scholarly journals 3279 First in Man

2019 ◽  
Vol 3 (s1) ◽  
pp. 45-45
Author(s):  
Laura Adang ◽  
Francesco Gavazzi ◽  
Valentina De Giorgis ◽  
Micaela De Simone ◽  
Elisa Fazzi ◽  
...  
Keyword(s):  
Skill Acquisition ◽  
Classification System ◽  
Developmental Trajectories ◽  
Spastic Paraparesis ◽  
Altered Mental Status ◽  
Developmental Trajectory ◽  
Global Developmental Delay ◽  
P Value ◽  
Kaplan Meier ◽  
Neurologic Disability

OBJECTIVES/SPECIFIC AIMS: A mimic of congenital infections and a rare genetic cause of interferon overproduction, Aicardi Goutières Syndrome (AGS) results in significant neurologic disability. AGS is caused by pathogenic changes in the intracellular nucleic acid sensing machinery (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1). All affected individuals exhibit neurologic impairment: from mild spastic paraparesis to severe tetraparesis and global developmental delay. We hypothesize that genotype influences the heterogeneous developmental trajectory found in AGS. METHODS/STUDY POPULATION: To characterize this spectrum, age and symptoms at presentation and longitudinal developmental skill acquisition was collected from an international cohort of children (n=88) with genetically confirmed AGS. RESULTS/ANTICIPATED RESULTS: We found that individuals present at variable ages, with the largest range in SAMHD1, ADAR, and IFIH1. There are 3 clusters of symptoms at presentation: altered mental status (irritability or lethargy), systemic inflammatory symptoms, and acute neurologic symptoms, with variability across all genotypes. By creating Kaplan-Meier curves for developmental milestones, we were able to create genotype-based developmental trajectories for the children affected by the 5 most common genotypes: TREX1, IFIH1, SAMHD1, ADAR, and RNASEH2B. Individuals with AGS secondary to TREX1 were the most severely affected, significantly less likely to reach milestones compared to the other genotypes, including head control, sitting, and nonspecific mama/dada (p-value <0.005). Individuals affected by SAMHD1, IFIH1, and ADAR collectively attained the most advanced milestones, with 44% of the population achieving a minimum of a single word and 31% able to walk independently. Three retrospective scales were also applied: Gross Motor Function Classification System, Manual Ability Classification Scale, and Communication Function Classification System. Within each genotypic cohort, there was pronounced heterogeneity. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results demonstrate the influence of genotype on early development, but also suggest the importance of other unidentified variables. These results underscore the need for deep phenotyping to better characterize subcohorts within the AGS population.

scholarly journals Developmental Outcomes of Aicardi Goutières Syndrome

2019 ◽  
Vol 35 (1) ◽  
pp. 7-16 ◽  
Author(s):  
Laura Adang ◽  
Francesco Gavazzi ◽  
Micaela De Simone ◽  
Elisa Fazzi ◽  
Jessica Galli ◽  
...  
Keyword(s):  
Classification System ◽  
Age Of Onset ◽  
Spastic Paraparesis ◽  
Altered Mental Status ◽  
Developmental Trajectory ◽  
Clinical Endpoints ◽  
Presenting Symptoms ◽  
Severe Intellectual Disability ◽  
Neurologic Disability ◽  
Early Features

Aicardi Goutières syndrome is a monogenic interferonopathy caused by abnormalities in the intracellular nucleic acid sensing machinery ( TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or IFIH1). Most individuals affected by Aicardi Goutières syndrome exhibit some degree of neurologic impairment, from spastic paraparesis with relatively preserved cognition to tetraparesis and severe intellectual disability. Because of this heterogeneity, it is important to fully characterize the developmental trajectory in Aicardi Goutières syndrome. To characterize the clinical presentation in Aicardi Goutières syndrome, early features were collected from an international cohort of children (n = 100) with genetically confirmed Aicardi Goutières syndrome. There was a heterogeneous age of onset, with overlapping clusters of presenting symptoms: altered mental status, systemic inflammatory symptoms, and acute neurologic disability. Next, we created genotype-specific developmental milestone acquisition curves. Individuals with microcephaly or TREX1-related Aicardi Goutières syndrome secondary were the most severely affected and less likely to reach milestones, including head control, sitting, and nonspecific mama/dada. Individuals affected by SAMHD1, IFIH1, and ADAR attained the most advanced milestones, with 44% achieving verbal communication and 31% independently ambulating. Retrospective function scales (Gross Motor Function Classification System, Manual Ability Classification System, and Communication Function Classification System) demonstrated that two-thirds of the Aicardi Goutières syndrome population are severely affected. Our results suggest multifactorial influences on developmental trajectory, including a strong contribution from genotype. Further studies are needed to identify the additional factors that influence overall outcomes to better counsel families and to design clinical trials with appropriate clinical endpoints.

Acquisition of Developmental Milestones in Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum and Other TUBB4A-Related Leukoencephalopathy

2021 ◽  
Vol 36 (10) ◽  
pp. 805-811 ◽  
Author(s):  
Francesco Gavazzi ◽  
Brittany A. Charsar ◽  
Catherine Williams ◽  
Justine Shults ◽  
Cesar A. Alves ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Late Onset ◽  
Developmental Trajectories ◽  
Disease Onset ◽  
Developmental Trajectory ◽  
Global Developmental Delay ◽  
Developmental Milestones ◽  
Clinical Endpoints ◽  
Neurologic Disorders ◽  
The Common

Mutations in TUBB4A are associated with a spectrum of neurologic disorders categorized as TUBB4A-related leukoencephalopathy. Affected children can present with global developmental delay or normal early development, followed by a variable loss of skills over time. Further research is needed to characterize the factors associated with the divergent developmental trajectories in this rare monogenic disorder because this phenotypic spectrum is not fully explained by genotype alone. To characterize early psychomotor features, developmental milestones and age of disease onset were collected from medical records (n=54 individuals). Three subcohorts were identified: individuals with the common p.Asp249Asn variant vs all other genotypes with either early (<12 months of age) or late onset of presentation. Individuals with the p.Asp249Asn variant or those with non-p.Asp249Asn genotypes with later disease onset attained key milestones, including head control, sitting, and independent walking. Subjects with early-onset, non-p.Asp249Asn–associated disease were less likely to achieve developmental milestones. Next, we defined the developmental severity as the percentage of milestones attained by age 2 years. The mild form was defined as attaining at least 75% of key developmental milestones. Among cohort categorized as mild, individuals with p.Asp249Asn variant were more likely to lose acquired abilities when compared with non-p.Asp249Asn individuals. Our results suggest multiple influences on developmental trajectory, including a strong contribution from genotype and age of onset. Further studies are needed to identify additional factors that influence overall outcomes to better counsel families and to design clinical trials with appropriate clinical endpoints.

Acquisition of Developmental Milestones in Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum and Other TUBB4A-Related Leukoencephalopathy

2021 ◽  
pp. 088307382100097
Author(s):  
Francesco Gavazzi ◽  
Brittany A. Charsar ◽  
Catherine Williams ◽  
Justine Shults ◽  
Cesar A. Alves ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Late Onset ◽  
Developmental Trajectories ◽  
Disease Onset ◽  
Developmental Trajectory ◽  
Global Developmental Delay ◽  
Developmental Milestones ◽  
Clinical Endpoints ◽  
Neurologic Disorders ◽  
The Common

Mutations in TUBB4A are associated with a spectrum of neurologic disorders categorized as TUBB4A-related leukoencephalopathy. Affected children can present with global developmental delay or normal early development, followed by a variable loss of skills over time. Further research is needed to characterize the factors associated with the divergent developmental trajectories in this rare monogenic disorder because this phenotypic spectrum is not fully explained by genotype alone. To characterize early psychomotor features, developmental milestones and age of disease onset were collected from medical records (n=54 individuals). Three subcohorts were identified: individuals with the common p.Asp249Asn variant vs all other genotypes with either early (<12 months of age) or late onset of presentation. Individuals with the p.Asp249Asn variant or those with non-p.Asp249Asn genotypes with later disease onset attained key milestones, including head control, sitting, and independent walking. Subjects with early-onset, non-p.Asp249Asn–associated disease were less likely to achieve developmental milestones. Next, we defined the developmental severity as the percentage of milestones attained by age 2 years. The mild form was defined as attaining at least 75% of key developmental milestones. Among cohort categorized as mild, individuals with p.Asp249Asn variant were more likely to lose acquired abilities when compared with non-p.Asp249Asn individuals. Our results suggest multiple influences on developmental trajectory, including a strong contribution from genotype and age of onset. Further studies are needed to identify additional factors that influence overall outcomes to better counsel families and to design clinical trials with appropriate clinical endpoints.

From a molar to a molecular approach to the developmental trajectory of syntax comprehension by persons with intellectual disability

2020 ◽  
Author(s):  
Bruno Facon
Keyword(s):  
Developmental Trajectories ◽  
Developmental Trajectory ◽  
Typically Developing ◽  
Cognitive Level ◽  
Cross Sectional ◽  
Test Items ◽  
Complex Sentences ◽  
Regression Curves ◽  
Cognitive Measure ◽  
Syntactic Skills

The aim was to investigate whether a progressive dissociation between the cognitive level and syntax comprehension occurs during the development of persons with intellectual disabilities (ID). Two cross-sectional developmental trajectory analyses were successively conducted. Study 1 comprised 615 typically developing participants and 615 participants with ID. Their total scores on a syntax comprehension test were regressed on a nonverbal cognitive measure and the slopes of the two groups’ regression lines were compared. In Study 2, logistic regression curves of the two groups for each of the 92 test items were compared. Results showed only negligible between-groups differences of developmental trajectories, whatever the level of analysis. The idea of a progressive dissociation between cognitive level and receptive syntactic skills of people with ID is not confirmed. However, a syntax test evaluating more complex sentences than those used in this study might show such a dissociation.

scholarly journals AB0337 TOFACITINIB MONOTHERAPY OR COMBINED WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS SHOW SIMILAR RETENTION OVER FOUR YEARS. REPORT FROM RHUMADATA ®

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1467.1-1467
Author(s):  
D. Choquette ◽  
L. Bessette ◽  
L. Choquette Sauvageau ◽  
I. Ferdinand ◽  
B. Haraoui ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Real World ◽  
Treatment Initiation ◽  
Retention Rate ◽  
Janus Kinase ◽  
P Value ◽  
Research Support ◽  
Medication Discontinuation ◽  
Kaplan Meier

Background:Since the introduction of biologic agents around the turn of the century, the scientific evidence shows that the majority of agents, independent of the therapeutic target, have a better outcome when used in combination with methotrexate (MTX). In 2014, tofacitinib (TOFA), an agent targeting Janus kinase 1 and 3, has reached the Canadian market with data showing that the combination with MTX may not be necessary [1,2].Objectives:To evaluate the efficacy and retention rate of TOFA in real-world patients with rheumatoid arthritis (RA).Methods:Two cohorts of patients prescribed TOFA was created. The first cohort was formed of patients who were receiving MTX concomitantly with TOFA (COMBO) and the other of patients using TOFA in monotherapy (MONO). MONO patients either never use MTX or were prescribed MTX post-TOFA initiation for at most 20% of the time they were on TOFA. COMBO patients received MTX at the time of TOFA initiation or were prescribed MTX post-TOFA initiation for at least 80% of the time. For all those patients, baseline demographic data definitions. Disease activity score and HAQ-DI were compared from the initiation of TOFA to the last visit. Time to medication discontinuation was extracted, and survival was estimated using Kaplan-Meier calculation for MONO and COMBO cohorts.Results:Overall, 194 patients were selected. Most were women (83%) on average younger than the men (men: 62.6 ± 11.0 years vs. women: 56.9 ± 12.1 years, p-value=0.0130). The patient’s assessments of global disease activity, pain and fatigue were respectively 5.0 ± 2.7, 5.2 ± 2.9, 5.1 ± 3.1 in the COMBO group and 6.2 ± 2.5, 6.5 ± 2.6, 6.3 ± 2.8 in the MONO group all differences being significant across groups. HAQ-DI at treatment initiation was 1.3 ± 0.7 and 1.5 ± 0.7 in the COMBO and MONO groups, respectively, p-value=0.0858. Similarly, the SDAI score at treatment initiation was 23.9 ± 9.4 and 25.2 ± 11.5, p-value=0.5546. Average changes in SDAI were -13.4 ± 15.5 (COMBO) and -8.9 ± 13.5 (MONO), p-value=0.1515, and changes in HAQ -0.21 ± 0.63 and -0.26 ± 0.74, p-value 0.6112. At treatment initiation, DAS28(4)ESR were 4.4 ± 1.4 (COMBO) and 4.6 ± 1.3 (MONO), p-value 0.5815, with respective average changes of -1.06 ± 2.07 and -0.70 ± 1.96, p-value=0.2852. The Kaplan-Meier analysis demonstrated that the COMBO and MONO retention curves were not statistically different (log-rank p-value=0.9318).Conclusion:Sustainability of TOFA in MONO or COMBO are not statistically different as are the changes in DAS28(4)ESR and SDAI. Despite this result, some patients may still benefit from combination with MTX.References:[1]Product Monograph - XELJANZ ® (tofacitinib) tablets for oral administration Initial U.S. Approval: 2012.[2] Reed GW, Gerber RA, Shan Y, et al. Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis [published online ahead of print, 2019 Nov 9].Rheumatol Ther. 2019;6(4):573–586. doi:10.1007/s40744-019-00177-4.Disclosure of Interests:Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Loïc Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant of: Pfizer, Abbvie, Amgen, Novartis, Speakers bureau: Pfizer, Amgen, Boulos Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Pfizer, Roche, and UCB, Speakers bureau: Pfizer, Speakers bureau: Amgen, BMS, Janssen, Pfizer, and UCB, Frédéric Massicotte Consultant of: Abbvie, Janssen, Lilly, Pfizer, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, Jean-Pierre Raynauld Consultant of: ArthroLab Inc., Marie-Anaïs Rémillard Consultant of: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Édith Villeneuve Consultant of: Abbvie, Amgen, BMS, Celgene, Pfizer, Roche, Sanofi-Genzyme,UCB, Paid instructor for: Abbvie, Speakers bureau: AbbVie, BMS, Pfizer, Roche, Louis Coupal: None declared

Game efficiency of elite male sitting volleyball players with regard to athletes’ physical impairment

2017 ◽  
Vol 13 (3) ◽  
pp. 383-390 ◽  
Author(s):  
Jolanta Marszałek ◽  
Bartosz Molik ◽  
Miguel-Angel Gomez
Keyword(s):  
Classification System ◽  
P Value ◽  
Female Group ◽  
Anthropometric Parameters ◽  
Male And Female ◽  
Game Analysis ◽  
Current Classification ◽  
Continue Research ◽  
Classification Procedures ◽  
Game Performance

The aim of this study was to illustrate differences in game efficiency in sitting volleyball of male and female elite athletes in terms of players’ impairment. Game analysis was conducted during World Championships in Sitting Volleyball in 2014. Modified Game Performance Sheet for Sitting Volleyball was used to assess players’ actions: attack, serve, block, block of serve, defense, and ball receiving. Coleman’s formulas were counted to obtain game efficiency of athletes. In statistics, Kruskal–Wallis test and Bonferroni correction were used (p value was set equal .005 and .003, respectively, in male and female group). 128 male and 91 female sitting volleyball athletes were included into this study. They were divided into groups in terms of impairment. There were no statistically significant differences in anthropometric parameters in male and female groups of players. Also, there were not statistically significant differences in game efficiency between players with different impairments in male as well as in female groups. This study did not confirm the current classification system in sitting volleyball (division into minimal disabled and disabled athletes). There is a need to continue research and find more evidences to substantiate or to change the current classification procedures in classification system in sitting volleyball.

scholarly journals Cognitive and School Functioning in Children and Adolescents with Chronic Pain: A Critical Review

2010 ◽  
Vol 15 (4) ◽  
pp. 238-244 ◽  
Author(s):  
Bruce D Dick ◽  
Rebecca Pillai Riddell
Keyword(s):  
Chronic Pain ◽  
Cognitive Function ◽  
Children And Adolescents ◽  
School Attendance ◽  
Developmental Trajectories ◽  
Critical Factor ◽  
Developmental Trajectory ◽  
Future Research ◽  
Research Directions ◽  
Future Research Directions

Cognitive function is a critical factor related to a child’s overall developmental trajectory. There is increasing evidence that chronic pain disrupts cognitive function in adults. Little is known about the nature or impact of cognitive disruption in children and adolescents with chronic pain. The present review examines the current literature related to cognitive function in children and adolescents with chronic pain, implications of these findings and future research directions. Nine studies on this topic were found, with a relatively recent increase in publications related to school attendance and subjective studies of school performance. The studies that were found on this topic suggested that chronic pain affects cognitive function in children but the scope of these effects on children’s function and developmental trajectories is not yet clear. While methodological issues surely make it difficult to study cognitive function in children with chronic pain, the potential gains from such research warrant a pursuit of such work. Much remains to be studied on this important topic.

Abstract 13: Sex Differences in Mortality Among Patients With Covid-19 Related Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Farhaan S Vahidy ◽  
Jennifer Meeks ◽  
Alan Pan ◽  
Thomas Potter ◽  
Osman Khan ◽  
...  
Keyword(s):  
Sex Differences ◽  
Sensitivity Analyses ◽  
Rank Test ◽  
P Value ◽  
Matched Sample ◽  
Healthcare Organizations ◽  
Time To Death ◽  
Kaplan Meier ◽  
Laboratory Confirmation ◽  
Icd 10

Introduction: Overall poor COVID-19 outcomes have been reported among males. We evaluated sex differences in mortality among patients with stroke related to COVID-19. Methods: Utilizing pooled deidentified data from 30 healthcare organizations, we identified COVID-19 patients via ICD-10 diagnosis or documented laboratory confirmation of SARS-CoV-2 RNA or antibodies. Patients with ICD-10 diagnoses of ischemic stroke or intracerebral hemorrhage within 30 days before or after the COVID-19 event were flagged. Male and female patients were propensity score (PS) matched on other demographic and comorbidity variables. Risk Ratio (RR) and 95% Confidence Interval (CI) for association between sex and 90-day mortality is reported. Kaplan-Meier analyses with log rank test (LRT) were conducted for time-to-death. As a sensitivity analysis, we only included a smaller sub-set with first instance of IS or ICH ± 30-days of COVID-19 diagnosis. Results: Among 149,410 COVID-19 patients, 1,618 (1.1%) had a stroke diagnosis ± 30-days of confirmed COVID-19. Of whom, 1,609 patients (847 males and 762 females) were included in primary analyses. Females were older (67.7 vs. 65.7 years) and were more likely to be of black race (34.1% vs. 27.6%). Females had a significantly higher proportion of chronic pulmonary disease (38.8% vs. 28.8%) and obesity (34.2% vs. 24.8%); whereas males had higher proportion of alcohol abuse (8.5% vs. 3.8%). A 1:1 PS algorithm yielded an optimally matched sample of 634 males and females each, balanced on all covariates. In the matched sample, 11.7% of females and 15.8% of males experienced 90-day mortality; RR (CI): 1.35 (1.02 - 1.78), LRT p value 0.04. Higher risk of 90-day mortality among males with COVID-19 and stroke was maintained in the sensitivity analyses, RR (CI): 1.47 (1.06 - 2.00), LRT p value = 0.03 (graphic). Conclusion: Future studies examining the socio-demographic and biological mechanisms for poor stroke outcomes among males with COVID-19 are needed.

Final report and long-term outcomes: Phase I trial of a HER2 intracellular plasmid-based vaccine in HER2+ advanced stage breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2619-2619
Author(s):  
Mary L. Disis ◽  
Yushe Dang ◽  
Andrew L. Coveler ◽  
Doreen Higgins ◽  
Jennifer Childs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Optimal Dose ◽  
P Value ◽  
Final Report ◽  
Linear Regression Models ◽  
Her2 Breast Cancer ◽  
Kaplan Meier ◽  
Number Of Patients ◽  
Vaccine Site

2619 Background: Vaccination with the intracellular domain (ICD) of HER2 in pre-clinical models is both immunogenic and protective against the development of mammary tumors. This study (NCT00436254) was designed to examine the safety and optimal immunogenic dose of a DNA-based vaccine encoding the HER2 ICD in subjects with HER2+ breast cancer. Methods: Sixty-six patients with stage III or IV HER2 + breast cancer in remission or with stable bone only disease were enrolled into three vaccine arms: 1 (10mcg dose of plasmid), 2 (100mcg) and 3 (500mcg). Vaccines were administered i.d. monthly for three immunizations. Endpoints included safety and optimal dose. HER2 specific IFN-gamma immune responses were evaluated and DNA persistence at the vaccine site was assessed. Toxicity and clinical outcomes were followed for 10 years. Results: The majority of vaccine-related toxicity was grade 1 (89%) and grade 2 (11%) and was not significantly different between the three dose arms. All Arms developed HER2 ICD immunity after vaccination, however, patients in Arm 2 and Arm 3 had significantly better immune responses (of higher magnitude and at most time points) than patients in Arm 1 (p=0.003 and p<0.001, respectively) after adjusting for baseline factors. At 60 weeks, the number of patients who maintained the greatest fold-difference in HER2 ICD immune responses from their baseline was highest in Arm 2 (73%) when compared to Arm 1 (47%) and Arm 3 (45%). Associations between ICD responses and plasmid DNA persistence at the vaccine site were estimated via linear regression models. HER ICD immunity after the end of immunizations, relative to baseline, was significantly lower in patients with DNA persistence at week 16 compared to those without persistence (p=0.02). Patients at the highest dose demonstrated the greatest incidence of plasmid persistence (92%) as compared to 33% in Arm 1 and 10% in Arm 2. The median time of follow-up was 118.6 months (Arm 1), 99.7 months (Arm 2), and 73.5 months (Arm 3). The median OS and PFS has not been reached in any Arm and did not differ with respect to treatment arm (Log-rank p-value 0.36 for OS, and 0.63 for PFS). However, we observed a separation of Kaplan-Meier curves for OS from about 40 months and curves for PFS from about 30 months, and the separation maintained until the end of the study for Arm 2 versus Arm 1 and Arm 3. One patient in Arm 2 developed lymphocytic colitis 2.2 years from enrollment deemed possibly related to vaccination. Conclusions: An intermediate dose (100mcg) of vaccine was immunogenic and associated with persistence of immunity at 60 weeks. A randomized phase II trial of the HER2 ICD plasmid-based vaccine in the neoadjuvant setting is in development. Clinical trial information: NCT00436254.

scholarly journals Multidimensional brain-age prediction reveals altered brain developmental trajectory in psychiatric disorders

2020 ◽  
Author(s):  
Xin Niu ◽  
Alexei Taylor ◽  
Russell T. Shinohara ◽  
John Kounios ◽  
Fengqing Zhang
Keyword(s):  
Psychiatric Disorders ◽  
Robust Regression ◽  
Developmental Trajectories ◽  
Brain Structures ◽  
Brain Regions ◽  
Developmental Trajectory ◽  
Imaging Features ◽  
Neuroimaging Data ◽  
Brain Age ◽  
Age Prediction

AbstractBrain regions change in different ways and at different rates. This staggered developmental unfolding is determined by genetics and postnatal experience and is implicated in the progression of psychiatric and neurological disorders. Neuroimaging-based brain-age prediction has emerged as an important new approach for studying brain development. However, the unidimensional brain-age estimates provided by previous methods do not capture the divergent developmental trajectories of various brain structures. Here we propose and illustrate an analytic pipeline to compute an index of multidimensional brain-age that provides regional age predictions. First, using a database of 556 subjects that includes psychiatric and neurological patients as well as healthy controls we conducted robust regression to characterize the developmental trajectory of each MRI-based brain-imaging feature. We then utilized cluster analysis to identify subgroups of imaging features with a similar developmental trajectory. For each identified cluster, we obtained a brain-age prediction by applying machine-learning models with imaging features belonging to each cluster. Brain-age predictions from multiple clusters form a multidimensional brain-age index (MBAI). The MBAI is more sensitive to alterations in brain structures and captured distinct regional change patterns. In particular, the MBAI provided a more flexible analysis of brain age across brain regions that revealed changes in specific structures in psychiatric disorders that would otherwise have been combined in a unidimensional brain age prediction. More generally, brain-age prediction using a subset of homogeneous features circumvents the curse of dimensionality in neuroimaging data.

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