Review on Contributing Factors to Anxiety in High-Functioning Autism

Individuals with autism spectrum disorder are characterised by difficulties in social communication, by restricted, repetitive behaviour and interests. Autism is a highly heterogeneous disorder; high-functioning individuals with autism have average or higher intelligence and superficially normal language skills. The lack of intellectual disability does not mean that they can overcome inherent difficulties in social communication and interaction. They struggle to negotiate social interactions and manage daily tasks in a neurotypical world. They are at risk of experiencing mental health difficulties compared to general population. One of the most common mental health difficulties co-occurring with high-functioning autism is anxiety, which is associated with poor individual, family, and social outcomes. The chapter reviews studies on the contributing factors to anxiety in high-functioning autism. Psychological, cognitive, and social factors seem to be important, while there are indications for the existence of some neurobiological basis. It also considers ideas as to how to tackle anxiety.

OTL-PEM: an optimization-based two-layer pointwise ensemble of surrogate models

The ensemble of surrogate models is increasingly implemented in practice for its more flexibility and robustness compared to the individual surrogate models. In this work, a novel pointwise ensemble of surrogate models named the optimization-based two-layer pointwise ensemble of surrogate model (OTL-PEM) is proposed. In the OTL-PEM, the framework of two-layer surrogate models is defined, where the data-surrogate models containing different types of individual surrogate models are to fit the given dataset, while the weight-surrogate models are modeled based on the cross-validation errors aiming to fit the pointwise weights of different individual surrogate models. To avoid the negative influence of the poor individual surrogate models, the model selection problem is transformed into several optimization problems which can be solved easily by the mature optimization algorithm to eliminate the globally poor surrogate models. In addition, the optimization space is extracted to alleviating the predictive instability caused by the extrapolation of the weight-surrogate models. Forty test functions are used to select the appropriate hyperparameters of the OTL-PEM, and to evaluate the performance of the OTL-PEM. The results indicate that the OTL-PEM can provide more accurate and robust approximation performance compared with individual surrogate models as well as other ensembles of surrogate models.

Prospective cohort study of the predictive value of inflammatory biomarkers over clinical variables in children and young people with cancer presenting with fever and neutropenia

Introduction Fever during chemotherapy induced neutropenia is a common and potentially life-threatening complication of the treatment of childhood cancer. Predictions of poor outcome could be enhanced by incorporating serum biomarkers of inflammation at presentation and reassessment. Methods A prospective cohort study was conducted of children under 18 years old, being treated for cancer or a cancer-like condition, who presented with fever (≥ 38.0°C) and neutropenia (neutrophil count < 0.5*109/L). Clinical features were recorded, along with three experimental inflammatory biomarkers: procalcitonin (PCT), interleukin-6 (IL-6) and interleukin-8 (IL-8). Outcomes included serious medical complications (SMC): any infection related mortality, critical care and organ support, severe sepsis, septic shock, significant microbiologically defined infection, or radiologically confirmed pneumonia. Results Biomarker assessments were undertaken in 43 episodes of fever and neutropenia, from 31 patients aged between four months and 17 years old (median six years): 20 were female and 22 had acute leukaemia. Five episodes of SMC were noted. PCT, IL-6 and IL-8 had poor individual discriminatory ability (C-statistic 0.48 to 0.60) and did not add to the value of clinical risk stratification tools. Insufficient data were collected to formally assess the value of repeated assessments. Conclusions Incorporating serum biomarkers of inflammation at presentation of episodes of fever with neutropenia in childhood does not clearly improve risk stratification. Repeated assessments over time may be of value.

Prevalence of depression and suicide ideation in Hong Kong doctors: a cross-sectional study

Depression amongst physicians can lead to poor individual and institutional outcomes. This study examined the prevalence and factors associated with depression and suicidal ideation amongst doctors in Hong Kong. Doctors who graduated from medical school at the University of Hong Kong between 1995 and 2014 were invited to participate in a survey measuring depressive symptoms, suicidal ideation and thoughts of self-harm, lifestyle behaviours, career satisfaction and socio-demographic characteristics. Data collection occurred between January and April 2016. The prevalence of screened-positive depression was 16.0% and 15.3% of respondents reported having suicidal ideation. Amongst those with positive depression screening scores, less than half reported having a diagnosed mood disorder. Sleeping fewer hours was associated with higher depression scores (P < 0.001) and an increased odds of meeting the cut-off for depression (P < 0.001). Factors associated with suicidal ideation included being unmarried (P = 0.012) and sleeping fewer hours (P = 0.022). Hong Kong doctors appear to have high rates of undiagnosed depression, and high levels of depressive symptoms and suicidal ideations. There is a need for greater awareness of the morbidity due to depression and to promote better mental health help-seeking among physicians. Barriers to mental health help-seeking need to be addressed and appropriate resources allocated to reduce suffering.

Understanding institutional barriers in the climate change adaptation planning process of the city of Beirut: vicious cycles and opportunities

Cities around the world are confronted with the need to put in place climate adaptation policies to protect citizens and properties from climate change impacts. This article applies components of the framework developed by Moser and Ekström (2010) onto empirical qualitative data to diagnose institutional barriers to climate change adaptation in the Municipality of Beirut, Lebanon. Our approach reveals the presence of two vicious cycles influencing each other. In the first cycle, the root cause barrier is major political interference generating competing priorities and poor individual interest in climate change. A second vicious cycle is derived from feedbacks caused by the first and leading to the absence of a dedicated department where sector specific climate risk information is gathered and shared with other departments, limited knowledge and scientific understanding, as well as a distorted framing or vision, where climate change is considered unrelated to other issues and is to be dealt with at higher levels of government. The article also highlights the need to analyze interlinkages between barriers in order to suggest how to overcome them. The most common way to overcome barriers according to interviewees is through national and international support followed by the creation of a data bank. These opportunities could be explored by national and international policy-makers to break the deadlock in Beirut.

Aggregating probabilistic predictions of the safety, efficacy, and timing of a COVID-19 vaccine

Safe, efficacious vaccines were developed to reduce the transmission of SARS-CoV-2 during the COVID-19 pandemic. But in the middle of 2020, vaccine effectiveness, safety, and the timeline for when a vaccine would be approved and distributed to the public was uncertain. To support public health decision making, we solicited trained forecasters and experts in vaccinology and infectious disease to provide monthly probabilistic predictions from July to September of 2020 of the efficacy, safety, timing, and delivery of a COVID-19 vaccine. We found, that despite sparse historical data, a consensus--a combination of human judgment probabilistic predictions--can quantify the uncertainty in clinical significance and timing of a potential vaccine. The consensus underestimated how fast a therapy would show a survival benefit and the high efficacy of approved COVID-19 vaccines. However, the consensus did make an accurate prediction for when a vaccine would be approved by the FDA. Compared to individual forecasters, the consensus was consistently above the 50th percentile of the most accurate forecasts. A consensus is a fast and versatile method to build probabilistic predictions of a developing vaccine that is robust to poor individual predictions. Though experts and trained forecasters did underestimate the speed of development and the high efficacy of a SARS-CoV-2 vaccine, consensus predictions can improve situational awareness for public health officials and for the public make clearer the risks, rewards, and timing of a vaccine.

Divergent Importance of Chronobiological Considerations in High- and Low-dose Melatonin Therapies

Melatonin has been used preclinically and clinically for different purposes. Some applications are related to readjustment of circadian oscillators, others use doses that exceed the saturation of melatonin receptors MT1 and MT2 and are unsuitable for chronobiological purposes. Conditions are outlined for appropriately applying melatonin as a chronobiotic or for protective actions at elevated levels. Circadian readjustments require doses in the lower mg range, according to receptor affinities. However, this needs consideration of the phase response curve, which contains a silent zone, a delay part, a transition point and an advance part. Notably, the dim light melatonin onset (DLMO) is found in the silent zone. In this specific phase, melatonin can induce sleep onset, but does not shift the circadian master clock. Although sleep onset is also under circadian control, sleep and circadian susceptibility are dissociated at this point. Other limits of soporific effects concern dose, duration of action and poor individual responses. The use of high melatonin doses, up to several hundred mg, for purposes of antioxidative and anti-inflammatory protection, especially in sepsis and viral diseases, have to be seen in the context of melatonin’s tissue levels, its formation in mitochondria, and detoxification of free radicals.