High-Reynolds Number Active Blowing Semi-Span Force Measurement System Development

Recent wind-tunnel tests at the NASA Langley Research Center National Transonic Facility utilized high-pressure bellows to route air to the model for evaluating aircraft circulation control. The introduction of these bellows within the Sidewall Model Support System significantly impacted the performance of the external sidewall mounted semi-span balance. As a result of this impact on the semi-span balance measurement performance, it became apparent that a new capability needed to be built into the National Transonic Facility s infrastructure to allow for performing pressure tare calibrations on the balance in order to properly characterize its performance under the influence of static bellows pressure tare loads and bellows thermal effects. The objective of this study was to design both mechanical calibration hardware and an experimental calibration design that can be employed at the facility in order to efficiently and precisely perform the necessary loadings in order to characterize the semi-span balance under the influence of multiple calibration factors (balance forces/moments and bellows pressure/temperature). Using statistical design of experiments, an experimental design was developed allowing for strategically characterizing the behavior of the semi-span balance for use in circulation control and propulsion-type flow control testing at the National Transonic Facility

Functional Activation and Effective Connectivity Differences in Adolescent Marijuana Users Performing a Simulated Gambling Task

Background. Adolescent marijuana use is associated with structural and functional differences in forebrain regions while performing memory and attention tasks. In the present study, we investigated neural processing in adolescent marijuana users experiencing rewards and losses. Fourteen adolescents with frequent marijuana use (\u3e5 uses per week) and 14 nonuser controls performed a computer task where they were required to guess the outcome of a simulated coin flip while undergoing magnetic resonance imaging. Results. Across all participants, ?Wins? and ?Losses? were associated with activations including cingulate, middle frontal, superior frontal, and inferior frontal gyri and declive activations. Relative to controls, users had greater activity in the middle and inferior frontal gyri, caudate, and claustrum during ?Wins? and greater activity in the anterior and posterior cingulate, middle frontal gyrus, insula, claustrum, and declive during ?Losses.? Effective connectivity analyses revealed similar overall network interactions among these regions for users and controls during both ?Wins? and ?Losses.? However, users and controls had significantly different causal interactions for 10 out of 28 individual paths during the ?Losses? condition. Conclusions. Collectively, these results indicate adolescent marijuana users have enhanced neural responses to simulated monetary rewards and losses and relatively subtle differences in effective connectivity

Defining Meyer's loop-temporal lobe resections, visual field deficits and diffusion tensor tractography

Anterior temporal lobe resection is often complicated by superior quadrantic visual field deficits (VFDs). In some cases this can be severe enough to prohibit driving, even if a patient is free of seizures. These deficits are caused by damage to Meyer's loop of the optic radiation, which shows considerable heterogeneity in its anterior extent. This structure cannot be distinguished using clinical magnetic resonance imaging sequences. Diffusion tensor tractography is an advanced magnetic resonance imaging technique that enables the parcellation of white matter. Using seed voxels antero-lateral to the lateral geniculate nucleus, we applied this technique to 20 control subjects, and 21 postoperative patients. All patients had visual fields assessed with Goldmann perimetry at least three months after surgery. We measured the distance from the tip of Meyer's loop to the temporal pole and horn in all subjects. In addition, we measured the size of temporal lobe resection using postoperative T1-weighted images, and quantified VFDs. Nine patients suffered VFDs ranging from 22% to 87% of the contralateral superior quadrant. In patients, the range of distance from the tip of Meyer's loop to the temporal pole was 24–43 mm (mean 34 mm), and the range of distance from the tip of Meyer's loop to the temporal horn was –15 to +9 mm (mean 0 mm). In controls the range of distance from the tip of Meyer's loop to the temporal pole was 24–47 mm (mean 35 mm), and the range of distance from the tip of Meyer's loop to the temporal horn was –11 to +9 mm (mean 0 mm). Both quantitative and qualitative results were in accord with recent dissections of cadaveric brains, and analysis of postoperative VFDs and resection volumes. By applying a linear regression analysis we showed that both distance from the tip of Meyer's loop to the temporal pole and the size of resection were significant predictors of the postoperative VFDs. We conclude that there is considerable variation in the anterior extent of Meyer's loop. In view of this, diffusion tensor tractography of the optic radiation is a potentially useful method to assess an individual patient's risk of postoperative VFDs following anterior temporal lobe resection

Controlling weapons circulation in a postcolonial militarised world

What are the politics of, and prospects for, contemporary weapons control? Human rights and humanitarian activists and scholars celebrate the gains made in the UN Arms Trade Treaty as a step towards greater human security. Critics counter that the treaty represents an accommodation with global militarism. Taking the tensions between arms transfer control and militarism as my starting point, I argue that the negotiating process and eventual treaty text demonstrate competing modes of militarism. Expressed in terms of sovereignty, political economy, or human security, all three modes are underpinned by ongoing imperial relations: racial, gendered and classed relations of asymmetry and hierarchy that persist despite formal sovereign equality. This means human security is a form of militarism rather than the antithesis of it. Drawing on primary sources from negotiations and participant observation with actors involved in the campaign for the ATT, the argument challenges the idea that human security has scored a victory over militarism. It also complicates our understanding of the nature of the accommodation with it, demonstrating the transformation as well as entrenchment of contemporary militarism. The argument reframes the challenges for controlling weapons circulation, placing the necessity for feminist, postcolonial anti-militarist critique front and centre

Heightened impulsivity: associated with family history of alcohol misuse, and a consequence of alcohol intake

BACKGROUND Youths with family history (FH) of alcoholism are at greater risk of developing alcohol use disorder (AUD); heightened impulsive behavior may underlie such increased vulnerability. Here, we studied waiting impulsivity (previously suggested to predispose to alcohol drinking) in young moderate-to-heavy social drinkers (18 to 33 years old) characterized as family history positive (FHP) and negative (FHN) following an alcoholic or nonalcoholic (placebo) drink. METHODS Two groups of young male and female social drinkers (n = 64) were administered an acute dose of alcohol (0.8 g/kg) or placebo. One group (FHP; n = 24) had first-degree relatives with problems of alcohol misuse; the other group (FHN) did not. Participants completed 4 variants of the Sx-5CSRTT, a task measuring waiting impulsivity. In addition, other types of impulsive behavior were tested (by means of the stop-signal task [SST]; information sampling task [IST]; Delay Discounting Questionnaire; 2-choice impulsivity paradigm; and time estimation task). RESULTS Young FHP adults showed more premature responding than FHN when evaluated under increased attentional load (high waiting impulsivity), while, in contrast, they presented a more conservative strategy on the IST (less impulsive behavior), compared to FHN. Acute alcohol impaired inhibitory control on the SST in all participants, and induced a marginal increase of premature responses, but did not affect other measures of impulsivity. CONCLUSIONS Assessing for exaggerated waiting impulsivity may provide a potential endophenotype associated with risk for the development of alcohol addiction (i.e., offspring of alcoholics)

"We're not short of people telling us what the problems are. We're short of people telling us what to do": An appraisal of public policy and mental health

Background: There is sustained interest in public health circles in assessing the effects of policies on health and health inequalities. We report on the theory, methods and findings of a project which involved an appraisal of current Scottish policy with respect to its potential impacts on mental health and wellbeing. Methods: We developed a method of assessing the degree of alignment between Government policies and the 'evidence base', involving: reviewing theoretical frameworks; analysis of policy documents, and nineteen in-depth interviews with policymakers which explored influences on, and barriers to cross-cutting policymaking and the use of research evidence in decisionmaking. Results: Most policy documents did not refer to mental health; however most referred indirectly to the determinants of mental health and well-being. Unsurprisingly research evidence was rarely cited; this was more common in health policy documents. The interviews highlighted the barriers to intersectoral policy making, and pointed to the relative value of qualitative and quantitative research, as well as to the imbalance of evidence between "what is known" and "what is to be done". Conclusion: Healthy public policy depends on effective intersectoral working between government departments, along with better use of research evidence to identify policy impacts. This study identified barriers to both these. We also demonstrated an approach to rapidly appraising the mental health effects of mainly non-health sector policies, drawing on theoretical understandings of mental health and its determinants, research evidence and policy documents. In the case of the social determinants of health, we conclude that an evidence-based approach to policymaking and to policy appraisal requires drawing strongly upon existing theoretical frameworks, as well as upon research evidence, but that there are significant practical barriers and disincentives

Design of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1)

Mutations in leucine-rich repeat kinase 2 (LRRK2), such as G2019S, are associated with an increased risk of developing Parkinson’s disease. Surrogates for the LRRK2 kinase domain based on checkpoint kinase 1 (CHK1) mutants were designed, expressed in insect cells infected with baculovirus, purified, and crystallized. X-ray structures of the surrogates complexed with known LRRK2 inhibitors rationalized compound potency and selectivity. The CHK1 10-point mutant was preferred, following assessment of surrogate binding affinity with LRRK2 inhibitors. Fragment hit-derived arylpyrrolo­[2,3-<i>b</i>]­pyridine LRRK2 inhibitors underwent structure-guided optimization using this crystallographic surrogate. LRRK2-pSer935 HEK293 IC₅₀ data for <b>22</b> were consistent with binding to Ala2016 in LRRK2 (equivalent to Ala147 in CHK1 10-point mutant structure). Compound <b>22</b> was shown to be potent, moderately selective, orally available, and brain-penetrant in wild-type mice, and confirmation of target engagement was demonstrated, with LRRK2-pSer935 IC₅₀ values for <b>22</b> in mouse brain and kidney being 1.3 and 5 nM, respectively