Diffusion of network innovation : implications for adoption of internet services

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science; and, Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1998.Includes bibliographical references (p. 51-53).by Mark S. Shuster.B.S.M.Eng

Aqueous alteration processes in Jezero crater, Mars—implications for organic geochemistry

The Perseverance rover landed in Jezero crater, Mars, in February 2021. We used the Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) instrument to perform deep-ultraviolet Raman and fluorescence spectroscopy of three rocks within the crater. We identify evidence for two distinct ancient aqueous environments at different times. Reactions with liquid water formed carbonates in an olivine-rich igneous rock. A sulfate-perchlorate mixture is present in the rocks, which probably formed by later modifications of the rocks by brine. Fluorescence signatures consistent with aromatic organic compounds occur throughout these rocks and are preserved in minerals related to both aqueous environments

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir With or Without Ribavirin in Patients With Kidney Disease

Introduction: Patients with hepatitis C virus (HCV) infection and chronic kidney disease (CKD) are a high-priority population for treatment. Methods: We performed a post hoc pooled efficacy and safety analysis that included HCV genotype 1–infected patients with compensated liver disease and CKD stages 1 to 3 who received the all-oral 3–direct-acting antiviral regimen of ombitasvir, paritaprevir, ritonavir, and dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) in 11 phase 3 clinical trials. Sustained virologic response rates at posttreatment week 12 (SVR12) and treatment-related adverse events (AEs), serious AEs, and renal-associated AEs are reported. Mean changes from baseline in serum creatinine and estimated glomerular filtration rate (eGFR) were calculated to assess changes in renal function. Factors associated with improved eGFR were assessed by stepwise logistic regression analysis of data from 7 trials in which baseline urinalysis was collected. Results: SVR12 rates in patients with stage 1, 2, and 3 CKD were 97% (439/453), 98% (536/547), and 97% (32/33), respectively, with OBV/PTV/r + DSV; and, 96% (1172/1221), 96% (1208/1254), and 93% (55/59), respectively, with OBV/PTV/r + DSV + RBV. Overall rates of serious AEs and renal AEs were 3% (95/3567) and 2% (56/3567), respectively. Factors associated with an eGFR increase of ≥10 ml/min per 1.73 m2 were baseline proteinuria, body mass index, nonblack race, and history of diabetes. Conclusion: OBV/PTV/r + DSV ± RBV achieved high SVR rates and was generally well tolerated irrespective of CKD stage. Keywords: chronic hepatitis C, chronic kidney disease, direct-acting antiviral, hepatitis C viru

A Patient-Centered Emergency Department Management Strategy for Sickle-Cell Disease Super-Utilizers

Introduction:A subpopulation of sickle-cell disease patients, termed super-utilizers, present frequently to emergency departments (EDs) for vaso-occlusive events and may consume disproportionate resources without broader health benefit. To address the health care needs of this vulnerable patient population, we piloted a multidisciplinary intervention seeking to create and use individualized patient care plans that to alter utilization through coordinated care. Our goals were to assess feasibility primarily, and to assess resource use secondarily.Methods: We evaluated the effects of a single-site interventional study targeted at a population of adult sickle-cell disease super-utilizers using a pre- and post-implementation design. The pre-intervention period was 06/01/13 to 12/31/13 (7 months) and the post-intervention period was 01/01/14 to 02/28/15 (14 months). Our approach included: patient-specific best practice advisories (BPA); an ED management protocol (figure 1); formation of a "medical home" for these patients.Results: For 10 subjects targeted initially we developed and implemented coordinated care plans; after deployment, we observed a tendency toward reduction in ED and inpatient utilization across all measured indices. Between the annualized pre- and post-implementation periods: ED visits decreased by 16.5 visits/pt-yr (95% CI, -1.32 to 34.2); ED length of state (LOS) decreased by 115.3 hours/pt-yr (95% CI, -82.9 to 313.5); in-patient admissions decreased by 4.20 admissions/pt-yr (95% CI, -1.73 to 10.1); in-patient LOS decreased by 35.8 hours/pt-yr (95% CI, -74.9 to 146.7); and visits where the patient left before treatment was reduced by an annualized total of 13.7 visits. We observed no patient mortality in our 10 subjects and no patient required admission to the ICU care 72 hours following discharge. Conclusion: This effort suggests that a targeted approach is both feasible and potentially effective, laying a foundation for broader study

За кадры. 1988. № 21 (2747)

7 апреля - Всемирный день здоровьяПрошел субботник / М. БачевВ парткоме институтаИ до каких же пор?!Столовая начинается с...? / О. ИвановО гуманитаризации технического образования / М. КатхановЗаботы профбюро / А. КенжебаевБлагородная цельВ зоне особого внимания / Е. ЭйхгорнПраво на награду / Н. ОреховаФраза? Нет, реальность / Т. Полякова, Н. Павлова...Вас слушают / Н. КуцанКто поможет "Мечте"?В залах НТБФавориты из прошлого / А. ТаенковПриглашает "Встреча"С любовью к людям / И. Суворин

Highly effective SNP-based association mapping and management of recessive defects in livestock.

The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings