Analysis of Multi-Directional Recycled Jute Fiber Composite Behavior Using Experimental, Numerical, and Analytical Methods

Composite materials are increasing in popularity as a material of choice in many engineering applications. Major industries using composites include automotive, construction, and sports equipment. Most of the knowledge, research, and technology that will help decrease the cost of composite materials have been aimed at developing synthetic fibers as the reinforcing constituent. This thesis characterizes jute fibers obtained as a byproduct from the coffee industry to determine if they can be viable in composite manufacturing. Experimental analysis, finite element analysis, and analytical modeling are used to characterize jute fiber based composites. Experimental analysis consists of jute fiber bundle tensile testing as well as tensile testing of multiple laminates. Finite element and analytical models were developed to simulate different composite characteristics and their influence on jute composites. Finite element models investigated the influences of fiber undulation, fiber damage, and matrix porosity. Results show that certain manufacturing precautions should be taken to minimize imperfections which have negative influences on the composite. Fiber damage has the largest influence when introduced near the top of the fiber wave and can cause normal stresses to increase 56%. Fiber undulation and matrix porosity also have noticeable influences on the composite

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

One-year retention effects of multiple-dose oxytocin treatment on repetitive behaviors, social responsiveness and attachment: A randomized, placebo-controlled trial.

Poster presentation at INSAR 2018status: publishe

The Effects of Four Weeks of Intranasal Oxytocin on Social Responsiveness and Repetitive and Restricted Behaviors in Autism Spectrum Disorders: A Randomized Controlled Trial

The effects of four weeks of intranasal oxytocin on social responsiveness and repetitive and restricted behaviors in autism spectrum disorders: A randomized controlled trial. S. Bernaerts, C. Dillen, J. Steyaert, and K. Alaerts Background: Autism spectrum disorders (ASDs) are characterized by impairments in social communication and interaction and repetitive and restricted behaviors. To date, no pharmacological treatment exists targeting the core symptoms of ASD, yet the past years, the pharmacological use of a neuropeptide, called oxytocin (OT), has gained increasing interest from the research community to explore its potential for elevating the core social deficits in ASD. OT is known to play a pivotal role in a variety of complex social behaviors by promoting a prosocial attitude and interpersonal bonding. Previous studies showed that exogenously administered OT can affect trust and feelings of attachment insecurity, reduce repetitive and restricted behaviors and increase social cognition. Objectives: A double-blind randomized placebo-controlled trial with thirty-four young adult men with ASD (17 OT/ 17 Placebo (PL)) was conducted to assess behavioral effects of OT therapy (i) at baseline; (ii) after four weeks of daily nasal spray administration; and (iii) four weeks post-treatment to assess potential retention effects. Methods: Doses of 24 IU oxytocin (Syntocinon®, Sigma-tau) or placebo nasal spray (PL) (saline natrium-chloride solution) (3 puffs in each nostril) were administered daily for four weeks. Primary outcome measures to assess treatment effects included the Social Responsiveness Scale (SRS) and the Repetitive Behavior Scale – Revised (RBS-R). Secondary outcome measures included assessments of changes in attachment (State Adult Attachment Scale (SAAM); Inventory of Parent and Peer Attachment (IPPA)); assessments of changes in mood state (Profile of Mood States questionnaire (POMS)); and assessments of changes is reports of quality of life (World Health Organization Quality of Life questionnaire (WHOQOL)). All participants were characterized using IQ and ADOS-scales. Thirty-four male individuals with ASD are currently enrolled in the study and recruitment is still ongoing. Results: After four weeks of OT nasal spray administration, self-reports on repetitive and restricted behaviors (RBS-R) were shown to be tentatively reduced in the OT group, not in the PL group (F(1, 31)=3.83, p=0.06) and of note, the effect of OT persisted until one month after the treatment (retention: F(1, 31)=4.02, p=0.05). Immediately after the four weeks of treatment, we found no significant effects of OT on social functioning as assessed using self- and informant-based reports of the SRS. Interestingly however, at the retention session, a significant effect was revealed for the informant-based SRS (F(1, 22)=4.90, p=0.04), indicating that clear improvements in social responsiveness emerged one month after cessation of the actual treatment (specifically for reports of social motivation (F(1, 22)=4.71, p=0.04) and social communication (F(1, 22)=7.39, p=0.01)). For the secondary outcome measures, only tentative effects were revealed, indicating improvements in self-reports of attachment immediately after the four-week treatment (F(1, 32)=3.32, p=0.08) (IPPA) and improvements in the experience of social relationships at the retention session one-month post-trial (F(1, 31)=3.07, p=0.09) (WHOQOL). Conclusions: The observed improvements after four weeks of daily treatment with intranasal OT in our primary outcome measures (assessing social responsiveness and repetitive and restricted behaviors) indicate that OT can induce long-term behavioral changes in individuals with ASD that outlast the time of intervention.status: accepte

