Mark D Roberts - Academia.edu (original) (raw)

Talks by Mark D Roberts

Papers by Mark D Roberts

The optimal threshold for initiating HIV treatment is unclear. To compare different thresholds fo... more The optimal threshold for initiating HIV treatment is unclear. To compare different thresholds for initiating HIV treatment. A validated computer simulation was used to weigh important harms from earlier initiation of antiretroviral therapy (toxicity, side effects, and resistance accumulation) against important benefits (decreased HIV-related mortality). Veterans Aging Cohort Study (5742 HIV-infected patients and 11 484 matched uninfected controls) and published reports. Individuals with newly diagnosed chronic HIV infection and varying viral loads (10,000, 30,000, 100,000, and 300,000 copies/mL) and ages (30, 40, and 50 years). Unlimited. Societal. Alternative thresholds for initiating antiretroviral therapy (CD4 counts of 200, 350, and 500 cells/mm3). Life-years and quality-adjusted life-years (QALYs). Although the simulation was biased against earlier treatment initiation because it used an upper-bound assumption for therapy-related toxicity, earlier treatment increased life expectancy and QALYs at age 30 years regardless of viral load (life expectancies with CD4 initiation thresholds of 500, 350, and 200 cells/mm3 were 18.2 years, 17.6 years, and 17.2 years, respectively, for a viral load of 10,000 copies/mL and 17.3 years, 15.9 years, and 14.5 years, respectively, for a viral load of 300,000 copies/mL), and increased life expectancies at age 40 years if viral loads were greater than 30 000 copies/mL (life expectancies were 12.5 years, 12.0 years, and 11.4 years, respectively, for a viral load of 300,000 copies/mL). Findings favoring early treatment were generally robust. Results favoring later treatment may not be valid. The findings may not be generalizable to women. This simulation suggests that earlier initiation of combination antiretroviral therapy is often favored compared with current recommendations.

Page 1. R&D and productivity: Estimating endogenous productivity∗ Ulrich Doraszelski† Harvard... more Page 1. R&D and productivity: Estimating endogenous productivity∗ Ulrich Doraszelski† Harvard University and CEPR Jordi Jaumandreu‡ ... Sample selection. A potential problem in the estimation of production functions is sam-ple selection. ...

Differential cross sections and analyzing powers have been obtained for the scattering of neutron... more Differential cross sections and analyzing powers have been obtained for the scattering of neutrons from the ground and first excited states of ^ {208}Pb. These new measurements include differential cross sections for elastic and inelastic neutron scattering at 8.0 MeV, and analyzing powers for elastic and inelastic neutron scattering at 6.0, 7.0, 8.0, 9.0, and 10.0 MeV. These data complement earlier work performed at Triangle Universities Nuclear Laboratory (TUNL) for elastic scattering of neutrons from ^{208 }Pb at 10.0, 14.0, and 17.0 MeV. All data were obtained using the TUNL pulsed beam facility and time -of-flight spectrometer. The data have been corrected for the effects of finite geometry, flux attenuation, and multiple scattering. The present elastic scattering data have been combined with the previously measured TUNL data and data measured elsewhere in order to obtain a detailed and high accuracy data set for neutron elastic scattering from ^{208}Pb over the 4.0 to 40.0 MeV energy range. This comprehensive data set has been described using the spherical optical model in which constant geometry fits, energy-dependent geometry fits, and fits incorporating the dispersion relation were performed. Although the overall description of the elastic n+^ {208}Pb scattering data was reasonably good using the various optical potentials, small systematic discrepancies remained at the backward angles of both the cross section and analyzing power data, and no optical model solution based on conventional Woods-Saxon form factors was found which could describe all of the details seen in the scattering data. To relax the constraint of having a Woods-Saxon form factor, the real central part of the optical model potential was modified using a Fourier-Bessel expansion of the real central potential. Individual fits at 6.0, 7.0, 8.0, 9.0, and 10.0 MeV, and fits to the combined 6.0 to 10.0 MeV data set were obtained using a Fourier -Bessel expansion of the real central potential and compared to fits using a conventional Woods-Saxon form factor.

