The reprogramming of a patient's immune system through genetic modification of the T cell compartment with chimeric antigen receptors (CARs) has led to durable remissions in chemotherapy-refractory B ...cell cancers. Targeting of solid cancers by CAR-T cells is dependent on their infiltration and expansion within the tumor microenvironment, and thus far, fewer clinical responses have been reported. Here, we report a phase 1 study (NCT02761915) in which we treated 12 children with relapsed/refractory neuroblastoma with escalating doses of second-generation GD2-directed CAR-T cells and increasing intensity of preparative lymphodepletion. Overall, no patients had objective clinical response at the evaluation point +28 days after CAR-T cell infusion using standard radiological response criteria. However, of the six patients receiving ≥10
/meter
CAR-T cells after fludarabine/cyclophosphamide conditioning, two experienced grade 2 to 3 cytokine release syndrome, and three demonstrated regression of soft tissue and bone marrow disease. This clinical activity was achieved without on-target off-tumor toxicity. Targeting neuroblastoma with GD2 CAR-T cells appears to be a valid and safe strategy but requires further modification to promote CAR-T cell longevity.
Global carbon intensity of crude oil production Masnadi, Mohammad S; El-Houjeiri, Hassan M; Schunack, Dominik ...
Science (American Association for the Advancement of Science),
08/2018, Letnik:
361, Številka:
6405
Journal Article
Recenzirano
Odprti dostop
New data enable targeted policy to lessen GHG emissions
Producing, transporting, and refining crude oil into fuels such as gasoline and diesel accounts for ∼15 to 40% of the “well-to-wheels” ...life-cycle greenhouse gas (GHG) emissions of transport fuels (
1
). Reducing emissions from petroleum production is of particular importance, as current transport fleets are almost entirely dependent on liquid petroleum products, and many uses of petroleum have limited prospects for near-term substitution (e.g., air travel). Better understanding of crude oil GHG emissions can help to quantify the benefits of alternative fuels and identify the most cost-effective opportunities for oil-sector emissions reductions (
2
). Yet, while regulations are beginning to address petroleum sector GHG emissions (
3
–
5
), and private investors are beginning to consider climate-related risk in oil investments (
6
), such efforts have generally struggled with methodological and data challenges. First, no single method exists for measuring the carbon intensity (CI) of oils. Second, there is a lack of comprehensive geographically rich datasets that would allow evaluation and monitoring of life-cycle emissions from oils. We have previously worked to address the first challenge by developing open-source oil-sector CI modeling tools OPGEE (
7
,
8
), supplementary materials (SM) 1.1. Here, we address the second challenge by using these tools to model well-to-refinery CI of all major active oil fields globally—and to identify major drivers of these emissions.
e13806 Background: Immune checkpoint inhibitor therapy-related (ICI) pneumonitis poses a significant challenge for patients with cancer. It is associated with increased clinical morbidity and ...mortality, often resulting in prolonged hospital stays and delays and/or discontinuation of cancer-directed treatment. Early detection and prompt treatment of ICI pneumonitis is critical to improve patient outcomes. Therefore, our institution implemented a remote patient monitoring (RPM) program leveraging in-home, electronic health record-integrated technology and virtual centralized nursing to monitor vital signs and patient symptoms in “high-risk” patients treated with immunotherapy. Methods: Patients receiving immunotherapy deemed to be “high-risk” for ICI pneumonitis seen at Mayo Clinic Rochester, Minnesota were offered enrollment in the RPM program beginning in June 2023. High-risk patients included those with pre-existing lung disease (chronic obstructive pulmonary disease, interstitial lung disease); those with a history of resolved ICI pneumonitis being rechallenged with immunotherapy; and those with grade 1 ICI pneumonitis continuing immunotherapy. Eligible patients who agreed to participate in the program were provided a kit consisting of RPM technology and electronic symptom questionnaires. The kit included an armband for continuous vital sign monitoring, a blood pressure monitor, a scale to measure weight, and a pre-connected cellular-enabled tablet for questionnaire answering. RPM data utilized real-time electronic health system integration and predetermined parameters to alert RPM nurses. Pre-specified escalation care pathways were then used to respond and escalate care, as necessary. The primary outcome of this pilot study was to assess the feasibility of implementing an RPM program in this patient population with a secondary outcome to determine the ability to detect ICI pneumonitis before significant clinical symptoms. Results: Sixteen patients were enrolled of whom 5 declined participation (2 due to inconvenience and 3 for unclear reasons) resulting in 11 patients who underwent monitoring. Five patients graduated monitoring without detection of ICI pneumonitis within a 4-month timeframe. Six patients are currently undergoing RPM. 372 alerts occurred of which 8 (2%) were escalated to physician review. These alerts included elevated heart rate in 4, shortness of breath in 3, and elevated blood pressure in 1. One patient was triaged to an emergency department and diagnosed with grade 2 ICI pneumonitis. Conclusions: We show that RPM in patients who are at high-risk for developing ICI pneumonitis can be effectively integrated into a care model and monitor pneumonitis related symptoms. Further studies are needed to prove whether RPM is beneficial in this population including other ICI toxicities.
This study aimed to estimate dietary sodium and potassium consumption among Jamaicans and evaluate associations with sociodemographic and clinical characteristics. A cross-sectional study was ...conducted using data from the Jamaica Health and Lifestyle Survey 2016-2017. Participants were noninstitutionalized Jamaicans aged ≥15 years. Trained staff collected sociodemographic and health data via interviewer-administered questionnaires and spot urine samples. The Pan American Health Organization formula was used to estimate 24-hour urine sodium and potassium excretion. High sodium level was defined as ≥2000 mg/day, and low potassium levels as <3510 mg/day (World Health Organization criteria). Associations between these outcomes and sociodemographic and clinical characteristics were explored using multivariable ANOVA models using log-transformed 24-hour urine sodium and potassium as outcome variables. Analyses included 1009 participants (368 males, 641 females; mean age 48.5 years). The mean sodium excretion was 3582 mg/day (males 3943 mg/day, females 3245 mg/day, P < .001). The mean potassium excretion was 2052 mg/day (males, 2210 mg/day; females, 1904 mg/day; P = .001). The prevalence of high sodium consumption was 66.6% (males 72.8%, females 60.7%, P < .001) and that of low potassium intake was 88.8% (85.1% males, 92.3% females, P < .001). Sodium consumption was inversely associated with older age, higher education, and low glomerular filtration rate but was directly associated with being male, current smoking, and obesity. Overall, males had higher sodium consumption than women, with the effect being larger among hypertensive men. Women with hypertension had lower sodium consumption than nonhypertensive women; however, hypertensive men had higher sodium consumption than nonhypertensive men. Potassium consumption was higher among men, persons with obesity, and those with high total cholesterol but was lower among men with "more than high school" education compared to men with "less than high school" education. We conclude that most Jamaican adults have diets high in sodium and low in potassium. In this study, sodium consumption was directly associated with male sex, obesity, and current smoking but was inversely associated with older age and higher education. High potassium consumption was associated with obesity and high cholesterol levels. These associations should be further explored in longitudinal studies and population-based strategies should be developed to address these cardiovascular risk factors.
With the changing configuration of power internationally, and the threat of terrorists getting hold of nuclear weapons, former deterrence strategies are less effective. Like "preventive diplomacy," ...some kind of "preventive refugee" knowledge about governance should be created and applied. ...I would like to highlight the review of The Past Can't Heal Us: The Dangers of Mandating Memory in the Name of Human Rights by Lea David.
PDF
