Scientific Consulting Group

Autism Spectrum Disorder (ASD) is a heterogenous condition that has no biologically relevant subtypes yet. Here, we utilized a multidimensional approach considering social deficits in ASD alongside negative valence and empathy dysfunction to distinguish ASD from Neurotypicals (NT) and to generate ASD subtypes using machine learning approaches. 114 subjects were analyzed, with 70 being NT and 44 ASD, all male with an IQ greater than 70, with 5 domains of personality (NEO-PI-r) and Reading the Mind the Eyes Test (RMET) scores included in the main classifier. We then used a multitude of behavioral (such as IQ, Broader Autism Phenotype, Autism Quotient, Interpersonal Reactivity Index) and clinical measures such as Autism Diagnostic Interview-Revised (ADI-R) alongside biological methods including DNA methylation of OXTR gene and resting-state functional connectivity (rsFC) to validate the putative subtypes. 30 ASD who received IN-OXT in a randomized, placebo-controlled, within-subject design and 17 new NT were part of the rs-FC analysis. A random forest tree algorithm was used to classify NT and ASD and Shapley Additive Explanation Values were used to describe the model and to cluster ASD subtypes using K-Means clustering. Three subtypes were generated with two of them being highly distinctive in behavioral and brain functional traits. One subtype named NASA (or Negative Affect and Social Aloofness) was characterized by high Neuroticism and Low warmth alongside lower rsFC between networks involved in social cognition, self-awareness, and sensory processing, such as Superior Temporal Sulcus and Sensorimotor Network; or ACC/Insula with visual cortex, Posterior Cingulate Cortex and visual cortex. The second subtype NADR (Neurocognitive and Affect Dysregulation with Resistance to Change) was characterized by higher DNA methylation of OXTR , hyperconnectivity between default mode network, reward areas and inferior frontal and fusiform networks. NADR has more cognitive difficulties and higher ADI-R scores as well as higher Neuroticism, higher personal distress, higher rigidity and lower openness. In a mixed model analysis, we found that IN-OXT in a dose dependent manner impacted NASA subtype by modulating rsFC between PCC and cerebellum and between Brainstem/Cerebellum and Parietal cortex to probably enhance social cognition and to reduce negative valence in this subtype.

Abstract Current climate change adaptation assessments are limited in their scope, accuracy, and relevance to local contexts. Here, we present an improved assessment approach using coproduction, applied to locally led adaptation (LLA) to flood risk in Tamale, Ghana. Through a multi-year process, including participatory ranking, focus groups, and household surveys, 11 solutions were assessed. Assessments considered multiple risk-reduction mechanisms, equity, sustainability, and co-impacts. Community-based and behavioural solutions, such as collective action and tree planting, were deemed most effective, whilst structural and technical solutions were ranked lower. By integrating these assessments into a flood risk model, we show that LLA approaches significantly reduced flood risk overall but did not address existing inequalities. Our results showcase the potential of coproduction to increase the scope and robustness of adaptation assessments and highlight practical challenges of delivering on the LLA principles in real-world settings.

[This corrects the article DOI: 10.1371/journal.pgph.0004612.].

Lost productivity is a common cause of cost overrun on construction projects and often results in construction claims. There are several different loss of productivity quantification methods and variants of those methods. Due to lack of adequate classification, the use of these methods is not well disciplined. For example, the implementation of the measured mile method can vary significantly between analysts or projects. This paper proposes a more rigorous classification system for loss of productivity quantification methods. This work first defines key dimensions of the hierarchy/matrix of the classification system, including productivity type, measurement perspective, data reliance, similarity requirement, analysis technique, work composition and divisions, causation, and others, and then places various loss of productivity quantification method implementations to different positions in the classification system. With this rigorous classification of loss of productivity methods, the variations between different method implementations can be clearly identified and the exact methodology can be applied to a construction claim in a well-defined and unambiguous manner.

A comprehensive review of existing toxicity and human exposure data for the ultraviolet filter avobenzone (butyl methoxydibenzoylmethane) was conducted to assess its safety as currently used in over-the-counter sunscreen formulations. Avobenzone has a suitable safety profile without any clear markers of toxicity or endpoints of concern. There are sufficient clinical studies and in vitro and in vivo toxicity studies in animal models to assess avobenzone’s pharmacokinetics, pharmacodynamics, and potential toxicological properties, supportive of its long history of safe use. No harmonized dermal absorption value was available, but the clinical data indicate low percutaneous absorption of avobenzone in humans (≤0.59% of the applied dose). There were no data to characterize the distribution of avobenzone; however, four tentative metabolites of avobenzone have been identified, and limited excretion in urine was demonstrated in human biomonitoring studies. Avobenzone generally did not cause dermal irritation or sensitization, but indications of photoallergy have been reported in clinical case studies. The acute toxicity profile indicated that avobenzone has minimal toxicity. The no-observed-adverse-effect level (NOAEL) for general toxicity from a rat dietary subchronic toxicity study was 450 mg/kg/day. There was no evidence of avobenzone effects on immune tissues or the estrogen, androgen, or thyroid systems. Although there were no formal 2-year carcinogenicity studies for avobenzone, a 90-day dietary exposure study in rats did not show any increase in hyperplasia of any tissue or evidence of cytotoxicity, and avobenzone has not shown any indication of genotoxicity either in vitro or in vivo. Together, this indicates that key events for modes of action for avobenzone are absent and carcinogenicity in humans is unlikely. Based on the selected rat subchronic NOAEL and conservative assumptions for estimating the systemic exposure dose (SED) from the application of sunscreen products, margins of exposure (defined as the ratio of NOAEL to SED) greater than 100 were obtained for avobenzone. Therefore, the available data show that avobenzone is unlikely to pose a risk to human health when used in sunscreen products at concentrations up to the permitted maximum usage levels in the United States and Canada, which is 3%.

Background Closed incision negative pressure wound therapy (ciNPWT) is a successful strategy to improve surgical outcomes. However, its use can be limited by the cost of electrically-powered ciNPWT systems, especially in developing countries. A novel negative pressure wound therapy (NPWT) device that utilizes a chemical reaction to create negative pressure promises to be significantly less costly. Method A first-in-human clinical study was completed to evaluate the safety and performance of a novel ciNPWT device(NCT04488666). The primary endpoint was the longevity of the delivery of negative pressure to the wound over seven days. Wound healing was assessed on day seven and day 30. Assessment of the scar quality on day 14 and day 30, exudate management, and ease of use were also undertaken. Results A total of 23 patients were enrolled in the study (mean age 65.0±11.9 years; mean BMI 30.9±6.8 kg/m2with a mean wound length of 7.6±2.6 cm, predominantly in elective cutaneous surgery and spinal surgery procedures. The new device was used to maintain negative pressure and manage wound exudate for a mean of 6.3±1.6 days per incision. The mean number of devices used per incision was 1.2±0.5. The Additional treatment; Serous discharge; Erythema; Purulent exudate; Separation of deep tissues; Isolation of bacteria; and Stay as inpatient for a prolonged period (over 14 days) or ASEPSISand the Patient and Observer Scar Assessment Scale (POSAS) scores indicated overall normal healing and scar quality.There were a total of nine adverse events in five patients. Wounds treated with the new device were not painful. Participant and clinician assessments showed that the devices were easy to use in the hospital and easy to manage at home with routine activities. The device made no audible sound during its use. Conclusion A novel, chemically-generated incisional negative pressure deviceperformed effectively in clinical practice and was shown to be convenient and easy to use. Future studies to assess the effects on surgical site complications are warranted.