Omega-3 Fatty Acids Improve Recovery, whereas Omega-6 Fatty Acids Worsen Outcome, after Spinal Cord Injury in the Adult Rat

Spinal cord injury (SCI) is a cause of major neurological disability, and no satisfactory treatment is currently available. Evidence suggests that polyunsaturated fatty acids (PUFAs) could target some of the pathological mechanisms that underlie damage after SCI. We examined the effects of treatment with PUFAs after lateral spinal cord hemisection in the rat. The ω-3 PUFAs α-linolenic acid and docosahexaenoic acid (DHA) injected 30 min after injury induced significantly improved locomotor performance and neuroprotection, including decreased lesion size and apoptosis and increased neuronal and oligodendrocyte survival. Evidence showing a decrease in RNA/DNA oxidation suggests that the neuroprotective effect of ω-3 PUFAs involved a significant antioxidant function. In contrast, animals treated with arachidonic acid, an ω-6 PUFA, had a significantly worse outcome than controls. We confirmed the neuroprotective effect of ω-3 PUFAs by examining the effects of DHA treatment after spinal cord compression injury. Results indicated that DHA administered 30 min after spinal cord compression not only greatly increased survival of neurons but also resulted in significantly better locomotor performance for up to 6 weeks after injury. This report shows a striking difference in efficacy between the effects of treatment with ω-3 and ω-6 PUFAs on the outcome of SCI, with ω-3 PUFAs being neuroprotective and ω-6 PUFAs having a damaging effect. Given the proven clinical safety of ω-3 PUFAs, our observations show that these PUFAs have significant therapeutic potential in SCI. In contrast, the use of preparations enriched in ω-6 PUFAs after injury could worsen outcome after SCI

Electrophysiological correlates of high-level perception during spatial navigation

We studied the electrophysiological basis of object recognition by recording scalp\ud electroencephalograms while participants played a virtual-reality taxi driver game.\ud Participants searched for passengers and stores during virtual navigation in simulated\ud towns. We compared oscillatory brain activity in response to store views that were targets or\ud nontargets (during store search) or neutral (during passenger search). Even though store\ud category was solely defined by task context (rather than by sensory cues), frontal ...\ud \u

Adolescent Experiences With Intrauterine Devices: A Qualitative Study

PURPOSE: The purpose of this study was to improve understanding of adolescents\u27 reasons for choosing an intrauterine device (IUD) and to explore experiences that led to continuation or discontinuation of the levonorgestrel intrauterine system (LNG-IUS) and the copper IUD (copper IUD). METHODS: We conducted focus groups (FGs) with adolescents and young women who were current or former IUD users stratified by IUD type and 12-month IUD continuation or discontinuation. All subjects were participants from the Contraceptive CHOICE Project. FG data were supplemented with in-depth interviews (IDIs). Data collection was continued until thematic saturation was reached. Transcripts were independently coded by two researchers, and interrater reliability was calculated using a Kappa coefficient. Analysis followed a standard text-analysis approach. RESULTS: Thirteen FGs and seven IDIs were conducted with 43 young women. Effectiveness, duration of use, convenience, and potential bleeding changes emerged as themes for both choosing and continuing IUDs. Some women chose the LNG-IUS to achieve amenorrhea, whereas copper IUD users wanted a nonhormonal method and continued menses. Copper IUD users cited expulsion and bleeding irregularities as reasons for discontinuation, whereas LNG-IUS users reported bleeding irregularities and continued pain as reasons for removal. IUD users noted an adjustment period of weeks to months in which side effects were present before lessening. CONCLUSIONS: Effectiveness, duration of use, convenience, and potential changes in bleeding patterns drove adolescents\u27 choice and continuation of an IUD. Bleeding changes and pain contributed to IUD discontinuation. Discussion of effectiveness, duration and convenience, and anticipatory guidance regarding post-insertion side effects may be important in counseling young women about IUDs

Outcome of neuropsychiatric symptoms related to an antiretroviral drug following its substitution by nevirapine: the RELAX study

Objectives: The primary objective was to evaluate the improvement in neuropsychiatric symptoms attributed to an antiretroviral drug after that drug was substituted with nevirapine. The secondary objective was to evaluate the impact on patient adherence and quality of life. Methods: A prospective, observational study was carried out that included patients with HIV-1 plasma suppression for whom an antiretroviral drug was substituted with nevirapine because of central nervous system (CNS) side effects, a Pittsburgh Sleep Quality Index (PSQI) score > 5 or a Hospital Anxiety and Depression Scale (HADS) score ≥ 10, and who had not initiated psychoactive drug treatment during the prior 6 weeks. Evaluations were carried out at baseline and 1 and 3 months after the switch using the PSQI, HADS, Epworth Sleepiness Scale, Medical Outcomes Study-Short Form 30 items (MOS-SF-30) and Simplified Medication Adherence Questionnaire (SMAQ). Results: A total of 129 patients were included in the study. The drug substituted was mainly efavirenz (89.9%), and reasons for the switch included sleep disturbances (75.2%), anxiety (65.1%), depression (38.7%), attention disturbances (31%), and other reasons (31%), with a mean of 2.4 neuropsychiatric disturbances per patient. A statistically significant improvement was observed in all the tests evaluating neuropsychiatric symptoms and adherence at 1 and 3 months. The CD4 lymphocyte count remained stable (P = 0.096). Three (2.3%) patients had a detectable plasma HIV-1 RNA at the end of the study. Nine patients (6.9%) withdrew because of nevirapine-related toxicity (rash in seven patients and hypertransaminasaemia in two patients, none of which were > grade 2). Conclusions: The switch to nevirapine from a drug causing neuropsychiatric disturbances (primarily efavirenz) in subjects with virological suppression was effective in resolving those disturbances, with an improvement in all the parameters studied. This led to better adherence to treatment and quality of life, with no detrimental effect on their immunological and virological controlBoehringer Ingelheim Spai

The Effect of Diluent Gases In The Shock Tube and Rapid Compression Machine

Studying the details of hydrocarbon chemistry in an internal combustion engine is not straightforward. A number of factors, including varying conditions of temperature and pressure, complex fluid motions, as well as variation in the composition of gasoline, render a meaningful characterization of the combusting system difficult. Some simplified experimental laboratory devices offer an alternative to complex engine environments: they remove some of the complexities that exist in real engines but retain the ability to work under engine-relevant conditions. The choice of simplified experimental devices is limited by the range of temperature and pressure at which they can operate; only the shock tube and rapid compression machine (RCM) can reach engine-relevant temperatures and pressures quickly enough and yet withstand the high pressures that occur after the ignition event. Both devices, however, suffer a common drawback: the use of inert diluent gases has been shown to affect the measured ignition delay time under some experimental conditions. Interestingly, this effect appears to be opposite in the shock tube and RCM: in the comparative study of the carrier gases argon and nitrogen, argon decreases the ignition delay time in the shock tube, but increases it in the RCM. This observation is investigated in more detail in this study

A Detailed Chemical Kinetic Reaction Mechanism for n-Alkane Hydrocarbons from n-Octane to n-Hexadecane

Detailed chemical kinetic reaction mechanisms have been developed to describe the pyrolysis and oxidation of the n-alkanes, including n-octane (n-C{sub 8}H{sub 18}), n-nonane (n-C{sub 9}H{sub 20}), n-decane (n-C{sub 10}H{sub 22}), n-undecane (n-C{sub 11}H{sub 24}), n-dodecane (n-C{sub 12}H{sub 26}), n-tridecane (n-C{sub 13}H{sub 28}), n-tetradecane (n-C{sub 14}H{sub 30}), n-pentadecane (n-C{sub 15}H{sub 32}), and n-hexadecane (n-C{sub 16}H{sub 34}). These mechanisms include both high temperature and low temperature reaction pathways. The mechanisms are based on previous mechanisms for n-heptane, using the same reaction class mechanism construction developed initially for n-heptane. Individual reaction class rules are as simple as possible in order to focus on the parallelism between all of the n-alkane fuels included in the mechanisms, and there is an intent to develop these mechanisms further in the future to incorporate greater levels of accuracy and predictive capability. Several of these areas for improvement are identified and explained in detail. These mechanisms are validated through comparisons between computed and experimental data from as many different sources as possible. In addition, numerical experiments are carried out to examine features of n-alkane combustion in which the detailed mechanisms can be used to compare processes in all of the n-alkane fuels. The mechanisms for all of these n-alkanes are presented as a single detailed mechanism, which can be edited to produce efficient mechanisms for any of the n-alkanes included, and the entire mechanism, with supporting thermochemical and transport data, together with an explanatory glossary explaining notations and structural details, will be available on our web page when the paper is accepted for publication

Long-term neural and physiological phenotyping of a single human

Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders

The genetic determinants of recurrent somatic mutations in 43,693 blood genomes

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences

A revised 1000 year atmospheric δ\u3csup\u3e13\u3c/sup\u3e C-CO2 record from Law Dome and South Pole, Antarctica

We present new measurements of δ13C of CO2 extracted from a high-resolution ice core from Law Dome (East Antarctica), together with firn measurements performed at Law Dome and South Pole, covering the last 150 years. Our analysis is motivated by the need to better understand the role and feedback of the carbon (C) cycle in climate change, by advances in measurement methods, and by apparent anomalies when comparing ice core and firn air δ13C records from Law Dome and South Pole. We demonstrate improved consistency between Law Dome ice, South Pole firn, and the Cape Grim (Tasmania) atmospheric δ13C data, providing evidence that our new record reliably extends direct atmospheric measurements back in time. We also show a revised version of early δ13C measurements covering the last 1000 years, with a mean preindustrial level of -6.50‰. Finally, we use a Kalman Filter Double Deconvolution to infer net natural CO2 fluxes between atmosphere, ocean, and land, which cause small δ13C deviations from the predominant anthropogenically induced δ13C decrease. The main features found from the previous δ13C record are confirmed, including the ocean as the dominant cause for the 1940 A.D. CO2 leveling. Our new record provides a solid basis for future investigation of the causes of decadal to centennial variations of the preindustrial atmospheric CO2 concentration. Those causes are of potential significance for predicting future CO2 levels and when attempting atmospheric verification of recent and future global carbon emission mitigation measures through Coupled Climate Carbon Cycle Models. Key Points New and revised, firn and ice δ13C-CO2 measurements from Antarctica Improve consistency between ice and firn δ13C-CO2 measurements Net natural CO2 fluxes between atmosphere, ocean and land inferred ©2013. American Geophysical Union. All Rights Reserved

Paper II: Calibration of the Swift ultraviolet/optical telescope

The Ultraviolet/Optical Telescope (UVOT) is one of three instruments onboard the Swift observatory. The photometric calibration has been published, and this paper follows up with details on other aspects of the calibration including a measurement of the point spread function with an assessment of the orbital variation and the effect on photometry. A correction for large scale variations in sensitivity over the field of view is described, as well as a model of the coincidence loss which is used to assess the coincidence correction in extended regions. We have provided a correction for the detector distortion and measured the resulting internal astrometric accuracy of the UVOT, also giving the absolute accuracy with respect to the International Celestial Reference System. We have compiled statistics on the background count rates, and discuss the sources of the background, including instrumental scattered light. In each case we describe any impact on UVOT measurements, whether any correction is applied in the standard pipeline data processing or whether further steps are recommended.Comment: Accepted for publication in MNRAS. 15 pages, 21 figures, 4 table