One-year retention effects of multiple-dose oxytocin treatment on repetitive behaviors, social responsiveness and attachment: A randomized, placebo-controlled trial.

Poster presentation at the "oxytocin workshop" in Ericestatus: publishe

Oxytocin treatment attenuates amygdala activity in autism: a treatment-mechanism study with long-term follow-up

Intranasal administration of the neuropeptide oxytocin (IN-OT) is increasingly considered as a potential treatment for targeting the core symptoms of autism spectrum disorder (ASD), but the effects of continual use on neural substrates are fairly unexplored and long-term effects are unknown. In this double-blind, randomized, placebo-controlled study, we investigated the effects of single-dose and multiple-dose IN-OT treatment (4 weeks of daily (24 IU) administrations) on brain activity related to processing emotional states. Thirty-eight adult men with ASD (aged between 18 and 35 years) underwent functional magnetic resonance imaging of the posterior superior temporal gyrus (pSTS) and amygdala regions while processing emotional states from point-light biological motion. In line with prior research, a single dose of IN-OT induced a reliable increase in pSTS brain activity during the processing of point-light biological motion, but no consistent long-term changes in pSTS activity were induced after the multiple-dose treatment. In terms of bilateral amygdala, the multiple-dose treatment induced a consistent attenuation in brain activity, which outlasted the period of actual administrations until four weeks and one year post-treatment. Critically, participants with stronger attenuations in amygdala-activity showed greater behavioral improvements, particularly in terms of self-reported feelings of avoidant attachment and social functioning. Together, these observations provide initial insights into the long-lasting neural consequences of chronic IN-OT use on amygdala functioning and provide first indications that the acute versus chronic effects of IN-OT administration may be qualitatively different. Larger studies are however warranted to further elucidate the long-term impact of IN-OT treatment on human neural substrates and its behavioral consequences.status: publishe

Oxytocin treatment attenuates amygdala activity in autism: a treatment-mechanism study with long-term follow-up

Intranasal administration of the neuropeptide oxytocin (IN-OT) is increasingly considered as a potential treatment for targeting the core symptoms of autism spectrum disorder (ASD), but the effects of continual use on neural substrates are fairly unexplored and long-term effects are unknown. In this double-blind, randomized, placebo-controlled study, we investigated the effects of single-dose and multiple-dose IN-OT treatment (4 weeks of daily (24 IU) administrations) on brain activity related to processing emotional states. Thirty-eight adult men with ASD (aged between 18 and 35 years) underwent functional magnetic resonance imaging of the posterior superior temporal gyrus (pSTS) and amygdala regions while processing emotional states from point-light biological motion. In line with prior research, a single dose of IN-OT induced a reliable increase in pSTS brain activity during the processing of point-light biological motion, but no consistent long-term changes in pSTS activity were induced after the multiple-dose treatment. In terms of bilateral amygdala, the multiple-dose treatment induced a consistent attenuation in brain activity, which outlasted the period of actual administrations until four weeks and one year post-treatment. Critically, participants with stronger attenuations in amygdala-activity showed greater behavioral improvements, particularly in terms of self-reported feelings of avoidant attachment and social functioning. Together, these observations provide initial insights into the long-lasting neural consequences of chronic IN-OT use on amygdala functioning and provide first indications that the acute versus chronic effects of IN-OT administration may be qualitatively different. Larger studies are however warranted to further elucidate the long-term impact of IN-OT treatment on human neural substrates and its behavioral consequences.ISSN:2158-318

Long-term effects of oxytocin on fronto-amygdala connectivity in autism: A randomized placebo-controlled trial

Autism spectrum disorders (ASD) are characterized by impairments in social interaction and repetitive and restricted behaviors. To date, no pharmacological treatment exists targeting the core symptoms of ASD, yet the pharmacological use of the neuropeptide oxytocin (OT) has gained interest from the research community to explore its potential for elevating social deficits in ASD. We aimed to examine neural and behavioral effects of single- and multiple-dose OT treatment and the possibility of retention effects one month post-treatment using a double-blind, randomized, placebo-controlled, between-subject clinical trial including thirty-eight adult men with ASD. A key question was to determine whether similar neural effects are observed after single- versus multiple-dose treatment; whether the neural effects are paralleled by behavioral improvements on core ASD symptoms and specifically, whether the observed effects can outlast the period of actual administration. Doses of 24 IU oxytocin (Syntocinon®, Sigma-tau) or placebo nasal spray (saline natrium-chloride solution) were administered daily for four weeks. Resting-state fMRI neuroimaging was adopted to evaluate ‘intrinsic’ OT-induced changes in functional connectivity of amygdala-prefrontal circuits at rest (medial prefrontal cortex and orbitofrontal cortex). Behavioral effects of OT treatment were primarily assessed on two core ASD symptoms via self-report questionnaires: restricted and repetitive behavior and social responsiveness, and secondarily, on self-reports of state attachment, trait attachment, and quality of life. Data showed that four-week OT-treatment (24 IU/day) reduced functional connectivity of the amygdala with prefrontal regions in the orbitofrontal cortex until one month post-treatment. Neural changes in amygdala-prefrontal coupling were shown to be paralleled by behavioral improvements in repetitive behavior, attachment avoidance and social motivation. These findings provide further insights into the biological mechanism by which oxytocin exerts its prosocial effects and the observation that the neural and behavioral effects outlasted the period of actual administration further supports the therapeutic potential of oxytocin interventions for ASD.status: accepte

Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up

Background: Intranasal administration of the "prosocial" neuropeptide oxytocin is increasingly explored as a potential treatment for targeting the core characteristics of autism spectrum disorder (ASD). However, long-term follow-up studies, evaluating the possibility of long-lasting retention effects, are currently lacking. Methods: Using a double-blind, randomized, placebo-controlled, parallel design, this pilot clinical trial explored the possibility of long-lasting behavioral effects of 4 weeks of intranasal oxytocin treatment (24 International Units once daily in the morning) in 40 adult men with ASD. To do so, self-report and informant-based questionnaires assessing core autism symptoms and characterizations of attachment were administered at baseline, immediately after 4 weeks of treatment (approximately 24 h after the last nasal spray administration), and at two follow-up sessions, 4 weeks and 1 year post-treatment. Results: No treatment-specific effects were identified in the primary outcome assessing social symptoms (Social Responsiveness Scale, self- and informant-rated). In particular, with respect to self-reported social responsiveness, improvements were evident both in the oxytocin and in the placebo group, yielding no significant between-group difference (p = .37). Also informant-rated improvements in social responsiveness were not significantly larger in the oxytocin, compared to the placebo group (between-group difference: p = .19). Among the secondary outcome measures, treatment-specific improvements were identified in the Repetitive Behavior Scale and State Adult Attachment Measure, indicating reductions in self-reported repetitive behaviors (p = .04) and reduced feelings of avoidance toward others (p = .03) in the oxytocin group compared to the placebo group, up to 1 month and even 1 year post-treatment. Treatment-specific effects were also revealed in screenings of mood states (Profile of Mood States), indicating higher reports of "vigor" (feeling energetic, active, lively) in the oxytocin, compared to the placebo group (p = .03). Conclusions: While no treatment-specific improvements were evident in terms of core social symptoms, the current observations of long-term beneficial effects on repetitive behaviors and feelings of avoidance are promising and suggestive of a therapeutic potential of oxytocin treatment for ASD. However, given the exploratory nature of this pilot study, future studies are warranted to evaluate the long-term effects of OT administration further. Trial registration: The trial was registered with the European Clinical Trial Registry (Eudract 2014-000586-45) on January 22, 2014 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000586-45/BE).status: publishe