On the survivability and detectability of terrestrial meteorites on the moon

Materials blasted into space from the surface of early Earth may preserve a unique record of our planet's early surface environment. Armstrong et al. (2002) pointed out that such materials, in the form of terrestrial meteorites, may exist on the Moon and be of considerable astrobiological interest if biomarkers from early Earth are preserved within them. Here, we report results obtained via the AUTODYN hydrocode to calculate the peak pressures within terrestrial meteorites on the lunar surface to assess their likelihood of surviving the impact. Our results confirm the order-of-magnitude estimates of Armstrong et al. (2002) that substantial survivability is to be expected, especially in the case of relatively low velocity (ca. 2.5 km/s) or oblique (≤45°) impacts, or both. We outline possible mechanisms for locating such materials on the Moon and conclude that searching for them would be a scientifically valuable activity for future lunar exploration

The Influence of Citrus urantium and Caffeine Complex versus Placebo on the Cardiac Autonomic Response: A Double Blind Crossover Design

Background: The purpose of this study was to examine the resting cardiac autonomic nervous system’s response to the ingestion of a complex containing Citrus aurantium + Caffeine (CA + C) and its influence on recovery following a high-intensity anaerobic exercise bout in habitual caffeine users. Methods: Ten physically active males (25.1 ± 3.9 years; weight 78.71 ± 9.53 kg; height 177.2 ± 4.6 cm; body fat 15.5 ± 3.13%) participated in this study, which consisted of two exhaustive exercise protocols in a randomized crossover design. On each visit the participants consumed either a CA + C (100 mg of CA and 100 mg of C) or placebo (dextrose) capsule. After consumption, participants were monitored throughout a 45-min ingestion period, then completed a repeated Wingate protocol, and were then monitored throughout a 45-min recovery period. Cardiac autonomic function (Heart Rate (HR) and Heart Rate Variability (HRV)) and plasma epinephrine (E) and norepinephrine(NE) were taken at four different time points; Ingestion period: baseline (I1), post-ingestion period (I2); Recovery period: immediately post-exercise (R1), post-recovery period (R2). Heart rate variability was assessed in 5-min increments. Results: A repeated measures ANOVA revealed significant time-dependent increases in HR, sympathetic relatedmarkers of HRV, and plasma E and NE at I2 only in the CA + C trial (p\u3c 0.05); however, no meaningful changes in parasympathetic markers of HRV were observed. Participants recovered in a similar time-dependent manner in all markers of HRV and catecholamines following the PLA and CA + C trials. Conclusion: The consumption of CA + C results in an increase of sympathetic activity during resting conditions without influencing parasympathetic activity. CA + C provides no influence over cardiac autonomic recovery

Sleep disturbance in movement disorders:insights, treatments and challenges

Sleep and circadian rhythm disturbances are central features of many movement disorders, exacerbating motor and non-motor symptoms and impairing quality of life. Understanding these disturbances to sleep is clinically important and may further our understanding of the underlying movement disorder. This review evaluates the current anatomical and neurochemical understanding of normal sleep and the recognised primary sleep disorders. In addition, we undertook a systematic review of the evidence for disruption to sleep across multiple movement disorders. Rapid eye movement sleep behaviour disorder has emerged as the most reliable prodromal biomarker for the alpha synucleinopathies, including Parkinson’s disease and multiple system atrophy, often preceding motor symptom onset by several years. Abnormal sleep has also been described for many other movement disorders, but further evidence is needed to determine whether this is a primary or secondary phenotypic component of the underlying condition. Medication used in the treatment of motor symptoms also affects sleep and can aggravate or cause certain sleep disorders. Within the context of movement disorders, there is also some suggestion of a shared underlying mechanism for motor and sleep pathophysiology, with evidence implicating thalamic and brainstem structures and monoaminergic neurotransmission. This review highlights the need for an understanding of normal and abnormal sleep within the movement disorder clinic, an ability to screen for specific causes of poor sleep and to treat sleep disturbance to improve quality of life. Key sleep disorders also act as important biomarkers and have implications in diagnosis, prognosis and the development of future therapies

A high-sensitivity electrochemiluminescence-based ELISA for the measurement of the oxidative stress biomarker, 3-nitrotyrosine, in human blood serum and cells

