Virtual Clinical Trials: One Step Forward, Two Steps Back

Virtual clinical trials have entered the medical research landscape. Today’s clinical trials recruit subjects online, obtain informed consent online, send treatments such as medications or devices to the subjects’ homes, and require subjects to record their responses online. Virtual clinical trials could be a way to democratize clinical research and circumvent geographical limitations by allowing access to clinical research for people who live far from traditional medical research centers. But virtual clinical trials also depart dramatically from traditional medical research studies in ways that can harm individuals and the public at large. This article addresses the issues presented by virtual clinical trials with regard to: (1) recruitment methods; (2) informed consent; (3) confidentiality; (4) potential risks to the subjects; and (5) the safety and efficacy of treatments that are approved

IRAC Observations of Taurus Pre-Main Sequence Stars

We present infrared photometry obtained with the IRAC camera on the Spitzer Space Telescope of a sample of 82 pre-main sequence stars and brown dwarfs in the Taurus star-forming region. We find a clear separation in some IRAC color-color diagrams between objects with and without disks. A few ``transition'' objects are noted, which correspond to systems in which the inner disk has been evacuated of small dust. Separating pure disk systems from objects with remnant protostellar envelopes is more difficult at IRAC wavelengths, especially for objects with infall at low rates and large angular momenta. Our results generally confirm the IRAC color classification scheme used in previous papers by Allen et al. and Megeath et al. to distinguish between protostars, T Tauri stars with disks, and young stars without (inner) disks. The observed IRAC colors are in good agreement with recent improved disk models, and in general accord with models for protostellar envelopes derived from analyzing a larger wavelength region. We also comment on a few Taurus objects of special interest. Our results should be useful for interpreting IRAC results in other, less well-studied star-forming regions.Comment: 29 pages 10 figures, to appear in Ap

Fusariosis de la espiga de trigo. Comportamiento de cultivares comerciales de trigo pan. Campaña 2019/20

El objetivo del presente informe es presentar los resultados de la evaluación de la resistencia a la FE de tipo II de algunos de los cultivares comerciales de trigo más difundidos a nivel nacional llevada adelante durante la campaña 2019/2020. Se espera que el conocimiento del comportamiento de estos materiales facilite la elección de cultivares en la decisión de siembra. A fin de uniformar las condiciones medioambientales a las que los materiales se expusieron, los cultivares fueron inoculados en el momento de plena antesis.EEA BalcarceFil: Franco, María Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Malbrán, Ismael. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina.Fil: Lori, Gladys. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina.Fil: Cendoya, María Gabriela. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina.Fil: Pontaroli, Ana Clara. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina

Piloting a Nationally Disseminated, Interactive Human Subjects Protection Program for Community Partners: Unexpected Lessons Learned from the Field

Funders, institutions, and research organizations are increasingly recognizing the need for human subjects protections training programs for those engaged in academic research. Current programs tend to be online and directed toward an audience of academic researchers. Research teams now include many nonacademic members, such as community partners, who are less likely to respond to either the method or the content of current online trainings. A team at the CTSA‐supported Michigan Institute for Clinical and Health Research at the University of Michigan developed a pilot human subjects protection training program for community partners that is both locally implemented and adaptable to local contexts, yet nationally consistent and deliverable from a central administrative source. Here, the developers of the program and the collaborators who participated in the pilot across the United States describe 10 important lessons learned that align with four major themes: The distribution of the program, the implementation of the program, the involvement of community engagement in the program, and finally lessons regarding the content of the program. These lessons are relevant to anyone who anticipates developing or improving a training program that is developed in a central location and intended for local implementation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106833/1/cts12155.pd

The Spitzer c2d Survey of Large, Nearby, Interstellar Clouds. IV. Lupus Observed with MIPS

We present maps of 7.78 square degrees of the Lupus molecular cloud complex at 24, 70, and $160\:\mu$m. They were made with the Spitzer Space Telescope's Multiband Imaging Photometer for Spitzer (MIPS) instrument as part of the Spitzer Legacy Program, ``From Molecular Cores to Planet-Forming Disks'' (c2d). The maps cover three separate regions in Lupus, denoted I, III, and IV. We discuss the c2d pipeline and how our data processing differs from it. We compare source counts in the three regions with two other data sets and predicted star counts from the Wainscoat model. This comparison shows the contribution from background galaxies in Lupus I. We also create two color magnitude diagrams using the 2MASS and MIPS data. From these results, we can identify background galaxies and distinguish them from probable young stellar objects. The sources in our catalogs are classified based on their spectral energy distribution (SED) from 2MASS and Spitzer wavelengths to create a sample of young stellar object candidates. From 2MASS data, we create extinction maps for each region and note a strong corresponence between the extinction and the $160\:\mu$m emission. The masses we derived in each Lupus cloud from our extinction maps are compared to masses estimated from $^{13}$CO and C$^{18}$O and found to be similar to our extinction masses in some regions, but significantly different in others. Finally, based on our color-magnitude diagrams, we selected 12 of our reddest candidate young stellar objects for individual discussion. Five of the 12 appear to be newly-discovered YSOs.Comment: 15 pages, 17 figures, uses emulateapj.cls. Accepted for publication in ApJ. A version with high-quality figures can be found at http://peggysue.as.utexas.edu/SIRTF

Natriuretic peptides and integrated risk assessment for cardiovascular disease. an individual-participant-data meta-analysis

BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention

Stillbirths: ending preventable deaths by 2030

Efforts to achieve the new worldwide goals for maternal and child survival will also prevent stillbirth and improve health and developmental outcomes. However, the number of annual stillbirths remains unchanged since 2011 and is unacceptably high: an estimated 2·6 million in 2015. Failure to consistently include global targets or indicators for stillbirth in post-2015 initiatives shows that stillbirths are hidden in the worldwide agenda. This Series paper summarises findings from previous papers in this Series, presents new analyses, and proposes specific criteria for successful integration of stillbirths into post-2015 initiatives for women’s and children’s health. Five priority areas to change the stillbirth trend include intentional leadership; increased voice, especially of women; implementation of integrated interventions with commensurate investment; indicators to measure effect of interventions and especially to monitor progress; and investigation into crucial knowledge gaps. The post-2015 agenda represents opportunities for all stakeholders to act together to end all preventable deaths, including stillbirths

Single DermaVir Immunization: Dose-Dependent Expansion of Precursor/Memory T Cells against All HIV Antigens in HIV-1 Infected Individuals

BACKGROUND: The GIHU004 study was designed to evaluate the safety and immunogenicity of three doses of DermaVir immunization in HIV-infected subjects on fully suppressive combination antiretroviral therapy (cART). METHODOLOGY/PRINCIPAL FINDINGS: This first-in-human dose escalation study was conducted with three topical DermaVir doses targeted to epidermal Langerhans cells to express fifteen HIV antigens in draining lymph nodes: 0.1 mg DNA targeted to two, 0.4 mg and 0.8 mg DNA targeted to four lymph nodes. Particularly, in the medium dose cohort 0.1 mg DNA was targeted per draining lymph node via ∼8 million Langerhans cells located in 80 cm(2) epidermis area. The 28-days study with 48-week safety follow-up evaluated HIV-specific T cell responses against Gag p17, Gag p24 and Gag p15, Tat and Rev antigens. DermaVir-associated side effects were mild, transient and not dose-dependent. Boosting of HIV-specific effector CD4(+) and CD8(+) T cells expressing IFN-gamma and IL-2 was detected against several antigens in every subject of the medium dose cohort. The striking result was the dose-dependent expansion of HIV-specific precursor/memory T cells with high proliferation capacity. In low, medium and high dose cohorts this HIV-specific T cell population increased by 325-, 136,202 and 50,759 counts after 4 weeks, and by 3,899, 9,878 and 18,382 counts after one year, respectively, compared to baseline. CONCLUSIONS/SIGNIFICANCE: Single immunization with the DermaVir candidate therapeutic vaccine was safe and immunogenic in HIV-infected individuals. Based on the potent induction of Gag, Tat and Rev-specific memory T cells, especially in the medium dose cohort, we speculate that DermaVir boost T cell responses specific to all the 15 HIV antigens expressed from the single DNA. For durable immune reactivity repeated DermaVir immunization might be required since the frequency of DermaVir-boosted HIV-specific memory T cells decreased during the 48-week follow up. TRIAL REGISTRATION: ClinicalTrial.gov NCT00712530

A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).

BACKGROUND: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation's sTBI Management Guidelines, as they were not evidence-based. METHODS: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists' decision tendencies were the focus of recommendations. RESULTS: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. CONCLUSIONS: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management