SIMULATION MODEL MANAGEMENT: RESOLVING THE TECHNOLOGICAL GAPS

Model management poses requirements and responsibilities that extend throughout the life cycle of a simulation model. Recent publications have identified major problems in cost and time overruns, which are traceable to deficiencies in project and sponsor management. Beginning with the division of the simulation model life cycle into seven phases, we define "model management" and develop the requirements for a Model Management System (MMS). The functional description of a MMS focuses on those phases that jointly characterize the model development effort. Recent research in simulation model development is described, and particular emphasis is given to the approach taken with the Conical Methodology

Hyphenated LC-ICP-MS/ESI-MS identification of halogenated metabolites in South African marine ascidian extracts

Extracts of 13 species of marine ascidian collected in Algoa Bay were analyzed by LC-ICP-MS/ESI-MS. This technique allows parallel analysis of the molecular species and the presence of certain elements. The LC-ICP-MS/ESI-MS technique was used to target iodinated metabolites in this study. Three ascidian species afforded the known 3,5–diiodo-4-methoxyphenethylamine (12), which was confirmedby the isolation of this metabolite fromAplidium monile.MS also suggested the presence of theknown 3,5–dibromo-4-methoxyphenethylamine (10) and the new 3-bromo-5–iodo-4-methoxyphenethylamine (11) in the A. monile extract. The presence of the known 3,5-dibromotetramethyltyrosine (21) and the new 3-iodotetramethyltyrosine (23) in extracts of an unidentified Didemnum species was similarly proposed from MS evidence. This is the first report of the occurrence of iodinated metabolites in South African marine invertebrates.IS

Mapping Activity Patterns to Quantify Risk of Violent Assault in Urban Environments

BACKGROUND: We collected detailed activity paths of urban youth to investigate the dynamic interplay between their lived experiences, time spent in different environments, and risk of violent assault. METHODS: We mapped activity paths of 10- to 24-year-olds, including 143 assault patients shot with a firearm, 206 assault patients injured with other types of weapons, and 283 community controls, creating a step-by-step mapped record of how, when, where, and with whom they spent time over a full day from waking up until going to bed or being assaulted. Case-control analyses compared cases with time-matched controls to identify risk factors for assault. Case-crossover analyses compared cases at the time of assault with themselves earlier in the day to investigate whether exposure increases acted to the trigger assault. RESULTS: Gunshot assault risks included being alone (odds ratio [OR] = 1.6, 95% confidence interval [CI] = 1.3, 1.9) and were lower in areas with high neighbor connectedness (OR = 0.7, 95% CI = 0.6, 0.8). Acquiring a gun (OR = 1.4, 95% CI = 1.1, 1.6) and entering areas with more vacancy, violence, and vandalism (OR = 1.7, 95% CI = 1.1, 2.7) appeared to trigger the risk of getting shot shortly thereafter. Nongunshot assault risks included being in areas with recreation centers (OR = 1.2, 95% CI = 1.1, 1.4). Entering an area with higher truancy (OR = 1.6, 95% CI = 1.1, 2.5) and more vacancy, violence, and vandalism appeared to trigger the risk of nongunshot assault. Risks varied by age group. CONCLUSIONS: We achieved a large-scale study of the activities of many boys, adolescents, and young men that systematically documented their experiences and empirically quantified risks for violence. Working at a temporal and spatial scale that is relevant to the dynamics of this phenomenon gave novel insights into triggers for violent assault

A quarter century of marine biodiscovery in Algoa bay, South Africa

Algoa Bay, the largest crenulate bay on the south-eastern coast of South Africa, is currently one of the most well-studied marine ecosystems in southern Africa. A plethora of endemic marine invertebrates inhabits the benthic reefs on the western edge of the Bay in close proximity to South Africa’s sixth largest city. Over the past 25 years, South African marine natural products chemists, together with international collaborators from the US National Cancer Institute and other US institutions, have focused their attention on Algoa Bay’s benthic marine invertebrates as a potential source of new anticancer compounds. This review commemorates a quarter of a century of marine biodiscovery in Algoa Bay and presents the structures and bioactivities of 49 new and 36 known specialized metabolites isolated from two molluscs, eight ascidians, and six sponges. Thirty-nine of these compounds were cytotoxic to cancer cells in vitro with 20 exhibiting moderate to potent cytotoxicity. Six other compounds exhibited antimicrobial activity. Foremost among the potential anticancer compounds is mandelalide A (38) from the Algoa Bay ascidian Lissoclinum species

Agreement Between Clinician-Rated Versus Patient-Reported Outcomes in Huntington Disease

BACKGROUND: Clinician-rated measures of functioning are often used as primary endpoints in clinical trials and other behavioral research in Huntington disease. As study costs for clinician-rated assessments are not always feasible, there is a question of whether patient self-report of commonly used clinician-rated measures may serve as acceptable alternatives in low risk behavioral trials. AIM: The purpose of this paper was to determine the level of agreement between self-report and clinician-ratings of commonly used functional assessment measures in Huntington disease. DESIGN: 486 participants with premanifest or manifest Huntington disease were examined. Total Functional Capacity, Functional Assessment, and Independence Scale assessments from the Unified Huntington Disease Rating scale were completed by clinicians; a self-report version was also completed by individuals with Huntington disease. Cronbach\u27s α was used to examine internal consistency, one-way analysis of variance was used to examine group differences, and paired t tests, kappa agreement coefficients, and intra-class correlations were calculated to determine agreement between raters. RESULTS: Internal consistency for self-reported ratings of functional capacity and ability were good. There were significant differences between those with premanifest, early-, and late-stage disease; those with later-stage disease reported less ability and independence than the other clinical groups. Although self-report ratings were not a perfect match with associated clinician-rated measures, differences were small. Cutoffs for achieving specified levels of agreement are provided. CONCLUSIONS: Depending on the acceptable margin of error in a study, self-reported administration of these functional assessments may be appropriate when clinician-related assessments are not feasible

