Adverse events associated with pediatric exposures to dextromethorphan

Study objective: Dextromethorphan is the most common over-the-counter (OTC) antitussive medication. We sought to characterize adverse events associated with dextromethorphan in children <12 years old from a surveillance program of OTC cough/cold medication exposures.

Methods: This is a retrospective case series of oral exposures to dextromethorphan with ≥1 adverse event from multiple U.S. sources (National Poison Data System, FDA Adverse Event Reporting System, manufacturer safety reports, news/media, medical literature) reported between 2008 and 2014. An expert panel determined the relationship between exposure and adverse events, estimated dose ingested, intent of exposure, and identified contributing factors to exposure.

Results: 1716 cases contained ≥1 adverse event deemed at least potentially related to dextromethorphan; 1417 were single product exposures. 773/1417 (55%) involved only one single-ingredient dextromethorphan product (dextromethorphan-only). Among dextromethorphan-only cases, 3% followed ingestion of a therapeutic dose; 78% followed an overdose. 69% involved unsupervised self-administration and 60% occurred in children <4 years old. No deaths or pathologic dysrhythmias occurred. Central nervous system [e.g., ataxia (N?=?420)] and autonomic symptoms [e.g., tachycardia (N?=?224)] were the most common adverse events. Flushing and/or urticarial rash occurred in 18.1% of patients. Dystonia occurred in 5.4%.

Conclusions: No fatalities were identified in this multifaceted surveillance program following a dextromethorphan-only ingestion. Adverse events were predominantly associated with overdose, most commonly affecting the central nervous and autonomic systems.     

Neuropsychological measurement of inhibitory control in posttraumatic stress disorder: An exploratory antisaccade paradigm

Objective: The aim of the study was to uncover inhibitory control dynamics and assess antisaccade eye-tracking tasks for relevance in a veteran posttraumatic stress disorder (PTSD) population. Method: Participants were 36 veterans enrolled at the Washington DC Veterans Affairs Medical Center. The groups (PTSD diagnosed vs. controls) did not vary between age and sex. Participants completed a testing battery of clinical neuropsychological measures and two different eye-tracking conditions, one that utilized face stimuli and one with standard shape stimuli, which test pro- (PS) and antisaccade (AS) eye movements. Results: Veterans with PTSD, t(33) = 2.2, p = .04, took longer to respond than controls in the standard condition AS. In the face condition, a group by task interaction was seen with increased latency for PTSD veterans in the AS versus PS task, F(3, 33) = 3.99, p = .05, with a large overall effect (Hedges’ g = 1.18, p < .001) compared to controls. After controlling for depression, analyses suggested that only the face condition AS task significantly predicted dimensions of PTSD symptomology measured by the Clinician Administered PTSD Scale (CAPS) for veterans with PTSD. Conclusions: This is the first study to extend AS findings to PTSD and suggests a specific capability to measure inhibitory control using eye-tracking technology. We discuss the notion that reduced capacity to regulate facial-related processing affects cognitive and attentional control networks of PTSD patients, potentially representing a core cognitive deficit.     

Transcranial magnetic stimulation of posterior parietal cortex affects decisions of hand choice

Deciding which hand to use for an action is one of the most frequent decisions people make in everyday behavior. Using a speeded reaching task, we provide evidence that hand choice entails a competitive decision process between simultaneously activated action plans for each hand. We then show that single-pulse transcranial magnetic stimulation to the left posterior parietal cortex biases this competitive process, leading to an increase in ipsilateral, left hand reaches. Stimulation of the right posterior parietal cortex did not alter hand choice, suggesting a hemispheric asymmetry in the representations of reach plans. These results are unique in providing causal evidence that the posterior parietal cortex is involved in decisions of hand choice.     

