcome. Gender differences in treatment outcomes have been observed in sub-Saharan Africa. To better understand antiretroviral treatment (ART) seeking behaviour in HIV-infected adults in rural Malawi. Qualitative interviews with male and female participants in an ART cohort study at a treatment site in rural northern Malawi triangulated with analysis of baseline clinical and demographic data for 365 individuals attending sequentially for ART screening between January 2008 and September 2009. 43% of the cohort presented with late stage HIV disease classified as WHO stage 3/4. Respondents reported that women's frequency of testing, health awareness and commitment to children led to earlier ART uptake and that men's commitment to wider social networks of influence, masculine ideals of strength, and success with sexual and marital partners led them to refuse treatment until they were sick. Quantitative analysis of the screening cohort provided supporting evidence for these expressed views. Overall, male gender (adjusted OR 2.3, 95% CI1.3-3.9) and never being married (adjusted OR 4.1, 95% CI1.5-11.5) were risk factors for late presentation, whereas having ≥3 dependent children was associated with earlier presentation (adjusted OR 0.31, 95% CI0.15-0.63), compared to those with no dependent children. Gender-specific barriers and facilitators operate throughout the whole process of seeking care. Further efforts to enrol men into care earlier should focus on the masculine characteristics that they value, and the risks to these of severe health decline. Our results emphasise the value of exploring as well as identifying behavioural correlates of late presentation.

Lower Respiratory Tract Infection and Short-Term Outcome in Patients With Acute Respiratory Distress Syndrome.

PubMed

Zampieri, Fernando G; Póvoa, Pedro; Salluh, Jorge I; Rodriguez, Alejandro; Valade, Sandrine; Andrade Gomes, José; Reignier, Jean; Molinos, Elena; Almirall, Jordi; Boussekey, Nicolas; Socias, Lorenzo; Ramirez, Paula; Viana, William N; Rouzé, Anahita; Nseir, Saad; Martin-Loeches, Ignacio

2018-01-01

To assess whether ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with mortality in critically ill patients with acute respiratory distress syndrome (ARDS). Post hoc analysis of prospective cohort study including mechanically ventilated patients from a multicenter prospective observational study (TAVeM study); VA-LRTI was defined as either ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP) based on clinical criteria and microbiological confirmation. Association between intensive care unit (ICU) mortality in patients having ARDS with and without VA-LRTI was assessed through logistic regression controlling for relevant confounders. Association between VA-LRTI and duration of mechanical ventilation and ICU stay was assessed through competing risk analysis. Contribution of VA-LRTI to a mortality model over time was assessed through sequential random forest models. The cohort included 2960 patients of which 524 fulfilled criteria for ARDS; 21% had VA-LRTI (VAT = 10.3% and VAP = 10.7%). After controlling for illness severity and baseline health status, we could not find an association between VA-LRTI and ICU mortality (odds ratio: 1.07; 95% confidence interval: 0.62-1.83; P = .796); VA-LRTI was also not associated with prolonged ICU length of stay or duration of mechanical ventilation. The relative contribution of VA-LRTI to the random forest mortality model remained constant during time. The attributable VA-LRTI mortality for ARDS was higher than the attributable mortality for VA-LRTI alone. After controlling for relevant confounders, we could not find an association between occurrence of VA-LRTI and ICU mortality in patients with ARDS.

Immediate Sequential Bilateral Pediatric Vitreoretinal Surgery: An International Multicenter Study.

PubMed

Yonekawa, Yoshihiro; Wu, Wei-Chi; Kusaka, Shunji; Robinson, Joshua; Tsujioka, Daishi; Kang, Kai B; Shapiro, Michael J; Padhi, Tapas R; Jain, Lubhani; Sears, Jonathan E; Kuriyan, Ajay E; Berrocal, Audina M; Quiram, Polly A; Gerber, Amanda E; Paul Chan, R V; Jonas, Karyn E; Wong, Sui Chien; Patel, C K; Abbey, Ashkan M; Spencer, Rand; Blair, Michael P; Chang, Emmanuel Y; Papakostas, Thanos D; Vavvas, Demetrios G; Sisk, Robert A; Ferrone, Philip J; Henderson, Robert H; Olsen, Karl R; Hartnett, M Elizabeth; Chau, Felix Y; Mukai, Shizuo; Murray, Timothy G; Thomas, Benjamin J; Meza, P Anthony; Drenser, Kimberly A; Trese, Michael T; Capone, Antonio

2016-08-01

To determine the feasibility and safety of bilateral simultaneous vitreoretinal surgery in pediatric patients. International, multicenter, interventional, retrospective case series. Patients 17 years of age or younger from 24 centers worldwide who underwent immediate sequential bilateral vitreoretinal surgery (ISBVS)-defined as vitrectomy, scleral buckle, or lensectomy using the vitreous cutter-performed in both eyes sequentially during the same anesthesia session. Clinical history, surgical details and indications, time under anesthesia, and intraoperative and postoperative ophthalmic and systemic adverse events were reviewed. Ocular and systemic adverse events. A total of 344 surgeries from 172 ISBVS procedures in 167 patients were included in the study. The mean age of the cohort was 1.3±2.6 years. Nonexclusive indications for ISBVS were rapidly progressive disease (74.6%), systemic morbidity placing the child at high anesthesia risk (76.0%), and residence remote from surgery location (30.2%). The most common diagnoses were retinopathy of prematurity (ROP; 72.7% [P < 0.01]; stage 3, 4.8%; stage 4A, 44.4%; stage 4B, 22.4%; stage 5, 26.4%), familial exudative vitreoretinopathy (7.0%), abusive head trauma (4.1%), persistent fetal vasculature (3.5%), congenital cataract (1.7%), posterior capsular opacification (1.7%), rhegmatogenous retinal detachment (1.7%), congenital X-linked retinoschisis (1.2%), Norrie disease (2.3%), and viral retinitis (1.2%). Mean surgical time was 143±59 minutes for both eyes. Higher ROP stage correlated with longer surgical time (P = 0.02). There were no reported intraoperative ocular complications. During the immediate postoperative period, 2 eyes from different patients demonstrated unilateral vitreous hemorrhage (0.6%). No cases of endophthalmitis, choroidal hemorrhage, or hypotony occurred. Mean total anesthesia time was 203±87 minutes. There were no cases of anesthesia-related death, malignant hyperthermia, anaphylaxis, or cardiac event. There was 1 case of reintubation (0.6%) and 1 case of prolonged oxygen desaturation (0.6%). Mean follow-up after surgery was 103 weeks, and anatomic success and globe salvage rates were 89.8% and 98.0%, respectively. This study found ISBVS to be a feasible and safe treatment paradigm for pediatric patients with bilateral vitreoretinal pathologic features when repeated general anesthesia is undesirable or impractical. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The emergence of temporal language in Nicaraguan Sign Language

PubMed Central

Kocab, Annemarie; Senghas, Ann; Snedeker, Jesse

2016-01-01

Understanding what uniquely human properties account for the creation and transmission of language has been a central goal of cognitive science. Recently, the study of emerging sign languages, such as Nicaraguan Sign Language (NSL), has offered the opportunity to better understand how languages are created and the roles of the individual learner and the community of users. Here, we examined the emergence of two types of temporal language in NSL, comparing the linguistic devices for conveying temporal information among three sequential age cohorts of signers. Experiment 1 showed that while all three cohorts of signers could communicate about linearly ordered discrete events, only the second and third generations of signers successfully communicated information about events with more complex temporal structure. Experiment 2 showed that signers could discriminate between the types of temporal events in a nonverbal task. Finally, Experiment 3 investigated the ordinal use of numbers (e.g., first, second) in NSL signers, indicating that one strategy younger signers might have for accurately describing events in time might be to use ordinal numbers to mark each event. While the capacity for representing temporal concepts appears to be present in the human mind from the onset of language creation, the linguistic devices to convey temporality do not appear immediately. Evidently, temporal language emerges over generations of language transmission, as a product of individual minds interacting within a community of users. PMID:27591549

Self-Debriefing vs Instructor Debriefing in a Pre-Internship Simulation Curriculum: Night on Call

PubMed Central

Oikawa, Sayaka; Turban, Joseph; Vincent, Dale; Mandai, Yasuhiro; Birkmire-Peters, Deborah

2016-01-01

This study sought to determine if learner self-performance assessment (SPA) and team-performance assessment (TPA) were different when simulation based education (SBE) was supported by self-debriefing (S-DB), compared to traditional facilitator-led debriefing (F-DB). “One-Night-On-Call,” an internship preparation curriculum, was selected to provide SBE. Participants worked as team members in 4 sequential bedside acute care problem-solving scenarios. Fifty-seven learners were randomized to 9 F-DB and 10 S-DB Teams. Participants completed SPA and TPA assessment checklist questionnaires immediately following the first and fourth (final) scenarios. Learner SPA and TPA scores improved overall from the first to the fourth scenarios (P <.05). F-DB versus S-DB cohorts did not differ in overall SPA scores. The F-DB average TPA score was 12.8 (SD±2.1) compared to a S-DB score of 14.1 (SD±2.1) (P =.001). F-DB participants' increase in TPA was due to increases in the Patient Assessment and Treatment sub-domains that exceeded corresponding improvements in the S-DB cohort. Self- debriefing strategies are equivalent to facilitator-led debriefing in some situations. Self-debriefing offers opportunities to enable simulation-based education by decreasing the number of required faculty debriefers, and may be uniquely well matched to simulation-based teamwork training. PMID:27239391

The emergence of temporal language in Nicaraguan Sign Language.

PubMed

Kocab, Annemarie; Senghas, Ann; Snedeker, Jesse

2016-11-01

Understanding what uniquely human properties account for the creation and transmission of language has been a central goal of cognitive science. Recently, the study of emerging sign languages, such as Nicaraguan Sign Language (NSL), has offered the opportunity to better understand how languages are created and the roles of the individual learner and the community of users. Here, we examined the emergence of two types of temporal language in NSL, comparing the linguistic devices for conveying temporal information among three sequential age cohorts of signers. Experiment 1 showed that while all three cohorts of signers could communicate about linearly ordered discrete events, only the second and third generations of signers successfully communicated information about events with more complex temporal structure. Experiment 2 showed that signers could discriminate between the types of temporal events in a nonverbal task. Finally, Experiment 3 investigated the ordinal use of numbers (e.g., first, second) in NSL signers, indicating that one strategy younger signers might have for accurately describing events in time might be to use ordinal numbers to mark each event. While the capacity for representing temporal concepts appears to be present in the human mind from the onset of language creation, the linguistic devices to convey temporality do not appear immediately. Evidently, temporal language emerges over generations of language transmission, as a product of individual minds interacting within a community of users. Copyright © 2016 Elsevier B.V. All rights reserved.

The development of loneliness from mid- to late adolescence: trajectory classes, personality traits, and psychosocial functioning.

PubMed

Vanhalst, Janne; Goossens, Luc; Luyckx, Koen; Scholte, Ron H J; Engels, Rutger C M E

2013-12-01

Although loneliness is a common problem across late adolescence, its developmental course has not been investigated in depth in this period of life. The present study aims to fill this gap by means of a five-wave cohort-sequential longitudinal study spanning ages 15 to 20 (N = 389). Both variable-centered (i.e., latent growth curve modeling) and person-centered (i.e., latent class growth analysis) approaches were used. Variable-centered analyses showed that loneliness generally decreased over time. Person-centered analyses pointed to considerable inter-individual differences in the development of loneliness, and identified five trajectory classes (i.e., stable low, low increasing, moderate decreasing, high increasing, and chronically high). These five trajectory classes were differentially related to personality traits at age 15 (i.e., extraversion, agreeableness, and emotional stability) and psychosocial functioning at age 20 (i.e., depressive symptoms, self-esteem, anxiety, and perceived stress). These findings underscore the additional value of studying subgroups regarding the development of loneliness. Copyright © 2012 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Ego-resiliency development from late adolescence to emerging adulthood: A ten-year longitudinal study.

PubMed

Alessandri, Guido; Eisenberg, Nancy; Vecchione, Michele; Caprara, Gian Vittorio; Milioni, Michela

2016-07-01

This study examined the development of ego-resiliency from late adolescence to emerging adulthood, using a 10-year cohort-sequential design. Participants were 335 Italian adolescents (173 females and 162 males), living, at the time of the study, in Genzano, a small city near to Rome. Latent growth curve analyses indicated that the developmental trajectory of ego-resiliency from 15 to 25 years is adequately described by a piecewise model that included separate growth profiles corresponding to different developmental stages. Essentially, ego-resiliency remained remarkably stable until the end of high school, and then encountered a phase of relative increase. Moreover, the trajectory of ego-resiliency from ages 15 to 19 was predicted by self-efficacy beliefs in managing negative emotions, and the trajectory from age 19 to 25 was predicted by experienced familial support and self-efficacy beliefs in expressing positive emotions at age 15. Experienced stressful life events also accounted for individuals' deviation from the typical ego-resiliency trajectory. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Sequential-Simultaneous Analysis of Japanese Children's Performance on the Japanese McCarthy.

ERIC Educational Resources Information Center

Ishikuma, Toshinori; And Others

This study explored the hypothesis that Japanese children perform significantly better on simultaneous processing than on sequential processing. The Kaufman Assessment Battery for Children (K-ABC) served as the criterion of the two types of mental processing. Regression equations to predict Sequential and Simultaneous processing from McCarthy…

Description and effects of sequential behavior practice in teacher education.

PubMed

Sharpe, T; Lounsbery, M; Bahls, V

1997-09-01

This study examined the effects of a sequential behavior feedback protocol on the practice-teaching experiences of undergraduate teacher trainees. The performance competencies of teacher trainees were analyzed using an alternative opportunities for appropriate action measure. Data support the added utility of sequential (Sharpe, 1997a, 1997b) behavior analysis information in systematic observation approaches to teacher education. One field-based undergraduate practicum using sequential behavior (i.e., field systems analysis) principles was monitored. Summarized are the key elements of the (a) classroom instruction provided as a precursor to the practice teaching experience, (b) practice teaching experience, and (c) field systems observation tool used for evaluation and feedback, including multiple-baseline data (N = 4) to support this approach to teacher education. Results point to (a) the strong relationship between sequential behavior feedback and the positive change in four preservice teachers' day-to-day teaching practices in challenging situational contexts, and (b) the relationship between changes in teacher practices and positive changes in the behavioral practices of gymnasium pupils. Sequential behavior feedback was also socially validated by the undergraduate participants and Professional Development School teacher supervisors in the study.

A Sequential Multiplicative Extended Kalman Filter for Attitude Estimation Using Vector Observations.

PubMed

Qin, Fangjun; Chang, Lubin; Jiang, Sai; Zha, Feng

2018-05-03

In this paper, a sequential multiplicative extended Kalman filter (SMEKF) is proposed for attitude estimation using vector observations. In the proposed SMEKF, each of the vector observations is processed sequentially to update the attitude, which can make the measurement model linearization more accurate for the next vector observation. This is the main difference to Murrell’s variation of the MEKF, which does not update the attitude estimate during the sequential procedure. Meanwhile, the covariance is updated after all the vector observations have been processed, which is used to account for the special characteristics of the reset operation necessary for the attitude update. This is the main difference to the traditional sequential EKF, which updates the state covariance at each step of the sequential procedure. The numerical simulation study demonstrates that the proposed SMEKF has more consistent and accurate performance in a wide range of initial estimate errors compared to the MEKF and its traditional sequential forms.

A Sequential Multiplicative Extended Kalman Filter for Attitude Estimation Using Vector Observations

PubMed Central

Qin, Fangjun; Jiang, Sai; Zha, Feng

2018-01-01

In this paper, a sequential multiplicative extended Kalman filter (SMEKF) is proposed for attitude estimation using vector observations. In the proposed SMEKF, each of the vector observations is processed sequentially to update the attitude, which can make the measurement model linearization more accurate for the next vector observation. This is the main difference to Murrell’s variation of the MEKF, which does not update the attitude estimate during the sequential procedure. Meanwhile, the covariance is updated after all the vector observations have been processed, which is used to account for the special characteristics of the reset operation necessary for the attitude update. This is the main difference to the traditional sequential EKF, which updates the state covariance at each step of the sequential procedure. The numerical simulation study demonstrates that the proposed SMEKF has more consistent and accurate performance in a wide range of initial estimate errors compared to the MEKF and its traditional sequential forms. PMID:29751538

What are the Patterns Between Depression, Smoking, Unhealthy Alcohol Use, and Other Substance Use Among Individuals Receiving Medical Care? A Longitudinal Study of 5479 Participants.

PubMed

Ruggles, Kelly V; Fang, Yixin; Tate, Janet; Mentor, Sherry M; Bryant, Kendall J; Fiellin, David A; Justice, Amy C; Braithwaite, R Scott

2017-07-01

To evaluate and characterize the structure of temporal patterns of depression, smoking, unhealthy alcohol use, and other substance use among individuals receiving medical care, and to inform discussion about whether integrated screening and treatment strategies for these conditions are warranted. Using the Veterans Aging Cohort Study (VACS) we measured depression, smoking, unhealthy alcohol use and other substance use (stimulants, marijuana, heroin, opioids) and evaluated which conditions tended to co-occur within individuals, and how this co-occurrence was temporally structured (i.e. concurrently, sequentially, or discordantly). Current depression was associated with current use of every substance examined with the exception of unhealthy alcohol use. Current unhealthy alcohol use and marijuana use were also consistently associated. Current status was strongly predicted by prior status (p < 0.0001; OR = 2.99-22.34) however, there were few other sequential relationships. Associations in the HIV infected and uninfected subgroups were largely the same with the following exceptions. Smoking preceded unhealthy alcohol use and current smoking was associated with current depression in the HIV infected subgroup only (p < 0.001; OR = 1.33-1.41 and p < 0.001; OR = 1.25-1.43). Opioid use and current unhealthy alcohol use were negatively associated only in the HIV negative subgroup (p = 0.01; OR = 0.75). Patterns of depression, smoking, unhealthy alcohol use, and other substance use were temporally concordant, particularly with regard to depression and substance use. These patterns may inform future development of more integrated screening and treatment strategies.

Inflammation, vitamin deficiencies and organ failure in critically ill patients.

PubMed

Corcoran, T B; O'Neill, M P; Webb, S A R; Ho, K M

2009-09-01

It is unknown whether biochemical vitamin deficiencies in critical illness are associated with severity of illness, organ dysfunction, inflammation or mortality. This nested cohort study recruited 98 patients admitted as emergencies to the intensive care unit, who had a stay of greater than 48 hours. Patient data were prospectively collected. Within the first 48 hours of admission, concentrations of C-reactive protein, vitamins A, E, B1, B12 and folate were measured on arterial blood. These measures were then repeated at least once during the later (> 48 hours) period of their stay. Seventy patients (71%) had completed vitamin studies eligible for inclusion in the analysis. Ten patients died (14.3%) during their hospital stay and mortality was associated with age, admission source and severity of illness scores. Vitamin B12 concentration was weakly associated with C-reactive protein concentrations on admission to the intensive care unit (r on days one and two = 0.4 [P = 0.002], 0.36 [P = 0.04], respectively) and with the Sequential Organ Failure Assessment score between days two and four (Spearman's r = 0.361 [P = 0.04], 0.42 [P = 0.02] and 0.48 [P = 0.02], respectively). Vitamin A concentration was weakly associated with the C-reactive protein concentrations on days one and five (Spearman's r = -0.5 [P = 0.001], -0.4 [P = 0.03], respectively). Change in deficiency status of any of the vitamins over time in the first week of intensive care admission did not appear to influence mortality. We conclude that while weak correlations were identified between vitamins A and B12 and C-reactive protein and Sequential Organ Failure Assessment scores, the importance of these associations and their relationship to hospital mortality remain to be determined.

Aging and sequential modulations of poorer strategy effects: An EEG study in arithmetic problem solving.

PubMed

Hinault, Thomas; Lemaire, Patrick; Phillips, Natalie

2016-01-01

This study investigated age-related differences in electrophysiological signatures of sequential modulations of poorer strategy effects. Sequential modulations of poorer strategy effects refer to decreased poorer strategy effects (i.e., poorer performance when the cued strategy is not the best) on current problem following poorer strategy problems compared to after better strategy problems. Analyses on electrophysiological (EEG) data revealed important age-related changes in time, frequency, and coherence of brain activities underlying sequential modulations of poorer strategy effects. More specifically, sequential modulations of poorer strategy effects were associated with earlier and later time windows (i.e., between 200- and 550 ms and between 850- and 1250 ms). Event-related potentials (ERPs) also revealed an earlier onset in older adults, together with more anterior and less lateralized activations. Furthermore, sequential modulations of poorer strategy effects were associated with theta and alpha frequencies in young adults while these modulations were found in delta frequency and theta inter-hemispheric coherence in older adults, consistent with qualitatively distinct patterns of brain activity. These findings have important implications to further our understanding of age-related differences and similarities in sequential modulations of cognitive control processes during arithmetic strategy execution. Copyright © 2015 Elsevier B.V. All rights reserved.

A 52-week prospective, cohort study of the effects of losartan with or without hydrochlorothiazide (HCTZ) in hypertensive patients with metabolic syndrome.

PubMed

Racine, N; Hamet, P; Sampalis, J S; Longo, N; Bastien, N

2010-11-01

The impact of an ARB, with or without hydrochlorothiazide (HCTZ), on glycaemic factors and the risk for developing diabetes in hypertensive patients with the metabolic syndrome have not been fully assessed. This was a 52-week multicentre, prospective, phase-IV, open-label, cohort study of losartan or losartan/HCTZ in hypertensive patients with metabolic syndrome. All subjects were treated initially with losartan 50 mg day(-1). Those not achieving target blood pressure (BP <140/90 mm Hg) were titrated sequentially to losartan 100 mg, losartan 100 mg/HCTZ 12.5 mg, losartan 100 mg/HCTZ 25 mg and finally to losartan 100 mg/HCTZ 25 mg and calcium-channel blocker (CCB), as required. The primary glycaemic outcome measure was change in fasting blood glucose (FBG) and glycosylated haemoglobin A1c (HbA1c) at 52 weeks of treatment. Among the 1897 potentially eligible patients enrolled in the study, 1714 fulfilled the screening criteria. During the 52-week treatment period of the study, FBG and HbA1c did not change significantly. Clinically important and statistically significant changes were observed for both the systolic (SBP) and diastolic BP (DBP) during the study treatment period, with an overall mean decrease of 16.95 mm Hg in SBP (P=0.001) and 9.84 mm Hg in DBP (P=0.001). The majority of the patients (77.3%) achieved a target BP of <140/90 mm Hg. In conclusion, losartan, either alone or in combination with HCTZ, is effective in managing hypertension without inducing any change in glycaemic parameters or increasing the risk for developing diabetes in hypertensive patients with the metabolic syndrome.

A sequential Cox approach for estimating the causal effect of treatment in the presence of time-dependent confounding applied to data from the Swiss HIV Cohort Study.

PubMed

Gran, Jon Michael; Røysland, Kjetil; Wolbers, Marcel; Didelez, Vanessa; Sterne, Jonathan A C; Ledergerber, Bruno; Furrer, Hansjakob; von Wyl, Viktor; Aalen, Odd O

2010-11-20

When estimating the effect of treatment on HIV using data from observational studies, standard methods may produce biased estimates due to the presence of time-dependent confounders. Such confounding can be present when a covariate, affected by past exposure, is both a predictor of the future exposure and the outcome. One example is the CD4 cell count, being a marker for disease progression for HIV patients, but also a marker for treatment initiation and influenced by treatment. Fitting a marginal structural model (MSM) using inverse probability weights is one way to give appropriate adjustment for this type of confounding. In this paper we study a simple and intuitive approach to estimate similar treatment effects, using observational data to mimic several randomized controlled trials. Each 'trial' is constructed based on individuals starting treatment in a certain time interval. An overall effect estimate for all such trials is found using composite likelihood inference. The method offers an alternative to the use of inverse probability of treatment weights, which is unstable in certain situations. The estimated parameter is not identical to the one of an MSM, it is conditioned on covariate values at the start of each mimicked trial. This allows the study of questions that are not that easily addressed fitting an MSM. The analysis can be performed as a stratified weighted Cox analysis on the joint data set of all the constructed trials, where each trial is one stratum. The model is applied to data from the Swiss HIV cohort study. Copyright © 2010 John Wiley & Sons, Ltd.

Orphan therapies: making best use of postmarket data.

PubMed

Maro, Judith C; Brown, Jeffrey S; Dal Pan, Gerald J; Li, Lingling

2014-08-01

Postmarket surveillance of the comparative safety and efficacy of orphan therapeutics is challenging, particularly when multiple therapeutics are licensed for the same orphan indication. To make best use of product-specific registry data collected to fulfill regulatory requirements, we propose the creation of a distributed electronic health data network among registries. Such a network could support sequential statistical analyses designed to detect early warnings of excess risks. We use a simulated example to explore the circumstances under which a distributed network may prove advantageous. We perform sample size calculations for sequential and non-sequential statistical studies aimed at comparing the incidence of hepatotoxicity following initiation of two newly licensed therapies for homozygous familial hypercholesterolemia. We calculate the sample size savings ratio, or the proportion of sample size saved if one conducted a sequential study as compared to a non-sequential study. Then, using models to describe the adoption and utilization of these therapies, we simulate when these sample sizes are attainable in calendar years. We then calculate the analytic calendar time savings ratio, analogous to the sample size savings ratio. We repeat these analyses for numerous scenarios. Sequential analyses detect effect sizes earlier or at the same time as non-sequential analyses. The most substantial potential savings occur when the market share is more imbalanced (i.e., 90% for therapy A) and the effect size is closest to the null hypothesis. However, due to low exposure prevalence, these savings are difficult to realize within the 30-year time frame of this simulation for scenarios in which the outcome of interest occurs at or more frequently than one event/100 person-years. We illustrate a process to assess whether sequential statistical analyses of registry data performed via distributed networks may prove a worthwhile infrastructure investment for pharmacovigilance.

Self-regulated learning of important information under sequential and simultaneous encoding conditions.

PubMed

Middlebrooks, Catherine D; Castel, Alan D

2018-05-01

Learners make a number of decisions when attempting to study efficiently: they must choose which information to study, for how long to study it, and whether to restudy it later. The current experiments examine whether documented impairments to self-regulated learning when studying information sequentially, as opposed to simultaneously, extend to the learning of and memory for valuable information. In Experiment 1, participants studied lists of words ranging in value from 1-10 points sequentially or simultaneously at a preset presentation rate; in Experiment 2, study was self-paced and participants could choose to restudy. Although participants prioritized high-value over low-value information, irrespective of presentation, those who studied the items simultaneously demonstrated superior value-based prioritization with respect to recall, study selections, and self-pacing. The results of the present experiments support the theory that devising, maintaining, and executing efficient study agendas is inherently different under sequential formatting than simultaneous. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Epidemiology and Changes in Mortality of Sepsis After the Implementation of Surviving Sepsis Campaign Guidelines.

PubMed

Herrán-Monge, Rubén; Muriel-Bombín, Arturo; García-García, Marta M; Merino-García, Pedro A; Martínez-Barrios, Miguel; Andaluz, David; Ballesteros, Juan Carlos; Domínguez-Berrot, Ana María; Moradillo-Gonzalez, Susana; Macías, Santiago; Álvarez-Martínez, Braulio; Fernández-Calavia, M José; Tarancón, Concepción; Villar, Jesús; Blanco, Jesús

2017-01-01

To determine the epidemiology and outcome of severe sepsis and septic shock after 9 years of the implementation of the Surviving Sepsis Campaign (SSC) and to build a mortality prediction model. This is a prospective, multicenter, observational study performed during a 5-month period in 2011 in a network of 11 intensive care units (ICUs). We compared our findings with those obtained in the same ICUs in a study conducted in 2002. The current cohort included 262 episodes of severe sepsis and/or septic shock, and the 2002 cohort included 324. The prevalence was 14% (95% confidence interval: 12.5-15.7) with no differences to 2002. The population-based incidence was 31 cases/100 000 inhabitants/year. Patients in 2011 had a significantly lower Acute Physiology and Chronic Health Evaluation II (APACHE II; 21.9 ± 6.6 vs 25.5 ± 7.07), Logistic Organ Dysfunction Score (5.6 ± 3.2 vs 6.3 ± 3.6), and Sequential Organ Failure Assessment (SOFA) scores on day 1 (8 ± 3.5 vs 9.6 ± 3.7; P < .01). The main source of infection was intraabdominal (32.5%) although microbiologic isolation was possible in 56.7% of cases. The 2011 cohort had a marked reduction in 48-hour (7% vs 14.8%), ICU (27.2% vs 48.2%), and in-hospital (36.7% vs 54.3%) mortalities. Most relevant factors associated with death were APACHE II score, age, previous immunosuppression and liver insufficiency, alcoholism, nosocomial infection, and Delta SOFA score. Although the incidence of sepsis/septic shock remained unchanged during a 10-year period, the implementation of the SSC guidelines resulted in a marked decrease in the overall mortality. The lower severity of patients on ICU admission and the reduced early mortality suggest an improvement in early diagnosis, better initial management, and earlier antibiotic treatment.

Cost effectiveness of total knee arthroplasty from a health care providers' perspective before and after introduction of an interdisciplinary clinical pathway--is investment always improvement?

PubMed

Krummenauer, Frank; Guenther, Klaus-Peter; Kirschner, Stephan

2011-12-14

Total knee arthroplasty (TKA) is an effective, but also cost-intensive health care intervention for end stage osteoarthritis. This investigation was designed to evaluate the cost-effectiveness of TKA before versus after introduction of an interdisciplinary clinical pathway from a University Orthopedic Surgery Department's cost perspective as an interdisciplinary full service health care provider. A prospective trial recruited two sequential cohorts of 132 and 128 consecutive patients, who were interviewed by means of the WOMAC questionnaire. Direct process costs from the health care providers' perspective were estimated according to the German DRG calculation framework. The health economic evaluation was based on margiual cost-effectveness ratios (MCERs); an individual marginal cost effectiveness relation≤100 € per % WOMAC index increase was considered as primary endpoint of the confirmatory cohort comparison. The interdisciplinary clinical pathway under consideration primarily consisted of a voluntary preoperative personal briefing of patients concerning postoperatively expectable progess in health status and optimum use of walking aids after surgery. All patients were supplied with written information on these topics, attendance of the personal briefing also included preoperative training for postoperative mobilisation by the Department's physiotherapeutic staff. An individual marginal cost effectiveness relation≤100 €/% WOMAC index increase was found in 38% of the patients in the pre pathway implementation cohort versus in 30% of the post pathway implementation cohort (Fisher p=0.278). Both cohorts showed substantial improvement in WOMAC scores (39 versus 35% in median), whereas the cohort did not differ significantly in the median WOMAC score before surgery (41% for the pre pathway cohort versus 44% for the post pathway cohort). Despite a locally significant decrease in costs (4303 versus 4194 € in median), the individual cost/benefit relation became worse after introduction of the pathway: for the first cohort the MCER was estimated 108 € per gained % WOMAC index increase (86-150 €/%) versus 118 €/% WOMAC gain (93-173 €/%) in the second cohort after pathway implementation. In summary, the proposed critical pathway for TKA could be shown to be significantly cost efficient, but not cost effective concerning functional outcome, when the above individual marginal cost effectiveness criterion was concentrated on. The introduction of an interdisciplinary clinical pathway does not necessarily improve patient related outcomes. On the contrary, cost effectiveness from the health care providers' perspective may even turn out remarkably reduced in the setting considered here (functional outcome assessment after treatment by a full service health care provider).

Cost effectiveness of total knee arthroplasty from a health care providers' perspective before and after introduction of an interdisciplinary clinical pathway - is investment always improvement?

PubMed Central

2011-01-01

Background Total knee arthroplasty (TKA) is an effective, but also cost-intensive health care intervention for end stage osteoarthritis. This investigation was designed to evaluate the cost-effectiveness of TKA before versus after introduction of an interdisciplinary clinical pathway from a University Orthopedic Surgery Department's cost perspective as an interdisciplinary full service health care provider. Methods A prospective trial recruited two sequential cohorts of 132 and 128 consecutive patients, who were interviewed by means of the WOMAC questionnaire. Direct process costs from the health care providers' perspective were estimated according to the German DRG calculation framework. The health economic evaluation was based on margiual cost-effectveness ratios (MCERs); an individual marginal cost effectiveness relation ≤ 100 € per % WOMAC index increase was considered as primary endpoint of the confirmatory cohort comparison. The interdisciplinary clinical pathway under consideration primarily consisted of a voluntary preoperative personal briefing of patients concerning postoperatively expectable progess in health status and optimum use of walking aids after surgery. All patients were supplied with written information on these topics, attendance of the personal briefing also included preoperative training for postoperative mobilisation by the Department's physiotherapeutic staff. Results An individual marginal cost effectiveness relation ≤ 100 €/% WOMAC index increase was found in 38% of the patients in the pre pathway implementation cohort versus in 30% of the post pathway implementation cohort (Fisher p = 0.278). Both cohorts showed substantial improvement in WOMAC scores (39 versus 35% in median), whereas the cohort did not differ significantly in the median WOMAC score before surgery (41% for the pre pathway cohort versus 44% for the post pathway cohort). Despite a locally significant decrease in costs (4303 versus 4194 € in median), the individual cost/benefit relation became worse after introduction of the pathway: for the first cohort the MCER was estimated 108 € per gained % WOMAC index increase (86 - 150 €/%) versus 118 €/% WOMAC gain (93 - 173 €/%) in the second cohort after pathway implementation. In summary, the proposed critical pathway for TKA could be shown to be significantly cost efficient, but not cost effective concerning functional outcome, when the above individual marginal cost effectiveness criterion was concentrated on. Conclusions The introduction of an interdisciplinary clinical pathway does not necessarily improve patient related outcomes. On the contrary, cost effectiveness from the health care providers' perspective may even turn out remarkably reduced in the setting considered here (functional outcome assessment after treatment by a full service health care provider). PMID:22168149

Sequential Effects on Speeded Information Processing: A Developmental Study

ERIC Educational Resources Information Center

Smulders, S.F.A.; Notebaert, W.; Meijer, M.; Crone, E.A.; van der Molen, M.W.; Soetens, E.

2005-01-01

Two experiments were performed to assess age-related changes in sequential effects on choice reaction time (RT). Sequential effects portray the influence of previous trials on the RT to the current stimulus. In Experiment 1, three age groups (7-9, 10-12, and 18-25 years) performed a spatially compatible choice task, with response-to-stimulus…

Lineup Composition, Suspect Position, and the Sequential Lineup Advantage

ERIC Educational Resources Information Center

Carlson, Curt A.; Gronlund, Scott D.; Clark, Steven E.

2008-01-01

N. M. Steblay, J. Dysart, S. Fulero, and R. C. L. Lindsay (2001) argued that sequential lineups reduce the likelihood of mistaken eyewitness identification. Experiment 1 replicated the design of R. C. L. Lindsay and G. L. Wells (1985), the first study to show the sequential lineup advantage. However, the innocent suspect was chosen at a lower rate…

Sequential and Simultaneous Processing Abilities of High-Functioning Autistic and Language-Impaired Children.

ERIC Educational Resources Information Center

Allen, Mark H.; And Others

1991-01-01

This study found that a group of 20 children (ages 6-12) with autism and a group of 20 children with developmental receptive language disorder both manifested a relative sequential processing deficit. The groups did not differ significantly on overall sequential and simultaneous processing capabilities relative to their degree of language…

A collaborative sequential meta-analysis of individual patient data from randomized trials of endovascular therapy and tPA vs. tPA alone for acute ischemic stroke: ThRombEctomy And tPA (TREAT) analysis: statistical analysis plan for a sequential meta-analysis performed within the VISTA-Endovascular collaboration.

PubMed

MacIsaac, Rachael L; Khatri, Pooja; Bendszus, Martin; Bracard, Serge; Broderick, Joseph; Campbell, Bruce; Ciccone, Alfonso; Dávalos, Antoni; Davis, Stephen M; Demchuk, Andrew; Diener, Hans-Christoph; Dippel, Diederik; Donnan, Geoffrey A; Fiehler, Jens; Fiorella, David; Goyal, Mayank; Hacke, Werner; Hill, Michael D; Jahan, Reza; Jauch, Edward; Jovin, Tudor; Kidwell, Chelsea S; Liebeskind, David; Majoie, Charles B; Martins, Sheila Cristina Ouriques; Mitchell, Peter; Mocco, J; Muir, Keith W; Nogueira, Raul; Saver, Jeffrey L; Schonewille, Wouter J; Siddiqui, Adnan H; Thomalla, Götz; Tomsick, Thomas A; Turk, Aquilla S; White, Philip; Zaidat, Osama; Lees, Kennedy R

2015-10-01

Endovascular treatment has been shown to restore blood flow effectively. Second-generation medical devices such as stent retrievers are now showing overwhelming efficacy in clinical trials, particularly in conjunction with intravenous recombinant tissue plasminogen activator. This statistical analysis plan utilizing a novel, sequential approach describes a prospective, individual patient data analysis of endovascular therapy in conjunction with intravenous recombinant tissue plasminogen activator agreed upon by the Thrombectomy and Tissue Plasminogen Activator Collaborative Group. This protocol will specify the primary outcome for efficacy, as 'favorable' outcome defined by the ordinal distribution of the modified Rankin Scale measured at three-months poststroke, but with modified Rankin Scales 5 and 6 collapsed into a single category. The primary analysis will aim to answer the questions: 'what is the treatment effect of endovascular therapy with intravenous recombinant tissue plasminogen activator compared to intravenous tissue plasminogen activator alone on full scale modified Rankin Scale at 3 months?' and 'to what extent do key patient characteristics influence the treatment effect of endovascular therapy?'. Key secondary outcomes include effect of endovascular therapy on death within 90 days; analyses of modified Rankin Scale using dichotomized methods; and effects of endovascular therapy on symptomatic intracranial hemorrhage. Several secondary analyses will be considered as well as expanding patient cohorts to intravenous recombinant tissue plasminogen activator-ineligible patients, should data allow. This collaborative meta-analysis of individual participant data from randomized trials of endovascular therapy vs. control in conjunction with intravenous thrombolysis will demonstrate the efficacy and generalizability of endovascular therapy with intravenous thrombolysis as a concomitant medication. © 2015 World Stroke Organization.

Assessing the effect of sodium dichloroisocyanurate concentration on transfer of Salmonella enterica serotype Typhimurium in wash water for production of minimally processed iceberg lettuce (Lactuca sativa L.).

PubMed

Maffei, D F; Sant'Ana, A S; Monteiro, G; Schaffner, D W; Franco, B D G M

2016-06-01

This study evaluated the impact of sodium dichloroisocyanurate (5, 10, 20, 30, 40, 50 and 250 mg l(-1) ) in wash water on transfer of Salmonella Typhimurium from contaminated lettuce to wash water and then to other noncontaminated lettuces washed sequentially in the same water. Experiments were designed mimicking the conditions commonly seen in minimally processed vegetable (MPV) processing plants in Brazil. The scenarios were as follows: (1) Washing one inoculated lettuce portion in nonchlorinated water, followed by washing 10 noninoculated portions sequentially. (2) Washing one inoculated lettuce portion in chlorinated water followed by washing five noninoculated portions sequentially. (3) Washing five inoculated lettuce portions in chlorinated water sequentially, followed by washing five noninoculated portions sequentially. (4) Washing five noninoculated lettuce portions in chlorinated water sequentially, followed by washing five inoculated portions sequentially and then by washing five noninoculated portions sequentially in the same water. Salm. Typhimurium transfer from inoculated lettuce to wash water and further dissemination to noninoculated lettuces occurred when nonchlorinated water was used (scenario 1). When chlorinated water was used (scenarios 2, 3 and 4), no measurable Salm. Typhimurium transfer occurred if the sanitizer was ≥10 mg l(-1) . Use of sanitizers in correct concentrations is important to minimize the risk of microbial transfer during MPV washing. In this study, the impact of sodium dichloroisocyanurate in the wash water on transfer of Salmonella Typhimurium from inoculated lettuce to wash water and then to other noninoculated lettuces washed sequentially in the same water was evaluated. The use of chlorinated water, at concentration above 10 mg l(-1) , effectively prevented Salm. Typhimurium transfer under several different washing scenarios. Conversely, when nonchlorinated water was used, Salm. Typhimurium transfer occurred in up to at least 10 noninoculated batches of lettuce washed sequentially in the same water. © 2016 The Society for Applied Microbiology.

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients.

PubMed

Cohen, Alexander T; Harrington, Robert A; Goldhaber, Samuel Z; Hull, Russell D; Wiens, Brian L; Gold, Alex; Hernandez, Adrian F; Gibson, C Michael

2016-08-11

Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218.).

Diesel exhaust exposure, wheezing and sneezing.

PubMed

Bernstein, David I

2012-07-01

The rising incidence of allergic disorders in developed countries is unexplained. Exposure to traffic related air pollutants may be an important cause of wheezing and asthma in childhood. Experimental evidence from human studies suggests that diesel exhaust particles, constituents of fine particulate matter less than 2.5 microns (PM(2.5)), may act to enhance IgE mediated aeroallergen sensitization and Th2 directed cytokine responses. To date, epidemiologic investigations indicate that children living in close proximity to heavily travelled roads are more likely to be atopic and wheeze. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort study was initiated to test the hypothesis that early high exposure to traffic related air pollutants is associated with early aeroallergen sensitization and allergic respiratory phenotypes. Using an exposure cohort design, more than 700 infants born to atopic parents were recruited at age 1 living either less than 400 meters (high traffic pollutant exposure) or greater than 1,500 meters (low exposure) from a major road. Children were medically evaluated and underwent skin prick testing with aeroallergen at screening, and re-evaluated sequentially at ages 1, 2, 3, 4, and 7. In this study, both proximity and land use regression (LUR) models of traffic air pollutant exposure have been assessed. Proximity to stop and go traffic with large concentrations of bus and truck traffic predicted persistent wheezing during infancy. The LUR model estimated elemental carbon attributable to traffic (ECAT) as a proxy for diesel exhaust particulate exposure. High ECAT was significantly associated with wheezing at age 1 as well as persistent wheezing at age 3. High mold exposure predicted a well defined asthma phenotype at age 7.

Bleeding impacting mortality after noncardiac surgery: a protocol to establish diagnostic criteria, estimate prognostic importance, and develop and validate a prediction guide in an international prospective cohort study

PubMed Central

Roshanov, Pavel S.; Eikelboom, John W.; Crowther, Mark; Tandon, Vikas; Borges, Flavia K.; Kearon, Clive; Lamy, Andre; Whitlock, Richard; Biccard, Bruce M.; Szczeklik, Wojciech; Guyatt, Gordon H.; Panju, Mohamed; Spence, Jessica; Garg, Amit X.; McGillion, Michael; VanHelder, Tomas; Kavsak, Peter A.; de Beer, Justin; Winemaker, Mitchell; Sessler, Daniel I.; Le Manach, Yannick; Sheth, Tej; Pinthus, Jehonathan H.; Thabane, Lehana; Simunovic, Marko R.I.; Mizera, Ryszard; Ribas, Sebastian; Devereaux, P.J.

2017-01-01

Introduction: Various definitions of bleeding have been used in perioperative studies without systematic assessment of the diagnostic criteria for their independent association with outcomes important to patients. Our proposed definition of bleeding impacting mortality after noncardiac surgery (BIMS) is bleeding that is independently associated with death during or within 30 days after noncardiac surgery. We describe our analysis plan to sequentially 1) establish the diagnostic criteria for BIMS, 2) estimate the independent contribution of BIMS to 30-day mortality and 3) develop and internally validate a clinical prediction guide to estimate patient-specific risk of BIMS. Methods: In the Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) study, we prospectively collected bleeding data for 16 079 patients aged 45 years or more who had noncardiac inpatient surgery between 2007 and 2011 at 12 centres in 8 countries across 5 continents. We will include bleeding features independently associated with 30-day mortality in the diagnostic criteria for BIMS. Candidate features will include the need for reoperation due to bleeding, the number of units of erythrocytes transfused, the lowest postoperative hemoglobin concentration, and the absolute and relative decrements in hemoglobin concentration from the preoperative value. We will then estimate the incidence of BIMS and its independent association with 30-day mortality. Last, we will construct and internally validate a clinical prediction guide for BIMS. Interpretation: This study will address an important gap in our knowledge about perioperative bleeding, with implications for the 200 million patients who undergo noncardiac surgery globally every year. Trial registration: ClinicalTrials.gov, no NCT00512109. PMID:28943515

Diesel Exhaust Exposure, Wheezing and Sneezing

PubMed Central

2012-01-01

The rising incidence of allergic disorders in developed countries is unexplained. Exposure to traffic related air pollutants may be an important cause of wheezing and asthma in childhood. Experimental evidence from human studies suggests that diesel exhaust particles, constituents of fine particulate matter less than 2.5 microns (PM2.5), may act to enhance IgE mediated aeroallergen sensitization and Th2 directed cytokine responses. To date, epidemiologic investigations indicate that children living in close proximity to heavily travelled roads are more likely to be atopic and wheeze. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort study was initiated to test the hypothesis that early high exposure to traffic related air pollutants is associated with early aeroallergen sensitization and allergic respiratory phenotypes. Using an exposure cohort design, more than 700 infants born to atopic parents were recruited at age 1 living either less than 400 meters (high traffic pollutant exposure) or greater than 1,500 meters (low exposure) from a major road. Children were medically evaluated and underwent skin prick testing with aeroallergen at screening, and re-evaluated sequentially at ages 1, 2, 3, 4, and 7. In this study, both proximity and land use regression (LUR) models of traffic air pollutant exposure have been assessed. Proximity to stop and go traffic with large concentrations of bus and truck traffic predicted persistent wheezing during infancy. The LUR model estimated elemental carbon attributable to traffic (ECAT) as a proxy for diesel exhaust particulate exposure. High ECAT was significantly associated with wheezing at age 1 as well as persistent wheezing at age 3. High mold exposure predicted a well defined asthma phenotype at age 7. PMID:22754710

Oxaliplatin-containing Preoperative Therapy in Locally Advanced Rectal Cancer: Local Response, Toxicity and Long-term Outcome.

PubMed

Dueland, S; Ree, A H; Grøholt, K K; Saelen, M G; Folkvord, S; Hole, K H; Seierstad, T; Larsen, S G; Giercksky, K E; Wiig, J N; Boye, K; Flatmark, K

2016-08-01

This non-randomised study was undertaken to examine oxaliplatin as possibly an intensifying component of sequential neoadjuvant therapy in locally advanced rectal cancer for improved local and metastatic outcome. Ninety-seven patients (57 T2-3 cases, 40 T4 cases) received two cycles of the Nordic FLOX regimen (oxaliplatin 85 mg/m(2) day 1 and bolus 5-fluorouracil 500 mg/m(2) and folinic acid 100 mg days 1 and 2) before long-course chemoradiotherapy with concomitant oxaliplatin and capecitabine, followed by pelvic surgery. Treatment toxicity, local tumour response and long-term outcome were recorded. Good histologic tumour regression was obtained in 72% of patients. Implementing protocol-specific dose adjustments, tolerance was acceptable and 95% of patients received the total prescribed radiation dose. Estimated 5 year progression-free and overall survival were 61% and 83%, respectively. T4 stage was associated with an inferior local response rate, which again was highly associated with impaired long-term outcome. In this cohort of rectal cancer patients dominated by T4 and advanced T3 cases given sequential oxaliplatin-containing preoperative therapy with acceptable toxicity, high tumour response rates and overall survival were obtained, consistent with both local and systemic effects. However, tumour response and long-term outcome remained inferior for a significant number of T4 cases, suggesting that the T4 entity is biologically heterogeneous with subgroups of patients eligible for further individualisation of therapy. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Early Astronomical Sequential Photography, 1873-1923

NASA Astrophysics Data System (ADS)

Bonifácio, Vitor

2011-11-01

In 1873 Jules Janssen conceived the first automatic sequential photographic apparatus to observe the eagerly anticipated 1874 transit of Venus. This device, the 'photographic revolver', is commonly considered today as the earliest cinema precursor. In the following years, in order to study the variability or the motion of celestial objects, several instruments, either manually or automatically actuated, were devised to obtain as many photographs as possible of astronomical events in a short time interval. In this paper we strive to identify from the available documents the attempts made between 1873 and 1923, and discuss the motivations behind them and the results obtained. During the time period studied astronomical sequential photography was employed to determine the time of the instants of contact in transits and occultations, and to study total solar eclipses. The technique was seldom used but apparently the modern film camera invention played no role on this situation. Astronomical sequential photographs were obtained both before and after 1895. We conclude that the development of astronomical sequential photography was constrained by the reduced number of subjects to which the technique could be applied.

Sequential causal inference: Application to randomized trials of adaptive treatment strategies

PubMed Central

Dawson, Ree; Lavori, Philip W.

2009-01-01

SUMMARY Clinical trials that randomize subjects to decision algorithms, which adapt treatments over time according to individual response, have gained considerable interest as investigators seek designs that directly inform clinical decision making. We consider designs in which subjects are randomized sequentially at decision points, among adaptive treatment options under evaluation. We present a sequential method to estimate the comparative effects of the randomized adaptive treatments, which are formalized as adaptive treatment strategies. Our causal estimators are derived using Bayesian predictive inference. We use analytical and empirical calculations to compare the predictive estimators to (i) the ‘standard’ approach that allocates the sequentially obtained data to separate strategy-specific groups as would arise from randomizing subjects at baseline; (ii) the semi-parametric approach of marginal mean models that, under appropriate experimental conditions, provides the same sequential estimator of causal differences as the proposed approach. Simulation studies demonstrate that sequential causal inference offers substantial efficiency gains over the standard approach to comparing treatments, because the predictive estimators can take advantage of the monotone structure of shared data among adaptive strategies. We further demonstrate that the semi-parametric asymptotic variances, which are marginal ‘one-step’ estimators, may exhibit significant bias, in contrast to the predictive variances. We show that the conditions under which the sequential method is attractive relative to the other two approaches are those most likely to occur in real studies. PMID:17914714

Sequential Tests of Multiple Hypotheses Controlling Type I and II Familywise Error Rates

PubMed Central

Bartroff, Jay; Song, Jinlin

2014-01-01

This paper addresses the following general scenario: A scientist wishes to perform a battery of experiments, each generating a sequential stream of data, to investigate some phenomenon. The scientist would like to control the overall error rate in order to draw statistically-valid conclusions from each experiment, while being as efficient as possible. The between-stream data may differ in distribution and dimension but also may be highly correlated, even duplicated exactly in some cases. Treating each experiment as a hypothesis test and adopting the familywise error rate (FWER) metric, we give a procedure that sequentially tests each hypothesis while controlling both the type I and II FWERs regardless of the between-stream correlation, and only requires arbitrary sequential test statistics that control the error rates for a given stream in isolation. The proposed procedure, which we call the sequential Holm procedure because of its inspiration from Holm’s (1979) seminal fixed-sample procedure, shows simultaneous savings in expected sample size and less conservative error control relative to fixed sample, sequential Bonferroni, and other recently proposed sequential procedures in a simulation study. PMID:25092948

Two-step sequential pretreatment for the enhanced enzymatic hydrolysis of coffee spent waste.

PubMed

Ravindran, Rajeev; Jaiswal, Swarna; Abu-Ghannam, Nissreen; Jaiswal, Amit K

2017-09-01

In the present study, eight different pretreatments of varying nature (physical, chemical and physico-chemical) followed by a sequential, combinatorial pretreatment strategy was applied to spent coffee waste to attain maximum sugar yield. Pretreated samples were analysed for total reducing sugar, individual sugars and generation of inhibitory compounds such as furfural and hydroxymethyl furfural (HMF) which can hinder microbial growth and enzyme activity. Native spent coffee waste was high in hemicellulose content. Galactose was found to be the predominant sugar in spent coffee waste. Results showed that sequential pretreatment yielded 350.12mg of reducing sugar/g of substrate, which was 1.7-fold higher than in native spent coffee waste (203.4mg/g of substrate). Furthermore, extensive delignification was achieved using sequential pretreatment strategy. XRD, FTIR, and DSC profiles of the pretreated substrates were studied to analyse the various changes incurred in sequentially pretreated spent coffee waste as opposed to native spent coffee waste. Copyright © 2017 Elsevier Ltd. All rights reserved.

Astrocytic tracer dynamics estimated from [1-¹¹C]-acetate PET measurements.

PubMed

Arnold, Andrea; Calvetti, Daniela; Gjedde, Albert; Iversen, Peter; Somersalo, Erkki

2015-12-01

We address the problem of estimating the unknown parameters of a model of tracer kinetics from sequences of positron emission tomography (PET) scan data using a statistical sequential algorithm for the inference of magnitudes of dynamic parameters. The method, based on Bayesian statistical inference, is a modification of a recently proposed particle filtering and sequential Monte Carlo algorithm, where instead of preassigning the accuracy in the propagation of each particle, we fix the time step and account for the numerical errors in the innovation term. We apply the algorithm to PET images of [1-¹¹C]-acetate-derived tracer accumulation, estimating the transport rates in a three-compartment model of astrocytic uptake and metabolism of the tracer for a cohort of 18 volunteers from 3 groups, corresponding to healthy control individuals, cirrhotic liver and hepatic encephalopathy patients. The distribution of the parameters for the individuals and for the groups presented within the Bayesian framework support the hypothesis that the parameters for the hepatic encephalopathy group follow a significantly different distribution than the other two groups. The biological implications of the findings are also discussed. © The Authors 2014. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

Protective resources and perceptions of stress in a multi-ethnic sample of school-age children.

PubMed

Taxis, J Carole; Rew, Lynn; Jackson, Kate; Kouzekanani, Kamiar

2004-01-01

To investigate the relationship among protective resources of social connectedness, coping skills, and the perception of stress in 613 Hispanic and White school-aged children. A secondary analysis of data, part of a longitudinal cohort-sequential study designed to investigate health-risk behaviors in school-age children. Data were collected by computer-assisted self-interviewing from a non-probability sample of 8-12-year-olds in three independent school districts. Hierarchical multiple regression analysis indicated that social connectedness and the frequency of coping strategies used accounted for 18.8% of the variation in stress. "Feeling sick" was the primary stressor of the participants, while the two most frequently endorsed coping strategies were "watch TV or listen to music" and "draw, write, or read something." The findings are significant because nurses working with children are in a strategic position to assess risk factors and protective resources related to stress and intervene in a timely manner to assist children and families develop resiliency.

Value of HIV patients with regular follow-up as in-house internal controls of flow cytometry measurement of lymphocyte subsets.

PubMed

de Carvalho Bittencourt, Marcelo; Kohler, Chantal; Henard, Sandrine; Rabaud, Christian; Béné, Marie C; Faure, Gilbert C

2013-01-01

Quality assessment in flow cytometry cannot obey the same rules as those applicable to the measurement of chemical analytes. However, regular follow-up of known patients may provide a robust in-house control of cell subsets evaluation. Sequential blood samples assessed for 32 HIV patients over several years and showing good stability were retrospectively assessed to establish coefficient of variations of the percentages of CD3+, CD4+, CD8+ cells, and CD4+ absolute counts (ACs). Mean relative standard variations for the whole cohort were of 0.04, 0.14, 0.08, and 0.18 for CD3%, CD4%, CD8%, and CD4 ACs, respectively. In-house follow-up of regularly checked compliant patients is a good alternative to traditional and costly repeatability and reproducibility studies for the validation of routine flow cytometry. © 2013 International Clinical Cytometry Society. Copyright © 2013 International Clinical Cytometry Society.

Value of HIV patients with regular follow-up as in-house internal controls of flow cytometry measurement of lymphocyte subsets.

PubMed

de Carvalho Bittencourt, Marcelo; Kohler, Chantal; Henard, Sandrine; Rabaud, Christian; Béné, Marie C; Faure, Gilbert C

2013-07-08

Background. Quality assessment in flow cytometry cannot obey the same rules as those applicable to the measurement of chemical analytes. However, regular follow-up of known patients may provide a robust in-house control of cell subsets evaluation. Methods. Sequential blood samples assessed for 32 HIV patients over several years and showing good stability were retrospectively assessed to establish coefficient of variations of the percentages of CD3+, CD4+, CD8+ cells and CD4+ absolute counts. Results. Mean relative standard variations for the whole cohort were of 0.04, 0.14, 0.08 and 0.18 for CD3%, CD4% CD8% and CD4 absolute counts respectively. Discussion. In-house follow up of regularly checked compliant patients is a good alternative to traditional and costly repeatability and reproducibility studies for the validation of routine flow cytometry. © 2013 Clinical Cytometry Society. Copyright © 2013 Clinical Cytometry Society.

Association between prolonged breast-feeding and early childhood caries: a hierarchical approach.

PubMed

Nunes, Ana Margarida Melo; Alves, Claudia Maria Coelho; Borba de Araújo, Fernando; Ortiz, Tânia Mara Lopes; Ribeiro, Marizélia Rodrigues Costa; Silva, Antônio Augusto Moura da; Ribeiro, Cecília Claudia Costa

2012-12-01

This study was conducted to investigate the association between prolonged breastfeeding and early childhood caries(ECC) with adjustment for important confounders, using hieraschical approach. This retrospective cohort study involved 260 low-income children (18-42 months). The number of decayed teeth was used as a measure of caries. Following a theoretical framework, the hierarchical model was built in a forward fashion, by adding the following levels in succession: level 1: age; level 2: social variables; level 3: health variables; level 4: behavioral variables; level 5: oral hygiene-related variables; level 6: oral hygiene quality measured by visible plaque; and level 7: contamination by mutans streptococci. Sequential forward multiple Poisson regression analysis was employed. Breast-feeding was not a risk factor for ECC after adjustment for some confounders (incidence density ratio, 1.15; 95% confidence interval, 0.84-1.59, P = 0.363). Prolonged breast-feeding was not a risk factor for ECC while age, high sucrose comption between main meals and the quality of oral higiene were associated with disease in children. © 2012 John Wiley & Sons A/S.

Sequential Aldol Condensation – Transition Metal-Catalyzed Addition Reactions of Aldehydes, Methyl Ketones and Arylboronic Acids

PubMed Central

Liao, Yuan-Xi; Xing, Chun-Hui; Israel, Matthew; Hu, Qiao-Sheng

2011-01-01

Sequential aldol condensation of aldehydes with methyl ketones followed by transition metal-catalyzed addition reactions of arylboronic acids to form β-substituted ketones is described. By using the 1,1′-spirobiindane-7,7′-diol (SPINOL)-based phosphite, an asymmetric version of this type of sequential reaction, with up to 92% ee, was also realized. Our study provided an efficient method to access β-substituted ketones and might lead to the development of other sequential/tandem reactions with transition metal-catalyzed addition reactions as the key step. PMID:21417359

Sequential aldol condensation-transition metal-catalyzed addition reactions of aldehydes, methyl ketones, and arylboronic acids.

PubMed

Liao, Yuan-Xi; Xing, Chun-Hui; Israel, Matthew; Hu, Qiao-Sheng

2011-04-15

Sequential aldol condensation of aldehydes with methyl ketones followed by transition metal-catalyzed addition reactions of arylboronic acids to form β-substituted ketones is described. By using the 1,1'-spirobiindane-7,7'-diol (SPINOL)-based phosphite, an asymmetric version of this type of sequential reaction, with up to 92% ee, was also realized. Our study provided an efficient method to access β-substituted ketones and might lead to the development of other sequential/tandem reactions with transition metal-catalyzed addition reactions as the key step. © 2011 American Chemical Society

Epsin Family Member 3 and Ribosome-Related Genes Are Associated with Late Metastasis in Estrogen Receptor-Positive Breast Cancer and Long-Term Survival in Non-Small Cell Lung Cancer Using a Genome-Wide Identification and Validation Strategy.

PubMed

Hellwig, Birte; Madjar, Katrin; Edlund, Karolina; Marchan, Rosemarie; Cadenas, Cristina; Heimes, Anne-Sophie; Almstedt, Katrin; Lebrecht, Antje; Sicking, Isabel; Battista, Marco J; Micke, Patrick; Schmidt, Marcus; Hengstler, Jan G; Rahnenführer, Jörg

2016-01-01

In breast cancer, gene signatures that predict the risk of metastasis after surgical tumor resection are mainly indicative of early events. The purpose of this study was to identify genes linked to metastatic recurrence more than three years after surgery. Affymetrix HG U133A and Plus 2.0 array datasets with information on metastasis-free, disease-free or overall survival were accessed via public repositories. Time restricted Cox regression models were used to identify genes associated with metastasis during or after the first three years post-surgery (early- and late-type genes). A sequential validation study design, with two non-adjuvantly treated discovery cohorts (n = 409) and one validation cohort (n = 169) was applied and identified genes were further evaluated in tamoxifen-treated breast cancer patients (n = 923), as well as in patients with non-small cell lung (n = 1779), colon (n = 893) and ovarian (n = 922) cancer. Ten late- and 243 early-type genes were identified in adjuvantly untreated breast cancer. Adjustment to clinicopathological factors and an established proliferation-related signature markedly reduced the number of early-type genes to 16, whereas nine late-type genes still remained significant. These nine genes were associated with metastasis-free survival (MFS) also in a non-time restricted model, but not in the early period alone, stressing that their prognostic impact was primarily based on MFS more than three years after surgery. Four of the ten late-type genes, the ribosome-related factors EIF4B, RPL5, RPL3, and the tumor angiogenesis modifier EPN3 were significantly associated with MFS in the late period also in a meta-analysis of tamoxifen-treated breast cancer cohorts. In contrast, only one late-type gene (EPN3) showed consistent survival associations in more than one cohort in the other cancer types, being associated with worse outcome in two non-small cell lung cancer cohorts. No late-type gene was validated in ovarian and colon cancer. Ribosome-related genes were associated with decreased risk of late metastasis in both adjuvantly untreated and tamoxifen-treated breast cancer patients. In contrast, high expression of epsin (EPN3) was associated with increased risk of late metastasis. This is of clinical relevance considering the well-understood role of epsins in tumor angiogenesis and the ongoing development of epsin antagonizing therapies.

Fluid accumulation during acute kidney injury in the intensive care unit.

PubMed

Berthelsen, R E; Perner, A; Jensen, A K; Jensen, J-U; Bestle, M H

2018-07-01

Fluid therapy is a ubiquitous intervention in patients admitted to the intensive care unit, but positive fluid balance may be associated with poor outcomes and particular in patients with acute kidney injury. Studies describing this have defined fluid overload either at specific time points or considered patients with a positive mean daily fluid balance as fluid overloaded. We wished to detail this further and performed joint model analyses of the association between daily fluid balance and outcome represented by mortality and renal recovery in patients admitted with acute kidney injury. We did a retrospective cohort study of patients admitted to the intensive care unit with acute kidney injury during a 2-year observation period. We used serum creatinine measurements to identify patients with acute kidney injury and collected sequential daily fluid balance during the first 5 days of admission to the intensive care unit. We used joint modelling techniques to correlate the development of fluid overload with survival and renal recovery adjusted for age, gender and disease severity. The cohort contained 863 patients with acute kidney injury of whom 460 (53%) and 254 (29%) developed 5% and 10% fluid overload, respectively. We found that both 5% and 10% fluid overload was correlated with reduced survival and renal recovery. Joint model analyses of fluid accumulation in patients admitted to the intensive care unit with acute kidney injury confirm that even a modest degree of fluid overload (5%) may be negatively associated with both survival and renal recovery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

[Follow-up of alcohol and/or cocaine dependents after their discharge from a therapeutic community: a pilot study].

PubMed

Lopez-Fernandez, Olatz; Ferrer-Pérez, Xavier; Lafarga-Lebey, Sandra; Honrubia-Serrano, María Luisa; Tudela-Marí, Maite

2011-01-01

In Spain, the Therapeutic Community (TC) constitutes a common model of treatment in the field of addictions, although there hardly exists any investigation about its efficiency and the persistence of its attainments. To evaluate the short, half and long term effects of treatment of addiction to alcohol or cocaine in the TC run by "Fundacion Salud y Comunidad" (Foundation Health and Community). descriptive pilot study, with a sequential design of cohort. 91 users completed a survey specifically designed to know their evolution at different follow-up periods (1, 3, 5 or 10 years after their exit from the TC): socio-demographic, psychoactive substance use, other variables related to the stay at the TC. Changes between before the TC and the present time regarding variables such as academic, labour, drug consumption, health, family and social adaptation and their criminal behaviour are described. the cohorts showed a relatively common previous socio-demographic pattern having received a similar treatment. The users reported to have diminished the frequent consumption of the main drug, having 48.9% never relapsed even through an occasional consumption of the drug/s. Also they perceived to have improved their health and family relations, as well as their aggressive behaviour and legal problems linked with their consumption of drug/s. after their rehabilitation in a TC, the users report a global decrease of the consumption of drugs and perceive an improvement of their health, family relations, violence and other problems linked to their former drug use.

Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide a for cancer of the oral cavity.

PubMed

Rigual, Nestor; Shafirstein, Gal; Cooper, Michele T; Baumann, Heinz; Bellnier, David A; Sunar, Ulas; Tracy, Erin C; Rohrbach, Daniel J; Wilding, Gregory; Tan, Wei; Sullivan, Maureen; Merzianu, Mihai; Henderson, Barbara W

2013-12-01

The primary objective was to evaluate safety of 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Patients with histologically proven oral dysplasia, carcinoma in situ, or early-stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies used an HPPH dose of 4 mg/m(2) and light doses from 50 to 140 J/cm(2). Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of STAT3 were assessed as potential indicators of PDT effective reaction. Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and carcinoma in situ and 82% for squamous cell carcinomas (SCC) lesions at 140 J/cm(2). The responses in the carcinoma in situ/dysplasia cohort are not durable. The PDT-induced STAT3 cross-links is significantly higher (P = 0.0033) in SCC than in carcinoma in situ/dysplasia for all light doses. HPPH-PDT is safe for the treatment of carcinoma in situ/dysplasia and early-stage cancer of the oral cavity. Early-stage oral HNSCC seems to respond better to HPPH-PDT in comparison with premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT-mediated photoreaction. ©2013 AACR.

Hyperdynamic left ventricular ejection fraction in the intensive care unit.

PubMed

Paonessa, Joseph R; Brennan, Thomas; Pimentel, Marco; Steinhaus, Daniel; Feng, Mengling; Celi, Leo Anthony

2015-08-07

Limited information exists on the etiology, prevalence, and significance of hyperdynamic left ventricular ejection fraction (HDLVEF) in the intensive care unit (ICU). Our aim in the present study was to compare characteristics and outcomes of patients with HDLVEF with those of patients with normal left ventricular ejection fraction in the ICU using a large, public, deidentified critical care database. We conducted a longitudinal, single-center, retrospective cohort study of adult patients who underwent echocardiography during a medical or surgical ICU admission at the Beth Israel Deaconess Medical Center using the Multiparameter Intelligent Monitoring in Intensive Care II database. The final cohort had 2867 patients, of whom 324 had HDLVEF, defined as an ejection fraction >70%. Patients with an ejection fraction <55% were excluded. Compared with critically ill patients with normal left ventricular ejection fraction, the finding of HDLVEF in critically ill patients was associated with female sex, increased age, and the diagnoses of hypertension and cancer. Patients with HDLVEF had increased 28-day mortality compared with those with normal ejection fraction in multivariate logistic regression analysis adjusted for age, sex, Sequential Organ Failure Assessment score, Elixhauser score for comorbidities, vasopressor use, and mechanical ventilation use (odds ratio 1.38, 95% confidence interval 1.039-1.842, p =0.02). The presence of HDLVEF portended increased 28-day mortality, and may be helpful as a gravity marker for prognosis in patients admitted to the ICU. Further research is warranted to gain a better understanding of how these patients respond to common interventions in the ICU and to determine if pharmacologic modulation of HDLVEF improves outcomes.

Single-Center Experience With Venovenous ECMO for Influenza-Related ARDS.

PubMed

Buchner, Jessica; Mazzeffi, Michael; Kon, Zachary; Menaker, Jay; Rubinson, Lewis; Bittle, Gregory; Pasrija, Chetan; Herr, Daniel

2018-06-01

This study was designed to determine whether venovenous extracorporeal membrane oxygenation (VV ECMO) reduced mortality in patients with influenza-related acute respiratory distress syndrome (ARDS). A retrospective cohort study was performed. Baseline characteristics of participants were compared and Kaplan-Meier survival analysis was used to compare survival at last medical center follow-up. Cox proportional hazards modeling also was performed to test for univariate associations between salient variables and mortality. A single-center ECMO referral university hospital. All patients admitted with influenza-related ARDS during the 2015 to 2016 influenza season. Mechanical ventilation alone versus mechanical ventilation and ECMO cannulation. A total of 26 patients with influenza-related ARDS were included in the cohort. Thirteen patients were treated with VV ECMO while 13 were not. Twelve of the ECMO patients and 8 of the non-ECMO patients were transferred from outside hospitals. Patients treated with ECMO were younger and had less hypertension and diabetes mellitus. There was no difference in baseline sequential organ failure assessment score between the 2 groups. In-hospital mortality for ECMO patients was 15.4% versus 46.7% for patients not treated with ECMO. Survival at last medical center follow-up was better in patients treated with ECMO (p = 0.02). Age, highest blood carbon dioxide level, and treatment without ECMO were all associated with increased mortality. Influenza-related ARDS has a high mortality rate and patients treated only with mechanical ventilation have worse outcome than those managed with VV ECMO. More liberal use of ECMO should be considered in patients with influenza-related ARDS. Copyright © 2017 Elsevier Inc. All rights reserved.

Strongyloides seroprevalence before and after an ivermectin mass drug administration in a remote Australian Aboriginal community

PubMed Central

Currie, Bart J.; Cheng, Allen C.; McCarthy, James; Carapetis, Jonathan R.; Holt, Deborah C.; Page, Wendy; Shield, Jennifer; Gundjirryirr, Roslyn; Mulholland, Eddie; Ward, Linda; Andrews, Ross M.

2017-01-01

Background Strongyloides seroprevalence is hyper-endemic in many Australian Aboriginal and Torres Strait Islander communities, ranging from 35–60%. We report the impact on Strongyloides seroprevalence after two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community. Methods Utilizing a before and after study design, we measured Strongyloides seroprevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined changes in serostatus. Serodiagnosis was undertaken by ELISA that used sonicated Strongyloides ratti antigen to detect anti-Strongyloides IgG. Non-pregnant participants weighing ≥15 kg were administered a single 200 μg/kg ivermectin dose, repeated after 10–42 days if Strongyloides and/or scabies was diagnosed; others followed a standard alternative algorithm. A questionnaire on clinical symptoms was administered to identify adverse events from treatment and self-reported symptoms associated with serostatus. Findings We surveyed 1013 participants at the baseline population census and 1060 (n = 700 from baseline cohort and 360 new entrants) at month 12. Strongyloides seroprevalence fell from 21% (175/818) at baseline to 5% at month 6. For participants from the baseline cohort this reduction was sustained at month 12 (34/618, 6%), falling to 2% at month 18 after the second MDA. For new entrants to the cohort at month 12, seroprevalence reduced from 25% (75/297) to 7% at month 18. Strongyloides positive seroconversions for the baseline cohort six months after each MDA were 2.5% (4/157) at month 6 and 1% at month 18, whilst failure to serorevert remained unchanged at 18%. At 12 months, eosinophilia was identified in 59% of baseline seropositive participants and 89% of seropositive new entrants, compared with 47%baseline seronegative participants and 51% seronegative new entrants. Seropositivity was not correlated with haemoglobin or any self-reported clinical symptoms. Clinical symptoms ascertained on the day of treatment and 24–72 hrs after, did not identify any adverse events. Significance Two community ivermectin MDAs delivered 12 months apart by trained Aboriginal researchers in collaboration with non-Indigenous researchers resulted in a sustained and significant reduction in Strongyloides seroprevalence over 18 months. Similar reductions were seen in the baseline cohort and new entrants. PMID:28505198

Establishing the Learning Curve of Robotic Sacral Colpopexy in a Start-up Robotics Program.

PubMed

Sharma, Shefali; Calixte, Rose; Finamore, Peter S

2016-01-01

To determine the learning curve of the following segments of a robotic sacral colpopexy: preoperative setup, operative time, postoperative transition, and room turnover. A retrospective cohort study to determine the number of cases needed to reach points of efficiency in the various segments of a robotic sacral colpopexy (Canadian Task Force II-2). A university-affiliated community hospital. Women who underwent robotic sacral colpopexy at our institution from 2009 to 2013 comprise the study population. Patient characteristics and operative reports were extracted from a patient database that has been maintained since the inception of the robotics program at Winthrop University Hospital and electronic medical records. Based on additional procedures performed, 4 groups of patients were created (A-D). Learning curves for each of the segment times of interest were created using penalized basis spline (B-spline) regression. Operative time was further analyzed using an inverse curve and sequential grouping. A total of 176 patients were eligible. Nonparametric tests detected no difference in procedure times between the 4 groups (A-D) of patients. The preoperative and postoperative points of efficiency were 108 and 118 cases, respectively. The operative points of proficiency and efficiency were 25 and 36 cases, respectively. Operative time was further analyzed using an inverse curve that revealed that after 11 cases the surgeon had reached 90% of the learning plateau. Sequential grouping revealed no significant improvement in operative time after 60 cases. Turnover time could not be assessed because of incomplete data. There is a difference in the operative time learning curve for robotic sacral colpopexy depending on the statistical analysis used. The learning curve of the operative segment showed an improvement in operative time between 25 and 36 cases when using B-spline regression. When the data for operative time was fit to an inverse curve, a learning rate of 11 cases was appreciated. Using sequential grouping to describe the data, no improvement in operative time was seen after 60 cases. Ultimately, we believe that efficiency in operative time is attained after 30 to 60 cases when performing robotic sacral colpopexy. The learning curve for preoperative setup and postoperative transition, which is reflective of anesthesia and nursing staff, was approximately 110 cases. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Immediate Sequential Bilateral Pediatric Vitreoretinal Surgery

PubMed Central

Yonekawa, Yoshihiro; Wu, Wei-Chi; Kusaka, Shunji; Robinson, Joshua; Tsujioka, Daishi; Kang, Kai B.; Shapiro, Michael J.; Padhi, Tapas R.; Jain, Lubhani; Sears, Jonathan E.; Kuriyan, Ajay E.; Berrocal, Audina M.; Quiram, Polly A.; Gerber, Amanda E.; Chan, R.V. Paul; Jonas, Karyn E.; Wong, Sui Chien; Patel, C.K.; Abbey, Ashkan M.; Spencer, Rand; Blair, Michael P.; Chang, Emmanuel Y.; Papakostas, Thanos D.; Vavvas, Demetrios G.; Sisk, Robert A.; Ferrone, Philip J.; Henderson, Robert H.; Olsen, Karl R.; Hartnett, M. Elizabeth; Chau, Felix Y.; Mukai, Shizuo; Murray, Timothy G.; Thomas, Benjamin J.; Meza, P. Anthony; Drenser, Kimberly A.; Trese, Michael T.; Capone, Antonio

2017-01-01

Purpose To determine the feasibility and safety of bilateral simultaneous vitreoretinal surgery in pediatric patients. Design International, multicenter, interventional, retrospective case series. Participants Patients 17 years of age or younger from 24 centers worldwide who underwent immediate sequential bilateral vitreoretinal surgery (ISBVS)—defined as vitrectomy, scleral buckle, or lensectomy using the vitreous cutter—performed in both eyes sequentially during the same anesthesia session. Methods Clinical history, surgical details and indications, time under anesthesia, and intraoperative and postoperative ophthalmic and systemic adverse events were reviewed. Main Outcome Measures Ocular and systemic adverse events. Results A total of 344 surgeries from 172 ISBVS procedures in 167 patients were included in the study. The mean age of the cohort was 1.3±2.6 years. Nonexclusive indications for ISBVS were rapidly progressive disease (74.6%), systemic morbidity placing the child at high anesthesia risk (76.0%), and residence remote from surgery location (30.2%). The most common diagnoses were retinopathy of prematurity (ROP; 72.7% [P < 0.01]; stage 3, 4.8%; stage 4A, 44.4%; stage 4B, 22.4%; stage 5, 26.4%), familial exudative vitreoretinopathy (7.0%), abusive head trauma (4.1%), persistent fetal vasculature (3.5%), congenital cataract (1.7%), posterior capsular opacification (1.7%), rhegmatogenous retinal detachment (1.7%), congenital X-linked retinoschisis (1.2%), Norrie disease (2.3%), and viral retinitis (1.2%). Mean surgical time was 143±59 minutes for both eyes. Higher ROP stage correlated with longer surgical time (P=0.02). There were no reported intraoperative ocular complications. During the immediate postoperative period, 2 eyes from different patients demonstrated unilateral vitreous haemorrhage (0.6%). No cases of endophthalmitis, choroidal hemorrhage, or hypotony occurred. Mean total anesthesia time was 203±87 minutes. There were no cases of anesthesia-related death, malignant hyperthermia, anaphylaxis, or cardiac event. There was 1 case of reintubation (0.6%) and 1 case of prolonged oxygen desaturation (0.6%). Mean follow-up after surgery was 103 weeks, and anatomic success and globe salvage rates were 89.8% and 98.0%, respectively. Conclusions This study found ISBVS to be a feasible and safe treatment paradigm for pediatric patients with bilateral vitreoretinal pathologic features when repeated general anesthesia is undesirable or impractical. PMID:27221737

Analyzing engagement in a web-based intervention platform through visualizing log-data.

PubMed

Morrison, Cecily; Doherty, Gavin

2014-11-13

Engagement has emerged as a significant cross-cutting concern within the development of Web-based interventions. There have been calls to institute a more rigorous approach to the design of Web-based interventions, to increase both the quantity and quality of engagement. One approach would be to use log-data to better understand the process of engagement and patterns of use. However, an important challenge lies in organizing log-data for productive analysis. Our aim was to conduct an initial exploration of the use of visualizations of log-data to enhance understanding of engagement with Web-based interventions. We applied exploratory sequential data analysis to highlight sequential aspects of the log data, such as time or module number, to provide insights into engagement. After applying a number of processing steps, a range of visualizations were generated from the log-data. We then examined the usefulness of these visualizations for understanding the engagement of individual users and the engagement of cohorts of users. The visualizations created are illustrated with two datasets drawn from studies using the SilverCloud Platform: (1) a small, detailed dataset with interviews (n=19) and (2) a large dataset (n=326) with 44,838 logged events. We present four exploratory visualizations of user engagement with a Web-based intervention, including Navigation Graph, Stripe Graph, Start-Finish Graph, and Next Action Heat Map. The first represents individual usage and the last three, specific aspects of cohort usage. We provide examples of each with a discussion of salient features. Log-data analysis through data visualization is an alternative way of exploring user engagement with Web-based interventions, which can yield different insights than more commonly used summative measures. We describe how understanding the process of engagement through visualizations can support the development and evaluation of Web-based interventions. Specifically, we show how visualizations can (1) allow inspection of content or feature usage in a temporal relationship to the overall program at different levels of granularity, (2) detect different patterns of use to consider personalization in the design process, (3) detect usability issues, (4) enable exploratory analysis to support the design of statistical queries to summarize the data, (5) provide new opportunities for real-time evaluation, and (6) examine assumptions about interactivity that underlie many summative measures in this field.

Analyzing Engagement in a Web-Based Intervention Platform Through Visualizing Log-Data

PubMed Central

2014-01-01

Background Engagement has emerged as a significant cross-cutting concern within the development of Web-based interventions. There have been calls to institute a more rigorous approach to the design of Web-based interventions, to increase both the quantity and quality of engagement. One approach would be to use log-data to better understand the process of engagement and patterns of use. However, an important challenge lies in organizing log-data for productive analysis. Objective Our aim was to conduct an initial exploration of the use of visualizations of log-data to enhance understanding of engagement with Web-based interventions. Methods We applied exploratory sequential data analysis to highlight sequential aspects of the log data, such as time or module number, to provide insights into engagement. After applying a number of processing steps, a range of visualizations were generated from the log-data. We then examined the usefulness of these visualizations for understanding the engagement of individual users and the engagement of cohorts of users. The visualizations created are illustrated with two datasets drawn from studies using the SilverCloud Platform: (1) a small, detailed dataset with interviews (n=19) and (2) a large dataset (n=326) with 44,838 logged events. Results We present four exploratory visualizations of user engagement with a Web-based intervention, including Navigation Graph, Stripe Graph, Start–Finish Graph, and Next Action Heat Map. The first represents individual usage and the last three, specific aspects of cohort usage. We provide examples of each with a discussion of salient features. Conclusions Log-data analysis through data visualization is an alternative way of exploring user engagement with Web-based interventions, which can yield different insights than more commonly used summative measures. We describe how understanding the process of engagement through visualizations can support the development and evaluation of Web-based interventions. Specifically, we show how visualizations can (1) allow inspection of content or feature usage in a temporal relationship to the overall program at different levels of granularity, (2) detect different patterns of use to consider personalization in the design process, (3) detect usability issues, (4) enable exploratory analysis to support the design of statistical queries to summarize the data, (5) provide new opportunities for real-time evaluation, and (6) examine assumptions about interactivity that underlie many summative measures in this field. PMID:25406097

Bilateral Sequential Cochlear Implantation in Patients With Enlarged Vestibular Aqueduct (EVA) Syndrome.

PubMed

Manzoor, Nauman F; Wick, Cameron C; Wahba, Marian; Gupta, Amit; Piper, Robin; Murray, Gail S; Otteson, Todd; Megerian, Cliff A; Semaan, Maroun T

2016-02-01

To analyze audiometric outcomes after bilateral cochlear implantation in patients with isolated enlarged vestibular aqueduct (EVA) syndrome and associated incomplete partition (IP) malformations. Secondary objective was to analyze rate of cerebrospinal fluid (CSF) gusher in patients with IP-EVA spectrum deformities and compare this with the existing literature. Retrospective chart review. Thirty-two patients with EVA syndrome who received unilateral or bilateral cochlear implants between June 1999 and January 2014 were identified in the University Hospitals Case Medical Center cochlear implant database. Isolated EVA (IEVA) and Incomplete Partition Type II (IP-II) malformations were identified by reviewing high-resolution computed tomography (HRCT) imaging. Demographic information, age at implantation, surgical details, postimplantation audiometric data including speech reception thresholds (SRT), word, and sentence scores were reviewed and analyzed. Intra- and postoperative complications were analyzed as well and compared with the literature. Seventeen patients (32 implanted ears) had pediatric cochlear implantation for EVA-associated hearing loss. Data from 16 controls (32 implanted ears) were used to compare audiometric and speech outcomes of EVA cohort. Mean age at implantation was 6.8 years for EVA cohort and 6.0 years for controls. There was no statistically significant difference in long-term postoperative SRT, monaurally aided word scores, and binaurally tested word scores between pediatric EVA group and controls. The EVA patients had a long-term mean sentence score of 85.92%. A subset of EVA patients implanted at mean age of 3.18 years (n = 15 ears) had similar audiometric outcomes to another control group with Connexin 26 mutations (n = 20 ears) implanted at a similar age. Further subset analysis revealed no significant differences in age at implantation, SRT, and word scores in patients with IEVA and IP-II malformation. There was no significant association between size of vestibular aqueduct and age at implantation. There was no CSF gusher or other intra- or postoperative complications reported in our series. Bilateral sequential cochlear implantation can be performed safely in patients with EVA. Audiometric outcomes are excellent and comparable to pediatric cochlear implant patients with no malformations. CSF gusher rates can be minimized by trans-round window approach. Further long-term studies are needed to identify differences within IP-EVA spectrum deformities, audiometric outcomes, and proportions of EVA patients who will need cochlear implantation for hearing rehabilitation.

Speech Perception and Production by Sequential Bilingual Children: A Longitudinal Study of Voice Onset Time Acquisition

PubMed Central

McCarthy, Kathleen M; Mahon, Merle; Rosen, Stuart; Evans, Bronwen G

2014-01-01

The majority of bilingual speech research has focused on simultaneous bilinguals. Yet, in immigrant communities, children are often initially exposed to their family language (L1), before becoming gradually immersed in the host country's language (L2). This is typically referred to as sequential bilingualism. Using a longitudinal design, this study explored the perception and production of the English voicing contrast in 55 children (40 Sylheti-English sequential bilinguals and 15 English monolinguals). Children were tested twice: when they were in nursery (52-month-olds) and 1 year later. Sequential bilinguals' perception and production of English plosives were initially driven by their experience with their L1, but after starting school, changed to match that of their monolingual peers. PMID:25123987

The cost and cost-effectiveness of rapid testing strategies for yaws diagnosis and surveillance.

PubMed

Fitzpatrick, Christopher; Asiedu, Kingsley; Sands, Anita; Gonzalez Pena, Tita; Marks, Michael; Mitja, Oriol; Meheus, Filip; Van der Stuyft, Patrick

2017-10-01

Yaws is a non-venereal treponemal infection caused by Treponema pallidum subspecies pertenue. The disease is targeted by WHO for eradication by 2020. Rapid diagnostic tests (RDTs) are envisaged for confirmation of clinical cases during treatment campaigns and for certification of the interruption of transmission. Yaws testing requires both treponemal (trep) and non-treponemal (non-trep) assays for diagnosis of current infection. We evaluate a sequential testing strategy (using a treponemal RDT before a trep/non-trep RDT) in terms of cost and cost-effectiveness, relative to a single-assay combined testing strategy (using the trep/non-trep RDT alone), for two use cases: individual diagnosis and community surveillance. We use cohort decision analysis to examine the diagnostic and cost outcomes. We estimate cost and cost-effectiveness of the alternative testing strategies at different levels of prevalence of past/current infection and current infection under each use case. We take the perspective of the global yaws eradication programme. We calculate the total number of correct diagnoses for each strategy over a range of plausible prevalences. We employ probabilistic sensitivity analysis (PSA) to account for uncertainty and report 95% intervals. At current prices of the treponemal and trep/non-trep RDTs, the sequential strategy is cost-saving for individual diagnosis at prevalence of past/current infection less than 85% (81-90); it is cost-saving for surveillance at less than 100%. The threshold price of the trep/non-trep RDT (below which the sequential strategy would no longer be cost-saving) is US$ 1.08 (1.02-1.14) for individual diagnosis at high prevalence of past/current infection (51%) and US$ 0.54 (0.52-0.56) for community surveillance at low prevalence (15%). We find that the sequential strategy is cost-saving for both diagnosis and surveillance in most relevant settings. In the absence of evidence assessing relative performance (sensitivity and specificity), cost-effectiveness is uncertain. However, the conditions under which the combined test only strategy might be more cost-effective than the sequential strategy are limited. A cheaper trep/non-trep RDT is needed, costing no more than US$ 0.50-1.00, depending on the use case. Our results will help enhance the cost-effectiveness of yaws programmes in the 13 countries known to be currently endemic. It will also inform efforts in the much larger group of 71 countries with a history of yaws, many of which will have to undertake surveillance to confirm the interruption of transmission.

Simultaneous versus sequential penetrating keratoplasty and cataract surgery.

PubMed

Hayashi, Ken; Hayashi, Hideyuki

2006-10-01

To compare the surgical outcomes of simultaneous penetrating keratoplasty and cataract surgery with those of sequential surgery. Thirty-nine eyes of 39 patients scheduled for simultaneous keratoplasty and cataract surgery and 23 eyes of 23 patients scheduled for sequential keratoplasty and secondary phacoemulsification surgery were recruited. Refractive error, regular and irregular corneal astigmatism determined by Fourier analysis, and endothelial cell loss were studied at 1 week and 3, 6, and 12 months after combined surgery in the simultaneous surgery group or after subsequent phacoemulsification surgery in the sequential surgery group. At 3 and more months after surgery, mean refractive error was significantly greater in the simultaneous surgery group than in the sequential surgery group, although no difference was seen at 1 week. The refractive error at 12 months was within 2 D of that targeted in 15 eyes (39%) in the simultaneous surgery group and within 2 D in 16 eyes (70%) in the sequential surgery group; the incidence was significantly greater in the sequential group (P = 0.0344). The regular and irregular astigmatism was not significantly different between the groups at 3 and more months after surgery. No significant difference was also found in the percentage of endothelial cell loss between the groups. Although corneal astigmatism and endothelial cell loss were not different, refractive error from target refraction was greater after simultaneous keratoplasty and cataract surgery than after sequential surgery, indicating a better outcome after sequential surgery than after simultaneous surgery.

Induction of simultaneous and sequential malolactic fermentation in durian wine.

PubMed

Taniasuri, Fransisca; Lee, Pin-Rou; Liu, Shao-Quan

2016-08-02

This study represented for the first time the impact of malolactic fermentation (MLF) induced by Oenococcus oeni and its inoculation strategies (simultaneous vs. sequential) on the fermentation performance as well as aroma compound profile of durian wine. There was no negative impact of simultaneous inoculation of O. oeni and Saccharomyces cerevisiae on the growth and fermentation kinetics of S. cerevisiae as compared to sequential fermentation. Simultaneous MLF did not lead to an excessive increase in volatile acidity as compared to sequential MLF. The kinetic changes of organic acids (i.e. malic, lactic, succinic, acetic and α-ketoglutaric acids) varied with simultaneous and sequential MLF relative to yeast alone. MLF, regardless of inoculation mode, resulted in higher production of fermentation-derived volatiles as compared to control (alcoholic fermentation only), including esters, volatile fatty acids, and terpenes, except for higher alcohols. Most indigenous volatile sulphur compounds in durian were decreased to trace levels with little differences among the control, simultaneous and sequential MLF. Among the different wines, the wine with simultaneous MLF had higher concentrations of terpenes and acetate esters while sequential MLF had increased concentrations of medium- and long-chain ethyl esters. Relative to alcoholic fermentation only, both simultaneous and sequential MLF reduced acetaldehyde substantially with sequential MLF being more effective. These findings illustrate that MLF is an effective and novel way of modulating the volatile and aroma compound profile of durian wine. Copyright © 2016 Elsevier B.V. All rights reserved.

Losing a dime with a satisfied mind: positive affect predicts less search in sequential decision making.

PubMed

von Helversen, Bettina; Mata, Rui

2012-12-01

We investigated the contribution of cognitive ability and affect to age differences in sequential decision making by asking younger and older adults to shop for items in a computerized sequential decision-making task. Older adults performed poorly compared to younger adults partly due to searching too few options. An analysis of the decision process with a formal model suggested that older adults set lower thresholds for accepting an option than younger participants. Further analyses suggested that positive affect, but not fluid abilities, was related to search in the sequential decision task. A second study that manipulated affect in younger adults supported the causal role of affect: Increased positive affect lowered the initial threshold for accepting an attractive option. In sum, our results suggest that positive affect is a key factor determining search in sequential decision making. Consequently, increased positive affect in older age may contribute to poorer sequential decisions by leading to insufficient search. 2013 APA, all rights reserved

Analysis of Optimal Sequential State Discrimination for Linearly Independent Pure Quantum States.

PubMed

Namkung, Min; Kwon, Younghun

2018-04-25

Recently, J. A. Bergou et al. proposed sequential state discrimination as a new quantum state discrimination scheme. In the scheme, by the successful sequential discrimination of a qubit state, receivers Bob and Charlie can share the information of the qubit prepared by a sender Alice. A merit of the scheme is that a quantum channel is established between Bob and Charlie, but a classical communication is not allowed. In this report, we present a method for extending the original sequential state discrimination of two qubit states to a scheme of N linearly independent pure quantum states. Specifically, we obtain the conditions for the sequential state discrimination of N = 3 pure quantum states. We can analytically provide conditions when there is a special symmetry among N = 3 linearly independent pure quantum states. Additionally, we show that the scenario proposed in this study can be applied to quantum key distribution. Furthermore, we show that the sequential state discrimination of three qutrit states performs better than the strategy of probabilistic quantum cloning.

A comparison of sequential and spiral scanning techniques in brain CT.

PubMed

Pace, Ivana; Zarb, Francis

2015-01-01

To evaluate and compare image quality and radiation dose of sequential computed tomography (CT) examinations of the brain and spiral CT examinations of the brain imaged on a GE HiSpeed NX/I Dual Slice 2CT scanner. A random sample of 40 patients referred for CT examination of the brain was selected and divided into 2 groups. Half of the patients were scanned using the sequential technique; the other half were scanned using the spiral technique. Radiation dose data—both the computed tomography dose index (CTDI) and the dose length product (DLP)—were recorded on a checklist at the end of each examination. Using the European Guidelines on Quality Criteria for Computed Tomography, 4 radiologists conducted a visual grading analysis and rated the level of visibility of 6 anatomical structures considered necessary to produce images of high quality. The mean CTDI(vol) and DLP values were statistically significantly higher (P <.05) with the sequential scans (CTDI(vol): 22.06 mGy; DLP: 304.60 mGy • cm) than with the spiral scans (CTDI(vol): 14.94 mGy; DLP: 229.10 mGy • cm). The mean image quality rating scores for all criteria of the sequential scanning technique were statistically significantly higher (P <.05) in the visual grading analysis than those of the spiral scanning technique. In this local study, the sequential technique was preferred over the spiral technique for both overall image quality and differentiation between gray and white matter in brain CT scans. Other similar studies counter this finding. The radiation dose seen with the sequential CT scanning technique was significantly higher than that seen with the spiral CT scanning technique. However, image quality with the sequential technique was statistically significantly superior (P <.05).

[Bilateral cochlear implants in children: acquisition of binaural hearing].

PubMed

Ramos-Macías, Angel; Deive-Maggiolo, Leopoldo; Artiles-Cabrera, Ovidio; González-Aguado, Rocío; Borkoski-Barreiro, Silvia A; Masgoret-Palau, Elizabeth; Falcón-González, Juan C; Bueno-Yanes, Jorge

2013-01-01

Several studies have indicated the benefit of bilateral cochlear implants in the acquisition of binaural hearing and bilateralism. In children with cochlear implants, is it possible to achieve binaurality after a second implant? When is the ideal time to implant them? The objective of this study was to analyse the binaural effect in children with bilateral implants and the differences between subjects with simultaneous and sequential implants with both short and long intervals. There were 90 patients between 1 and 2 years of age (the first surgery), implanted between 2000 and 2008. Of these, 25 were unilateral users and 65 bilateral; 17 patients had received simultaneous implants, 29 had sequential implants before 12 months after the first one (short interimplant period) and 19 after 12 months (long period). All of them were tested for silent and noisy verbal perception and a tonal threshold audiometry was performed. The silent perception test showed that the simultaneous and short period sequential implant patients (mean: 84.67%) versus unilateral and long period sequential implants (mean: 79.66%), had a statistically-significant difference (P=0,23). Likewise, the noisy perception test showed a difference with statistical significance (P=0,22) comparing the simultaneous implanted and short period sequential implants (mean, 77.17%) versus unilateral implanted and long period sequential ones (mean: 69.32%). The simultaneous and sequential short period implants acquired the advantages of binaural hearing. Copyright © 2012 Elsevier España, S.L. All rights reserved.

The Contrasting Relationships between Betaine and Homocysteine in Two Clinical Cohorts are Associated with Plasma Lipids and Drug Treatments

PubMed Central

Lever, Michael; George, Peter M.; Atkinson, Wendy; Elmslie, Jane L.; Slow, Sandy; Molyneux, Sarah L.; Troughton, Richard W.; Richards, A. Mark; Frampton, Christopher M.; Chambers, Stephen T.

2012-01-01

Background Urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). We aimed to confirm this in subjects with established vascular disease. Methods The correlation between betaine excretion and homocysteine was compared in samples collected from subjects 4 months after hospitalization for an acute coronary episode (ACS study, 415 urine samples) and from 158 sequential patients visiting a lipid disorders clinic. Principal findings In contrast to the lipid clinic study, betaine excretion and plasma homocysteine did not correlate in the total ACS cohort. Differences between the patient groups included age, non-HDL cholesterol and medication. In ACS subjects with below median betaine excretion, excretion correlated (using log transformed data) negatively with plasma homocysteine (r = −0.17, p = 0.019, n = 199), with no correlation in the corresponding subset of the lipid clinic subjects. In ACS subjects with above median betaine excretion a positive trend (r = +0.10) between betaine excretion and homocysteine was not significant; the corresponding correlation in lipid clinic subjects was r = +0.42 (p = 0.0001). In ACS subjects, correlations were stronger when plasma non-HDL cholesterol and betaine excretion were above the median, r = +0.20 (p = 0.045); in subjects above median non-HDL cholesterol and below median betaine excretion, r = −0.26 (p = 0.012). ACS subjects taking diuretics or proton pump inhibitors had stronger correlations, negative with lower betaine excretion and positive with higher betaine excretion. Conclusions Betaine excretion correlates with homocysteine in subjects with elevated blood lipids. PMID:22396767

The Hispanic Paradox and Predictors of Mortality in an Aging Bi-ethnic Cohort of Mexican Americans and European Americans: The San Antonio Longitudinal Study of Aging

PubMed Central

Espinoza, Sara E.; Jung, Inkyung; Hazuda, Helen

2013-01-01

OBJECTIVES To examine predictors of mortality in aging Mexican Americans (MAs) and European Americans (EAs). DESIGN Longitudinal, observational cohort study. SETTING Socioeconomically diverse neighborhoods in San Antonio, Texas. PARTICIPANTS Three hundred and ninety-four MA and 355 EA community-dwelling older adults (65+) who completed the baseline examination (1992–96) of the San Antonio Longitudinal Study of Aging (SALSA) and for whom vital status was ascertained over an average 8.2 years of follow-up. MEASUREMENTS Ethnic group was classified using a validated algorithm. Hazards ratios (HR) for mortality were estimated using Cox proportional hazards models with age, sex, ethnic group, education, income, frailty, diabetes with and without complications, comorbidity, cognition, depressive symptoms, and body mass index included as predictors in sequential models. RESULTS At baseline, MAs had higher prevalence of diabetes and frailty and lower socioeconomic status (SES) compared to EAs. The age- and sex-adjusted ethnic HR (MA vs. EA) for mortality was 1.54 (95% CI: 1.17–2.03). After adjusting for SES, the ethnic HR was no longer significant (HR = 1.16, 95% CI: 0.83–1.61). In the final model, comorbidity, diabetes with complications, depressive symptoms, and cognitive impairment were significant independent risk factors for mortality. CONCLUSION Contrary to the Hispanic paradox, MAs were at increased risk of mortality. Moreover, this ethnic disparity was largely explained by SES differences. Significant independent predictors of mortality, regardless of ethnic group, included diabetes with complications, comorbidity, depressive symptoms and cognitive impairment. Mortality reduction in older MAs requires attention to both socioeconomic disparities and disease factors. PMID:24000922

Spiritual coping of older people in Malta and Australia (part 1).

PubMed

Baldacchino, Donia R; Bonello, Lilian; Debattista, Clifford J

This descriptive sequential explanatory study, which forms part of a larger study, investigated the use of spiritual coping strategies by three cohort groups of Maltese older residents in three phases. The theoretical model of causal pathway for mental health based on monotheistic religions (Christianity, Judaism, and Islam) guided the study. Participants were recruited from four private homes: two in Australia (n=30), two in Malta (n=43) and two state residences also in Malta (n=64). The residents (n=137; men n=103, women n=34), mean (M) age 72.8 years, were all Roman Catholics, mobile and with a minimum residence of 6 months. The quantitative data (phase I) were collected by the Maltese version of the Spiritual Coping Strategies scale ( Baldacchino and Buhagiar, 2003 ). The qualitative findings in phase II derived from the face-to-face interviews and focus groups explain the use of spiritual coping strategies and how they contributed toward coping with institutionalisation. Significant differences were found in spiritual coping (F=11.434; p=0.001; degree of freedom (df)=2) whereby the cohort in Australia scored the highest scores in the total spiritual coping (M=48.60; standard deviation (SD)=6.251), religious coping (M=23.47; SD=2.145) and existential coping (M=25.13; SD=6.033). No significant differences were found in the total spiritual coping between subgroups of mobility and demographic characteristics except by gender (Student's t-test (t)=2.455; p=0.015) whereby women (M=22.09; SD=4.325) scored higher than the men (M=19.67; SD=4.508). Australian private homes reported the highest (significant) mean scores in total spiritual coping, religious coping and existential coping. Recommendations were set for clinical practice and management, nursing education, and further research.

Introduction of inactivated poliovirus vaccine leading into the polio eradication endgame strategic plan; Hangzhou, China, 2010-2014.

PubMed

Liu, Yan; Wang, Jun; Liu, Shijun; Du, Jian; Wang, Liang; Gu, Wenwen; Xu, Yuyang; Zuo, Shuyan; Xu, Erping; An, Zhijie

2017-03-01

China's Expanded Program on Immunization (EPI) has provided 4 doses of oral poliovirus vaccine (OPV) since the 1970s. Inactivated poliovirus vaccine (IPV) became available in 2010 in Hangzhou as a private-sector, parent-chosen alternative to OPV. In 2015, WHO recommended that countries with all-OPV vaccination schedules introduce at least one dose of IPV, to mitigate risk associated with the withdrawal of type 2 OPV. We analyzed polio vaccine coverage and utilization in Hangzhou to determine patterns of IPV use and the occurrence of vaccine-associated paralytic polio (VAPP) in the various patterns identified. Children born between 2010 and 2014 and registered in Hangzhou's Immunization Information System (HZIIS) were included. VAPP cases were detected through the acute flaccid paralysis surveillance system. We used descriptive epidemiological methods to determine IPV and OPV usage patterns and VAPP occurrence. HZIIS data from 566,894 children were analyzed. Coverage levels of polio vaccine were greater than 92% for each birth cohort. Percentages of children using OPV-only, IPV-only, and IPV/OPV sequential schedules were 70.57%, 27.01% and 2.41%, respectively. IPV-only schedule utilization increased by birth cohort regardless of geographical area or whether the child was locally-born. The highest use of an all-IPV schedule (79.85%) was among urban, locally-born children in the 2014 birth cohort. Five VAPP cases were identified during the study years; all cases occurred following the first polio vaccine dose, which was always OPV for the cases. Type 2 vaccine virus was isolated from 2 VAPP cases, and type 2 and type 3 vaccine virus was isolated from one VAPP case. The incidence of VAPP in the 2010-2014 birth cohorts was 3.76 per 1million doses of OPV. Children in Hangzhou had high polio vaccination coverage. IPV-only schedule use increased by year, and was highest in urban areas among locally-born children. All cases of VAPP were associated with the first dose of OPV. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vivo comparison of simultaneous versus sequential injection technique for thermochemical ablation in a porcine model.

PubMed

Cressman, Erik N K; Shenoi, Mithun M; Edelman, Theresa L; Geeslin, Matthew G; Hennings, Leah J; Zhang, Yan; Iaizzo, Paul A; Bischof, John C

2012-01-01

To investigate simultaneous and sequential injection thermochemical ablation in a porcine model, and compare them to sham and acid-only ablation. This IACUC-approved study involved 11 pigs in an acute setting. Ultrasound was used to guide placement of a thermocouple probe and coaxial device designed for thermochemical ablation. Solutions of 10 M acetic acid and NaOH were used in the study. Four injections per pig were performed in identical order at a total rate of 4 mL/min: saline sham, simultaneous, sequential, and acid only. Volume and sphericity of zones of coagulation were measured. Fixed specimens were examined by H&E stain. Average coagulation volumes were 11.2 mL (simultaneous), 19.0 mL (sequential) and 4.4 mL (acid). The highest temperature, 81.3°C, was obtained with simultaneous injection. Average temperatures were 61.1°C (simultaneous), 47.7°C (sequential) and 39.5°C (acid only). Sphericity coefficients (0.83-0.89) had no statistically significant difference among conditions. Thermochemical ablation produced substantial volumes of coagulated tissues relative to the amounts of reagents injected, considerably greater than acid alone in either technique employed. The largest volumes were obtained with sequential injection, yet this came at a price in one case of cardiac arrest. Simultaneous injection yielded the highest recorded temperatures and may be tolerated as well as or better than acid injection alone. Although this pilot study did not show a clear advantage for either sequential or simultaneous methods, the results indicate that thermochemical ablation is attractive for further investigation with regard to both safety and efficacy.

Better together: reduced compliance after sequential versus simultaneous bilateral hearing aids fitting.

PubMed

Lavie, Limor; Banai, Karen; Attias, Joseph; Karni, Avi

2014-03-01

The purpose of this study was to determine the effects of sequential versus simultaneous bilateral hearing aids fitting on patient compliance. Thirty-six older adults with hearing impairment participated in this study. Twelve were fitted with bilateral hearing aids simultaneously. The remaining participants were fitted sequentially: One hearing aid (to the left or to the right ear) was used initially; 1 month later, the other ear was also fitted with a hearing aid for bilateral use. Self-reports on usefulness and compliance were elicited after the first and second months of hearing aid use. In addition, the number of hours the hearing aids were used was extracted from the data loggings of each device. Simultaneous fitting resulted in high levels of compliance and consistent usage throughout the study period. Sequential fitting resulted in abrupt reduction in compliance and hours of use once the second hearing aid was added, both in the clinical scoring and in the data loggings. Simultaneous fitting of bilateral hearing aids results in better compliance compared with sequential fitting. The addition of a second hearing aid after a relatively short period of monaural use may lead to inconsistent use of both hearing aids.

Increasing efficiency of preclinical research by group sequential designs

PubMed Central

Piper, Sophie K.; Rex, Andre; Florez-Vargas, Oscar; Karystianis, George; Schneider, Alice; Wellwood, Ian; Siegerink, Bob; Ioannidis, John P. A.; Kimmelman, Jonathan; Dirnagl, Ulrich

2017-01-01

Despite the potential benefits of sequential designs, studies evaluating treatments or experimental manipulations in preclinical experimental biomedicine almost exclusively use classical block designs. Our aim with this article is to bring the existing methodology of group sequential designs to the attention of researchers in the preclinical field and to clearly illustrate its potential utility. Group sequential designs can offer higher efficiency than traditional methods and are increasingly used in clinical trials. Using simulation of data, we demonstrate that group sequential designs have the potential to improve the efficiency of experimental studies, even when sample sizes are very small, as is currently prevalent in preclinical experimental biomedicine. When simulating data with a large effect size of d = 1 and a sample size of n = 18 per group, sequential frequentist analysis consumes in the long run only around 80% of the planned number of experimental units. In larger trials (n = 36 per group), additional stopping rules for futility lead to the saving of resources of up to 30% compared to block designs. We argue that these savings should be invested to increase sample sizes and hence power, since the currently underpowered experiments in preclinical biomedicine are a major threat to the value and predictiveness in this research domain. PMID:28282371

Characteristics, Outcomes, and Predictability of Critically Ill Obstetric Patients: A Multicenter Prospective Cohort Study.

PubMed

Vasquez, Daniela N; Das Neves, Andrea V; Vidal, Laura; Moseinco, Miriam; Lapadula, Jorge; Zakalik, Graciela; Santa-Maria, Analía; Gomez, Raúl A; Capalbo, Mónica; Fernandez, Claudia; Agüero-Villareal, Enrique; Vommaro, Santiago; Moretti, Marcelo; Soli, Silvana B; Ballestero, Florencia; Sottile, Juan P; Chapier, Viviana; Lovesio, Carlos; Santos, José; Bertoletti, Fernando; Intile, Alfredo D; Desmery, Pablo M; Estenssoro, Elisa

2015-09-01

To evaluate pregnant/postpartum patients requiring ICUs admission in Argentina, describe characteristics of mothers and outcomes for mothers/babies, evaluate risk factors for maternal-fetal-neonatal mortality; and compare outcomes between patients admitted to public and private health sectors. Multicenter, prospective, national cohort study. Twenty ICUs in Argentina (public, 8 and private, 12). Pregnant/postpartum (< 42 d) patients admitted to ICU. None. Three hundred sixty-two patients were recruited, 51% from the public health sector and 49% from the private. Acute Physiology and Chronic Health Evaluation II was 8 (4-12); predicted/observed mortality, 7.6%/3.6%; hospital length of stay, 7 days (5-13 d); and fetal-neonatal losses, 17%. Public versus private health sector patients: years of education, 9 ± 3 versus 15 ± 3; transferred from another hospital, 43% versus 12%; Acute Physiology and Chronic Health Evaluation II, 9 (5-13.75) versus 7 (4-9); hospital length of stay, 10 days (6-17 d) versus 6 days (4-9 d); prenatal care, 75% versus 99.4%; fetal-neonatal losses, 25% versus 9% (p = 0.000 for all); and mortality, 5.4% versus 1.7% (p = 0.09). Complications in ICU were multiple-organ dysfunction syndrome (34%), shock (28%), renal dysfunction (25%), and acute respiratory distress syndrome (20%); all predominated in the public sector. Sequential Organ Failure Assessment (during first 24 hr of admission) score of at least 6.5 presented the best discriminative power for maternal mortality. Independent predictors of maternal-fetal-neonatal mortality were Acute Physiology and Chronic Health Evaluation II, education level, prenatal care, and admission to tertiary hospitals. Patients spent a median of 7 days in hospital; 3.6% died. Maternal-fetal-neonatal mortality was determined not only by acuteness of illness but to social and healthcare aspects like education, prenatal control, and being cared in specialized hospitals. Sequential Organ Failure Assessment (during first 24 hr of admission), easier to calculate than Acute Physiology and Chronic Health Evaluation II, was a better predictor of maternal outcome. Evident health disparities existed between patients admitted to public versus private hospitals: the former received less prenatal care, were less educated, were more frequently transferred from other hospitals, were sicker at admission, and developed more complications; maternal and fetal-neonatal mortality were higher. These findings point to the need of redesigning healthcare services to account for these inequities.

First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica.

PubMed

Rolan, Paul E; O'Neill, Gilmore; Versage, Eve; Rana, Jitesh; Tang, Yongqiang; Galluppi, Gerald; Aycardi, Ernesto

2015-01-01

To evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica. This was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28. Beyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain scores. BG00010 was rapidly distributed, with a prolonged terminal elimination phase. These data support the development of BG00010 for the treatment of neuropathic pain. ClinicalTrials.gov NCT00961766.

Heritability of the Severity of the Metabolic Syndrome in Whites and Blacks in 3 Large Cohorts.

PubMed

Musani, Solomon K; Martin, Lisa J; Woo, Jessica G; Olivier, Michael; Gurka, Matthew J; DeBoer, Mark D

2017-04-01

Although dichotomous criteria for the metabolic syndrome (MetS) appear heritable, it is not known whether MetS severity as assessed by a continuous MetS score is heritable and whether this varies by race. We used SOLAR (Sequential Oligogenic Linkage Analysis Routines) to evaluate heritability of Adult Treatment Panel-III MetS and a sex- and race-specific MetS severity Z score among 3 large familial cohorts: the JHS (Jackson Heart Study, 1404 black participants), TOPS (Take Off Pounds Sensibly, 1947 white participants), and PLRS (Princeton Lipid Research Study, 229 black and 527 white participants). Heritability estimates were larger for Adult Treatment Panel-III MetS among black compared with white cohort members (JHS 0.48; 95% confidence interval [CI], 0.28-0.68 and PLRS blacks 0.93 [95% CI, 0.73-1.13] versus TOPS 0.21 [95% CI, -0.18 to 0.60] and PLRS whites 0.27 [95% CI, -0.04 to 0.58]). The difference by race narrowed when assessing heritability of the MetS severity score (JHS 0.52 [95% CI, 0.38, 0.66] and PLRS blacks 0.64 [95% CI, 0.13-1.15] versus TOPS 0.23 [95% CI, 0.15-0.31] and PLRS whites 0.60 [95% CI, 0.33-0.87]). There was a high degree of genetic and phenotypic correlation between MetS severity and the individual components of MetS among all groups, although the genetic correlations failed to reach statistical significance among PLRS blacks. Meta-analyses revealed a combined heritability estimate for Adult Treatment Panel-III MetS of 0.24 (95% CI, 0.11-0.36) and for the MetS severity score of 0.50 (95% CI, -0.05 to 0.99). MetS severity seems highly heritable among whites and blacks. This continuous MetS severity Z score may provide a more useful means of characterizing phenotypic MetS in genetic studies by minimizing racial differences. © 2017 American Heart Association, Inc.

Hospitalist management of vaso-occlusive pain crisis in patients with sickle cell disease using a pathway of care.

PubMed

Allen Liles, Edmund; Kirsch, Jonathan; Gilchrist, Michael; Adem, Mukhtar

2014-04-01

Patients with sickle cell disease (SCD) suffer from intermittent vaso-occlusive pain crises (VOCs). These crises lead to frequent hospitalizations, significant morbidity, and increased mortality risk. Care pathways can enhance efficiency and quality of care. Our study sought to evaluate the development and implementation of a care pathway for patients with SCD experiencing VOCs. The University of North Carolina (UNC) Comprehensive Sickle Cell Program provides all levels of care for a large population of patients with sickle cell anemia. All patients admitted to UNC Hospitals with SCD VOCs from January 2009 through June 2011 were evaluated. During this time period, we also assessed sequential prospective cohorts during progressive phases of developing and implementing a quality improvement and pathway of care program for this patient population in our study. The developed pathway entailed geographic localization for VOC patients, a single group of faculty physicians caring for these patients, and early use of patient-controlled analgesia (PCA) to achieve pain control. Physicians from the UNC Hospital Medicine Program were responsible for the initiatives. Cohorts were compared to a baseline historical control. Outcomes of interest included patient length of stay (LOS) in the hospital, 30-day readmission rate, need for transfusion, incidence of acute chest syndrome, use of naloxone, and use of PCA. Compared with an historical baseline cohort, the development and implementation of a VOC care pathway for patients with SCD led to reduction in average hospital LOS by 1.44 days (P < 0.05) and an increase in use of PCAs (P < 0.05). Patient readmission rates, number of transfusions, incidence of acute chest syndrome, and use of naloxone did not significantly change. Hospitalist-led management of patients with SCD VOCs using a care pathway that emphasizes early, aggressive PCA-based pain control is associated with reduced hospital LOS. The LOS reduction seen in our study is clinically meaningful. Notably, other measures of patient outcomes and quality of care metrics did not change significantly, and some trended towards improvement.

The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.

PubMed

Finn, Richard S; Crown, John P; Lang, Istvan; Boer, Katalin; Bondarenko, Igor M; Kulyk, Sergey O; Ettl, Johannes; Patel, Ravindranath; Pinter, Tamas; Schmidt, Marcus; Shparyk, Yaroslav; Thummala, Anu R; Voytko, Nataliya L; Fowst, Camilla; Huang, Xin; Kim, Sindy T; Randolph, Sophia; Slamon, Dennis J

2015-01-01

Palbociclib (PD-0332991) is an oral, small-molecule inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 with preclinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens. We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer. In this open-label, randomised phase 2 study, postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate. Patients were enrolled in two separate cohorts that accrued sequentially: in cohort 1, patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone, whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both. In both cohorts, patients were randomly assigned 1:1 via an interactive web-based randomisation system, stratified by disease site and disease-free interval, to receive continuous oral letrozole 2.5 mg daily or continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 (instead of cohort 2 alone). The study is ongoing but closed to accrual; these are the results of the final analysis of progression-free survival. The study is registered with the ClinicalTrials.gov, number NCT00721409. Between Dec 22, 2009, and May 12, 2012, we randomly assigned 165 patients, 84 to palbociclib plus letrozole and 81 to letrozole alone. At the time of the final analysis for progression-free survival (median follow-up 29.6 months [95% CI 27.9-36.0] for the palbociclib plus letrozole group and 27.9 months [25.5-31.1] for the letrozole group), 41 progression-free survival events had occurred in the palbociclib plus letrozole group and 59 in the letrozole group. Median progression-free survival was 10.2 months (95% CI 5.7-12.6) for the letrozole group and 20.2 months (13.8-27.5) for the palbociclib plus letrozole group (HR 0.488, 95% CI 0.319-0.748; one-sided p=0.0004). In cohort 1 (n=66), median progression-free survival was 5.7 months (2.6-10.5) for the letrozole group and 26.1 months (11.2-not estimable) for the palbociclib plus letrozole group (HR 0.299, 0.156-0.572; one-sided p<0.0001); in cohort 2 (n=99), median progression-free survival was 11.1 months (7.1-16.4) for the letrozole group and 18.1 months (13.1-27.5) for the palbociclib plus letrozole group (HR 0.508, 0.303-0.853; one-sided p=0.0046). Grade 3-4 neutropenia was reported in 45 (54%) of 83 patients in the palbociclib plus letrozole group versus one (1%) of 77 patients in the letrozole group, leucopenia in 16 (19%) versus none, and fatigue in four (4%) versus one (1%). Serious adverse events that occurred in more than one patient in the palbociclib plus letrozole group were pulmonary embolism (three [4%] patients), back pain (two [2%]), and diarrhoea (two [2%]). No cases of febrile neutropenia or neutropenia-related infections were reported during the study. 11 (13%) patients in the palbociclib plus letrozole group and two (2%) in the letrozole group discontinued the study because of adverse events. The addition of palbociclib to letrozole in this phase 2 study significantly improved progression-free survival in women with advanced oestrogen receptor-positive and HER2-negative breast cancer. A phase 3 trial is currently underway. Pfizer. Copyright © 2015 Elsevier Ltd. All rights reserved.

AAV5-Factor VIII Gene Transfer in Severe Hemophilia A.

PubMed

Rangarajan, Savita; Walsh, Liron; Lester, Will; Perry, David; Madan, Bella; Laffan, Michael; Yu, Hua; Vettermann, Christian; Pierce, Glenn F; Wong, Wing Y; Pasi, K John

2017-12-28

Patients with hemophilia A rely on exogenous factor VIII to prevent bleeding in joints, soft tissue, and the central nervous system. Although successful gene transfer has been reported in patients with hemophilia B, the large size of the factor VIII coding region has precluded improved outcomes with gene therapy in patients with hemophilia A. We infused a single intravenous dose of a codon-optimized adeno-associated virus serotype 5 (AAV5) vector encoding a B-domain-deleted human factor VIII (AAV5-hFVIII-SQ) in nine men with severe hemophilia A. Participants were enrolled sequentially into one of three dose cohorts (low dose [one participant], intermediate dose [one participant], and high dose [seven participants]) and were followed through 52 weeks. Factor VIII activity levels remained at 3 IU or less per deciliter in the recipients of the low or intermediate dose. In the high-dose cohort, the factor VIII activity level was more than 5 IU per deciliter between weeks 2 and 9 after gene transfer in all seven participants, and the level in six participants increased to a normal value (>50 IU per deciliter) that was maintained at 1 year after receipt of the dose. In the high-dose cohort, the median annualized bleeding rate among participants who had previously received prophylactic therapy decreased from 16 events before the study to 1 event after gene transfer, and factor VIII use for participant-reported bleeding ceased in all the participants in this cohort by week 22. The primary adverse event was an elevation in the serum alanine aminotransferase level to 1.5 times the upper limit of the normal range or less. Progression of preexisting chronic arthropathy in one participant was the only serious adverse event. No neutralizing antibodies to factor VIII were detected. The infusion of AAV5-hFVIII-SQ was associated with the sustained normalization of factor VIII activity level over a period of 1 year in six of seven participants who received a high dose, with stabilization of hemostasis and a profound reduction in factor VIII use in all seven participants. In this small study, no safety events were noted, but no safety conclusions can be drawn. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov number, NCT02576795 ; EudraCT number, 2014-003880-38 .).

Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial.

PubMed

Steinhoff, Mark C; Katz, Joanne; Englund, Janet A; Khatry, Subarna K; Shrestha, Laxman; Kuypers, Jane; Stewart, Laveta; Mullany, Luke C; Chu, Helen Y; LeClerq, Steven C; Kozuki, Naoko; McNeal, Monica; Reedy, Adriana M; Tielsch, James M

2017-09-01

Influenza immunisation during pregnancy is recommended but not widely implemented in some low-income regions. We assessed the safety and efficacy in mothers and infants of year-round maternal influenza immunisation in Nepal, where influenza viruses circulate throughout the year. In this phase 4, randomised, placebo-controlled trial, we enrolled two consecutive sequential annual cohorts of pregnant women from the Sarlahi district in southern Nepal. We randomised mothers 1:1 to receive seasonally recommended trivalent inactivated influenza vaccine or saline placebo in blocks of eight, stratified by gestational age at enrolment (17-25 weeks vs 26-34 weeks). Women were eligible if they were married, 15-40 years of age, 17-34 weeks' gestation at enrolment, and had not previously received any influenza vaccine that season. We collected serum samples before and after immunisation, and cord blood from a subset of women and infants. Staff masked to allocation made home visits every week from enrolment to 6 months after delivery. Midnasal swabs for respiratory virus PCR testing were collected during maternal acute febrile respiratory infections, and from infants with any respiratory symptom. We assessed vaccine immunogenicity, safety, and three primary outcomes: the incidence of maternal influenza-like illness in pregnancy and 0-180 days postpartum, the incidence of low birthweight (<2500 g), and the incidence of laboratory-confirmed infant influenza disease from 0 to 180 days. This trial is registered with ClinicalTrials.gov, number NCT01034254. From April 25, 2011, to Sept 9, 2013, we enrolled 3693 women in two cohorts of 2090 (1041 assigned to placebo and 1049 to vaccine) and 1603 (805 assigned to placebo and 798 to vaccine), with 3646 liveborn infants (cohort 1, 999 in placebo group and 1010 in vaccine group; cohort 2, 805 in placebo group and 798 in vaccine group). Immunisation reduced maternal febrile influenza-like illness with an overall efficacy of 19% (95% CI 1 to 34) in the combined cohorts; 9% efficacy (-16 to 29) in the first cohort, and 36% efficacy (9 to 55) in the second cohort. For laboratory-confirmed influenza infections in infants aged 0-6 months, immunisation had an overall efficacy for the combined cohorts of 30% (95% CI 5 to 48); in the first cohort, the efficacy was 16% (-19 to 41), and in the second cohort it was 60% (26 to 88). Maternal immunisation reduced the rates of low birthweight by 15% (95% CI 3-25) in both cohorts combined. The rate of small for gestational age infants was not modified by immunisation. The number of adverse events was similar regardless of immunisation status. Miscarriage occurred in three (0·2%) participants in the placebo group versus five (0·3%) in the vaccine group, stillbirth occurred in 31 (1·7%) versus 33 (1·8%), and congenital defects occurred in 18 (1·0%) versus 20 (1·1%). Five women died in the placebo group and three died in the vaccine group. The number of infant deaths at age 0-6 months was similar in each group (50 in the placebo group and 61 in the vaccine group). No serious adverse events were associated with receipt of immunisation. Year-round maternal influenza immunisation significantly reduced maternal influenza-like illness, influenza in infants, and low birthweight over the entire course of the study, indicating the strategy could be useful in subtropical regions. Bill & Melinda Gates Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Correlated sequential tunneling through a double barrier for interacting one-dimensional electrons

NASA Astrophysics Data System (ADS)

Thorwart, M.; Egger, R.; Grifoni, M.

2005-07-01

The problem of resonant tunneling through a quantum dot weakly coupled to spinless Tomonaga-Luttinger liquids has been studied. We compute the linear conductance due to sequential tunneling processes upon employing a master equation approach. Besides the previously used lowest-order golden rule rates describing uncorrelated sequential tunneling processes, we systematically include higher-order correlated sequential tunneling (CST) diagrams within the standard Weisskopf-Wigner approximation. We provide estimates for the parameter regions where CST effects can be important. Focusing mainly on the temperature dependence of the peak conductance, we discuss the relation of these findings to previous theoretical and experimental results.

Kullback-Leibler information function and the sequential selection of experiments to discriminate among several linear models. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Sidik, S. M.

1972-01-01

A sequential adaptive experimental design procedure for a related problem is studied. It is assumed that a finite set of potential linear models relating certain controlled variables to an observed variable is postulated, and that exactly one of these models is correct. The problem is to sequentially design most informative experiments so that the correct model equation can be determined with as little experimentation as possible. Discussion includes: structure of the linear models; prerequisite distribution theory; entropy functions and the Kullback-Leibler information function; the sequential decision procedure; and computer simulation results. An example of application is given.

Accuracy of a rapid real-time polymerase chain reaction assay for diagnosis of group B Streptococcus colonization in a cohort of HIV-infected pregnant women.

PubMed

Gouvea, Maria Isabel S; Joao, Esau C; Teixeira, Maria de Lourdes B; Read, Jennifer S; Fracalanzza, Sergio E L; Souza, Claudia T V; Souza, Maria José de; Torres Filho, Helio M; Leite, Cassiana C F; do Brasil, Pedro E A A

2017-05-01

There are limited data regarding Xpert performance to detect Group B Streptococcus (GBS) in HIV-infected pregnant women. We evaluated the accuracy of a rapid real-time polymerase chain reaction (PCR) test in a cohort of HIV-infected women. At 35-37 weeks of pregnancy, a pair of combined rectovaginal swabs were collected for two GBS assays in a cohort of sequentially included HIV-infected women in Rio de Janeiro: (1) culture; and (2) real-time PCR assay [GeneXpert GBS (Cepheid, Sunnyvale, CA)]. Using culture as the reference, sensitivity, specificity, positive and negative-likelihood ratios were estimated. From June 2012 to February 2015, 337 pregnant women met inclusion criteria. One woman was later excluded, due to failure to obtain a result in the index test; 336 were included in the analyses. The GBS colonization rate was 19.04%. Sensitivity and specificity of the GeneXpert GBS assay were 85.94% (95% CI: 75.38-92.42) and 94.85% (95% CI: 91.55-96.91), respectively. Positive and negative predictive values were 79.71% (95% CI: 68.78-87.51) and 96.63% (95% CI: 93.72-98.22), respectively. GeneXpert GBS is an acceptable test for the identification of GBS colonization in HIV-infected pregnant women and represents a reasonable option to detect GBS colonization in settings where culture is not feasible.

Therapeutic effect for liver-metastasized tumor by sequential intravenous injection of anionic polymer and cationic lipoplex of siRNA.

PubMed

Hattori, Yoshiyuki; Arai, Shohei; Kikuchi, Takuto; Ozaki, Kei-Ichi; Kawano, Kumi; Yonemochi, Etsuo

2016-04-01

Previously, we developed a novel siRNA transfer method to the liver by sequential intravenous injection of anionic polymer and cationic liposome/siRNA complex (cationic lipoplex). In this study, we investigated whether siRNA delivered by this sequential injection could significantly suppress mRNA expression of the targeted gene in liver metastasis and inhibit tumor growth. When cationic lipoplex was intravenously injected into mice bearing liver metastasis of human breast tumor MCF-7 at 1 min after intravenous injection of chondroitin sulfate C (CS) or poly-l-glutamic acid (PGA), siRNA was accumulated in tumor-metastasized liver. In terms of a gene silencing effect, sequential injections of CS or PGA plus cationic lipoplex of luciferase siRNA could reduce luciferase activity in liver MCF-7-Luc metastasis. Regarding the side effects, sequential injections of CS plus cationic lipoplex did not exhibit hepatic damage or induction of inflammatory cytokines in serum after repeated injections, but sequential injections of PGA plus cationic lipoplex did. Finally, sequential injections of CS plus cationic lipoplex of protein kinase N3 siRNA could suppress tumor growth in the mice bearing liver metastasis. From these findings, sequential injection of CS and cationic lipoplex of siRNA might be a novel systemic method of delivering siRNA to liver metastasis.

Children's Reproduction of Modeled Sequential Actions. Final Report.

ERIC Educational Resources Information Center

Uzgiris, Ina C.

This paper describes seven interrelated studies concerned with children's understanding of sequential actions and with the effects of observing a model on this understanding. A total of 546 elementary and secondary school students served as subjects for the studies. The tasks for all of the studies involved deriving the pattern for a sequence from…

Early variation of quick sequential organ failure assessment score to predict in-hospital mortality in emergency department patients with suspected infection.

PubMed

Najla, Lemachatti; Mar, Ortega; Andrea, Penaloza; Le Borgne, Pierrick; Claret, Pierre-Géraud; Occelli, Céline; Truchot, Jennifer; Dumas, Florence; Feral-Pierssens, Anne-Laure; Andrianjafy, Héry; Beaune, Sebastien; Yordanov, Youri; Hausfater, Pierre; Riou, Bruno; Bloom, Ben; Krastinova, Evguenia; Freund, Yonathan

2018-05-15

The quick sequential organ failure assessment (qSOFA) score showed good prognostic performance in patients with suspicion of infection in the emergency department (ED). However, previous studies only assessed the performance of individual values of qSOFA during the ED stay. As this score may vary over short timeframes, the optimal time of measurement, and the prognostic value of its variation are unclear. The objective of the present study was to prospectively assess the prognostic value of the change in qSOFA over the first 3 h (ΔqSOFA=qSOFA at 3 h-qSOFA at inclusion). This is an international prospective cohort study conducted in 17 EDs in France, Belgium, and Spain. From November 2016 to March 2017, patients with a suspected infection and a qSOFA score of 2 or higher were included and followed up until death or hospital discharge. qSOFA was measured at inclusion, 1 h and 3 h. Primary end point was in-hospital mortality, truncated at 28 days. Of 534 recruited patients, 512 were included in the analysis. The qSOFA was improved at 3 h (ΔqSOFA<0) in 287 (55%) patients. Overall in-hospital mortality was 27%: 44% when ΔqSOFA greater than 0, 36% when ΔqSOFA=0, and 18% when ΔqSOFA less than 0. A positive ΔqSOFA was independently associated with reduced in-hospital mortality (adjusted hazard ratio of 0.48, 95% confidence interval: 0.34-0.68). After modeling qSOFA kinetics in the first 3 h, there was a significant difference in adjusted slopes between patients who died and those who survived (0.15, 95% confidence interval: 0.09-0.22, P<0.001). In patients with suspected infection presenting to the ED with a qSOFA of 2 or higher, the early change in qSOFA is a strong independent predictor of mortality.

Safety, immunogenicity, and clinical outcomes in patients with Morquio A syndrome participating in 2 sequential open-label studies of elosulfase alfa enzyme replacement therapy (MOR-002/MOR-100), representing 5 years of treatment.

PubMed

Hendriksz, Christian; Santra, Saikat; Jones, Simon A; Geberhiwot, Tarekegn; Jesaitis, Lynne; Long, Brian; Qi, Yulan; Hawley, Sara M; Decker, Celeste

2018-04-01

Elosulfase alfa is an enzyme replacement therapy for Morquio A syndrome (mucopolysaccharidosis IVA), a multisystemic progressive lysosomal storage disorder. This report includes the primary treatment outcomes and immunogenicity profile of elosulfase alfa in patients with Morquio A syndrome from 2 sequential studies, MOR-002 (ClinicalTrials.govNCT00884949) and MOR-100 (NCT01242111), representing >5 years of clinical study data. MOR-002 was an open-label, single-arm phase 1/2 study that evaluated the pharmacokinetics, safety, immunogenicity, and preliminary efficacy of 3 sequential doses of elosulfase alfa (0.1, 1.0, and 2.0 mg/kg/week) in patients with Morquio A syndrome (n = 20) over 36 weeks, followed by an optional 36- to 48-week treatment period using elosulfase alfa 1.0 mg/kg once weekly (qw). During the 0.1 mg/kg dosing phase, 1 patient discontinued due to a type I hypersensitivity adverse event (AE), and that patient's sibling voluntarily discontinued in the absence of AEs. An additional patient discontinued due to recurrent infusion reactions during the 1.0 mg/kg continuation phase. The remaining 17 patients completed MOR-002 and enrolled in MOR-100, an open-label, long-term extension study that further evaluated safety and clinical outcomes with elosulfase alfa administered at 2.0 mg/kg qw. During the course of MOR-100, patients were given the option of receiving elosulfase alfa infusions at home with nursing assistance. Over the course of both studies, all patients experienced ≥1 AE and most patients experienced a drug-related AE, generally of mild or moderate severity. Hypersensitivity reactions reported as related to study drug occurred in 25% of patients. Thirteen patients who chose to receive infusions at home had the same tolerability and safety profile, as well as comparable compliance rates, as patients who chose to receive on-site infusions. All patients developed antibodies to elosulfase alfa. Positivity for neutralizing antibodies was associated with increased drug half-life and decreased drug clearance. Despite formation of antidrug-binding (total antidrug antibodies, TAb) and in vitro neutralizing antibodies (NAb) in all patients, these types of immunogenicity to elosulfase alfa were not correlated with safety or clinical outcomes. In contrast with the reported natural history of Morquio A, no trends toward decreasing endurance, respiratory function, or ability to perform activities of daily living were observed in this cohort over the 5-year period. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The involvement of immunoglobulin E isotype switch in scleroderma skin tissue.

PubMed

Ohtsuka, Tsutomu; Yamazaki, Soji

2005-08-01

The involvement of mast cell, which is activated by immunoglobulin E (IgE), has been reported in the formation of systemic sclerosis (SSc) abnormality. IgE is generated with isotype switch. During isotype switch, switch circles resulting from direct mu to epsilon, or from sequential mu to gamma via epsilon switching will be created. We studied whether switching occurs in SSc. We used nested polymerase chain reaction to analyze the S fragments from switch circles. Fifty-two patients with SSc, and 62 healthy women were studied. Neither of 62 normal skin tissues showed direct switch, nor sequential switch. Neither of seven normal whole blood cells showed direct switch, nor sequential switch. In 52SSc skin tissues, three (5.8%) showed direct switch, and two (3.8%) showed sequential switch. As a result, five (9.6%) of SSc skin tissue showed immunogobulin E class switch. These results were confirmed by DNA sequencing. These results demonstrated that isotype switch to the epsilon locus achieved by direct and/or sequential switch are involved in SSc skin.

[Co-composting high moisture vegetable waste and flower waste in a sequential fed operation].

PubMed

Zhang, Xiangfeng; Wang, Hongtao; Nie, Yongfeng

2003-11-01

Co-composting of high moisture vegetable wastes (celery and cabbage) and flower wastes (carnation) were studied in a sequential fed bed. The preliminary materials of composting were celery and carnation wastes. The sequential fed materials of composting were cabbage wastes and were fed every 4 days. Moisture content of mixture materials was between 60% and 70%. Composting was done in an aerobic static bed of composting based temperature feedback and control via aeration rate regulation. Aeration was ended when temperature of the pile was about 40 degrees C. Changes of composting of temperature, aeration rate, water content, organic matter, ash, pH, volume, NH4(+)-N, and NO3(-)-N were studied. Results show that co-composting of high moisture vegetable wastes and flower wastes, in a sequential fed aerobic static bed based temperature feedback and control via aeration rate regulation, can stabilize organic matter and removal water rapidly. The sequential fed operation are effective to overcome the difficult which traditional composting cannot applied successfully where high moisture vegetable wastes in more excess of flower wastes, such as Dianchi coastal.

Numerical study on the sequential Bayesian approach for radioactive materials detection

NASA Astrophysics Data System (ADS)

Qingpei, Xiang; Dongfeng, Tian; Jianyu, Zhu; Fanhua, Hao; Ge, Ding; Jun, Zeng

2013-01-01

A new detection method, based on the sequential Bayesian approach proposed by Candy et al., offers new horizons for the research of radioactive detection. Compared with the commonly adopted detection methods incorporated with statistical theory, the sequential Bayesian approach offers the advantages of shorter verification time during the analysis of spectra that contain low total counts, especially in complex radionuclide components. In this paper, a simulation experiment platform implanted with the methodology of sequential Bayesian approach was developed. Events sequences of γ-rays associating with the true parameters of a LaBr3(Ce) detector were obtained based on an events sequence generator using Monte Carlo sampling theory to study the performance of the sequential Bayesian approach. The numerical experimental results are in accordance with those of Candy. Moreover, the relationship between the detection model and the event generator, respectively represented by the expected detection rate (Am) and the tested detection rate (Gm) parameters, is investigated. To achieve an optimal performance for this processor, the interval of the tested detection rate as a function of the expected detection rate is also presented.

Comparison of simultaneous and sequential SPECT imaging for discrimination tasks in assessment of cardiac defects.

PubMed

Trott, C M; Ouyang, J; El Fakhri, G

2010-11-21

Simultaneous rest perfusion/fatty-acid metabolism studies have the potential to replace sequential rest/stress perfusion studies for the assessment of cardiac function. Simultaneous acquisition has the benefits of increased signal and lack of need for patient stress, but is complicated by cross-talk between the two radionuclide signals. We consider a simultaneous rest (99m)Tc-sestamibi/(123)I-BMIPP imaging protocol in place of the commonly used sequential rest/stress (99m)Tc-sestamibi protocol. The theoretical precision with which the severity of a cardiac defect and the transmural extent of infarct can be measured is computed for simultaneous and sequential SPECT imaging, and their performance is compared for discriminating (1) degrees of defect severity and (2) sub-endocardial from transmural defects. We consider cardiac infarcts for which reduced perfusion and metabolism are observed. From an information perspective, simultaneous imaging is found to yield comparable or improved performance compared with sequential imaging for discriminating both severity of defect and transmural extent of infarct, for three defects of differing location and size.

Sequential Computerized Mastery Tests--Three Simulation Studies

ERIC Educational Resources Information Center

Wiberg, Marie

2006-01-01

A simulation study of a sequential computerized mastery test is carried out with items modeled with the 3 parameter logistic item response theory model. The examinees' responses are either identically distributed, not identically distributed, or not identically distributed together with estimation errors in the item characteristics. The…

Proceedings of the Conference on the Design of Experiments in Army Research, Development and Testing (29th)

DTIC Science & Technology

1984-06-01

SEQUENTIAL TESTING (Bldg. A, Room C) 1300-1330 ’ 1330-1415 1415-1445 1445-1515 BREAK 1515-1545 A TRUNCATED SEQUENTIAL PROBABILITY RATIO TEST J...suicide optical data operational testing reliability random numbers bootstrap methods missing data sequential testing fire support complex computer model carcinogenesis studies EUITION Of 1 NOV 68 I% OBSOLETE a ...contributed papers can be ascertained from the titles of the

Impact of breastfeeding duration on age at menarche.

PubMed

Al-Sahab, Ban; Adair, Linda; Hamadeh, Mazen J; Ardern, Chris I; Tamim, Hala

2011-05-01

The study aims to assess the relation between breastfeeding duration and age at menarche. Analysis was based on a cohort of 994 Filipino girls born in 1983-1984 and followed up from infancy to adulthood by the Cebu Longitudinal Health and Nutrition Survey. The main outcome was self-reported age at menarche. Cox regression was used to investigate the relation between duration of exclusive and any breastfeeding with age at menarche with adjustment sequentially for specific sets of known socioeconomic, maternal, genetic, and prenatal confounders. The estimated median of age at menarche was 13.08 years. After adjustment for potential confounders of the association of breastfeeding with age at menarche, exclusive breastfeeding duration retained an independent and significant association with age at menarche. An increase in 1 month of exclusive breastfeeding decreases the hazard of attaining earlier menarche by 6% (hazard ratio = 0.94, 95% confidence interval: 0.90, 0.98). Any breastfeeding duration was not associated with age at menarche. Although this is the first longitudinal study that reveals a negative association between exclusive breastfeeding and early menarche, the relation is still elusive. Further longitudinal studies within different contexts are warranted to assess the generalizability of these findings.

Vertigo-related cerebral blood flow changes on magnetic resonance imaging.

PubMed

Chang, Feiyan; Li, Zhongshi; Xie, Sheng; Liu, Hui; Wang, Wu

2014-11-01

A prospective study using magnetic resonance imaging on a consecutive cohort of patients with cervical vertigo. To quantitatively investigate the cerebral blood flow (CBF) changes associated with cervical vertigo by using 3-dimensional pseudocontinuous arterial spin labeling. Previous studies reported blood flow velocity reduction in posterior circulation during vertigo. However, the detailed information of CBF related to cervical vertigo has not been provided. A total of 33 patients with cervical vertigo and 14 healthy volunteers were recruited in this study. Three-dimensional pseudocontinuous arterial spin labeling was performed on each subject to evaluate the CBF before and after the cervical hyperextension-hyperflexion movement tests, which was used to induce cervical vertigo. Repeated-measures analysis of variance was conducted to assess the effect of subjects and tests. There were time effects of CBF in the territory of bilateral superior cerebellar artery, bilateral posterior cerebral artery, bilateral middle cerebral artery, and right anterior cerebral artery, but no group effect was observed. The analysis of CBF revealed a significant main effect of tests (P=0.024) and participants (P=0.038) in the dorsal pons. Cervical vertigo onset may be related to CBF reduction in the dorsal pons, which sequentially evokes the vestibular nuclei. 2.

Sequential Requests and the Problem of Message Sampling.

ERIC Educational Resources Information Center

Cantrill, James Gerard

S. Jackson and S. Jacobs's criticism of "single message" designs in communication research served as a framework for a study that examined the differences between various sequential request paradigms. The study sought to answer the following questions: (1) What were the most naturalistic request sequences assured to replicate…

A meta-analysis of the association between gestational diabetes mellitus and chronic hepatitis B infection during pregnancy

PubMed Central

2014-01-01

Background Chronic hepatitis B (CHB) infection during pregnancy is associated with insulin resistance. A meta-analytic technique was used to quantify the evidence of an association between CHB infection and the risk of gestational diabetes (GDM) among pregnant women. Methods We searched PubMed for studies up to September 5th 2013. Additional studies were obtained from other sources. We selected studies using a cohort-study design and reported a quantitative association between CHB infection during pregnancy and risk of GDM. A total of 280 articles were identified, of which fourteen publications involving 439,514 subjects met the inclusion criteria. A sequential algorithm was used to reduce between-study heterogeneity, and further meta-analysis was conducted using a random-effects model. Results Ten out of the fourteen studies were highly homogeneous, indicating an association of 1.11 [the adjusted odds ratio, 95% confidence interval 0.96 - 1.28] between CHB infection during pregnancy and the risk of developing GDM. The heterogeneity of the additional four studies may be due to selection bias or possible aetiological differences for special subsets of pregnant women. Conclusions These results indicate that CHB infection during pregnancy is not associated with an increased risk of developing GDM among pregnant women except those from Iran. PMID:24618120

Assessment of in vitro cyto/genotoxicity of sequentially treated electroplating effluent on the human hepatocarcinoma HuH-7 cell line.

PubMed

Naik, Umesh Chandra; Das, Mihir Tanay; Sauran, Swati; Thakur, Indu Shekhar

2014-03-01

The present study compares in vitro toxicity of electroplating effluent after the batch treatment process with that obtained after the sequential treatment process. Activated charcoal prepared from sugarcane bagasse through chemical carbonization, and tolerant indigenous bacteria, Bacillus sp. strain IST105, were used individually and sequentially for the treatment of electroplating effluent. The sequential treatment involving activated charcoal followed by bacterial treatment removed 99% of Cr(VI) compared with the batch processes, which removed 40% (charcoal) and 75% (bacteria), respectively. Post-treatment in vitro cyto/genotoxicity was evaluated by the MTT test and the comet assay in human HuH-7 hepatocarcinoma cells. The sequentially treated sample showed an increase in LC50 value with a 6-fold decrease in comet-assay DNA migration compared with that of untreated samples. A significant decrease in DNA migration and an increase in LC50 value of treated effluent proved the higher effectiveness of the sequential treatment process over the individual batch processes. Copyright © 2014 Elsevier B.V. All rights reserved.

A combined model based on spleen stiffness measurement and Baveno VI criteria to rule out high-risk varices in advanced chronic liver disease.

PubMed

Colecchia, Antonio; Ravaioli, Federico; Marasco, Giovanni; Colli, Agostino; Dajti, Elton; Di Biase, Anna Rita; Bacchi Reggiani, Maria Letizia; Berzigotti, Annalisa; Pinzani, Massimo; Festi, Davide

2018-05-03

Recently, Baveno VI guidelines suggested that esophagogastroduodenoscopy (EGD) can be avoided in patients with compensated advanced chronic liver disease (cACLD) who have a liver stiffness measurement (LSM) <20 kPa and platelet count >150,000/mm 3 . We aimed to: assess the performance of spleen stiffness measurement (SSM) in ruling out patients with high-risk varices (HRV); validate Baveno VI criteria in a large population and assess how the sequential use of Baveno VI criteria and SSM could safely avoid the need for endoscopy. We retrospectively analyzed 498 patients with cACLD who had undergone LSM/SSM by transient elastography (TE) (FibroScan®), platelet count and EGDs from 2012 to 2016 referred to our tertiary centre. The new combined model was validated internally by a split-validation method, and externally in a prospective multicentre cohort of 115 patients. SSM, LSM, platelet count and Child-Pugh-B were independent predictors of HRV. Applying the newly identified SSM cut-off (≤46 kPa) or Baveno VI criteria, 35.8% and 21.7% of patients in the internal validation cohort could have avoided EGD, with only 2% of HRVs being missed with either model. The combination of SSM with Baveno VI criteria would have avoided an additional 22.5% of EGDs, reaching a final value of 43.8% spared EGDs, with <5% missed HRVs. Results were confirmed in the prospective external validation cohort, as the combined Baveno VI/SSM ≤46 model would have safely spared (0 HRV missed) 37.4% of EGDs, compared to 16.5% when using the Baveno VI criteria alone. A non-invasive prediction model combining SSM with Baveno VI criteria may be useful to rule out HRV and could make it possible to avoid a significantly larger number of unnecessary EGDs compared to Baveno VI criteria only. Spleen stiffness measurement assessed by transient elastography, the most widely used elastography technique, is a non-invasive technique that can help the physician to better stratify the degree of portal hypertension and the risk of esophageal varices in patients with compensated advanced chronic liver disease. Performing spleen stiffness measurement together with liver stiffness measurement during the same examination is simple and fast and this sequential model can identify a greater number of patients that can safely avoid endoscopy, which is an invasive and expensive examination. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

A modular, prospective, semi-automated drug safety monitoring system for use in a distributed data environment.

PubMed

Gagne, Joshua J; Wang, Shirley V; Rassen, Jeremy A; Schneeweiss, Sebastian

2014-06-01

The aim of this study was to develop and test a semi-automated process for conducting routine active safety monitoring for new drugs in a network of electronic healthcare databases. We built a modular program that semi-automatically performs cohort identification, confounding adjustment, diagnostic checks, aggregation and effect estimation across multiple databases, and application of a sequential alerting algorithm. During beta-testing, we applied the system to five databases to evaluate nine examples emulating prospective monitoring with retrospective data (five pairs for which we expected signals, two negative controls, and two examples for which it was uncertain whether a signal would be expected): cerivastatin versus atorvastatin and rhabdomyolysis; paroxetine versus tricyclic antidepressants and gastrointestinal bleed; lisinopril versus angiotensin receptor blockers and angioedema; ciprofloxacin versus macrolide antibiotics and Achilles tendon rupture; rofecoxib versus non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs) and myocardial infarction; telithromycin versus azithromycin and hepatotoxicity; rosuvastatin versus atorvastatin and diabetes and rhabdomyolysis; and celecoxib versus ns-NSAIDs and myocardial infarction. We describe the program, the necessary inputs, and the assumed data environment. In beta-testing, the system generated four alerts, all among positive control examples (i.e., lisinopril and angioedema; rofecoxib and myocardial infarction; ciprofloxacin and tendon rupture; and cerivastatin and rhabdomyolysis). Sequential effect estimates for each example were consistent in direction and magnitude with existing literature. Beta-testing across nine drug-outcome examples demonstrated the feasibility of the proposed semi-automated prospective monitoring approach. In retrospective assessments, the system identified an increased risk of myocardial infarction with rofecoxib and an increased risk of rhabdomyolysis with cerivastatin years before these drugs were withdrawn from the market. Copyright © 2014 John Wiley & Sons, Ltd.

Sequential population study of the impact of earthquakes on the emotional and behavioural well-being of 4-year-olds in Canterbury, New Zealand.

PubMed

Thomson, Janine; Seers, Kara; Frampton, Chris; Hider, Phil; Moor, Stephanie

2016-01-01

Exposure to a large natural disaster can lead to behavioural disturbances, developmental delay and anxiety among young children. Although most children are resilient, some will develop mental health problems. Major earthquakes occurred in Canterbury, New Zealand, in September 2010 and February 2011. A community screening tool assessing behavioural and emotional problems in children, the Strengths and Difficulties Questionnaire, has been reported by parents (SDQ-P) and teachers (SDQ-T) of all 4-year-olds in the region since 2008. Mean total and subtest scores for the SDQ-P and SDQ-T were compared across periods before, during and after the earthquakes in sequential population cohorts of children. Comparisons across the periods were made in relation to the proportions of children defined by New Zealand norms as 'abnormal'. Results were also compared between zones considered to have been exposed to higher or lower impact from the earthquakes. Parent mean total SDQ scores did not change between periods before, during and after the earthquakes. Teacher mean SDQ total scores significantly reduced (improved) when compared between baseline and post-earthquake periods. Mean SDQ pro-social scores from both teachers and parents increased (strengthened) when compared between baseline and post-earthquake periods. Results did not significantly vary according to a measure of impact from the earthquakes. The main finding that a population-based measure of behavioural and emotional problems among children was not deleteriously impacted by the earthquakes is surprising and is not consistent with other research findings. Further work is needed to explore the health needs of children in Canterbury based on methodological improvements. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Robust sequential working memory recall in heterogeneous cognitive networks

PubMed Central

Rabinovich, Mikhail I.; Sokolov, Yury; Kozma, Robert

2014-01-01

Psychiatric disorders are often caused by partial heterogeneous disinhibition in cognitive networks, controlling sequential and spatial working memory (SWM). Such dynamic connectivity changes suggest that the normal relationship between the neuronal components within the network deteriorates. As a result, competitive network dynamics is qualitatively altered. This dynamics defines the robust recall of the sequential information from memory and, thus, the SWM capacity. To understand pathological and non-pathological bifurcations of the sequential memory dynamics, here we investigate the model of recurrent inhibitory-excitatory networks with heterogeneous inhibition. We consider the ensemble of units with all-to-all inhibitory connections, in which the connection strengths are monotonically distributed at some interval. Based on computer experiments and studying the Lyapunov exponents, we observed and analyzed the new phenomenon—clustered sequential dynamics. The results are interpreted in the context of the winnerless competition principle. Accordingly, clustered sequential dynamics is represented in the phase space of the model by two weakly interacting quasi-attractors. One of them is similar to the sequential heteroclinic chain—the regular image of SWM, while the other is a quasi-chaotic attractor. Coexistence of these quasi-attractors means that the recall of the normal information sequence is intermittently interrupted by episodes with chaotic dynamics. We indicate potential dynamic ways for augmenting damaged working memory and other cognitive functions. PMID:25452717

Using Zebra-speech to study sequential and simultaneous speech segregation in a cochlear-implant simulation.

PubMed

Gaudrain, Etienne; Carlyon, Robert P

2013-01-01

Previous studies have suggested that cochlear implant users may have particular difficulties exploiting opportunities to glimpse clear segments of a target speech signal in the presence of a fluctuating masker. Although it has been proposed that this difficulty is associated with a deficit in linking the glimpsed segments across time, the details of this mechanism are yet to be explained. The present study introduces a method called Zebra-speech developed to investigate the relative contribution of simultaneous and sequential segregation mechanisms in concurrent speech perception, using a noise-band vocoder to simulate cochlear implants. One experiment showed that the saliency of the difference between the target and the masker is a key factor for Zebra-speech perception, as it is for sequential segregation. Furthermore, forward masking played little or no role, confirming that intelligibility was not limited by energetic masking but by across-time linkage abilities. In another experiment, a binaural cue was used to distinguish the target and the masker. It showed that the relative contribution of simultaneous and sequential segregation depended on the spectral resolution, with listeners relying more on sequential segregation when the spectral resolution was reduced. The potential of Zebra-speech as a segregation enhancement strategy for cochlear implants is discussed.

Using Zebra-speech to study sequential and simultaneous speech segregation in a cochlear-implant simulation

PubMed Central

Gaudrain, Etienne; Carlyon, Robert P.

2013-01-01

Previous studies have suggested that cochlear implant users may have particular difficulties exploiting opportunities to glimpse clear segments of a target speech signal in the presence of a fluctuating masker. Although it has been proposed that this difficulty is associated with a deficit in linking the glimpsed segments across time, the details of this mechanism are yet to be explained. The present study introduces a method called Zebra-speech developed to investigate the relative contribution of simultaneous and sequential segregation mechanisms in concurrent speech perception, using a noise-band vocoder to simulate cochlear implants. One experiment showed that the saliency of the difference between the target and the masker is a key factor for Zebra-speech perception, as it is for sequential segregation. Furthermore, forward masking played little or no role, confirming that intelligibility was not limited by energetic masking but by across-time linkage abilities. In another experiment, a binaural cue was used to distinguish target and masker. It showed that the relative contribution of simultaneous and sequential segregation depended on the spectral resolution, with listeners relying more on sequential segregation when the spectral resolution was reduced. The potential of Zebra-speech as a segregation enhancement strategy for cochlear implants is discussed. PMID:23297922

Functional Pathway Analysis Using SCNP of FLT3 Receptor Pathway Deregulation in AML Provides Prognostic Information Independent from Mutational Status

PubMed Central

Cesano, Alessandra; Putta, Santosh; Rosen, David B.; Cohen, Aileen C.; Gayko, Urte; Mathi, Kavita; Woronicz, John; Hawtin, Rachael E.; Cripe, Larry; Sun, Zhuoxin; Tallman, Martin S.; Paietta, Elisabeth

2013-01-01

FMS-like tyrosine kinase 3 receptor (FLT3) internal tandem duplication (ITD) mutations result in constitutive activation of this receptor and have been shown to increase the risk of relapse in patients with acute myeloid leukemia (AML); however, substantial heterogeneity in clinical outcomes still exists within both the ITD mutated and unmutated AML subgroups, suggesting alternative mechanisms of disease relapse not accounted by FLT3 mutational status. Single cell network profiling (SCNP) is a multiparametric flow cytometry based assay that simultaneously measures, in a quantitative fashion and at the single cell level, both extracellular surface marker levels and changes in intracellular signaling proteins in response to extracellular modulators. We previously reported an initial characterization of FLT3 ITD-mediated signaling using SCNP. Herein SCNP was applied sequentially to two separate cohorts of samples collected from elderly AML patients at diagnosis. In the first (training) study, AML samples carrying unmutated, wild-type FLT3 (FLT3 WT) displayed a wide range of induced signaling, with a fraction having signaling profiles comparable to FLT3 ITD AML samples. Conversely, the FLT3 ITD AML samples displayed more homogeneous induced signaling, with the exception of patients with low (<40%) mutational load, which had profiles comparable to FLT3 WT AML samples. This observation was then confirmed in an independent (verification) cohort. Data from the second cohort were also used to assess the association between SCNP data and disease-free survival (DFS) in the context of FLT3 and nucleophosmin (NPM1) mutational status among patients who achieved complete remission (CR) to induction chemotherapy. The combination of SCNP read outs together with FLT3 and NPM1 molecular status improved the DFS prediction accuracy of the latter. Taken together, these results emphasize the value of comprehensive functional assessment of biologically relevant signaling pathways in AML as a basis for the development of highly predictive tests for guidance of post-remission therapy. PMID:23431389

The usefulness of administrative databases for identifying disease cohorts is increased with a multivariate model.

PubMed

van Walraven, Carl; Austin, Peter C; Manuel, Douglas; Knoll, Greg; Jennings, Allison; Forster, Alan J

2010-12-01

Administrative databases commonly use codes to indicate diagnoses. These codes alone are often inadequate to accurately identify patients with particular conditions. In this study, we determined whether we could quantify the probability that a person has a particular disease-in this case renal failure-using other routinely collected information available in an administrative data set. This would allow the accurate identification of a disease cohort in an administrative database. We determined whether patients in a randomly selected 100,000 hospitalizations had kidney disease (defined as two or more sequential serum creatinines or the single admission creatinine indicating a calculated glomerular filtration rate less than 60 mL/min/1.73 m²). The independent association of patient- and hospitalization-level variables with renal failure was measured using a multivariate logistic regression model in a random 50% sample of the patients. The model was validated in the remaining patients. Twenty thousand seven hundred thirteen patients had kidney disease (20.7%). A diagnostic code of kidney disease was strongly associated with kidney disease (relative risk: 34.4), but the accuracy of the code was poor (sensitivity: 37.9%; specificity: 98.9%). Twenty-nine patient- and hospitalization-level variables entered the kidney disease model. This model had excellent discrimination (c-statistic: 90.1%) and accurately predicted the probability of true renal failure. The probability threshold that maximized sensitivity and specificity for the identification of true kidney disease was 21.3% (sensitivity: 80.0%; specificity: 82.2%). Multiple variables available in administrative databases can be combined to quantify the probability that a person has a particular disease. This process permits accurate identification of a disease cohort in an administrative database. These methods may be extended to other diagnoses or procedures and could both facilitate and clarify the use of administrative databases for research and quality improvement. Copyright © 2010 Elsevier Inc. All rights reserved.

The application of intraoperative transit time flow measurement to accurately assess anastomotic quality in sequential vein grafting

PubMed Central

Yu, Yang; Zhang, Fan; Gao, Ming-Xin; Li, Hai-Tao; Li, Jing-Xing; Song, Wei; Huang, Xin-Sheng; Gu, Cheng-Xiong

2013-01-01

OBJECTIVES Intraoperative transit time flow measurement (TTFM) is widely used to assess anastomotic quality in coronary artery bypass grafting (CABG). However, in sequential vein grafting, the flow characteristics collected by the conventional TTFM method are usually associated with total graft flow and might not accurately indicate the quality of every distal anastomosis in a sequential graft. The purpose of our study was to examine a new TTFM method that could assess the quality of each distal anastomosis in a sequential graft more reliably than the conventional TTFM approach. METHODS Two TTFM methods were tested in 84 patients who underwent sequential saphenous off-pump CABG in Beijing An Zhen Hospital between April and August 2012. In the conventional TTFM method, normal blood flow in the sequential graft was maintained during the measurement, and the flow probe was placed a few centimetres above the anastomosis to be evaluated. In the new method, blood flow in the sequential graft was temporarily reduced during the measurement by placing an atraumatic bulldog clamp at the graft a few centimetres distal to the anastomosis to be evaluated, while the position of the flow probe remained the same as in the conventional method. This new TTFM method was named the flow reduction TTFM. Graft flow parameters measured by both methods were compared. RESULTS Compared with the conventional TTFM, the flow reduction TTFM resulted in significantly lower mean graft blood flow (P < 0.05); in contrast, yielded significantly higher pulsatility index (P < 0.05). Diastolic filling was not significantly different between the two methods and was >50% in both cases. Interestingly, the flow reduction TTFM identified two defective middle distal anastomoses that the conventional TTFM failed to detect. Graft flows near the defective distal anastomoses were improved substantially after revision. CONCLUSIONS In this study, we found that temporary reduction of graft flow during TTFM seemed to enhance the sensitivity of TTFM to less-than-critical anastomotic defects in a sequential graft and to improve the overall accuracy of the intraoperative assessment of anastomotic quality in sequential vein grafting. PMID:24000314

Comparison of Image Quality and Radiation Dose of Coronary Computed Tomography Angiography Between Conventional Helical Scanning and a Strategy Incorporating Sequential Scanning

PubMed Central

Einstein, Andrew J.; Wolff, Steven D.; Manheimer, Eric D.; Thompson, James; Terry, Sylvia; Uretsky, Seth; Pilip, Adalbert; Peters, M. Robert

2009-01-01

Radiation dose from coronary computed tomography angiography may be reduced using a sequential scanning protocol rather than a conventional helical scanning protocol. Here we compare radiation dose and image quality from coronary computed tomography angiography in a single center between an initial period during which helical scanning with electrocardiographically-controlled tube current modulation was used for all patients (n=138) and after adoption of a strategy incorporating sequential scanning whenever appropriate (n=261). Using the sequential-if-appropriate strategy, sequential scanning was employed in 86.2% of patients. Compared to the helical-only strategy, this strategy was associated with a 65.1% dose reduction (mean dose-length product of 305.2 vs. 875.1 and mean effective dose of 14.9 mSv vs. 5.2 mSv, respectively), with no significant change in overall image quality, step artifacts, motion artifacts, or perceived image noise. For the 225 patients undergoing sequential scanning, the dose-length product was 201.9 ± 90.0 mGy·cm, while for patients undergoing helical scanning under either strategy, the dose-length product was 890.9 ± 293.3 mGy·cm (p<0.0001), corresponding to mean effective doses of 3.4 mSv and 15.1 mSv, respectively, a 77.5% reduction. Image quality was significantly greater for the sequential studies, reflecting the poorer image quality in patients undergoing helical scanning in the sequential-if-appropriate strategy. In conclusion, a sequential-if-appropriate diagnostic strategy reduces dose markedly compared to a helical-only strategy, with no significant difference in image quality. PMID:19892048

Sequential high intensity focused ultrasound (HIFU) ablation in the treatment of benign multinodular goitre: an observational retrospective study.

PubMed

Lang, Brian H H; Woo, Yu-Cho; Chiu, Keith Wan-Hang

2018-03-19

Assessing the efficacy and safety of sequential high-intensity focused ultrasound (HIFU) ablation in a multinodular goitre (MNG) by comparing them with single HIFU ablation. One hundred and four (84.6%) patients underwent single ablation of a single nodule (group I), while 19 (15.4%) underwent sequential ablation of two relatively-dominant nodules in a MNG (group II). Extent of shrinkage per nodule [by volume reduction ratio (VRR)], pain scores (by 0-10 visual analogue scale) during and after ablation, and rate of vocal cord palsy (VCP), skin burn and nausea/vomiting were compared between the two groups. All 19 (100%) sequential ablations completed successfully. The 3- and 6-month VRR of each nodule were comparable between the two groups (p > 0.05) and in group II, the 3- and 6-month VRR between the first and second nodules were comparable (p = 0.710 and p = 0.548, respectively). Pain score was significantly higher in group II in the morning after ablation (2.29 vs 1.15, p = 0.047) and nausea/vomiting occurred significantly more frequently in group II (15.8% vs 0.0%, p = 0.012). However, VCP and skin burn were comparable (p > 0.05). Sequential ablation had comparable efficacy and safety as single ablation. However, patients undergoing sequential ablation are at higher likelihood of pain in the following morning and nausea/vomiting after ablation. • Sequential HIFU ablation is well-tolerated in patients with two dominant thyroid nodules • More pain is experienced in the morning following sequential HIFU ablation • More nausea/vomiting is experienced following sequential HIFU ablation.

Mixing modes in a population-based interview survey: comparison of a sequential and a concurrent mixed-mode design for public health research.

PubMed

Mauz, Elvira; von der Lippe, Elena; Allen, Jennifer; Schilling, Ralph; Müters, Stephan; Hoebel, Jens; Schmich, Patrick; Wetzstein, Matthias; Kamtsiuris, Panagiotis; Lange, Cornelia

2018-01-01

Population-based surveys currently face the problem of decreasing response rates. Mixed-mode designs are now being implemented more often to account for this, to improve sample composition and to reduce overall costs. This study examines whether a concurrent or sequential mixed-mode design achieves better results on a number of indicators of survey quality. Data were obtained from a population-based health interview survey of adults in Germany that was conducted as a methodological pilot study as part of the German Health Update (GEDA). Participants were randomly allocated to one of two surveys; each of the surveys had a different design. In the concurrent mixed-mode design ( n  = 617) two types of self-administered questionnaires (SAQ-Web and SAQ-Paper) and computer-assisted telephone interviewing were offered simultaneously to the respondents along with the invitation to participate. In the sequential mixed-mode design ( n  = 561), SAQ-Web was initially provided, followed by SAQ-Paper, with an option for a telephone interview being sent out together with the reminders at a later date. Finally, this study compared the response rates, sample composition, health indicators, item non-response, the scope of fieldwork and the costs of both designs. No systematic differences were identified between the two mixed-mode designs in terms of response rates, the socio-demographic characteristics of the achieved samples, or the prevalence rates of the health indicators under study. The sequential design gained a higher rate of online respondents. Very few telephone interviews were conducted for either design. With regard to data quality, the sequential design (which had more online respondents) showed less item non-response. There were minor differences between the designs in terms of their costs. Postage and printing costs were lower in the concurrent design, but labour costs were lower in the sequential design. No differences in health indicators were found between the two designs. Modelling these results for higher response rates and larger net sample sizes indicated that the sequential design was more cost and time-effective. This study contributes to the research available on implementing mixed-mode designs as part of public health surveys. Our findings show that SAQ-Paper and SAQ-Web questionnaires can be combined effectively. Sequential mixed-mode designs with higher rates of online respondents may be of greater benefit to studies with larger net sample sizes than concurrent mixed-mode designs.

The Constructivist Approach? I Have Heard about It but I Have Never Seen It: "An Example of Exploratory Sequential Mixed Design Study"

ERIC Educational Resources Information Center

Polat, Ahmet; Dogan, Soner; Demir, Selçuk Besir

2016-01-01

The present study was undertaken to investigate the quality of education based on the views of the students attending social studies education departments at the Faculties of Education and to determine the existing problems and present suggestions for their solutions. The study was conducted according to exploratory sequential mixed method. In…

The Constructivist Approach? I Have Heard about It but I Have Never Seen It "An Example of Exploratory Sequential Mixed Design Study"

ERIC Educational Resources Information Center

Polat, Ahmet; Dogan, Soner; Demir, Selçuk Besir

2016-01-01

The present study was undertaken to investigate the quality of education based on the views of the students attending social studies education departments at the Faculties of Education and to determine the existing problems and present suggestions for their solutions. The study was conducted according to exploratory sequential mixed method. In…

Concurrent versus sequential sorafenib therapy in combination with radiation for hepatocellular carcinoma.

PubMed

Wild, Aaron T; Gandhi, Nishant; Chettiar, Sivarajan T; Aziz, Khaled; Gajula, Rajendra P; Williams, Russell D; Kumar, Rachit; Taparra, Kekoa; Zeng, Jing; Cades, Jessica A; Velarde, Esteban; Menon, Siddharth; Geschwind, Jean F; Cosgrove, David; Pawlik, Timothy M; Maitra, Anirban; Wong, John; Hales, Russell K; Torbenson, Michael S; Herman, Joseph M; Tran, Phuoc T

2013-01-01

Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design.

Concurrent versus Sequential Sorafenib Therapy in Combination with Radiation for Hepatocellular Carcinoma

PubMed Central

Chettiar, Sivarajan T.; Aziz, Khaled; Gajula, Rajendra P.; Williams, Russell D.; Kumar, Rachit; Taparra, Kekoa; Zeng, Jing; Cades, Jessica A.; Velarde, Esteban; Menon, Siddharth; Geschwind, Jean F.; Cosgrove, David; Pawlik, Timothy M.; Maitra, Anirban; Wong, John; Hales, Russell K.; Torbenson, Michael S.; Herman, Joseph M.; Tran, Phuoc T.

2013-01-01

Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design. PMID:23762417

Effects of Training Auditory Sequential Memory and Attention on Reading.

ERIC Educational Resources Information Center

Klein, Pnina S.; Schwartz, Allen A.

1979-01-01

The study, involving 92 second and third graders with deficits in reading and auditory sequential memory (ASM), examined the possibility of improving ASM through training and the relationship between this training and reading ability. (Author/CL)

The Integration of Study and Work-Integrated Learning Experience through the Sequential, Embedded Completion of Tertiary Qualifications

ERIC Educational Resources Information Center

Whannell, Patricia; Humphries, Judy; Whannell, Robert; Usher, Kim

2015-01-01

A number of different models have been developed to integrate both Vocational Education and Training (VET) and university study with a view to producing work-ready graduates. This paper describes one joint initiative which allows students to integrate their theoretical study and work-integrated learning (WIL) experience by supporting a sequential,…

Planning and Instruction and the Social Studies Curriculum: A Discourse on Design and Delivery Systems.

ERIC Educational Resources Information Center

Peters, Richard

A model for Continuous-Integrated-Sequential (C/I/S) curricula for social studies education is presented. The design advocated involves ensuring continuity of instruction from grades K-12, an integration of social studies disciplines, and a sequential process of refining and reinforcing concept and skills from grade-to-grade along the K-12…

Patterns of drug use from adolescence to young adulthood: III. Predictors of progression.

PubMed Central

Yamaguchi, K; Kandel, D B

1984-01-01

Possible linkages of influence among classes of drugs in the observed sequential progression from adolescence to young adulthood are investigated through event history analyses. Three stages are examined: initiation to marijuana, to the use of other illicit drugs, and to prescribed psychoactive drugs. The data are based on a follow-up cohort of former adolescents representative of high school students in grade 10 and 11 in New York State who were reinterviewed nine years later at ages 24-25. The sequential order between alcohol and/or cigarettes and marijuana reflects not only the effect of the use of legal drugs on marijuana initiation, but also age effects on onset of these drugs, controlling for individual characteristics measured in adolescence; marijuana use by one's friends in adolescence is an additional important predictor of marijuana initiation. Prior use of marijuana is necessary for progression to other illicit drugs. Multiple factors are involved in the progression to prescribed drugs, with adolescent depressive symptomatology and use of other illicit drugs important for both sexes, and maternal use of psychoactive drugs, dropping out of school, and prior use of marijuana of additional importance for women. Although licit drugs influence initiation into marijuana independently of age effects, it is especially for the progression from marijuana to other illicit drugs that the earlier drug is associated with the progression to a higher stage drug. PMID:6742253

Photodynamic Therapy with 3-(1’-hexyloxyethyl) pyropheophorbide a (HPPH) for Cancer of the Oral Cavity

PubMed Central

Rigual, Nestor; Shafirstein, Gal; Cooper, Michele T.; Baumann, Heinz; Bellnier, David A.; Sunar, Ulas; Tracy, Erin C.; Rohrbach, Daniel J.; Wilding, Gregory; Tan, Wei; Sullivan, Maureen; Merzianu, Mihai; Henderson, Barbara W.

2013-01-01

Purpose The primary objective was to evaluate safety of 3-(1’-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Experimental Design Patients with histologically proven oral dysplasia, carcinoma in situ (CiS ) or early stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies employed an HPPH dose of 4 mg/m2 and light doses from 50 to 140 J/cm2. Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of signal transducer and activator of transcription 3 (STAT3) were assessed as potential indicators of PDT effective reaction. Results Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and CiS, and 82% for SCCs lesions at 140 J/cm2. The responses in the CiS/dysplasia cohort are not durable. The PDT induced STAT3 cross-links is significantly higher (P=0.0033) in SCC than in CiS/dysplasia for all light-doses. Conclusion HPPH-PDT is safe for the treatment of CiS/dysplasia and early stage cancer of the oral cavity. Early stage oral HNSCC appears to respond better to HPPH-PDT in comparison to premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT mediated photoreaction. PMID:24088736

Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts

PubMed Central

Cohen, Sophie; Innes, Steve; Geelen, Sibyl P. M.; Wells, Jonathan C. K.; Smit, Colette; Wolfs, Tom F. W.; van Eck-Smit, Berthe L. F.; Kuijpers, Taco W.; Reiss, Peter; Scherpbier, Henriette J.

2015-01-01

Objective Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in need for lifelong treatment. Methods We assessed regional fat distribution over time, measured with sequential DEXA-scans in HIV-infected children on cART in cohorts from South Africa (SA) and the Netherlands (NL), and in healthy controls (SA). Limb and trunk fat Z-scores were calculated with the lambda-mu-sigma (LMS) method. Multivariable linear regression models with mixed effects were used to investigate the effect of cART compounds on body fat distribution over time. Results In total, 218 children underwent 445 DEXA assessments with a median follow-up of 3.5 years. Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013). In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z-score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003). Conclusions Our study shows that subcutaneous fat loss is still prevalent in HIV-infected children on cART, and is strongly associated with cumulative stavudine exposure. These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally. PMID:26148119

Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts.

PubMed

Cohen, Sophie; Innes, Steve; Geelen, Sibyl P M; Wells, Jonathan C K; Smit, Colette; Wolfs, Tom F W; van Eck-Smit, Berthe L F; Kuijpers, Taco W; Reiss, Peter; Scherpbier, Henriette J; Pajkrt, Dasja; Bunders, Madeleine J

2015-01-01

Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in need for lifelong treatment. We assessed regional fat distribution over time, measured with sequential DEXA-scans in HIV-infected children on cART in cohorts from South Africa (SA) and the Netherlands (NL), and in healthy controls (SA). Limb and trunk fat Z-scores were calculated with the lambda-mu-sigma (LMS) method. Multivariable linear regression models with mixed effects were used to investigate the effect of cART compounds on body fat distribution over time. In total, 218 children underwent 445 DEXA assessments with a median follow-up of 3.5 years. Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013). In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z-score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003). Our study shows that subcutaneous fat loss is still prevalent in HIV-infected children on cART, and is strongly associated with cumulative stavudine exposure. These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally.

Individual- and community-level correlates of cigarette-smoking trajectories from age 13 to 32 in a U.S. population-based sample.

PubMed

Fuemmeler, Bernard; Lee, Chien-Ti; Ranby, Krista W; Clark, Trenette; McClernon, F Joseph; Yang, Chongming; Kollins, Scott H

2013-09-01

Characterizing smoking behavior is important for informing etiologic models and targeting prevention efforts. This study explored the effects of both individual- and community-level variables in predicting cigarette use vs. non-use and level of use among adolescents as they transition into adulthood. Data on 14,779 youths (53% female) were drawn from the National Longitudinal Study of Adolescent Health (Add Health); a nationally representative longitudinal cohort. A cohort sequential design allowed for examining trajectories of smoking typologies from age 13 to 32 years. Smoking trajectories were evaluated by using a zero-inflated Poisson (ZIP) latent growth analysis and latent class growth analysis modeling approach. Significant relationships emerged between both individual- and community-level variables and smoking outcomes. Maternal and peer smoking predicted increases in smoking over development and were associated with a greater likelihood of belonging to any of the four identified smoking groups versus Non-Users. Conduct problems and depressive symptoms during adolescence were related to cigarette use versus non-use. State-level prevalence of adolescent smoking was related to greater cigarette use during adolescence. Individual- and community-level variables that distinguish smoking patterns within the population aid in understanding cigarette use versus non-use and the quantity of cigarette use into adulthood. Our findings suggest that efforts to prevent cigarette use would benefit from attention to both parental and peer smoking and individual well-being. Future work is needed to better understand the role of variables in the context of multiple levels (individual and community-level) on smoking trajectories. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Learning trajectories of children with special health care needs across the severity spectrum.

PubMed

Goldfeld, Sharon; O'Connor, Meredith; Quach, Jon; Tarasuik, Joanne; Kvalsvig, Amanda

2015-01-01

A significant proportion of school-aged children experience special health care needs (SCHN) and seek care from pediatricians with a wide range of condition types and severity levels. This study examines the learning pathways of children with established (already diagnosed at school entry) and emerging (teacher identified) SHCN from school entry through the elementary school years. The Longitudinal Study of Australian Children (LSAC) is a nationally representative clustered cross-sequential sample of 2 cohorts of Australian children which commenced in May 2004. Data were analyzed from the LSAC kindergarten cohort (n = 4,983), as well as a subsample of 720 children for whom teachers also completed the Australian Early Development Index checklist, a measure of early childhood development at school entry that includes SHCN. Latent class analysis was utilized to establish 3 academic trajectories from 4-5 to 10-11 years: high (24.3%), average (49.8%), and low (23.6%). Descriptive statistics revealed a trend for both children with established and emerging SHCN to fall into weaker performing learning pathways. Multinomial logistic regression focusing on those children with emerging SHCN confirmed this pattern of results, even after adjustment for covariates (relative risk 3.06, 95% confidence interval 1.03-9.10). Children who additionally had low socioeconomic standing were particularly at risk. Even children with less complex SCHN are at risk for academic failure. Early identification, together with integrated health and educational support, may promote stronger pathways of educational attainment for these children. Achieving these better outcomes will require the involvement of both educational and health practitioners. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study

PubMed Central

Tomio, Jun; Takahashi, Hideto; Ichikawa, Masao; Nishida, Masamichi; Morimura, Naoto; Sakamoto, Tetsuya

2013-01-01

Objectives To evaluate the effectiveness of pre-hospital adrenaline (epinephrine) administered by emergency medical services to patients with out of hospital cardiac arrest. Design Controlled propensity matched retrospective cohort study, in which pairs of patients with or without (control) adrenaline were created with a sequential risk set matching based on time dependent propensity score. Setting Japan’s nationwide registry database of patients with out of hospital cardiac arrest registered between January 2007 and December 2010. Participants Among patients aged 15-94 with out of hospital cardiac arrest witnessed by a bystander, we created 1990 pairs of patients with and without adrenaline with an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia (VF/VT) and 9058 pairs among those with non-VF/VT. Main outcome measures Overall and neurologically intact survival at one month or at discharge, whichever was earlier. Results After propensity matching, pre-hospital administration of adrenaline by emergency medical services was associated with a higher proportion of overall survival (17.0% v 13.4%; unadjusted odds ratio 1.34, 95% confidence interval 1.12 to 1.60) but not with neurologically intact survival (6.6% v 6.6%; 1.01, 0.78 to 1.30) among those with VF/VT; and higher proportions of overall survival (4.0% v 2.4%; odds ratio 1.72, 1.45 to 2.04) and neurologically intact survival (0.7% v 0.4%; 1.57, 1.04 to 2.37) among those with non-VF/VT. Conclusions Pre-hospital administration of adrenaline by emergency medical services improves the long term outcome in patients with out of hospital cardiac arrest, although the absolute increase of neurologically intact survival was minimal. PMID:24326886

Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study.

PubMed

Nakahara, Shinji; Tomio, Jun; Takahashi, Hideto; Ichikawa, Masao; Nishida, Masamichi; Morimura, Naoto; Sakamoto, Tetsuya

2013-12-10

To evaluate the effectiveness of pre-hospital adrenaline (epinephrine) administered by emergency medical services to patients with out of hospital cardiac arrest. Controlled propensity matched retrospective cohort study, in which pairs of patients with or without (control) adrenaline were created with a sequential risk set matching based on time dependent propensity score. Japan's nationwide registry database of patients with out of hospital cardiac arrest registered between January 2007 and December 2010. Among patients aged 15-94 with out of hospital cardiac arrest witnessed by a bystander, we created 1990 pairs of patients with and without adrenaline with an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia (VF/VT) and 9058 pairs among those with non-VF/VT. Overall and neurologically intact survival at one month or at discharge, whichever was earlier. After propensity matching, pre-hospital administration of adrenaline by emergency medical services was associated with a higher proportion of overall survival (17.0% v 13.4%; unadjusted odds ratio 1.34, 95% confidence interval 1.12 to 1.60) but not with neurologically intact survival (6.6% v 6.6%; 1.01, 0.78 to 1.30) among those with VF/VT; and higher proportions of overall survival (4.0% v 2.4%; odds ratio 1.72, 1.45 to 2.04) and neurologically intact survival (0.7% v 0.4%; 1.57, 1.04 to 2.37) among those with non-VF/VT. Pre-hospital administration of adrenaline by emergency medical services improves the long term outcome in patients with out of hospital cardiac arrest, although the absolute increase of neurologically intact survival was minimal.

High data rate coding for the space station telemetry links.

NASA Technical Reports Server (NTRS)

Lumb, D. R.; Viterbi, A. J.

1971-01-01

Coding systems for high data rates were examined from the standpoint of potential application in space-station telemetry links. Approaches considered included convolutional codes with sequential, Viterbi, and cascaded-Viterbi decoding. It was concluded that a high-speed (40 Mbps) sequential decoding system best satisfies the requirements for the assumed growth potential and specified constraints. Trade-off studies leading to this conclusion are viewed, and some sequential (Fano) algorithm improvements are discussed, together with real-time simulation results.

Time-lapse evaluation of human embryo development in single versus sequential culture media--a sibling oocyte study.

PubMed

Ciray, Haydar Nadir; Aksoy, Turan; Goktas, Cihan; Ozturk, Bilgen; Bahceci, Mustafa

2012-09-01

To compare the dynamics of early development between embryos cultured in single and sequential media. Randomized, comparative study. Private IVF centre. A total of 446 metaphase II oocytes from 51 couples who underwent oocyte retrieval procedure for intracytoplasmic sperm injection. Forty-nine resulted in embryo transfer. Oocytes were split between single and sequential media produced by the same manufacturer and cultured in a time-lapse incubator. Morphokinetic parameters until the embryos reached the 5-cell stage (t5), utilization, clinical pregnancy and implantation rates. Embryos cultured in single media were advanced from the first mitosis cycle and reached 2- to 5-cell stages earlier. There was not any difference between the durations for cell cycle two (cc2 = t3-t2) and s2 (t4-t3). The utilization, clinical pregnancy and implantation rates did not differ between groups. The proportion of cryopreserved day 6 embryos to two pronuclei oocytes was significantly higher in sequential than in single media. Morphokinetics of embryo development vary between single and sequential culture media at least until the 5-cell stage. The overall clinical and embryological parameters remain similar regardless of the culture system.

Acute kidney injury in critically ill patients with haematological malignancies: results of a multicentre cohort study from the Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie.

PubMed

Darmon, Michael; Vincent, François; Canet, Emmanuel; Mokart, Djamel; Pène, Frédéric; Kouatchet, Achille; Mayaux, Julien; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Lebert, Christine; Perez, Pierre; Renault, Anne; Meert, Anne-Pascale; Benoit, Dominique; Hamidfar, Rebecca; Jourdain, Mercé; Schlemmer, Benoit; Chevret, Sylvie; Lemiale, Virginie; Azoulay, Elie

2015-12-01

Cancer patients are at high risk for acute kidney injury (AKI), which is associated with high morbidity and mortality. We sought to appraise the incidence, risk factors, and outcome of AKI in a large multicentre cohort study of critically ill patients with haematological malignancies. We used a retrospective analysis of a prospectively collected database. The study was carried out in 17 university or university-affiliated centres in France and Belgium between 2010 and 2012. AKI was defined according to the Acute Kidney Injury Network (AKIN) definition. Of the 1011 patients admitted into the intensive care unit (ICU) during the study period, 1009 were included in this study. According to the AKIN definition, 671 patients (66.5%) developed an AKI during their ICU stay, of which 258 patients (38.4%) were AKI stage 1, 75 patients (11.2%) AKI stage 2 and 338 patients (50.4%) AKI stage 3. After adjustment for confounders, main adverse risk factors of AKI were older age, severity [non-renal Sequential Organ Failure Assessment (SOFA)], history of hypertension, tumour lysis syndrome, exposure to nephrotoxic agents and myeloma. Hospital mortality was 44.3% in patients with AKI and 25.4% in patients without AKI (P < 0.0001). After adjustment for confounders, AKI was independently associated with hospital mortality [OR 1.65 (95% CI 1.19-2.29)]. Overall, 271 patients required renal replacement therapy (RRT), of whom 57.2% died during their hospital stay as compared with 31.2% (P < 0.0001) in those not requiring RRT. Two-thirds of critically ill patients with haematological malignancies developed AKI. Hospital mortality in this population of patients developing AKI or requiring RRT is close to that in general ICU population. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Revascularization of Left Coronary System Using a Skeletonized Left Internal Mammary Artery　- Sequential vs. Separate Grafting.

PubMed

Ji, Qiang; Shi, YunQing; Xia, LiMin; Ma, RunHua; Shen, JinQiang; Lai, Hao; Ding, WenJun; Wang, ChunSheng

2017-12-25

To evaluate in-hospital and mid-term outcomes of sequential vs. separate grafting of in situ skeletonized left internal mammary artery (LIMA) to the left coronary system in a single-center, propensity-matched study.Methods and Results:After propensity score-matching, 120 pairs of patients undergoing first scheduled isolated coronary artery bypass grafting (CABG) with in situ skeletonized LIMA grafting to the left anterior descending artery (LAD) territory were entered into a sequential group (sequential grafting of LIMA to the diagonal artery and then to the LAD) or a control group (separate grafting of LIMA to the LAD). The in-hospital and follow-up clinical outcomes and follow-up LIMA graft patency were compared. Both propensity score-matched groups had similar in-hospital and follow-up clinical outcomes. Sequential LIMA grafting was not found to be an independent predictor of adverse events. During a follow-up period of 27.0±7.3 months, 99.1% patency for the diagonal site and 98.3% for the LAD site were determined by coronary computed tomographic angiography after sequential LIMA grafting, both of which were similar with graft patency of separate grafting of in situ skeletonized LIMA to the LAD. Revascularization of the left coronary system using a skeletonized LIMA resulted in excellent in-hospital and mid-term clinical outcomes and graft patency using sequential grafting.

Evidence for decreased interaction and improved carotenoid bioavailability by sequential delivery of a supplement.

PubMed

Salter-Venzon, Dawna; Kazlova, Valentina; Izzy Ford, Samantha; Intra, Janjira; Klosner, Allison E; Gellenbeck, Kevin W

2017-05-01

Despite the notable health benefits of carotenoids for human health, the majority of human diets worldwide are repeatedly shown to be inadequate in intake of carotenoid-rich fruits and vegetables, according to current health recommendations. To address this deficit, strategies designed to increase dietary intakes and subsequent plasma levels of carotenoids are warranted. When mixed carotenoids are delivered into the intestinal tract simultaneously, competition occurs for micelle formation and absorption, affecting carotenoid bioavailability. Previously, we tested the in vitro viability of a carotenoid mix designed to deliver individual carotenoids sequentially spaced from one another over the 6 hr transit time of the human upper gastrointestinal system. We hypothesized that temporally and spatially separating the individual carotenoids would reduce competition for micelle formation, improve uptake, and maximize efficacy. Here, we test this hypothesis in a double-blind, repeated-measure, cross-over human study with 12 subjects by comparing the change of plasma carotenoid levels for 8 hr after oral doses of a sequentially spaced carotenoid mix, to a matched mix without sequential spacing. We find the carotenoid change from baseline, measured as area under the curve, is increased following consumption of the sequentially spaced mix compared to concomitant carotenoids delivery. These results demonstrate reduced interaction and regulation between the sequentially spaced carotenoids, suggesting improved bioavailability from a novel sequentially spaced carotenoid mix.

CFD simulation of hemodynamics in sequential and individual coronary bypass grafts based on multislice CT scan datasets.

PubMed

Hajati, Omid; Zarrabi, Khalil; Karimi, Reza; Hajati, Azadeh

2012-01-01

There is still controversy over the differences in the patency rates of the sequential and individual coronary artery bypass grafting (CABG) techniques. The purpose of this paper was to non-invasively evaluate hemodynamic parameters using complete 3D computational fluid dynamics (CFD) simulations of the sequential and the individual methods based on the patient-specific data extracted from computed tomography (CT) angiography. For CFD analysis, the geometric model of coronary arteries was reconstructed using an ECG-gated 64-detector row CT. Modeling the sequential and individual bypass grafting, this study simulates the flow from the aorta to the occluded posterior descending artery (PDA) and the posterior left ventricle (PLV) vessel with six coronary branches based on the physiologically measured inlet flow as the boundary condition. The maximum calculated wall shear stress (WSS) in the sequential and the individual models were estimated to be 35.1 N/m(2) and 36.5 N/m(2), respectively. Compared to the individual bypass method, the sequential graft has shown a higher velocity at the proximal segment and lower spatial wall shear stress gradient (SWSSG) due to the flow splitting caused by the side-to-side anastomosis. Simulated results combined with its surgical benefits including the requirement of shorter vein length and fewer anastomoses advocate the sequential method as a more favorable CABG method.

Sequential Research Needs in Evolving Disciplines of Social Practice.

ERIC Educational Resources Information Center

Knowles, Malcolm S.

The author suggests that the emerging fields of social practice (such as recreation, social work, and adult education) must all go through a sequential pattern of research needs, first superficially, and then in ever deeper cycles. The six phases of these research needs are: definition of the field (survey and descriptive studies, census studies,…

An Overview of Markov Chain Methods for the Study of Stage-Sequential Developmental Processes

ERIC Educational Resources Information Center

Kapland, David

2008-01-01

This article presents an overview of quantitative methodologies for the study of stage-sequential development based on extensions of Markov chain modeling. Four methods are presented that exemplify the flexibility of this approach: the manifest Markov model, the latent Markov model, latent transition analysis, and the mixture latent Markov model.…

Sequential voluntary cough and aspiration or aspiration risk in Parkinson's disease.

PubMed

Hegland, Karen Wheeler; Okun, Michael S; Troche, Michelle S

2014-08-01

Disordered swallowing, or dysphagia, is almost always present to some degree in people with Parkinson's disease (PD), either causing aspiration or greatly increasing the risk for aspiration during swallowing. This likely contributes to aspiration pneumonia, a leading cause of death in this patient population. Effective airway protection is dependent upon multiple behaviors, including cough and swallowing. Single voluntary cough function is disordered in people with PD and dysphagia. However, the appropriate response to aspirate material is more than one cough, or sequential cough. The goal of this study was to examine voluntary sequential coughing in people with PD, with and without dysphagia. Forty adults diagnosed with idiopathic PD produced two trials of sequential voluntary cough. The cough airflows were obtained using pneumotachograph and facemask and subsequently digitized and recorded. All participants received a modified barium swallow study as part of their clinical care, and the worst penetration-aspiration score observed was used to determine whether the patient had dysphagia. There were significant differences in the compression phase duration, peak expiratory flow rates, and amount of air expired of the sequential cough produced by participants with and without dysphagia. The presence of dysphagia in people with PD is associated with disordered cough function. Sequential cough, which is important in removing aspirate material from large- and smaller-diameter airways, is also impaired in people with PD and dysphagia compared with those without dysphagia. There may be common neuroanatomical substrates for cough and swallowing impairment in PD leading to the co-occurrence of these dysfunctions.

A Longitudinal Study in Adults with Sequential Bilateral Cochlear Implants: Time Course for Individual Ear and Bilateral Performance

ERIC Educational Resources Information Center

Reeder, Ruth M.; Firszt, Jill B.; Holden, Laura K.; Strube, Michael J.

2014-01-01

Purpose: The purpose of this study was to examine the rate of progress in the 2nd implanted ear as it relates to the 1st implanted ear and to bilateral performance in adult sequential cochlear implant recipients. In addition, this study aimed to identify factors that contribute to patient outcomes. Method: The authors performed a prospective…

A Cross-Validation Study of Sequential-Simultaneous Processing at Ages 2 1/2-12 1/2 Using the Kaufman Assessment Battery for Children (K-ABC).

ERIC Educational Resources Information Center

Kamphaus, Randy W.; And Others

The development of two types of mental processing (sequential and simultaneous) in preschool and elementary children was examined in this study. Specifically, the aims of the study were to develop a revised set of tasks based upon previous findings (Naglieri, Kaufman, Kaufman, & Kamphaus, 1981; Kaufman, Kaufman, Kamphaus, & Naglieri, in…

The sequential structure of brain activation predicts skill.

PubMed

Anderson, John R; Bothell, Daniel; Fincham, Jon M; Moon, Jungaa

2016-01-29

In an fMRI study, participants were trained to play a complex video game. They were scanned early and then again after substantial practice. While better players showed greater activation in one region (right dorsal striatum) their relative skill was better diagnosed by considering the sequential structure of whole brain activation. Using a cognitive model that played this game, we extracted a characterization of the mental states that are involved in playing a game and the statistical structure of the transitions among these states. There was a strong correspondence between this measure of sequential structure and the skill of different players. Using multi-voxel pattern analysis, it was possible to recognize, with relatively high accuracy, the cognitive states participants were in during particular scans. We used the sequential structure of these activation-recognized states to predict the skill of individual players. These findings indicate that important features about information-processing strategies can be identified from a model-based analysis of the sequential structure of brain activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Classical and sequential limit analysis revisited

NASA Astrophysics Data System (ADS)

Leblond, Jean-Baptiste; Kondo, Djimédo; Morin, Léo; Remmal, Almahdi

2018-04-01

Classical limit analysis applies to ideal plastic materials, and within a linearized geometrical framework implying small displacements and strains. Sequential limit analysis was proposed as a heuristic extension to materials exhibiting strain hardening, and within a fully general geometrical framework involving large displacements and strains. The purpose of this paper is to study and clearly state the precise conditions permitting such an extension. This is done by comparing the evolution equations of the full elastic-plastic problem, the equations of classical limit analysis, and those of sequential limit analysis. The main conclusion is that, whereas classical limit analysis applies to materials exhibiting elasticity - in the absence of hardening and within a linearized geometrical framework -, sequential limit analysis, to be applicable, strictly prohibits the presence of elasticity - although it tolerates strain hardening and large displacements and strains. For a given mechanical situation, the relevance of sequential limit analysis therefore essentially depends upon the importance of the elastic-plastic coupling in the specific case considered.

A path-level exact parallelization strategy for sequential simulation

NASA Astrophysics Data System (ADS)

Peredo, Oscar F.; Baeza, Daniel; Ortiz, Julián M.; Herrero, José R.

2018-01-01

Sequential Simulation is a well known method in geostatistical modelling. Following the Bayesian approach for simulation of conditionally dependent random events, Sequential Indicator Simulation (SIS) method draws simulated values for K categories (categorical case) or classes defined by K different thresholds (continuous case). Similarly, Sequential Gaussian Simulation (SGS) method draws simulated values from a multivariate Gaussian field. In this work, a path-level approach to parallelize SIS and SGS methods is presented. A first stage of re-arrangement of the simulation path is performed, followed by a second stage of parallel simulation for non-conflicting nodes. A key advantage of the proposed parallelization method is to generate identical realizations as with the original non-parallelized methods. Case studies are presented using two sequential simulation codes from GSLIB: SISIM and SGSIM. Execution time and speedup results are shown for large-scale domains, with many categories and maximum kriging neighbours in each case, achieving high speedup results in the best scenarios using 16 threads of execution in a single machine.

Juvenile justice girls' depressive symptoms and suicidal ideation 9 years after Multidimensional Treatment Foster Care.

PubMed

Kerr, David C R; DeGarmo, David S; Leve, Leslie D; Chamberlain, Patricia

2014-08-01

Multidimensional Treatment Foster Care (MTFC) has been found to reduce delinquency among girls in juvenile justice through 2-year follow-up. Given that such girls are at elevated risk for suicide and depression into adulthood, we tested MTFC effects on long-term trajectories of suicidal ideation and depressive symptoms. Girls (N = 166; mean [SD] age = 15.3 [1.2] years; 68% White) with a recent criminal referral who were mandated to out-of-home care were enrolled in 2 sequential cohorts. Girls were randomized to receive MTFC (n = 81) or group care (GC) treatment as usual (TAU; n = 85); the second MTFC cohort also received modules targeting substance use and risky sexual behavior. Depressive symptoms and suicidal ideation were assessed repeatedly through early adulthood (mean [SD] follow-up = 8.8 [2.9] years). Suicide attempt history was assessed in early adulthood. Girls assigned to MTFC showed significantly greater decreases in depressive symptoms across the long-term follow-up than GC girls (π = -.86, p < .05). Decreases in suicidal ideation rates were slightly stronger in MTFC than in GC as indicated by a marginal main effect (odds ratio [OR] = .92, p < .10) and a significant interaction that favored MTFC in the second cohort relative to the first (OR = .88, p < .01). There were no significant MTFC effects on suicide attempt. MTFC decreased depressive symptoms and suicidal thinking beyond the decreases attributable to time and TAU. Thus, MTFC has further impact on girls' lives than originally anticipated. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Juvenile Justice Girls’ Depressive Symptoms and Suicidal Ideation Nine Years After Multidimensional Treatment Foster Care

PubMed Central

Kerr, David C. R.; DeGarmo, David S.; Leve, Leslie D.; Chamberlain, Patricia

2014-01-01

Objective Multidimensional Treatment Foster Care (MTFC) has been found to reduce delinquency among girls in juvenile justice through 2-year follow-up. Given that such girls are at elevated risk for suicide and depression into adulthood, we tested MTFC effects on long term trajectories of suicidal ideation and depressive symptoms. Method Girls [n =166; mean (SD) age = 15.3 (1.2) years; 68 % Caucasian] with a recent criminal referral who were mandated to out-of-home care were enrolled in two sequential cohorts. Girls were randomized to receive MTFC (n =81) or group care (GC) treatment as usual (TAU; n =85); the second MTFC cohort also received modules targeting substance use and risky sexual behavior. Depressive symptoms and suicidal ideation were assessed repeatedly through early adulthood [mean (SD) follow-up = 8.8 (2.9) years]. Suicide attempt history was assessed in early adulthood. Results Girls assigned to MTFC showed significantly greater decreases in depressive symptoms across the long-term follow-up than GC girls (π = −.86, p < .05). Decreases in suicidal ideation rates were slightly stronger in MTFC than in GC as indicated by a marginal main effect [odds ratio (OR) = .92, p < .10] and a significant interaction that favored MTFC in the second cohort relative to the first [OR = .88, p < .01]. There were no significant MTFC effects on suicide attempt. Conclusions MTFC decreased depressive symptoms and suicidal thinking beyond the decreases attributable to time and TAU. Thus, MTFC has further impact on girls’ lives than originally anticipated. PMID:24731234

Assessment of sequential same arm agreement of blood pressure measurements by a CVProfilor DO-2020 versus a Baumanometer mercury sphygmomanometer.

PubMed

Prisant, L M; Resnick, L M; Hollenberg, S M

2001-06-01

The aim of this study was to assess the accuracy of sequential same arm blood pressure measurement by the mercury sphygmomanometer with the oscillometric blood pressure measurements from a device that also determines arterial elasticity. A prospective, multicentre, clinical study evaluated sequential same arm blood pressure measurements, using a mercury sphygmomanometer (Baumanometer, W. A. Baum Co., Inc., Copiague, New York, USA) and an oscillometric non-invasive device that calculates arterial elasticity (CVProfilor DO-2020 Cardiovascular Profiling System, Hypertension Diagnostics, Inc., Eagan, Minnesota, USA). Blood pressure was measured supine in triplicate, 3 min apart in a randomized sequence after a period of rest. The study population of 230 normotensive and hypertensive subjects included 57% females, 51% Caucasians, and 33% African Americans. The mean difference between test methods of systolic blood pressure, diastolic blood pressure, and heart rate was -3.2 +/- 6.9 mmHg, +0.8 +/- 5.9 mmHg, and +1.0 +/- 5.7 beats/minute. For systolic and diastolic blood pressure, 60.9 and 70.4% of sequential measurements by each method were within +/- 5 mmHg. Few or no points fell beyond the mean +/- 2 standard deviations lines for each cuff bladder size. Sequential same arm measurements of the CVProfilor DO-2020 Cardiovascular Profiling System measures blood pressure by an oscillometric method (dynamic linear deflation) with reasonable agreement with a mercury sphygmomanometer.

Developmental trajectories of male physical violence and theft: relations to neurocognitive performance.

PubMed

Barker, Edward D; Séguin, Jean R; White, Helene Raskin; Bates, Marsha E; Lacourse, Eric; Carbonneau, René; Tremblay, Richard E

2007-05-01

Neurocognitive mechanisms have long been hypothesized to influence developmental trajectories of antisocial behavior. However, studies examining this association tend to aggregate a variety of problem behaviors that may be differently affected by neurocognitive deficits. To describe the developmental trajectories of physical violence and theft from adolescence to adulthood, their associations, and the neurocognitive characteristics of individuals following different patterns of trajectory association. Accelerated cohort-sequential, longitudinal design. Rutgers Health and Human Development Project. Six hundred ninety-eight men. Self-reports of physical violence (ages 12-24 years) and theft (ages 12-31 years) were collected across 5 waves. Neurocognitive performance was assessed with executive function and verbal IQ tests between late adolescence and early adulthood. The majority (55%) of subjects showed an increased frequency of theft during the study period, while only a minority (13%) evinced an increasing frequency of physical violence. Executive function and verbal IQ performance were negatively related to high frequency of physical violence but were unrelated to theft [corrected]. Developmental trajectories of physical violence and theft during adolescence and early adulthood are different and differently related to neurocognitive functioning. Global indexes of antisocial behavior mask the development of antisocial behavior subtypes and putative causal mechanisms.

How and why children change in aggression and delinquency from childhood to adolescence: moderation of overreactive parenting by child personality.

PubMed

de Haan, A D; Prinzie, P; Deković, M

2010-06-01

This study examines how and why children change in aggression and delinquency from age 6 to 15 years. Besides assessing the shape of the developmental trajectories of aggression and delinquency, we investigated whether child personality characteristics, parenting, and interactions between these two predict the development of aggression/delinquency. Employing a cohort-sequential design, data from the Flemish Study on Parenting, Personality, and Development were used. The sample consisted of 586 children aged 6-9 years at the first assessment, and their parents. Mothers, fathers, and teachers rated child personality at Time 1 using the Hierarchical Personality Inventory for Children, and mothers and fathers rated externalizing behaviors at the first, second, and third assessment using the Child Behavior Checklist. Parents rated their own overreactive parenting at Time 1 with the Parenting Scale. Aggression and delinquency showed differential, though interrelated development. Less extraverted, benevolent and conscientious children, and more imaginative children were more susceptible to overreactivity. The model replicated across fathers' overreactivity. Parents of children who are less extraverted, benevolent and conscientious, or more imaginative, are in particular need of being supported in developing and maintaining effective disciplinary techniques.

An overview of history, pathogenesis and treatment of perforated peptic ulcer disease with evaluation of prognostic scoring in adults.

PubMed

Prabhu, V; Shivani, A

2014-01-01

Peptic ulcer disease including both gastric and duodenal ulcer form a substantial part of patients seeking surgical opinion world-wide. The concept of acid in peptic ulcer disease, which was the basis of treatment of peptic ulcer was revolutionized by the discovery of H2-receptor antagonists, that led to the principle of acid suppression therapy for duodenal ulcer which followed decades of preference for surgical interventions in the form of gastric resections, vagotomy etc., After the discovery of Helicobacter pylori organism as the causative factor a triple drug regime was identified to treat peptic disease which was further modified to sequential therapy to avoid antibiotic resistance. This recognition has not concluded the chapter on peptic ulcers. The management of ulcer disease and its complications remain a surgical challenge. All the materials for this review have been accessed from various internet search engines. The references have been narrowed down to 34 by excluding cross references, duplicated citations, pediatric studies, case reports, iatrogenic and malignant perforations and including microbiological, immunohistochemistry references and studies with more than a sample size of ten. Case control, cohort studies, prospective/retrospective, metaanalytical studies were preferred in that order. This article attempts to take an overview of all aspects of the management of peptic ulcer.

Exploring how nurses assess, monitor and manage acute pain for adult critically ill patients in the emergency department: protocol for a mixed methods study.

PubMed

Varndell, Wayne; Fry, Margaret; Elliott, Doug

2017-08-01

Many critically ill patients experience moderate to severe acute pain that is frequently undetected and/or undertreated. Acute pain in this patient cohort not only derives from their injury and/or illness, but also as a consequence of delivering care whilst stabilising the patient. Emergency nurses are increasingly responsible for the safety and wellbeing of critically ill patients, which includes assessing, monitoring and managing acute pain. How emergency nurses manage acute pain in critically ill adult patients is unknown. The objective of this study is to explore how emergency nurses manage acute pain in critically ill patients in the Emergency Department. In this paper, we provide a detailed description of the methods and protocol for a multiphase sequential mixed methods study, exploring how emergency nurses assess, monitor and manage acute pain in critically ill adult patients. The objective, method, data collection and analysis of each phase are explained. Justification of each method and data integration is described. Synthesis of findings will generate a comprehensive picture of how emergency nurses' perceive and manage acute pain in critically ill adult patients. The results of this study will form a knowledge base to expand theory and inform research and practice.

An Overview of History, Pathogenesis and Treatment of Perforated Peptic Ulcer Disease with Evaluation of Prognostic Scoring in Adults

PubMed Central

Prabhu, V; Shivani, A

2014-01-01

Peptic ulcer disease including both gastric and duodenal ulcer form a substantial part of patients seeking surgical opinion world-wide. The concept of acid in peptic ulcer disease, which was the basis of treatment of peptic ulcer was revolutionized by the discovery of H2-receptor antagonists, that led to the principle of acid suppression therapy for duodenal ulcer which followed decades of preference for surgical interventions in the form of gastric resections, vagotomy etc., After the discovery of Helicobacter pylori organism as the causative factor a triple drug regime was identified to treat peptic disease which was further modified to sequential therapy to avoid antibiotic resistance. This recognition has not concluded the chapter on peptic ulcers. The management of ulcer disease and its complications remain a surgical challenge. All the materials for this review have been accessed from various internet search engines. The references have been narrowed down to 34 by excluding cross references, duplicated citations, pediatric studies, case reports, iatrogenic and malignant perforations and including microbiological, immunohistochemistry references and studies with more than a sample size of ten. Case control, cohort studies, prospective/retrospective, metaanalytical studies were preferred in that order. This article attempts to take an overview of all aspects of the management of peptic ulcer. PMID:24669326

PC_Eyewitness and the sequential superiority effect: computer-based lineup administration.

PubMed

MacLin, Otto H; Zimmerman, Laura A; Malpass, Roy S

2005-06-01

Computer technology has become an increasingly important tool for conducting eyewitness identifications. In the area of lineup identifications, computerized administration offers several advantages for researchers and law enforcement. PC_Eyewitness is designed specifically to administer lineups. To assess this new lineup technology, two studies were conducted in order to replicate the results of previous studies comparing simultaneous and sequential lineups. One hundred twenty university students participated in each experiment. Experiment 1 used traditional paper-and-pencil lineup administration methods to compare simultaneous to sequential lineups. Experiment 2 used PC_Eyewitness to administer simultaneous and sequential lineups. The results of these studies were compared to the meta-analytic results reported by N. Steblay, J. Dysart, S. Fulero, and R. C. L. Lindsay (2001). No differences were found between paper-and-pencil and PC_Eyewitness lineup administration methods. The core findings of the N. Steblay et al. (2001) meta-analysis were replicated by both administration procedures. These results show that computerized lineup administration using PC_Eyewitness is an effective means for gathering eyewitness identification data.

Political attitudes in adolescence and emerging adulthood: Developmental changes in mean level, polarization, rank-order stability, and correlates.

PubMed

Rekker, Roderik; Keijsers, Loes; Branje, Susan; Meeus, Wim

2015-06-01

This three-wave cohort-sequential longitudinal study (N = 1302) examined the development of two core political attitudes, economic egalitarianism and ethnocentrism, among Dutch youths between age 12 and 31. Longitudinal regression analyses revealed a curvilinear mean level development for both attitudes, reflecting an increased disagreement with economic redistribution and multiculturalism around late adolescence. Furthermore, attitudes became decreasingly polarized (i.e., less extreme) and increasingly stable with age. Finally, several effects of attitudes' correlates gradually changed: The effect of educational level on ethnocentrism increased with age, whereas the effect of gender diminished. Regional effects on ethnocentrism developed as youths resided in a new area. No age-related change was found in the effect of parental SES. Overall, these findings support the idea that attitudes mature during the formative phase of adolescence and that this process slows down during emerging adulthood. Furthermore, these results support developmental explanations for the association between attitudes and their correlates. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Alcohol Outcome Expectancies as Socially Shared and Socialized Beliefs

PubMed Central

Donovan, John E.; Molina, Brooke S. G.; Kelly, Thomas M.

2008-01-01

Alcohol expectancies are important predictors of alcohol involvement in both adolescents and adults, yet little research has examined the social origins and transmission of these beliefs. This paper examined alcohol outcome expectancies collected in a cohort-sequential longitudinal study of 452 families with children followed over seven waves. Children completed interviews every six months, and parents completed interviews annually. Eighteen of 27 alcohol expectancies were highly consensual, being endorsed by significantly more than 67% of the mothers and fathers. These consensual expectancies were also highly stable over a 3-year period. Over the same period, children increased their adoption of both the positive and negative consensual alcohol expectancies. Unconditional latent growth modeling showed that piece-wise growth models with a transition at age 12 fit the data best. Both the positive and negative consensual expectancies were adopted at a faster rate between ages 8.5 and 11.5 than between ages 12 and 13.5. For negative expectancies, there was no further growth between ages 12 and 13.5. Taken together, these findings support the conceptualization of alcohol outcome expectancies as socially-shared and transmitted beliefs. PMID:19586141

Lymph node status as a prognostic factor after palliative resection of primary tumor for patients with metastatic colorectal cancer.

PubMed

Li, Qingguo; Wang, Changjian; Li, Yaqi; Li, Xinxiang; Xu, Ye; Cai, Guoxiang; Lian, Peng; Cai, Sanjun

2017-07-18

Lymph node (LN) status is one of the most important predictors for M0 colorectal cancer patients. However, its clinical impact on stage IV colorectal cancer remains unclear. The study aimed to explore the prognostic value of LN status after palliative resection of primary tumor for patients with metastatic colorectal cancer (mCRC). We combined analyses of mCRC patients in Surveillance, Epidemiology and End Results (SEER) database and Fudan University Shanghai Cancer Center (FUSCC).A total of 17,553 patients with mCRC were identified in SEER database. X-tile program was adopted to identify 2 and 10 as optimal cutoff values for negative lymph node (NLN) count to divide patients into 3 subgroups of high, middle and low risk of cancer related death. N stage and NLN count were verified as independent prognostic factors in multivariate analyses of patients in whole cohort and in subgroup analyses of each N stage (P<0.05). Validation of FUSCC cohort of patients demonstrated that metastatic tumor burden (P = 0.042), NLN count (P = 0.039) and sequential chemotherapy (P = 0.040) were significant predictors of poorer CSS. Specifically, the prognosis of patients at stage N0 was significantly more favorable than that of patients at stage N2 (P = 0.038). In conclusion, primary tumor LN status was a strong predictor of CSS after palliative resection of metastatic colorectal cancer. Advanced N stage and small number of NLN were correlated with high risk of cancer related death after palliative resection of primary tumor.

Impact of an Ivermectin Mass Drug Administration on Scabies Prevalence in a Remote Australian Aboriginal Community.

PubMed

Kearns, Thérèse M; Speare, Richard; Cheng, Allen C; McCarthy, James; Carapetis, Jonathan R; Holt, Deborah C; Currie, Bart J; Page, Wendy; Shield, Jennifer; Gundjirryirr, Roslyn; Bundhala, Leanne; Mulholland, Eddie; Chatfield, Mark; Andrews, Ross M

2015-10-01

Scabies is endemic in many Aboriginal and Torres Strait Islander communities, with 69% of infants infected in the first year of life. We report the outcomes against scabies of two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community. Utilizing a before and after study design, we measured scabies prevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined disease acquisition and treatment failures. Scabies infestations were diagnosed clinically with additional laboratory investigations for crusted scabies. Non-pregnant participants weighing ≥15 kg were administered a single 200 μg/kg ivermectin dose, repeated after 2-3 weeks if scabies was diagnosed, others followed a standard alternative algorithm. We saw >1000 participants at each population census. Scabies prevalence fell from 4% at baseline to 1% at month 6. Prevalence rose to 9% at month 12 amongst the baseline cohort in association with an identified exposure to a presumptive crusted scabies case with a higher prevalence of 14% amongst new entries to the cohort. At month 18, scabies prevalence fell to 2%. Scabies acquisitions six months after each MDA were 1% and 2% whilst treatment failures were 6% and 5% respectively. Scabies prevalence reduced in the six months after each MDA with a low risk of acquisition (1-2%). However, in a setting where living conditions are conducive to high scabies transmissibility, exposure to presumptive crusted scabies and population mobility, a sustained reduction in prevalence was not achieved. Australian New Zealand Clinical Trial Register (ACTRN-12609000654257).

Inflammatory Bowel Diseases Can Adversely Impact Domains of Sexual Function Such as Satisfaction with Sex Life.

PubMed

Eluri, Swathi; Cross, Raymond K; Martin, Christopher; Weinfurt, Kevin P; Flynn, Kathryn E; Long, Millie D; Chen, Wenli; Anton, Kristen; Sandler, Robert S; Kappelman, Michael D

2018-06-01

Aspects of sexual health, which can be adversely affected by chronic disease, have been inadequately explored in inflammatory bowel disease (IBD). We evaluated patient-reported interest in sexual activity and satisfaction with sex life in a large cohort of IBD patients. We conducted a cross-sectional study within the Crohn's and Colitis Foundation Partners Internet cohort. Sequential participants completed a 6-question supplemental online survey to examine sexual interest and satisfaction using the Patient-Reported Outcome Measurement Information System ® (PROMIS ® ) Sexual Function and Satisfaction measures. One-sample t tests were used to compare interest and satisfaction scores to general population norms. Among 2569 individuals, 1639 had Crohn's disease (CD), 930 had ulcerative colitis (UC) or indeterminate colitis, and 71% were women. Mean PROMIS scores for sexual interest were comparable to the general US population in men (CD: 49 and UC: 48 vs. population mean 50) and women (CD: 41 and UC: 40 vs. population mean 42). However, sexual satisfaction scores were lower than the US population in men (CD: 48 and UC: 48 vs. 51) and women (CD: 47 and UC: 46 vs. 49), p < 0.01 for both. Older age, disease activity, depression, anxiety, and pain were associated with lower interest and satisfaction and lowered IBD-specific quality of life. IBD patients in a large online survey had similar levels of sexual interest but decreased sexual satisfaction compared to the general population. Exploring these sexual health domains during clinical encounters can aid in improving IBD quality of life.

Legacy phosphorus in calcareous soils: Effects of long-term poultry litter application

USDA-ARS?s Scientific Manuscript database

The effect of manure application on soil phosphorus has been intensively studied with modifications of the Hedley sequential fractionation procedure, X ray absorption near edge structure spectroscopy, and 31P nuclear magnetic resonance. Modern sequential fractionation techniques, coupled with phosph...

Sequential-Simultaneous Processing and Reading Skills in Primary Grade Children.

ERIC Educational Resources Information Center

McRae, Sandra G.

1986-01-01

The study examined relationships between two modes of information processing, simultaneous and sequential, and two sets of reading skills, word recognition and comprehension, among 40 second and third grade students. Results indicated there is a relationship between simultaneous processing and reading comprehension. (Author)

Group-sequential three-arm noninferiority clinical trial designs

PubMed Central

Ochiai, Toshimitsu; Hamasaki, Toshimitsu; Evans, Scott R.; Asakura, Koko; Ohno, Yuko

2016-01-01

We discuss group-sequential three-arm noninferiority clinical trial designs that include active and placebo controls for evaluating both assay sensitivity and noninferiority. We extend two existing approaches, the fixed margin and fraction approaches, into a group-sequential setting with two decision-making frameworks. We investigate the operating characteristics including power, Type I error rate, maximum and expected sample sizes, as design factors vary. In addition, we discuss sample size recalculation and its’ impact on the power and Type I error rate via a simulation study. PMID:26892481

Using timed event sequential data in nursing research.

PubMed

Pecanac, Kristen E; Doherty-King, Barbara; Yoon, Ju Young; Brown, Roger; Schiefelbein, Tony

2015-01-01

Measuring behavior is important in nursing research, and innovative technologies are needed to capture the "real-life" complexity of behaviors and events. The purpose of this article is to describe the use of timed event sequential data in nursing research and to demonstrate the use of this data in a research study. Timed event sequencing allows the researcher to capture the frequency, duration, and sequence of behaviors as they occur in an observation period and to link the behaviors to contextual details. Timed event sequential data can easily be collected with handheld computers, loaded with a software program designed for capturing observations in real time. Timed event sequential data add considerable strength to analysis of any nursing behavior of interest, which can enhance understanding and lead to improvement in nursing practice.

Corrected Mean-Field Model for Random Sequential Adsorption on Random Geometric Graphs

NASA Astrophysics Data System (ADS)

Dhara, Souvik; van Leeuwaarden, Johan S. H.; Mukherjee, Debankur

2018-03-01

A notorious problem in mathematics and physics is to create a solvable model for random sequential adsorption of non-overlapping congruent spheres in the d-dimensional Euclidean space with d≥ 2 . Spheres arrive sequentially at uniformly chosen locations in space and are accepted only when there is no overlap with previously deposited spheres. Due to spatial correlations, characterizing the fraction of accepted spheres remains largely intractable. We study this fraction by taking a novel approach that compares random sequential adsorption in Euclidean space to the nearest-neighbor blocking on a sequence of clustered random graphs. This random network model can be thought of as a corrected mean-field model for the interaction graph between the attempted spheres. Using functional limit theorems, we characterize the fraction of accepted spheres and its fluctuations.

Exploring the Factors That Affect the Intention to Use Collaborative Technologies: The Differing Perspectives of Sequential/Global Learners

ERIC Educational Resources Information Center

Huang, Yong-Ming

2015-01-01

The use of collaborative technologies in learning has received considerable attention in recent years, but few studies to date have examined the factors that affect sequential and global learners' intention to use such technologies. Previous studies have shown that the learners of different learning styles have different needs for educational…

A Longitudinal Study in Children with Sequential Bilateral Cochlear Implants: Time Course for the Second Implanted Ear and Bilateral Performance

ERIC Educational Resources Information Center

Reeder, Ruth M.; Firszt, Jill B.; Cadieux, Jamie H.; Strube, Michael J.

2017-01-01

Purpose: Whether, and if so when, a second-ear cochlear implant should be provided to older, unilaterally implanted children is an ongoing clinical question. This study evaluated rate of speech recognition progress for the second implanted ear and with bilateral cochlear implants in older sequentially implanted children and evaluated localization…

International students' experience of a western medical school: a mixed methods study exploring the early years in the context of cultural and social adjustment compared to students from the host country.

PubMed

McGarvey, A; Brugha, R; Conroy, R M; Clarke, E; Byrne, E

2015-07-02

Few studies have addressed the challenges associated with international students as they adapt to studying medicine in a new host country. Higher level institutions have increasing numbers of international students commencing programmes. This paper explores the experiences of a cohort of students in the early years of medical school in Ireland, where a considerable cohort are from an international background. A mixed exploratory sequential study design was carried out with medical students in the preclinical component of a five year undergraduate programme. Data for the qualitative phase was collected through 29 semi-structured interviews using the peer interview method. Thematic analysis from this phase was incorporated to develop an online questionnaire combined with components of the Student Adaptation to College Questionnaire and Student Integration Questionnaire. First year students were anonymously surveyed online. The Mokken Scaling procedure was used to investigate the students' experiences, both positive and negative. Three main themes are identified; social adjustment, social alienation and cultural alienation. The response rate for the survey was 49% (467 Respondents). The Mokken Scaling method identified the following scales (i) Positive experience of student life; (ii) Social alienation, which comprised of negative items about feeling lonely, not fitting in, being homesick and (iii) Cultural alienation, which included the items of being uncomfortable around cultural norms of dress and contact between the sexes. With the threshold set to H = 0.4. Subscales of the positive experiences of student life scale are explored further. Overall student adjustment to a western third level college was good. Students from regions where cultural distance is greatest reported more difficulties in adjusting. Students from these regions also demonstrate very good adaptation. Some students from the host country and more similar cultural backgrounds were also struggling. Acculturation is more complex than being associated with cultural distance and worthy of further exploration.

Simultaneous sequential monitoring of efficacy and safety led to masking of effects.

PubMed

van Eekelen, Rik; de Hoop, Esther; van der Tweel, Ingeborg

2016-08-01

Usually, sequential designs for clinical trials are applied on the primary (=efficacy) outcome. In practice, other outcomes (e.g., safety) will also be monitored and influence the decision whether to stop a trial early. Implications of simultaneous monitoring on trial decision making are yet unclear. This study examines what happens to the type I error, power, and required sample sizes when one efficacy outcome and one correlated safety outcome are monitored simultaneously using sequential designs. We conducted a simulation study in the framework of a two-arm parallel clinical trial. Interim analyses on two outcomes were performed independently and simultaneously on the same data sets using four sequential monitoring designs, including O'Brien-Fleming and Triangular Test boundaries. Simulations differed in values for correlations and true effect sizes. When an effect was present in both outcomes, competition was introduced, which decreased power (e.g., from 80% to 60%). Futility boundaries for the efficacy outcome reduced overall type I errors as well as power for the safety outcome. Monitoring two correlated outcomes, given that both are essential for early trial termination, leads to masking of true effects. Careful consideration of scenarios must be taken into account when designing sequential trials. Simulation results can help guide trial design. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of neostriatal 6-OHDA lesion on performance in a rat sequential reaction time task.

PubMed

Domenger, D; Schwarting, R K W

2008-10-31

Work in humans and monkeys has provided evidence that the basal ganglia, and the neurotransmitter dopamine therein, play an important role for sequential learning and performance. Compared to primates, experimental work in rodents is rather sparse, largely due to the fact that tasks comparable to the human ones, especially serial reaction time tasks (SRTT), had been lacking until recently. We have developed a rat model of the SRTT, which allows to study neural correlates of sequential performance and motor sequence execution. Here, we report the effects of dopaminergic neostriatal lesions, performed using bilateral 6-hydroxydopamine injections, on performance of well-trained rats tested in our SRTT. Sequential behavior was measured in two ways: for one, the effects of small violations of otherwise well trained sequences were examined as a measure of attention and automation. Secondly, sequential versus random performance was compared as a measure of sequential learning. Neurochemically, the lesions led to sub-total dopamine depletions in the neostriatum, which ranged around 60% in the lateral, and around 40% in the medial neostriatum. These lesions led to a general instrumental impairment in terms of reduced speed (response latencies) and response rate, and these deficits were correlated with the degree of striatal dopamine loss. Furthermore, the violation test indicated that the lesion group conducted less automated responses. The comparison of random versus sequential responding showed that the lesion group did not retain its superior sequential performance in terms of speed, whereas they did in terms of accuracy. Also, rats with lesions did not improve further in overall performance as compared to pre-lesion values, whereas controls did. These results support previous results that neostriatal dopamine is involved in instrumental behaviour in general. Also, these lesions are not sufficient to completely abolish sequential performance, at least when acquired before lesion as tested here.

Success of a weight loss plan for overweight dogs: The results of an international weight loss study

PubMed Central

Flanagan, John; Bissot, Thomas; Hours, Marie-Anne; Moreno, Bernabe; Feugier, Alexandre

2017-01-01

Introduction Obesity is a global concern in dogs with an increasing prevalence, and effective weight loss solutions are required that work in different geographical regions. The main objective was to conduct an international, multi-centre, weight loss trial to determine the efficacy of a dietary weight loss intervention in obese pet dogs. Methods A 3-month prospective observational cohort study of weight loss in 926 overweight dogs was conducted at 340 veterinary practices in 27 countries. Commercially available dry or wet weight loss diets were used, with the initial energy allocation being 250–335 kJ/kg target body weight0.75/day (60–80 kcal/kg target body weight0.75/day) depending on sex and neuter status. The primary outcome measure was percentage weight loss; the main secondary outcomes were changes in activity, quality of life, and food-seeking behaviour, which were subjectively determined from owner descriptions. Results At baseline, median (range) age was 74 (12 to 193) months and median body condition score was 8 (range 7–9). 896 of the 926 dogs (97%) lost weight, with mean weight loss being 11.4 ±5.84%. Sexually intact dogs lost more weight than neutered dogs (P = 0.001), whilst female dogs lost more weight than male dogs (P = 0.007), with the difference being more pronounced in North and South American dogs (median [Q1, Q3]: female: 11.5% [8.5%, 14.5%]; male: 9.1% [6.3%, 12.1%], P = 0.053) compared with those from Europe (female: 12.3% [8.9%, 14.9%]; male: 10.9% [8.6%, 15.4%]). Finally, subjective scores for activity (P<0.001) and quality of life (P<0.001) increased sequentially, whilst scores for food-seeking behaviour decreased sequentially (P<0.001) during the study. Conclusion This is the largest international multi-centre weight loss study conducted to date in obese dogs. Most dogs lost a clinically significant amount of weight, although there were notable differences between dogs of different sex, neuter status and in different geographical locations. PMID:28886096

Similar outcome of allogeneic stem cell transplantation after myeloablative and sequential conditioning regimen in patients with refractory or relapsed acute myeloid leukemia: A study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

PubMed

Decroocq, Justine; Itzykson, Raphaël; Vigouroux, Stéphane; Michallet, Mauricette; Yakoub-Agha, Ibrahim; Huynh, Anne; Beckerich, Florence; Suarez, Felipe; Chevallier, Patrice; Nguyen-Quoc, Stéphanie; Ledoux, Marie-Pierre; Clement, Laurence; Hicheri, Yosr; Guillerm, Gaëlle; Cornillon, Jérôme; Contentin, Nathalie; Carre, Martin; Maillard, Natacha; Mercier, Mélanie; Mohty, Mohamad; Beguin, Yves; Bourhis, Jean-Henri; Charbonnier, Amandine; Dauriac, Charles; Bay, Jacques-Olivier; Blaise, Didier; Deconinck, Eric; Jubert, Charlotte; Raus, Nicole; Peffault de Latour, Regis; Dhedin, Nathalie

2018-03-01

Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions. We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%). Fifty-eight patients received a sequential approach and 41 patients a myeloablative conditioning regimen. Only 6 patients received prophylactic donor lymphocytes infusions. With a median follow-up of 48 months, 2-year overall survival was 39%, 95% confidence interval (CI) (24-53) in the myeloablative group versus 33%, 95% CI (21-45) in the sequential groups (P = .39), and 2-year cumulative incidence of relapse (CIR) was 57% versus 50% respectively (P = .99). Nonrelapse mortality was not higher in the myeloablative group (17% versus 15%, P = .44). In multivariate analysis, overall survival, CIR and nonrelapse mortality remained similar between the two groups. However, in multivariate analysis, sequential conditioning led to fewer acute grade II-IV graft versus host disease (GVHD) (HR for sequential approach = 0.37; 95% CI: 0.21-0.65; P < .001) without a significant impact on chronic GVHD (all grades and extensive). In young patients with refractory or relapsed AML, myeloablative transplant and sequential approach offer similar outcomes except for a lower incidence of acute GvHD after a sequential transplant. © 2018 Wiley Periodicals, Inc.

A Bayesian Theory of Sequential Causal Learning and Abstract Transfer.

PubMed

Lu, Hongjing; Rojas, Randall R; Beckers, Tom; Yuille, Alan L

2016-03-01

Two key research issues in the field of causal learning are how people acquire causal knowledge when observing data that are presented sequentially, and the level of abstraction at which learning takes place. Does sequential causal learning solely involve the acquisition of specific cause-effect links, or do learners also acquire knowledge about abstract causal constraints? Recent empirical studies have revealed that experience with one set of causal cues can dramatically alter subsequent learning and performance with entirely different cues, suggesting that learning involves abstract transfer, and such transfer effects involve sequential presentation of distinct sets of causal cues. It has been demonstrated that pre-training (or even post-training) can modulate classic causal learning phenomena such as forward and backward blocking. To account for these effects, we propose a Bayesian theory of sequential causal learning. The theory assumes that humans are able to consider and use several alternative causal generative models, each instantiating a different causal integration rule. Model selection is used to decide which integration rule to use in a given learning environment in order to infer causal knowledge from sequential data. Detailed computer simulations demonstrate that humans rely on the abstract characteristics of outcome variables (e.g., binary vs. continuous) to select a causal integration rule, which in turn alters causal learning in a variety of blocking and overshadowing paradigms. When the nature of the outcome variable is ambiguous, humans select the model that yields the best fit with the recent environment, and then apply it to subsequent learning tasks. Based on sequential patterns of cue-outcome co-occurrence, the theory can account for a range of phenomena in sequential causal learning, including various blocking effects, primacy effects in some experimental conditions, and apparently abstract transfer of causal knowledge. Copyright © 2015 Cognitive Science Society, Inc.

Interkinetic and migratory behavior of a cohort of neocortical neurons arising in the early embryonic murine cerebral wall

NASA Technical Reports Server (NTRS)

Takahashi, T.; Nowakowski, R. S.; Caviness, V. S. Jr

1996-01-01

Neocortical neuronogenesis occurs in the pseudostratified ventricular epithelium (PVE) where nuclei of proliferative cells undergo interkinetic nuclear movement. A fraction of daughter cells exits the cell cycle as neurons (the quiescent, or Q, fraction), whereas a complementary fraction remains in the cell cycle (the proliferative, or P, fraction). By means of sequential thymidine and bromodeoxyuridine injections in mouse on embryonic day 14, we have monitored the proliferative and post-mitotic migratory behaviors of 1 and 2 hr cohorts of PVE cells defined by the injection protocols. Soon after mitosis, the Q fraction partitions into a rapidly exiting (up to 50 microns/hr) subpopulation (Qr) and a more slowly exiting (6 microns/hr) subpopulation (Qs). Qr and Qs are separated as two distributions on exit from the ventricular zone with an interpeak distance of approximately 40 microns. Cells in Qr and Qs migrate through the intermediate zone with no significant change in the interpeak distance, suggesting that they migrate at approximately the same velocities. The rate of migration increases with ascent through the intermediate zone (average 2-6.4 microns/hr) slowing only transiently on entry into the developing cortex. Within the cortex, Qr and Qs merge to form a single distribution most concentrated over layer V.

A Metacognitive Visuospatial Working Memory Training for Children

ERIC Educational Resources Information Center

Caviola, Sara; Mammarella, Irene C.; Cornoldi, Cesare; Lucangeli, Daniela

2009-01-01

The paper studies whether visuospatial working memory (VSWM) and, specifically, recall of sequential-spatial information, can be improved by metacognitive training. Twenty-two fourth-grade children were involved in seven sessions of sequential-spatial memory training, while twenty-four children attended lessons given by their teacher. The…

SEQUENTIAL EXTRACTIONS FOR PARTITIONING OF ARSENIC ON HYDROUS IRON OXIDES AND IRON SULFIDES

EPA Science Inventory

The objective of this study was to use model solids to test solutions designed to extract arsenic from relatively labile solid phase fractions. The use of sequential extractions provides analytical constraints on the identification of mineral phases that control arsenic mobility...

Mathematical Problem Solving through Sequential Process Analysis

ERIC Educational Resources Information Center

Codina, A.; Cañadas, M. C.; Castro, E.

2015-01-01

Introduction: The macroscopic perspective is one of the frameworks for research on problem solving in mathematics education. Coming from this perspective, our study addresses the stages of thought in mathematical problem solving, offering an innovative approach because we apply sequential relations and global interrelations between the different…

Adjuvant sequential chemo and radiotherapy improves the oncological outcome in high risk endometrial cancer

PubMed Central

Signorelli, Mauro; Lissoni, Andrea Alberto; De Ponti, Elena; Grassi, Tommaso; Ponti, Serena

2015-01-01

Objective Evaluation of the impact of sequential chemoradiotherapy in high risk endometrial cancer (EC). Methods Two hundred fifty-four women with stage IB grade 3, II and III EC (2009 FIGO staging), were included in this retrospective study. Results Stage I, II, and III was 24%, 28.7%, and 47.3%, respectively. Grade 3 tumor was 53.2% and 71.3% had deep myometrial invasion. One hundred sixty-five women (65%) underwent pelvic (+/- aortic) lymphadenectomy and 58 (22.8%) had nodal metastases. Ninety-eight women (38.6%) underwent radiotherapy, 59 (23.2%) chemotherapy, 42 (16.5%) sequential chemoradiotherapy, and 55 (21.7%) were only observed. After a median follow-up of 101 months, 78 women (30.7%) relapsed and 91 women (35.8%) died. Sequential chemoradiotherapy improved survival rates in women who did not undergo nodal evaluation (disease-free survival [DFS], p=0.040; overall survival [OS], p=0.024) or pelvic (+/- aortic) lymphadenectomy (DFS, p=0.008; OS, p=0.021). Sequential chemoradiotherapy improved both DFS (p=0.015) and OS (p=0.014) in stage III, while only a trend was found for DFS (p=0.210) and OS (p=0.102) in stage I-II EC. In the multivariate analysis, only age (≤65 years) and sequential chemoradiotherapy were statistically related to the prognosis. Conclusion Sequential chemoradiotherapy improves survival rates in high risk EC compared with chemotherapy or radiotherapy alone, in particular in stage III. PMID:26197768

Analyzing change in short-term longitudinal research using cohort-sequential designs.

PubMed

Anderson, E R

1993-12-01

This article illustrates a method for approximating longitudinal data analysis by combining information from different overlapping age groups to form a single developmental growth curve. Using this method, hypotheses about the form of growth, the extent of individual differences in growth, and factors that affect the rate and pattern of growth are investigated. The example used to illustrate this method examines the growth of externalizing behavior and of negativity in parent-child relationships during early adolescence using assessments from multiple methods and multiple informants. These 3 dimensions changed significantly during this period, with parental negativity increasing more rapidly after age 12. However, there were substantial individual differences in the pattern of change in these dimensions. Gender of child and type of family situation (nondivorced, divorced, and remarried) were investigated as possible factors affecting change.

Changes in transthoracic impedance during sequential biphasic defibrillation.

PubMed

Deakin, Charles D; Ambler, Jonathan J S; Shaw, Steven

2008-08-01

Sequential monophasic defibrillation reduces transthoracic impedance (TTI) and progressively increases current flow for any given energy level. The effect of sequential biphasic shocks on TTI is unknown. We therefore studied patients undergoing elective cardioversion using a biphasic waveform to establish whether this is a phenomenon seen in the clinical setting. Adults undergoing elective DC cardioversion for atrial flutter or fibrillation received sequential transthoracic shocks using an escalating protocol (70J, 100J, 150J, 200J, and 300J) with a truncated exponential biphasic waveform. TTI was calculated through the defibrillator circuit and recorded electronically. Successful cardioversion terminated further defibrillation shocks. A total of 58 patients underwent elective cardioversion. Cardioversion was successful in 93.1% patients. First shock TTI was 92.2 [52.0-126.0]Omega (n=58) and decreased significantly with each sequential shock. Mean TTI in patients receiving five shocks (n=5) was 85.0Omega. Sequential biphasic defibrillation decreases TTI in a similar manner to that seen with monophasic waveforms. The effect is likely during defibrillation during cardiac arrest by the quick succession in which shocks are delivered and the lack of cutaneous blood flow which limits the inflammatory response. The ability of biphasic defibrillators to adjust their waveform according to TTI is likely to minimise any effect of these findings on defibrillation efficacy.

Sequential Voluntary Cough and Aspiration or Aspiration Risk in Parkinson’s Disease

PubMed Central

Hegland, Karen Wheeler; Okun, Michael S.; Troche, Michelle S.

2015-01-01

Background Disordered swallowing, or dysphagia, is almost always present to some degree in people with Parkinson’s disease (PD), either causing aspiration or greatly increasing the risk for aspiration during swallowing. This likely contributes to aspiration pneumonia, a leading cause of death in this patient population. Effective airway protection is dependent upon multiple behaviors, including cough and swallowing. Single voluntary cough function is disordered in people with PD and dysphagia. However, the appropriate response to aspirate material is more than one cough, or sequential cough. The goal of this study was to examine voluntary sequential coughing in people with PD, with and without dysphagia. Methods Forty adults diagnosed with idiopathic PD produced two trials of sequential voluntary cough. The cough airflows were obtained using pneumotachograph and facemask and subsequently digitized and recorded. All participants received a modified barium swallow study as part of their clinical care, and the worst penetration–aspiration score observed was used to determine whether the patient had dysphagia. Results There were significant differences in the compression phase duration, peak expiratory flow rates, and amount of air expired of the sequential cough produced by participants with and without dysphagia. Conclusions The presence of dysphagia in people with PD is associated with disordered cough function. Sequential cough, which is important in removing aspirate material from large- and smaller-diameter airways, is also impaired in people with PD and dysphagia compared with those without dysphagia. There may be common neuroanatomical substrates for cough and swallowing impairment in PD leading to the co-occurrence of these dysfunctions. PMID:24792231

Radiofrequency catheter ablation of idiopathic ventricular arrhythmias originating from intramural foci in the left ventricular outflow tract: efficacy of sequential versus simultaneous unipolar catheter ablation.

PubMed

Yamada, Takumi; Maddox, William R; McElderry, H Thomas; Doppalapudi, Harish; Plumb, Vance J; Kay, G Neal

2015-04-01

Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the efficacy of sequential and simultaneous unipolar radiofrequency catheter ablation from the endocardial and epicardial sides in treating intramural LVOT VAs. Fourteen consecutive LVOT VAs, which required sequential or simultaneous irrigated unipolar radiofrequency ablation from the endocardial and epicardial sides for their elimination, were studied. The first ablation was performed at the site with the earliest local ventricular activation and best pace map on the endocardial or epicardial side. When the first ablation was unsuccessful, the second ablation was delivered on the other surface. If this sequential unipolar ablation failed, simultaneous unipolar ablation from both sides was performed. The first ablation was performed on the epicardial side in 9 VAs and endocardial side in 5 VAs. The intramural LVOT VAs were successfully eliminated by the sequential (n=9) or simultaneous (n=5) unipolar catheter ablation. Simultaneous ablation was most likely to be required for the elimination of the VAs when the distance between the endocardial and epicardial ablation sites was >8 mm and the earliest local ventricular activation time relative to the QRS onset during the VAs of <-30 ms was recorded at those ablation sites. LVOT VAs originating from intramural foci could usually be eliminated by sequential unipolar radiofrequency ablation and sometimes required simultaneous ablation from both the endocardial and epicardial sides. © 2015 American Heart Association, Inc.

Individuation of Pairs of Objects in Infancy

ERIC Educational Resources Information Center

Leslie, Alan M.; Chen, Marian L.

2007-01-01

Looking-time studies examined whether 11-month-old infants can individuate two pairs of objects using only shape information. In order to test individuation, the object pairs were presented sequentially. Infants were familiarized either with the sequential pairs, disk-triangle/disk-triangle (XY/XY), whose shapes differed within but not across…

Decomposition of Copper (II) Sulfate Pentahydrate: A Sequential Gravimetric Analysis.

ERIC Educational Resources Information Center

Harris, Arlo D.; Kalbus, Lee H.

1979-01-01

Describes an improved experiment of the thermal dehydration of copper (II) sulfate pentahydrate. The improvements described here are control of the temperature environment and a quantitative study of the decomposition reaction to a thermally stable oxide. Data will suffice to show sequential gravimetric analysis. (Author/SA)

Sequential Dependencies in Driving

ERIC Educational Resources Information Center

Doshi, Anup; Tran, Cuong; Wilder, Matthew H.; Mozer, Michael C.; Trivedi, Mohan M.

2012-01-01

The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find…

The Motivating Language of Principals: A Sequential Transformative Strategy

ERIC Educational Resources Information Center

Holmes, William Tobias

2012-01-01

This study implemented a Sequential Transformative Mixed Methods design with teachers (as recipients) and principals (to give voice) in the examination of principal talk in two different school accountability contexts (Continuously Improving and Continuously Zigzag) using the conceptual framework of Motivating Language Theory. In phase one,…

Simultaneity, Sequentiality, and Speed: Organizational Messages about Multiple-Task Completion

ERIC Educational Resources Information Center

Stephens, Keri K.; Cho, Jaehee K.; Ballard, Dawna I.

2012-01-01

Workplace norms for task completion increasingly value speed and the ability to accomplish multiple tasks at once. This study situates this popularized issue of multitasking within the context of chronemics scholarship by addressing related issues of simultaneity, sequentiality, and speed. Ultimately, we consider 2 multiple-task completion…

The Quality of French Minority Students' Fictional Texts: A Study of the Influence of a Preferential Cognitive Style and Writing Strategy Scaffolding

ERIC Educational Resources Information Center

Cavanagh, Martine Odile; Langevin, Rene

2010-01-01

The object of this exploratory study was to test two hypotheses. The first was that a student's preferential cognitive style, sequential or simultaneous, can negatively affect the imaginative fiction texts that he or she produces. The second hypothesis was that students possessing a sequential or simultaneous preferential cognitive style would…

Implementing Quality Criteria in Designing and Conducting a Sequential Quan [right arrow] Qual Mixed Methods Study of Student Engagement with Learning Applied Research Methods Online

ERIC Educational Resources Information Center

Ivankova, Nataliya V.

2014-01-01

In spite of recent methodological developments related to quality assurance in mixed methods research, practical examples of how to implement quality criteria in designing and conducting sequential QUAN [right arrow] QUAL mixed methods studies to ensure the process is systematic and rigorous remain scarce. This article discusses a three-step…

Sensitivity Analysis in Sequential Decision Models.

PubMed

Chen, Qiushi; Ayer, Turgay; Chhatwal, Jagpreet

2017-02-01

Sequential decision problems are frequently encountered in medical decision making, which are commonly solved using Markov decision processes (MDPs). Modeling guidelines recommend conducting sensitivity analyses in decision-analytic models to assess the robustness of the model results against the uncertainty in model parameters. However, standard methods of conducting sensitivity analyses cannot be directly applied to sequential decision problems because this would require evaluating all possible decision sequences, typically in the order of trillions, which is not practically feasible. As a result, most MDP-based modeling studies do not examine confidence in their recommended policies. In this study, we provide an approach to estimate uncertainty and confidence in the results of sequential decision models. First, we provide a probabilistic univariate method to identify the most sensitive parameters in MDPs. Second, we present a probabilistic multivariate approach to estimate the overall confidence in the recommended optimal policy considering joint uncertainty in the model parameters. We provide a graphical representation, which we call a policy acceptability curve, to summarize the confidence in the optimal policy by incorporating stakeholders' willingness to accept the base case policy. For a cost-effectiveness analysis, we provide an approach to construct a cost-effectiveness acceptability frontier, which shows the most cost-effective policy as well as the confidence in that for a given willingness to pay threshold. We demonstrate our approach using a simple MDP case study. We developed a method to conduct sensitivity analysis in sequential decision models, which could increase the credibility of these models among stakeholders.

Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

PubMed

Arguedas, A; Soley, C; Loaiza, C; Rincon, G; Guevara, S; Perez, A; Porras, W; Alvarado, O; Aguilar, L; Abdelnour, A; Grunwald, U; Bedell, L; Anemona, A; Dull, P M

2010-04-19

This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity. Copyright 2010 Elsevier Ltd. All rights reserved.

