Adaptive Dynamics (United States)

The purpose of this study was to assess the validity of an autism e-screener, Paisley, when utilized in a clinical research setting via a tablet application. The Paisley application used a series of play-based activities, all of which incorporated varying aspects of the ASD-PEDS. Participants included children (18-36 months; n = 198) referred for evaluation of autism spectrum disorder (ASD) and community providers (n = 66) with differing levels of familiarity with ASD. Community providers administered the Paisley application to children who then completed a comprehensive psychological evaluation. Based on comprehensive evaluation, 75% of children met diagnostic criteria for ASD. Paisley scores were significantly higher for children diagnosed with ASD (15.06) versus those not diagnosed (9.34). The newly determined cutoff ASD-PEDS cutoff score of 13 had significantly higher specificity and positive predictive value than the originally proposed cutoff of 11. Results support the use of Paisley by community providers to identify autism risk in toddlers. Limitations and strengths of the work, as well as opportunities for future clinical validation, are described.

Thiol-ene/acrylate shape memory polymers (SMPs) have sufficient stiffness for facile insertion and precision placement and soften after exposure to physiological conditions to reduce the mechanical mismatch with body tissue. As a result, they have demonstrated excellent potential as substrates for various flexible bioelectronic devices, such as cochlear implants, nerve cuffs, cortical probes, plexus blankets, and spinal cord stimulators. To enhance the shape recovery properties and softening effect of SMPs under physiological conditions, we designed and implemented a new class of SMPs as bioelectronics substrates. In detail, we introduced dopamine acrylamide (DAc) as a hydrophilic monomer into a current thiol-ene polymer network. Dry and soaked dynamic mechanical analyses were performed to evaluate the thermomechanical properties, softening kinetics under wet conditions, and shape recovery properties. Modification of SMPs by DAc provided an improved softening effect and shape recovery speed under physiological conditions. Here, we report a new strategy for designing SMPs with enhanced shape recovery properties and lower moduli than previously reported SMPs under physiological conditions without sacrificing stiffness at room temperature by introducing a hydrophilic monomer.

BackgroundThe anti-CTLA-4 immuno-oncology therapy (IO) is limited in clinical efficacy due to its on-target toxicities. ADG116 is a fully human IgG1 monoclonal antibody that targets a unique and highly conserved epitope of CTLA-4. ADG116 enables a controlled T cell activation via partial CD80/86 ligand blockade and promotes strong Treg depletion in the tumor microenvironment via enhanced ADCC. In preclinical studies, ADG116 has been shown to be more potent and better tolerated than ipilimumab. We believe ADG116 can offer a better therapeutic window for this class of molecules, especially when combined with anti-PD-1 therapies.MethodsADG116 monotherapy [10 dose levels from 0.003 to 15 mg/kg (mpk)] and ADG116 (3 or 6 mpk) plus Tori (240 mg) combination therapy were administered Q3W intravenously. The primary endpoints are safety and tolerability; the secondary endpoints are PK, ORR per RECIST 1.1, and PFS.ResultsAs of July 14, 2022, 45 patients (pts) were treated with ADG116 monotherapy, among which 3, 4, 6, 18, and 3 pts received 1, 3, 6, 10, and 15 mpk dose, respectively. The median age was 62; 62% received ≥3 prior lines of therapies, and 31% progressed after prior IO therapies. Only 1 DLT [Grade (G) 4 hyperglycemia] was observed (10 mpk), and MTD was not reached. Only 3 pts showed G3 or above treatment-related AEs (TRAEs); common TRAEs (>10%) consisted of diarrhea, pruritis, and fatigue. Disease control rate is 35% across doses of 3 1 mg/kg (range 30-80%). An initial partial response was observed from a patient with Kaposi’s sarcoma (15 mpk). Dose expansion is ongoing at 10 mpk.Nine pts received ADG116/Tori combination therapy. The median age was 59; 11% received > 3 prior lines of therapies, and none had prior IO therapies. At 6 mpk ADG116/Tori, two pts developed DLTs (2/3; G3 myocarditis & G3 diarrhea). At 3 mpk ADG116/Tori, 1 DLT (1/6, G3 diarrhea) was observed, and five pts are still on treatment (2-5 cycles). One pt with recurrent platinum-refractory HNSCC has a confirmed complete response (CR) and is still on the study (cycle 5). Detailed safety and efficacy data from this study will be reported.ConclusionsADG116 monotherapy has cleared multiple dose levels including 15 mpk, a dose higher than any reported anti-CTLA-4 class agents in the repeat dose setting. ADG116 (3 mpk)/Tori (240mg) Q3W continuous dosing showed a manageable safety profile and encouraging efficacy including CR, supporting its further clinical evaluation.AcknowledgementsWe would like to acknowledge the editorial support from Ami Celeste KnoeflerTrial RegistrationClinical trial identification: NCT04501276Ethics ApprovalThe study obtained ethics approvals from the following Ethics Committee(s)/Institutional Review Board(s), the number/ID of the approval(s),1. Macquarie University HREC; ID: 520-2166-4335-5132. National Health Group Central IRB; ID: 2021/008243. Bellberry HREC; ID: 2020-04-397-AA4. Salus IRB; ID: IORG00056745. CHAMG IRB; ID: 2021-10-064-001-HE0016. Yonsei University Health System IRB; ID: 2021-2495-002/4-2021-14547. Samsung Medical Center IRB; ID: 2021-09-053-0018. WCG IRB; ID: 2021-4916All participants of this clinical study gave informed consent before taking part.ConsentWritten informed consent was obtained from patients for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Two months ago, European neuroradiologists and neurosurgeons were planning their respective annual congresses in spring and summer, the best time of year in Europe and the United States. Suddenly an "earthquake" from Asia hit our shores. Italy was one of the first countries to be affected and

Pneumonia still becomes a public health problems that causing pain and death on toddlers. There are many factors which may influence the increase of pneumonia incidence on toddlers, from the aspect of kid individuals and house anvironment such as ventilation, residential density and the presence of smokers. In 2016 found 760 cases of pneumonia that took place in Yogyakarta Country. One area of this district with high influence of pneumonia is Public Health Center of Gondomanan, this area increased the number of pneumonia incidence in 2014-2016. This research used Cross Sectional research design with Chi Square analysis. The sample of this research is 54 respondents were obtained by Purposive Sampling technique. Instrument is used questionnaired to measure ventilation, residential density and the presence of smokers observation. Showed that there was a correlation between ventilation (p=0.000; RP=2.786), residential density (p=0.007; RP=2.043), the presence of smokers (p=0.002; RP=2.2) with pneumonia incidence on toddlers, in the Area of Puskesmas Gondomanan, Yogyakarta. Ventilation, residential density, and the presence of smokers is Correlation with pneumonia incidence on toddlers in one area of Yogyakarta.<p> </p>

El objetivo del artículo Concepciones de Conflicto Escolar: Un estudio del conflicto desde la perspectiva de los estudiantes, se centra en divulgar los hallazgos de la investigación homónima sobre las concepciones de conflicto que tienen los estudiantes de una Institución Educativa ubicada en Pereira, Risaralda, desde el enfoque de las teorías implícitas. Se plantearon como objetivos específicos identificar y analizar las concepciones de conflicto de los estudiantes del grupo focal elegido. La investigación fue cualitativa, de corte interpretativo; se utilizaron dos técnicas: la entrevista semiestructurada y el grupo focal. El análisis mostró las divergencias y convergencias signicativas en los discursos de los estudiantes respecto del conflicto escolar, lo que propicia nuevas concepciones de este fenómeno en las instituciones educativas. Un hallazgo considerable es que los estudiantes son conscientes de que las situaciones no son naturalmente conflictivas; consideran que el conflicto se origina por actitudes agresivas o intolerantes de sus pares.

Thirty-day readmission rates after percutaneous coronary intervention (PCI) have been related to adverse prognosis, and represent one of the most investigated indicators of quality of care. These data, however, derive from non-European centers evaluating all-cause readmissions, without stratification for diagnosis. All consecutive patients undergoing PCI at our center from January 2009 to December 2011 were enrolled. Thirty-day readmissions related to postinfarction angina, myocardial infarction, unstable angina or heart failure were defined as acute coronary syndrome (ACS) or heart failure rehospitalizations. Major cardiac adverse event (MACE) was the primary outcome, and its single components (death, myocardial infarction and repeated revascularization) the secondary ones. A total of 1192 patients were included; among them, 53 (4.7%) were readmitted within 30 days, and 25 (2.1%) were classified as ACS/heart failure related. During hospitalization, patients with ACS/heart failure readmissions were more likely to suffer a periprocedural myocardial infarction (22 vs. 4%; P = 0.012), and to undergo PCI at 30 days (52 vs. 0.5%; P < 0.001). Logistic regression analysis indicated that periprocedural myocardial infarction represented the only independent predictor of an ACS/heart failure readmission [odds ratio (OR) 4.5; 1.1-16.8; P = 0.047]. After a median follow-up of 787 days (434-1027; first and third quartiles), patients with a 30-day ACS/heart failure readmission experienced higher rates of MACE, all-cause death and myocardial infarction (64 vs. 21%, P < 0.001; 28 vs. 6%, P = 0.017; and 20 vs. 2.7%, P < 0.001, respectively). Cox multivariate analysis indicated that ACS/heart failure 30-day readmissions were independently related to an increased risk of all-cause death (OR 3.3; 1.1-8.8; P = 0.02), differently from 30-day non-ACS/heart failure readmissions (OR 3.1; 0.7-12.9; P = 0.12). Thirty-day readmissions after PCI in an Italian center are infrequent, and only those patients with ACS/heart failure show a detrimental impact on prognosis who have periprocedural myocardial infarction as the only independent predictor.