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Mental health professionals generally view major depression and suicidality as pathological responses to stress that elicit aversive responses from others. An alternative hypothesis grounded in evolutionary theory contends that depression and suicidality are honest signals of need in response to adversity that can increase support from reluctant others when there are conflicts of interest. To test this hypothesis, we examined responses to emotional signals in a preregistered experimental vignette study involving claims of substantial need in the presence of conflicts of interest and private information about the signaler's true level of need. In a sample of 1240 participants recruited from Amazon Mechanical Turk, costlier signals like depression and suicidality increased perceptions of need, reduced perceptions of manipulativeness, and increased likelihood of support compared to simple verbal requests and crying without further symptoms. The effect of signaling on likelihood of support was largely mediated by the effect of signaling on participants' belief that the signaler was genuinely in need. Our results support the hypothesis that depression and suicidality, apparent human universals, are credible signals of need that elicit more support than verbal requests, sad expressions, and crying when there are conflicts of interest.

To evaluate the effect of supplementing beef cattle with a ruminal probiotic consisting of native rumen microbes (NRM; Chordicoccus furentiruminis, Prevotella albensis, and Succinivibrio dextrinosolvens) on methane (CH4) emissions, growth performance, carcass characteristics, and plasma metabolites, Angus × SimAngus-crossbred steers (n = 32; 8 per pen) and heifers (n = 48; 12 per pen) with an initial body weight (BW) of 353 ± 64 kg were used in randomized complete block design. Cattle were blocked by sex and BW and randomly assigned to 1 of 2 treatments (2 pens per treatment). Treatments consisted of diets offered for ad libitum intake with (NRM) or without (CON) the inclusion of the ruminal probiotic. Cattle were fed a growing diet for 49 d followed by a ground corn-based diet for 124 ± 27 d until reaching the targeted final BW (635 kg for steers and 590 kg for heifers). Methane emissions were estimated using the GreenFeed system (n = 12 per treatment) prior to trial commencement (baseline; period 1), and on three (2, 3, and 4), and two (5 and 6) different sampling periods throughout the growing and finishing stage, respectively. All data were analyzed using the PROC MIXED procedure of SAS. For CH4 production (g/d), there was a tendency for an NRM supplementation × period interaction (P = 0.07) where cattle-fed diets with NRM had lower production of methane in periods 3 and 4. Including NRM in the diet decreased CH4 yield (g/kg of dry matter intake (DMI)) by 20%. For CH4 emission intensity (g/kg of average daily gain (ADG)), an interaction (P0.01) of NRM supplementation × period occurred. In periods 2 and 3, cattle-fed diets with NRM inclusion had lower CH4 emission intensity than CON cattle. During the 84-d period when all cattle were still on the finishing diet, feeding NRM increased (P = 0.02) ADG and tended to increase (P = 0.10) DMI. At the end of the 84-d period, cattle-fed NRM tended to be heavier (P = 0.06) than CON cattle. Cattle supplemented with NRM required less (P = 0.04) days on feed to reach the targeted final BW. No differences (P ≤ 0.11) were detected for gain-to-feed ratio and carcass characteristics. Cattle-fed NRM had greater abundance of uncultured rumen bacteria that may improve rumen digestion when fed a high grain diet and potentially promote the reduction of enteric CH4 production. Results from this study suggest that daily administration of NRM may be a strategy to mitigate methanogenesis and improve the growth performance of beef cattle.Greenhouse gas emissions are a major concern in the beef industry. This study examined the effects of supplementation with ruminal probiotics consisting of three native ruminal microbes (NRM) for their influence on methane reduction and growth performance of beef cattle. Eighty Angus × SimAngus-crossbred cattle were grouped by sex and weight, randomly assigned to a treatment group, control or NRM supplementation, and subsequently fed commercially relevant diets for at least 134 d with or without NRM supplementation until they reached a target finishing weight. Methane emissions and growth performance metrics were recorded at regular intervals. Cattle-fed diets with NRM had a greater average daily gain during most part of the experimental period, required fewer days to reach the finishing weight, and emitted less methane than cattle in the control treatment. Supplementing NRM can be a viable method to reduce greenhouse gas emissions while improving the performance of beef cattle-fed concentrates-based diets.

Acute oesophageal obstruction from food bolus impaction is often triggered by underlying oesophageal pathology, both benign and malignant. These can be readily detected with standard investigations such as oesophagoscopy or computed tomography. Zenker’s diverticulum (ZD) is a benign condition frequently presenting with chronic dysphagia or may be asymptomatic. We report the case of an 81-year-old man with a previously undiagnosed 1-cm ZD causing complete oesophageal obstruction secondary to localized oedema from an impacted ibuprofen tablet. Although initial clinical, endoscopic and radiological findings were equivocal and suspicious for upper oesophageal malignancy, symptoms rapidly settled in response to systemic corticosteroids. The diagnosis was later confirmed on barium swallow with no other clinical, radiological or histopathological abnormalities identified. In conclusion, ZD is an uncommon cause of acute oesophageal obstruction which may occur in diverticula of all sizes. Surgery should be performed in patients with recurrent symptoms or large diverticula.

