Risk factors and medical resource utilization of respiratory syncytial virus, human metapneumovirus, and influenza-related hospitalizations in adults—a global study during the 2017–2019 epidemic seasons (hospitalized acute respiratory tract infection [HARTI] study)

Background: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza are respiratory pathogens leading to hospitalization in adults. Our understanding of the disease burden is limited to data from single-center or 1-season studies in elderly patients. The HARTI study allows comparison of risk factors for progression to severe disease and medical resources utilization (MRU) during and post-hospitalization in adults diagnosed with influenza, RSV, or hMPV. Methods: This was a prospective global study in adults hospitalized with acute respiratory tract infection (40 centers, 12 countries). Participants with influenza, RSV, or hMPV were enrolled in a substudy and followed for up to 3 months postdischarge. Results: Overall, 366 influenza, 238 RSV, and 100 hMPV-infected participants enrolled in the substudy. RSV participants were older and had greater frequency of risk factors and longer duration of symptoms before hospitalization than influenza participants. The RSV and hMPV groups received more bronchodilators, corticosteroids, and oxygen supplementation. No significant differences in intensive care unit admissions or complications were observed. Readmission occurred in 20%-33% of patients within 3 months postdischarge, with the highest rates for RSV and hMPV. In-hospital death occurred in 2.5% of RSV, 1.6% of influenza, and 2% of hMPV participants. In multivariate analyses, length of stay was independently associated with country, renal disease, and increased age; probability of receiving supplemental oxygen was associated with pathogen (hMPV \u3e RSV \u3e influenza), abnormal chest x-ray, and increased age. Conclusions: Although influenza is more frequent, the HARTI study demonstrates greater frequency of underlying risk factors and MRU for RSV and hMPV vs influenza in hospitalized adults, indicating a need for effective interventions

Microfluidics for the detection of minimal residual disease in acute myeloid leukemia patients using circulating leukemic cells selected from blood

Microfluidic assay for the selection of circulating leukemic cells from peripheral blood for the early detection of minimal residual disease in acute myeloid leukemia patients

2007 Annual progress report synopsis of the Center for Structures of Membrane Proteins

A synopsis of the 2007 annual progress report for the Center for Structures of Membrane Proteins, a specialized center of the Protein Structure Initiative

Telaprevir twice daily is noninferior to telaprevir every 8 hours for patients with chronic hepatitis C.

Background & Aims We performed an open-label, multicenter, phase 3 study of the safety and efficacy of twice-daily telaprevir in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1 infection, including those with cirrhosis. Methods Patients were randomly assigned to groups treated with telaprevir 1125 mg twice daily or 750 mg every 8 hours plus peginterferon alfa-2a and ribavirin for 12 weeks; patients were then treated with peginterferon alfa-2a and ribavirin alone for 12 weeks if their level of HCV RNA at week 4 was <25 IU/mL or for 36 weeks if their level was higher. The primary objective was to demonstrate noninferiority of telaprevir twice daily versus every 8 hours in producing a sustained virological response 12 weeks after the end of therapy (SVR12) (based on a -11% lower limit of the 95% lower confidence interval for the difference between groups). Results At baseline, of 740 patients, 85% had levels of HCV RNA ≥800,000 IU/mL, 28% had fibrosis (F3-F4), 14% had cirrhosis (F4), 57% were infected with HCV genotype 1a, and 71% had the non-CC IL28B genotype. Of patients who were treated with telaprevir twice daily, 74.3% achieved SVR12 compared with 72.8% of patients who were treated with telaprevir every 8 hours (difference in response, 1.5%; 95% confidence interval, -4.9% to 12.0%), so telaprevir twice daily is noninferior to telaprevir every 8 hours. All subgroups of patients who were treated with telaprevir twice daily versus those who were treated every 8 hours had similar rates of SVR12. The most frequent adverse events (AEs) in the telaprevir phase were fatigue (47%), pruritus (43%), anemia (42%), nausea (37%), rash (35%), and headache (26%); serious AEs were reported in 9% of patients. Rates of AEs and serious AEs were similar or slightly higher among patients treated with telaprevir every 8 hours. Conclusions Based on a phase 3 trial, telaprevir twice daily is noninferior to every 8 hours in producing SVR12, with similar levels of safety and tolerability. These results support use of telaprevir twice daily in patients with chronic HCV genotype 1 infection, including those with cirrhosis. ClinicalTrials.gov, Number: NCT0124176