American Journal of Health System Pharmacy Ajhp Official Journal of the American Society of Health System Pharmacists, May 1, 2003

The development of a multidisciplinary inpatient medication education program is described. A mul... more The development of a multidisciplinary inpatient medication education program is described. A multidisciplinary group designed and implemented a medication education program with defined roles for both nurses and pharmacists. Nurses provided medication education to patients during each medication administration using specially designed assessment and teaching tools. The nursing staff submitted requests for pharmacist consultations for patients with complex medication regimens, who were admitted because of a drug-related problem or who required additional teaching as determined through the medication education assessment form. A complex medication regimen was defined as the administration of oral medication more than five different times per day, the start of at least 5 new medications that would be continued at discharge, or the prescribing of at least 10 medications to be taken daily that would be continued at discharge. Pharmacists provided education for 19% of admitted patients during a six-month period. As a result of pharmacists&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; interactions with prescribers and nurses, the number of medications was reduced in 12% of these patients, and the number of medication administrations each day was reduced in 19% of patients. In addition, for 33% of patients, pharmacists contacted the prescriber to make recommendations beyond the scope of the medication education program that optimized and simplified the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s drug regimen. The development of a structured medication education program allowed patients to receive medication education throughout their hospitalization from both nurses and pharmacists. Pharmacists provided education for patients at highest risk for noncompliance or poor outcomes. Full implementation of a medication education program involving staff pharmacists is planned.

Applied and Environmental Microbiology, Apr 1, 1999

Utilization of ferrioxamines as sole sources of iron distinguishes Salmonella enterica serotypes ... more Utilization of ferrioxamines as sole sources of iron distinguishes Salmonella enterica serotypes Typhimurium and Enteritidis from a number of related species, including Escherichia coli. Ferrioxamine supplements have therefore been used in preenrichment and selection media to increase the bacterial growth rate while selectivity is maintained. We characterized the determinants involved in utilization of ferrioxamines B, E, and G by S. enterica serotype Typhimurium by performing siderophore cross-feeding bioassays. Transport of all three ferric siderophores across the outer membrane was dependent on the FoxA receptor encoded by the Furrepressible foxA gene. However, only the transport of ferrioxamine G was dependent on the energy-transducing protein TonB, since growth stimulation of a tonB strain by ferrioxamines B and E was observed, albeit at lower efficiencies than in the parental strain. Transport across the inner membrane was dependent on the periplasmic binding protein-dependent ABC transporter complex comprising FhuBCD, as has been reported for other hydroxamate siderophores of enteric bacteria. The distribution of the foxA gene in the genus Salmonella, as indicated by DNA hybridization studies and correlated with the ability to utilize ferrioxamine E, was restricted to subspecies I, II, and IIIb, and this gene was absent from subspecies IIIa, IV, VI, and VII (formerly subspecies IV) and Salmonella bongori (formerly subspecies V). S. enterica serotype Typhimurium mutants with either a transposon insertion or a defined nonpolar frameshift (؉2) mutation in the foxA gene were not able to utilize any of the three ferrioxamines tested. A strain carrying the nonpolar foxA mutation exhibited a significantly reduced ability to colonize rabbit ileal loops compared to the foxA ؉ parent. In addition, a foxA mutant was markedly attenuated in mice inoculated by either the intragastric or intravenous route. Mice inoculated with the foxA mutant were protected against subsequent challenge by the foxA ؉ parent strain.

Draft Program Plan For Tns the Next Step After the Tokamak Fusion Test Reactor Part 1 Summary, Oct 1, 1977

A draft program plan for TNS was prepared which consists of two basic parts-an R and D Needs Asse... more A draft program plan for TNS was prepared which consists of two basic parts-an R and D Needs Assessment and a Project Plan with schedules and necessary implementation steps. In this effort, questions concerning (1) the present basis for the TNS program, (2) the principal gaps in the supporting program, and (3) the necessary actions to be taken to implement the TNS program were examined. The study supported the thesis that the physics and technology bases do exist from which to start the TNS design as a central fusion program goal. Specific recommendations are made to emphasize those physics, technology, and engineering areas in which there are program gaps. In the project engineering study, basic schedule with close support from the R and D program is developed from which recommendations on administrative actions and areas for further elucidation are made. Presented in summary form are the findings of the study, the development of the principal theses, and the recommendation to ERDA-DMFE.

Journal of the American College of Cardiology, Jul 31, 1988

MARK ROBERTS, MD, RICHARD W. NESTO, MD. FACC 16. ~rws,y JM. McKny RG. Helkr GV. Royal HD. Air AV.... more MARK ROBERTS, MD, RICHARD W. NESTO, MD. FACC 16. ~rws,y JM. McKny RG. Helkr GV. Royal HD. Air AV. Grossman W. Simukuneous assessmen, of IeR venbiculur systolic and diasmbc dysfuncliun during pacing-induced ischemid. Circulation 1985:71:8@-X0. 47. R&ID LA. Wiikemeyer WJ. YoungJB. er al. Len vermiculardianolic performance rd rcr, and during exercise in patienls wi,h eoronay anery diwaac. Circutrliun 198l:bi: 12?&37. 48 Abenawli 7. Rub!er S. Fisher "1. Axclmd H. %ckemn KP. E~crcm tacing wlh mycardial scindgaphy in arymplnmalic diabolic males. Circulation ,%,:b3:5MA

Journal of Head Trauma Rehabilitation, 2006

Objectives: This study evaluated the relative efficacy of a community rehabilitation service and ... more Objectives: This study evaluated the relative efficacy of a community rehabilitation service and a more traditional outpatient service for carers of people with an acquired brain injury. Methods: Seventeen carers who had received a community intervention were retrospectively compared with 24 carers who had received an outpatient service. Dependent variables were level of met family need, a measure of family dysfunction, carer psychopathology, and carer emotional acceptance. Results: The community sample fared significantly better on all measures except carer psychopathology. Conclusions: These results suggest that community-based services have efficacy for the carer and family. There is a clear need for large clinical trials using standardized instruments to establish what models of service delivery benefit carers.

Infection and Immunity, Apr 1, 1999

In Escherichia coli, extracytoplasmic stress is partially controlled by the alternative sigma fac... more In Escherichia coli, extracytoplasmic stress is partially controlled by the alternative sigma factor, RpoE ( E ). In response to environmental stress or alteration in the protein content of the cell envelope, E upregulates the expression of a number of genes, including htrA. It has been shown that htrA is required for intramacrophage survival and virulence in Salmonella typhimurium. To investigate whether E -regulated genes other than htrA are involved in salmonella virulence, we inactivated the rpoE gene of S. typhimurium SL1344 by allelic exchange and compared the phenotype of the mutant (GVB311) in vitro and in vivo with its parent and an isogenic htrA mutant (BRD915). Unlike E. coli, E is not required for the growth and survival of S. typhimurium at high temperatures. However, GVB311 did display a defect in its ability to utilize carbon sources other than glucose. GVB311 was more sensitive to hydrogen peroxide, superoxide, and antimicrobial peptides than SL1344 and BRD915. Although able to invade both macrophage and epithelial cell lines normally, the rpoE mutant was defective in its ability to survive and proliferate in both cell lines. The effect of the rpoE mutation on the intracellular behavior of S. typhimurium was greater than that of the htrA mutation. Both GVB311 and BRD915 were highly attenuated in mice. Neither strain was able to kill mice via the oral route, and the 50% lethal dose (LD 50 ) for both strains via the intravenous (i.v.) route was very high. The i.v. LD 50 s for SL1344, BRD915, and GVB311 were <10, 5.5 ؋ 10 5 , and 1.24 ؋ 10 7 CFU, respectively. Growth in murine tissues after oral and i.v. inoculation was impaired for both the htrA and rpoE mutant, with the latter mutant being more severely affected. Neither mutant was able to translocate successfully from the Peyer's patches to other organs after oral infection or to proliferate in the liver and spleen after i.v. inoculation. However, the htrA mutant efficiently colonized the livers and spleens of mice infected i.v., but the rpoE mutant did not. Previous studies have shown that salmonella htrA mutants are excellent live vaccines. In contrast, oral immunization of mice with GVB311 was unable to protect any of the mice from oral challenge with SL1344. Furthermore, i.v. immunization with a large dose (ϳ10 6 CFU) of GVB311 protected less than half of the orally challenged mice. Thus, our results indicate that genes in the E regulon other than htrA play a critical role in the virulence and immunogenicity of S. typhimurium.