Roadside surveys have shown that cannabis is the most frequently detected drug after alcohol in drivers (Berning et al. 2015). Legalization of cannabis has been reported to increase the proportion ...

This research was conducted to highlight the utility of considering clinical psychology concepts in judgment and decision research. Our overarching thesis is that the judgments and choices people make may often be influenced by clinically relevant phenomena, and that understanding these relationships can, in a reciprocal fashion, help advance our understanding of judgment and decision making as well as specific clinical diagnoses and proclivities. We focused on histrionic personality disorder and conducted four studies that show that histrionic symptomology predicts preferences and choices that facilitate grabbing others’ attention, even when such choices cost more money, and are at the expense of giving up more tangible features. In addition to demonstrating a new implication of the histrionic personality, we provide insight into the process underlying this tendency and discuss implications for mental health service providers.

The objective of this study was to evaluate the effects of two rumen-native microbial feed supplements (MFS) on milk production, milk composition, and feed efficiency. A total of 90 multiparous cows between 40 and 60 d in milk were enrolled in a randomized block design study. Within each block (baseline milk yield), cows were randomly assigned to: control (no microbial feed supplementation), MFS1 (0.33 g/kg total mixed ration [TMR] of an MFS containing a minimum of Clostridium beijerinckii at 2 × 106 CFU/g and Pichia kudriavzevii at 2 × 107 CFU/g), or MFS2 (0.33 g/kg TMR of a MFS containing a minimum of C. beijerinckii at 2 × 106 CFU/g, P. kudriavzevii at 2 × 107 CFU/g, Ruminococcus bovis at 2 × 107 CFU/g, and Butyrivibrio fibrisolvens at 2 × 107 CFU/g). Cows were housed in a single group and fed the study diets ad libitum for 270 d. Individual milk yield was recorded using electronic milk meters, and milk fat and protein were measured using optical in-line analyzers at each of two daily milkings. Treatment and treatment by time effects were assessed through multiple linear regression analyses. Treatment effects were observed for milk and energy-corrected milk (ECM) yields, milk fat and protein yields and concentrations, dry matter intake (DMI), and feed efficiency; those effects were conditional to time for milk yield, DMI, and feed efficiency. Overall, milk, ECM, fat, and protein yields were higher for MFS2 compared with control cows (+3.0, 3.7, 0.12, and 0.12 kg/d, respectively). Compared with MFS1, milk yield was higher and protein yield tended to be higher for MFS2 cows (+2.9 and 0.09 kg/d, respectively). In contrast, MFS1 cows produced 0.17 and 0.08 units of percentage per day more fat and protein than MFS2 cows, and 0.07 units of percentage per day more protein than control cows. Dry matter intake and feed efficiency were higher for MFS2 cows compared with MFS1 cows (+1.3 kg/d and 0.06, respectively), and feed efficiency was higher for MFS2 cows compared with control cows (+0.04). Where observed, treatment by time effects suggest that the effects of MFS2 were more evident as time progressed after supplementation was initiated. No effects of microbial supplementation were observed on body weight, body condition score, somatic cell count, or clinical mastitis case incidence. In conclusion, the supplementation of MFS2 effectively improved economically important outcomes such as milk yield, solids, and feed efficiency.This study evaluates the effects of two rumen-native microbial feed supplements (MFS) on milk yield, composition, and feed efficiency in lactating dairy cows. Ninety multiparous Holstein cows between 40 and 60 d in milk were assigned to control (no microbial feed supplementation), MFS1 (Clostridium beijerinckii and Pichia kudriavzevii), or MFS2 (C. beijerinckii, P. kudriavzevii, Ruminococcus bovis, and Butyrivibrio fibrisolvens) total mixed ration supplementation. Overall, MFS2 cows had higher milk and milk component yields than control and MFS1, while MFS1 cows had higher milk component concentrations than control and MFS2. Feed efficiency was higher for MFS2 compared with control and MFS1 cows. Microbial feed supplementation improved economically important outcomes such as milk yield, solids, and feed efficiency.

Objective: The objective of this study was to compare the variability in vehicle control for sober young adult drivers (18–23 years old) who either use cannabis but are not acutely exposed or do no...

Objective Reports indicate that cannabis users will adapt their driving to compensate for the perceived drug effects of cannabis. This analysis examined the relationship between driver perceptions of their state contrasted with objective measures of their performance while operating a motor vehicle. Methods Data was collected from ten subjects in a study examining the effects of cannabis on driving performance. Driving performance was collected on the NADS quarter-cab miniSim, a limited field of view non-motion simulator, approximately two hours after cannabis inhalation. Driving measures of both lateral and longitudinal control were included in our analysis. Subjective measures of the effects of cannabis were collected at peak and prior to driving, using visual analog scales. Data were analyzed using the SAS GLM Select procedure with subjective effect, dosing condition (placebo vs 6.9% THC), and driving event as independent measures. The stepwise selection method was used. Results The analysis of each of the subjective effects showed significant differences between the placebo and the active cannabis dosed conditions. While we found variance in difference between group means, there was greater variability between subject values. We found that subjective measures were predictive of variance in driver inputs, such as steering frequency and steering reversal rate. Variance in SDLP and other driving performance measures, however, were predicted by dosing condition. Conclusions Overall, some of the effects perceived by the driver were better related to changes in driver inputs rather than the presence of cannabis itself. Changes in performance measures such as SDLP are better explained by dosing condition. Thus, driver's perceptions may result in changes to driving behavior that could mitigate the effect of cannabis. For both lateral and longitudinal control, an increasing perception of stimulation produced a positive effect on performance. Our results provide a better understanding of how different strains of cannabis, which produce different subjective experiences for users, could impact driving safety. Specifically, we found drug effects that produce more stimulation results in less impact on driving, while those that produce a more stoned or high feeling results in a greater negative effect on driving.

Background Fever phobia, the unfounded fear regarding the potential harms of fever in children, has been internationally documented among parents. This fear causes anxiety in parents and health professionals are regularly consulted for advice. Objectives This study aimed to investigate the knowledge, beliefs and recommended treatments among Australian nurses, pharmacists, general practitioners and paediatricians in the management of febrile children. Design, setting and participants This was an online cross-sectional survey of Australian nurses, pharmacists, general practitioners and paediatricians designed to evaluate the knowledge and preferred recommendations in the management of febrile children. Methods The health professionals were recruited via Facebook. Demographic information, knowledge, beliefs and preferred treatments were collected through the online survey, and responses were compared across professions. Results Of the 839 health professionals who completed the survey, 52.0% correctly identified a fever as 38 °C or above. Overall, 23.6% underestimated the temperature that constitutes a fever. Respondents reported concerns leaving fever untreated in children, with dehydration (65.1%), seizures (65.2%), serious illness (34.4%) and brain damage (29.9%) the most common concerns. Pharmacists were more likely to hold these concerns. The beliefs that reducing a child's fever with medication will reduce the risk of harm (34.7%) and prevent febrile convulsions (51.1%) were prevalent among respondents. These beliefs were more common among pharmacists. Pharmacists were also more likely to recommend parents monitor a child's temperature (48.5%) and give medication to reduce fever (64.6%). Conclusions Australian nurses, pharmacists, general practitioners and paediatricians reported many misconceptions surrounding the definition of fever, the potential harms of fever and its management, which may perpetuate parental fears. These misconceptions were most common among pharmacists. Continuing professional development is essential to ease unfounded concerns and ensure the safe and judicious care of febrile children.

Although evidence suggests cannabis impairs driving, its driving-performance effects are not fully characterized. We aimed to establish cannabis' effects on driving longitudinal control (with and without alcohol, drivers' most common drug combination) relative to psychoactive ∆(9) -tetrahydrocannabinol (THC) blood concentrations. Current occasional (≥1×/last 3 months, ≤3 days per week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500 mg placebo, low (2.9%), or high (6.7%) THC vaporized cannabis over 10 min ad libitum in separate sessions (within-subject, six conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives 0.5-1.3 h post-inhalation. Blood and breath alcohol samples were collected before (0.17 and 0.42 h) and after (1.4 and 2.3 h) driving. We evaluated the mean speed (relative to limit), standard deviation (SD) of speed, percent time spent >10% above/below the speed limit (percent speed high/percent speed low), longitudinal acceleration, and ability to maintain headway relative to a lead vehicle (headway maintenance) against blood THC and breath alcohol concentrations (BrAC). In N=18 completing drivers, THC was associated with a decreased mean speed, increased percent speed low and increased mean following distance during headway maintenance. BrAC was associated with increased SD speed and increased percent speed high, whereas THC was not. Neither was associated with altered longitudinal acceleration. A less-than-additive THC*BrAC interaction was detected in percent speed high (considering only non-zero data and excluding an outlying drive event), suggesting cannabis mitigated drivers' tendency to drive faster with alcohol. Cannabis was associated with slower driving and greater headway, suggesting a possible awareness of impairment and attempt to compensate. Copyright © 2016 John Wiley & Sons, Ltd.

BACKGROUND In driving-under-the-influence cases, blood typically is collected approximately 1.5–4 h after an incident, with unknown last intake time. This complicates blood Δ9-tetrahydrocannabinol (THC) interpretation, owing to rapidly decreasing concentrations immediately after inhalation. We evaluated how decreases in blood THC concentration before collection may affect interpretation of toxicological results. METHODS Adult cannabis smokers (≥1×/3 months, ≤3 days/week) drank placebo or low-dose alcohol (approximately 0.065% peak breath alcohol concentration) 10 min before inhaling 500 mg placebo, 2.9%, or 6.7% vaporized THC (within-individuals), then took simulated drives 0.5–1.3 h postdose. Blood THC concentrations were determined before and up to 8.3 h postdose (limit of quantification 1 μg/L). RESULTS In 18 participants, observed Cmax (at 0.17 h) for active (2.9 or 6.7% THC) cannabis were [median (range)] 38.2 μg/L (11.4–137) without alcohol and 47.9 μg/L (13.0–210) with alcohol. THC Cmax concentration decreased 73.5% (3.3%–89.5%) without alcohol and 75.1% (11.5%–85.4%) with alcohol in the first half-hour after active cannabis and 90.3% (76.1%–100%) and 91.3% (53.8%–97.0%), respectively, by 1.4 h postdose. When residual THC (from previous self-administration) was present, concentrations rapidly decreased to preinhalation baselines and fluctuated around them. During-drive THC concentrations previously associated with impairment (≥8.2 μg/L) decreased to median CONCLUSIONS Forensic blood THC concentrations may be lower than common per se cutoffs despite greatly exceeding them while driving. Concentrations during driving cannot be back-extrapolated because of unknown time after intake and interindividual variability in rates of decrease.

OBJECTIVE: To use EEG biomarkers derived from a short, easily administered neurocognitive testbed to determine acute cannabis intoxication and its effect on driving performance in a driving simulator. METHODS: The data analyzed were from a study examining the relationship between psychomotor task performance, EEG data, and driving performance in a simulator. EEG data was collected using STAT(®) X-24 EEG Wireless Sensor Headset, which was worn during the psychomotor and driving tasks. Driving data were collected for segments of consistent driving environments including urban driving, urban curves, interstate, interstate curves, dark rural, and rural straightaways. Dependent measures included measures of lateral and longitudinal vehicle control. RESULTS: There was a significant relationship between impaired driving performance as indicated by increased standard deviation of lane position and EEG power in slow theta band (3–5 Hz) in parietal and occipital areas. CONCLUSIONS: These results, combined with our prior reported results, suggest that EEG and ECG acquired concurrent with neuropsychological tests hold potential to provide a highly sensitive, specific and dose dependent profile of cannabis intoxication and level of impairment.

Distracted and drug-influenced driving presents a major risk for traffic safety morbidity and mortality. As part of an ongoing research program, we examined the effects of a commonly prescribed combination of medications for pain relief: alprazolam, a benzodiazepine, and a hydrocodone preparation, a combination opiate and acetaminophen, on a simulated driving protocol.Utilizing a within-subjects design, we recruited 8 healthy experienced drivers without major physical and psychological histories. Using a double-blind, placebo-controlled crossover design, we administered placebo, alprazolam alone, hydrocodone/acetaminophen, and the combination of the 2 drugs in a standardized simulated driving protocol. Measures of lateral and longitudinal control were collected and the data were reduced and statically analyzed.The study observed clear detrimental effects of alprazolam on driving measures of lateral control and longitudinal control. Driving appeared to more aberrant at higher speeds and in rural scenarios. There were no statistical differences between hydrocodone and placebo. A measure of sedation showed that subjects rated alprazolam as more sedating than both hydrocodone and placebo.The findings suggest that impairing effects of this commonly prescribed combination of pharmacologic agents impact simulated driving performance. Negative changes in driving performance included measures of lateral and longitudinal control, although the deleterious effects on lateral control measures such as standard deviation of lane position (SDLP) were larger and more robust. Although the number of subjects was small, thus making it more difficult to draw conclusions on the narcotic effects, these results suggest that in this combination of central nervous system (CNS)-active drugs the benzodiazepine alprazolam accounted for the majority of impairing drug effects. The effect sizes associated with the hydrocodone preparation ranged from very small to medium. These results have potential implications for prescribing physicians and dispensing pharmacists, traffic safety experts, law enforcement officers, and patients themselves.

Vaporized cannabis and concurrent cannabis and alcohol intake are commonplace. We evaluated the subjective effects of cannabis, with and without alcohol, relative to blood and oral fluid (OF, advantageous for cannabis exposure screening) cannabinoid concentrations and OF/blood and OF/plasma vaporized-cannabinoid relationships. Healthy adult occasional-to-moderate cannabis smokers received a vaporized placebo or active cannabis (2.9% and 6.7% Δ(9) -tetrahydrocannabinol, THC) with or without oral low-dose alcohol (~0.065g/210L peak breath alcohol concentration [BrAC]) in a within-subjects design. Blood and OF were collected up to 8.3 h post-dose and subjective effects measured at matched time points with visual-analogue scales and 5-point Likert scales. Linear mixed models evaluated subjective effects by THC concentration, BrAC, and interactions. Effects by time point were evaluated by dose-wise analysis of variance (ANOVA). OF versus blood or plasma cannabinoid ratios and correlations were evaluated in paired-positive specimens. Nineteen participants (13 men) completed the study. Blood THC concentration or BrAC significantly associated with subjective effects including 'high', while OF contamination prevented significant OF concentration associations

Oral fluid (OF) is an advantageous matrix for cannabis detection, with on-site tests available for roadside drug-impaired driver screening. Limited data exist for device performance following consumption of vaporized cannabis, which reduces exposure to harmful combustion by-products. We assessed cannabinoid OF disposition, with and without alcohol, and evaluated on-site Drager® DrugTest 5000 performance (Drager) following controlled vaporization of cannabis. Forty-three cannabis smokers (≥1×/3 months, ≤3 days/week) reported 10–16 h prior to dosing, and drank placebo or low-dose alcohol [target ~0.065 % peak breath-alcohol concentration (BrAC)] 10 min prior to inhaling 500 mg of placebo, low-dose [2.9 % ∆9-tetrahydrocannabinol (THC)], or high-dose (6.7 % THC) vaporized cannabis (within-subjects; six possible alcohol–cannabis combinations; 19 completers). BrAC readings and OF (Quantisal™, Drager) were collected before and up to 8.3 h post-dose. Median [range] maximum OF concentrations (C max) for low and high doses (no alcohol, N = 19) were 848 [32.1–18,230] and 764 [25.1–23,680] µg/l THC; 6.0 [0–100] and 26.8 [1.0–1106] µg/l cannabidiol; 54.4 [1.8–941] and 29.7 [0–766] µg/l cannabinol; and 24.1 [0–686] and 18.0 [0–414] ng/l 11-nor-9-carboxy-THC (THCCOOH). Lack of significant differences in THC concentration between low doses and high doses indicated that participants may have titrated doses. THC, cannabidiol and cannabinol C max values were immediately post-inhalation, but metabolite THCCOOH t max showed interindividual variability. Concurrent alcohol did not affect OF cannabinoid concentrations or on-site test sensitivity. With a THC confirmation cutoff of 5 µg/l, Drager sensitivity, specificity, and efficiency were 60.8, 98.2, and 82.5 %. Drager had lower sensitivity after 6.7 % THC vaporization (53.8 %, THC ≥2 µg/l confirmation cutoff) than reported following smoking a 6.8 % THC cigarette, but high specificity (99.3 %) and comparable efficiency (65.0 %). Vaporized THC bioavailability may be lower than that when smoked. Confirmation cutoff, time course, intake histories, and additional cannabinoid analytes also affect OF interpretation.

Investigate how novice drivers with autism spectrum disorder (ASD) differ from experienced drivers and whether virtual reality driving simulation training (VRDST) improves ASD driving performance. 51 novice ASD drivers (mean age 17.96 years, 78% male) were randomized to routine training (RT) or one of three types of VRDST (8-12 sessions). All participants followed DMV behind-the-wheel training guidelines for earning a driver's license. Participants were assessed pre- and post-training for driving-specific executive function (EF) abilities and tactical driving skills. ASD drivers showed worse baseline EF and driving skills than experienced drivers. At post-assessment, VRDST significantly improved driving and EF performance over RT. This study demonstrated feasibility and potential efficacy of VRDST for novice ASD drivers.

We performed a retrospective chart review of 50 youths with Autism Spectrum Disorder (ASD), prescribed amitriptyline (AMI) for hyperactivity and impulsivity. Data was systematically extracted from 50 outpatient clinic charts, including AMI treatment duration, dose, trough levels and adverse events. Mean age was 9.4 years (4.6-17.9); 40 were males and 10 females. 30 % had failed atomoxetine and 40 % had failed ≥3 ADHD medications. Mean dose was 1.3 ± 0.6 mg/kg/day, mean trough level 114.1 ± 50.5 ng/ml, mean duration 3.4 years. Clinical Global Impressions Scale-Improvement (CGI-I) was ≤2 in 60 % of patients at the final visit, and in 82 % of patients for at least 50 % of follow-ups. Cautious use of low dose AMI shows promise for treatment-resistant youth with ASD accompanied by hyperactivity, impulsivity, aggression and self injury.

Unethical athletes and their mentors have long arrogated scientific and medical advances to enhance athletic performance, thus gaining a dishonest competitive advantage. Building on advances in genetics, a new threat arises from athletes using gene therapy techniques in the same manner that some abused performance-enhancing drugs were used. Gene doping, as this is known, may produce spectacular physiologic alterations to dramatically enhance athletic abilities or physical appearance. Furthermore, gene doping may present pernicious problems for the regulatory agencies and investigatory laboratories that are entrusted to keep sporting events fair and ethical. Performance-enhanced genetics will likewise present unique challenges to physicians in many spheres of their practice.

