Viral infections are common and are potentially life-threatening in patients with moderate to severe primary immunodeficiency disorders. Because T-cell immunity contributes to the control of many ...viral pathogens, adoptive immunotherapy with virus-specific T cells (VSTs) has been a logical and effective way of combating severe viral disease in immunocompromised patients in multiple phase 1 and 2 clinical trials. Common viral targets include cytomegalovirus, Epstein-Barr virus, and adenovirus, though recent published studies have successfully targeted additional pathogens, including HHV6, BK virus, and JC virus. Though most studies have used VSTs derived from allogenic stem cell donors, the use of banked VSTs derived from partially HLA-matched donors has shown efficacy in multicenter settings. Hence, this approach could shorten the time for patients to receive VST therapy thus improving accessibility. In this review, we discuss the usage of VSTs for patients with primary immunodeficiency disorders in clinical trials, as well as future potential targets and methods to broaden the applicability of virus-directed T-cell immunotherapy for this vulnerable patient population.
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This essay examines Charles Brockden Brown’s first novel, Wieland (1798), particularly as it engages and critiques gender and nationalism in the fictive treatment of familicidal murders that took ...place in the eighteenth century. More broadly, Brown’s novel highlights the competing realities facing men and women in the early republic, as they navigated the shifting landscape of political and religious ideology in the turbulence of post-Revolutionary America. A close examination of Wieland offers a revealing glimpse into the tensions between patriarchy and femininity, republicanism and religion, and competing masculinities in the newly born republic that was limitlessly optimistic even as it was beset by national and familial violence.
In this issue of Blood, Brigida et al1 demonstrate that null mutations in ARPC1B result in combined immunodeficiency because of defects in T-cell migration, lymphoproliferation, and formation of the ...immune synapse, and further show that these abnormalities may be rescued by transduction of wild-type ARPC1B.
Patients with blood disorders who are immune suppressed are at increased risk for infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Sequelae of infection can ...include severe respiratorydisease and/or prolonged duration of viral shedding. Cellular therapies may protect these vulnerable patients by providing anti-viral cellular immunity and/or immune modulation. In this recent Review of the field, phase I/II trials evaluating adoptive cellular therapies with virus-specific T cells or natural killer cells are described along with trials evaluating the safety, feasibility, and preliminary efficacy of immune modulating cellular therapies including regulatory T cells and mesenchymal stromal cells. In addition, the immunological basis for these therapies is discussed.
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•Dolichogenidea tasmanica exhibited a sigmoid functional response in wind tunnels and enclosed cages.•Parasitism rates were lower in the cages, possibly due to the lack of moving air ...which provides a directional cue.•Recent experience with high host densities increases the searching rate of D. tasmanica.•At lower host densities that are characteristic of wild populations, D. tasmanica responded in a density-dependent manner.•This manner should contribute to suppression of pest populations before they reach economically damage levels.
Dolichogenidea tasmanica (Hymenoptera: Braconidae) is the most commonly collected parasitoid of light brown apple moth, Epiphyas postvittana (Lepidoptera: Tortricidae; LBAM) in Australia. We studied the functional response of D. tasmanica, and the effect of recent experience on this behavior. The functional response was evaluated in wind tunnels and enclosed cages. In both arenas, D. tasmanica exhibited a sigmoid functional response, but there was no clear tendency for a deceleration in the functional response curve at high host densities as would be expected with a typical type III functional response. Another experiment revealed that recent experience with high host densities increases the proportion of hosts parasitized by D. tasmanica, which explains much of the difference between the observed functional response curve and a typical type III curve. In general the searching behavior of D. tasmanica varies in response to host density in a manner that directly affects its searching rate. Our results have contributed to understanding the behavior of this parasitoid and indicate its capacity to control its host under laboratory conditions. At lower host densities that are characteristic of field populations, D. tasmanica responded in a density-dependent manner that should contribute to suppression of pest populations before they reach economically damaging levels.
Prior research has hypothesized the Sequential Organ Failure Assessment (SOFA) score to be a poor predictor of mortality in mechanically ventilated patients with COVID-19. Yet, several U.S. states ...have proposed SOFA-based algorithms for ventilator triage during crisis standards of care. Using a large cohort of mechanically ventilated patients with COVID-19, we externally validated the predictive capacity of the preintubation SOFA score for mortality prediction with and without other commonly used algorithm elements.