Med Decis Making, 2003

Highly active antiretroviral therapy (HAART) prolongs short-term survival in patients with HIV/AI... more Highly active antiretroviral therapy (HAART) prolongs short-term survival in patients with HIV/AIDS. HAART has only been available since 1996; thus, no long-term survival data are available. Computer simulation models extrapolating short-term survival data can provide estimates of long-term survival. These survival estimates may assist patients and clinicians in HAART treatment planning. The authors construct a computer simulation model based on observational data to estimate long-term survival in a cohort of HIV/AIDS patients undergoing treatment with HAART. The authors use data from the Collaboration in HIV Outcomes Research-US (CHORUS) observational cohort (N = 4791), the published literature, and US Life Tables to specify a computer simulation model of expected survival accounting for baseline CD4 cell count, progressive HAART treatment failure, progressive risk of HAART on treatment mortality, and age-associated mortality. Time to treatment failure for each of three rounds of HAART and risk of mortality on-treatment were estimated using parametric survival models with censoring of follow-up fit to CHORUS data. Off-treatment survival after HAART failure was estimated from the pre-HAART literature. Age-associated mortality was taken from US Life Tables. Median projected survivals stratified by baseline CD4 cell count subgroups were CD4 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 200 cells/mm3, 15.4 years; CD4 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 200 cells/mm3, 8.5 years; and CD4 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 50 cells/mm3, 5.5 years. These values are 4 to 6 years longer than pre-HAART cohorts. The sensitivity analyses showed that the model survival predictions were most sensitive to the treatment failure rate, the on-treatment mortality rate, and the number of treatment rounds. Computer simulation modeling of long-term survival of patients with HIV/AIDS on HAART--accounting for differential treatment failure and death rates stratified by CD4 cell count and age-associated mortality--suggests a relatively consistent 4- to 6-year survival benefit over pre-HAART therapies.

Preventing Chronic Disease, Sep 1, 2010

INTRODUCTION: We assessed the cost-effectiveness of a community-based, modified Diabetes Preventi... more INTRODUCTION: We assessed the cost-effectiveness of a community-based, modified Diabetes Prevention Program (DPP) designed to reduce risk factors for type 2 diabetes and cardiovascular disease.METHODS: We developed a Markov decision model to compare costs and effectiveness of a modified DPP intervention with usual care during a 3-year period. Input parameters included costs and outcomes from 2 projects that implemented a community-based modified DPP for participants with metabolic syndrome, and from other sources. The model discounted future costs and benefits by 3% annually.RESULTS: At 12 months, usual care reduced relative risk of metabolic syndrome by 12.1%. A modified DPP intervention reduced relative risk by 16.2% and yielded life expectancy gains of 0.01 quality-adjusted life-years (3.67 days) at an incremental cost of 34.50(34.50 (34.50(3,420 per quality-adjusted life-year gained). In 1-way sensitivity analyses, results were sensitive to probabilities that risk factors would be reduced with or without a modified DPP and that patients would enroll in an intervention, undergo testing, and acquire diabetes with or without an intervention if they were risk-factor-positive. Results were also sensitive to utilities for risk-factor-positive patients. In probabilistic sensitivity analysis, the intervention cost less than $20,000 per quality-adjusted life-year gained in approximately 78% of model iterations.CONCLUSION: We consider the modified DPP delivered in community and primary care settings a sound investment.