BACKGROUND: Effects of cannabis, the most commonly encountered non-alcohol drug in driving under the influence cases, are heavily debated. We aim to determine how blood Δ(9)-tetrahydrocannabinol (THC) concentrations relate to driving impairment, with and without alcohol. METHODS: Current occasional (≥1×/last 3 months, ≤3days/week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500mg placebo, low (2.9%)-THC, or high (6.7%)-THC vaporized cannabis over 10min ad libitum in separate sessions (within-subject design, 6 conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives (∼0.8h duration). Blood, oral fluid (OF), and breath alcohol samples were collected before (0.17h, 0.42h) and after (1.4h, 2.3h) driving that occurred 0.5-1.3h after inhalation. We evaluated standard deviations of lateral position (lane weave, SDLP) and steering angle, lane departures/min, and maximum lateral acceleration. RESULTS: In N=18 completers (13 men, ages 21-37years), cannabis and alcohol increased SDLP. Blood THC concentrations of 8.2 and 13.1μg/L during driving increased SDLP similar to 0.05 and 0.08g/210L breath alcohol concentrations, the most common legal alcohol limits. Cannabis-alcohol SDLP effects were additive rather than synergistic, with 5μg/L THC+0.05g/210L alcohol showing similar SDLP to 0.08g/210L alcohol alone. Only alcohol increased lateral acceleration and the less-sensitive lane departures/min parameters. OF effectively documented cannabis exposure, although with greater THC concentration variability than paired blood samples. CONCLUSIONS: SDLP was a sensitive cannabis-related lateral control impairment measure. During drive blood THC ≥8.2μg/L increased SDLP similar to notably-impairing alcohol concentrations. Despite OF's screening value, OF variability poses challenges in concentration-based effects interpretation. Language: en

Objective: To examine the association between parental obsessive-compulsive disorder (OCD) and emotional and behavioural disorders in offspring. Method: Demographic, clinical, and diagnostic data were collected from parents with OCD, control subjects, and their respective offspring. Offspring were reassessed at a 2-year follow-up. Results: Probands with OCD and controls were relatively well matched for age, gender, race, educational rating, and marital status. Offspring of OCD probands were at greater risk than offspring of controls for dimensionally measured anxiety, depression, somatization, and social problems. OCD offspring were significantly more likely than control offspring to have lifetime overanxious disorder, separation anxiety disorder, OCD, or ‘any anxiety disorder’. Female gender in the parent with OCD, evidence of family dysfunction, and high symptom levels in offspring were predictive of broadly defined OCD at follow-up. Conclusion: Children having a parent with OCD are more likely than control offspring to have social, emotional, and behavioural disorders.

BACKGROUND Increased medical and legal cannabis intake is accompanied by greater use of cannabis vaporization and more cases of driving under the influence of cannabis. Although simultaneous Δ9-tetrahydrocannabinol (THC) and alcohol use is frequent, potential pharmacokinetic interactions are poorly understood. Here we studied blood and plasma vaporized cannabinoid disposition, with and without simultaneous oral low-dose alcohol. METHODS Thirty-two adult cannabis smokers (≥1 time/3 months, ≤3 days/week) drank placebo or low-dose alcohol (target approximately 0.065% peak breath-alcohol concentration) 10 min before inhaling 500 mg placebo, low-dose (2.9%) THC, or high-dose (6.7%) THC vaporized cannabis (6 within-individual alcohol-cannabis combinations). Blood and plasma were obtained before and up to 8.3 h after ingestion. RESULTS Nineteen participants completed all sessions. Median (range) maximum blood concentrations (Cmax) for low and high THC doses (no alcohol) were 32.7 (11.4–66.2) and 42.2 (15.2–137) μg/L THC, respectively, and 2.8 (0–9.1) and 5.0 (0–14.2) μg/L 11-OH-THC. With alcohol, low and high dose Cmax values were 35.3 (13.0–71.4) and 67.5 (18.1–210) μg/L THC and 3.7 (1.4–6.0) and 6.0 (0–23.3) μg/L 11-OH-THC, significantly higher than without alcohol. With a THC detection cutoff of ≥1 μg/L, ≥16.7% of participants remained positive 8.3 h postdose, whereas ≤21.1% were positive by 2.3 h with a cutoff of ≥5 μg/L. CONCLUSIONS Vaporization is an effective THC delivery route. The significantly higher blood THC and 11-OH-THC Cmax values with alcohol possibly explain increased performance impairment observed from cannabis-alcohol combinations. Chosen driving-related THC cutoffs should be considered carefully to best reflect performance impairment windows. Our results will help facilitate forensic interpretation and inform the debate on drugged driving legislation.

This research paper explores how different drug mechanisms within a single class of drugs can produces different profiles of driving impairment. Prior research has failed to consider these mechanistic differences and often utilizes less controlled study methodologies. The potential impact of differing mechanistic effects is important for practitioners but remains unclear for most drugs. Twentynine licensed drivers in good general health completed one of two miniSim™ studies using a validated, standardized, driving impairment scenario. Both drugs caused degradation in lateral control measures of standard deviation of lane position (SDLP) and number of lane departures, however only diphenhydramine was found to cause a significant change in steering bandwidth. The studied drugs differed in their effects on all longitudinal driving measures with diphenhydramine effecting speed and alprazolam effecting the standard deviation of speed. Difference in therapeutic mechanism of action results in differing pharmacodynamic driving performance outcomes. This analysis reinforces the importance of careful consideration of a drug’s specific mechanism of action when considering a sedating drug’s impact on a patient’s ability to safely operate a motor vehicle.

To determine the safety and efficacy of fluvoxamine for the treatment of children and adolescents with obsessive-compulsive disorder (OCD) with a double-blind, placebo-controlled, multicenter study.Subjects, aged 8 to 17 years, meeting DSM-III-R criteria for OCD were recruited from July 1991 to August 1994. After a 7- to 14-day single-blind, placebo washout/screening period, subjects were randomly assigned to fluvoxamine 50 to 200 mg/day or placebo for 10 weeks. Subjects who had not responded after 6 weeks could discontinue the double-blind phase of the study and enter a long-term, open-label trial of fluvoxamine. Analyses used an intent-to-treat sample with a last-observation-carried-forward method.Mean Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores with fluvoxamine were significantly (p.05) different from those with placebo at weeks 1, 2, 3, 4, 6, and 10. Significant (p.05) differences between fluvoxamine and placebo were observed for all secondary outcome measures at all visits. Based on a 25% reduction of CY-BOCS scores, 42% of subjects taking fluvoxamine were responders compared with 26% taking placebo. Forty-six (19 fluvoxamine, 27 placebo) of 120 randomized subjects discontinued early. Adverse events with a placebo-adjusted rate greater than 10% were insomnia and asthenia.Fluvoxamine has a rapid onset of action and is well tolerated and efficacious for the short-term treatment of pediatric OCD.

Secondary chromosomal changes are known to develop in Philadelphia chromosome-negative (Ph-) cells of chronic myelogenous leukemia (CML) patients after treatment with imatinib mesylate, an ABL kinase inhibitor. We report here a novel case of a pericentric inversion of chromosome 16 as the sole cytogenetic abnormality in Ph- cells after treatment of Ph+ CML with imatinib.

Blood samples were obtained from 10 male autistic children ages 7-15 years and 10 age-matched, male, healthy controls. Lymphocyte subsets (helper-inducer, suppressor-cytotoxic, total T, and total B cells) were enumerated using monoclonal antibodies and flow cytometry. Bound and soluble interleukin-2 receptors were assayed in unstimulated blood samples and in cell cultures following 72-hour stimulation with phytohemagglutinin. The children with autism had a lower percentage of helper-inducer cells and a lower helper:suppressor ratio, with both measures inversely related to the severity of autistic symptoms (r = - .56 and - .68, respectively). A lower percentage of lymphocytes expressing bound interleukin-2 receptors following mitogenic stimulation was also noted, and this too was inversely related to the severity of autistic symptoms.

For over a century now, athletes in all levels of accomplishment—amateur, professional, Olympic—pursued biological substances, pharmacological agents, and covert doping procedures to obtain any edge in competition leading to greater achievement. As athletic pursuits became more competitive, and more lucrative, any additional improvement in performance leads to increased individual recognition, greater rewards, and increased acclaim—perhaps worldwide accolades. Thus performance-enhancing drugs (PEDs) were developed to improve athletic numbers by enhancing cognition, stamina, strength, and power above and beyond what accepted traditional training methods produced. Chemists and pharmacologists superseded the known PEDs—which included stimulants, anabolic steroids, growth hormones, metabolic regulators, and diuretics—with powerful esoteric substances derived from contemporary medical research advancements. Athletes reportedly now abuse compounds affecting cellular organelles and biochemical processes down to the nuclear transcription/translation level. However, all substances that enhance performance will also cause side effects with potential serious or lethal consequences. It behooves athletes, coaches, and trainers to educate themselves on the risks—legal, biological, psychological—in using these substances.

SPECT using N-Isopropyl I-123 IMP was performed, as part of a neuropsychiatric evaluation, on 10 patients with the DSM III-R diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) and 6 patients from a non-ADHD mixed psychiatric group used as controls for comparison. Mean regional I-123 IMP SPECT region of interest (ROI) count ratios (left to right) demonstrated that the ADHD patients had greater overall hemispheric I-123 IMP uptake asymmetry with less activity in the left frontal and left parietal regions in comparison to control patients. Both groups demonstrated similar I-123 IMP uptake asymmetry in the temporal regions. These findings are consistent with previous studies of brain physiology in ADHD implicating regional cortical perfusion and metabolism abnormalities in areas which are involved in the control of attentional processes.

A self-report scale for the symptoms of Tourette's syndrome was designed to be quickly and easily completed by children, adolescents, or adults. The Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey (MOVES) generates scores on five subscales: Motor Tics, Vocal Tics, Obsessions, Compulsions, and Associated Symptoms (echolalia, echopraxia, coprolalia, copropraxia). Subscales scores can be combined to form a Tic Subscale or an Obsessive-Compulsive Subscale. A sample of patients with Tourette's syndrome (n = 30) scored significantly higher on the Total Scale and in all Subscales, in comparison with nonreferred community controls (n = 26) and psychiatric controls (n = 23). The MOVES subscales correlated significantly (Pearson = 0.6-0.8) with independent examiner-rated scales, including the Yale Tourette's Syndrome Global Severity Scale, Shapiro Tourette Clinical Rating Scale, and two scales for obsessive and compulsive symptoms (Assessor, Beaumont). The MOVES appeared sensitive to clinical cha...

Starting at 8 weeks and continuing until 23 weeks (nut drop) after anthesis,1 m2 explants from cotyledons of immature seeds were extracted from Juglans nigra fruits. Explants were placed on Woody Plant Medium with 1 g l-1 casein hydrolysate and 30 g l-1 sucrose. The explants remained in light for 4 weeks on primary media containing a 3×3 factorial of 0.05, 0.5, or 5.0 μM thidiazuron (TDZ) and 0.1, 1.0, or 10.0 μM 2,4-d. Explants were transferred to a secondary medium containing no plant growth regulators and incubated in darkness for 11 weeks. The greatest number of somatic embryos was produced 8, 10, and 12 weeks after anthesis from explants on media with 0.5 or 5.0 μM TDZ and 0.1 or 1.0 μM 2,4-d. Explants produced the greatest callus volume and dry weight 10, 12, and 14 weeks after anthesis. Throughout the study, callus generally increased with increasing concentrations of both TDZ and 2,4-d.

Immature and mature nonstratified seeds of white ash (Fraxinus americana L.) were dissected transversely and 2/3 of each seed was placed onto agar-solidified Murashige and Skoog medium. Adventitious buds, shoots, and somatic embryos formed on callus, cotyledons, and hypocotyls of the resulting seedlings. Shoot organogenesis was induced on explants cultured on medium with 10 μM thidiazuron but not on explants on media with benzyladenine (BA) or isopentenyladenine. Not all seed sources were equally capable of shoot organogenesis and embryogenesis. Atypical of adventitious regeneration of other woody plants, mature seed explants of white ash were more organogenic with shoots that elongated better than explants from immature seeds. Somatic embryogenesis was observed in cultures where mature seeds were first cultured for 4 weeks on a medium containing 10 μM adenine 2,4-dichlorophenoxyacetic acid in combination with 0.1 and 1.0 μM thidiazuron, followed by transfer to a medium containing 0.05 μM 6-benzyladenine and 0.5 μM naphthaleneacetic acid. Adventitious shoots and epicotyls from both seedlings and germinated somatic embryos were rooted under intermittent mist and acclimatized to the greenhouse.

Axillary shoots from three selected white ash (Fraxinus americana L.) clones were harvested from in vitro shoot cultures. Roots were initiated by pulsing excised shoots for eight days in the dark in MS medium supplemented with 2% sucrose, 0.7% agar, 5 μM NAA, and 1 μM IBA. Pulsed shoots were transferred to a root elongation medium consisting of 25% MS macrosalts, full-strength microsalts and organics, 1% sucrose, 0.7% agar and no auxins. When roots were visible (6–10 days after transfer to root elongation medium), microplants were transferred to vessels containing the same minimal medium and tall fescue (Festuca elatior var. arundinacea (Schreb.) Wimm.) leaf extracts, leaf leachates, or soil leachates from plant boxes with and without tall fescue sod. After four weeks in vitro, primary adventitious and secondary root growth was reduced by extracts obtained from 5 and 10 g ground leaves per 100 ml of medium. Leachates obtained from 5 g soaked leaves per 100 ml of medium stimulated primary root growth. Soil leachates from bare soil also stimulated primary root growth. Variation was observed among the clones for root growth when plantlets were grown in extracts or leachates from tall fescue.

Introduction: The concept of subclinical obsessive-compulsive disorder is explored using data from a “high-risk” study of offspring of persons with (OCD) and offspring of controls. Offspring with OCD were compared to those with subclinical OCD, and those without either condition. Subclinical OCD is defined as the presence of obsessions and/or compulsions without functional impairment.Methods: Adults with OCD and their offspring 7–18 years of age were recruited through a tertiary care center psychiatric outpatient clinic, while controls (and their children) were recruited via advertisement. Parents and offspring were assessed using structured interviews and validated questionnaires at baseline and follow-up interviews.Results: Offspring from both proband groups were pooled to create three subject groups: group 1, offspring with neither condition (n=43); group 2, offspring with subclinical OCD (n=24); and group 3, offspring with full OCD (n=11). Offspring with subclinical OCD held the middle ground for most comparisons. They were more symptomatic than offspring without either condition (group 1), but less symptomatic than subjects with OCD (group 3). Across the board, comparisons of diagnoses, Child Behavior Checklist (CBCL) results; Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey results; and Leyton Obsessional Inventory (LOI) results were associated with subject group at baseline and follow-up. In post-hoc comparisons, subjects with subclinical OCD had fewer comorbid anxiety disorders and lower CBCL internalizing scale scores at follow-up. Parents of children with OCD had higher LOI symptom and severity scores than parents in those of groups 1 or 2.Conclusion: The findings suggest that subclinical OCD holds the middle ground between full-blown OCD and having neither condition in terms of obsessive-compulsive symptoms and severity, tics, associated mood/anxiety disorders, and general functioning. At least in persons at risk for OCD, the presence of subclinical OCD may herald the onset of OCD, though in others may be an independent condition that does not lead to full OCD.