Summary Although low-grade gliomas (LGG) have a less aggressive course than do high-grade gliomas, the outcome of these tumours is ultimately fatal in most patients. Both the tumour and its treatment ...can cause disabling morbidity, particularly of cognitive functions. Because many patients present with seizures only, with no other signs and symptoms, maintenance of quality of life and function constitutes a particular challenge in LGG. The slow growth pattern of most LGG, and the rare radiological true responses despite a favourable clinical response to treatment, interferes with the use of progression-free survival as the primary endpoint in trials. Overall survival as an endpoint brings logistical challenges, and is sensitive to other non-investigational salvage therapies. Clinical trials for LGG need to consider other measures of patient benefit such as cognition, symptom burden, and seizure activity, to establish whether improved survival is reflected in prolonged wellbeing. This Review investigates clinical and imaging endpoints in trials of LGG, and provides response assessment in neuro-oncology (RANO) criteria for non-enhancing tumours. Additionally, other measures for patients with brain tumours that assess outcome are described. Similar considerations are relevant for trials of high-grade gliomas, although for these tumours survival is shorter and survival endpoints generally have more value than they do for LGG.
Summary
The emergence of coronavirus disease 2019 (COVID‐19) has led to high demand for intensive care services worldwide. However, the mortality of patients admitted to the intensive care unit (ICU) ...with COVID‐19 is unclear. Here, we perform a systematic review and meta‐analysis, in line with PRISMA guidelines, to assess the reported ICU mortality for patients with confirmed COVID‐19. We searched MEDLINE, EMBASE, PubMed and Cochrane databases up to 31 May 2020 for studies reporting ICU mortality for adult patients admitted with COVID‐19. The primary outcome measure was death in intensive care as a proportion of completed ICU admissions, either through discharge from the ICU or death. The definition thus did not include patients still alive on ICU. Twenty‐four observational studies including 10,150 patients were identified from centres across Asia, Europe and North America. In‐ICU mortality in reported studies ranged from 0 to 84.6%. Seven studies reported outcome data for all patients. In the remaining studies, the proportion of patients discharged from ICU at the point of reporting varied from 24.5 to 97.2%. In patients with completed ICU admissions with COVID‐19 infection, combined ICU mortality (95%CI) was 41.6% (34.0–49.7%), I2 = 93.2%). Sub‐group analysis by continent showed that mortality is broadly consistent across the globe. As the pandemic has progressed, the reported mortality rates have fallen from above 50% to close to 40%. The in‐ICU mortality from COVID‐19 is higher than usually seen in ICU admissions with other viral pneumonias. Importantly, the mortality from completed episodes of ICU differs considerably from the crude mortality rates in some early reports.
Abstract
Attosecond chronoscopy is central to the understanding of ultrafast electron dynamics in matter from gas to the condensed phase with attosecond temporal resolution. It has, however, not yet ...been possible to determine the timing of individual partial waves, and steering their contribution has been a substantial challenge. Here, we develop a polarization-skewed attosecond chronoscopy serving as a partial wave meter to reveal the role of each partial wave from the angle-resolved photoionization phase shifts in rare gas atoms. We steer the relative ratio between different partial waves and realize a magnetic-sublevel-resolved atomic phase shift measurement. Our experimental observations are well supported by time-dependent R-matrix numerical simulations and analytical soft-photon approximation analysis. The symmetry-resolved, partial-wave analysis identifies the transition rate and phase shift property in the attosecond photoelectron emission dynamics. Our findings provide critical insights into the ubiquitous attosecond optical timer and the underlying attosecond photoionization dynamics.
The goal of nonrestorative or non- and microinvasive caries treatment (fluoride- and nonfluoride-based interventions) is to manage the caries disease process at a lesion level and minimize the loss ...of sound tooth structure. The purpose of this systematic review and network meta-analysis was to summarize the available evidence on nonrestorative treatments for the outcomes of 1) arrest or reversal of noncavitated and cavitated carious lesions on primary and permanent teeth and 2) adverse events. We included parallel and split-mouth randomized controlled trials where patients were followed for any length of time. Studies were identified with MEDLINE and Embase via Ovid, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews. Pairs of reviewers independently conducted the selection of studies, data extraction, risk-of-bias assessments, and assessment of the certainty in the evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Data were synthesized with a random effects model and a frequentist approach. Forty-four trials (48 reports) were eligible, which included 7,378 participants and assessed the effect of 22 interventions in arresting or reversing noncavitated or cavitated carious lesions. Four network meta-analyses suggested that sealants + 5% sodium fluoride (NaF) varnish, resin infiltration + 5% NaF varnish, and 5,000-ppm F (1.1% NaF) toothpaste or gel were the most effective for arresting or reversing noncavitated occlusal, approximal, and noncavitated and cavitated root carious lesions on primary and/or permanent teeth, respectively (low- to moderate-certainty evidence). Study-level data indicated that 5% NaF varnish was the most effective for arresting or reversing noncavitated facial/lingual carious lesions (low certainty) and that 38% silver diamine fluoride solution applied biannually was the most effective for arresting advanced cavitated carious lesions on any coronal surface (moderate to high certainty). Preventing the onset of caries is the ultimate goal of a caries management plan. However, if the disease is present, there is a variety of effective interventions to treat carious lesions nonrestoratively.
Streptozotocin (STZ)-induced diabetes mellitus (DM) offers a very cost-effective and expeditious technique that can be used in most strains of rodents, opening the field of DM research to an array of ...genotypic and phenotypic options that would otherwise be inaccessible. Despite widespread use of STZ in small animal models, the data available concerning drug preparation, dosing and administration, time to onset and severity of DM, and any resulting moribundity and mortality are often limited and inconsistent. Because of this, investigators inexperienced with STZ-induced diabetes may find it difficult to precisely design new studies with this potentially toxic chemical and account for the severity of DM it is capable of inducing. Until a better option becomes available, attempts need to be made to address shortcomings with current STZ-induced DM models. In this paper we review the literature and provide data from our pancreatic islet transplantation experiments using single high-dose STZ-induced DM in NCr athymic nude mice with hopes of providing clarification for study design, suggesting refinements to the process, and developing a more humane process of chemical diabetes induction.
Summary
The COVID‐19 pandemic continues to cause critical illness and deaths internationally. Up to 31 May 2020, mortality in patients admitted to intensive care units (ICU) with COVID‐19 was 41.6%. ...Since then, changes in therapeutics and management may have improved outcomes. Also, data from countries affected later in the pandemic are now available. We searched MEDLINE, Embase, PubMed and Cochrane databases up to 30 September 2020 for studies reporting ICU mortality among adult patients with COVID‐19 and present an updated systematic review and meta‐analysis. The primary outcome measure was death in intensive care as a proportion of completed ICU admissions, either through discharge from intensive care or death. We identified 52 observational studies including 43,128 patients, and first reports from the Middle East, South Asia and Australasia, as well as four national or regional registries. Reported mortality was lower in registries compared with other reports. In two regions, mortality differed significantly from all others, being higher in the Middle East and lower in a single registry study from Australasia. Although ICU mortality (95%CI) was lower than reported in June (35.5% (31.3–39.9%) vs. 41.6% (34.0–49.7%)), the absence of patient‐level data prevents a definitive evaluation. A lack of standardisation of reporting prevents comparison of cohorts in terms of underlying risk, severity of illness or outcomes. We found that the decrease in ICU mortality from COVID‐19 has reduced or plateaued since May 2020 and note the possibility of some geographical variation. More standardisation in reporting would improve the ability to compare outcomes from different reports.
These evidence-based guidelines have been produced after a systematic literature review of a range of issues involving prevention, diagnosis and treatment of hospital-acquired pneumonia (HAP). ...Prevention is structured into sections addressing general issues, equipment, patient procedures and the environment, whereas in treatment, the structure addresses the use of antimicrobials in prevention and treatment, adjunctive therapies and the application of clinical protocols. The sections dealing with diagnosis are presented against the clinical, radiological and microbiological diagnosis of HAP. Recommendations are also made upon the role of invasive sampling and quantitative microbiology of respiratory secretions in directing antibiotic therapy in HAP/ventilator-associated pneumonia.
Photometric surveys such as Kepler have the precision to identify exoplanet and eclipsing binary candidates from only a single transit. K2, with its 75 d campaign duration, is ideally suited to ...detect significant numbers of single-eclipsing objects. Here we develop a Bayesian transit-fitting tool (‘Namaste: An Mcmc Analysis of Single Transit Exoplanets’) to extract orbital information from single transit events. We achieve favourable results testing this technique on known Kepler planets, and apply the technique to seven candidates identified from a targeted search of K2 campaigns 1, 2 and 3. We find EPIC203311200 to host an excellent exoplanet candidate with a period, assuming zero eccentricity, of
$540 ^{+410}_{-230}$
d and a radius of 0.51 ± 0.05R
Jup. We also find six further transit candidates for which more follow-up is required to determine a planetary origin. Such a technique could be used in the future with TESS, PLATO and ground-based photometric surveys such as NGTS, potentially allowing the detection of planets in reach of confirmation by Gaia.
We use R-matrix with time-dependence theory, with spin-orbit effects included, to study krypton irradiated by two time-delayed extreme ultraviolet ultrashort pulses. The first pulse excites the atom ...to 4s24p55s. The second pulse then excites 4s4p65s autoionizing levels, whose population can be observed through their subsequent decay. By varying the time delay between the two pulses, we are able to control the excitation pathway to the autoionizing states. The use of cross-polarized light pulses allows us to isolate the two-photon pathway, with one photon taken from each pulse.
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