BACKGROUND:Cardiac arrest in hospitalized children is associated with poor outcomes, but no contemporary study has reported whether the trends in survival have changed over time. In this study, we ...examined temporal trends in survival for pediatric patients with an in-hospital pulseless cardiac arrest and pediatric patients with a nonpulseless cardiopulmonary resuscitation event from 2000 to 2018.
METHODS:This was an observational study of hospitalized pediatric patients (≤18 years of age) who received cardiopulmonary resuscitation from January 2000 to December 2018 and were included in the Get With The Guidelines-Resuscitation registry, a United States–based in-hospital cardiac arrest registry. The primary outcome was survival to hospital discharge, and the secondary outcome was return of spontaneous circulation (binary outcomes). Generalized estimation equations were used to obtain unadjusted trends in outcomes over time. Separate analyses were performed for patients with a pulseless cardiac arrest and patients with a nonpulseless event (bradycardia with poor perfusion) requiring cardiopulmonary resuscitation. A subgroup analysis was conducted for shockable versus nonshockable initial rhythms in pulseless events.
RESULTS:A total of 7433 patients with a pulseless cardiac arrest and 5751 patients with a nonpulseless event were included for the analyses. For pulseless cardiac arrests, survival was 19% (95% CI, 11%–29%) in 2000 and 38% (95% CI, 34%–43%) in 2018, with an absolute change of 0.67% (95% CI, 0.40%–0.95%; P<0.001) per year, although the increase in survival appeared to stagnate following 2010. Return of spontaneous circulation also increased over time, with an absolute change of 0.83% (95% CI, 0.53%–1.14%; P<0.001) per year. We found no interaction between survival to hospital discharge and the initial rhythm. For nonpulseless events, survival was 57% (95% CI, 39%–75%) in 2000 and 66% (95% CI, 61%–72%) in 2018, with an absolute change of 0.80% (95% CI, 0.32%–1.27%; P=0.001) per year.
CONCLUSIONS:Survival has improved for pediatric events requiring cardiopulmonary resuscitation in the United States, with a 19% absolute increase in survival for in-hospital pulseless cardiac arrests and a 9% absolute increase in survival for nonpulseless events between 2000 and 2018. However, survival from pulseless cardiac arrests appeared to have reached a plateau following 2010.
To revise the current juvenile idiopathic arthritis (JIA) International League of Associations for Rheumatology (ILAR) classification criteria with an evidence-based approach, using clinical and ...routine laboratory measures available worldwide, to identify homogeneous clinical groups and to distinguish those forms of chronic arthritis typically seen only in children from the childhood counterpart of adult diseases.
The overall project consists of 4 steps. This work represents Step 1, a Delphi Web-based consensus and Step 2, an international nominal group technique (NGT) consensus conference for the new provisional Pediatric Rheumatology International Trials Organization JIA classification criteria. A future large data collection of at least 1000 new-onset JIA patients (Step 3) followed by analysis and NGT consensus (Step 4) will provide data for the evidence-based validation of the JIA classification criteria.
In Step 1, three Delphi rounds of interactions were implemented to revise the 7 ILAR JIA categories. In Step 2, forty-seven questions with electronic voting were implemented to derive the new proposed criteria. Four disorders were proposed: (a) systemic JIA; (b) rheumatoid factor-positive JIA; (c) enthesitis/spondylitis-related JIA; and (d) early-onset antinuclear antibody-positive JIA. The other forms were gathered under the term "others." These will be analyzed during the prospective data collection using a list of descriptors to see whether the clustering of some of them could identify homogeneous entities.
An international consensus was reached to identify different proposed homogeneous chronic disorders that fall under the historical term
. These preliminary criteria will be formally validated with a dedicated project.
Cultured trabecular meshwork (TM) cells are a valuable model system to study the cellular mechanisms involved in the regulation of conventional outflow resistance and thus intraocular pressure; and ...their dysfunction resulting in ocular hypertension. In this review, we describe the standard procedures used for the isolation of TM cells from several animal species including humans, and the methods used to validate their identity. Having a set of standard practices for TM cells will increase the scientific rigor when used as a model, and enable other researchers to replicate and build upon previous findings.
•Comprehensive review of techniques to culture TM cells are presented.•Helpful tips for culturing TM cells are described.•First set of consensus standards for TM cell research is defined.
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The availability of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is currently limited because they are produced mainly by marine fisheries that cannot keep pace ...with the demands of the growing market for these products. A sustainable non-animal source of EPA and DHA is needed. Metabolic engineering of the oleaginous yeast Yarrowia lipolytica resulted in a strain that produced EPA at 15% of dry cell weight. The engineered yeast lipid comprises EPA at 56.6% and saturated fatty acids at less than 5% by weight, which are the highest and the lowest percentages, respectively, among known EPA sources. Inactivation of the peroxisome biogenesis gene PEX10 was crucial in obtaining high EPA yields and may increase the yields of other commercially desirable lipid-related products. This technology platform enables the production of lipids with tailored fatty acid compositions and provides a sustainable source of EPA.
In the setting of conventional radiation therapy, even when combined with immunotherapy, head and neck cancer often recurs locally and regionally. Elective nodal irradiation (ENI) is commonly ...employed to decrease regional recurrence. Given our developing understanding that immune cells are radio-sensitive, and that T cell priming occurs in the draining lymph nodes (DLNs), we hypothesize that radiation therapy directed at the primary tumor only will increase the effectiveness of immunotherapies. We find that ENI increases local, distant, and metastatic tumor growth. Multi-compartmental analysis of the primary/distant tumor, the DLNs, and the blood shows that ENI decreases the immune response systemically. Additionally, we find that ENI decreases antigen-specific T cells and epitope spreading. Treating the primary tumor with radiation and immunotherapy, however, fails to reduce regional recurrence, but this is reversed by either concurrent sentinel lymph node resection or irradiation. Our data support using lymphatic sparing radiation therapy for head and neck cancer.
There is growing interest in digital PCR (dPCR) because technological progress makes it a practical and increasingly affordable technology. dPCR allows the precise quantification of nucleic acids, ...facilitating the measurement of small percentage differences and quantification of rare variants. dPCR may also be more reproducible and less susceptible to inhibition than quantitative real-time PCR (qPCR). Consequently, dPCR has the potential to have a substantial impact on research as well as diagnostic applications. However, as with qPCR, the ability to perform robust meaningful experiments requires careful design and adequate controls. To assist independent evaluation of experimental data, comprehensive disclosure of all relevant experimental details is required. To facilitate this process we present the Minimum Information for Publication of Quantitative Digital PCR Experiments guidelines. This report addresses known requirements for dPCR that have already been identified during this early stage of its development and commercial implementation. Adoption of these guidelines by the scientific community will help to standardize experimental protocols, maximize efficient utilization of resources, and enhance the impact of this promising new technology.
Once called a 'classically non-describable two-valuedness' by Pauli, the electron spin forms a qubit that is naturally robust to electric fluctuations. Paradoxically, a common control strategy is the ...integration of micromagnets to enhance the coupling between spins and electric fields, which, in turn, hampers noise immunity and adds architectural complexity. Here we exploit a switchable interaction between spins and orbital motion of electrons in silicon quantum dots, without a micromagnet. The weak effects of relativistic spin-orbit interaction in silicon are enhanced, leading to a speed up in Rabi frequency by a factor of up to 650 by controlling the energy quantization of electrons in the nanostructure. Fast electrical control is demonstrated in multiple devices and electronic configurations. Using the electrical drive, we achieve a coherence time T
≈ 50 μs, fast single-qubit gates with T
= 3 ns and gate fidelities of 99.93%, probed by randomized benchmarking. High-performance all-electrical control improves the prospects for scalable silicon quantum computing.
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Previous incidence estimates may no longer reflect the
current public health burden of cardiac arrest in hospitalized adult and
pediatric patients across the United States. The aim of this study was ...to
estimate the contemporary annual incidence of in-hospital cardiac arrest
in adults and children across the United States and to describe trends in
incidence between 2008 and 2017.
Using the Get With The Guidelines–
Resuscitation registry, we developed a negative binomial regression
model to estimate the incidence of index pulseless in-hospital cardiac
arrest based on hospital-level characteristics. The model was used to
predict the number of in-hospital cardiac arrests in all US hospitals,
using data from the American Hospital Association Annual Survey.
We performed separate analyses for adult (≥18 years) and pediatric
(<18 years) cardiac arrests. Additional analyses were performed for
recurrent cardiac arrests and pediatric patients requiring cardiopulmonary
resuscitation for poor perfusion (nonpulseless events). The average
annual incidence of in-hospital cardiac arrest in the United States was
estimated at 292 000 (95% prediction interval, 217 600–503 500) adult
and 15 200 pediatric cases, of which 7100 (95% prediction interval,
4400–9900) cases were pulseless cardiac arrests and 8100 (95%
prediction interval, 4700–11 500) cases were nonpulseless events. The
rate of adult cardiac arrests increased over time, while pediatric events
remained more stable. When including both index and recurrent inhospital
cardiac arrests, the average annual incidence was estimated at
357 900 (95% prediction interval, 247 100–598 400) adult and 19 900
pediatric cases, of which 8300 (95% prediction interval, 4900–11 200)
cases were pulseless cardiac arrests and 11 600 (95% prediction interval,
6400–16 700) cases were nonpulseless events.
There are ≈292 000 adult in-hospital cardiac arrests and
15 200 pediatric in-hospital events in the United States each year. This
study provides contemporary estimates of the public health burden of
cardiac arrest among hospitalized patients.
In migrating cells, integrin-based focal adhesions (FAs) assemble in protruding lamellipodia in association with rapid filamentous actin (F-actin) assembly and retrograde flow. How dynamic F-actin is ...coupled to FA is not known. We analyzed the role of vinculin in integrating F-actin and FA dynamics by vinculin gene disruption in primary fibroblasts. Vinculin slowed F-actin flow in maturing FA to establish a lamellipodium-lamellum border and generate high extracellular matrix (ECM) traction forces. In addition, vinculin promoted nascent FA formation and turnover in lamellipodia and inhibited the frequency and rate of FA maturation. Characterization of a vinculin point mutant that specifically disrupts F-actin binding showed that vinculin-F-actin interaction is critical for these functions. However, FA growth rate correlated with F-actin flow speed independently of vinculin. Thus, vinculin functions as a molecular clutch, organizing leading edge F-actin, generating ECM traction, and promoting FA formation and turnover, but vinculin is dispensible for FA growth.
Internalized homonegativity (IH) is an important variable affecting the wellbeing of lesbian, gay, and bisexual (LGB) persons. We included 201 studies in a systematic mapping review of IH. Most ...studies were conducted in North America and examined IH as a predictor of poor health. The primary focus of 14 studies was IH scale measurement, and, in total, these studies detailed nine distinct scales. Eighteen studies compared levels of IH in LGB populations, four described prevention programs, and one investigated IH using qualitative methods. Our review indicates that further research is needed, particularly qualitative research and ways to ameliorate IH.
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