Multicenter, retrospective cohort study using electronic health record data.
Eighty-six U.S. health systems.
Patients with COVID-19 hospitalized between January 1, 2020, and February 14, 2021, and subsequently initiated on mechanical ventilation.
None.
Among 15,122 mechanically ventilated patients with COVID-19, SOFA score alone demonstrated poor discriminant accuracy for inhospital mortality in mechanically ventilated patients using the validation cohort (area under the receiver operating characteristic curve AUC, 0.66; 95% CI, 0.65-0.67). Discriminant accuracy was even poorer using SOFA score categories (AUC, 0.54; 95% CI, 0.54-0.55). Age alone demonstrated greater discriminant accuracy for inhospital mortality than SOFA score (AUC, 0.71; 95% CI, 0.69-0.72). Discriminant accuracy for mortality improved upon addition of age to the continuous SOFA score (AUC, 0.74; 95% CI, 0.73-0.76) and categorized SOFA score (AUC, 0.72; 95% CI, 0.71-0.73) models, respectively. The addition of comorbidities did not substantially increase model discrimination. Of 36 U.S. states with crisis standards of care guidelines containing ventilator triage algorithms, 31 (86%) feature the SOFA score. Of these, 25 (81%) rely heavily on the SOFA score (12 exclusively propose SOFA; 13 place highest weight on SOFA or propose SOFA with one other variable).
In a U.S. cohort of over 15,000 ventilated patients with COVID-19, the SOFA score displayed poor predictive accuracy for short-term mortality. Our findings warrant reappraisal of the SOFA score's implementation and weightage in existing ventilator triage pathways in current U.S. crisis standards of care guidelines.
Regional climate modeling using convection‐permitting models (CPMs; horizontal grid spacing <4 km) emerges as a promising framework to provide more reliable climate information on regional to local ...scales compared to traditionally used large‐scale models (LSMs; horizontal grid spacing >10 km). CPMs no longer rely on convection parameterization schemes, which had been identified as a major source of errors and uncertainties in LSMs. Moreover, CPMs allow for a more accurate representation of surface and orography fields. The drawback of CPMs is the high demand on computational resources. For this reason, first CPM climate simulations only appeared a decade ago. In this study, we aim to provide a common basis for CPM climate simulations by giving a holistic review of the topic. The most important components in CPMs such as physical parameterizations and dynamical formulations are discussed critically. An overview of weaknesses and an outlook on required future developments is provided. Most importantly, this review presents the consolidated outcome of studies that addressed the added value of CPM climate simulations compared to LSMs. Improvements are evident mostly for climate statistics related to deep convection, mountainous regions, or extreme events. The climate change signals of CPM simulations suggest an increase in flash floods, changes in hail storm characteristics, and reductions in the snowpack over mountains. In conclusion, CPMs are a very promising tool for future climate research. However, coordinated modeling programs are crucially needed to advance parameterizations of unresolved physics and to assess the full potential of CPMs.
Key Points
Convection‐permitting climate models reduce errors in large‐scale models
Added value in convective processes, regional extremes, and over mountains
Discusses challenges/potentials of convection‐permitting climate simulations
Amazon forests have experienced frequent and severe droughts in the past two decades. However, little is known about the large-scale legacy of droughts on carbon stocks and dynamics of forests. Using ...systematic sampling of forest structure measured by LiDAR waveforms from 2003 to 2008, here we show a significant loss of carbon over the entire Amazon basin at a rate of 0.3 ± 0.2 (95% CI) PgC yr
after the 2005 mega-drought, which continued persistently over the next 3 years (2005-2008). The changes in forest structure, captured by average LiDAR forest height and converted to above ground biomass carbon density, show an average loss of 2.35 ± 1.80 MgC ha
a year after (2006) in the epicenter of the drought. With more frequent droughts expected in future, forests of Amazon may lose their role as a robust sink of carbon, leading to a significant positive climate feedback and exacerbating warming trends.
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