169 research outputs found

    Feasibility of the modified sequential organ function assessment score in a resource-constrained setting: a prospective observational study.

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    BackgroundSub-Saharan Africa has a great burden of critical illness with limited health care resources. We evaluated the feasibility and utility of the modified Sequential Organ Function Assessment (mSOFA) score in assessing morbidity and mortality in the National Referral Hospital's intensive care unit (ICU) for one year.MethodsWe conducted a prospective, observational cohort study on patients above 12 years of age admitted to the ICU at Mulago Hospital (Kampala, Uganda). All SOFA scores were determined at admission and at 48 h. We modified the SOFA score by replacing the PaO2/FiO2 ratio with SPO2/FiO2. The primary outcome was ICU mortality.ResultsThis ICU cohort of 118 patients had a mean age of 37 years and an ICU mortality rate of 46.6%. Non-survivors had higher initial (7.7 SD 3.8 vs. 5.5 SD 3.3; p = 0.007), mean (8.1 SD 3.9 vs 4.7 SD 2.6; p < 0.001) and highest mSOFA scores (9.4 SD 4.2 vs. 5.8 SD 3.2; p < 0.001), with an increase of 1.0 (SD 3.1) mSOFA on average after 48 h when compared to survivors (p < 0.001). The area under the receiver operating characteristic curves for each mSOFA category was: initial-0.68, mean-0.76, highest-0.76 and delta mSOFA-0.74. Multivariate logistic regression analysis showed no significant association between mSOFA scores and mortality.ConclusionOur results confirm that calculation of the mSOFA score is feasible for an ICU population in a resource-limited country. More data are needed to test for an association between mSOFA and mortality

    NSF SSTEM MIRRORS Data 2018-2021

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    With five years of funding from the National Science Foundation\u27s Scholarships in Science, Technology, Engineering and Mathematics (S-STEM) program, John Carroll University (JCU) will provide scholarships to 32 students with demonstrated financial need and academic promise. The scholarships will be awarded to first-year and transfer students who are pursuing bachelor\u27s degrees in STEM in Biology, Chemistry, Mathematics, Computer Science and Physics. The Scholars in the program will receive academic support that includes a STEM-specific orientation, a summer bridge program, cohort advising, and curricula introducing scientific thinking and research.The project goals are to improve one-year retention and four-year graduation rates, and to train and graduate scholars who will meet local, regional, and national demands for a STEM-educated workforce. This project will provide evidence-based academic and student support services designed to support the transition and success of JCU transfer student cohorts. These services include a STEM living-learning community (LLC), peer-led team learning, career development, summer research fellowships, and travel to scientific meetings. This project will contribute to education research by investigating the role of reflection (i.e., conscientious evaluation of new knowledge or experiences) in the development of student-scientists, and the influence of STEM LLCs on student persistence and sense of well-being. The ongoing process of reflection is critical for academic success, social well-being, and vocational self-efficacy. However, the importance of reflection as a tool for success in STEM disciplines is unknown. This project will assess reflection as a tool to increase retention and performance in STEM experimentally, by monitoring performance indicators for S-STEM Scholars compared to the pool of S-STEM-eligible students who were not selected for a scholarship and therefore did not participate in the program\u27s reflection activities. Finally, this project will help provide S-STEM students the opportunity to be successful in high-demand STEM disciplines

    Investigating the Lymphatic System by Dual-Color Elemental Mass Spectrometry Imaging

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    Secondary lymphedema accompanied with strong restrictions in quality of life is still major side effects in cancer therapy. Therefore, dedicated diagnostic tools and further investigation of the lymphatic system are crucial to improve lymphedema therapy. In this pilot study, a method for quantitative analysis of the lymphatic system in a rat model by laser ablation (LA) with inductively coupled plasma mass spectrometry imaging (ICP-MSI) is presented. As a possible lymph marker, thulium(III)(1R,4R,7R,10R)-α,α′,α′′,α′′′-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (Tm-DOTMA) is introduced and compared to the clinically used magnetic resonance imaging contrast agent gadolinium(III)2,2′,2′′-(10-((2R,3S)-1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate (Gd-DO3A-butrol). Gadobutrol functioned as standard contrast media in MRI lymphangiography to detect lymphatic flow qualitatively. Thus, Tm-DOTMA was investigated as lymphatic marker to detect lymphatic flow quantitatively. Both contrast agents were successfully used to visualize the lymphatic flow in successive lymph nodes in LA-ICP-MS due to lower limits of detection compared to MRI. Furthermore, the distribution of contrast agents by multicolored imaging showed accumulation in specific areas (sectors) of the lymph nodes after application of contrast agents in different areas

    Fast Attitude Maneuvers for the Lunar Reconnaissance Orbiter

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    This paper describes a new operational capability for fast attitude maneuvering that is being developed for the Lunar Reconnaissance Orbiter (LRO). The LRO hosts seven scientific instruments. For some instruments, it is necessary to per-form large off-nadir slews to collect scientific data. The accessibility of off-nadir science targets has been limited by slew rates and/or occultation, thermal and power constraints along the standard slew path. The new fast maneuver (FastMan) algorithm employs a slew path that autonomously avoids constraint violations while simultaneously minimizing the slew time. The FastMan algo-rithm will open regions of observation that were not previously feasible and improve the overall science return for LRO's extended mission. The design of an example fast maneuver for LRO's Lunar Orbiter Laser Altimeter that reduc-es the slew time by nearly 40% is presented. Pre-flight, ground-test, end-to-end tests are also presented to demonstrate the readiness of FastMan. This pioneer-ing work is extensible and has potential to improve the science data collection return of other NASA spacecraft, especially those observatories in extended mission phases where new applications are proposed to expand their utility

    Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial

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    BACKGROUND Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes. AIMS To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia. METHOD A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0-13 weeks and 0-39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods. RESULTS There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were ÂŁ1510 and ÂŁ1522 less for the mirtazapine group compared with placebo and sertraline respectively. CONCLUSIONS In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers

    Combined Prospective Seroconversion and PCR Data of Selected Cohorts Indicate a High Rate of Subclinical SARS-CoV-2 Infections—an Open Observational Study in Lower Saxony, Germany

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    Despite lockdown measures, intense symptom-based PCR, and antigen testing, the SARS-CoV-2 pandemic spread further. In this open observational study conducted in Lower Saxony, Germany, voluntary SARS-CoV-2 PCR tests were performed from April 2020 until June 2021, supported by serum antibody testing to prove whether PCR testing in subjects with none or few symptoms of COVID-19 is a suitable tool to manage the pandemic. In different mobile stations, 4,817 subjects from three different working fields participated in the PCR testing. Serum antibody screening using the SARS-CoV-2 ViraChip IgG (Viramed, Germany) and the Elecsys Anti-SARS-CoV-2 assay (Roche, Germany) was performed alongside virus neutralization testing. Subjects were questioned regarding comorbidities and COVID-19 symptoms. Fifty-one subjects with acute SARS-CoV-2 infection were detected of which 31 subjects did not show any symptoms possibly characteristic for COVID-19. An additional 37 subjects reported a previous SARS-CoV-2 infection (total prevalence 1.82%). Seroconversion was discovered in 58 subjects with known SARS-CoV-2 infection and in 58 subjects that never had a positive PCR test. The latter had a significantly lower Charlson Comorbidity Index, and one third of them were asymptomatic. In 50% of all seroconverted subjects, neutralizing serum antibodies (NAbs) were detectable in parallel to N/S1 (n = 16) or N/S1/S2 antigen specific antibodies (n = 40) against SARS-CoV-2. NAb titers decreased within 100 days after PCR-confirmed SARS-CoV-2 acute infection by at least 2.5-fold. A relatively high rate of subclinical SARS-CoV-2 infections may contribute to the spread of SARS-CoV-2, suggesting that in addition to other intervention strategies, systematic screening of asymptomatic persons by PCR testing may significantly enable better pandemic control

    IL-12p70–producing patient DC vaccine elicits Tc1-polarized immunity

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    Background. Systemic administration of IL-12p70 has demonstrated clinical activity in cancer patients, but dose-limiting toxicities have hindered its incorporation in vaccine formulations. Here, we report on the immunological and clinical outcomes upon vaccination with CD40L/IFN-γ–matured, IL-12p70–producing DCs. Methods. 7 HLA-A*0201(+) newly diagnosed stage IV melanoma patients were immunized against the gp100 melanoma antigen using autologous peptide-pulsed, CD40L/IFN-γ–matured DCs. PBMCs were taken weekly for immune monitoring by tetramer analysis and functional assays. CT imaging was performed at baseline, week 9, and week 18 for clinical assessment using RECIST. Results. 6 of 7 treated patients developed sustained T cell immunity to all 3 melanoma gp100 antigen–derived peptides. 3 of the 6 immunological responders developed confirmed clinical responses (1 complete remission >4 years, 2 partial response). Importantly, DC vaccine–derived IL-12p70 levels positively correlated with time to progression (P = 0.019, log-rank), as did T-cytotoxic 1 (Tc1) immunity, as assessed by IFN-γ/IL-13 and IFN-γ/IL-5 ratios (P = 0.035 and P = 0.030, respectively, log-rank). In contrast, a pathway-specific defect in IL-12p35 transcription was identified upon CD40L/IFN-γ activation in clinical nonresponder patient DCs, and gp100-specific T cells from these patients displayed a Tc2 phenotype. Incorporation of TLR3 and TLR8 agonists into the CD40L/IFN-γ activation protocol corrected the IL-12p70 production defect in DCs derived from clinical nonresponder patients. Conclusion. These findings underscore the essential role of IL-12p70 in the development of therapeutic type 1 antigen–specific CD8(+) T cell immunity in humans with cancer. Trial registration. Clinicaltrials.gov NCT00683670. Funding. Barnes-Jewish Hospital Foundation, Siteman Cancer Frontier Fund, Washington University/JNJ Translational Medicine Award, and NCI (P30 CA91842)

    Mobile SARS‑CoV‑2 screening facilities for rapid deployment and university-based diagnostic laboratory

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    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a public crisis. Many medical and public institutions and businesses went into isolation in response to the pandemic. Because SARS-CoV-2 can spread irrespective of a patient's course of disease, these institutions’ continued operation or reopening based on the assessment and control of virus spread can be supported by targeted population screening. For this purpose, virus testing in the form of polymerase chain reaction (PCR) analysis and antibody detection in blood can be central. Mobile SARS-CoV-2 screening facilities with a built-in biosafety level (BSL)-2 laboratory were set up to allow the testing offer to be brought close to the subject group's workplace. University staff members, their expertise, and already available equipment were used to implement and operate the screening facilities and a certified diagnostic laboratory. This operation also included specimen collection, transport, PCR and antibody analysis, and informing subjects as well as public health departments. Screening facilities were established at different locations such as educational institutions, nursing homes, and companies providing critical supply chains for health care. Less than 4 weeks after the first imposed lockdown in Germany, a first mobile testing station was established featuring a build-in laboratory with two similar stations commencing operation until June 2020. During the 15-month project period, approximately 33,000 PCR tests and close to 7000 antibody detection tests were collected and analyzed. The presented approach describes the required procedures that enabled the screening facilities and laboratories to collect and process several hundred specimens each day under difficult conditions. This report can assist others in establishing similar setups for pandemic scenarios
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