The generation of 3-nitrotyrosine, within proteins, is a post-translational modification resulting from oxidative or nitrative stress. It has been suggested that this modification could be used as a biomarker for inflammatory diseases. Despite the superiority of mass spectrometry-based determinations of nitrotyrosine, in a high-throughput clinical setting the measurement of nitrotyrosine by an enzyme-linked immunosorbent assay (ELISA) is likely to be more cost-effective. ELISAs offer an alternative means to detect nitrotyrosine, but many commercially available ELISAs are insufficiently sensitive to detect nitrotyrosine in healthy human serum. Here, we report the development, validation and clinical application of a novel electrochemiluminescence-based ELISA for nitrotyrosine which provides superior sensitivity (e.g. a 50-fold increase in sensitivity compared with one of the tested commercial colorimetric ELISAs). This nitrotyrosine ELISA has the following characteristics: a lower limit of quantitation of 0.04 nM nitrated albumin equivalents; intra- and inter-assay coefficients of variation of 6.5% and 11.3%, respectively; a mean recovery of 106 ± 3% and a mean linearity of 0.998 ± 0.001. Far higher nitration levels were measured in normal human blood cell populations when compared to plasma. Mass spectrometry was used to validate the new ELISA method. The analysis of the same set of chemically modified albumin samples using the ELISA method and mass spectrometry showed good agreement for the relative levels of nitration present in each sample. The assay was applied to serum samples from patients undergoing elective surgery which induces the human inflammatory response. Matched samples were collected before and one day after surgery. An increase in nitration was detected following surgery (median (IQR): 0.59 (0.00–1.34) and 0.97 (0.00–1.70) nitrotyrosine (fmol of nitrated albumin equivalents/mg protein) for pre- and post-surgery respectively. The reported assay is suitable for nitrotyrosine determination in patient serum samples, and may also be applicable as a means to determine oxidative stress in primary and cultured cell populations

Enhanced resistance in Theobroma cacao against oomycete and fungal pathogens by secretion of phosphatidylinositol-3-phosphate-binding proteins

The internalization of some oomycete and fungal pathogen effectors into host plant cells has been reported to be blocked by proteins that bind to the effectors' cell entry receptor, phosphatidylinositol-3-phosphate (PI3P). This finding suggested a novel strategy for disease control by engineering plants to secrete PI3P-binding proteins. In this study, we tested this strategy using the chocolate tree Theobroma cacao. Transient expression and secretion of four different PI3P-binding proteins in detached leaves of T. cacao greatly reduced infection by two oomycete pathogens, Phytophthora tropicalis and Phytophthora palmivora, which cause black pod disease. Lesion size and pathogen growth were reduced by up to 85%. Resistance was not conferred by proteins lacking a secretory leader, by proteins with mutations in their PI3P-binding site, or by a secreted PI4P-binding protein. Stably transformed, transgenic T. cacao plants expressing two different PI3P-binding proteins showed substantially enhanced resistance to both P. tropicalis and P. palmivora, as well as to the fungal pathogen Colletotrichum theobromicola. These results demonstrate that secretion of PI3P-binding proteins is an effective way to increase disease resistance in T. cacao, and potentially in other plants, against a broad spectrum of pathogens.This is the publisher’s final pdf. The article is copyrighted by Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd. and published by Wiley Open Access. It can be found at: http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291467-7652Keywords: phosphatidylinositol-3-phosphate-binding protein, oomycetes, disease resistance, fungi, Theobroma cacao, effectorsKeywords: phosphatidylinositol-3-phosphate-binding protein, oomycetes, disease resistance, fungi, Theobroma cacao, effector

Smoking Cessation Intervention for Severe Mental Ill Health Trial (SCIMITAR+) : study protocol for a randomised controlled trial

BACKGROUND: Smoking is highly prevalent among people who have experience of severe mental ill health, contributing to their poor physical health. Despite the 'culture' of smoking in mental health services, people with severe mental ill health often express a desire to quit smoking; however, the services currently available to aid quitting are those which are widely available to the general population and may not be suitable or effective for people with severe mental ill health. The aim of this study is to explore the effectiveness and cost-effectiveness of a bespoke smoking-cessation intervention specifically targeted at people with severe mental ill health. METHODS/DESIGN: SCIMITAR+ is a multicentre, pragmatic, two-arm, parallel-group, individually randomised controlled trial. We aim to recruit 400 participants aged 18 years and above with a documented diagnosis of bipolar disorder, schizophrenia or schizoaffective disorder who smoke. Potentially eligible participants identified in primary or secondary care will be screened, and baseline data collected. Eligible, consenting participants will be randomly allocated to one of two groups. In the intervention arm, the participant will be assigned a mental health professional trained to deliver smoking-cessation interventions who will work with the participant and participant's GP or mental health specialist to provide an individually tailored smoking-cessation service. The comparator arm will be usual care - following current NICE guidelines for smoking cessation, in line with general guidance that is offered to all smokers, with no specific adaptation or enhancement in relation to severe mental ill health. The primary outcome will be self-reported smoking cessation at 12 months verified by expired carbon monoxide (CO) measurement. Secondary outcome measures include Body Mass Index at 12 months, the Fagerström Test for Nicotine Dependence, Motivation to Quit questionnaire, SF-12, PHQ-9, GAD-7, EQ-5D-5 L, and health service utilisation at 6 and 12 months. The economic evaluation at 12 months will be conducted in the form of an incremental cost-effectiveness analysis. DISCUSSION: SCIMITAR+ trial is the largest trial to our knowledge to investigate the effectiveness of a bespoke smoking-cessation service for people with severe mental ill health. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number, ISRCTN72955454 . Registered on 16 January 2015

Efficacy and Tolerability of Pharmacotherapies to Aid Smoking Cessation in Adolescents

Abstract Adolescent smoking remains a public health problem. Despite concerns regarding adolescent nicotine dependence, few well-designed smoking cessation studies have been conducted with teen smokers. This is particularly true regarding pharmacological treatments for nicotine dependence. Currently, pharmacological aids are not recommended for treating adolescent nicotine dependence, as efficacy has not been shown in this population. This review includes studies that have examined the efficacy of pharmacotherapy for smoking abstinence and/or reduction in cigarette consumption among adolescent smokers who want to quit smoking, lab-based adolescent studies that have examined the effectiveness of these medications in reducing cravings and/or withdrawal symptoms, and/or studies that have assessed the tolerability of medications for smoking cessation in adolescent smokers. This review provides information on the pharmacologic action of each medication, the efficacy of each medication for adolescent smoking cessation, the tolerability of each medication based on reported adverse events, and compliance with the medication protocols. Thirteen relevant articles were identified and included in the review. Nicotine patch, nicotine gum, nicotine nasal spray, bupropion, and varenicline have been studied in adolescent smokers. The adverse events reported in the studies on pharmacology for adolescent smoking suggest that the side effect profiles for nicotine replacement therapy, bupropion, and varenicline are similar to those reported in adult studies. There is some evidence of efficacy of nicotine patch and bupropion at end of treatment (efficacy of varenicline has not been assessed), but none of the medications included in this review were efficacious in promoting long-term smoking cessation among adolescent smokers. It is noted that many of the study protocols did not follow the recommended dose or length of pharmacotherapy for adults, rendering it difficult to determine the true efficacy of medication for adolescent smoking cessation. Future efficacy studies are warranted before recommending pharmacotherapy for adolescent smoking cessation. Adolescent Smoking and Pharmacotherapy Adolescent smoking remains a high priority public health concern. The U.S. Department of Health and Human Services has retained the goal of reducing adolescent smoking rates in the Healthy People 2020 initiative. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Considering that over 80% of adult smokers begin smoking prior to age of 18, Relatively few well-designed smoking cessation studies have been conducted with teen smokers. This is particularly true regarding pharmacological treatments for nicotine dependence. To date, nicotine replacement, bupropion (Zyban), and varenicline have been approved as therapies for adult smokers and the recommended treatment for adult nicotine dependence is a combination of psychotherapy and pharmacotherapy. Methods Study Identification and Inclusion Searches were conducted through the PubMed and PsycINFO online databases (through May 2011) and were limited to "English Language" and "Human." The following keywords were used in the initial search "smoking cessation", "adolescent OR teen" and then limited by the separate use of the following terms: "bupropion", "Zyban", "nicotine replacement therapy", "varenicline", "Chantix", "nicotine patch", "nicotine gum", "nicotine nasal spray", and "pharmacotherapy." Only studies that targeted adolescent smokers for recruitment and enrollment were included. In addition, studies referenced in relevant review articles, metaanalyses, and all selected articles were examined. The searches yielded 14 relevant studies that included pharmacotherapy for adolescent nicotine dependence. One study was excluded from the review because the focus was on reduction of smoking among adolescents that did not want to quit and did not include data on adverse events. Nicotine replacement therapy This review focuses on nicotine replacement therapy (NRT) that has been evaluated for smoking cessation among adolescent smokers (nicotine patch, gum, and spray); however, there are other nicotine replacement products approved for smoking cessation, including a nicotine inhaler, a nicotine lozenge and, in some countries outside of the United States, a nicotine sublingual tablet. Nicotine replacement therapy (NRT) replaces the nicotine delivered while smoking to reduce craving and withdrawal symptoms and is available in different forms and dosages depending on the number of cigarettes smoked. Open-label studies- The earliest study to use NRT with adolescent smokers was conducted by Smith and colleagues in 1996. No adverse events were associated with discontinuation of patch therapy. Hurt et al. conducted a larger open-label study (n = 101) that coupled six weeks of 15 mg/ 16-hour NP therapy with an optional brief individual counseling session at the first clinic visit. Randomized clinical trials (RCT)- The first randomized, double-blind, placebocontrolled study of NRT was conducted by Hanson et al. in 2003. [16] Initial dose and titration schedules were based on the teens' level of cigarette consumption. Participants (n = 100) received 10 weeks