A year-round satellite sea-ice thickness record from CryoSat-2.

Arctic sea ice is diminishing with climate warming1 at a rate unmatched for at least 1,000 years2. As the receding ice pack raises commercial interest in the Arctic3, it has become more variable and mobile4, which increases safety risks to maritime users5. Satellite observations of sea-ice thickness are currently unavailable during the crucial melt period from May to September, when they would be most valuable for applications such as seasonal forecasting6, owing to major challenges in the processing of altimetry data7. Here we use deep learning and numerical simulations of the CryoSat-2 radar altimeter response to overcome these challenges and generate a pan-Arctic sea-ice thickness dataset for the Arctic melt period. CryoSat-2 observations capture the spatial and the temporal patterns of ice melting rates recorded by independent sensors and match the time series of sea-ice volume modelled by the Pan-Arctic Ice Ocean Modelling and Assimilation System reanalysis8. Between 2011 and 2020, Arctic sea-ice thickness was 1.87 ± 0.10 m at the start of the melting season in May and 0.82 ± 0.11 m by the end of the melting season in August. Our year-round sea-ice thickness record unlocks opportunities for understanding Arctic climate feedbacks on different timescales. For instance, sea-ice volume observations from the early summer may extend the lead time of skilful August-October sea-ice forecasts by several months, at the peak of the Arctic shipping season.

Limited recovery following a massive seagrass decline in subarctic eastern Canada.

Over the last few decades, there has been an increasing recognition for seagrasses' contribution to the functioning of nearshore ecosystems and climate change mitigation. Nevertheless, seagrass ecosystems have been deteriorating globally at an accelerating rate during recent decades. In 2017, research into the condition of eelgrass (Zostera marina) along the eastern coast of James Bay, Canada, was initiated in response to reports of eelgrass decline by the Cree First Nations of Eeyou Istchee. As part of this research, we compiled and analyzed two decades of eelgrass cover data and three decades of eelgrass monitoring data (biomass and density) to detect changes and assess possible environmental drivers. We detected a major decline in eelgrass condition between 1995 and 1999, which encompassed the entire east coast of James Bay. Surveys conducted in 2019 and 2020 indicated limited changes post-decline, for example, low eelgrass cover (<25%), low aboveground biomass, smaller shoots than before 1995, and marginally low densities persisted at most sites. Overall, the synthesized datasets show a 40% loss of eelgrass meadows with >50% cover in eastern James Bay since 1995, representing the largest scale eelgrass decline documented in eastern Canada since the massive die-off event that occurred in the 1930s along the North Atlantic coast. Using biomass data collected since 1982, but geographically limited to the sector of the coast near the regulated La Grande River, generalized additive modeling revealed eelgrass meadows are affected by local sea surface temperature, early ice breakup, and higher summer freshwater discharge. Our results caution against assuming subarctic seagrass ecosystems have avoided recent global declines or will benefit from ongoing climate warming.

Effects of high dose transdermal nicotine replacement in cigarette smokers.

RATIONALE: Nicotine replacement therapies (NRT) have been evaluated to facilitate cigarette smoking reduction in smokers unwilling or unable to quit. In most of these studies, only conventional doses of NRT have been tested and higher doses may be required to result in significant reductions in smoking and in biomarkers of exposure. OBJECTIVE: To determine if higher NRT doses in conjunction with smoking are safe and may promote significant reductions in cigarette smoking and biomarkers of exposure. METHODS: A dose-ranging, within-subject design was implemented to evaluate the effects of 15, 30 and 45 mg nicotine-patch treatment on measures of safety and the extent of smoking reduction and biomarker exposure per cigarette in smokers (N=20 completers) not immediately interested in quitting. RESULTS: Concurrent smoking and NRT were generally tolerated and resulted in no changes in blood pressure or heart rate. Slightly less than 10% of the study sample was not given the highest dose of NRT due to side effects. Self-reported cigarette smoking decreased with increasing doses of nicotine replacement and significant reductions were observed for total NNAL (a carcinogen biomarker) and carbon monoxide. However, even at the 45 mg dose, increased carbon monoxide and total NNAL per cigarette occurred, even though cotinine levels increased on average, 69.3% from baseline. CONCLUSIONS: The present results suggest that the use of high dose NRT is safe, leads to significant reductions in smoking (-49%), significant but less reductions in total NNAL (-24%) and carbon monoxide (-37%) due to compensatory smoking.

Pilot study of the effects of lisdexamfetamine on cocaine use: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Amphetamine analogs have been demonstrated to have some efficacy in reducing use in cocaine dependent individuals. However, these agents also have potential for abuse. Lisdexamfetamine (LDX), a lysine+dextroamphetamine formulation, has been approved for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) and as a prodrug, has less abuse potential. OBJECTIVE: This pilot study sought to evaluate the safety, tolerability, and efficacy of LDX as a candidate treatment for cocaine dependence. METHODS: A randomized, double-blind, placebo-controlled parallel group study served to evaluate LDX in 43 cocaine-dependent individuals: (1) placebo (PBO; 0mg, n=21), (2) LDX (70mg, n=22). Participants received medication for 14 weeks. Cocaine use was determined based on urine analysis for benzoylecgonine (BE; a cocaine metabolite). RESULTS: Retention rates were higher though not significantly different in the PBO (71.4%) than the LDX condition (57.1%). Compared to those in the PBO condition, those receiving LDX were more likely to report experiencing (ps<0.05) diarrhea (45.5% vs. 14.3%), headaches (45.5% vs. 9.5%), and anxiety (31.8% vs. 4.8%). No differences in medication conditions were observed for blood pressure, heart rate, or body weight. In the randomized sample, no differences in cocaine use were seen. Those receiving LDX reported significantly less craving for cocaine than participants receiving PBO. CONCLUSIONS: LDX did not significantly reduce cocaine use compared to PBO in the randomized sample.

Extended-Release Mixed Amphetamine Salts vs Placebo for Comorbid Adult Attention-Deficit/Hyperactivity Disorder and Cocaine Use Disorder: A Randomized Clinical Trial.

IMPORTANCE: Adult attention-deficit/hyperactivity disorder (ADHD) is prevalent but often unrecognized, in part because it tends to co-occur with other disorders such as substance use disorders. Cocaine use disorder is one such disorder with high co-occurrence of ADHD. OBJECTIVE: To examine whether treatment of co-occurring ADHD and cocaine use disorder with extended-release mixed amphetamine salts is effective at both improving ADHD symptoms and reducing cocaine use. DESIGN, SETTING, AND PARTICIPANTS: Thirteen-week, randomized, double-blind, 3-arm, placebo-controlled trial of participants meeting DSM-IV-TR criteria for both ADHD and cocaine use disorder conducted between December 1, 2007, and April 15, 2013, at 2 academic health center substance abuse treatment research sites. One hundred twenty-six adults diagnosed as having comorbid ADHD and cocaine use disorder were randomized to extended-release mixed amphetamine salts or placebo. Analysis was by intent-to-treat population. INTERVENTIONS: Participants received extended-release mixed amphetamine salts (60 or 80 mg) or placebo daily for 13 weeks and participated in weekly individual cognitive behavioral therapy. MAIN OUTCOMES AND MEASURES: For ADHD, percentage of participants achieving at least a 30% reduction in ADHD symptom severity, measured by the Adult ADHD Investigator Symptom Rating Scale; for cocaine use, cocaine-negative weeks (by self-report of no cocaine use and weekly benzoylecgonine urine screens) during maintenance medication (weeks 2-13) and percentage of participants achieving abstinence for the last 3 weeks. RESULTS: More patients achieved at least a 30% reduction in ADHD symptom severity in the medication groups (60 mg: 30 of 40 participants [75.0%]; odds ratio [OR] = 5.23; 95% CI, 1.98-13.85; P < .001; and 80 mg: 25 of 43 participants [58.1%]; OR = 2.27; 95% CI, 0.94-5.49; P = .07) compared with placebo (17 of 43 participants [39.5%]). The odds of a cocaine-negative week were higher in the 80-mg group (OR = 5.46; 95% CI, 2.25-13.27; P < .001) and 60-mg group (OR = 2.92; 95% CI, 1.15-7.42; P = .02) compared with placebo. Rates of continuous abstinence in the last 3 weeks were greater for the medication groups than the placebo group: 30.2% for the 80-mg group (OR = 11.87; 95% CI, 2.25-62.62; P = .004) and 17.5% for the 60-mg group (OR = 5.85; 95% CI, 1.04-33.04; P = .04) vs 7.0% for placebo. CONCLUSIONS AND RELEVANCE: Extended-release mixed amphetamine salts in robust doses along with cognitive behavioral therapy are effective for treatment of co-occurring ADHD and cocaine use disorder, both improving ADHD symptoms and reducing cocaine use. The data suggest the importance of screening and treatment of ADHD in adults presenting with cocaine use disorder. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00553319.

Effects of progesterone treatment on smoked cocaine response in women.

The effects of female sex hormones on responses to cocaine have not been systematically investigated in women. In this study, the safety and efficacy of acute progesterone treatment on smoked cocaine response was examined in female cocaine users. Five women had two experimental sessions during the early follicular phase, within 3-9 days after the beginning of their menses. In each experimental session, subjects received a single 200-mg dose of progesterone or placebo orally. Starting 2 h after the medication treatment, subjects received three deliveries of 0.4-mg/kg smoked cocaine 30 min apart. Progesterone treatment, compared to placebo, did not affect the blood pressure and heart rate changes in response to cocaine deliveries. For subjective responses to cocaine, the average of five-item Cocaine Effects Questionnaire (CEQ) was attenuated under progesterone treatment compared to placebo. For individual items of CEQ, progesterone treatment was associated with diminished rating of "feel the effect of last dose" in response to cocaine. These preliminary results suggest that acute progesterone treatment, given during the early follicular phase, may attenuate some of the subjective effects of cocaine. Further studies are warranted to examine the effects of progesterone treatment on cocaine dependence.

Interventions to increase use of nicotine gum: a randomized, controlled, single-blind trial.

Medication noncompliance with smoking cessation pharmacotherapies is a significant problem in both research and clinical settings. This randomized, controlled, single-blind study compared three single-session psychological interventions to increase use of nicotine gum during a 15-day treatment period. A total of 97 adult smokers were randomized to receive standard treatment (ST, n = 31), brief feedback (BF, n = 32) plus ST, or contingency management (CM; i.e., payment for chewing at least 12 pieces/day on 10 of 15 intervention days, n = 34) plus ST and BF. Only the CM condition led to significantly greater average daily gum use (pieces/day: ST, 6.17; BF, 7.81; CM, 10.17 [p values <.05]) and higher rates of compliance (ST, 13.6%; BF, 25.2%; CM, 65.6% [p values <.001]). No differences were observed in smoking abstinence, nicotine withdrawal, or urinary cotinine as a function of treatment. Implications of the present findings are discussed, including application to clinical trials and extension to real-world use of nicotine gum.

Labetalol treatment enhances the attenuation of tobacco withdrawal symptoms by nicotine in abstinent smokers.

The noradrenergic system may mediate some of the acute physiological effects of nicotine and nicotine withdrawal symptoms. This study examined the effects of labetalol, an alpha- and beta-adrenergic receptor blocker, on acute physiological and subjective effects of intravenous nicotine and on tobacco withdrawal symptoms. Five female and four male smokers participated in a double-blind, placebo-controlled, crossover study. Following overnight abstinence from smoking, subjects were treated orally with a single 100- or 200-mg dose of labetalol or placebo in each of three experimental sessions. Two hours after the medication treatment, subjects received an intravenous injection of 15 microg/kg nicotine. The nicotine-induced increases in heart rate were attenuated with the high dose of labetalol. No treatment effects were found for systolic or diastolic blood pressure changes. For the subjective effects of nicotine, treatment with both high and low doses of labetalol enhanced the ratings of "head rush" and "drug strength." The attenuation of tobacco withdrawal symptoms following intravenous nicotine administration was significantly greater with high-dose labetalol treatment, compared with placebo. These results support the proposed role of adrenergic receptors in nicotine withdrawal symptoms. The utility of adrenergic blockers, in combination with nicotine replacement therapies, for smoking cessation needs to be examined further in controlled clinical trials.