Darwinian selection for sites of Asn-linked glycosylation in phylogenetically disparate eukaryotes and viruses

Numerous protists and rare fungi have truncated Asn-linked glycan precursors and lack N-glycan-dependent quality control (QC) systems for glycoprotein folding in the endoplasmic reticulum. Here, we show that the abundance of sequons (NXT or NXS), which are sites for N-glycosylation of secreted and membrane proteins, varies by more than a factor of 4 among phylogenetically diverse eukaryotes, based on a few variables. There is positive correlation between the density of sequons and the AT content of coding regions, although no causality can be inferred. In contrast, there appears to be Darwinian selection for sequons containing Thr, but not Ser, in eukaryotes that have N-glycan-dependent QC systems. Selection for sequons with Thr, which nearly doubles the sequon density in human secreted and membrane proteins, occurs by an increased conditional probability that Asn and Thr are present in sequons rather than elsewhere. Increasing sequon densities of the hemagglutinin (HA) of influenza viruses A/H3N2 and A/H1N1 during the past few decades of human infection also result from an increased conditional probability that Asn, Thr, and Ser are present in sequons rather than elsewhere. In contrast, there is no selection on sequons by this mechanism in HA of A/H5N1 or 2009 A/H1N1 (Swine flu). Very strong selection for sequons with both Thr and Ser in glycoprotein of M_r 120,000 (gp120) of HIV and related retroviruses results from this same mechanism, as well as amino acid composition bias and increases in AT content. We conclude that there is Darwinian selection for sequons in phylogenetically disparate eukaryotes and viruses.     

From the Cover: Efficient computation of optimal actions

Optimal choice of actions is a fundamental problem relevant to fields as diverse as neuroscience, psychology, economics, computer science, and control engineering. Despite this broad relevance the abstract setting is similar: we have an agent choosing actions over time, an uncertain dynamical system whose state is affected by those actions, and a performance criterion that the agent seeks to optimize. Solving problems of this kind remains hard, in part, because of overly generic formulations. Here, we propose a more structured formulation that greatly simplifies the construction of optimal control laws in both discrete and continuous domains. An exhaustive search over actions is avoided and the problem becomes linear. This yields algorithms that outperform Dynamic Programming and Reinforcement Learning, and thereby solve traditional problems more efficiently. Our framework also enables computations that were not possible before: composing optimal control laws by mixing primitives, applying deterministic methods to stochastic systems, quantifying the benefits of error tolerance, and inferring goals from behavioral data via convex optimization. Development of a general class of easily solvable problems tends to accelerate progress—as linear systems theory has done, for example. Our framework may have similar impact in fields where optimal choice of actions is relevant.     

江西省山丘型血吸虫病传播控制地区野生动物血吸虫感染调查

目的　掌握江西省山丘型血吸虫病传播控制地区野生动物血吸虫感染情况，为实施精准防控措施及实现血吸虫病传播阻断和消除目标提供科学依据。方法　选择江西省血吸虫病疫情较重的山丘型流行区瑞昌市和彭泽县的5个流行村作为调查村。在调查村有螺环境捕捉野鼠等野生动物，收集来自调查村的野生动物肝脏，检查其血吸虫感染情况。在调查村采用间接血凝试验（IHA）筛查、粪便尼龙绢袋集卵孵化法和改良加藤厚涂片法检测人群血吸虫感染，采用粪便塑料杯顶管孵化法检测家畜血吸虫感染；采用系统抽样结合环境抽查法调查钉螺分布，采用环介导等温扩增技术（LAMP）检测钉螺血吸虫感染。结果　在调查村捕获、收购野鼠、黄鼠狼、野猪、麂子和野兔等野生动物或肝脏样本240只（份），其中捕获野鼠172只，血吸虫感染率为2.91%，其他野生动物未发现血吸虫感染；野鼠、麂子和野猪肝毛细线虫感染率分别为12.21%、1.96%和12.50%。调查村人群和家畜中均未发现血吸虫感染；各村平均钉螺密度在0.13～0.80只/0.1 m2，在1个村发现2只检测管钉螺有血吸虫阳性。结论　江西省山丘型传播控制地区野生动物在血吸虫病传播中的作用和潜在风险仍不可忽视；应继续加强监测，并采取有针对性防治措施，以巩固血吸虫病防治成果。