The majority of known Toxoplasma gondii isolates from Europe and North America belong to three clonal lines that differ dramatically in their virulence, depending on the host. To identify the ...responsible genes, we mapped virulence in F₁ progeny derived from crosses between type II and type III strains, which we introduced into mice. Five virulence (VIR) loci were thus identified, and for two of these, genetic complementation showed that a predicted protein kinase (ROP18 and ROP16, respectively) is the key molecule. Both are hypervariable rhoptry proteins that are secreted into the host cell upon invasion. These results suggest that secreted kinases unique to the Apicomplexa are crucial in the host-pathogen interaction.
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IMPORTANCE: Earlier egg and peanut introduction probably reduces risk of egg and peanut allergy, respectively, but it is uncertain whether food allergy as a whole can be prevented using earlier ...allergenic food introduction. OBJECTIVE: To investigate associations between timing of allergenic food introduction to the infant diet and risk of food allergy. DATA SOURCES: In this systematic review and meta-analysis, Medline, Embase, and CENTRAL databases were searched for articles from database inception to December 29, 2022. Search terms included infant, randomized controlled trial, and terms for common allergenic foods and allergic outcomes. STUDY SELECTION: Randomized clinical trials evaluating age at allergenic food introduction (milk, egg, fish, shellfish, tree nuts, wheat, peanuts, and soya) during infancy and immunoglobulin E (IgE)–mediated food allergy from 1 to 5 years of age were included. Screening was conducted independently by multiple authors. DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. Data were extracted in duplicate and synthesized using a random-effects model. The Grading of Recommendations, Assessment, Development, and Evaluation framework was used to assess certainty of evidence. MAIN OUTCOMES AND MEASURES: Primary outcomes were risk of IgE-mediated allergy to any food from 1 to 5 years of age and withdrawal from the intervention. Secondary outcomes included allergy to specific foods. RESULTS: Of 9283 titles screened, data were extracted from 23 eligible trials (56 articles, 13 794 randomized participants). There was moderate-certainty evidence from 4 trials (3295 participants) that introduction of multiple allergenic foods from 2 to 12 months of age (median age, 3-4 months) was associated with reduced risk of food allergy (risk ratio RR, 0.49; 95% CI, 0.33-0.74; I2 = 49%). Absolute risk difference for a population with 5% incidence of food allergy was −26 cases (95% CI, −34 to −13 cases) per 1000 population. There was moderate-certainty evidence from 5 trials (4703 participants) that introduction of multiple allergenic foods from 2 to 12 months of age was associated with increased withdrawal from the intervention (RR, 2.29; 95% CI, 1.45-3.63; I2 = 89%). Absolute risk difference for a population with 20% withdrawal from the intervention was 258 cases (95% CI, 90-526 cases) per 1000 population. There was high-certainty evidence from 9 trials (4811 participants) that introduction of egg from 3 to 6 months of age was associated with reduced risk of egg allergy (RR, 0.60; 95% CI, 0.46-0.77; I2 = 0%) and high-certainty evidence from 4 trials (3796 participants) that introduction of peanut from 3 to 10 months of age was associated with reduced risk of peanut allergy (RR, 0.31; 95% CI, 0.19-0.51; I2 = 21%). Evidence for timing of introduction of cow’s milk and risk of cow’s milk allergy was very low certainty. CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, earlier introduction of multiple allergenic foods in the first year of life was associated with lower risk of developing food allergy but a high rate of withdrawal from the intervention. Further work is needed to develop allergenic food interventions that are safe and acceptable for infants and their families.
Abstract
We report on the discovery of FRB 20200120E, a repeating fast radio burst (FRB) with a low dispersion measure (DM) detected by the Canadian Hydrogen Intensity Mapping Experiment FRB project. ...The source DM of 87.82 pc cm
−3
is the lowest recorded from an FRB to date, yet it is significantly higher than the maximum expected from the Milky Way interstellar medium in this direction (∼50 pc cm
−3
). We have detected three bursts and one candidate burst from the source over the period 2020 January–November. The baseband voltage data for the event on 2020 January 20 enabled a sky localization of the source to within ≃14 arcmin
2
(90% confidence). The FRB localization is close to M81, a spiral galaxy at a distance of 3.6 Mpc. The FRB appears on the outskirts of M81 (projected offset ∼20 kpc) but well inside its extended H
i
and thick disks. We empirically estimate the probability of a chance coincidence with M81 to be <10
−2
. However, we cannot reject a Milky Way halo origin for the FRB. Within the FRB localization region, we find several interesting cataloged M81 sources and a radio point source detected in the Very Large Array Sky Survey. We search for prompt X-ray counterparts in Swift Burst Alert Telescope and Fermi/GBM data, and, for two of the FRB 20200120E bursts, we rule out coincident SGR 1806−20-like X-ray bursts. Due to the proximity of FRB 20200120E, future follow-up for prompt multiwavelength counterparts and subarcsecond localization could be constraining of proposed FRB models.
Objectives This study sought to determine the pre-operative risk factors related to late bleeding, stroke, and pump thrombosis in patients with HeartMate II (HMII) left ventricular assist devices ...(LVADs) (Thoratec Corporation, Pleasanton, California) that might influence tailored improvements in patient management. Background Adverse events in LVAD patients remain high. It is unclear whether pre-operative characteristics influence the likelihood of the development of post-operative hemorrhagic or thrombotic complications. Knowing which patients are at greater risk might assist in tailoring anticoagulation therapy for certain patients. Methods Advanced heart failure patients (n = 956) discharged from the hospital after LVAD implantation in the HMII bridge to transplantation (n = 405) and destination therapy (n = 551) clinical trials were retrospectively evaluated. Bleeding requiring surgery or transfusion of >2 U of packed red blood cells, stroke (hemorrhagic and ischemic), and pump thrombosis were tracked from hospital discharge until patient outcome. Results Adverse event rates for post-discharge bleeding (0.67 events/patient-year) were higher than those for hemorrhagic stroke (0.05), ischemic stroke (0.04), and pump thrombosis (0.03). The main sites of bleeding included gastrointestinal (45% of events), wound (12%), and epistaxis (4%). Older age (>65 years) (hazard ratio HR: 1.31), lower pre-operative hematocrit (≤31%) (HR: 1.31), ischemic etiology (HR: 1.35), and female (HR: 1.45) were statistically significant multivariable risk factors for bleeding. Female (HR: 1.92) and 65 years of age and younger (HR: 1.94) were multivariable risk factors for hemorrhagic stroke, whereas female (HR: 1.84) and history of diabetes (HR: 1.99) were risk factors for ischemic stroke. Female (HR: 1.90) and higher body mass index (HR: 1.71/10 kg/m2 increase) were also multivariable risk factors for pump thrombosis. Conclusions The risk of bleeding and thrombotic events during LVAD support differs by patient demographics, including sex, age, body mass index, and etiology of heart failure. Further studies should focus on the potential of tailored anticoagulation strategies in these subgroups.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Rising temperatures will impact urban communities, which are growing as a proportion of the global population. However, the effects of increasing temperature may not be felt equally, with ...less wealthy neighbourhoods experiencing hotter thermal environments in some urban areas because of geographic location and tree cover. While relationships have been drawn between wealth inequality and temperature in urban areas, these rarely project into the future or combine humidity and air temperatures into ‘wet-bulb temperature’ at fine spatial resolution, which is more directly relevant to the human experienced environment. Here I present an analysis of present and future wet-bulb temperatures in Hong Kong, an economically developed subtropical city in South-East Asia. I couple census data with recently available 30 × 30 m resolution climate models to examine how the income of districts and their physical characteristics are correlated with human-experienced local temperatures. I uncover evidence of thermal inequity, with wealthier districts exhibiting cooler conditions than less wealthy districts. Projecting into the future using three different climate change scenarios I demonstrate that wet-bulb temperatures considered dangerous to human survival may be commonly experienced in Hong Kong by the end of the century. However, the wealthiest districts of Hong Kong are likely to have a thermal safety margin of at least 25–30 years more than the least wealthy districts before these dangerous temperatures are reached. Due to the high population density and economic importance of the region, these findings have significant implications for public health and urban planning as global temperatures continue to rise.
Monarch butterfly (Danaus plexippus) decline over the past 25 years has received considerable public and scientific attention, in large part because its decline, and that of its milkweed (Asclepias ...spp.) host plant, have been linked to genetically modified (GM) crops and associated herbicide use. Here, we use museum and herbaria specimens to extend our knowledge of the dynamics of both monarchs and milkweeds in the United States to more than a century, from 1900 to 2016. We show that both monarchs and milkweeds increased during the early 20th century and that recent declines are actually part of a much longer-term decline in both monarchs and milkweed beginning around 1950. Herbicide-resistant crops, therefore, are clearly not the only culprit and, likely, not even the primary culprit: Not only did monarch and milkweed declines begin decades before GM crops were introduced, but other variables, particularly a decline in the number of farms, predict common milkweed trends more strongly over the period studied here.
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Central Park is an iconic feature of New York City, which was the first and one of the hardest hit cities in the United States by the Coronavirus. State-level stay-at-home order, raising COVID-19 ...cases, as well as the public’s personal concerns regarding exposure to the virus, led to a significant reduction of Central Park visitation. We utilized extensive cellphone tracking data to conduct one of the pioneering empirical studies assessing the economic impact of COVID-19 on urban parks. We integrated the difference-in-difference (DID) design with the recreation-demand model. The DID design aids in identifying the causal impacts, controlling for unobservable factors that might confound the treatment effects of interest. Concurrently, the recreational demand model examines the driving factors of visitation changes and enables us to estimate the welfare changes experienced by New York City’s residents. Our findings shine a light on the substantial, yet often overlooked, welfare loss triggered by the pandemic. The analysis indicates that the pandemic resulted in a 94% reduction in visitation, corresponding to an annual consumer surplus loss of $450 million. We noted a rebound in visitation following the initial outbreak, influenced by shifts in government policy, weather conditions, holiday periods, and personal characteristics.
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Under what circumstances do armed groups in conflict choose to use terrorist bombings? This article challenges the conventional wisdom that terrorist bombings are done by either ideologically-driven ...or weak armed groups who have no reasonable prospect of success on the battlefield. Drawing from Mao's theory of protracted struggle, it argues that terrorist bombings are a weapon of choice for armed groups that have transitioned into capable fighting armies but lack the degree of popular support they need to be a serious political contender. Using data on attributed terrorist bombings from 1998-2005, it finds that Islamist groups and older armed groups with sizeable membership are more likely to use terrorist bombings than smaller or newer groups.
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Objectives This study sought to assess the impact of continuous flow left ventricular assist devices (LVADs) on functional capacity and heart failure-related quality of life. Background Newer ...continuous-flow LVAD are smaller and quieter than pulsatile-flow LVADs. Methods Data from advanced heart failure patients enrolled in the HeartMate II LVAD (Thoratec Corporation, Pleasanton, California) bridge to transplantation (BTT) (n = 281) and destination therapy (DT) (n = 374) trials were analyzed. Functional status (New York Heart Association NYHA functional class, 6-min walk distance, patient activity scores), and quality of life (Minnesota Living With Heart Failure MLWHF and Kansas City Cardiomyopathy Questionnaires KCCQ) were collected before and after LVAD implantation. Results Compared with baseline, LVAD patients demonstrated early and sustained improvements in functional status and quality of life. Most patients had NYHA functional class IV symptoms at baseline. Following implant, 82% (BTT) and 80% (DT) of patients at 6 months and 79% (DT) at 24 months improved to NYHA functional class I or II. Mean 6-min walk distance in DT patients was 204 m in patients able to ambulate at baseline, which improved to 350 and 360 m at 6 and 24 months. There were also significant and sustained improvements from baseline in both BTT and DT patients in median MLWHF scores (by 40 and 42 U in DT patients, or 52% and 55%, at 6 and 24 months, respectively), and KCCQ overall summary scores (by 39 and 41 U, or 170% and 178%). Conclusions Use of a continuous flow LVAD in advanced heart failure patients results in clinically relevant improvements in functional capacity and heart failure-related quality of life.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bone is a complex tissue that provides mechanical support for muscles and joints, protection for vital organs, a mineral reservoir that is essential for calcium homeostasis, and the environment and ...niches required for haematopoiesis. The regulation of bone mass in mammals is governed by a complex interplay between bone-forming cells termed osteoblasts and bone-resorbing cells termed osteoclasts, and is guided physiologically by a diverse set of hormones, cytokines and growth factors. The balance between these processes changes over time, causing an elevated risk of fractures with age. Osteoclasts may also be activated in the cancer setting, leading to bone pain, fracture, spinal cord compression and other significant morbidities. This Review chronicles the events that led to an increased understanding of bone resorption, the elucidation of the signalling pathway mediated by osteoprotegerin, receptor activator of NF-κB (RANK) and RANK ligand (RANKL) and its role in osteoclast biology, as well as the evolution of recombinant RANKL antagonists, which culminated in the development of the therapeutic RANKL-targeted antibody denosumab.
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