A NASA-wide approach toward cost-effective, high-quality software through reuse

NASA Langley Research Center sponsored the second Workshop on NASA Research in Software Reuse on May 5-6, 1992 at the Research Triangle Park, North Carolina. The workshop was hosted by the Research Triangle Institute. Participants came from the three NASA centers, four NASA contractor companies, two research institutes and the Air Force's Rome Laboratory. The purpose of the workshop was to exchange information on software reuse tool development, particularly with respect to tool needs, requirements, and effectiveness. The participants presented the software reuse activities and tools being developed and used by their individual centers and programs. These programs address a wide range of reuse issues. The group also developed a mission and goals for software reuse within NASA. This publication summarizes the presentations and the issues discussed during the workshop

COMT Val158Met Polymorphism Exerts Sex-Dependent Effects on fMRI Measures of Brain Function

Evidence suggests that dopamine levels in the prefrontal cortex (PFC) modulate executive functions. A key regulator of PFC dopamine is catechol-O-methyltransferase (COMT). The activity level of the COMT enzyme are influenced by sex and the Val158Met polymorphism (rs4680) of the COMT gene, with male sex and Val alleles both being associated with higher bulk enzyme activity, and presumably lower PFC dopamine. COMT genotype has not only been associated with individual differences in frontal dopamine-mediated behaviors, but also with variations in neuroimaging measures of brain activity and functional connectivity. In this study, we investigated whether COMT genotype predicts individual differences in neural activity and connectivity, and whether such effects are sex-dependent. We tested 93 healthy adults (48 females), genotyped for the Val158Met polymorphism, in a delay discounting task and at rest during fMRI. Delay discounting behavior was predicted by an interaction of COMT genotype and sex, consistent with a U-shaped relationship with enzyme activity. COMT genotype and sex similarly exhibited U-shaped relationships with individual differences in neural activation, particularly among networks that were most engaged by the task, including the default-mode network. Effects of COMT genotype and sex on functional connectivity during rest were also U-shaped. In contrast, flexible reorganization of network connections across task conditions varied linearly with COMT among both sexes. These data provide insight into the potential influences of COMT-regulated variations in catecholamine levels on brain function, which may represent endophenotypes for disorders of impulsivity

Neural Systems Underlying Individual Differences in Intertemporal Decision-making

Excessively choosing immediate over larger future rewards, or delay discounting (DD), associates with multiple clinical conditions. Individual differences in DD likely depend on variations in the activation of and functional interactions between networks, representing possible endophenotypes for associated disorders, including alcohol use disorders (AUDs). Numerous fMRI studies have probed the neural bases of DD, but investigations of large-scale networks remains scant. We addressed this gap by testing whether activation within large-scale networks during “Now/Later” decision-making predicts individual differences in DD. To do so, we scanned 95 social drinkers (18–40 years; 50 females) using fMRI during hypothetical choices between small monetary amounts available “today” or larger amounts available later. We identified neural networks engaged during Now/Later choice using independent component analysis (ICA) and tested the relationship between component activation and degree of DD. The activity of two components during Now/Later choice correlated with individual DD rates: a temporal lobe network positively correlated with DD, while a frontoparietal-striatal network negatively correlated with DD. Activation differences between these networks predicted individual differences in DD and their negative correlation during Now/Later choice suggests functional competition. A generalized psychophysiological interactions (gPPI) analysis confirmed a decrease in their functional connectivity during decision-making. The functional connectivity of these two networks negatively correlates with alcohol-related harm, potentially implicating these networks in AUDs. These findings provide novel insight into the neural underpinnings of individual differences in impulsive decision making with potential implications for addiction and related disorders in which impulsivity is a defining feature

Food insecurity and severe mental illness: understanding the hidden problem and how to ask about food access during routine healthcare

