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The World Central Kitchen cookbook : feeding humanity, feeding hope
A captivating collection of stories and recipes from renowned chefs, local cooks, and celebrity friends of José Andrés's beloved nonprofit World Central Kitchen (WCK), which feeds communities impacted by natural disasters and humanitarian crises; with a foreword from Stephen Colbert.
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Evaluation of a semi‐automated von Willebrand factor multimer assay, the Hydragel 5 von Willebrand multimer, by two European Centers
The phenotypic diagnosis of von Willebrand disease (VWD) is a multistep process with classification dependent on the quantification of von Willebrand factor (VWF) multimeric structure. VWF multimer analysis is a technically challenging, lengthy and non‐standardised assay, usually performed in specialist laboratories. Recently, a new semi‐automated multimer assay, the Hydragel 5 von Willebrand multimers (H5VWM) has become available.
This study, performed in two European centres, compared existing in‐house multimer assays to the H5VWM in individuals with and without VWD.
Overall agreement of 91.1% was observed in 74 individuals with normal VWF levels, 57 patients grouped as type 1 VWD, 33 type 2A, 16 type 2B, 28 type 2M, 11 type 2N. Patients tested following Desmopressin or VWF concentrate, with thrombotic thrombocytopenic purpura and acquired von Willebrand syndrome were also evaluated. Many of the discrepancies between methods were in patients with genetic mutations linked to more than one type of VWD including p.R1374C/H and p.R1315C. Quantifiable multimer results were available within one working day. Densitometry improved the interpretation of the multimers with slight structural variations that were not apparent by visual inspection of the in‐house method.
5VWM was a rapid, sensitive, standardised assay which used existing technology and could be included as an initial screen of VWF multimers in a VWD diagnostic algorithm in conjunction with traditional multimer analysis.
Journal Article
Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence
Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV) to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs) during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I) then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections.
Journal Article
Challenges and opportunities for mitigating nitrous oxide emissions from fertilized cropping systems
Nitrous oxide (N₂O) is often the largest single component of the greenhouse-gas budget of individual cropping systems, as well as for the US agricultural sector as a whole. Here, we highlight the factors that make mitigating N₂O emissions from fertilized agroecosystems such a difficult challenge, and discuss how these factors limit the effectiveness of existing practices and therefore require new technologies and fresh ideas. Modification of the rate, source, placement, and/or timing of nitrogen fertilizer application has in some cases been an effective way to reduce N₂O emissions. However, the efficacy of existing approaches to reducing N₂O emissions while maintaining crop yields across locations and growing seasons is uncertain because of the interaction of multiple factors that regulate several different N₂O-producing processes in soil. Although these processes have been well studied, our understanding of key aspects and our ability to manage them to mitigate N₂O emissions remain limited.
Journal Article
A review of patient-reported outcome measures to assess female infertility-related quality of life
Background
Infertility has a negative impact on quality of life (QoL) and well-being of affected individuals and couples. A variety of patient-reported outcome (PRO) measures to assess infertility-related QoL are available; however, there is a concern regarding potential issues with their development methodology, validation and use. This review aimed to i) identify PRO measures used in infertility interventional studies ii) assess validation evidence to identify a reliable, valid PRO measure to assess changes in QoL or treatment satisfaction in clinical studies with female patients following treatment with novel therapies iii) identify potential gaps in evidence for validity.
Methods
A structured literature search of Medline, Embase, and the Cochrane Library (accessed in September 2015) was conducted using pre-defined search terms. The identified publications were reviewed applying eligibility criteria to select interventional female infertility studies using PROs. Infertility-specific PRO measures assessing QoL, treatment satisfaction or psychiatric health, and included in studies by ≥2 research groups were selected and critically reviewed in light of scientific and regulatory guidance (e.g. FDA PRO Guidance for Industry) for evidence of content validity, psychometric strength, and patient acceptability.
