A plain language summary of atezolizumab compared with single-agent chemotherapy in participants with non-small cell lung cancer who should not receive platinum-based chemotherapy (the IPSOS study).

What is this summary about?This plain language summary reports the results of the IPSOS clinical study. This study looked at treatment with atezolizumab (a type of immunotherapy) compared with single-agent chemotherapy (1 chemotherapy drug; either vinorelbine or gemcitabine) in participants receiving their first treatment for advanced or metastatic non-small cell lung cancer (NSCLC).People with advanced or metastatic NSCLC are often treated with platinum-based chemotherapy, which is a combination of 2 drugs. However, a doctor may decide that some people are not suitable candidates for platinum-based chemotherapy because they are too weak, or they are older and have other medical conditions. These people who should not receive platinum-based chemotherapy are often treated with 1 chemotherapy drug (single-agent chemotherapy) instead.People who are weaker, older, or have other medical problems are often not allowed to participate in clinical trials for new medicines. Therefore, these patients are not well represented in clinical trials. The IPSOS study focused on these under-represented patients.The IPSOS study compared how well atezolizumab worked compared with single-agent chemotherapy (vinorelbine or gemcitabine) in participants who should not receive platinum-based chemotherapy.Researchers collected information about the health of participants for an average of more than 3 years after starting treatment.What were the results?Compared with single-agent chemotherapy, atezolizumab improved how long participants lived after starting treatment. After 2 years, the percentage of participants still alive was twice as high in the atezolizumab group (24%) compared with the chemotherapy group (12%), despite over 50% of patients in the chemotherapy group who were still alive at 2 years receiving subsequent immunotherapy. Throughout their treatment, participants in the atezolizumab group reported no change in their health and ability to function and enjoy life, while participants in the chemotherapy group reported worsening in some of these measures. Compared with single-agent chemotherapy, atezolizumab was associated with a similar rate of serious side effects (those that were life-threatening, needed hospital care, or caused lasting problems or death) related to treatment and half the rate of severe side effects (those considered medically important by a person’s doctor; also called ‘Grade 3, 4, or 5’) related to treatment.What do the results of the study mean?Atezolizumab is now approved by the European Medicines Agency and can be used as a first treatment for people with advanced or metastatic NSCLC who aren’t able to receive platinum-based chemotherapy.[Box: see text]. en

Ecological Guild Evolution and the Discovery of the World's Smallest Vertebrate

Living vertebrates vary drastically in body size, yet few taxa reach the extremely minute size of some frogs and teleost fish. Here we describe two new species of diminutive terrestrial frogs from the megadiverse hotspot island of New Guinea, one of which represents the smallest known vertebrate species, attaining an average body size of only 7.7 mm. Both new species are members of the recently described genus Paedophryne, the four species of which are all among the ten smallest known frog species, making Paedophryne the most diminutive genus of anurans. This discovery highlights intriguing ecological similarities among the numerous independent origins of diminutive anurans, suggesting that minute frogs are not mere oddities, but represent a previously unrecognized ecological guild

Search for continuous gravitational waves from known pulsars in the first part of the fourth LIGO-Virgo-KAGRA observing run

Continuous gravitational waves (CWs) emission from neutron stars carries information about their internal structure and equation of state, and it can provide tests of general relativity. We present a search for CWs from a set of 45 known pulsars in the first part of the fourth LIGO–Virgo–KAGRA observing run, known as O4a. We conducted a targeted search for each pulsar using three independent analysis methods considering single-harmonic and dual-harmonic emission models. We find no evidence of a CW signal in O4a data for both models and set upper limits on the signal amplitude and on the ellipticity, which quantifies the asymmetry in the neutron star mass distribution. For the single-harmonic emission model, 29 targets have the upper limit on the amplitude below the theoretical spin-down limit. The lowest upper limit on the amplitude is 6.4 × 10−27 for the young energetic pulsar J0537−6910, while the lowest constraint on the ellipticity is 8.8 × 10−9 for the bright nearby millisecond pulsar J0437−4715. Additionally, for a subset of 16 targets, we performed a narrowband search that is more robust regarding the emission model, with no evidence of a signal. We also found no evidence of nonstandard polarizations as predicted by the Brans–Dicke theory

A search using GEO600 for gravitational waves coincident with fast radio bursts from SGR 1935+2154

The magnetar SGR 1935+2154 is the only known Galactic source of fast radio bursts (FRBs). FRBs from SGR 1935+2154 were first detected by the Canadian Hydrogen Intensity Mapping Experiment (CHIME)/FRB and the Survey for Transient Astronomical Radio Emission 2 in 2020 April, after the conclusion of the LIGO, Virgo, and KAGRA Collaborations' O3 observing run. Here, we analyze four periods of gravitational wave (GW) data from the GEO600 detector coincident with four periods of FRB activity detected by CHIME/FRB, as well as X-ray glitches and X-ray bursts detected by NICER and NuSTAR close to the time of one of the FRBs. We do not detect any significant GW emission from any of the events. Instead, using a short-duration GW search (for bursts ≤1 s) we derive 50% (90%) upper limits of 1048 (1049) erg for GWs at 300 Hz and 1049 (1050) erg at 2 kHz, and constrain the GW-to-radio energy ratio to ≤1014−1016. We also derive upper limits from a long-duration search for bursts with durations between 1 and 10 s. These represent the strictest upper limits on concurrent GW emission from FRBs

Swift-BAT GUANO follow-up of gravitational-wave triggers in the Third LIGO–Virgo–KAGRA Observing Run

We present results from a search for X-ray/gamma-ray counterparts of gravitational-wave (GW) candidates from the third observing run (O3) of the LIGO–Virgo–KAGRA network using the Swift Burst Alert Telescope (Swift-BAT). The search includes 636 GW candidates received with low latency, 86 of which have been confirmed by the offline analysis and included in the third cumulative Gravitational-Wave Transient Catalogs (GWTC-3). Targeted searches were carried out on the entire GW sample using the maximum-likelihood Non-imaging Transient Reconstruction and Temporal Search pipeline on the BAT data made available via the GUANO infrastructure. We do not detect any significant electromagnetic emission that is temporally and spatially coincident with any of the GW candidates. We report flux upper limits in the 15–350 keV band as a function of sky position for all the catalog candidates. For GW candidates where the Swift-BAT false alarm rate is less than 10−3 Hz, we compute the GW–BAT joint false alarm rate. Finally, the derived Swift-BAT upper limits are used to infer constraints on the putative electromagnetic emission associated with binary black hole mergers

Clinical applications of PD-L1 bioassays for cancer immunotherapy

Abstract Programmed death ligand 1 (PD-L1) has emerged as a biomarker that can help to predict responses to immunotherapies targeted against PD-L1 and its receptor (PD-1). Companion tests for evaluating PD-L1 expression as a biomarker of response have been developed for many cancer immunotherapy agents. These assays use a variety of detection platforms at different levels (protein, mRNA), employ diverse biopsy and surgical samples, and have disparate positivity cutoff points and scoring systems, all of which complicate the standardization of clinical decision-making. This review summarizes the current understanding and ongoing investigations regarding PD-L1 expression as a potential biomarker for clinical outcomes of anti-PD-1/PD-L1 immunotherapy