Error-analysis and comparison to analytical models of numerical waveforms produced by the NRAR Collaboration

The Numerical-Relativity-Analytical-Relativity (NRAR) collaboration is a joint effort between members of the numerical relativity, analytical relativity and gravitational-wave data analysis communities. The goal of the NRAR collaboration is to produce numerical-relativity simulations of compact binaries and use them to develop accurate analytical templates for the LIGO/Virgo Collaboration to use in detecting gravitational-wave signals and extracting astrophysical information from them. We describe the results of the first stage of the NRAR project, which focused on producing an initial set of numerical waveforms from binary black holes with moderate mass ratios and spins, as well as one non-spinning binary configuration which has a mass ratio of 10. All of the numerical waveforms are analysed in a uniform and consistent manner, with numerical errors evaluated using an analysis code created by members of the NRAR collaboration. We compare previously-calibrated, non-precessing analytical waveforms, notably the effective-one-body (EOB) and phenomenological template families, to the newly-produced numerical waveforms. We find that when the binary's total mass is ~100-200 solar masses, current EOB and phenomenological models of spinning, non-precessing binary waveforms have overlaps above 99% (for advanced LIGO) with all of the non-precessing-binary numerical waveforms with mass ratios <= 4, when maximizing over binary parameters. This implies that the loss of event rate due to modelling error is below 3%. Moreover, the non-spinning EOB waveforms previously calibrated to five non-spinning waveforms with mass ratio smaller than 6 have overlaps above 99.7% with the numerical waveform with a mass ratio of 10, without even maximizing on the binary parameters.Comment: 51 pages, 10 figures; published versio

Testing General Relativity with Present and Future Astrophysical Observations

One century after its formulation, Einstein's general relativity has maderemarkable predictions and turned out to be compatible with all experimentaltests. Most of these tests probe the theory in the weak-field regime, and thereare theoretical and experimental reasons to believe that general relativityshould be modified when gravitational fields are strong and spacetime curvatureis large. The best astrophysical laboratories to probe strong-field gravity areblack holes and neutron stars, whether isolated or in binary systems. We reviewthe motivations to consider extensions of general relativity. We present a(necessarily incomplete) catalog of modified theories of gravity for whichstrong-field predictions have been computed and contrasted to Einstein'stheory, and we summarize our current understanding of the structure anddynamics of compact objects in these theories. We discuss current bounds onmodified gravity from binary pulsar and cosmological observations, and wehighlight the potential of future gravitational wave measurements to inform uson the behavior of gravity in the strong-field regime

Epidemiology of soil-transmitted helminths following sustained implementation of routine preventive chemotherapy: Demographics and baseline results of a cluster randomised trial in southern Malawi.

Malawi has successfully leveraged multiple delivery platforms to scale-up and sustain the implementation of preventive chemotherapy (PCT) for the control of morbidity caused by soil-transmitted helminths (STH). Sentinel monitoring demonstrates this strategy has been successful in reducing STH infection in school-age children, although our understanding of the contemporary epidemiological profile of STH across the broader community remains limited. As part of a multi-site trial evaluating the feasibility of interrupting STH transmission across three countries, this study aimed to describe the baseline demographics and the prevalence, intensity and associated risk factors of STH infection in Mangochi district, southern Malawi. Between October-December 2017, a community census was conducted across the catchment area of seven primary healthcare facilities, enumerating 131,074 individuals across 124 villages. A cross-sectional parasitological survey was then conducted between March-May 2018 in the censused area as a baseline for a cluster randomised trial. An age-stratified random sample of 6,102 individuals were assessed for helminthiasis by Kato-Katz and completed a detailed risk-factor questionnaire. The age-cluster weighted prevalence of any STH infection was 7.8% (95% C.I. 7.0%-8.6%) comprised predominantly of hookworm species and of entirely low-intensity infections. The presence and intensity of infection was significantly higher in men and in adults. Infection was negatively associated with risk factors that included increasing levels of relative household wealth, higher education levels of any adult household member, current school attendance, or recent deworming. In this setting of relatively high coverage of sanitation facilities, there was no association between hookworm and reported access to sanitation, handwashing facilities, or water facilities. These results describe a setting that has reduced the prevalence of STH to a very low level, and confirms many previously recognised risk-factors for infection. Expanding the delivery of anthelmintics to groups where STH infection persist could enable Malawi to move past the objective of elimination of morbidity, and towards the elimination of STH. Trial registration: NCT03014167

Continuum-based models and concepts for the transport of nanoparticles in saturated porous media: A state-of-the-science review

Environmental applications of nanoparticles (NP) increasingly result in widespread NP distribution within porous media where they are subject to various concurrent transport mechanisms including irreversible deposition, attachment/detachment (equilibrium or kinetic), agglomeration, physical straining, site-blocking, ripening, and size exclusion. Fundamental research in NP transport is typically conducted at small scale, and theoretical mechanistic modeling of particle transport in porous media faces challenges when considering the simultaneous effects of transport mechanisms. Continuum modeling approaches, in contrast, are scalable across various scales ranging from column experiments to aquifer. They have also been able to successfully describe the simultaneous occurrence of various transport mechanisms of NP in porous media such as blocking/straining or agglomeration/deposition/detachment. However, the diversity of model equations developed by different authors and the lack of effective approaches for their validation present obstacles to the successful robust application of these models for describing or predicting NP transport phenomena. This review aims to describe consistently all the important NP transport mechanisms along with their representative mathematical continuum models as found in the current scientific literature. Detailed characterizations of each transport phenomenon in regards to their manifestation in the column experiment outcomes, i.e., breakthrough curve (BTC) and residual concentration profile (RCP), are presented to facilitate future interpretations of BTCs and RCPs. The review highlights two NP transport mechanisms, agglomeration and size exclusion, which are potentially of great importance in controlling the fate and transport of NP in the subsurface media yet have been widely neglected in many existing modeling studies. A critical limitation of the continuum modeling approach is the number of parameters used upon application to larger scales and when a series of transport mechanisms are involved. We investigate the use of simplifying assumptions, such as the equilibrium assumption, in modeling the attachment/detachment mechanisms within a continuum modelling framework. While acknowledging criticisms about the use of this assumption for NP deposition on a mechanistic (process) basis, we found that its use as a description of dynamic deposition behavior in a continuum model yields broadly similar results to those arising from a kinetic model. Furthermore, we show that in two dimensional (2-D) continuum models the modeling efficiency based on the Akaike information criterion (AIC) is enhanced for equilibrium vs kinetic with no significant reduction in model performance. This is because fewer parameters are needed for the equilibrium model compared to the kinetic model. Two major transport regimes are identified in the transport of NP within porous media. The first regime is characterized by higher particle-surface attachment affinity than particle-particle attachment affinity, and operative transport mechanisms of physicochemical filtration, blocking, and physical retention. The second regime is characterized by the domination of particle-particle attachment tendency over particle-surface affinity. In this regime although physicochemical filtration as well as straining may still be operative, ripening is predominant together with agglomeration and further subsequent retention. In both regimes careful assessment of NP fate and transport is necessary since certain combinations of concurrent transport phenomena leading to large migration distances are possible in either case