Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Indirect search for dark matter from the Galactic Center and halo with the Super-Kamiokande detector

We present a search for an excess of neutrino interactions due to dark matter in the form of weakly interacting massive particles (WIMPs) annihilating in the Galactic center or halo based on the data set of Super-Kamiokande-I, -II, -III and -IV taken from 1996 to 2016. We model the neutrino flux, energy, and flavor distributions assuming WIMP self-annihilation is dominant to ν ¯ ν , μ + μ − , b ¯ b , or W + W − . The excess is in comparison to atmospheric neutrino interactions which are modeled in detail and fit to data. Limits on the self-annihilation cross section ⟨ σ A V ⟩ are derived for WIMP masses in the range 1 GeV to 10 TeV, reaching as low as 9.6 × 10 − 23     cm 3   s − 1 for 5 GeV WIMPs in b ¯ b mode and 1.2 × 10 − 24     cm 3   s − 1 for 1 GeV WIMPs in ν ¯ ν mode. The obtained sensitivity of the Super-Kamiokande detector to WIMP masses below several tens of GeV is the best among similar indirect searches to date

Search for neutrinos in coincidence with gravitational wave events from the LIGO–Virgo O3a observing run with the Super-Kamiokande detector

The Super-Kamiokande detector can be used to search for neutrinos in time coincidence with gravitational waves detected by the LIGO–Virgo Collaboration (LVC). Both low-energy (7–100 MeV) and high-energy (0.1–105 GeV) samples were analyzed in order to cover a very wide neutrino spectrum. Follow-ups of 36 (out of 39) gravitational waves reported in the GWTC-2 catalog were examined; no significant excess above the background was observed, with 10 (24) observed neutrinos compared with 4.8 (25.0) expected events in the high-energy (low-energy) samples. A statistical approach was used to compute the significance of potential coincidences. For each observation, p-values were estimated using neutrino direction and LVC sky map; the most significant event (GW190602_175927) is associated with a post-trial p-value of 7.8% (1.4σ). Additionally, flux limits were computed independently for each sample and by combining the samples. The energy emitted as neutrinos by the identified gravitational wave sources was constrained, both for given flavors and for all flavors assuming equipartition between the different flavors, independently for each trigger and by combining sources of the same nature

Diffuse supernova neutrino background search at Super-Kamiokande

A new search for the diffuse supernova neutrino background (DSNB) flux has been conducted at Super-Kamiokande (SK), with a $22.5\times2970$-kton$\cdot$day exposure from its fourth operational phase IV. The new analysis improves on the existing background reduction techniques and systematic uncertainties and takes advantage of an improved neutron tagging algorithm to lower the energy threshold compared to the previous phases of SK. This allows for setting the world's most stringent upper limit on the extraterrestrial $\bar{\nu}_e$ flux, for neutrino energies below 31.3 MeV. The SK-IV results are combined with the ones from the first three phases of SK to perform a joint analysis using $22.5\times5823$ kton$\cdot$days of data. This analysis has the world's best sensitivity to the DSNB $\bar{\nu}_e$ flux, comparable to the predictions from various models. For neutrino energies larger than 17.3 MeV, the new combined $90\%$ C.L. upper limits on the DSNB $\bar{\nu}_e$ flux lie around $2.7$ cm$^{-2}$$\cdot$$\text{sec}^{-1}$, strongly disfavoring the most optimistic predictions. Finally, potentialities of the gadolinium phase of SK and the future Hyper-Kamiokande experiment are discussed.Comment: 42 pages, 37 figures, 14 table

Searching for supernova bursts in Super-Kamiokande IV

Super-Kamiokande has been searching for neutrino bursts characteristic of core-collapse supernovae continuously, in real time, since the start of operations in 1996. The present work focuses on detecting more distant supernovae whose event rate may be too small to trigger in real time, but may be identified using an offline approach. The analysis of data collected from 2008 to 2018 found no evidence of distant supernovae bursts. This establishes an upper limit of 0.29 yr−1 on the rate of core-collapse supernovae out to 100 kpc at 90% C.L. For supernovae that fail to explode and collapse directly to black holes the limit reaches to 300 kpc

Validation Aspects of Water Treatment Systems for Pharmaceutical Products

The goal of conducting validation is to demonstrate that a process, when operated within established limits, produces a product of consistent and specified quality with a high degree of assurance. Validation of water treatment systems is necessary to obtain water with all desired quality attributes. This also provides a framework to establish a total control over the process which monitors safety, efficacy and ultimately, the process outcomes. The present overview is an attempt to discuss various aspects of validation including different approaches, components of water treatment systems, equipment qualifications, phases of performance testing, documentation and post-validation monitoring

Synthesis and biological activity of 16β-morpholinosteroid derivatives

363-367Fusion of morpholine at the 16 position of the steroid nucleus has been carried out to prepare monoquaternary 6,7 and 8 and bisquaternary ammonium compounds 13 and 14. Compounds 13 and 14 partly resemble chandonium iodide in structure. All the compounds have been evaluated for their neuromuscular blocking and ganglion blocking activities. The compounds 3, 4 5, 11 and 12 have been screened for antineoplastic activity at NCI, Bethesda