of NP therapy and cognitive-behavioral therapy and a contingency management procedure. There were no significant differences between groups in biologically verified, 7-day point prevalence abstinence at end of treatment (Week 10) (28.0% NP vs. 24.0% placebo), 30-day point prevalence abstinence (20.0% NP vs. 18.0% placebo), or continuous abstinence from the quit date. Compared to the placebo patch group, the active NP group experienced a significantly lower craving score and overall withdrawal symptom score. Participants in the placebo patch group reported more headaches than those in the active NP group (75.6% vs. 56.3%, respectively). None reported dropping out as a result of an adverse event and no significant differences in dropout rates or medication compliance were observed across the treatment groups. A community-based, double-blind pilot RCT was conducted by Roddy and colleagues with 98 regular smokers (defined as > 1 cigarette per day or < 1 cigarette per day but reported past or anticipated withdrawal). Moolchan and colleagues Finally, Rubinstein et al. conducted a pilot randomized trial of nicotine nasal spray (NNS) in 40 adolescent smokers. Summary of efficacy See Safety/tolerability None of the studies reported any severe or life-threatening side effects. The adverse events reported by adolescents for NRT were similar to those reported by adult smokers. Of the NRT studies, only three reported discontinuation of study medication during treatment due to an adverse event. Special considerations for use in adolescent smokers Controversy remains over the use of NRT in adolescents. Studies with animals indicate that nicotine can elicit neuronal damage and long-term changes in synaptic function, suggesting that there could be long-term adverse consequences of nicotine exposure in adolescence. Bupropion Bupropion was initially marketed as an atypical antidepressant and was approved in 1997, under the name Zyban, as the first non-nicotine medication to aid in smoking cessation for adults. Bupropion inhibits the reuptake of dopamine and norepinephrine in the central nervous system Randomized clinical trials (RCT)-Four RCTs have assessed the efficacy of bupropion for smoking cessation with adolescents. In the only study to examine bupropion SR in combination with NP therapy, Killen and colleagues randomized adolescent smokers (n = 211) to receive eight weeks of NP therapy and nine weeks of either 150 mg/day bupropion SR or placebo pills. Finally, Gray and colleagues examined the efficacy of 300 mg/day bupropion SR and contingency management (CM). Summary of efficacy See None of the studies with 300 mg/day bupropion SR were longer than six weeks in duration. The full dose was well tolerated by adolescent smokers and resulted in higher end of treatment abstinence than 150 mg/day bupropion SR in the only adolescent multi-dose study. However, similar to the few multi-dose studies in adults, the higher dose did not produce a better outcome at follow-up. Paediatr Drugs. Author manuscript; available in PMC 2012 April 4. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Given that none of the studies that have examined the use of bupropion SR for adolescent nicotine dependence followed the dosage recommendations for adult smokers, a future study that adheres to these guidelines is warranted. Safety/tolerability The most common adverse events reported by adolescent smokers were similar to those reported by their adult counterparts Although bupropion SR was generally well tolerated by adolescent smokers, hospitalizations occurred on three occasions. One was due to the intentional ingestion of Jimson weed in combination with bupropion SR, resulting in an anticholinergic crisis. Compliance rates Three of the five studies provided compliance data, but the methods used to assess compliance varied across the three studies. Special considerations for use in adolescent smokers Zyban contains the same active ingredient as the antidepressant medications Wellbutrin, Wellbutrin SR, and Wellbutrin XL. In 2004, the FDA directed manufacturers to add a "black box" to the health professional label of all antidepressants warning that antidepressants increased the risk compared to placebo of suicidal thinking and suicidal behavior in NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript children, adolescents, and young adults in short-term studies of major depressive disorder and other psychiatric disorders. In the RCTs with bupropion SR for smoking cessation in adolescent smokers, two adverse events were deemed to be intentional suicide attempts. Varenicline In 2006, the United States FDA approved varenicline as a prescription-only pharmacological aid for adult smoking cessation. It is also an approved smoking cessation aid in some countries outside of the U.S. Varenicline is a selective nicotinic acetylcholine receptor partial antagonist that binds to the α 4 β 2 receptor subtype, thereby reducing the reinforcing effects of nicotine. Due to its mixed agonist-antagonist properties, varenicline is effective at relieving craving and withdrawal during abstinence and blocking the reinforcing effects of smoking. Literature on varenicline in adolescent smokers One RCT examined the pharmacokinetics, safety and tolerability of varenicline in adolescent smokers