Results
The literature search and hand-searching yielded 122 publications; 78 unique PRO measures assessing QoL, treatment satisfaction or psychiatric health were identified. Five PRO measures met the selection criteria for detailed review: Fertility Quality of Life (FertiQoL); Fertility Problem Inventory (FPI); Fertility Problem Stress (FPS); Infertility Questionnaire (IFQ); Illness Cognitions Questionnaire adapted for Infertility (ICQ-I). None of the PRO measures met all validation criteria. The FertiQoL was the most widely used infertility-specific PRO measure to assess QoL in interventional studies, with reasonable evidence for adequate content validity, psychometric strength, and linguistic validation. However, gaps in evidence remain including test-retest reliability and thresholds for interpreting clinically important changes. While the FPI demonstrated reasonable evidence for content and psychometric validity, its utility as an outcome measure is limited by a lack of recall period.
Conclusion
The FertiQoL and the FPI are potentially useful measures of infertility-related QoL in interventional studies. Further research is recommended to address gaps in evidence and confirm both PRO measures as reliable assessments of patient outcomes.
Journal Article
CD4 on CD8+T Cells Directly Enhances Effector Function and Is a Target for HIV Infection
Costimulation of purified CD8+T lymphocytes induces de novo expression of CD4, suggesting a previously unrecognized function for this molecule in the immune response. Here, we report that the CD4 molecule plays a direct role in CD8+T cell function by modulating expression of IFN-γ and Fas ligand, two important CD8+T cell effector molecules. CD4 expression also allows infection of CD8 cells by HIV, which results in down-regulation of the CD4 molecule and impairs the induction of IFN-γ, Fas ligand, and the cytotoxic responses of activated CD8+T cells. Thus, the CD4 molecule plays a direct role in CD8 T cell function, and infection of these cells by HIV provides an additional reservoir for the virus and also may contribute to the immunodeficiency seen in HIV disease.
Journal Article
Just culture and restorative just culture in healthcare settings: a scoping review of interventions, activities, factors and outcomes
Background
Just culture and, more recently, restorative just culture interventions are increasingly recognised as nonpunitive approaches to the reporting of incidents in which healthcare professionals trust that they will receive fair treatment and support. However, despite this recognition, evidence concerning the range of interventions, implementation strategies and factors for successful outcomes supported by systematic approaches remains limited. This review sought to address this gap.
Methods
We searched PubMed, HBE, CINAHL, PsycINFO, Scopus, Embase and grey literature from January 2000 to December 2024. We included peer-reviewed studies or quality improvement reports of any design and used an iterative, inductive approach to thematically categorise the data supplemented with descriptive statistics.
Results
We analysed 36 interventions across six thematic categories, which were a mix of just culture or restorative just culture interventions or existing safety interventions used to operationalise these approaches. Barriers and enablers to implementation included system improvements and accountability, a safe and supportive culture, leadership support, engagement and participation, organisational influences and external influences. Seven outcomes were identified: knowledge and confidence, communication and engagement in incident reporting, leadership engagement and support, shift towards a just, learning and safety culture, continuous improvement in processes, impact on patient safety outcomes and organisational benefits. A challenge was found in identifying the specific activities and factors contributing to the success of the interventions.
Conclusions
The interventions identified in this review are reflective of just culture and restorative just culture as a growing area in terms of quality and safety and incident management practices. The results suggest a number of preexisting safety interventions that can be used to operationalise these approaches, with restorative culture adding a further step of addressing the harm to the healthcare professional, crossing the boundaries of traditional patient safety functions to include Human Resources, Organisational Development and even Union functions. This review progresses the study of just culture and restorative just culture from a traditional quality improvement approach to implementation science. However, further work is needed to refine definitions to capture the extent and progress of preexisting work in this field and to develop implementation methodologies that identify relationships between interventions, barriers, enablers, outcomes and systematic methods for implementation.
Journal Article
Characteristics of Unruptured Compared to Ruptured Intracranial Aneurysms: A Multicenter Case–Control Study
Abstract
BACKGROUND
Only a minority of intracranial aneurysms rupture to cause subarachnoid hemorrhage.
OBJECTIVE
To test the hypothesis that unruptured aneurysms have different characteristics and risk factor profiles compared to ruptured aneurysms.
METHODS
We recruited patients with unruptured aneurysms or aneurysmal subarachnoid hemorrhages at 22 UK hospitals between 2011 and 2014. Demographic, clinical, and imaging data were collected using standardized case report forms. We compared risk factors using multivariable logistic regression.
RESULTS
A total of 2334 patients (1729 with aneurysmal subarachnoid hemorrhage, 605 with unruptured aneurysms) were included (mean age 54.22 yr). In multivariable analyses, the following variables were independently associated with rupture status: black ethnicity (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.29-4.56, compared to white) and aneurysm location (anterior cerebral artery/anterior communicating artery [OR 3.21; 95% CI 2.34-4.40], posterior communicating artery [OR 3.92; 95% CI 2.67-5.74], or posterior circulation [OR 3.12; 95% CI 2.08-4.70], compared to middle cerebral artery). The following variables were inversely associated with rupture status: antihypertensive medication (OR 0.65; 95% CI 0.49-0.84), hypercholesterolemia (0.64 OR; 95% CI 0.48-0.85), aspirin use (OR 0.28; 95% CI 0.20-0.40), internal carotid artery location (OR 0.53; 95% CI 0.38-0.75), and aneurysm size (per mm increase; OR 0.76; 95% CI 0.69-0.84).
CONCLUSION
We show substantial differences in patient and aneurysm characteristics between ruptured and unruptured aneurysms. These findings support the hypothesis that different pathological mechanisms are involved in the formation of ruptured aneurysms and incidentally detected unruptured aneurysms. The potential protective effect of aspirin might justify randomized prevention trials in patients with unruptured aneurysms.
Journal Article
Repeatability of commercially available visible and near infrared proximal soil sensors
Integration of reflectance sensors into commercial planter or tillage components have allowed for dense quantification of spatial soil variability. However, little is known about sensor performance and reproducibility. Therefore, research was conducted in Missouri, USA in 2019 to determine (i) how well sensors can estimate soil organic matter (OM) and (ii) whether sensor output would be repeatable among sensing dates. Soil sensor data were collected across three weeks on an alluvial soil with the Precision Planting SmartFirmer and Veris iScan. Output layers used in analyses included OM and the proprietary Furrow Moisture variable from the SmartFirmer, as well as OM, reflectance and soil apparent electrical conductivity from the iScan. Ground-truthing soil samples were collected at 0–50 mm on the first date to determine OM and on all dates to determine soil gravimetric water content. Results showed OM estimations by the iScan, which included the manufacturer’s specified field-specific calibration, were reproducible among the three sensing dates, with average root mean square error (RMSE) across dates of 2.02 g kg−1. SmartFirmer results showed OM was over-estimated in areas of low OM, and under-estimated in areas of high OM when compared to laboratory-measured data (R2 = 0.34; RMSE = 6.90 g kg−1). Additionally, variability existed in OM estimations between dates in areas that were lower in laboratory-measured OM, soil moisture and clay content. These results suggest real-time estimations of OM may be subject to variability, and local information is likely necessary for consistent soil reflectance-based OM estimations.
Journal Article
Coughing up $2.7mQuiz show winner, wife and lecturer arrested
The arrests of Royal Engineer Charles Ingram, 38, his wife Diana, 37, and Tecwen Whittock, 51, came after a two-month investigation by Scotland Yard. The cheque had been withheld amid allegations he was secretly helped by Mr Whittock, who was in the studio audience, signalling the answers by coughing. The Ingrams were arrested at their home in Easterton, Wiltshire, and taken to Salisbury police station to be questioned. Mr Whittock was detained at his home in Whitchurch, Cardiff, and taken to a nearby police station.
Newspaper Article