Halogenated oxindole and indoles from the South African marine ascidian Distaplia skoogi:

The known 3,6-dibromoindole (1), 6-bromo-3-chloroindole (2) and 6-bromo-2-oxindole (3) were isolated from the marine ascidian (sea squirt) Distapia skoogi collected from Algoa Bay, South Africa. Standard spectroscopic techniques were used to elucidate the structures of 1-3. All three compounds were found to be moderately cytotoxic to metastatic MDA-MB-231 breast cancer cells

Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis

Liver disease is a major cause of mortality among HIV-infected persons. There is limited information about the extent to which HIV disease severity impacts liver disease progression

Homicide and geographic access to gun dealers in the United States

<p>Abstract</p> <p>Background</p> <p>Firearms are the most commonly used weapon to commit homicide in the U.S. Virtually all firearms enter the public marketplace through a federal firearms licensee (FFL): a store or individual licensed by the federal government to sell firearms. Whether FFLs contribute to gun-related homicide in areas where they are located, in which case FFLs may be a homicide risk factor that can be modified, is not known.</p> <p>Methods</p> <p>Annual county-level data (1993–1999) on gun homicide rates and rates of FFLs per capita were analyzed using negative binomial regression controlling for socio-demographic characteristics. Models were run to evaluate whether the relation between rates of FFLs and rates of gun homicide varied over the study period and across counties according to their level of urbanism (defined by four groupings, as below). Also, rates of FFLs were compared against FS/S – which is the proportion of suicides committed by firearm and is thought to be a good proxy for firearm availability in a region – to help evaluate how well the FFL variable is serving as a way to proxy firearm availability in each of the county types of interest.</p> <p>Results</p> <p>In major cities, gun homicide rates were higher where FFLs were more prevalent (rate ratio [RR] = 1.70, 95% CI 1.03–2.81). This association increased (p < 0.01) from 1993 (RR = 1.69) to 1999 (RR = 12.72), due likely to federal reforms that eliminated low-volume dealers, making FFL prevalence a more accurate exposure measure over time. No association was found in small towns. In other cities and in suburbs, gun homicide rates were significantly lower where FFLs were more prevalent, with associations that did not change over the years of the study period. FFL prevalence was correlated strongly (positively) with FS/S in major cities only, suggesting that the findings for how FFL prevalence relates to gun homicide may be valid for the findings pertaining to major cities but not to counties of other types.</p> <p>Conclusion</p> <p>Modification of FFLs through federal, state, and local regulation may be a feasible intervention to reduce gun homicide in major cities.</p

Adaptations of Avian Flu Virus Are a Cause for Concern

We are in the midst of a revolutionary period in the life sciences. Technological capabilities have dramatically expanded, we have a much improved understanding of the complex biology of selected microorganisms, and we have a much improved ability to manipulate microbial genomes. With this has come unprecedented potential for better control of infectious diseases and significant societal benefit. However, there is also a growing risk that the same science will be deliberately misused and that the consequences could be catastrophic. Efforts to describe or define life-sciences research of particular concern have focused on the possibility that knowledge or products derived from such research, or new technologies, could be directly misapplied with a sufficiently broad scope to affect national or global security. Research that might greatly enhance the harm caused by microbial pathogens has been of special concern (1–3). Until now, these efforts have suffered from a lack of specificity and a paucity of concrete examples of “dual use research of concern” (3). Dual use is defined as research that could be used for good or bad purposes. We are now confronted by a potent, real-world example

Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease

Objective: To determine the motor phenotype of LRRK2 G2019S mutation carriers. LRRK2 mutation carriers were previously reported to manifest the tremor dominant motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared with the postural instability and gait difficulty (PIGD) phenotype. Design: Cross-sectional observational study. Setting: Thirteen movement disorders centers. Participants: Nine hundred twenty-five early-onset Parkinson disease cases defined as age at onset younger than 51 years. Main Outcome Measures: LRRK2 mutation status and Parkinson disease motor phenotype: tremor dominant or PIGD. Demographic information, family history of Parkinson disease, and the Unified Parkinson's Disease Rating Scale score were collected on all participants. DNA samples were genotyped for LRRK2 mutations (G2019S, I2020T, R1441C, and Y1699C). Logistic regression was used to examine associations of G2019S mutation status with motor phenotype adjusting for disease duration, Ashkenazi Jewish ancestry, levodopa dose, and family history of Parkinson disease. Results: Thirty-four cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be Ashkenazi Jewish (55.9% vs 11.9%; P < .001) but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (P = .03) and were more likely to have a PIGD phenotype (92.3% vs 58.9%; P = .003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and Ashkenazi Jewish ancestry (odds ratio, 17.7; P < .001). Conclusion: Early-onset Parkinson disease G2019S LRRK2 carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course