Work–Family Conflict and Mental Health Among Female Employees: A Sequential Mediation Model via Negative Affect and Perceived Stress

PubMed Central

Zhou, Shiyi; Da, Shu; Guo, Heng; Zhang, Xichao

2018-01-01

After the implementation of the universal two-child policy in 2016, more and more working women have found themselves caught in the dilemma of whether to raise a baby or be promoted, which exacerbates work–family conflicts among Chinese women. Few studies have examined the mediating effect of negative affect. The present study combined the conservation of resources model and affective events theory to examine the sequential mediating effect of negative affect and perceived stress in the relationship between work–family conflict and mental health. A valid sample of 351 full-time Chinese female employees was recruited in this study, and participants voluntarily answered online questionnaires. Pearson correlation analysis, structural equation modeling, and multiple mediation analysis were used to examine the relationships between work–family conflict, negative affect, perceived stress, and mental health in full-time female employees. We found that women’s perceptions of both work-to-family conflict and family-to-work conflict were significant negatively related to mental health. Additionally, the results showed that negative affect and perceived stress were negatively correlated with mental health. The 95% confidence intervals indicated the sequential mediating effect of negative affect and stress in the relationship between work–family conflict and mental health was significant, which supported the hypothesized sequential mediation model. The findings suggest that work–family conflicts affected the level of self-reported mental health, and this relationship functioned through the two sequential mediators of negative affect and perceived stress. PMID:29719522

Work-Family Conflict and Mental Health Among Female Employees: A Sequential Mediation Model via Negative Affect and Perceived Stress.

PubMed

Zhou, Shiyi; Da, Shu; Guo, Heng; Zhang, Xichao

2018-01-01

After the implementation of the universal two-child policy in 2016, more and more working women have found themselves caught in the dilemma of whether to raise a baby or be promoted, which exacerbates work-family conflicts among Chinese women. Few studies have examined the mediating effect of negative affect. The present study combined the conservation of resources model and affective events theory to examine the sequential mediating effect of negative affect and perceived stress in the relationship between work-family conflict and mental health. A valid sample of 351 full-time Chinese female employees was recruited in this study, and participants voluntarily answered online questionnaires. Pearson correlation analysis, structural equation modeling, and multiple mediation analysis were used to examine the relationships between work-family conflict, negative affect, perceived stress, and mental health in full-time female employees. We found that women's perceptions of both work-to-family conflict and family-to-work conflict were significant negatively related to mental health. Additionally, the results showed that negative affect and perceived stress were negatively correlated with mental health. The 95% confidence intervals indicated the sequential mediating effect of negative affect and stress in the relationship between work-family conflict and mental health was significant, which supported the hypothesized sequential mediation model. The findings suggest that work-family conflicts affected the level of self-reported mental health, and this relationship functioned through the two sequential mediators of negative affect and perceived stress.

Physiological responses and evaluation of effects of BMI, smoking and drinking in high altitude acclimatization: a cohort study in Chinese Han young males.

PubMed

Peng, Qian-Qian; Basang, Zhuoma; Cui, Chao-Ying; Li, Lei; Qian, Ji; Gesang, Quzhen; Yang, La; La, Zong; De, Yang; Dawa, Puchi; Qu, Ni; Suo, Qu; Dan, Zhen; Xiao, Duoji; Wang, Xiao-Feng; Jin, Li

2013-01-01

High altitude acclimatization is a series of physiological responses taking places when subjects go to altitude. Many factors could influence these processes, such as altitude, ascending speed and individual characteristics. In this study, based on a repeated measurement design of three sequential measurements at baseline, acute phase and chronic phase, we evaluated the effect of BMI, smoking and drinking on a number of physiological responses in high altitude acclimatization by using mixed model and partial least square path model on a sample of 755 Han Chinese young males. We found that subjects with higher BMI responses were reluctant to hypoxia. The effect of smoking was not significant at acute phase. But at chronic phase, red blood cell volume increased less while respiratory function increased more for smoking subjects compared with nonsmokers. For drinking subjects, red blood cell volume increased less than nondrinkers at both acute and chronic phases, while blood pressures increased more than nondrinkers at acute phase and respiratory function, red blood cell volume and oxygen saturation increased more than nondrinkers at chronic phase. The heavy and long-term effect of smoking, drinking and other factors in high altitude acclimatization needed to be further studied.

Physiological Responses and Evaluation of Effects of BMI, Smoking and Drinking in High Altitude Acclimatization: A Cohort Study in Chinese Han Young Males

PubMed Central

Cui, Chao-ying; Li, Lei; Qian, Ji; Gesang, Quzhen; Yang, La; La, Zong; De, Yang; Dawa, Puchi; Qu, Ni; Suo, Qu; Dan, Zhen; Xiao, Duoji; Wang, Xiao-feng; Jin, Li

2013-01-01

High altitude acclimatization is a series of physiological responses taking places when subjects go to altitude. Many factors could influence these processes, such as altitude, ascending speed and individual characteristics. In this study, based on a repeated measurement design of three sequential measurements at baseline, acute phase and chronic phase, we evaluated the effect of BMI, smoking and drinking on a number of physiological responses in high altitude acclimatization by using mixed model and partial least square path model on a sample of 755 Han Chinese young males. We found that subjects with higher BMI responses were reluctant to hypoxia. The effect of smoking was not significant at acute phase. But at chronic phase, red blood cell volume increased less while respiratory function increased more for smoking subjects compared with nonsmokers. For drinking subjects, red blood cell volume increased less than nondrinkers at both acute and chronic phases, while blood pressures increased more than nondrinkers at acute phase and respiratory function, red blood cell volume and oxygen saturation increased more than nondrinkers at chronic phase. The heavy and long-term effect of smoking, drinking and other factors in high altitude acclimatization needed to be further studied. PMID:24260204

Effect of MR Imaging Contrast Thresholds on Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes: A Subgroup Analysis of the ACRIN 6657/I-SPY 1 TRIAL

PubMed Central

Li, Wen; Arasu, Vignesh; Newitt, David C.; Jones, Ella F.; Wilmes, Lisa; Gibbs, Jessica; Kornak, John; Joe, Bonnie N.; Esserman, Laura J.; Hylton, Nola M.

2016-01-01

Functional tumor volume (FTV) measurements by dynamic contrast-enhanced magnetic resonance imaging can predict treatment outcomes for women receiving neoadjuvant chemotherapy for breast cancer. Here, we explore whether the contrast thresholds used to define FTV could be adjusted by breast cancer subtype to improve predictive performance. Absolute FTV and percent change in FTV (ΔFTV) at sequential time-points during treatment were calculated and investigated as predictors of pathologic complete response at surgery. Early percent enhancement threshold (PEt) and signal enhancement ratio threshold (SERt) were varied. The predictive performance of resulting FTV predictors was evaluated using the area under the receiver operating characteristic curve. A total number of 116 patients were studied both as a full cohort and in the following groups defined by hormone receptor (HR) and HER2 receptor subtype: 45 HR+/HER2−, 39 HER2+, and 30 triple negatives. High AUCs were found at different ranges of PEt and SERt levels in different subtypes. Findings from this study suggest that the predictive performance to treatment response by MRI varies by contrast thresholds, and that pathologic complete response prediction may be improved through subtype-specific contrast enhancement thresholds. A validation study is underway with a larger patient population. PMID:28066808

Spontaneous hypothermia on intensive care unit admission is a predictor of unfavorable neurological outcome in patients after resuscitation: an observational cohort study.

PubMed

den Hartog, Alexander W; de Pont, Anne-Cornélie J M; Robillard, Laure B M; Binnekade, Jan M; Schultz, Marcus J; Horn, Janneke

2010-01-01

A large number of patients resuscitated for primary cardiac arrest arrive in the intensive care unit (ICU) with a body temperature < 35.0 degrees C. The aim of this observational cohort study was to determine the association between ICU admission temperature and neurological outcome in this patient group. Demographics and parameters influencing neurological outcome were retrieved from the charts of all patients resuscitated for primary cardiac arrest and treated with induced mild hypothermia in our ICU from January 2006 until January 2008. Patients were divided into two groups according to their body temperature on ICU admission: a hypothermia group (< 35.0 degrees C) and a non-hypothermia group (>or=35.0 degrees C). Neurological outcome after six months was assessed by means of the Glasgow Outcome Score (GOS), with GOS 1 to 3 defined as unfavorable and GOS 4 to 5 as favorable. A logistic regression model was used to analyze the influence of the different parameters on neurological outcome. The data of 105 consecutive patients resuscitated for primary cardiac arrest and treated with induced mild hypothermia were analyzed. Median ICU admission temperature was 35.1 degrees C (interquartile range (IQR) 34.3 to 35.7). After six months, 61% of the patients had an unfavorable outcome (59% died and 2% were severely disabled), whereas 39% had a favorable outcome (moderate disability or good recovery). Among patients with spontaneous hypothermia on ICU admission, the percentage with unfavorable outcome was higher (69% versus 50%, P = 0.05). Logistic regression showed that age, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores and spontaneous hypothermia on ICU admission all had an increased odds ratio (OR) for an unfavorable outcome after six months. Spontaneous hypothermia had the strongest association with unfavorable outcome (OR 2.6, 95% CI (confidence interval) 1.1 to 5.9), which became even stronger after adjustment for age, presenting heart rhythm, APACHE II and SOFA scores (OR 3.8, CI 1.3 to 11.0). In this observational cohort study, spontaneous hypothermia on ICU admission was the strongest predictor of an unfavorable neurological outcome in patients resuscitated for primary cardiac arrest.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort.

PubMed

Lam, Raymond W; Milev, Roumen; Rotzinger, Susan; Andreazza, Ana C; Blier, Pierre; Brenner, Colleen; Daskalakis, Zafiris J; Dharsee, Moyez; Downar, Jonathan; Evans, Kenneth R; Farzan, Faranak; Foster, Jane A; Frey, Benicio N; Geraci, Joseph; Giacobbe, Peter; Feilotter, Harriet E; Hall, Geoffrey B; Harkness, Kate L; Hassel, Stefanie; Ismail, Zahinoor; Leri, Francesco; Liotti, Mario; MacQueen, Glenda M; McAndrews, Mary Pat; Minuzzi, Luciano; Müller, Daniel J; Parikh, Sagar V; Placenza, Franca M; Quilty, Lena C; Ravindran, Arun V; Salomons, Tim V; Soares, Claudio N; Strother, Stephen C; Turecki, Gustavo; Vaccarino, Anthony L; Vila-Rodriguez, Fidel; Kennedy, Sidney H

2016-04-16

Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. ClinicalTrials.gov identifier NCT01655706 . Registered July 27, 2012.

Sequential memory: Binding dynamics

NASA Astrophysics Data System (ADS)

Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

2015-10-01

Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

Characteristics of sequential targeting of brain glioma for transferrin-modified cisplatin liposome.

PubMed

Lv, Qing; Li, Li-Min; Han, Min; Tang, Xin-Jiang; Yao, Jin-Na; Ying, Xiao-Ying; Li, Fan-Zhu; Gao, Jian-Qing

2013-02-28

Methods on how to improve the sequential targeting of glioma subsequent to passing of drug through the blood-brain barrier (BBB) have been occasionally reported. However, the characteristics involved are poorly understood. In the present study, cisplatin (Cis) liposome (lipo) was modified with transferrin (Tf) to investigate the characteristics of potential sequential targeting to glioma. In bEnd3/C6 co-culture BBB models, higher transport efficiency across the BBB and cytotoxicity in basal C6 cells induced by Cis-lipo(Tf) than Cis-lipo and Cis-solution, suggest its sequential targeting effect. Interestingly, similar liposomal morphology as that of donor compartment was first demonstrated in the receptor solution of BBB models. Meanwhile, a greater acquisition in the lysosome of bEnd3, distributed sequentially into the nucleus of C6 cells were found for the Cis-lipo(Tf). Pre-incubation of chlorpromazine and Tf inhibited this process, indicating that a clathrin-dependent endocytosis is involved in the transport of Cis-lipo(Tf) across the BBB. Copyright © 2013 Elsevier B.V. All rights reserved.

A sampling and classification item selection approach with content balancing.

PubMed

Chen, Pei-Hua

2015-03-01

Existing automated test assembly methods typically employ constrained combinatorial optimization. Constructing forms sequentially based on an optimization approach usually results in unparallel forms and requires heuristic modifications. Methods based on a random search approach have the major advantage of producing parallel forms sequentially without further adjustment. This study incorporated a flexible content-balancing element into the statistical perspective item selection method of the cell-only method (Chen et al. in Educational and Psychological Measurement, 72(6), 933-953, 2012). The new method was compared with a sequential interitem distance weighted deviation model (IID WDM) (Swanson & Stocking in Applied Psychological Measurement, 17(2), 151-166, 1993), a simultaneous IID WDM, and a big-shadow-test mixed integer programming (BST MIP) method to construct multiple parallel forms based on matching a reference form item-by-item. The results showed that the cell-only method with content balancing and the sequential and simultaneous versions of IID WDM yielded results comparable to those obtained using the BST MIP method. The cell-only method with content balancing is computationally less intensive than the sequential and simultaneous versions of IID WDM.

Enhancing the performance of tungsten doped InZnO thin film transistors via sequential ambient annealing

NASA Astrophysics Data System (ADS)

Park, Hyun-Woo; Song, Aeran; Kwon, Sera; Choi, Dukhyun; Kim, Younghak; Jun, Byung-Hyuk; Kim, Han-Ki; Chung, Kwun-Bum

2018-03-01

This study suggests a sequential ambient annealing process as an excellent post-treatment method to enhance the device performance and stability of W (tungsten) doped InZnO thin film transistors (WIZO-TFTs). Sequential ambient annealing at 250 °C significantly enhanced the device performance and stability of WIZO-TFTs, compared with other post-treatment methods, such as air ambient annealing and vacuum ambient annealing at 250 °C. To understand the enhanced device performance and stability of WIZO-TFT with sequential ambient annealing, we investigate the correlations between device performance and stability and electronic structures, such as band alignment, a feature of the conduction band, and band edge states below the conduction band. The enhanced performance of WIZO-TFTs with sequential ambient annealing is related to the modification of the electronic structure. In addition, the dominant mechanism responsible for the enhanced device performance and stability of WIZO-TFTs is considered to be a change in the shallow-level and deep-level band edge states below the conduction band.

Sequential (as Opposed to Simultaneous) Antibiotic Therapy Improves Helicobacter pylori Eradication in the Pediatric Population: A Meta-Analysis.

PubMed

Lau, Christine S M; Ward, Amanda; Chamberlain, Ronald S

2016-06-01

Helicobacter pylori is a common infection associated with many gastrointestinal diseases. Triple or quadruple therapy is the current recommendation for H pylori eradication in children but is associated with success rates as low as 50%. Recent studies have demonstrated that a 10-day sequential therapy regimen, rather than simultaneous antibiotic administration, achieved eradication rates of nearly 95%. This meta-analysis found that sequential therapy increased eradication rates by 14.2% (relative risk [RR] = 1.142; 95% confidence interval [CI] = 1.082-1.207; P < .001). Ten-day sequential therapy significantly improved H pylori eradication rates compared to the 7-day standard therapy (RR = 1.182; 95% CI = 1.102-1.269; p < .001) and 10-day standard therapy (RR = 1.179; 95% CI = 1.074-1.295; P = .001), but had lower eradication rates compared to 14-day standard therapy (RR = 0.926; 95% CI = 0.811-1.059; P = .261). The use of sequential therapy is associated with increased H pylori eradication rates in children compared to standard therapy of equal or shorter duration. © The Author(s) 2015.

Sequential memory: Binding dynamics.

PubMed

Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

2015-10-01

Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories-episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

Three-dimensional mapping of equiprobable hydrostratigraphic units at the Frenchman Flat Corrective Action Unit, Nevada Test Site

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

Shirley, C.; Pohlmann, K.; Andricevic, R.

1996-09-01

Geological and geophysical data are used with the sequential indicator simulation algorithm of Gomez-Hernandez and Srivastava to produce multiple, equiprobable, three-dimensional maps of informal hydrostratigraphic units at the Frenchman Flat Corrective Action Unit, Nevada Test Site. The upper 50 percent of the Tertiary volcanic lithostratigraphic column comprises the study volume. Semivariograms are modeled from indicator-transformed geophysical tool signals. Each equiprobable study volume is subdivided into discrete classes using the ISIM3D implementation of the sequential indicator simulation algorithm. Hydraulic conductivity is assigned within each class using the sequential Gaussian simulation method of Deutsch and Journel. The resulting maps show the contiguitymore » of high and low hydraulic conductivity regions.« less

Sequential Syndrome Decoding of Convolutional Codes

NASA Technical Reports Server (NTRS)

Reed, I. S.; Truong, T. K.

1984-01-01

The algebraic structure of convolutional codes are reviewed and sequential syndrome decoding is applied to those codes. These concepts are then used to realize by example actual sequential decoding, using the stack algorithm. The Fano metric for use in sequential decoding is modified so that it can be utilized to sequentially find the minimum weight error sequence.

Sequential two-photon double ionization of noble gases by circularly polarized XUV radiation

NASA Astrophysics Data System (ADS)

Gryzlova, E. V.; Grum-Grzhimailo, A. N.; Kuzmina, E. I.; Strakhova, S. I.

2014-10-01

Photoelectron angular distributions (PADs) and angular correlations between two emitted electrons in sequential two-photon double ionization (2PDI) of atoms by circularly polarized radiation are studied theoretically. In particular, the sequential 2PDI of the valence n{{p}6} shell in noble gas atoms (neon, argon, krypton) is analyzed, accounting for the first-order corrections to the dipole approximation. Due to different selection rules in ionization transitions, the circular polarization of photons causes some new features of the cross sections, PADs and angular correlation functions in comparison with the case of linearly polarized photons.

Comparing multiple imputation methods for systematically missing subject-level data.

PubMed

Kline, David; Andridge, Rebecca; Kaizar, Eloise

2017-06-01

When conducting research synthesis, the collection of studies that will be combined often do not measure the same set of variables, which creates missing data. When the studies to combine are longitudinal, missing data can occur on the observation-level (time-varying) or the subject-level (non-time-varying). Traditionally, the focus of missing data methods for longitudinal data has been on missing observation-level variables. In this paper, we focus on missing subject-level variables and compare two multiple imputation approaches: a joint modeling approach and a sequential conditional modeling approach. We find the joint modeling approach to be preferable to the sequential conditional approach, except when the covariance structure of the repeated outcome for each individual has homogenous variance and exchangeable correlation. Specifically, the regression coefficient estimates from an analysis incorporating imputed values based on the sequential conditional method are attenuated and less efficient than those from the joint method. Remarkably, the estimates from the sequential conditional method are often less efficient than a complete case analysis, which, in the context of research synthesis, implies that we lose efficiency by combining studies. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Sequential roles of primary somatosensory cortex and posterior parietal cortex in tactile-visual cross-modal working memory: a single-pulse transcranial magnetic stimulation (spTMS) study.

PubMed

Ku, Yixuan; Zhao, Di; Hao, Ning; Hu, Yi; Bodner, Mark; Zhou, Yong-Di

2015-01-01

Both monkey neurophysiological and human EEG studies have shown that association cortices, as well as primary sensory cortical areas, play an essential role in sequential neural processes underlying cross-modal working memory. The present study aims to further examine causal and sequential roles of the primary sensory cortex and association cortex in cross-modal working memory. Individual MRI-based single-pulse transcranial magnetic stimulation (spTMS) was applied to bilateral primary somatosensory cortices (SI) and the contralateral posterior parietal cortex (PPC), while participants were performing a tactile-visual cross-modal delayed matching-to-sample task. Time points of spTMS were 300 ms, 600 ms, 900 ms after the onset of the tactile sample stimulus in the task. The accuracy of task performance and reaction time were significantly impaired when spTMS was applied to the contralateral SI at 300 ms. Significant impairment on performance accuracy was also observed when the contralateral PPC was stimulated at 600 ms. SI and PPC play sequential and distinct roles in neural processes of cross-modal associations and working memory. Copyright © 2015 Elsevier Inc. All rights reserved.

A prospective group sequential study evaluating a new type of fully covered self-expandable metal stent for the treatment of benign biliary strictures (with video).

PubMed

Poley, Jan-Werner; Cahen, Djuna L; Metselaar, Herold J; van Buuren, Henk R; Kazemier, Geert; van Eijck, Casper H J; Haringsma, Jelle; Kuipers, Ernst J; Bruno, Marco J

2012-04-01

Fully-covered self expandable metal stents (fcSEMSs) are an alternative to progressive plastic stenting for the treatment of benign biliary strictures (BBS) with the prospect of a higher treatment efficacy and the need for fewer ERCPs, thereby reducing the burden for patients and possibly costs. Key to this novel treatment is safe stent removal. To investigate the feasibility and safety of stent removal of a fcSEMS with a proximal retrieval lasso: a long wire thread integrated in the proximal ends of the wire mesh that hangs freely in the stent lumen. Pulling it enables gradual removal of the stent inside-out. A secondary aim was success of stricture resolution. Non-randomized, prospective follow-up study with 3 sequential cohorts of 8 patients with BBS. Academic tertiary referral center. Eligible patients had strictures either postsurgical (post-cholecystectomy (LCx) or liver transplantation (OLT)), due to chronic pancreatitis (CP), or papillary stenosis (PF). Strictures had to be located at least 2 cm below the liver hilum. All patients had one plastic stent in situ across the stricture and had not undergone previous treatment with either multiple plastic stents or fcSEMS. The first cohort of patients underwent stent placement for 2 months, followed by 3 months if the stricture had not resolved. The second and third cohort started with 3 months and 4 months, respectively, both followed by another 4 months if indicated. Treatment success was defined by stricture resolution at cholangiography, the ability to pass an inflated extraction balloon and clinical follow-up (at least 6 months). safety of stent removal. Secondary outcomes were complications and successful stricture resolution. A total of 23 patients (11 female; 20-67 yrs) were eligible for final analysis. One patient developed a malignant neuroendocrine tumor in the setting of CP. Strictures were caused by CP (13), OLT (6), LCx (3) and PF (1). In total 39 fcSEMS were placed and removed. Removals were easy and without complications. Transient pain after insertion was common (13 of 23/56%) but was easily managed by analgesics in all patients. Other complications were cholecystitis (1), cholangitis due to stent migration (1, stent replaced) or stent clogging (2, managed endoscopically) and worsening of CP (2). In these patients, the fcSEMS was removed and replaced after pancreatic sphincterotomy and PD stent placement. Median follow-up was 15 months (range 11-25). Overall treatment success was 61% (14/23); in the CP group 46%, in the remaining patients 80% (p = 0.11). Patients with stricture resolution after removal of the first stent (n = 7; success 6/7) showed a trent towards a more sustained treatment success than patients who needed a 2nd stent placement (n = 16; success 8/16); p = 0.12). Small number of patients with regard to secondary outcomes. Removal of a new type of fcSEMS with a proximal retrieval lasso in patients with BBS proved easy and uncomplicated. Treatment success for CP strictures was higher compared to what is known from results of progressive plastic stenting protocols. For other indications treatment success was comparable to progressive plastic stenting, but with the prospect of fewer ERCP procedures. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

The In-Session and Long-Term Role of a Significant Other in Motivational Enhancement Therapy for Alcohol Use Disorders

PubMed Central

Bourke, Emilie; Magill, Molly; Apodaca, Timothy R.

2016-01-01

Objective To examine how significant other (SO) language in support of or against client abstinence from alcohol influences clients’ in-session speech and drinking behavior over the 9 months post-Motivational Enhancement Therapy (MET). Method Sequential analyses were used to examine the language of Project MATCH clients who invited an SO to participate in an MET session. Hierarchical regressions investigated the predictive relationship between SO language and clients’ post-treatment drinking behavior. A cohort analytic design compared the change language of these SO-involved participants against a matched group who chose client-only therapy. Results 'SO Support Change' language increased the odds of client Change Talk in the next utterance (p < .01). SO Support Change did not significantly predict reduced post-treatment drinking whereas 'SO Against Change' significantly predicted an increase in average drinks per drinking day (DDD) across months 7-9 post-MET (p = .04). In the matched comparison, the proportion of change-related client language was comparable across the SO-involved and client-only groups. Conclusions Motivational interviewing theory was supported by the sequential association between SO and client language as well as the predictive link between SO Against Change and client drinking intensity. Given the centrality of pro-sobriety language in the literature, it was surprising that SO Support Change did not predict alcohol use outcomes. Findings are discussed in relation to contemporary treatment process research and clinical practice. PMID:26951920

Asymmetric inner wedge group sequential tests with applications to verifying whether effective drug concentrations are similar in adults and children.

PubMed

Hampson, Lisa V; Fisch, Roland; Van, Linh M; Jaki, Thomas

2017-02-10

Extrapolating from information available on one patient group to support conclusions about another is common in clinical research. For example, the findings of clinical trials, often conducted in highly selective patient cohorts, are routinely extrapolated to wider populations by policy makers. Meanwhile, the results of adult trials may be used to support conclusions about the effects of a medicine in children. For example, if the effective concentration of a drug can be assumed to be similar in adults and children, an appropriate paediatric dosing rule may be found by 'bridging', that is, by matching the adult effective concentration. However, this strategy may result in children receiving an ineffective or hazardous dose if, in fact, effective concentrations differ between adults and children. When there is uncertainty about the equality of effective concentrations, some pharmacokinetic-pharmacodynamic data may be needed in children to verify that differences are small. In this paper, we derive optimal group sequential tests that can be used to verify this assumption efficiently. Asymmetric inner wedge tests are constructed that permit early stopping to accept or reject an assumption of similar effective drug concentrations in adults and children. Asymmetry arises because the consequences of under- and over-dosing may differ. We show how confidence intervals can be obtained on termination of these tests and illustrate the small sample operating characteristics of designs using simulation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Obstacles for the Teaching of 8th Grade TR History of Revolution and Kemalism Course According to the Constructivist Approach (An Example of Exploratory Sequential Mixed Method Design)

ERIC Educational Resources Information Center

Karademir, Yavuz; Demir, Selcuk Besir

2015-01-01

The aim of this study is to ascertain the problems social studies teachers face in the teaching of topics covered in 8th grade TRHRK Course. The study was conducted in line with explanatory sequential mixed method design, which is one of the mixed research method, was used. The study involves three phases. In the first step, exploratory process…

Delay test generation for synchronous sequential circuits

NASA Astrophysics Data System (ADS)

Devadas, Srinivas

1989-05-01

We address the problem of generating tests for delay faults in non-scan synchronous sequential circuits. Delay test generation for sequential circuits is a considerably more difficult problem than delay testing of combinational circuits and has received much less attention. In this paper, we present a method for generating test sequences to detect delay faults in sequential circuits using the stuck-at fault sequential test generator STALLION. The method is complete in that it will generate a delay test sequence for a targeted fault given sufficient CPU time, if such a sequence exists. We term faults for which no delay test sequence exists, under out test methodology, sequentially delay redundant. We describe means of eliminating sequential delay redundancies in logic circuits. We present a partial-scan methodology for enhancing the testability of difficult-to-test of untestable sequential circuits, wherein a small number of flip-flops are selected and made controllable/observable. The selection process guarantees the elimination of all sequential delay redundancies. We show that an intimate relationship exists between state assignment and delay testability of a sequential machine. We describe a state assignment algorithm for the synthesis of sequential machines with maximal delay fault testability. Preliminary experimental results using the test generation, partial-scan and synthesis algorithm are presented.

Parallelization of sequential Gaussian, indicator and direct simulation algorithms

NASA Astrophysics Data System (ADS)

Nunes, Ruben; Almeida, José A.

2010-08-01

Improving the performance and robustness of algorithms on new high-performance parallel computing architectures is a key issue in efficiently performing 2D and 3D studies with large amount of data. In geostatistics, sequential simulation algorithms are good candidates for parallelization. When compared with other computational applications in geosciences (such as fluid flow simulators), sequential simulation software is not extremely computationally intensive, but parallelization can make it more efficient and creates alternatives for its integration in inverse modelling approaches. This paper describes the implementation and benchmarking of a parallel version of the three classic sequential simulation algorithms: direct sequential simulation (DSS), sequential indicator simulation (SIS) and sequential Gaussian simulation (SGS). For this purpose, the source used was GSLIB, but the entire code was extensively modified to take into account the parallelization approach and was also rewritten in the C programming language. The paper also explains in detail the parallelization strategy and the main modifications. Regarding the integration of secondary information, the DSS algorithm is able to perform simple kriging with local means, kriging with an external drift and collocated cokriging with both local and global correlations. SIS includes a local correction of probabilities. Finally, a brief comparison is presented of simulation results using one, two and four processors. All performance tests were carried out on 2D soil data samples. The source code is completely open source and easy to read. It should be noted that the code is only fully compatible with Microsoft Visual C and should be adapted for other systems/compilers.

The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java.

PubMed

Kosasih, Herman; Alisjahbana, Bachti; Nurhayati; de Mast, Quirijn; Rudiman, Irani F; Widjaja, Susana; Antonjaya, Ungke; Novriani, Harli; Susanto, Nugroho H; Jusuf, Hadi; van der Ven, Andre; Beckett, Charmagne G; Blair, Patrick J; Burgess, Timothy H; Williams, Maya; Porter, Kevin R

2016-02-01

Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology of dengue in a given area is critical to understanding the disease and devising effective public health strategies. Here, we report the results from a prospective cohort study of 4380 adults in West Java, Indonesia, from 2000-2004 and 2006-2009. A total of 2167 febrile episodes were documented and dengue virus infections were confirmed by RT-PCR or serology in 268 cases (12.4%). The proportion ranged from 7.6 to 41.8% each year. The overall incidence rate of symptomatic dengue virus infections was 17.3 cases/1,000 person years and between September 2006 and April 2008 asymptomatic infections were 2.6 times more frequent than symptomatic infections. According to the 1997 WHO classification guidelines, there were 210 dengue fever cases, 53 dengue hemorrhagic fever cases (including one dengue shock syndrome case) and five unclassified cases. Evidence for sequential dengue virus infections was seen in six subjects. All four dengue virus serotypes circulated most years. Inapparent dengue virus infections were predominantly associated with DENV-4 infections. Dengue virus was responsible for a significant percentage of febrile illnesses in an adult population in West Java, Indonesia, and this percentage varied from year to year. The observed incidence rate during the study period was 43 times higher than the reported national or provincial rates during the same time period. A wide range of clinical severity was observed with most infections resulting in asymptomatic disease. The circulation of all four serotypes of dengue virus was observed in most years of the study.

The role of life-course socioeconomic and lifestyle factors in the intergenerational transmission of the metabolic syndrome: results from the LifeLines Cohort Study.

PubMed

Klijs, Bart; Angelini, Viola; Mierau, Jochen O; Smidt, Nynke

2016-08-01

The risk of metabolic syndrome is associated between parents and offspring, but studies are inconsistent on differences by sex of parents and offspring. Our aim is to investigate to what extent metabolic syndrome present in fathers and mothers is associated with risk of metabolic syndrome in sons and daughters. Furthermore, we investigate to what extent these associations are explained by socioeconomic factors and health behaviours. We used data from the LifeLines Cohort Study (N = 7239). Metabolic syndrome was defined according to the NCEP-ATPIII criteria. Logistic regression analyses were performed to investigate associations of metabolic syndrome present in parents with the risk of metabolic syndrome in offspring. Analyses were sequentially adjusted for: age and sex; childhood factors (socioeconomic position and parental smoking); and adult factors (education, income, smoking, physical activity, alcohol intake, and dietary factors). Multivariate regression analysis adjusted for age and sex showed associations of the metabolic syndrome between father-son: odds ratio (OR) [95% confidence interval (CI)] 2.41 (1.93-3.00), father-daughter: OR (95% CI) 1.80 (1.39-2.33)), mother-son: OR (95% CI) 1.82 (1.44-2.29) and mother-daughter: OR (95% CI) 1.97 (1.52-2.55). Furthermore, each individual factor underlying the metabolic syndrome in parents was associated with metabolic syndrome in offspring, but not for all parent-offspring combinations. None of the parent-offspring associations was attenuated when adjusting for socioeconomic factors and health behaviours. High risk of metabolic syndrome is transmitted from fathers and mothers to sons and daughters. Our results suggest that this transmission is irrespective of the socioeconomic position and health behaviours of the offspring. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Random sequential adsorption of cubes

NASA Astrophysics Data System (ADS)

Cieśla, Michał; Kubala, Piotr

2018-01-01

Random packings built of cubes are studied numerically using a random sequential adsorption algorithm. To compare the obtained results with previous reports, three different models of cube orientation sampling were used. Also, three different cube-cube intersection algorithms were tested to find the most efficient one. The study focuses on the mean saturated packing fraction as well as kinetics of packing growth. Microstructural properties of packings were analyzed using density autocorrelation function.

A Comparison of Right Unilateral and Sequential Bilateral Repetitive Transcranial Magnetic Stimulation for Major Depression: A Naturalistic Clinical Australian Study.

PubMed

Galletly, Cherrie A; Carnell, Benjamin L; Clarke, Patrick; Gill, Shane

2017-03-01

A great deal of research has established the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. However, questions remain about the optimal method to deliver treatment. One area requiring consideration is the difference in efficacy between bilateral and unilateral treatment protocols. This study aimed to compare the effectiveness of sequential bilateral rTMS and right unilateral rTMS. A total of 135 patients participated in the study, receiving either bilateral rTMS (N = 57) or right unilateral rTMS (N = 78). Treatment response was assessed using the Hamilton depression rating scale. Sequential bilateral rTMS had a higher response rate than right unilateral (43.9% vs 30.8%), but this difference was not statistically significant. This was also the case for remission rates (33.3% vs 21.8%, respectively). Controlling for pretreatment severity of depression, the results did not indicate a significant difference between the protocols with regard to posttreatment Hamilton depression rating scale scores. The current study found no statistically significant differences in response and remission rates between sequential bilateral rTMS and right unilateral rTMS. Given the shorter treatment time and the greater safety and tolerability of right unilateral rTMS, this may be a better choice than bilateral treatment in clinical settings.

Comparison of human embryomorphokinetic parameters in sequential or global culture media.

PubMed

Kazdar, Nadia; Brugnon, Florence; Bouche, Cyril; Jouve, Guilhem; Veau, Ségolène; Drapier, Hortense; Rousseau, Chloé; Pimentel, Céline; Viard, Patricia; Belaud-Rotureau, Marc-Antoine; Ravel, Célia

2017-08-01

A prospective study on randomized patients was conducted to determine how morphokinetic parameters are altered in embryos grown in sequential versus global culture media. Eleven morphokinetic parameters of 160 single embryos transferred were analyzed by time lapse imaging involving two University-affiliated in vitro fertilization (IVF) centers. We found that the fading of the two pronuclei occurred earlier in global (22.56±2.15 hpi) versus sequential media (23.63±2.71 hpi; p=0.0297). Likewise, the first cleavage started earlier at 24.52±2.33 hpi vs 25.76±2.95 hpi (p=0.0158). Also, the first cytokinesis was shorter in global medium, lasting 18±10.2 minutes in global versus 36±37.8 minutes in sequential culture medium (p <0.0001). We also observed a significant shortening in the duration of the 2-cell stage in sequential medium: 10.64 h±2.75 versus 11.66 h±1.11 in global medium (p=0.0225) which suggested a faster progression of the embryos through their first mitotic cell cycle. In conclusion, morphokinetic analysis of human embryos by Time lapse imaging reveals significant differences in five kinetic variables according to culture medium. Our study highlights the need to adapt morphokinetic analysis accordingly to the type of media used to best support human early embryo development.

Glycerol production by Oenococcus oeni during sequential and simultaneous cultures with wine yeast strains.

PubMed

Ale, Cesar E; Farías, Marta E; Strasser de Saad, Ana M; Pasteris, Sergio E

2014-07-01

Growth and fermentation patterns of Saccharomyces cerevisiae, Kloeckera apiculata, and Oenococcus oeni strains cultured in grape juice medium were studied. In pure, sequential and simultaneous cultures, the strains reached the stationary growth phase between 2 and 3 days. Pure and mixed K. apiculata and S. cerevisiae cultures used mainly glucose, producing ethanol, organic acids, and 4.0 and 0.1 mM glycerol, respectively. In sequential cultures, O. oeni achieved about 1 log unit at 3 days using mainly fructose and L-malic acid. Highest sugars consumption was detected in K. apiculata supernatants, lactic acid being the major end-product. 8.0 mM glycerol was found in 6-day culture supernatants. In simultaneous cultures, total sugars and L-malic acid were used at 3 days and 98% of ethanol and glycerol were detected. This study represents the first report of the population dynamics and metabolic behavior of yeasts and O. oeni in sequential and simultaneous cultures and contributes to the selection of indigenous strains to design starter cultures for winemaking, also considering the inclusion of K. apiculata. The sequential inoculation of yeasts and O. oeni would enhance glycerol production, which confers desirable organoleptic characteristics to wines, while organic acids levels would not affect their sensory profile. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bursts and heavy tails in temporal and sequential dynamics of foraging decisions.

PubMed

Jung, Kanghoon; Jang, Hyeran; Kralik, Jerald D; Jeong, Jaeseung

2014-08-01

A fundamental understanding of behavior requires predicting when and what an individual will choose. However, the actual temporal and sequential dynamics of successive choices made among multiple alternatives remain unclear. In the current study, we tested the hypothesis that there is a general bursting property in both the timing and sequential patterns of foraging decisions. We conducted a foraging experiment in which rats chose among four different foods over a continuous two-week time period. Regarding when choices were made, we found bursts of rapidly occurring actions, separated by time-varying inactive periods, partially based on a circadian rhythm. Regarding what was chosen, we found sequential dynamics in affective choices characterized by two key features: (a) a highly biased choice distribution; and (b) preferential attachment, in which the animals were more likely to choose what they had previously chosen. To capture the temporal dynamics, we propose a dual-state model consisting of active and inactive states. We also introduce a satiation-attainment process for bursty activity, and a non-homogeneous Poisson process for longer inactivity between bursts. For the sequential dynamics, we propose a dual-control model consisting of goal-directed and habit systems, based on outcome valuation and choice history, respectively. This study provides insights into how the bursty nature of behavior emerges from the interaction of different underlying systems, leading to heavy tails in the distribution of behavior over time and choices.

A Sequential Analysis of Parent-Child Interactions in Anxious and Nonanxious Families

ERIC Educational Resources Information Center

Williams, Sarah R.; Kertz, Sarah J.; Schrock, Matthew D.; Woodruff-Borden, Janet

2012-01-01

Although theoretical work has suggested that reciprocal behavior patterns between parent and child may be important in the development of childhood anxiety, most empirical work has failed to consider the bidirectional nature of interactions. The current study sought to address this limitation by utilizing a sequential approach to exploring…

Discovering Visual Scanning Patterns in a Computerized Cancellation Test

ERIC Educational Resources Information Center

Huang, Ho-Chuan; Wang, Tsui-Ying

2013-01-01

The purpose of this study was to develop an attention sequential mining mechanism for investigating the sequential patterns of children's visual scanning process in a computerized cancellation test. Participants had to locate and cancel the target amongst other non-targets in a structured form, and a random form with Chinese stimuli. Twenty-three…

Two Tales of Time: Uncovering the Significance of Sequential Patterns among Contribution Types in Knowledge-Building Discourse

ERIC Educational Resources Information Center

Chen, Bodong; Resendes, Monica; Chai, Ching Sing; Hong, Huang-Yao

2017-01-01

As collaborative learning is actualized through evolving dialogues, temporality inevitably matters for the analysis of collaborative learning. This study attempts to uncover sequential patterns that distinguish "productive" threads of knowledge-building discourse. A database of Grade 1-6 knowledge-building discourse was first coded for…

(Pea)nuts and Bolts of Visual Narrative: Structure and Meaning in Sequential Image Comprehension

ERIC Educational Resources Information Center

Cohn, Neil; Paczynski, Martin; Jackendoff, Ray; Holcomb, Phillip J.; Kuperberg, Gina R.

2012-01-01

Just as syntax differentiates coherent sentences from scrambled word strings, the comprehension of sequential images must also use a cognitive system to distinguish coherent narrative sequences from random strings of images. We conducted experiments analogous to two classic studies of language processing to examine the contributions of narrative…

Spatial-Sequential and Spatial-Simultaneous Working Memory in Individuals with Williams Syndrome

ERIC Educational Resources Information Center

Lanfranchi, Silvia; De Mori, Letizia; Mammarella, Irene C.; Carretti, Barbara; Vianello, Renzo

2015-01-01

The aim of the present study was to compare visuospatial working memory performance in 18 individuals with Williams syndrome (WS) and 18 typically developing (TD) children matched for nonverbal mental age. Two aspects were considered: task presentation format (i.e., spatial-sequential or spatial-simultaneous), and level of attentional control…

Sequential Pharmacotherapy for Children with Comorbid Attention-Deficit/hyperactivity and Anxiety Disorders.

ERIC Educational Resources Information Center

Abikoff, Howard; McGough, James; Vitiello, Benedetto; McCracken, James; Davies, Mark; Walkup, John; Riddle, Mark; Oatis, Melvin; Greenhill, Laurence; Skrobala, Anne; March, John; Gammon, Pat; Robinson, James; Lazell, Robert; McMahon, Donald J.; Ritz, Louise

2005-01-01

Objective: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by clinically significant anxiety, but few empirical data guide treatment of children meeting full DSM-IV criteria for ADHD and anxiety disorders (ADHD/ANX). This study examined the efficacy of sequential pharmacotherapy for ADHD/ANX children. Method: Children, age 6…

Effect of Same-day Sequential Exposure to Nitrogen Dioxide and Ozone on Cardiac and Ventilatory Function in Mice

EPA Science Inventory

This study examines the cardiac and ventilatory effects of sequential exposure to nitrogen dioxide and then ozone. The data show that mice exposed to both gases have increased arrhythmia and breathing changes not observed in the other groups. Although the mechanisms underlying ai...

Poor Performance on Serial Visual Tasks in Persons with Reading Disabilities: Impaired Working Memory?

ERIC Educational Resources Information Center

Ram-Tsur, Ronit; Faust, Miriam; Zivotofsky, Ari Z.

2008-01-01

The present study investigates the performance of persons with reading disabilities (PRD) on a variety of sequential visual-comparison tasks that have different working-memory requirements. In addition, mediating relationships between the sequential comparison process and attention and memory skills were looked for. Our findings suggest that PRD…

Krebs cycle metabolon formation: metabolite concentration gradient enhanced compartmentation of sequential enzymes.

PubMed

Wu, Fei; Pelster, Lindsey N; Minteer, Shelley D

2015-01-25

Dynamics of metabolon formation in mitochondria was probed by studying diffusional motion of two sequential Krebs cycle enzymes in a microfluidic channel. Enhanced directional co-diffusion of both enzymes against a substrate concentration gradient was observed in the presence of intermediate generation. This reveals a metabolite directed compartmentation of metabolic pathways.

Proportion Congruent Effects in the Absence of Sequential Congruent Effects

ERIC Educational Resources Information Center

Torres-Quesada, Maryem; Milliken, Bruce; Lupiáñez, Juan; Funes, María Jesús

2014-01-01

A debated question in the cognitive control field is whether cognitive control is best conceptualized as a collection of distinct control mechanisms or a single general purpose mechanism. In an attempt to answer this question, previous studies have dissociated two well-known effects related to cognitive control: sequential congruence and…

Judgments Relative to Patterns: How Temporal Sequence Patterns Affect Judgments and Memory

ERIC Educational Resources Information Center

Kusev, Petko; Ayton, Peter; van Schaik, Paul; Tsaneva-Atanasova, Krasimira; Stewart, Neil; Chater, Nick

2011-01-01

RESix experiments studied relative frequency judgment and recall of sequentially presented items drawn from 2 distinct categories (i.e., city and animal). The experiments show that judged frequencies of categories of sequentially encountered stimuli are affected by certain properties of the sequence configuration. We found (a) a "first-run…

Associations among measures of sequential processing in motor and linguistics tasks in adults with and without a family history of childhood apraxia of speech: a replication study.

PubMed

Button, Le; Peter, Beate; Stoel-Gammon, Carol; Raskind, Wendy H

2013-03-01

The purpose of this study was to address the hypothesis that childhood apraxia of speech (CAS) is influenced by an underlying deficit in sequential processing that is also expressed in other modalities. In a sample of 21 adults from five multigenerational families, 11 with histories of various familial speech sound disorders, 3 biologically related adults from a family with familial CAS showed motor sequencing deficits in an alternating motor speech task. Compared with the other adults, these three participants showed deficits in tasks requiring high loads of sequential processing, including nonword imitation, nonword reading and spelling. Qualitative error analyses in real word and nonword imitations revealed group differences in phoneme sequencing errors. Motor sequencing ability was correlated with phoneme sequencing errors during real word and nonword imitation, reading and spelling. Correlations were characterized by extremely high scores in one family and extremely low scores in another. Results are consistent with a central deficit in sequential processing in CAS of familial origin.

Sequential bilateral cochlear implantation improves working performance, quality of life, and quality of hearing.

PubMed

Härkönen, Kati; Kivekäs, Ilkka; Rautiainen, Markus; Kotti, Voitto; Sivonen, Ville; Vasama, Juha-Pekka

2015-05-01

This prospective study shows that working performance, quality of life (QoL), and quality of hearing (QoH) are better with two compared with a single cochlear implant (CI). The impact of the second CI on the patient's QoL is as significant as the impact of the first CI. To evaluate the benefits of sequential bilateral cochlear implantation in working, QoL, and QoH. We studied working performance, work-related stress, QoL, and QoH with specific questionnaires in 15 patients with unilateral CI scheduled for sequential CI of another ear. Sound localization performance and speech perception in noise were measured with specific tests. All questionnaires and tests were performed before the second CI surgery and 6 and 12 months after its activation. Bilateral CIs increased patients' working performance and their work-related stress and fatigue decreased. Communication with co-workers was easier and patients were more active in their working environment. Sequential bilateral cochlear implantation improved QoL, QoH, sound localization, and speech perception in noise statistically significantly.

Devaluation and sequential decisions: linking goal-directed and model-based behavior

PubMed Central

Friedel, Eva; Koch, Stefan P.; Wendt, Jean; Heinz, Andreas; Deserno, Lorenz; Schlagenhauf, Florian

2014-01-01

In experimental psychology different experiments have been developed to assess goal–directed as compared to habitual control over instrumental decisions. Similar to animal studies selective devaluation procedures have been used. More recently sequential decision-making tasks have been designed to assess the degree of goal-directed vs. habitual choice behavior in terms of an influential computational theory of model-based compared to model-free behavioral control. As recently suggested, different measurements are thought to reflect the same construct. Yet, there has been no attempt to directly assess the construct validity of these different measurements. In the present study, we used a devaluation paradigm and a sequential decision-making task to address this question of construct validity in a sample of 18 healthy male human participants. Correlational analysis revealed a positive association between model-based choices during sequential decisions and goal-directed behavior after devaluation suggesting a single framework underlying both operationalizations and speaking in favor of construct validity of both measurement approaches. Up to now, this has been merely assumed but never been directly tested in humans. PMID:25136310

[Approach to percutaneous nephrolithotomy. Comparison of the procedure in a one-shot versus the sequential with metal dilata].

PubMed

Sedano-Portillo, Ismael; Ochoa-León, Gastón; Fuentes-Orozco, Clotilde; Irusteta-Jiménez, Leire; Michel-Espinoza, Luis Rodrigo; Salazar-Parra, Marcela; Cuesta-Márquez, Lizbeth; González-Ojeda, Alejandro

2017-01-01

Percutaneous nephrolithotomy is an efficient approach for treatment of different types of kidney stones. Various types of access techniques have been described like sequential dilatation and one-shot procedure. To determine the differences in time of exposure to X-rays and hemoglobin levels between techniques. Controlled clinical trial. Patients older than 18 years with complex/uncomplicated kidney stones, without urine infection were included. They were assigned randomly to one of the two techniques. Response variables were determined before and 24 h after procedures. 59 patients were included: 30 underwent one-shot procedure (study-group) and 29 sequential dilatation (control-group). Baseline characteristics were similar. Study group had a lower postoperative hemoglobin decline than control group (0.81 vs. 2.03 g/dl, respectively; p < 0.001); X-ray exposure time (69.6 vs. 100.62 s; p < 0.001) and postoperative creatinine serum levels (0.93 ± 0.29 vs. 1.13 ± 0.4 mg/dl; p = 0.039). No significant differences in postoperative morbidity were found. One-shot technique demonstrated better results compared to sequential dilatation.

Associations among measures of sequential processing in motor and linguistics tasks in adults with and without a family history of childhood apraxia of speech: A replication study

PubMed Central

BUTTON, LE; PETER, BEATE; STOEL-GAMMON, CAROL; RASKIND, WENDY H.

2013-01-01

The purpose of this study was to address the hypothesis that childhood apraxia of speech (CAS) is influenced by an underlying deficit in sequential processing that is also expressed in other modalities. In a sample of 21 adults from five multigenerational families, 11 with histories of various familial speech sound disorders, 3 biologically related adults from a family with familial CAS showed motor sequencing deficits in an alternating motor speech task. Compared with the other adults, these three participants showed deficits in tasks requiring high loads of sequential processing, including nonword imitation, nonword reading and spelling. Qualitative error analyses in real word and nonword imitations revealed group differences in phoneme sequencing errors. Motor sequencing ability was correlated with phoneme sequencing errors during real word and nonword imitation, reading and spelling. Correlations were characterized by extremely high scores in one family and extremely low scores in another. Results are consistent with a central deficit in sequential processing in CAS of familial origin. PMID:23339292

Effect of sequential dry heat and hydrogen peroxide treatment on inactivation of Salmonella Typhimurium on alfalfa seeds and seeds germination.

PubMed

Hong, Eun-Jeong; Kang, Dong-Hyun

2016-02-01

The purpose of this study was to inactivate Salmonella Typhimurium on alfalfa seeds without having negative effect on seed germination. Inoculated alfalfa seeds were treated with dry heat at 60, 70 or 80 °C for 0, 12, 18 or 24 h followed by 2% hydrogen peroxide solution (10 min). Populations of Salmonella on alfalfa seeds treated with dry heat alone (60, 70 or 80 °C) for up to 24 h were reduced by 0.26-2.76 log CFU/g, and sequential treatment with dry heat and H2O2 reduced populations by 1.66-3.60 log CFU/g. The germination percentage of seeds subjected to sequential treatments was significantly enhanced to up to 97%, whereas that of untreated seeds was only 79.5%. This study suggests that sequential treatment with dry heat and hydrogen peroxide is applicable for reducing levels of Salmonella on seeds while simultaneously enhancing seeds germinability. Copyright © 2015. Published by Elsevier Ltd.

Nonelective surgery at night and in-hospital mortality: Prospective observational data from the European Surgical Outcomes Study.

PubMed

van Zaane, Bas; van Klei, Wilton A; Buhre, Wolfgang F; Bauer, Peter; Boerma, E Christiaan; Hoeft, Andreas; Metnitz, Philipp; Moreno, Rui P; Pearse, Rupert; Pelosi, Paolo; Sander, Michael; Vallet, Benoit; Pettilä, Ville; Vincent, Jean-Louis; Rhodes, Andrew

2015-07-01

Evidence suggests that sleep deprivation associated with night-time working may adversely affect performance resulting in a reduction in the safety of surgery and anaesthesia. Our primary objective was to evaluate an association between nonelective night-time surgery and in-hospital mortality. We hypothesised that urgent surgery performed during the night was associated with higher in-hospital mortality and also an increase in the duration of hospital stay and the number of admissions to critical care. A prospective cohort study. This is a secondary analysis of a large database related to perioperative care and outcome (European Surgical Outcome Study). Four hundred and ninety-eight hospitals in 28 European countries. Men and women older than 16 years who underwent nonelective, noncardiac surgery were included according to time of the procedure. None. Primary outcome was in-hospital mortality; the secondary outcome was the duration of hospital stay and critical care admission. Eleven thousand two hundred and ninety patients undergoing urgent surgery were included in the analysis with 636 in-hospital deaths (5.6%). Crude mortality odds ratios (ORs) increased sequentially from daytime [426 deaths (5.3%)] to evening [150 deaths (6.0%), OR 1.14; 95% confidence interval 0.94 to 1.38] to night-time [60 deaths (8.3%), OR 1.62; 95% confidence interval 1.22 to 2.14]. Following adjustment for confounding factors, surgery during the evening (OR 1.09; 95% confidence interval 0.91 to 1.31) and night (OR 1.20; 95% confidence interval 0.9 to 1.6) was not associated with an increased risk of postoperative death. Admittance rate to an ICU increased sequentially from daytime [891 (11.1%)], to evening [347 (13.8%)] to night time [149 (20.6%)]. In patients undergoing nonelective urgent noncardiac surgery, in-hospital mortality was associated with well known risk factors related to patients and surgery, but we did not identify any relationship with the time of day at which the procedure was performed. Clinicaltrials.gov identifier: NCT01203605.

Effect of a Faith-Based Education Program on Self-Assessed Physical, Mental and Spiritual (Religious) Health Parameters.

PubMed

Cronjé, Frans J; Sommers, Levenda S; Faulkner, James K; Meintjes, W A J; Van Wijk, Charles H; Turner, Robert P

2017-02-01

The aim of the study was to determine the effect of attending a faith-based education program (FBEP) on self-assessed physical, mental and spiritual health parameters. The study was designed as a prospective, observational, cohort study of individuals attending a 5-day FBEP. Out of 2650 sequential online registrants, those previously unexposed to the FBEP received automated invitations to complete 5 sequential Self-Assessment Questionnaire's (SAQ's) containing: (1) Duke University Religion Index (DUREL); (2) Negative Religious Coping (N-RCOPE); (3) Perceived Stress Scale (PSS); (4) Center for Epidemiology and Statistics-Depression Scale (CES-D); (5) Brief Illness Perception Questionnaire (BIPQ); and the (6) State Trait Anxiety Inventory (STAI). Pre-attendance SAQ (S1) was repeated immediately post-FBEP (S2), at 30 days (S3), 90 days (S4) and after 1 year (S5). Of 655 invited, 274 (42 %) succeeded, 242 (37 %) failed and 139 (21 %) declined to complete S1. Of the 274, 37 (14 %) were excluded at on-site interview; 26 (9 %) never attended the FBEP (i.e., controls: 5♂; 21♀; 27-76 years); and 211 (77 %) participated (i.e., cases: 105♂; 106♀; 18-84 years) and were analyzed over time: 211 (S1); 192 (S2); 99 (S3); 52 (S4); 51 (S5). IRB approval was via the Human Research Ethics Committee of Stellenbosch University. DUREL showed significant, sustained changes in Intrinsic Religiosity. N-RCOPE showed significant, lasting improvement. In others, median values dropped significantly immediately after the FBEP (S1:S2) for STAI-State p < 0.0001; PSS p < 0.0001; BIPQ p < 0.0001; and CES-D p < 0.0001; and at 1 month (S1:S3) for STAI-Trait p < 0.001; all changes were sustained (S3 through S5). This FBEP produced statistically and clinically significant changes; these lasted in those followed up >1 year.

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.

[Sequential degradation of p-cresol by photochemical and biological methods].

PubMed

Karetnikova, E A; Chaĭkovskaia, O N; Sokolova, I V; Nikitina, L I

2008-01-01

Sequential photo- and biodegradation of p-cresol was studied using a mercury lamp, as well as KrCl and XeCl excilamps. Preirradiation of p-cresol at a concentration of 10(-4) M did not affect the rate of its subsequent biodegradation. An increase in the concentration of p-cresol to 10(-3) M and in the duration preliminary UV irradiation inhibited subsequent biodegradation. Biodegradation of p-cresol was accompanied by the formation of a product with a fluorescence maximum at 365 nm (lambdaex 280 nm), and photodegradation yielded a compound fluorescing at 400 nm (lambdaex 330 nm). Sequential UV and biodegradation led to the appearance of bands in the fluorescence spectra that were ascribed to p-cresol and its photolysis products. It was shown that sequential use of biological and photochemical degradation results in degradation of not only the initial toxicant but also the metabolites formed during its biodegradation.

Deficits in sequential processing manifest in motor and linguistic tasks in a multigenerational family with childhood apraxia of speech

PubMed Central

PETER, BEATE; BUTTON, LE; STOEL-GAMMON, CAROL; CHAPMAN, KATHY; RASKIND, WENDY H.

2013-01-01

The purpose of this study was to evaluate a global deficit in sequential processing as candidate endophenotypein a family with familial childhood apraxia of speech (CAS). Of 10 adults and 13 children in a three-generational family with speech sound disorder (SSD) consistent with CAS, 3 adults and 6 children had past or present SSD diagnoses. Two preschoolers with unremediated CAS showed a high number of sequencing errors during single-word production. Performance on tasks with high sequential processing loads differentiated between the affected and unaffected family members, whereas there were no group differences in tasks with low processing loads. Adults with a history of SSD produced more sequencing errors during nonword and multisyllabic real word imitation, compared to those without such a history. Results are consistent with a global deficit in sequential processing that influences speech development as well as cognitive and linguistic processing. PMID:23339324

Visual short-term memory for sequential arrays.

PubMed

Kumar, Arjun; Jiang, Yuhong

2005-04-01

The capacity of visual short-term memory (VSTM) for a single visual display has been investigated in past research, but VSTM for multiple sequential arrays has been explored only recently. In this study, we investigate the capacity of VSTM across two sequential arrays separated by a variable stimulus onset asynchrony (SOA). VSTM for spatial locations (Experiment 1), colors (Experiments 2-4), orientations (Experiments 3 and 4), and conjunction of color and orientation (Experiment 4) were tested, with the SOA across the two sequential arrays varying from 100 to 1,500 msec. We find that VSTM for the trailing array is much better than VSTM for the leading array, but when averaged across the two arrays VSTM has a constant capacity independent of the SOA. We suggest that multiple displays compete for retention in VSTM and that separating information into two temporally discrete groups does not enhance the overall capacity of VSTM.

The distribution of individual cabinet positions in coalition governments: A sequential approach

PubMed Central

Meyer, Thomas M.; Müller, Wolfgang C.

2015-01-01

Abstract Multiparty government in parliamentary democracies entails bargaining over the payoffs of government participation, in particular the allocation of cabinet positions. While most of the literature deals with the numerical distribution of cabinet seats among government parties, this article explores the distribution of individual portfolios. It argues that coalition negotiations are sequential choice processes that begin with the allocation of those portfolios most important to the bargaining parties. This induces conditionality in the bargaining process as choices of individual cabinet positions are not independent of each other. Linking this sequential logic with party preferences for individual cabinet positions, the authors of the article study the allocation of individual portfolios for 146 coalition governments in Western and Central Eastern Europe. The results suggest that a sequential logic in the bargaining process results in better predictions than assuming mutual independence in the distribution of individual portfolios. PMID:27546952

An adaptive two-stage sequential design for sampling rare and clustered populations

USGS Publications Warehouse

Brown, J.A.; Salehi, M.M.; Moradi, M.; Bell, G.; Smith, D.R.

2008-01-01

How to design an efficient large-area survey continues to be an interesting question for ecologists. In sampling large areas, as is common in environmental studies, adaptive sampling can be efficient because it ensures survey effort is targeted to subareas of high interest. In two-stage sampling, higher density primary sample units are usually of more interest than lower density primary units when populations are rare and clustered. Two-stage sequential sampling has been suggested as a method for allocating second stage sample effort among primary units. Here, we suggest a modification: adaptive two-stage sequential sampling. In this method, the adaptive part of the allocation process means the design is more flexible in how much extra effort can be directed to higher-abundance primary units. We discuss how best to design an adaptive two-stage sequential sample. ?? 2008 The Society of Population Ecology and Springer.

A Process Improvement Evaluation of Sequential Compression Device Compliance and Effects of Provider Intervention.

PubMed

Beachler, Jason A; Krueger, Chad A; Johnson, Anthony E

This process improvement study sought to evaluate the compliance in orthopaedic patients with sequential compression devices and to monitor any improvement in compliance following an educational intervention. All non-intensive care unit orthopaedic primary patients were evaluated at random times and their compliance with sequential compression devices was monitored and recorded. Following a 2-week period of data collection, an educational flyer was displayed in every patient's room and nursing staff held an in-service training event focusing on the importance of sequential compression device use in the surgical patient. Patients were then monitored, again at random, and compliance was recorded. With the addition of a simple flyer and a single in-service on the importance of mechanical compression in the surgical patient, a significant improvement in compliance was documented at the authors' institution from 28% to 59% (p < .0001).

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.

Sequential capillary electrophoresis analysis using optically gated sample injection and UV/vis detection.

PubMed

Liu, Xiaoxia; Tian, Miaomiao; Camara, Mohamed Amara; Guo, Liping; Yang, Li

2015-10-01

We present sequential CE analysis of amino acids and L-asparaginase-catalyzed enzyme reaction, by combing the on-line derivatization, optically gated (OG) injection and commercial-available UV-Vis detection. Various experimental conditions for sequential OG-UV/vis CE analysis were investigated and optimized by analyzing a standard mixture of amino acids. High reproducibility of the sequential CE analysis was demonstrated with RSD values (n = 20) of 2.23, 2.57, and 0.70% for peak heights, peak areas, and migration times, respectively, and the LOD of 5.0 μM (for asparagine) and 2.0 μM (for aspartic acid) were obtained. With the application of the OG-UV/vis CE analysis, sequential online CE enzyme assay of L-asparaginase-catalyzed enzyme reaction was carried out by automatically and continuously monitoring the substrate consumption and the product formation every 12 s from the beginning to the end of the reaction. The Michaelis constants for the reaction were obtained and were found to be in good agreement with the results of traditional off-line enzyme assays. The study demonstrated the feasibility and reliability of integrating the OG injection with UV/vis detection for sequential online CE analysis, which could be of potential value for online monitoring various chemical reaction and bioprocesses. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The influence of the selection of macronutrients coupled with dietary energy density on the performance of broiler chickens.

PubMed

Liu, Sonia Y; Chrystal, Peter V; Cowieson, Aaron J; Truong, Ha H; Moss, Amy F; Selle, Peter H

2017-01-01

A total of 360 male Ross 308 broiler chickens were used in a feeding study to assess the influence of macronutrients and energy density on feed intakes from 10 to 31 days post-hatch. The study comprised ten dietary treatments from five dietary combinations and two feeding approaches: sequential and choice feeding. The study included eight experimental diets and each dietary combination was made from three experimental diets. Choice fed birds selected between three diets in separate feed trays at the same time; whereas the three diets were offered to sequentially fed birds on an alternate basis during the experimental period. There were no differences between starch and protein intakes between choice and sequentially fed birds (P > 0.05) when broiler chickens selected between diets with different starch, protein and lipid concentrations. When broiler chickens selected between diets with different starch and protein but similar lipid concentrations, both sequentially and choice fed birds selected similar ratios of starch and protein intake (P > 0.05). However, when broiler chickens selected from diets with different protein and lipid but similar starch concentrations, choice fed birds had higher lipid intake (129 versus 118 g/bird, P = 0.027) and selected diets with lower protein concentrations (258 versus 281 g/kg, P = 0.042) than birds offered sequential diet options. Choice fed birds had greater intakes of the high energy diet (1471 g/bird, P < 0.0001) than low energy (197 g/bird) or medium energy diets (663 g/bird) whilst broiler chickens were offered diets with different energy densities but high crude protein (300 g/kg) or digestible lysine (17.5 g/kg) concentrations. Choice fed birds had lower FCR (1.217 versus 1.327 g/g, P < 0.0001) and higher carcass yield (88.1 versus 87.3%, P = 0.012) than sequentially fed birds. This suggests that the dietary balance between protein and energy is essential for optimal feed conversion efficiency. The intake path of macronutrients from 10-31 days in choice and sequential feeding groups were plotted and compared with the null path if broiler chickens selected equal amounts of the three diets in the combination. Regardless of feeding regimen, the intake paths of starch and protein are very close to the null path; however, lipid and protein intake paths in choice fed birds are father from the null path than sequentially fed birds.

The influence of the selection of macronutrients coupled with dietary energy density on the performance of broiler chickens

PubMed Central

Chrystal, Peter V.; Cowieson, Aaron J.; Truong, Ha H.; Moss, Amy F.; Selle, Peter H.

2017-01-01

A total of 360 male Ross 308 broiler chickens were used in a feeding study to assess the influence of macronutrients and energy density on feed intakes from 10 to 31 days post-hatch. The study comprised ten dietary treatments from five dietary combinations and two feeding approaches: sequential and choice feeding. The study included eight experimental diets and each dietary combination was made from three experimental diets. Choice fed birds selected between three diets in separate feed trays at the same time; whereas the three diets were offered to sequentially fed birds on an alternate basis during the experimental period. There were no differences between starch and protein intakes between choice and sequentially fed birds (P > 0.05) when broiler chickens selected between diets with different starch, protein and lipid concentrations. When broiler chickens selected between diets with different starch and protein but similar lipid concentrations, both sequentially and choice fed birds selected similar ratios of starch and protein intake (P > 0.05). However, when broiler chickens selected from diets with different protein and lipid but similar starch concentrations, choice fed birds had higher lipid intake (129 versus 118 g/bird, P = 0.027) and selected diets with lower protein concentrations (258 versus 281 g/kg, P = 0.042) than birds offered sequential diet options. Choice fed birds had greater intakes of the high energy diet (1471 g/bird, P < 0.0001) than low energy (197 g/bird) or medium energy diets (663 g/bird) whilst broiler chickens were offered diets with different energy densities but high crude protein (300 g/kg) or digestible lysine (17.5 g/kg) concentrations. Choice fed birds had lower FCR (1.217 versus 1.327 g/g, P < 0.0001) and higher carcass yield (88.1 versus 87.3%, P = 0.012) than sequentially fed birds. This suggests that the dietary balance between protein and energy is essential for optimal feed conversion efficiency. The intake path of macronutrients from 10–31 days in choice and sequential feeding groups were plotted and compared with the null path if broiler chickens selected equal amounts of the three diets in the combination. Regardless of feeding regimen, the intake paths of starch and protein are very close to the null path; however, lipid and protein intake paths in choice fed birds are father from the null path than sequentially fed birds. PMID:29053729

Controlling firearms use in Australia: has the 1996 gun law reform produced the decrease in rates of suicide with this method?

PubMed

Klieve, Helen; Barnes, Michael; De Leo, Diego

2009-04-01

Observed reductions in firearm suicides in Australia have been linked to the 1997 national firearms agreement (NFA) introduced following the 1996 Port Arthur massacre. The NFA placed strong access restrictions on firearms. To assess the impact of legislative restrictions on the incidence of firearm suicide in Queensland and explore alternative or contributory factors behind observed declines. The Queensland suicide register (QSR) provided detailed information on all male suicides in Queensland (1990-2004), with additional data for Australia (1968-2004) accessed from other official sources. Trends in suicide rates pre/post NFA, and in method selection, were assessed using negative binomial regressions. Changing method selection patterns were examined using a cohort analysis of 5 years of age classes for Australian males. The observed reduction in firearms suicides was initiated prior to the 1997 introduction of the NFA in Queensland and Australia, with a clear decline observed in Australian figures from 1988. No significant difference was found in the rate pre/post the introduction of the NFA in Queensland; however, a significant difference was found for Australian data, the quality of which is noticeably less satisfactory. A marked age-difference in method choice was observed through a cohort analysis demonstrating both time and age influences. Within sequential birth cohorts, rates of firearms suicides decreased in younger males but increased in hanging suicides; this trend was far less marked in older males. The implemented restrictions may not be responsible for the observed reductions in firearms suicide. Data suggest that a change in social and cultural attitudes could have contributed to the shift in method preference.

The dynamic role of parental influences in preventing adolescent smoking initiation.

PubMed

Mahabee-Gittens, E Melinda; Xiao, Yang; Gordon, Judith S; Khoury, Jane C

2013-04-01

As adolescents grow, protective parental influences become less important and peer influences take precedence in adolescent's initiation of smoking. It is unknown how and when this occurs. We sought to: prospectively estimate incidence rates of smoking initiation from late childhood through mid-adolescence, identify important risk and protective parental influences on smoking initiation, and examine their dynamic nature in order to identify key ages. Longitudinal data from the National Survey of Parents and Youth of 8 nationally representative age cohorts (9-16 years) of never smokers in the U.S. were used (N=5705 dyads at baseline). Analysis involved a series of lagged logistic regression models using a cohort-sequential design. The mean sample cumulative incidence rates of tobacco use increased from 1.8% to 22.5% between the 9 and 16 years old age cohorts. Among risk factors, peer smoking was the most important across all ages; 11-15 year-olds who spent time with peers who smoked had 2 to 6.5 times higher odds of initiating smoking. Parent-youth connectedness significantly decreased the odds of smoking initiation by 14-37% in 11-14 year-olds; parental monitoring and punishment for smoking decreased the odds of smoking initiation risk by 36-59% in 10-15 year-olds, and by 15-28% in 12-14 year-olds, respectively. Parental influences are important in protecting against smoking initiation across adolescence. At the same time, association with peers who smoke is a very strong risk factor. Our findings provide empirical evidence to suggest that in order to prevent youth from initiating smoking, parents should be actively involved in their adolescents' lives and guard them against association with peers who smoke. Copyright © 2013 Elsevier Ltd. All rights reserved.

Outcomes of Diagnostic Exome Sequencing in Patients With Diagnosed or Suspected Autism Spectrum Disorders.

PubMed

Rossi, Mari; El-Khechen, Dima; Black, Mary Helen; Farwell Hagman, Kelly D; Tang, Sha; Powis, Zöe

2017-05-01

Exome sequencing has recently been proved to be a successful diagnostic method for complex neurodevelopmental disorders. However, the diagnostic yield of exome sequencing for autism spectrum disorders has not been extensively evaluated in large cohorts to date. We performed diagnostic exome sequencing in a cohort of 163 individuals with autism spectrum disorder (66.3%) or autistic features (33.7%). The diagnostic yield observed in patients in our cohort was 25.8% (42 of 163) for positive or likely positive findings in characterized disease genes, while a candidate genetic etiology was reported for an additional 3.3% (4 of 120) of patients. Among the positive findings in the patients with autism spectrum disorder or autistic features, 61.9% were the result of de novo mutations. Patients presenting with psychiatric conditions or ataxia or paraplegia in addition to autism spectrum disorder or autistic features were significantly more likely to receive positive results compared with patients without these clinical features (95.6% vs 27.1%, P < 0.0001; 83.3% vs 21.2%, P < 0.0001, respectively). The majority of the positive findings were in recently identified autism spectrum disorder genes, supporting the importance of diagnostic exome sequencing for patients with autism spectrum disorder or autistic features as the causative genes might evade traditional sequential or panel testing. These results suggest that diagnostic exome sequencing would be an efficient primary diagnostic method for patients with autism spectrum disorders or autistic features. Moreover, our data may aid clinicians to better determine which subset of patients with autism spectrum disorder with additional clinical features would benefit the most from diagnostic exome sequencing. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of efficacy and safety of levofloxacin-containing versus standard sequential therapy in eradication of Helicobacter pylori infection in Korea.

PubMed

Lee, Hyuk; Hong, Sung Noh; Min, Byung-Hoon; Lee, Jun Haeng; Rhee, Poong-Lyul; Lee, Yong Chan; Kim, Jae J

2015-02-01

Declining of eradication rates for Helicobacter pylori in Korea may be partly from the increasing prevalence of antibiotic resistance, especially clarithromycin resistance. To compare the efficacy and the safety of using 10-day standard sequential therapy and levofloxacin-containing sequential therapy as a first-line treatment for Helicobacter pylori eradication in Korea. A total of 200 patients with proven Helicobacter pylori infection randomly received 10-day standard sequential therapy (n = 100) or levofloxacin-containing sequential therapy (n = 100). The standard sequential therapy group received rabeprazole and amoxicillin for 5 days, followed by rabeprazole, clarithromycin, and metronidazole for 5 more days. The levofloxacin-containing sequential therapy group was treated with rabeprazole and amoxicillin for 5 days, followed by rabeprazole, levofloxacin, and metronidazole for 5 more days. Intention-to-treat eradication rates were 79.0% and 78.0% for groups of standard sequential and levofloxacin-containing sequential therapy, respectively (P = 0.863). Per-protocol eradication rates were 84.9% and 81.3%, respectively, for these two therapies (P = 0.498). There were no significant differences between the groups in regard to the eradication rates and adverse events. The 10-day levofloxacin-containing sequential regimen and the standard sequential regimen showed the similar eradication rates of Helicobacter pylori in Korea. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Double-blind photo lineups using actual eyewitnesses: an experimental test of a sequential versus simultaneous lineup procedure.

PubMed

Wells, Gary L; Steblay, Nancy K; Dysart, Jennifer E

2015-02-01

Eyewitnesses (494) to actual crimes in 4 police jurisdictions were randomly assigned to view simultaneous or sequential photo lineups using laptop computers and double-blind administration. The sequential procedure used in the field experiment mimicked how it is conducted in actual practice (e.g., using a continuation rule, witness does not know how many photos are to be viewed, witnesses resolve any multiple identifications), which is not how most lab experiments have tested the sequential lineup. No significant differences emerged in rates of identifying lineup suspects (25% overall) but the sequential procedure produced a significantly lower rate (11%) of identifying known-innocent lineup fillers than did the simultaneous procedure (18%). The simultaneous/sequential pattern did not significantly interact with estimator variables and no lineup-position effects were observed for either the simultaneous or sequential procedures. Rates of nonidentification were not significantly different for simultaneous and sequential but nonidentifiers from the sequential procedure were more likely to use the "not sure" response option than were nonidentifiers from the simultaneous procedure. Among witnesses who made an identification, 36% (41% of simultaneous and 32% of sequential) identified a known-innocent filler rather than a suspect, indicating that eyewitness performance overall was very poor. The results suggest that the sequential procedure that is used in the field reduces the identification of known-innocent fillers, but the differences are relatively small.

Precise algorithm to generate random sequential adsorption of hard polygons at saturation

NASA Astrophysics Data System (ADS)

Zhang, G.

2018-04-01

Random sequential adsorption (RSA) is a time-dependent packing process, in which particles of certain shapes are randomly and sequentially placed into an empty space without overlap. In the infinite-time limit, the density approaches a "saturation" limit. Although this limit has attracted particular research interest, the majority of past studies could only probe this limit by extrapolation. We have previously found an algorithm to reach this limit using finite computational time for spherical particles and could thus determine the saturation density of spheres with high accuracy. In this paper, we generalize this algorithm to generate saturated RSA packings of two-dimensional polygons. We also calculate the saturation density for regular polygons of three to ten sides and obtain results that are consistent with previous, extrapolation-based studies.

Precise algorithm to generate random sequential adsorption of hard polygons at saturation.

PubMed

Zhang, G

2018-04-01

Random sequential adsorption (RSA) is a time-dependent packing process, in which particles of certain shapes are randomly and sequentially placed into an empty space without overlap. In the infinite-time limit, the density approaches a "saturation" limit. Although this limit has attracted particular research interest, the majority of past studies could only probe this limit by extrapolation. We have previously found an algorithm to reach this limit using finite computational time for spherical particles and could thus determine the saturation density of spheres with high accuracy. In this paper, we generalize this algorithm to generate saturated RSA packings of two-dimensional polygons. We also calculate the saturation density for regular polygons of three to ten sides and obtain results that are consistent with previous, extrapolation-based studies.

Support for distinct subcomponents of spatial working memory: a double dissociation between spatial-simultaneous and spatial-sequential performance in unilateral neglect.

PubMed

Wansard, Murielle; Bartolomeo, Paolo; Bastin, Christine; Segovia, Fermín; Gillet, Sophie; Duret, Christophe; Meulemans, Thierry

2015-01-01

Over the last decade, many studies have demonstrated that visuospatial working memory (VSWM) can be divided into separate subsystems dedicated to the retention of visual patterns and their serial order. Impaired VSWM has been suggested to exacerbate left visual neglect in right-brain-damaged individuals. The aim of this study was to investigate the segregation between spatial-sequential and spatial-simultaneous working memory in individuals with neglect. We demonstrated that patterns of results on these VSWM tasks can be dissociated. Spatial-simultaneous and sequential aspects of VSWM can be selectively impaired in unilateral neglect. Our results support the hypothesis of multiple VSWM subsystems, which should be taken into account to better understand neglect-related deficits.

Sequential Testing: Basics and Benefits

DTIC Science & Technology

1978-03-01

Eii~TARADC6M and x _..TECHNICAL REPORT NO. 12325 SEQUENTIAL TESTING: BASICS AND BENEFITS / i * p iREFERENCE CP...Sequential Testing: Basics and Benefits Contents Page I. Introduction and Summary II. Sequential Analysis 2 III. Mathematics of Sequential Testing 4 IV...testing. The added benefit of reduced energy needs are inherent in this testing method. The text was originally released by the authors in 1972. The text

Historical time to disease progression and progression-free survival in patients with recurrent/refractory neuroblastoma treated in the modern era on Children's Oncology Group early-phase trials.

PubMed

London, Wendy B; Bagatell, Rochelle; Weigel, Brenda J; Fox, Elizabeth; Guo, Dongjing; Van Ryn, Collin; Naranjo, Arlene; Park, Julie R

2017-12-15

Early-phase trials in patients with recurrent neuroblastoma historically used an objective "response" of measureable disease (Response Evaluation Criteria In Solid Tumors [RECIST], without bone/bone marrow assessment) to select agents for further study. Historical cohorts may be small and potentially biased; to the authors' knowledge, disease recurrence studies from international registries are outdated. Using a large recent cohort of patients with recurrent/refractory neuroblastoma from Children's Oncology Group (COG) modern-era early-phase trials, the authors determined outcome and quantified parameters for designing future studies. The first early-phase COG trial enrollment (sequential) of 383 distinct patients with recurrent/refractory neuroblastoma on 23 phase 1, 3 phase 1/2, and 9 phase 2 trials (August 2002 to January 2014) was analyzed for progression-free survival (PFS), overall survival (OS), and time to disease progression (TTP). Planned frontline therapy for patients with high-risk neuroblastoma included hematopoietic stem cell transplantation (approximately two-thirds of patients underwent ≥1 hematopoietic stem cell transplantation); 13.2% of patients received dinutuximab. From the time of the patient's first early-phase trial enrollment (383 patients), the 1-year and 4-year PFS rates ( ± standard error) were 21% ± 2% and 6% ± 1%, respectively, whereas the 1-year and 4-year OS rates were 57% ± 3% and 20% ± 2%, respectively. The median TTP was 58 days (interquartile range, 31-183 days [350 patients]); the median follow-up was 25.3 months (33 patients were found to be without disease recurrence/progression). The median time from diagnosis to first disease recurrence/progression was 18.7 months (range, 1.4-64.8 months) (176 patients). MYCN amplification and 11q loss of heterozygosity were prognostic of worse PFS and OS (P = .003 and P<.0001, respectively, and P = .02 and P = .03, respectively) after early-phase trial enrollment. This recent COG cohort of patients with recurrent/refractory neuroblastoma is inclusive and representative. To the authors' knowledge, the current study is the first meta-analysis of PFS, TTP, and OS within the context of modern therapy. These results will inform the design of future phase 2 studies by providing a) historical context during the search for more effective agents; and, b) factors prognostic of PFS and OS after disease recurrence to stratify randomization. Cancer 2017;123:4914-23. © 2017 American Cancer Society. © 2017 American Cancer Society.

Sequential search leads to faster, more efficient fragment-based de novo protein structure prediction.

PubMed

de Oliveira, Saulo H P; Law, Eleanor C; Shi, Jiye; Deane, Charlotte M

2018-04-01

Most current de novo structure prediction methods randomly sample protein conformations and thus require large amounts of computational resource. Here, we consider a sequential sampling strategy, building on ideas from recent experimental work which shows that many proteins fold cotranslationally. We have investigated whether a pseudo-greedy search approach, which begins sequentially from one of the termini, can improve the performance and accuracy of de novo protein structure prediction. We observed that our sequential approach converges when fewer than 20 000 decoys have been produced, fewer than commonly expected. Using our software, SAINT2, we also compared the run time and quality of models produced in a sequential fashion against a standard, non-sequential approach. Sequential prediction produces an individual decoy 1.5-2.5 times faster than non-sequential prediction. When considering the quality of the best model, sequential prediction led to a better model being produced for 31 out of 41 soluble protein validation cases and for 18 out of 24 transmembrane protein cases. Correct models (TM-Score > 0.5) were produced for 29 of these cases by the sequential mode and for only 22 by the non-sequential mode. Our comparison reveals that a sequential search strategy can be used to drastically reduce computational time of de novo protein structure prediction and improve accuracy. Data are available for download from: http://opig.stats.ox.ac.uk/resources. SAINT2 is available for download from: https://github.com/sauloho/SAINT2. saulo.deoliveira@dtc.ox.ac.uk. Supplementary data are available at Bioinformatics online.

Electromagnetic-induction logging to monitor changing chloride concentrations

USGS Publications Warehouse

Metzger, Loren F.; Izbicki, John A.

2013-01-01

Water from the San Joaquin Delta, having chloride concentrations up to 3590 mg/L, has intruded fresh water aquifers underlying Stockton, California. Changes in chloride concentrations at depth within these aquifers were evaluated using sequential electromagnetic (EM) induction logs collected during 2004 through 2007 at seven multiple-well sites as deep as 268 m. Sequential EM logging is useful for identifying changes in groundwater quality through polyvinyl chloride-cased wells in intervals not screened by wells. These unscreened intervals represent more than 90% of the aquifer at the sites studied. Sequential EM logging suggested degrading groundwater quality in numerous thin intervals, typically between 1 and 7 m in thickness, especially in the northern part of the study area. Some of these intervals were unscreened by wells, and would not have been identified by traditional groundwater sample collection. Sequential logging also identified intervals with improving water quality—possibly due to groundwater management practices that have limited pumping and promoted artificial recharge. EM resistivity was correlated with chloride concentrations in sampled wells and in water from core material. Natural gamma log data were used to account for the effect of aquifer lithology on EM resistivity. Results of this study show that a sequential EM logging is useful for identifying and monitoring the movement of high-chloride water, having lower salinities and chloride concentrations than sea water, in aquifer intervals not screened by wells, and that increases in chloride in water from wells in the area are consistent with high-chloride water originating from the San Joaquin Delta rather than from the underlying saline aquifer.

Eradication rate of Helicobacter Pylori infection is directly influenced by adherence to therapy in children.

PubMed

Kotilea, Kallirroi; Mekhael, Joyce; Salame, Assaad; Mahler, Tania; Miendje-Deyi, Veronique Yvette; Cadranel, Samy; Bontems, Patrick

2017-08-01

Current commonly accepted strategies to eradicate Helicobacter pylori in children are a 10-day sequential treatment or a triple therapy for 7-14 days. To avoid further expensive and possibly risky investigations as well as induction of secondary antimicrobial resistance, a success rate of elimination strategies over 90% in a per-protocol analysis is the target goal but rates observed in clinical trials are lower. Antimicrobial resistance is a well-recognized risk factor for treatment failure; therefore, only a treatment tailored to susceptibility testing should be recommended. Adherence to therapy is also a risk factor for treatment failure but that has been poorly studied. The purpose of this study was to evaluate the influence of adherence to therapy on the elimination rates obtained with different treatment regimens. Cohort study analysis of children, aged 2-17 years, treated for Helicobacter pylori infection between October 2011 and December 2013. As a routine clinical practice, children infected with a strain susceptible to clarithromycin and to metronidazole received either a sequential regimen or a 10-day triple therapy while children infected with a strain resistant to clarithromycin or metronidazole received a 10-day triple regimen tailored to antimicrobial susceptibility. The eradication rate was assessed by a negative 13 C-urea breath test performed at least 8 weeks after the end of the treatment and adherence evaluated using a diary. One hundred forty-five children (67 girls/78 boys, median age 9.7 years) fulfilled the inclusion criteria, 118 being infected with a strain susceptible to both clarithromycin and metronidazole, 10 with a clarithromycin resistant, and 17 with a metronidazole resistant strain. A sequential regimen was prescribed in 44, a triple therapy containing clarithromycin in 84 and containing metronidazole in 17. Follow-up data were available for 130/145 and clearance of the infection observed in 105 of them. A concordance of more than 90% between the prescribed and the ingested drugs was observed in 109 children, between 50 and 90% in eight, less than 50% in 11 while these data were unknown for 2/130. A successful eradication was achieved for 89.9% of patients that received at least 90% of the prescribed drugs, whereas the eradication rate for nonadherent patients was 36.6%. Adherence above 90% was significantly higher in the absence of chronic concomitant disease, in the absence of adverse event and results in a significantly higher eradication rate. With the proposed strategy and an adherence higher than 90%, eradication was obtained in 98/109 children, the rate being only significantly superior to 90% with the sequential regimen. Adherence to therapy is a very important factor for the outcome and has to be assessed when evaluating the outcome of an H. pylori eradication regimen in order to understand the reasons of treatment failure. As we treated only after evaluation of the resistance of the H. Pylori strains, we were expecting to reach the given objective of 90% successful treatment. Children with adherence to treatment above 90% had a successful outcome of 89,9%, whereas nonadherent had a successful outcome of 36,8%. This is the first time that adherence has been assessed accurately. © 2017 John Wiley & Sons Ltd.

Cost-Utility Analysis of Cochlear Implantation in Australian Adults.

PubMed

Foteff, Chris; Kennedy, Steven; Milton, Abul Hasnat; Deger, Melike; Payk, Florian; Sanderson, Georgina

2016-06-01

Sequential and simultaneous bilateral cochlear implants are emerging as appropriate treatment options for Australian adults with sensory deficits in both cochleae. Current funding of Australian public hospitals does not provide for simultaneous bilateral cochlear implantation (CI) as a separate surgical procedure. Previous cost-effectiveness studies of sequential and simultaneous bilateral CI assumed 100% of unilaterally treated patients' transition to a sequential bilateral CI. This assumption does not place cochlear implantation in the context of the generally treated population. When mutually exclusive treatment options exist, such as unilateral CI, sequential bilateral CI, and simultaneous bilateral CI, the mean costs of the treated populations are weighted in the calculation of incremental cost-utility ratios. The objective was to evaluate the cost-utility of bilateral hearing aids (HAs) compared with unilateral, sequential, and simultaneous bilateral CI in Australian adults with bilateral severe to profound sensorineural hearing loss. Cost-utility analysis of secondary sources input to a Markov model. Australian health care perspective, lifetime horizon with costs and outcomes discounted 5% annually. Bilateral HAs as treatment for bilateral severe to profound sensorineural hearing loss compared with unilateral, sequential, and simultaneous bilateral CI. Incremental costs per quality adjusted life year (AUD/QALY). When compared with bilateral hearing aids the incremental cost-utility ratio for the CI treatment population was AUD11,160/QALY. The incremental cost-utility ratio was weighted according to the number of patients treated unilaterally, sequentially, and simultaneously, as these were mutually exclusive treatment options. No peer-reviewed articles have reported the incremental analysis of cochlear implantation in a continuum of care for surgically treated populations with bilateral severe to profound sensorineural hearing loss. Unilateral, sequential, and simultaneous bilateral CI were cost-effective when compared with bilateral hearing aids. Technologies that reduce the total number of visits for a patient could introduce additional cost efficiencies into clinical practice.

Benefit and predictive factors for speech perception outcomes in pediatric bilateral cochlear implant recipients.

PubMed

Chang, Young-Soo; Hong, Sung Hwa; Kim, Eun Yeon; Choi, Ji Eun; Chung, Won-Ho; Cho, Yang-Sun; Moon, Il Joon

2018-05-18

Despite recent advancement in the prediction of cochlear implant outcome, the benefit of bilateral procedures compared to bimodal stimulation and how we predict speech perception outcomes of sequential bilateral cochlear implant based on bimodal auditory performance in children remain unclear. This investigation was performed: (1) to determine the benefit of sequential bilateral cochlear implant and (2) to identify the associated factors for the outcome of sequential bilateral cochlear implant. Observational and retrospective study. We retrospectively analyzed 29 patients with sequential cochlear implant following bimodal-fitting condition. Audiological evaluations were performed; the categories of auditory performance scores, speech perception with monosyllable and disyllables words, and the Korean version of Ling. Audiological evaluations were performed before sequential cochlear implant with the bimodal fitting condition (CI1+HA) and one year after the sequential cochlear implant with bilateral cochlear implant condition (CI1+CI2). The good Performance Group (GP) was defined as follows; 90% or higher in monosyllable and bisyllable tests with auditory-only condition or 20% or higher improvement of the scores with CI1+CI2. Age at first implantation, inter-implant interval, categories of auditory performance score, and various comorbidities were analyzed by logistic regression analysis. Compared to the CI1+HA, CI1+CI2 provided significant benefit in categories of auditory performance, speech perception, and Korean version of Ling results. Preoperative categories of auditory performance scores were the only associated factor for being GP (odds ratio=4.38, 95% confidence interval - 95%=1.07-17.93, p=0.04). The children with limited language development in bimodal condition should be considered as the sequential bilateral cochlear implant and preoperative categories of auditory performance score could be used as the predictor in speech perception after sequential cochlear implant. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Evaluating Bias of Sequential Mixed-Mode Designs against Benchmark Surveys

ERIC Educational Resources Information Center

Klausch, Thomas; Schouten, Barry; Hox, Joop J.

2017-01-01

This study evaluated three types of bias--total, measurement, and selection bias (SB)--in three sequential mixed-mode designs of the Dutch Crime Victimization Survey: telephone, mail, and web, where nonrespondents were followed up face-to-face (F2F). In the absence of true scores, all biases were estimated as mode effects against two different…

Developing L2 Pragmatic Competence in Mandarin Chinese: Sequential Realization of Requests

ERIC Educational Resources Information Center

Su, Yunwen; Ren, Wei

2017-01-01

The present study explored the development of second language (L2) Chinese learners' ability to negotiate requests in interactions. It investigated the effect of proficiency on learners' use of request strategies and internal modifications and on their sequential realization of requests in L2 Chinese. Twenty-four American English learners of L2…

Functions Represented as Linear Sequential Data: Relationships between Presentation and Student Responses

ERIC Educational Resources Information Center

Ayalon, Michal; Watson, Anne; Lerman, Steve

2015-01-01

This study investigates students' ways of attending to linear sequential data in two tasks, and conjectures possible relationships between those ways and elements of the task design. Drawing on the substantial literature about such situations, we focus for this paper on linear rate of change, and on covariation and correspondence approaches to…

Successful ELF Communications and Implications for ELT: Sequential Analysis of ELF Pronunciation Negotiation Strategies

ERIC Educational Resources Information Center

Matsumoto, Yumi

2011-01-01

This is a qualitative study of nonnative English speakers who speak English as a lingua franca (ELF) in their graduate student dormitory in the United States, a community of practice (Wegner, 2004) comprised almost entirely of second language users. Using a sequential analysis (Koshik, 2002; Markee, 2000; Sacks, Schegloff, & Jefferson, 1974;…

The Minimum Requirements of Language Control: Evidence from Sequential Predictability Effects in Language Switching

ERIC Educational Resources Information Center

Declerck, Mathieu; Koch, Iring; Philipp, Andrea M.

2015-01-01

The current study systematically examined the influence of sequential predictability of languages and concepts on language switching. To this end, 2 language switching paradigms were combined. To measure language switching with a random sequence of languages and/or concepts, we used a language switching paradigm that implements visual cues and…

A Cross-Cultural Validation of the Sequential-Simultaneous Theory of Intelligence in Children.

ERIC Educational Resources Information Center

Moon, Soo-Back; McLean, James E.; Kaufman, Alan S.

2003-01-01

The Kaufman Assessment Battery for Children - Korean (K-ABC-K) was developed to assess the intelligence and achievement of preschool and school-aged Korean children. This study examined the validity of the Sequential Processing, Simultaneous Processing and Achievement scales of the K-ABC-K. The factor analyses provided strong support for the…

The Role of Semantic Transfer in Clitic Drop among Simultaneous and Sequential Chinese-Spanish Bilinguals

ERIC Educational Resources Information Center

Cuza, Alejandro; Perez-Leroux, Ana Teresa; Sanchez, Liliana

2013-01-01

This study examines the acquisition of the featural constraints on clitic and null distribution in Spanish among simultaneous and sequential Chinese-Spanish bilinguals from Peru. A truth value judgment task targeted the referential meaning of null objects in a negation context. Objects were elicited via two clitic elicitation tasks that targeted…

How Cognitive Styles Affect the Learning Behaviors of Online Problem-Solving Based Discussion Activity: A Lag Sequential Analysis

ERIC Educational Resources Information Center

Wu, Sheng-Yi; Hou, Huei-Tse

2015-01-01

Cognitive styles play an important role in influencing the learning process, but to date no relevant study has been conducted using lag sequential analysis to assess knowledge construction learning patterns based on different cognitive styles in computer-supported collaborative learning activities in online collaborative discussions. This study…

Trial-to-Trial Modulations of the Simon Effect in Conditions of Attentional Limitations : Evidence from Dual Tasks

ERIC Educational Resources Information Center

Fischer, Rico; Plessow, Franziska; Kunde, Wilfried; Kiesel, Andrea

2010-01-01

Interference effects are reduced after trials including response conflict. This sequential modulation has often been attributed to a top-down mediated adaptive control mechanism and/or to feature repetition mechanisms. In the present study we tested whether mechanisms responsible for such sequential modulations are subject to attentional…

Beyond Grand Rounds: A Comprehensive and Sequential Intervention to Improve Identification of Delirium

ERIC Educational Resources Information Center

Ramaswamy, Ravishankar; Dix, Edward F.; Drew, Janet E.; Diamond, James J.; Inouye, Sharon K.; Roehl, Barbara J. O.

2011-01-01

Purpose of the Study: Delirium is a widespread concern for hospitalized seniors, yet is often unrecognized. A comprehensive and sequential intervention (CSI) aiming to effect change in clinician behavior by improving knowledge about delirium was tested. Design and Methods: A 2-day CSI program that consisted of progressive 4-part didactic series,…

Molecular Etiology of Hereditary Single-Side Deafness: Its Association With Pigmentary Disorders and Waardenburg Syndrome.

PubMed

Kim, Shin Hye; Kim, Ah Reum; Choi, Hyun Seok; Kim, Min Young; Chun, Eun Hi; Oh, Seung-Ha; Choi, Byung Yoon

2015-10-01

Unilateral sensorineural hearing loss (USNHL)/single-side deafness (SSD) is a frequently encountered disability in children. The etiology of a substantial portion of USNHL/SSD still remains unknown, and genetic causes have not been clearly elucidated. In this study, the authors evaluated the heritability of USNHL/SSD.The authors sequentially recruited 50 unrelated children with SSD. For an etiologic diagnosis, we performed a rigorous review on the phenotypes of family members of all children and conducted, if necessary, molecular genetic tests including targeted exome sequencing of 129 deafness genes.Among the 50 SSD children cohort, the authors identify 4 (8%) unrelated SSD probands from 4 families (SH136, SB173, SB177, and SB199) with another hearing impaired family members. Notably, all 4 probands in our cohort with a familial history of SSD also have pigmentary abnormalities such as brown freckles or premature gray hair within first degree relatives, which may indicate that genes whose products are involved with pigmentary disorder could be candidates for heritable SSD. Indeed, SH136 and SB199 turned out to segregate a mutation in MITF and PAX3, respectively, leading to a molecular diagnosis of Waardenburg syndrome (WS).We report, for the first time in the literature, a significant heritability of pediatric SSD. There is a strong association between the heritability of USNHL/SSD and the pigmentary abnormality, shedding a new light on the understanding of the molecular basis of heritable USNHL/SSD. In case of children with congenital SSD, it would be mandatory to rigorously screen pigmentary abnormalities. WS should also be included in the differential diagnosis of children with USNHL/SSD, especially in a familial form.

Restoration of the centre of rotation in primary total hip arthroplasty: the influence of acetabular floor depth and reaming technique.

PubMed

Meermans, G; Doorn, J Van; Kats, J-J

2016-12-01

One goal of total hip arthroplasty is to restore normal hip anatomy. The aim of this study was to compare displacement of the centre of rotation (COR) using a standard reaming technique with a technique in which the acetabulum was reamed immediately peripherally and referenced off the rim. In the first cohort the acetabulum was reamed to the floor followed by sequentially larger reamers. In the second cohort the acetabulum was only reamed peripherally, starting with a reamer the same size as the native femoral head. Anteroposterior pelvic radiographs were analysed for acetabular floor depth and vertical and horizontal position of the COR. Horizontally, the mean medial displacement of the COR was 0.8 mm (standard deviation (sd) 1.4) in the peripheral remaing group and 5.0 mm (sd 3.30) in the standard reaming group (p < 0.001). Vertically, the mean superior displacement of the COR was 0.7 mm (sd 1.3) in the peripheral reaming group and 3.7 mm (sd 2.6) in the standard reaming group (p < 0.001). In the standard reaming group, there was a strong correlation between the pre-operative acetabular floor depth and displacement of the COR (p < 0.001). Reaming the acetabulum to the floor can lead to significant displacement of the COR medially and superiorly. This displacement is related to the pre-operative acetabular floor depth and cannot always be compensated by using a high offset stem. Cite this article: Bone Joint J 2016;98-B:1597-603. ©2016 The British Editorial Society of Bone & Joint Surgery.

Commonality of Risk Factors for Mothers' Poor Oral Health and General Health: Baseline Analysis of a Population-Based Birth Cohort Study.

PubMed

Ha, Diep H; Spencer, A John; Thomson, W Murray; Scott, Jane A; Do, Loc G

2018-04-01

Objective The association between and commonality of risk factors for poor self-rated oral health (SROH) and general health (SRGH) among new mothers has not been reported. The purpose of this paper is to assess the commonality of risk factors for poor SROH and SRGH, and self-reported obesity and dental pain, among a population-based sample of new mothers in Australia. It also investigated health conditions affecting new mothers' general health. Methods Data collected at baseline of a population-based birth cohort was used. Mothers of newborns in Adelaide were approached to participate. Mothers completed a questionnaire collecting data on socioeconomic status (SES), health behaviours, dental pain, SROH, self-reported height and weight and SRGH. Analysis was conducted sequentially from bivariate to multivariable regression to estimate prevalence rate (PR) of reporting poor/fair SROH and SRGH. Results of the 1895 new mothers, some 21 and 6% rated their SROH and SRGH as poor/fair respectively. Dental pain was associated with low income and smoking status, while being obese was associated with low SES, low education and infrequent tooth brushing. SROH and SRGH was associated with low SES, smoking, and dental pain. SROH was also associated with SRGH [PR: 3.06 (2.42-3.88)]. Conclusion for practice There was a commonality of factors associated with self-rated oral health and general health. Strong associations between OH and GH were also observed. Given the importance of maternal health for future generations, there would be long-term societal benefit from addressing common risk factors for OH and GH in integrated programs.

Impact of an Ivermectin Mass Drug Administration on Scabies Prevalence in a Remote Australian Aboriginal Community

PubMed Central

Kearns, Thérèse M.; Speare, Richard; Cheng, Allen C.; McCarthy, James; Carapetis, Jonathan R.; Holt, Deborah C.; Currie, Bart J.; Page, Wendy; Shield, Jennifer; Gundjirryirr, Roslyn; Bundhala, Leanne; Mulholland, Eddie; Chatfield, Mark; Andrews, Ross M.

2015-01-01

Background Scabies is endemic in many Aboriginal and Torres Strait Islander communities, with 69% of infants infected in the first year of life. We report the outcomes against scabies of two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community. Methods Utilizing a before and after study design, we measured scabies prevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined disease acquisition and treatment failures. Scabies infestations were diagnosed clinically with additional laboratory investigations for crusted scabies. Non-pregnant participants weighing ≥15 kg were administered a single 200 μg/kg ivermectin dose, repeated after 2–3 weeks if scabies was diagnosed, others followed a standard alternative algorithm. Principal Findings We saw >1000 participants at each population census. Scabies prevalence fell from 4% at baseline to 1% at month 6. Prevalence rose to 9% at month 12 amongst the baseline cohort in association with an identified exposure to a presumptive crusted scabies case with a higher prevalence of 14% amongst new entries to the cohort. At month 18, scabies prevalence fell to 2%. Scabies acquisitions six months after each MDA were 1% and 2% whilst treatment failures were 6% and 5% respectively. Conclusion Scabies prevalence reduced in the six months after each MDA with a low risk of acquisition (1–2%). However, in a setting where living conditions are conducive to high scabies transmissibility, exposure to presumptive crusted scabies and population mobility, a sustained reduction in prevalence was not achieved. Clinical Trial Registration Australian New Zealand Clinical Trial Register (ACTRN—12609000654257). PMID:26516764

Reproducibility of Digital PCR Assays for Circulating Tumor DNA Analysis in Advanced Breast Cancer

PubMed Central

Hrebien, Sarah; O’Leary, Ben; Beaney, Matthew; Schiavon, Gaia; Fribbens, Charlotte; Bhambra, Amarjit; Johnson, Richard; Turner, Nicholas

2016-01-01

Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48–72 hours after collection. Plasma DNA was analysed with multiplex digital PCR (mdPCR) assays for hotspot mutations in PIK3CA, ESR1 and ERBB2, and for AKT1 E17K. There was 94.8% (91/96) agreement in mutation calling between immediate and delayed processed tubes, kappa 0.88 95% CI 0.77–0.98). Discordance in mutation calling resulted from low allele frequency and likely stochastic effects. In concordant samples there was high correlation in mutant copies per ml plasma (r2 = 0.98; p<0.0001). There was elevation of total cell free plasma DNA concentrations in 10.3% of delayed processed tubes, although overall quantification of total cell free plasma DNA had similar prognostic effects in immediate (HR 3.6) and delayed (HR 3.0) tubes. There was moderate agreement in changes in allele fraction between sequential samples in quantitative mutation tracking (r = 0.84, p = 0.0002). Delayed processing of samples using preservative tubes allows for centralized ctDNA digital PCR mutation screening in advanced breast cancer. The potential of preservative tubes in quantitative mutation tracking requires further research. PMID:27760227

Reproducibility of Digital PCR Assays for Circulating Tumor DNA Analysis in Advanced Breast Cancer.

PubMed

Hrebien, Sarah; O'Leary, Ben; Beaney, Matthew; Schiavon, Gaia; Fribbens, Charlotte; Bhambra, Amarjit; Johnson, Richard; Garcia-Murillas, Isaac; Turner, Nicholas

2016-01-01

Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48-72 hours after collection. Plasma DNA was analysed with multiplex digital PCR (mdPCR) assays for hotspot mutations in PIK3CA, ESR1 and ERBB2, and for AKT1 E17K. There was 94.8% (91/96) agreement in mutation calling between immediate and delayed processed tubes, kappa 0.88 95% CI 0.77-0.98). Discordance in mutation calling resulted from low allele frequency and likely stochastic effects. In concordant samples there was high correlation in mutant copies per ml plasma (r2 = 0.98; p<0.0001). There was elevation of total cell free plasma DNA concentrations in 10.3% of delayed processed tubes, although overall quantification of total cell free plasma DNA had similar prognostic effects in immediate (HR 3.6) and delayed (HR 3.0) tubes. There was moderate agreement in changes in allele fraction between sequential samples in quantitative mutation tracking (r = 0.84, p = 0.0002). Delayed processing of samples using preservative tubes allows for centralized ctDNA digital PCR mutation screening in advanced breast cancer. The potential of preservative tubes in quantitative mutation tracking requires further research.

Resident training in a new robotic thoracic surgery program.

PubMed

White, Yasmine N; Dedhia, Priya; Bergeron, Edward J; Lin, Jules; Chang, Andrew A; Reddy, Rishindra M

2016-03-01

The volume of robot-assisted operations has drastically increased over the past decade. New programs have focused on training surgeons, whereas resident training has lagged behind. The objective of this study was to evaluate our institutional experience with resident participation in thoracic robotic surgery cases since the initiation of our program. The first 100 robotic thoracic surgery cases at our institution were retrospectively reviewed and categorized into three sequential cohorts. Procedure type, patient and operative characteristics, level of resident participation (primary surgeon [PS] or assistant), and postoperative variables were evaluated. Of the first 100 cases, 38% were lung resections, 23% were esophageal operations, and 20% were sympathectomies. The distribution of cases changed over time with the proportion of pulmonary resections significantly increasing. Patient age (P < 0.05), body mass index (P = not significant [NS]), and comorbidities (P = NS) increased over time. Resident participation as PS increased from 33%-59% between the early and late cohorts (P < 0.05). A subset analysis of the 20 lobectomies (7 attending PS, 13 residents) showed similar patient characteristics (P = NS): age (67 versus 69), body mass index (29.5 versus 26.1), and American Society of Anesthesiologists category (2.8 versus 2.8). Operative and postoperative characteristics were also similar (P = NS) regardless of PS: operative time (260 versus 249 min), estimated blood loss (187 versus 203 mL), and length of stay (4.8 versus 4.7 d). Residents can participate as the PS in a variety of thoracic operations during the implementation of a robotics program. Operative time, estimated blood loss, and length of stay were similar regardless of level of resident participation. Copyright © 2016 Elsevier Inc. All rights reserved.

How age and gender predict illness course in a first-episode nonaffective psychosis cohort.

PubMed

Drake, Richard J; Addington, Jean; Viswanathan, Ananth C; Lewis, Shôn W; Cotter, Jack; Yung, Alison R; Abel, Kathryn M

2016-03-01

Male gender and young age at onset of schizophrenia are traditionally associated with poor treatment outcome and often used to determine prognosis. However, many studies use nonincident samples and fail to adjust for symptom severity at onset. We hypothesized that age and gender would influence severity of presentation but would not predict outcome after adjustment for symptoms at presentation. 628 people with first-episode ICD-9 and DSM-IV nonaffective psychosis from 2 historical cohorts recruited from sequential presentations in Canada and the United Kingdom (1996-1998) were assessed prospectively at presentation and over 12-18 months using the Positive and Negative Syndrome Scale (PANSS). Models of the age-at-onset distributions with 2 underlying modes at similar ages in women (ages 23 years and 47 years) and men (ages 22 years and 46 years) had relatively good fits compared to single-mode models (χ(2)1 better by 9.2 for females, 8.0 for males, both P < .05). At presentation, scores for negative symptoms were 1.84 points worse for males (95% CI, 1.05 to 2.58; P < .001) in a mixed effects model. Younger age also predicted higher negative scores at presentation (partial correlation r = -0.18, P < .01; P < .001 in the mixed effects model). Findings were similar for cognitive-disorganized symptoms. However, after controlling for baseline symptoms, age at onset and gender did not significantly predict subsequent symptom course in the mixed effects models. Gender and age at onset are independently associated with symptoms at presentation but not with medium-term course of schizophrenia. This finding reinforces the importance of early identification and prevention of severe negative symptoms at first episode, whatever an individual's age and gender. © Copyright 2016 Physicians Postgraduate Press, Inc.

Non-polio enterovirus association with persistent diarrhea in children as revealed by a follow-up study of an Indian cohort during the first two years of life.

PubMed

Rao, Durga C; Reddy, Harikrishna; Sudheendra, K; Raghavendra, A; Varadharaj, Vembuli; Edula, Surekha; Goparaju, Ramya; Ratnakar, Bharath; Srinivasa Rao, Arni S R; Maiya, Padmanabha P; Ananda Babu, M

2014-09-01

We recently reported significant association of non-polio enteroviruses (NPEVs) with acute diarrhea in children. Persistent diarrhea (PD) remains a major cause of morbidity and mortality in infants below two years of age in developing countries. Understanding age-dependent frequency and duration of NPEV infections is important to determine their association with persistent diarrhea and disease burden. A cohort of 140 infants was followed for 6 months to 2 years of age to determine the frequency, duration, and association with PD of NPEV infections in comparison with rotavirus and other agents. Stool samples were collected every 14 days, and diarrheal episodes and their duration were recorded. Enteroviruses were characterized by RT-PCR and VP1 gene sequence analysis, rotavirus by electropherotyping, and other agents by PCR. Of 4545 samples, negative for oral polio vaccine strains, 3907 (85.96%) and 638 (14.04%) were NPEV-negative and NPEV-positive, respectively, representing 403 (8.87%) infection episodes. About 68% of NPEV infections occurred during the first year with every child having at least one episode lasting between four days and four months. Approximately 38% and 22% of total diarrheal episodes were positive for NPEV and RV, respectively. While about 18% of NPEV infection episodes were associated with diarrhea, 6% being persistent, 13% of total diarrheal episodes were persistent involving infections by monotype NPEV strains or sequential infections by multiple strains and other agents. This is the first report revealing NPEVs as the single most frequently and persistently detected viral pathogen in every PD episode. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular Etiology of Hereditary Single-Side Deafness

PubMed Central

Kim, Shin Hye; Kim, Ah Reum; Choi, Hyun Seok; Kim, Min Young; Chun, Eun Hi; Oh, Seung-Ha; Choi, Byung Yoon

2015-01-01

Abstract Unilateral sensorineural hearing loss (USNHL)/single-side deafness (SSD) is a frequently encountered disability in children. The etiology of a substantial portion of USNHL/SSD still remains unknown, and genetic causes have not been clearly elucidated. In this study, the authors evaluated the heritability of USNHL/SSD. The authors sequentially recruited 50 unrelated children with SSD. For an etiologic diagnosis, we performed a rigorous review on the phenotypes of family members of all children and conducted, if necessary, molecular genetic tests including targeted exome sequencing of 129 deafness genes. Among the 50 SSD children cohort, the authors identify 4 (8%) unrelated SSD probands from 4 families (SH136, SB173, SB177, and SB199) with another hearing impaired family members. Notably, all 4 probands in our cohort with a familial history of SSD also have pigmentary abnormalities such as brown freckles or premature gray hair within first degree relatives, which may indicate that genes whose products are involved with pigmentary disorder could be candidates for heritable SSD. Indeed, SH136 and SB199 turned out to segregate a mutation in MITF and PAX3, respectively, leading to a molecular diagnosis of Waardenburg syndrome (WS). We report, for the first time in the literature, a significant heritability of pediatric SSD. There is a strong association between the heritability of USNHL/SSD and the pigmentary abnormality, shedding a new light on the understanding of the molecular basis of heritable USNHL/SSD. In case of children with congenital SSD, it would be mandatory to rigorously screen pigmentary abnormalities. WS should also be included in the differential diagnosis of children with USNHL/SSD, especially in a familial form. PMID:26512583

Who will have Sustainable Employment After a Back Injury? The Development of a Clinical Prediction Model in a Cohort of Injured Workers.

PubMed

Shearer, Heather M; Côté, Pierre; Boyle, Eleanor; Hayden, Jill A; Frank, John; Johnson, William G

2017-09-01

Purpose Our objective was to develop a clinical prediction model to identify workers with sustainable employment following an episode of work-related low back pain (LBP). Methods We used data from a cohort study of injured workers with incident LBP claims in the USA to predict employment patterns 1 and 6 months following a workers' compensation claim. We developed three sequential models to determine the contribution of three domains of variables: (1) basic demographic/clinical variables; (2) health-related variables; and (3) work-related factors. Multivariable logistic regression was used to develop the predictive models. We constructed receiver operator curves and used the c-index to measure predictive accuracy. Results Seventy-nine percent and 77 % of workers had sustainable employment at 1 and 6 months, respectively. Sustainable employment at 1 month was predicted by initial back pain intensity, mental health-related quality of life, claim litigation and employer type (c-index = 0.77). At 6 months, sustainable employment was predicted by physical and mental health-related quality of life, claim litigation and employer type (c-index = 0.77). Adding health-related and work-related variables to models improved predictive accuracy by 8.5 and 10 % at 1 and 6 months respectively. Conclusion We developed clinically-relevant models to predict sustainable employment in injured workers who made a workers' compensation claim for LBP. Inquiring about back pain intensity, physical and mental health-related quality of life, claim litigation and employer type may be beneficial in developing programs of care. Our models need to be validated in other populations.

Optimization of a novel sequential alkalic and metal salt pretreatment for enhanced delignification and enzymatic saccharification of corn cobs.

PubMed

Sewsynker-Sukai, Yeshona; Gueguim Kana, E B

2017-11-01

This study presents a sequential sodium phosphate dodecahydrate (Na 3 PO 4 ·12H 2 O) and zinc chloride (ZnCl 2 ) pretreatment to enhance delignification and enzymatic saccharification of corn cobs. The effects of process parameters of Na 3 PO 4 ·12H 2 O concentration (5-15%), ZnCl 2 concentration (1-5%) and solid to liquid ratio (5-15%) on reducing sugar yield from corn cobs were investigated. The sequential pretreatment model was developed and optimized with a high coefficient of determination value (0.94). Maximum reducing sugar yield of 1.10±0.01g/g was obtained with 14.02% Na 3 PO 4 ·12H 2 O, 3.65% ZnCl 2 and 5% solid to liquid ratio. Scanning electron microscopy (SEM) and Fourier Transform Infrared analysis (FTIR) showed major lignocellulosic structural changes after the optimized sequential pretreatment with 63.61% delignification. In addition, a 10-fold increase in the sugar yield was observed compared to previous reports on the same substrate. This sequential pretreatment strategy was efficient for enhancing enzymatic saccharification of corn cobs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluating specificity of sequential extraction for chemical forms of lead in artificially-contaminated and field-contaminated soils.

PubMed

Tai, Yiping; McBride, Murray B; Li, Zhian

2013-03-30

In the present study, we evaluated a commonly employed modified Bureau Communautaire de Référence (BCR test) 3-step sequential extraction procedure for its ability to distinguish forms of solid-phase Pb in soils with different sources and histories of contamination. When the modified BCR test was applied to mineral soils spiked with three forms of Pb (pyromorphite, hydrocerussite and nitrate salt), the added Pb was highly susceptible to dissolution in the operationally-defined "reducible" or "oxide" fraction regardless of form. When three different materials (mineral soil, organic soil and goethite) were spiked with soluble Pb nitrate, the BCR sequential extraction profiles revealed that soil organic matter was capable of retaining Pb in more stable and acid-resistant forms than silicate clay minerals or goethite. However, the BCR sequential extraction for field-collected soils with known and different sources of Pb contamination was not sufficiently discriminatory in the dissolution of soil Pb phases to allow soil Pb forms to be "fingerprinted" by this method. It is concluded that standard sequential extraction procedures are probably not very useful in predicting lability and bioavailability of Pb in contaminated soils. Copyright © 2013 Elsevier B.V. All rights reserved.

Optimal pacing modes after cardiac transplantation: is synchronisation of recipient and donor atria beneficial?

PubMed Central

Parry, Gareth; Malbut, Katie; Dark, John H; Bexton, Rodney S

1992-01-01

Objective—To investigate the response of the transplanted heart to different pacing modes and to synchronisation of the recipient and donor atria in terms of cardiac output at rest. Design—Doppler derived cardiac output measurements at three pacing rates (90/min, 110/min and 130/min) in five pacing modes: right ventricular pacing, donor atrial pacing, recipient-donor synchronous pacing, donor atrial-ventricular sequential pacing, and synchronous recipient-donor atrial-ventricular sequential pacing. Patients—11 healthy cardiac transplant recipients with three pairs of epicardial leads inserted at transplantation. Results—Donor atrial pacing (+11% overall) and donor atrial-ventricular sequential pacing (+8% overall) were significantly better than right ventricular pacing (p < 0·001) at all pacing rates. Synchronised pacing of recipient and donor atrial segments did not confer additional benefit in either atrial or atrial-ventricular sequential modes of pacing in terms of cardiac output at rest at these fixed rates. Conclusions—Atrial pacing or atrial-ventricular sequential pacing appear to be appropriate modes in cardiac transplant recipients. Synchronisation of recipient and donor atrial segments in this study produced no additional benefit. Chronotropic competence in these patients may, however, result in improved exercise capacity and deserves further investigation. PMID:1389737

Classification and Sequential Pattern Analysis for Improving Managerial Efficiency and Providing Better Medical Service in Public Healthcare Centers

PubMed Central

Chung, Sukhoon; Rhee, Hyunsill; Suh, Yongmoo

2010-01-01

Objectives This study sought to find answers to the following questions: 1) Can we predict whether a patient will revisit a healthcare center? 2) Can we anticipate diseases of patients who revisit the center? Methods For the first question, we applied 5 classification algorithms (decision tree, artificial neural network, logistic regression, Bayesian networks, and Naïve Bayes) and the stacking-bagging method for building classification models. To solve the second question, we performed sequential pattern analysis. Results We determined: 1) In general, the most influential variables which impact whether a patient of a public healthcare center will revisit it or not are personal burden, insurance bill, period of prescription, age, systolic pressure, name of disease, and postal code. 2) The best plain classification model is dependent on the dataset. 3) Based on average of classification accuracy, the proposed stacking-bagging method outperformed all traditional classification models and our sequential pattern analysis revealed 16 sequential patterns. Conclusions Classification models and sequential patterns can help public healthcare centers plan and implement healthcare service programs and businesses that are more appropriate to local residents, encouraging them to revisit public health centers. PMID:21818426

A Bayesian sequential design with adaptive randomization for 2-sided hypothesis test.

PubMed

Yu, Qingzhao; Zhu, Lin; Zhu, Han

2017-11-01

Bayesian sequential and adaptive randomization designs are gaining popularity in clinical trials thanks to their potentials to reduce the number of required participants and save resources. We propose a Bayesian sequential design with adaptive randomization rates so as to more efficiently attribute newly recruited patients to different treatment arms. In this paper, we consider 2-arm clinical trials. Patients are allocated to the 2 arms with a randomization rate to achieve minimum variance for the test statistic. Algorithms are presented to calculate the optimal randomization rate, critical values, and power for the proposed design. Sensitivity analysis is implemented to check the influence on design by changing the prior distributions. Simulation studies are applied to compare the proposed method and traditional methods in terms of power and actual sample sizes. Simulations show that, when total sample size is fixed, the proposed design can obtain greater power and/or cost smaller actual sample size than the traditional Bayesian sequential design. Finally, we apply the proposed method to a real data set and compare the results with the Bayesian sequential design without adaptive randomization in terms of sample sizes. The proposed method can further reduce required sample size. Copyright © 2017 John Wiley & Sons, Ltd.

Sequential analysis in neonatal research-systematic review.

PubMed

Lava, Sebastiano A G; Elie, Valéry; Ha, Phuong Thi Viet; Jacqz-Aigrain, Evelyne

2018-05-01

As more new drugs are discovered, traditional designs come at their limits. Ten years after the adoption of the European Paediatric Regulation, we performed a systematic review on the US National Library of Medicine and Excerpta Medica database of sequential trials involving newborns. Out of 326 identified scientific reports, 21 trials were included. They enrolled 2832 patients, of whom 2099 were analyzed: the median number of neonates included per trial was 48 (IQR 22-87), median gestational age was 28.7 (IQR 27.9-30.9) weeks. Eighteen trials used sequential techniques to determine sample size, while 3 used continual reassessment methods for dose-finding. In 16 studies reporting sufficient data, the sequential design allowed to non-significantly reduce the number of enrolled neonates by a median of 24 (31%) patients (IQR - 4.75 to 136.5, p = 0.0674) with respect to a traditional trial. When the number of neonates finally included in the analysis was considered, the difference became significant: 35 (57%) patients (IQR 10 to 136.5, p = 0.0033). Sequential trial designs have not been frequently used in Neonatology. They might potentially be able to reduce the number of patients in drug trials, although this is not always the case. What is known: • In evaluating rare diseases in fragile populations, traditional designs come at their limits. About 20% of pediatric trials are discontinued, mainly because of recruitment problems. What is new: • Sequential trials involving newborns were infrequently used and only a few (n = 21) are available for analysis. • The sequential design allowed to non-significantly reduce the number of enrolled neonates by a median of 24 (31%) patients (IQR - 4.75 to 136.5, p = 0.0674).

Reducing sedation time for thyroplasty with arytenoid adduction with sequential anesthetic technique.

PubMed

Saadeh, Charles K; Rosero, Eric B; Joshi, Girish P; Ozayar, Esra; Mau, Ted

2017-12-01

To determine the extent to which a sequential anesthetic technique 1) shortens time under sedation for thyroplasty with arytenoid adduction (TP-AA), 2) affects the total operative time, and 3) changes the voice outcome compared to TP-AA performed entirely under sedation/analgesia. Case-control study. A new sequential anesthetic technique of performing most of the TP-AA surgery under general anesthesia (GA), followed by transition to sedation/analgesia (SA) for voice assessment, was developed to achieve smooth emergence from GA. Twenty-five TP-AA cases performed with the sequential GA-SA technique were compared with 25 TP-AA controls performed completely under sedation/analgesia. The primary outcome measure was the time under sedation. Voice improvement, as assessed by Consensus Auditory-Perceptual Evaluation of Voice, and total operative time were secondary outcome measures. With the conventional all-SA anesthetic, the duration of SA was 209 ± 26.3 minutes. With the sequential GA-SA technique, the duration of SA was 79.0 ± 18.9 minutes, a 62.3% reduction (P < 0.0001). There was no significant difference in the total operative time (209.5 vs. 200.9 minutes; P = 0.42) or in voice outcome. This sequential anesthetic technique has been easily adopted by multiple anesthesiologists and nurse anesthetists at our institution. TP-AA is effectively performed under sequential GA-SA technique with a significant reduction in the duration of time under sedation. This allows the surgeon to perform the technically more challenging part of the surgery under GA, without having to contend with variability in patient tolerance for laryngeal manipulation under sedation. 3b. Laryngoscope, 127:2813-2817, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Outcomes of simultaneous resections for patients with synchronous colorectal liver metastases.

PubMed

Slesser, A A P; Chand, M; Goldin, R; Brown, G; Tekkis, P P; Mudan, S

2013-12-01

The aim of this study was to determine the outcomes associated with simultaneous resections compared to patients undergoing sequential resections for synchronous colorectal liver metastases. Consecutive patients undergoing hepatic resections between 2000 and 2012 for synchronous colorectal liver metastases were identified from a prospectively maintained database. Of the 112 hepatic resections that were performed, 36 were simultaneous resections and 76 were sequential resections. There was no difference in disease severity: number of metastases (P 0.228), metastatic size (P 0.58), the primary tumour nodal status (P 0.283), CEA (P 0.387) or the presence of extra-hepatic metastases (P 1.0). Major hepatic resections were performed in 23 (64%) and 60 (79%) of patients in the simultaneous and sequential groups respectively (P 0.089). Intra-operatively no differences were found in blood loss (P 1.0), duration of surgery (P 0.284) or number of adverse events (P 1.0). There were no differences in post-operative complications (P 0.161) or post-operative mortality (P 0.241). The length of hospital stay was 14 (95% CI 12.0-18.0) and 18.5 (95% CI 16.0-23.0) days in the simultaneous and sequential groups respectively (P 0.03). The 3-year overall survival was 75% and 64% in the simultaneous and sequential groups respectively (P 0.379). The 3-year hepatic recurrence free survival was 61% and 46% in the simultaneous and sequential groups respectively (P 0.254). Simultaneous resections result in similar short-term and long-term outcomes as patients receiving sequential resections with comparable metastatic disease and are associated with a significant reduction in the length of stay. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Sequential prescriptions: Arguments for a change of therapeutic patterns in treatment resistant depressions].

PubMed

Allouche, G

2016-02-01

Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses and recurrences, in antidepressant maintenance. These data support the interest of therapeutic strategies based on evolutionary criteria. Sequential models inspired by statistical methods may incorporate the effects of a future treatment by measuring the current one. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Exploring the sequential lineup advantage using WITNESS.

PubMed

Goodsell, Charles A; Gronlund, Scott D; Carlson, Curt A

2010-12-01

Advocates claim that the sequential lineup is an improvement over simultaneous lineup procedures, but no formal (quantitatively specified) explanation exists for why it is better. The computational model WITNESS (Clark, Appl Cogn Psychol 17:629-654, 2003) was used to develop theoretical explanations for the sequential lineup advantage. In its current form, WITNESS produced a sequential advantage only by pairing conservative sequential choosing with liberal simultaneous choosing. However, this combination failed to approximate four extant experiments that exhibited large sequential advantages. Two of these experiments became the focus of our efforts because the data were uncontaminated by likely suspect position effects. Decision-based and memory-based modifications to WITNESS approximated the data and produced a sequential advantage. The next step is to evaluate the proposed explanations and modify public policy recommendations accordingly.

Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy: Results of a Matched Pair Analysis.

PubMed

Markovina, Stephanie; Youssef, Fady; Roy, Amit; Aggarwal, Sonya; Khwaja, Shariq; DeWees, Todd; Tan, Benjamin; Hunt, Steven; Myerson, Robert J; Chang, Daniel T; Parikh, Parag J; Olsen, Jeffrey R

2017-10-01

To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a significant multivariate predictor for improved outcome when including patients treated with NCRT at another institution. Published by Elsevier Inc.

[Clinical effect of Saccharomyces boulardii powder combined with azithromycin sequential therapy in treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia].

PubMed

Chen, Qi-Fen; Zhang, Yi-Wei

2018-02-01

To investigate the clinical effect of Saccharomyces boulardii powder combined with azithromycin sequential therapy in the treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia. A total of 88 children with diarrhea secondary to Mycoplasma pneumoniae pneumonia between June 2015 and March 2017 were divided into control group and study group using a random number table, with 44 children in each group. The children in the control group were given routine treatment combined with azithromycin sequential therapy, and those in the study group were given oral Saccharomyces boulardii powder in addition to the treatment in the control group until the end of azithromycin sequential therapy. After the treatment ended, the two groups were compared in terms of time to improvement of clinical symptoms, length of hospital stay, clinical outcome, defecation frequency before and after treatment, condition of intestinal dysbacteriosis, and incidence of adverse events. Compared with the control group, the study group had significantly shorter time to improvement of clinical symptoms and length of hospital stay (P<0.05). The study group had a significantly higher response rate than the control group (P<0.05). On days 3 and 5 of treatment, the study group had a significant reduction in defecation frequency compared with the control group (P<0.05). The study group had a significantly lower rate of intestinal dysbacteriosis than the control group (P<0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05). In the treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia, Saccharomyces boulardii powder combined with azithromycin sequential therapy can improve clinical symptoms, shorten the length of hospital stay, reduce defecation frequency and the incidence of intestinal dysbacteriosis, and improve clinical outcomes, and does not increase the risk of adverse events.

Sequential disinfection of E. coli O157:H7 on shredded lettuce leaves by aqueous chlorine dioxide, ozonated water, and thyme essential oil

NASA Astrophysics Data System (ADS)

Singh, Nepal; Singh, Rakesh K.; Bhunia, Arun K.; Stroshine, Richard L.; Simon, James E.

2001-03-01

There have been numerous studies on effectiveness of different sanitizers for microbial inactivation. However, results obtained from different studies indicate that microorganism cannot be easily removed from fresh cut vegetables because of puncture and cut surfaces with varying surface topographies. In this study, three step disinfection approach was evaluated for inactivation of E. coli O157:H7 on shredded lettuce leaves. Sequential application of thyme oil, ozonated water, and aqueous chlorine dioxide was evaluated in which thyme oil was applied first followed by ozonated water and aqueous chlorine dioxide. Shredded lettuce leaves inoculated with cocktail culture of E. coli O157:H7 (C7927, EDL 933 and 204 P), were washed with ozonated water (15 mg/l for 10min), aqueous chlorine dioxide (10 mg/l,for 10min) and thyme oil suspension (0.1%, v/v for 5min). Washing of lettuce leaves with ozonated water, chlorine dioxide and thyme oil suspension resulted in 0.44, 1.20, and 1.46 log reduction (log10 cfu/g), respectively. However, the sequential treatment achieved approximately 3.13 log reductions (log10 cfu/g). These results demonstrate the efficacy of sequential treatments in decontaminating shredded lettuce leaves containing E. coli O157:H7.

Optimal Sequential Rules for Computer-Based Instruction.

ERIC Educational Resources Information Center

Vos, Hans J.

1998-01-01

Formulates sequential rules for adapting the appropriate amount of instruction to learning needs in the context of computer-based instruction. Topics include Bayesian decision theory, threshold and linear-utility structure, psychometric model, optimal sequential number of test questions, and an empirical example of sequential instructional…

Developmental Trajectories of Male Physical Violence and Theft

PubMed Central

Barker, Edward D.; Séguin, Jean R.; White, Helene Raskin; Bates, Marsha E.; Lacourse, Éric; Carbonneau, René; Tremblay, Richard E.

2012-01-01

Context Neurocognitive mechanisms have long been hypothesized to influence developmental trajectories of antisocial behavior. However, studies examining this association tend to aggregate a variety of problem behaviors that may be differently affected by neurocognitive deficits. Objective To describe the developmental trajectories of physical violence and theft from adolescence to adulthood, their associations, and the neurocognitive characteristics of individuals following different patterns of trajectory association. Design Accelerated cohort-sequential, longitudinal design. Setting Rutgers Health and Human Development Project. Participants Six hundred ninety-eight men. Main Outcome Measures Self-reports of physical violence (ages 12–24 years) and theft (ages 12–31 years) were collected across 5 waves. Neurocognitive performance was assessed with executive function and verbal IQ tests between late adolescence and early adulthood. Results The majority (55%) of subjects showed an increased frequency of theft during the study period, while only a minority (13%) evinced an increasing frequency of physical violence. Executive function and verbal IQ performance were negatively related to high frequency of physical violence but positively related to high frequency of theft. Conclusions Developmental trajectories of physical violence and theft during adolescence and early adulthood are different and differently related to neurocognitive functioning. Global indexes of antisocial behavior mask the development of antisocial behavior subtypes and putative causal mechanisms. PMID:17485611

Innate biology versus lifestyle behaviour in the aetiology of obesity and type 2 diabetes: the GLACIER Study.

PubMed

Poveda, Alaitz; Koivula, Robert W; Ahmad, Shafqat; Barroso, Inês; Hallmans, Göran; Johansson, Ingegerd; Renström, Frida; Franks, Paul W

2016-03-01

We compared the ability of genetic (established type 2 diabetes, fasting glucose, 2 h glucose and obesity variants) and modifiable lifestyle (diet, physical activity, smoking, alcohol and education) risk factors to predict incident type 2 diabetes and obesity in a population-based prospective cohort of 3,444 Swedish adults studied sequentially at baseline and 10 years later. Multivariable logistic regression analyses were used to assess the predictive ability of genetic and lifestyle risk factors on incident obesity and type 2 diabetes by calculating the AUC. The predictive accuracy of lifestyle risk factors was similar to that yielded by genetic information for incident type 2 diabetes (AUC 75% and 74%, respectively) and obesity (AUC 68% and 73%, respectively) in models adjusted for age, age(2) and sex. The addition of genetic information to the lifestyle model significantly improved the prediction of type 2 diabetes (AUC 80%; p = 0.0003) and obesity (AUC 79%; p < 0.0001) and resulted in a net reclassification improvement of 58% for type 2 diabetes and 64% for obesity. These findings illustrate that lifestyle and genetic information separately provide a similarly high degree of long-range predictive accuracy for obesity and type 2 diabetes.

The heritable basis of gene-environment interactions in cardiometabolic traits.

PubMed

Poveda, Alaitz; Chen, Yan; Brändström, Anders; Engberg, Elisabeth; Hallmans, Göran; Johansson, Ingegerd; Renström, Frida; Kurbasic, Azra; Franks, Paul W

2017-03-01

Little is known about the heritable basis of gene-environment interactions in humans. We therefore screened multiple cardiometabolic traits to assess the probability that they are influenced by genotype-environment interactions. Fourteen established environmental risk exposures and 11 cardiometabolic traits were analysed in the VIKING study, a cohort of 16,430 Swedish adults from 1682 extended pedigrees with available detailed genealogical, phenotypic and demographic information, using a maximum likelihood variance decomposition method in Sequential Oligogenic Linkage Analysis Routines software. All cardiometabolic traits had statistically significant heritability estimates, with narrow-sense heritabilities (h 2 ) ranging from 24% to 47%. Genotype-environment interactions were detected for age and sex (for the majority of traits), physical activity (for triacylglycerols, 2 h glucose and diastolic BP), smoking (for weight), alcohol intake (for weight, BMI and 2 h glucose) and diet pattern (for weight, BMI, glycaemic traits and systolic BP). Genotype-age interactions for weight and systolic BP, genotype-sex interactions for BMI and triacylglycerols and genotype-alcohol intake interactions for weight remained significant after multiple test correction. Age, sex and alcohol intake are likely to be major modifiers of genetic effects for a range of cardiometabolic traits. This information may prove valuable for studies that seek to identify specific loci that modify the effects of lifestyle in cardiometabolic disease.

The English proficiency and academic language skills of Australian bilingual children during the primary school years.

PubMed

Dennaoui, Kamelia; Nicholls, Ruth Jane; O'Connor, Meredith; Tarasuik, Joanne; Kvalsvig, Amanda; Goldfeld, Sharon

2016-04-01

Evidence suggests that early proficiency in the language of school instruction is an important predictor of academic success for bilingual children. This study investigated whether English-proficiency at 4-5 years of age predicts academic language and literacy skills among Australian bilingual children at 10-11 years of age, as part of the Longitudinal Study of Australian Children ( LSAC, 2012 ). The LSAC comprises a nationally representative clustered cross-sequential sample of Australian children. Data were analysed from a sub-sample of 129 bilingual children from the LSAC Kindergarten cohort (n = 4983), for whom teachers completed the Australian Early Development Index (AEDI) checklist (a population measure of early childhood development) and the Academic Rating Scale (ARS) language and literacy subscale. Linear regression analyses revealed that bilingual children who commenced school with stronger English proficiency had higher academic language and literacy scores at the end of primary school (β = 0.45). English proficiency remained a significant predictor, even when accounting for gender and socio-economic disadvantage (β = 0.38). The findings indicate that bilingual children who begin school without English proficiency are at risk of difficulties with academic language and literacy, even after 6 years of schooling. Risk factors need to be identified so early support can be targeted towards the most vulnerable children.

Reducing interaction in simultaneous paired stimulation with CI.

PubMed

Vellinga, Dirk; Bruijn, Saskia; Briaire, Jeroen J; Kalkman, Randy K; Frijns, Johan H M

2017-01-01

In this study simultaneous paired stimulation of electrodes in cochlear implants is investigated by psychophysical experiments in 8 post-lingually deaf subjects (and one extra subject who only participated in part of the experiments). Simultaneous and sequential monopolar stimulation modes are used as references and are compared to channel interaction compensation, partial tripolar stimulation and a novel sequential stimulation strategy named phased array compensation. Psychophysical experiments are performed to investigate both the loudness integration during paired stimulation at the main electrodes as well as the interaction with the electrode contact located halfway between the stimulating pair. The study shows that simultaneous monopolar stimulation has more loudness integration on the main electrodes and more interaction in between the electrodes than sequential stimulation. Channel interaction compensation works to reduce the loudness integration at the main electrodes, but does not reduce the interaction in between the electrodes caused by paired stimulation. Partial tripolar stimulation uses much more current to reach the needed loudness, but shows the same interaction in between the electrodes as sequential monopolar stimulation. In phased array compensation we have used the individual impedance matrix of each subject to calculate the current needed on each electrode to exactly match the stimulation voltage along the array to that of sequential stimulation. The results show that the interaction in between the electrodes is the same as monopolar stimulation. The strategy uses less current than partial tripolar stimulation, but more than monopolar stimulation. In conclusion, the paper shows that paired stimulation is possible if the interaction is compensated.

Bursts and Heavy Tails in Temporal and Sequential Dynamics of Foraging Decisions

PubMed Central

Jung, Kanghoon; Jang, Hyeran; Kralik, Jerald D.; Jeong, Jaeseung

2014-01-01

A fundamental understanding of behavior requires predicting when and what an individual will choose. However, the actual temporal and sequential dynamics of successive choices made among multiple alternatives remain unclear. In the current study, we tested the hypothesis that there is a general bursting property in both the timing and sequential patterns of foraging decisions. We conducted a foraging experiment in which rats chose among four different foods over a continuous two-week time period. Regarding when choices were made, we found bursts of rapidly occurring actions, separated by time-varying inactive periods, partially based on a circadian rhythm. Regarding what was chosen, we found sequential dynamics in affective choices characterized by two key features: (a) a highly biased choice distribution; and (b) preferential attachment, in which the animals were more likely to choose what they had previously chosen. To capture the temporal dynamics, we propose a dual-state model consisting of active and inactive states. We also introduce a satiation-attainment process for bursty activity, and a non-homogeneous Poisson process for longer inactivity between bursts. For the sequential dynamics, we propose a dual-control model consisting of goal-directed and habit systems, based on outcome valuation and choice history, respectively. This study provides insights into how the bursty nature of behavior emerges from the interaction of different underlying systems, leading to heavy tails in the distribution of behavior over time and choices. PMID:25122498

Adapting the Surgical Apgar Score for Perioperative Outcome Prediction in Liver Transplantation: A Retrospective Study

PubMed Central

Pearson, Amy C. S.; Subramanian, Arun; Schroeder, Darrell R.; Findlay, James Y.

2017-01-01

Background The surgical Apgar score (SAS) is a 10-point scale using the lowest heart rate, lowest mean arterial pressure, and estimated blood loss (EBL) during surgery to predict postoperative outcomes. The SAS has not yet been validated in liver transplantation patients, because typical blood loss usually exceeds the highest EBL category. Our primary aim was to develop a modified SAS for liver transplant (SAS-LT) by replacing the EBL parameter with volume of red cells transfused. We hypothesized that the SAS-LT would predict death or severe complication within 30 days of transplant with similar accuracy to current scoring systems. Methods A retrospective cohort of consecutive liver transplantations from July 2007 to November 2013 was used to develop the SAS-LT. The predictive ability of SAS-LT for early postoperative outcomes was compared with Model for End-stage Liver Disease, Sequential Organ Failure Assessment, and Acute Physiology and Chronic Health Evaluation III scores using multivariable logistic regression and receiver operating characteristic analysis. Results Of 628 transplants, death or serious perioperative morbidity occurred in 105 (16.7%). The SAS-LT (receiver operating characteristic area under the curve [AUC], 0.57) had similar predictive ability to Acute Physiology and Chronic Health Evaluation III, model for end-stage liver disease, and Sequential Organ Failure Assessment scores (0.57, 0.56, and 0.61, respectively). Seventy-nine (12.6%) patients were discharged from the ICU in 24 hours or less. These patients’ SAS-LT scores were significantly higher than those with a longer stay (7.0 vs 6.2, P < 0.01). The AUC on multivariable modeling remained predictive of early ICU discharge (AUC, 0.67). Conclusions The SAS-LT utilized simple intraoperative metrics to predict early morbidity and mortality after liver transplant with similar accuracy to other scoring systems at an earlier postoperative time point. PMID:29184910

Comparison of indium-labeled-leukocyte imaging with sequential technetium-gallium scanning in the diagnosis of low-grade musculoskeletal sepsis. A prospective study

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

Merkel, K.D.; Brown, M.L.; Dewanjee, M.K.

We prospectively compared sequential technetium-gallium imaging with indium-labeled-leukocyte imaging in fifty patients with suspected low-grade musculoskeletal sepsis. Adequate images and follow-up examinations were obtained for forty-two patients. The presence or absence of low-grade sepsis was confirmed by histological and bacteriological examinations of tissue specimens taken at surgery in thirty of the forty-two patients. In these thirty patients, the sensitivity of sequential Tc-Ga imaging was 48 per cent, the specificity was 86 per cent, and the accuracy was 57 per cent, whereas the sensitivity of the indium-labeled-leukocyte technique was 83 per cent, the specificity was 86 per cent, and the accuracymore » was 83 per cent. When the additional twelve patients for whom surgery was deemed unnecessary were considered, the sensitivity of sequential Tc-Ga imaging was 50 per cent, the specificity was 78 per cent, and the accuracy was 62 per cent, as compared with a sensitivity of 83 per cent, a specificity of 94 per cent, and an accuracy of 88 per cent with the indium-labeled-leukocyte method. In patients with a prosthesis the indium-labeled-leukocyte image was 94 per cent accurate, compared with 75 per cent accuracy for sequential Tc-Ga imaging. Statistical analysis of these data demonstrated that the indium-labeled-leukocyte technique was superior to sequential Tc-Ga imaging in detecting areas of low-grade musculoskeletal sepsis.« less

Precise algorithm to generate random sequential adsorption of hard polygons at saturation

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

Zhang, G.

Random sequential adsorption (RSA) is a time-dependent packing process, in which particles of certain shapes are randomly and sequentially placed into an empty space without overlap. In the infinite-time limit, the density approaches a "saturation'' limit. Although this limit has attracted particular research interest, the majority of past studies could only probe this limit by extrapolation. We have previously found an algorithm to reach this limit using finite computational time for spherical particles, and could thus determine the saturation density of spheres with high accuracy. Here in this paper, we generalize this algorithm to generate saturated RSA packings of two-dimensionalmore » polygons. We also calculate the saturation density for regular polygons of three to ten sides, and obtain results that are consistent with previous, extrapolation-based studies.« less

Precise algorithm to generate random sequential adsorption of hard polygons at saturation

DOE PAGES

Zhang, G.

2018-04-30

Random sequential adsorption (RSA) is a time-dependent packing process, in which particles of certain shapes are randomly and sequentially placed into an empty space without overlap. In the infinite-time limit, the density approaches a "saturation'' limit. Although this limit has attracted particular research interest, the majority of past studies could only probe this limit by extrapolation. We have previously found an algorithm to reach this limit using finite computational time for spherical particles, and could thus determine the saturation density of spheres with high accuracy. Here in this paper, we generalize this algorithm to generate saturated RSA packings of two-dimensionalmore » polygons. We also calculate the saturation density for regular polygons of three to ten sides, and obtain results that are consistent with previous, extrapolation-based studies.« less

Simultaneous vs. sequential treatment for smoking and weight management in tobacco quitlines: 6 and 12 month outcomes from a randomized trial.

PubMed

Bush, Terry; Lovejoy, Jennifer; Javitz, Harold; Torres, Alula Jimenez; Wassum, Ken; Tan, Marcia M; Spring, Bonnie

2018-05-31

Smoking cessation often results in weight gain which discourages many smokers from quitting and can increase health risks. Treatments to reduce cessation-related weight gain have been tested in highly controlled trials of in-person treatment, but have never been tested in a real-world setting, which has inhibited dissemination. The Best Quit Study (BQS) is a replication and "real world" translation using telephone delivery of a prior in-person efficacy trial. randomized control trial in a quitline setting. Eligible smokers (n = 2540) were randomized to the standard 5-call quitline intervention or quitline plus simultaneous or sequential weight management. Regression analyses tested effectiveness of treatments on self-reported smoking abstinence and weight change at 6 and 12 months. Study enrollees were from 10 commercial employer groups and three state quitlines. Participants were between ages 18-72, 65.8% female, 68.2% white; 23.0% Medicaid-insured, and 76.3% overweight/obese. The follow-up response rate was lower in the simultaneous group than the control group at 6 months (p = 0.01). While a completers analysis of 30-day point prevalence abstinence detected no differences among groups at 6 or 12 months, multiply imputed abstinence showed quit rate differences at 6 months for:simultaneous (40.3%) vs. sequential (48.3%), p = 0.034 and simultaneous vs. control (44.9%), p = 0.043. At 12 months, multiply imputed abstinence, was significantly lower for the simultaneous group (40.7%) vs. control (46.0%), p < 0.05 and vs. sequential (46.3%), p < 0.05. Weight gain at 6 and 12 months was minimal and not different among treatment groups. The sequential group completed fewer total calls (3.75) vs. control (4.16) and vs. simultaneous group (3.83), p = 0.01, and fewer weight calls (0.94) than simultaneous (2.33), p < 0.0001. The number of calls completed predicted 30-day abstinence, p < 0.001, but not weight outcomes. This study offers a model for evaluating population-level public health interventions conducted in partnership with tobacco quitlines. Simultaneous (vs. sequential) delivery of phone/web weight management with cessation treatment in the quitline setting may adversely affect quit rate. Neither a simultaneous nor sequential approach to addressing weight produced any benefit on suppressing weight gain. This study highlights the need and the challenges of testing intensive interventions in real-world settings. ClinicalTrials.gov Identifier: NCT01867983 . Registered: May 30, 2013.

G-sequentially connectedness for topological groups with operations

NASA Astrophysics Data System (ADS)

Mucuk, Osman; Cakalli, Huseyin

2016-08-01

It is a well-known fact that for a Hausdorff topological group X, the limits of convergent sequences in X define a function denoted by lim from the set of all convergent sequences in X to X. This notion has been modified by Connor and Grosse-Erdmann for real functions by replacing lim with an arbitrary linear functional G defined on a linear subspace of the vector space of all real sequences. Recently some authors have extended the concept to the topological group setting and introduced the concepts of G-sequential continuity, G-sequential compactness and G-sequential connectedness. In this work, we present some results about G-sequentially closures, G-sequentially connectedness and fundamental system of G-sequentially open neighbourhoods for topological group with operations which include topological groups, topological rings without identity, R-modules, Lie algebras, Jordan algebras, and many others.