The proton spin sum rule chiral bag prediction, an update

We reevaluate a quark model prediction using the new QCD evolution function calculated to the 3 loop order and conclude that this model compares favorably with the new experimental results.Comment: 10 pages, 2 figures available by request, give fax numbe

Euclid: On the reduced shear approximation and magnification bias for Stage IV cosmic shear experiments

Stage IV weak lensing experiments will offer more than an order of magnitude leap in precision. We must therefore ensure that our analyses remain accurate in this new era. Accordingly, previously ignored systematic effects must be addressed. In this work, we evaluate the impact of the reduced shear approximation and magnification bias, on the information obtained from the angular power spectrum. To first-order, the statistics of reduced shear, a combination of shear and convergence, are taken to be equal to those of shear. However, this approximation can induce a bias in the cosmological parameters that can no longer be neglected. A separate bias arises from the statistics of shear being altered by the preferential selection of galaxies and the dilution of their surface densities, in high-magnification regions. The corrections for these systematic effects take similar forms, allowing them to be treated together. We calculate the impact of neglecting these effects on the cosmological parameters that would be determined from Euclid, using cosmic shear tomography. We also demonstrate how the reduced shear correction can be calculated using a lognormal field forward modelling approach. These effects cause significant biases in Omega_m, n_s, sigma_8, Omega_DE, w_0, and w_a of -0.51 sigma, -0.36 sigma, 0.37 sigma, 1.36 sigma, -0.66 sigma, and 1.21 sigma, respectively. We then show that these lensing biases interact with another systematic: the intrinsic alignment of galaxies. Accordingly, we develop the formalism for an intrinsic alignment-enhanced lensing bias correction. Applying this to Euclid, we find that the additional terms introduced by this correction are sub-dominant

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov: NCT01578239, EudraCT: 2011-005049-11

Analysis of shared heritability in common disorders of the brain

Paroxysmal Cerebral Disorder

Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors

Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1, 2, 3) and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can inhibit neuroendocrine tumor (NET) growth more robustly than octreotide in vitro. This open-label, phase II study assessed the clinical activity of pasireotide in treatment-naïve patients with metastatic grade 1 or 2 NETs. Patients with metastatic pancreatic and extra-pancreatic NETs were treated with pasireotideLAR (60 mg every 4 weeks). Previous systemic therapy, including octreotide and lanreotide, was not permitted. Tumor assessments were performed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was progression-free survival (PFS). The secondary end points in cluded over all survival (OS), over all radiographic responserate (ORR), and safety. Twenty-nine patients were treated with pasireotide LAR (60 mg every 4 weeks) and 28 were evaluable for response. The median PFS was 11 months. The most favorable effect was observed in patients with low hepatic tumor burden, normal baseline chromogranin A, and high tumoral SSTR5 expression. Median OS has not been reached; the 30-monthOSrate was 70%. The best radiographic response was partial response inone patient (4%), stable disease in 17 patients (60%), and progressive disease in ten patients (36%). Although grade 3/4 toxicities were rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia including 14% grade 3 hyperglycemia. Although pasireotide appears to be an effective antiproliferative agent in the treatment of advanced NETs, the high incidence of hyperglycemia raises concerns regarding its suitability as a first-line systemic agent in unselected patients. SSTR5 expression is a potentially predictive biomarker for response

Self-organizing 3D human trunk neuromuscular organoids

Neuromuscular networks assemble during early human embryonic development and are essential for the control of body movement. Previous neuromuscular junction modeling efforts using human pluripotent stem cells (hPSCs) generated either spinal cord neurons or skeletal muscles in monolayer culture. Here, we use hPSC-derived axial stem cells, the building blocks of the posterior body, to simultaneously generate spinal cord neurons and skeletal muscle cells that self-organize to generate human neuromuscular organoids (NMOs) that can be maintained in 3D for several months. Single-cell RNA-sequencing of individual organoids revealed reproducibility across experiments and enabled the tracking of the neural and mesodermal differentiation trajectories as organoids developed and matured. NMOs contain functional neuromuscular junctions supported by terminal Schwann cells. They contract and develop central pattern generator-like neuronal circuits. Finally, we successfully use NMOs to recapitulate key aspects of myasthenia gravis pathology, thus highlighting the significant potential of NMOs for modeling neuromuscular diseases in the future