Monitoring Toxicity Associated with Parenteral Sodium Stibogluconate in the Day-Case Management of Returned Travellers with New World Cutaneous Leishmaniasi

Sodium stibogluconate (SbV), a pentavalent antimonial, administered parenterally, is the recommended treatment for South American cutaneous leishmaniasis, caused by Leishmania Viannia, which is a neglected disease that affects many people resident in Central and South America, as well as travellers to the areas. Antimonials have been used for the treatment of leishmaniasis since the 1930s. We report the toxicity experienced by a series of NWCL patients receiving SbV in a resource-rich setting. This study also evaluates administration of the drug to patients without admitting them to hospital. The administration of parenteral SbV was associated with myelosuppression, derangement of markers of liver function and prolongation of the QT interval on electrocardiography, although these effects were not found to be associated with adverse clinical events, and the majority of doses of SbV were administered without cause for hospital admission. Our data shows that parenteral SbV treatment may be provided with reduced monitoring for toxicity than is currently done, and on an outpatient-basis, without endangering safety. Such practice, with reduced demands on local finances and the healthcare workforce, would be desirable in more resource-limited settings

Representing the function and sensitivity of coastal interfaces in earth system models

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Ward, N. D., Megonigal, J. P., Bond-Lamberty, B., Bailey, V. L., Butman, D., Canuel, E. A., Diefenderfer, H., Ganju, N. K., Goni, M. A., Graham, E. B., Hopkinson, C. S., Khangaonkar, T., Langley, J. A., McDowell, N. G., Myers-Pigg, A. N., Neumann, R. B., Osburn, C. L., Price, R. M., Rowland, J., Sengupta, A., Simard, M., Thornton, P. E., Tzortziou, M., Vargas, R., Weisenhorn, P. B., & Windham-Myers, L. Representing the function and sensitivity of coastal interfaces in earth system models. Nature Communications, 11(1), (2020): 2458, doi:10.1038/s41467-020-16236-2.Between the land and ocean, diverse coastal ecosystems transform, store, and transport material. Across these interfaces, the dynamic exchange of energy and matter is driven by hydrological and hydrodynamic processes such as river and groundwater discharge, tides, waves, and storms. These dynamics regulate ecosystem functions and Earth’s climate, yet global models lack representation of coastal processes and related feedbacks, impeding their predictions of coastal and global responses to change. Here, we assess existing coastal monitoring networks and regional models, existing challenges in these efforts, and recommend a path towards development of global models that more robustly reflect the coastal interface.Funding for this work was provided by Pacific Northwest National Laboratory (PNNL) Laboratory Directed Research & Development (LDRD) as part of the Predicting Ecosystem Resilience through Multiscale Integrative Science (PREMIS) Initiative. PNNL is operated by Battelle for the U.S. Department of Energy under Contract DE-AC05-76RL01830. Additional support to J.P.M. was provided by the NSF-LTREB program (DEB-0950080, DEB-1457100, DEB-1557009), DOE-TES Program (DE-SC0008339), and the Smithsonian Institution. This manuscript was motivated by discussions held by co-authors during a three-day workshop at PNNL in Richland, WA: The System for Terrestrial Aquatic Research (STAR) Workshop: Terrestrial-Aquatic Research in Coastal Systems. The authors thank PNNL artist Nathan Johnson for preparing the figures in this manuscript and Terry Clark, Dr. Charlette Geffen, and Dr. Nancy Hess for their aid in organizing the STAR workshop. The authors thank all workshop participants not listed as authors for their valuable insight: Lihini Aluwihare (contributed to biogeochemistry discussions and development of concept for Fig. 3), Gautam Bisht (contributed to modeling discussion), Emmett Duffy (contributed to observational network discussions), Yilin Fang (contributed to modeling discussion), Jeremy Jones (contributed to biogeochemistry discussions), Roser Matamala (contributed to biogeochemistry discussions), James Morris (contributed to biogeochemistry discussions), Robert Twilley (contributed to biogeochemistry discussions), and Jesse Vance (contributed to observational network discussions). A full report on the workshop discussions can be found at https://www.pnnl.gov/publications/star-workshop-terrestrial-aquatic-research-coastal-systems

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo