Measurement of the Positive Muon Anomalous Magnetic Moment to 0.20 ppm

We present a new measurement of the positive muon magnetic anomaly, a_{μ}≡(g_{μ}-2)/2, from the Fermilab Muon g-2 Experiment using data collected in 2019 and 2020. We have analyzed more than 4 times the number of positrons from muon decay than in our previous result from 2018 data. The systematic error is reduced by more than a factor of 2 due to better running conditions, a more stable beam, and improved knowledge of the magnetic field weighted by the muon distribution, ω[over ˜]_{p}^{'}, and of the anomalous precession frequency corrected for beam dynamics effects, ω_{a}. From the ratio ω_{a}/ω[over ˜]_{p}^{'}, together with precisely determined external parameters, we determine a_{μ}=116 592 057(25)×10^{-11} (0.21 ppm). Combining this result with our previous result from the 2018 data, we obtain a_{μ}(FNAL)=116 592 055(24)×10^{-11} (0.20 ppm). The new experimental world average is a_{μ}(exp)=116 592 059(22)×10^{-11} (0.19 ppm), which represents a factor of 2 improvement in precision

A Phase 1 first-in-human trial to evaluate the safety and tolerability of CCT3833, an oral panRAF inhibitor, in patients with advanced solid tumours, including metastatic melanoma.

Background: Over 70,000 patients are diagnosed with malignant melanoma in the USA every year with a high proportion occurring in young people. Although treatments targeting the mitogen activated protein kinase signal transduction pathway including BRAF inhibitors have improved survival for patients with BRAF mutated melanoma, their utility is limited by intrinsic and acquired resistance of diverse mechanisms. Patients with a RAS mutated melanoma also represent a current unmet need. CCT3833 is a potent inhibitor of mutant BRAF, CRAF and SRC kinases. Preclinical data using CCT3833 in a range of mutant RAF or RAS cell lines in vitro and human tumour xenograft models in vivo demonstrated activity, including melanoma patient-derived xenografts with intrinsic or acquired resistance to selective BRAF inhibitors. These data support clinical development of CCT3833 in humans. Methods: This ongoing open-label, multi-centre Phase I trial of CCT3833 is in two parts; an initial dose escalation stage (Part A) in a rolling six design, followed by a dose expansion (Part B). The primary objectives are to evaluate the safety and tolerability profile of CCT3833 and establish the Recommended Phase 2 Dose (RP2D). CCT3833 is administered orally once daily on a continuous basis over a 28-day cycle. In Part A, a single dose is administered for safety and pharmacokinetic (PK) purposes prior to commencing continuous dosing. Secondary objectives include characterisation of the PK profile and correlation with tolerability / efficacy of CCT3833 in humans and assessment of response (radiological or clinical), supported by PD analyses. Eligible subjects include patients with advanced solid malignancies with performance status 0 to 1, fit for entry into a Phase 1 clinical trial. Part B will enrol patients with BRAF- or RAS- mutated metastatic melanoma into 3 cohorts i) treatment naïve V600E BRAF mutant melanoma ii) V600E BRAF mutant melanoma with progression on BRAF inhibitor therapy or iii) RAS mutant melanoma. Three cohorts of the dose escalation have been completed without DLT. Enrolment to cohort 4 began in January 2016. Clinical trial information: NCT02437227. Clinical trial information: NCT0243722

Quality of life of patients using intermittent urinary catheterization

Objectives: measure and compare the quality of life of neurogenic bladder patients using intermittent urinary catheterization who were going through rehabilitation in Brazil and Portugal. Method: multicenter, quantitative, cross-sectional, observational-analytic and correlational study executed in Brazil and Portugal. Two data collection tools were used, being one questionnaire with sociodemographic and clinical data and the World Health Organization Quality of Life-bref. Patients were included who were over 18 years of age, suffering from neurogenic urinary bladder and using intermittent urinary catheterization. Results: in the sample of Brazilian (n = 170) and Portuguese (n = 52) patients, respectively, most patients were single (87-51.2%; 25-48.1%), had finished primary education (47-45.3%; 31-59.6%) and were retired (70-41.2%; 21-40.4%). Spinal cord injury was the main cause of using the urinary catheter in both countries. The Brazilian patients presented higher mean quality of life scores in the psychological domain (68.9) and lower scores in the physical domain (58.9). The Portuguese patients presented higher scores in the psychological domain (68.4) and lower scores in the environment domain (59.4). The execution of intermittent urinary self-catheterization was significant for both countries. Conclusions: in the two countries, these patients’ quality of life can be determined by the improvement in the urinary symptoms, independence, self-confidence, social relationships and access to work activities.Objetivos: mensurar y comparar la calidad de vida de pacientes con vejiga neurogénica en uso de cateterismo vesical intermitente durante el proceso de rehabilitación en Brasil y en Portugal. Método: estudio multicéntrico, Brasil y Portugal, cuantitativo, trasversal, observacional-analítico y correlacional. Fueron utilizados dos instrumentos de recolecta, un cuestionario de datos sociodemográficos y clínicos y el World Health Organization Quality Life-bref. Fueron inclusos pacientes mayores de 18 años, con vejiga urinaria neurogénica, y usuarios de cateterismo vesical intermitente. Resultados: en la muestra de pacientes brasileños (n = 170) y portugueses (n = 52), respectivamente, la mayoría era soltera (87-51,2%; 25-48,1%), con educación fundamental (47-45,3%; 31-59,6%), jubilada (70-41,2%; 21-40,4%). La lesión medular fue la principal causa del uso del catéter urinario en los dos países. En promedio, los pacientes brasileños presentaron scores de calidad de vida superiores en el dominio psicológico (68,9) e inferiores en el dominio físico (58,9). Los pacientes portugueses presentaron scores superiores en el dominio psicológico (68,4) y inferiores en el dominio ambiente (59,4). La ejecución del autocateterismo vesical intermitente fue significativa para los dos países. Conclusiones: en los dos países, la calidad de vida de esos pacientes puede ser determinada por la mejora de los síntomas urinarios, de la independencia, autoconfianza, relaciones sociales y acceso a actividades laborales.Objetivos: mensurar e comparar a qualidade de vida de pacientes com bexiga neurogênica em uso do cateterismo urinário intermitente em processo de reabilitação, no Brasil e em Portugal. Método: estudo multicêntrico, Brasil e Portugal, quantitativo, transversal, observacional-analítico e correlacional. Foram utilizados dois instrumentos de coleta, um questionário de dados sociodemográficos e clínicos e World Health Organization Quality Life-bref. Foram inclusos pacientes maiores de 18 anos, com bexiga urinária neurogênica, e usuários do cateterismo urinário intermitente. Resultados: na amostra de pacientes brasileiros (n = 170) e portugueses (n = 52), respectivamente, a maioria era solteira (87-51,2%; 25-48,1%), com ensino fundamental (47-45,3%; 31-59,6%), aposentada (70-41,2%; 21-40,4%). A lesão medular foi a principal causa do uso do cateter urinário nos dois países. Os pacientes brasileiros apresentaram média de escores mais elevados de qualidade de vida no domínio psicológico (68,9) e menos elevados no domínio físico (58,9). Os pacientes portugueses apresentaram escores mais elevados no domínio psicológico (68,4) e menos no domínio ambiente (59,4). A realização do autocateterismo urinário intermitente foi significativa para os dois países. Conclusões: nos dois países, a qualidade de vida desses pacientes pode ser determinada pela melhora dos sintomas urinários, da independência, autoconfiança, relações sociais e acesso a atividades laborais