Alliance for Scientific Autism Intervention: System Components and Outcome Data from High-Quality Service Delivery Organizations.

Promoting excellence in autism intervention is arguably more urgent than ever for the field of applied behavior analysis. To fulfill this objective, autism agencies must operate from validated program systems and do so with fidelity. Program components include, but are not limited to, staff training and evaluation of clinical skills, functional personnel roles designed to promote positive outcomes for those served, and professional staff-communication-skill repertoires.

Global assessment of marine plastic exposure risk for oceanic birds.

Plastic pollution is distributed patchily around the world's oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation.

Commonly Used Therapeutics Associated with Changes in Arousal Inhibit GABAR Activation.

GABA receptor-positive modulators are well-known to induce sedation, sleep, and general anesthesia. Conversely, GABA receptor negative allosteric modulators (GABARNAMs) can increase arousal and induce seizures. Motivated by our studies with patients with hypersomnia, and our discovery that two GABARNAMs can restore the Excitation/Inhibition (E/I) balance in vitro and arousal in vivo, we chose to screen 11 compounds that have been reported to modulate arousal, to see if they shared a GABA-related mechanism.

Sulfur- and phosphorus-standardized metal quantification of biological specimens using inductively coupled plasma mass spectrometry.

This protocol describes how inductively coupled plasma mass spectrometry (ICP-MS) can quantify metals, sulfur, and phosphorus present in biological specimens. The high sensitivity of ICP-MS enables detection of these elements at very low concentrations, and absolute quantification is achieved with standard curves. Sulfur or phosphorus standardization reduces variability that arises because of slight differences in sample composition.

Mitochondrial Proteostasis Requires Genes Encoded in a Neurodevelopmental Syndrome Locus.

Eukaryotic cells maintain proteostasis through mechanisms that require cytoplasmic and mitochondrial translation. Genetic defects affecting cytoplasmic translation perturb synapse development, neurotransmission, and are causative of neurodevelopmental disorders, such as Fragile X syndrome. In contrast, there is little indication that mitochondrial proteostasis, either in the form of mitochondrial protein translation and/or degradation, is required for synapse development and function.

Global political responsibility for the conservation of albatrosses and large petrels.

Migratory marine species cross political borders and enter the high seas, where the lack of an effective global management framework for biodiversity leaves them vulnerable to threats. Here, we combine 10,108 tracks from 5775 individual birds at 87 sites with data on breeding population sizes to estimate the relative year-round importance of national jurisdictions and high seas areas for 39 species of albatrosses and large petrels. Populations from every country made extensive use of the high seas, indicating the stake each country has in the management of biodiversity in international waters.

Systems Analysis of the 22q11.2 Microdeletion Syndrome Converges on a Mitochondrial Interactome Necessary for Synapse Function and Behavior.

Neurodevelopmental disorders offer insight into synaptic mechanisms. To unbiasedly uncover these mechanisms, we studied the 22q11.2 syndrome, a recurrent copy number variant, which is the highest schizophrenia genetic risk factor.

Randomized double-blind trial of amifostine versus placebo for radiation-induced xerostomia in patients with head and neck cancer.

Introduction: The role of the radioprotector amifostine in ameliorating radiotherapy side effects in head and neck squamous cell carcinoma (HNSCC) is controversial. This trial aimed to determine whether pretreatment with amifostine reduced the incidence of Radiation Therapy Oncology Group grade ≥2 acute and late xerostomia in patients receiving definitive or adjuvant radiotherapy for HNSCC, without reducing tumour control or survival.

Methods: Between 14 September 2001 and 8 November 2004, 44 Royal Adelaide Hospital patients were randomized double-blind to receive amifostine (200 mg/m IV) or placebo (normal saline IV) 5 days/week, prior to standard radiotherapy (60-70 Gy), each having ≥75% of the parotids treated to ≥40 Gy.

Fatal methemoglobinemia complicating alkaptonuria (ochronosis): a rare presentation.

A 61-year-old female died in hospital with multiple organ failure 4 weeks following presentation with acute kidney injury, hemolytic anemia and methemoglobinemia. At autopsy, brown to black discoloration of cartilages was observed. Histology revealed brown pigmentation of the hyaline cartilage, with focal full-thickness erosion of the articular hyaline cartilage, characteristic of alkaptonuria (ochronosis).

Ebstein Anomaly and Sudden Childhood Death.

A 13-year-old girl is reported who died suddenly and unexpectedly in her sleep from previously undiagnosed Ebstein anomaly. At autopsy, there was dilatation of the right atrium with marked dilatation of the right auricle and apical displacement of the tricuspid valve into the right ventricular cavity with atrialization of the upper portion of the right ventricle. There were also prominent dysplastic changes in both the septal and posterior leaflets of the tricuspid valve with thickening of the valve and fusion of leaflets to the wall of the ventricle.

Rigor, reproducibility, and in vitro cerebrospinal fluid assays: The devil in the details.

Divergent results and misinterpretation of non-significant findings remain problematic in science – especially in retrospective, hypothesis generating, translational research. When such divergence occurs, it is imperative that the cause of the divergence be established. In their recent paper in , Dauvilliers challenged our earlier finding that cerebrospinal fluid (CSF) from some patients with unexplained excessive daytime sleepiness enhances the activation of GABA receptors (GABA-R).

The Proteome of BLOC-1 Genetic Defects Identifies the Arp2/3 Actin Polymerization Complex to Function Downstream of the Schizophrenia Susceptibility Factor Dysbindin at the Synapse.

Unlabelled: Proteome modifications downstream of monogenic or polygenic disorders have the potential to uncover novel molecular mechanisms participating in pathogenesis and/or extragenic modification of phenotypic expression. We tested this idea by determining the proteome sensitive to genetic defects in a locus encoding dysbindin, a protein required for synapse biology and implicated in schizophrenia risk. We applied quantitative mass spectrometry to identify proteins expressed in neuronal cells the abundance of which was altered after downregulation of the schizophrenia susceptibility factor dysbindin (Bloc1s8) or two other dysbindin-interacting polypeptides, which assemble into the octameric biogenesis of lysosome-related organelles complex 1 (BLOC-1).

Clarithromycin in γ-aminobutyric acid-Related hypersomnolence: A randomized, crossover trial.

Objective: Some central hypersomnolence syndromes are associated with a positive allosteric modulator of γ-aminobutyric acid (GABA)-A receptors in cerebrospinal fluid. Negative allosteric modulators of GABA-A receptors, including clarithromycin, have been reported to reduce sleepiness in these patients. We sought to systematically assess the effects of clarithromycin on objective vigilance and subjective sleepiness.

Quality indicators for prostate radiotherapy: are patients disadvantaged by receiving treatment in a 'generalist' centre?

Introduction: The purpose of this retrospective review was to evaluate concordance with evidence-based quality indicator guidelines for prostate cancer patients treated radically in a 'generalist' (as distinct from 'sub-specialist') centre. We were concerned that the quality of treatment may be lower in a generalist centre. If so, the findings could have relevance for many radiotherapy departments that treat prostate cancer.

Improvement in daytime sleepiness with clarithromycin in patients with GABA-related hypersomnia: Clinical experience.

The macrolide antibiotic clarithromycin can enhance central nervous system excitability, possibly by antagonism of GABA-A receptors. Enhancement of GABA signaling has recently been demonstrated in a significant proportion of patients with central nervous system hypersomnias, so we sought to determine whether clarithromycin might provide symptomatic benefit in these patients. We performed a retrospective review of all patients treated with clarithromycin for hypersomnia, in whom cerebrospinal fluid enhanced GABA-A receptor activity in vitro in excess of controls, excluding those with hypocretin deficiency or definite cataplexy.

The molecular basis of restless legs syndrome.

Restless legs syndrome (RLS) disrupts sleep in a substantial proportion of the population and is associated with higher cross-sectional rates of affective illness and cardiovascular disease. While dopamine and iron availability in the brain modulate emergence of symptoms, and dopamine agonists and iron alleviate the sensory symptoms and motor signs of RLS, the biology of the disorder is incompletely understood. Genetic factors, as opposed to environmental ones, account for most of the disease variance.

Modeling the genetic basis for human sleep disorders in Drosophila.

Sleep research in Drosophila is not only here to stay, but is making impressive strides towards helping us understand the biological basis for and the purpose of sleep-perhaps one of the most complex and enigmatic of behaviors. Thanks to over a decade of sleep-related studies in flies, more molecular methods are being applied than ever before towards understanding the genetic basis of sleep disorders. The advent of high-throughput technologies that can rapidly interrogate whole genomes, epigenomes and proteomes, has also revolutionized our ability to detect genetic variants that might be causal for a number of sleep disorders.

Chronic interferon-α decreases dopamine 2 receptor binding and striatal dopamine release in association with anhedonia-like behavior in nonhuman primates.

Neuroimaging studies in humans have demonstrated that inflammatory cytokines target basal ganglia function and presynaptic dopamine (DA), leading to symptoms of depression. Cytokine-treated nonhuman primates also exhibit evidence of altered DA metabolism in association with depressive-like behaviors. To further examine cytokine effects on striatal DA function, eight rhesus monkeys (four male, four female) were administered interferon (IFN)-α (20 MIU/m(2) s.

An emerging role for Cullin-3 mediated ubiquitination in sleep and circadian rhythm: insights from Drosophila.

Although the neurophysiological correlates of sleep have been thoroughly described, genetic mechanisms that control sleep architecture, long surmised from ethological studies, family histories and clinical observations, have only been investigated during the past decade. Key contributions to the molecular understanding of sleep have come from studies in Drosophila, benefitting from a strong history of circadian rhythm research. For instance, a number of recent papers have highlighted the role of the E3 ubiquitin ligase Cullin-3 in the regulation of circadian rhythm and sleep.

Modulation of vigilance in the primary hypersomnias by endogenous enhancement of GABAA receptors.

The biology underlying excessive daytime sleepiness (hypersomnolence) is incompletely understood. After excluding known causes of sleepiness in 32 hypersomnolent patients, we showed that, in the presence of 10 μM γ-aminobutyric acid (GABA), cerebrospinal fluid (CSF) from these subjects stimulated GABA(A) receptor function in vitro by 84.0 ± 40.

Diagnosis and management of the epilepsies in children: a summary of the partial update of the 2012 NICE epilepsy guideline.

The epilepsies of childhood are a heterogeneous group of disorders with different causes, treatments and outcomes. The choice of anti-epileptic drug is largely determined by its effectiveness in a specific epilepsy syndrome, or seizure type(s) if a syndrome cannot be readily identified, and the drug's safety profile. There are minimal randomised controlled trial data to help inform this decision.