Trade Study Analysis for TNS Tokamaks.

A series of parametric trade studies was performed to consistently evaluate the relative.costs and performance parameters of D-T burning tokamaks over a range of plasma sizes and toroidal field (TF) coil technologies. Four different types of TF coil technologies were investigated: water-cooled copper coils, superconducting NbTi and Nb{sub 3}Sn coils, and a "hybrid" coil arrangement consisting of a· normal conducting Cu coil nested within a superconducting NbTi coil. Results of the analysis indicate for TNS operation, for example, that for a given plasma beta at ignition, the Cu TF coil devices are least expensive, followed by the Nb{sub 3}Sn, NbTi, and NbTi/Cu options. Other conclusions and trends resulting from the study are presented and analyzed

Determination of the Spawning Season of Bigmouth Sleeper in Puerto Rico by Examination of Gonad Maturation and Reproductive Hormone Cycles

Bigmouth sleepers, Gobiomorus dormitor, are diadromous fish that have potential for hatchery production as both food and sport fish and for conservation purposes. Understanding of bigmouth sleeper maturation and seasonal hormone cycling are necessary in order to realize hatchery production. Therefore, seasonal trends in gonadosomatic index (GSI) and plasma vitellogenin, estradiol, progesterone and total testosterone concentrations were examined in wild and captive populations in Puerto Rico during the presumed spawning season. The spawning season for wild river populations of bigmouth sleepers was protracted over several months, but peaks in male testosterone (6.5 ng/mL) and female vitellogenin (11.3 ng/mL), estradiol (3.3 ng/mL), and GSI (9.5—12.0%) demonstrated that the bigmouth sleeper spawning season occurred primarily in July and August in southwestern Puerto Rico. Captive female broodstock held in shallow hatchery ponds demonstrated accelerated maturation, presumably due to warmer water temperatures in the ponds. Therefore, induced and natural spawning attempts using captive female bigmouth sleeper broodstock should be conducted from June through July. However, advanced gonadal maturation and increased testosterone production in captive males was minimal. Hence, induced spawning for captive rearing purposes should use wild broodstock captured during the peak of the natural spawning season in July and August

Genomic Resources for Asparagales

Enormous genomic resources have been developed for plants in the monocot order Poales; however, it is not known how useful these resources will be for other economically important monocots. Asparagales are a monophyletic order sister to class Commelinanae that carries Poales, and is the second most economically important monocot order. Development of genomic resources for and their application to Asparagales are challenging because of huge nuclear genomes and the relatively long generation times required to develop segregating families. We synthesized a normalized eDNA library of onion (Allium cepa) and produced II ,008 unique expressed sequence tags (ESTs) for comparative genomic analyses of Asparagales and Poales. Alignments of onion ESTs, Poales ESTs, and genomic sequences from rice were used to design oligonucleotide primers amplifying genomic regions from asparagus, garlic, and onion. Sequence analyses of these genomic regions revealed microsatellites, insertions/deletions, and single nucleotide polymorphisms for comparative mapping of rice and Asparagales vegetables. Initial mapping revealed no obvious synteny at the recombinationallevel between onion and rice, indicating that genomic resources developed for Poales may not be applicable to the monocots as a whole. Genomic analyses of Asparagales would greatly benefit from EST sequencing and deep-coverage, large-insert genomic libraries of representative small-genome model species within the higher and lower Asparagales, such as asparagus and orchid, respectively

Trade Study Analysis for TNS Tokamaks.

A series of parametric trade studies was performed to consistently evaluate the relative.costs and performance parameters of D-T burning tokamaks over a range of plasma sizes and toroidal field (TF) coil technologies. Four different types of TF coil technologies were investigated: water-cooled copper coils, superconducting NbTi and Nb{sub 3}Sn coils, and a "hybrid" coil arrangement consisting of a· normal conducting Cu coil nested within a superconducting NbTi coil. Results of the analysis indicate for TNS operation, for example, that for a given plasma beta at ignition, the Cu TF coil devices are least expensive, followed by the Nb{sub 3}Sn, NbTi, and NbTi/Cu options. Other conclusions and trends resulting from the study are presented and analyzed

Nucleus Accumbens Adenosine A2A Receptors Regulate Exertion of Effort by Acting on the Ventral Striatopallidal Pathway

Goal-directed actions are sensitive to work-related response costs, and dopamine in nucleus accumbens is thought to modulate the exertion of effort in motivated behavior. Dopamine-rich striatal areas such as nucleus accumbens also contain high numbers of adenosine A2A receptors, and, for that reason, the behavioral and neurochemical effects of the adenosine A2A receptor agonist CGS 21680 [2-p-(2-carboxyethyl) phenethylamino-5′-N-ethylcarboxamidoadenosine] were investigated. Stimulation of accumbens adenosine A2A receptors disrupted performance of an instrumental task with high work demands (i.e., an interval lever-pressing schedule with a ratio requirement attached) but had little effect on a task with a lower work requirement. Immunohistochemical studies revealed that accumbens neurons that project to the ventral pallidum showed adenosine A2A receptors immunoreactivity. Moreover, activation of accumbens A2A receptors by local injections of CGS 21680 increased extracellular GABA levels in the ventral pallidum. Combined contralateral injections of CGS 21680 into the accumbens and the GABAA agonist muscimol into ventral pallidum (i.e., “disconnection” methods) also impaired response output, indicating that these structures are part of a common neural circuitry regulating the exertion of effort. Thus, accumbens adenosine A2A receptors appear to regulate behavioral activation and effort-related processes by modulating the activity of the ventral striatopallidal pathway. Research on the effort-related functions of these forebrain systems may lead to a greater understanding of pathological features of motivation, such as psychomotor slowing, anergia, and fatigue in depression

Patient and public involvement in designing and conducting doctoral research: the whys and the hows

YesPublic and patient involvement (PPI) has been shown to have a positive impact on health and social care research. However, adequate examples describing how to operationalise effective PPI, especially in doctoral studies, are lacking. Hence, doctoral researchers new to research, or those with limited experience, can be discouraged from facilitating PPI in their research. This paper aims to describe and discuss in detail the approaches used by four doctoral researchers to incorporate PPI at different stages of their research studies from study design to disseminating findings. We aim to inform other doctoral researchers about the challenges and limitations relating to PPI that we faced. Through these, we share pragmatic recommendations for facilitating PPI during doctoral studies. The description of four case studies demonstrated that PPI could be incorporated at various stages during doctoral research. This has had a beneficial impact on our research study progression, researcher self-esteem and lastly, helped alleviate researcher isolation during doctoral studies.Supported by Research Design Service Yorkshire and the Humber (RDSYH), the National Institute for Health Research (NIHR) Yorkshire and Humber Patient Safety Translational Research Centre (NIHR Yorkshire and Humber PSTRC). This paper presents independent research funded by NIHR under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0317-20010).Research Development Fund Publication Prize Award winner, July 2019

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Residual lung lesions after completion of chemotherapy for gestational trophoblastic neoplasia: should we operate?

The significance of residual lung metastasis from malignant gestational trophoblastic neoplasm (GTN) after the completion of chemotherapy is unknown. We currently do not advocate resection of these masses. Here, we investigate the outcome of these patients. Patients with residual lung abnormalities after the completion of treatment for GTN were compared to those who had a complete radiological resolution of the disease. None of the residual masses post-treatment were surgically removed. In all, 76 patients were identified. Overall 53 (70%) patients had no radiological abnormality on CXR or CT after completion of treatment. Eight (11%) patients had residual disease on CXR alone 15 patients had residual disease on CT (19%). During follow-up, two patients (2.6%) relapsed. One of these had had a complete radiological response post-treatment whereas the other had residual disease on CT. Patients with residual lung lesions after completing treatment for GTN do not appear to have an increased chance of relapse compared to those with no residual abnormality. We continue to recommend that these patients do not require pulmonary surgery for these lesions

Shaping a screening file for maximal lead discovery efficiency and effectiveness: elimination of molecular redundancy

High Throughput Screening (HTS) is a successful strategy for finding hits and leads that have the opportunity to be converted into drugs. In this paper we highlight novel computational methods used to select compounds to build a new screening file at Pfizer and the analytical methods we used to assess their quality. We also introduce the novel concept of molecular redundancy to help decide on the density of compounds required in any region of chemical space in order to be confident of running successful HTS campaigns