SUMMARY Food insecurity occurs when an individual lacks the financial resources to ensure reliable access to sufficient food to meet their dietary, nutritional and social needs. Adults living with mental ill health, particularly severe mental illness, are more likely to experience food insecurity than the general adult population. Despite this, most interventions and policy reforms in recent years have been aimed at children and families, with little regard for other vulnerable groups. Initiating a conversation about access to food can be tricky and assessing for food insecurity does not happen in mental health settings. This article provides an overview of food insecurity and how it relates to mental ill health. With reference to research evidence, the reader will gain an understanding of food insecurity, how it can be assessed and how food-insecure individuals with severe mental illness can be supported. Finally, we make policy recommendations to truly address this driver of health inequality.</jats:p

Age modulates the effect of COMT genotype on delay discounting behavior

A form of impulsivity, the tendency to choose immediate over delayed rewards (delay-discounting) has been associated with a single nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene (COMTval158met; rs4680). However, existing data regarding the nature of this association conflicts. We have previously reported that adults homozygous for valine (val) at the COMTval158met SNP demonstrate greater delay-discounting than do methionine (met) allele carriers (Boettiger et al. 2007). In contrast, a recent study of adolescent males found that those with the met/met genotype demonstrate greater delay-discounting than do val-allele carriers (Paloyelis et al. 2010). Based on reported age-related changes in frontal dopamine function and COMT expression, we hypothesized that the association of COMT genotype with delay-discounting behavior is modulated by age from late adolescence to young adulthood

The Effect of Amnion-derived Cellular Cytokine Solution on the Epithelialization of Partial-thickness Donor Site Wounds in Normal and Streptozotocin-induced Diabetic Swine

Objective: The purpose of this study was to determine whether amnion-derived cellular cytokine solution (ACCS) could improve the quality of epithelialization and accelerate closure of dermatome-created partial-thickness wounds in normal and streptozotocin-induced diabetic pigs. Methods: Dermatome-created partial-thickness wounds were sealed with wound chambers in healthy and diabetic pigs and were injected with ACCS. Wound fluid was exchanged daily for total protein concentration, and biopsies were taken on days 6, 8, 10, and 12. Epithelialization, thickness of epidermis, number of epidermal cell layers, and rete ridges were evaluated. Results: The macroscopic appearance of the wounds and speed of healing was similar in all groups at each time point. All wounds were healed by day 6. The epidermis was thicker in the ACCS-treated diabetic wounds than in the controls (140.6 μm vs 82.7 μm on day 12 in diabetic pigs). There were more cell layers (13 vs 7.7) in ACCS-treated diabetic pigs on day 12. The number of rete ridges per 2.5 mm was greater on day 12 in the ACCS-treated diabetic wounds (13 vs 8). There was also a significant increase in the number of rete ridges in ACCS-treated nondiabetic pigs but no difference in epidermal thickness or number of cell layers. Conclusion: In diabetic pigs, we found a significantly thicker epidermis and more cell layers and rete ridges in the ACCS-treated wounds. Healthy pigs showed more rete ridges but no difference in thickness of epidermis or number of cell layers on day 12

Effect of bupivacaine lozenges on oral mucositis pain:a randomized controlled multicenter phase II study

Abstract. Introduction:. A nonblinded parallel-group randomized controlled study investigated the efficacy and tolerability of repeated administration of a bupivacaine lozenge (25 mg) as pain management for oral mucositis pain in head and neck cancer patients as add-on to standard systemic pain management. Objective:. The primary end point was the difference between the intervention group (Lozenge group) and the Control group in daily mean pain scores in the oral cavity or pharynx (whichever was higher). Method:. Fifty patients from 2 hospitals in Denmark were randomized 1:1 to 7 days of treatment with bupivacaine lozenges (taken up to every 2 hours) plus standard pain treatment minus topical lidocaine (Lozenge group) or standard pain treatment including topical lidocaine (Control group). The efficacy analysis included 38 patients, as 12 patients were excluded because of changes in study design and missing data. Results:. Mean pain in the oral cavity or pharynx (whichever was higher) was significantly lower 60 minutes after taking lozenges (35 mm [n = 22]) than for the Control group (51 mm [n = 16]) (difference between groups −16 mm, 95% confidence interval: −26 to −6, P = 0.0032). Pain in the oral cavity was also significantly lower in the Lozenge group (18 mm) vs the Control group (36 mm, P = 0.0002). Pharyngeal mucositis pain did not differ significantly (37 mm [Lozenge group] vs 48 mm [Control group], P = 0.0630). No serious adverse events were reported. Conclusion:. These results show that the bupivacaine lozenge as an add-on to standard pain treatment had a clinically significant pain-relieving effect in patients with oral mucositis. ClinicalTrials.gov:. NCT02252926

Gene therapy with Angiotensin-(1-9) preserves left ventricular systolic function after myocardial infarction

BACKGROUND: Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin angiotensin system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic minipump in mice. Here, we investigate whether gene transfer of Ang-(1-9) is cardioprotective in a murine model of myocardial infarction (MI). OBJECTIVES: To evaluate effects of Ang-(1-9) gene therapy on myocardial structural and functional remodeling post infarction. METHODS: C57BL/6 mice underwent permanent left anterior descending coronary artery ligation and cardiac function was assessed using echocardiography for 8 weeks followed by a terminal measurement of left ventricular (LV) pressure-volume loops. Ang-(1-9) was delivered by adeno-associated viral vector via single tail vein injection immediately following induction of MI. Direct effects of Ang-(1-9) on cardiomyocyte excitation–contraction coupling and cardiac contraction were evaluated in isolated mouse and human cardiomyocytes and in an ex vivo Langendorff perfused whole heart model. RESULTS: Gene delivery of Ang-(1-9) significantly reduced sudden cardiac death post-MI. Pressure–volume measurements revealed complete restoration of end systolic pressure, ejection fraction, end systolic volume and the end diastolic pressure–volume relationship by Ang-(1-9) treatment. Stroke volume and cardiac output were significantly increased versus sham. Histological analysis revealed only mild effects on cardiac hypertrophy and fibrosis, but a significant increase in scar thickness. Direct assessment of Ang-(1-9) on isolated cardiomyocytes demonstrated a positive inotropic effect via increasing calcium transient amplitude and increasing contractility. Ang-(1-9) increased contraction in the Langendorff model through a protein kinase A-dependent mechanism. CONCLUSIONS: Our novel findings show that Ang-(1-9) gene therapy preserves LV systolic function post-MI, restoring cardiac function. Furthermore, Ang-(1-9) has a direct effect on cardiomyocyte 3 calcium handling through a protein kinase A-dependent mechanism. These data highlight Ang-(1-9) gene therapy as a potential new strategy in the context of MI

Long-term outcome data from 121 patients treated with Gamma Knife stereotactic radiosurgery as salvage therapy for focally recurrent high-grade gliomas.

Introduction: We examined patient outcomes after Gamma Knife stereotactic radiosurgery (GKSRS) salvage therapy for recurrent high-grade gliomas (HGGs) to determine whether tumor grade or lesion size affected overall survival (OS) and progression-free survival (PFS). Methods: This single-center retrospective study assessed radiographic response and clinical outcomes following GKSRS salvage treatment of recurrent malignant gliomas (January 2005-March 2014). Results: A total of 121 patients (67 female) with 132 tumors were treated. Median (range) PFS was 4.7 (3.9-5.4) months for the cohort, 6.8 (4.6-8.9) months for initial grade 2 tumors, 4.2 (1.9-6.5) months for initial grade 3 tumors, and 4.3 (3.7-4.9) months for initial grade 4 tumors. Patients with small lesions (≤6.7 cm Conclusions: GKSRS offers meaningful salvage therapy with minimal morbidity in appropriately selected patients with focally recurrent HGGs