Prospects for Constraining Cosmology with the Extragalactic Cosmic Microwave Background Temperature

Observers have demonstrated that it is now feasible to measure the cosmic microwave background (CMB) temperature at high redshifts. We explore the possible constraints on cosmology which might ultimately be derived from such measurements. Besides providing a consistency check on standard and alternative cosmologies, possibilities include: constraints on the inhomogeneity and anisotropy of the universe at intermediate redshift $z ^<_\sim 10$; an independent probe of peculiar motions with respect to the Hubble flow; and constraining the epoch of reionization. We argue that the best possibility is as a probe of peculiar motions. We show, however, that the current measurement uncertainty ($\Delta T= \pm 0.002$K) in the local present absolute CMB temperature imposes intrinsic limits on the use of such CMB temperature measurements as a cosmological probe. At best, anisotropies at intermediate redshift could only be constrained at a level of $^>_\sim 0.1$ and peculiar motions could only be determined to an uncertainty of $^>_\sim 311$ km s$^{-1}$. If the high $z$ CMB temperature can only be measured with a precision comparable to the uncertainty of the local interstellar CMB temperature, then peculiar motions could be determined to an uncertainty of $1101 (1+z)^{-1} [\Delta T_{CMB}(z)/0.01 K] km s^{-1}$.Comment: 8 pages 2 Figures, PRD Submitte

Below-elbow cast sufficient for treatment of minimally displaced metaphyseal both-bone fractures of the distal forearm in children: long-term results of a randomized controlled multicenter trial

Background and purpose — We have previously shown that children with minimally displaced metaphyseal both-bone forearm fractures, who were treated with a below-elbow cast (BEC) instead of an above-elbow cast (AEC), experienced more comfort, less interference in daily activities, and similar functional outcomes at 7 months’ follow-up (FU). This study evaluates outcomes at 7 years’ follow-up. Patients and methods — A secondary analysis was performed of the 7 years’ follow-up data from our RCT. Primary outcome was loss of forearm rotation compared with the contralateral forearm. Secondary outcomes were patient-reported outcome measures (PROMs) consisting of the ABILHAND-kids and the DASH questionnaire, grip strength, radiological assessment, and cosmetic appearance. Results — The mean length of FU was 7.3 years (5.9–8.7). Of the initial 66 children who were included in the RCT, 51 children were evaluated at long-term FU. Loss of forearm rotation and secondary outcomes were similar in the 2 treatment groups. Interpretation — We suggest that children with minimally displaced metaphyseal both-bone forearm fractures should be treated with a below-elbow cast

Development of a Peripherally Restricted 5-HT2B Partial Agonist for Treatment of Pulmonary Arterial Hypertension

Ligands for the serotonin 2B receptor (5-HT2B) have shown potential to treat pulmonary arterial hypertension in preclinical models but cannot be used in humans because of predicted off-target neurological effects. The aim of this study was to develop novel systemically restricted compounds targeting 5-HT2B. Here, we show that mice treated with VU6047534 had decreased RVSP compared with control treatment in both the prevention and intervention studies using Sugen-hypoxia. VU6047534 is a novel 5-HT2B partial agonist that is peripherally restricted and able to both prevent and treat Sugen-hypoxia–induced pulmonary arterial hypertension. We have synthesized and characterized a structurally novel series of 5-HT2B ligands with high potency and selectivity for the 5-HT2B receptor subtype. Next-generation 5-HT2B ligands with similar characteristics, and predicted to be systemically restricted in humans, are currently advancing to investigational new drug–enabling studies

Measurement of the Atmospheric Muon Spectrum from 20 to 3000 GeV

The absolute muon flux between 20 GeV and 3000 GeV is measured with the L3 magnetic muon spectrometer for zenith angles ranging from 0 degree to 58 degree. Due to the large exposure of about 150 m2 sr d, and the excellent momentum resolution of the L3 muon chambers, a precision of 2.3 % at 150 GeV in the vertical direction is achieved. The ratio of positive to negative muons is studied between 20 GeV and 500 GeV, and the average vertical muon charge ratio is found to be 1.285 +- 0.003 (stat.) +- 0.019 (syst.).Comment: Total 32 pages, 9Figure

International union of basic and clinical pharmacology. Cx. Classification of receptors for 5-hydroxytryptamine; pharmacology and function

5-HT receptors expressed throughout the human body are targets for established therapeutics and various drugs in development. Their diversity of structure and function reflects the important role 5-HT receptors play in physiologic and pathophysiological processes. The present review offers a framework for the official receptor nomenclature and a detailed understanding of each of the 14 5-HT receptor subtypes, their roles in the systems of the body, and, where appropriate, the (potential) utility of therapeutics targeting these receptors

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt