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Prior to becoming chondritic meteorites, primordial solids were a poorly consolidated mix of mm-scale igneous inclusions (chondrules) and high-porosity sub-μm dust (matrix). We used high-resolution numerical simulations to track the effect of impact-induced compaction on these materials. Here we show that impact velocities as low as 1.5 km s −1 were capable of heating the matrix to >1,000 K, with pressure–temperature varying by >10 GPa and >1,000 K over ~100 μm. Chondrules were unaffected, acting as heat-sinks: matrix temperature excursions were brief. As impact-induced compaction was a primary and ubiquitous process, our new understanding of its effects requires that key aspects of the chondrite record be re-evaluated: palaeomagnetism, petrography and variability in shock level across meteorite groups. Our data suggest a lithification mechanism for meteorites, and provide a ‘speed limit’ constraint on major compressive impacts that is inconsistent with recent models of solar system orbital architecture that require an early, rapid phase of main-belt collisional evolution. Collisions between primordial planetesimals led to the formation of our asteroids and meteorites. Here, the authors use modelling to explore the compaction of planetsimals, tracking how pressure, temperature and porosity may have varied during the impacts, helping interpret early Solar System processes.

This study aimed to investigate the distribution of congenital toxoplasmosis in the state of Minas Gerais, Southeastern Brazil and describe the demographic and socioeconomic profile of the municipalities associated with the disease. An ecological study was conducted using socioeconomic indicators of a database (MGSSRI) created by Fundação João Pinheiro (a government technical support agency of Minas Gerais), in order to show the development of the municipalities in the state. The prevalence of toxoplasmosis was the outcome and the items of the MGSSRI were the explanatory variables. Of 146 307 newborns screened (November 2006 to May 2007), 190 had congenital toxoplasmosis, yielding a prevalence of 1·3/1000, ranging from 0 to 76·9/1000 in the municipalities. The multivariate model indicated a higher occurrence of toxoplasmosis in municipalities with smaller populations and worse indexes of tax performance. Congenital toxoplasmosis appears to be a neglected disease in the state of Minas Gerais, given the high prevalence found and its concentration in municipalities with worse socioeconomic indexes.

Purpose The school environment may positively influence student health behaviours and learning. This study aimed to investigate the association between cities' quality of education and adolescent students' oral health-related behaviours. Methods Cross-sectional study using data of the 2015 Brazilian National Adolescent School-Based Health Survey and other public databases. The sample was composed of adolescents ( N  = 23,674) from public schools of the 27 Brazilian state capitals. Outcomes were four oral health-related behaviours: toothbrushing, sweets and soft-drink consumption, and dental visits. The explanatory variable was the cities' quality of education, measured by the Brazilian Basic Education Development Index. Covariates were individual (sociodemographic) and contextual (socioeconomic, oral health coverage and oral health-promoting schools). Multilevel logistic regression was performed considering two levels: individual (adolescents) and contextual (city). Results The prevalence of the outcomes were: low daily toothbrushing frequency 6.7% (95% CI 6.0–7.4); high weekly sweets consumption 41.5% (95% CI 40.3–42.7); high weekly soft-drink consumption 28.5% (95% CI 27.2–29.9); and low frequency of annual dental visits 31.2% (95% CI 30.1–32.3). In the adjusted models, cities whose schools had higher scores of education quality were more likely to have students with low toothbrushing frequency and high frequency of sweets consumption. Conclusion The cities' quality of education was associated with unhealthy oral health-related behaviours, particularly the frequency of toothbrushing and sweets consumption. Therefore, appropriate health promotion strategies as well as high-quality education are needed in schools.

Aim To evaluate the effect of malocclusion among adolescents on their families’ oral health-related quality of life (OHRQoL). Methods A consecutive sample of 125 parents/caregivers of Brazilian adolescents was chosen. Participants were asked to answer the Brazilian version of the Family Impact Scale (FIS). The main independent variable was adolescents’ malocclusion, which was measured with the Dental Aesthetic Index. Gender, age, and family monthly income were the other independent variables. Data analysis involved descriptive statistics, Mann–Whitney test, and univariate and multiple logistic regression. Results Among the 125 participants initially admitted to the present study, two were excluded so that 123 parents/caregivers participated providing a response rate of 98.4 %. The overall FIS score revealed a more frequent effect for families of adolescents who presented malocclusion ( P  = 0.005). Significant findings were also observed for parental emotions ( P  = 0.022), family conflict ( P  = 0.010), and financial burden ( P  = 0.010) subscales. When the independent variables family monthly income and malocclusion were inserted together in the regression model, families with a monthly income of <5 Brazilian minimum wages (approximately US$ 325.00 per month) were more likely to have a worse OHRQoL, and families whose adolescents presented malocclusion were 3.55 more likely to have a poorer quality of life than those families whose adolescents did not present malocclusion. Conclusions Families of adolescents with malocclusion were more likely to report a worse OHRQoL.

Aim To evaluate the effect of the first 12 months of orthodontic treatment on the quality of life of Brazilian adolescents and to examine the evaluative properties of the short form of the Child Perceptions Questionnaire (CPQ 11–14 ). Study design and methods This study involved a sample of 101 adolescents undergoing orthodontic treatment with a fixed appliance. Participants were asked to answer the Brazilian version of the short form of the CPQ 11–14 before treatment (T1) and 12 months after the placement of the fixed appliance (T2). Statistical analysis was carried out using the Wilcoxon signed-rank test and the Bonferroni correction for the overall score and the short form of the CPQ 11–14 subscales. Responsiveness of the measure and the minimal clinically important difference (MCID) were also evaluated. Results and statistics Out of the 101 individuals originally admitted to this study, three were excluded due to cessation of treatment and failure to return the questionnaire, providing a response rate of 97.0 %. Statistically, significant improvements were found in the overall score ( P  < 0.001) as well as in both emotional well-being ( P  < 0.001) and social well-being ( P  = 0.007) subscales. The reductions in score were associated with an effect of size showing moderate clinically meaningful changes in the overall score and in the functional limitations, emotional well-being and social well-being. The MCID was 3.35. Conclusion The first 12 months of orthodontic treatment with a fixed appliance had a positive effect on the quality of life of western adolescents.

Previously optimised postharvest treatments were compared to conventional chlorinated water treatment in terms of their effects on the overall quality of tomato (‘Zinac’) during storage at 10 °C. The treatments in question were water heat treatment (WHT = 40 °C, 30 min), ultrasounds (US = 45 kHz, 80 %, 30 min), thermosonication (TS = 40 °C, 30 min, 45 kHz, 80 %) and ultraviolet irradiation (UV-C: 0.97 kJ m −2 ). The quality factors evaluated were colour, texture, sensorial analysis, mass loss, antioxidant capacity, total phenolic content, peroxidase and pectin methylesterase enzymatic activities, and microbial load reduction. The results demonstrate that all treatments tested preserve tomato quality to some extent during storage at 10 °C. WHT, TS and UV-C proved to be more efficient on minimising colour and texture changes with the additional advantage of microbial load reduction, leading to a shelf life extension when compared to control trials. However, at the end of storage, with exception of WHT samples, the antioxidant activity and phenolic content of treated samples was lower than for control samples. Moreover, sensorial results were well correlated with instrumental colour experimental data. This study presents alternative postharvest technologies that improve tomato (Zinac) quality during shelf life period and minimise the negative impact of conventional chlorinated water on human safety, health and environment.

Surface morphologies and space weathering features of Ryugu samples

Targeted inhibition of the PD-L1–PD-1 pathway might be further amplified through combination of PD-1 or PD-L1 inhibitors with novel anti-TIGIT inhibitory immune checkpoint agents, such as tiragolumab. In the CITYSCAPE trial, we aimed to assess the preliminary efficacy and safety of tiragolumab plus atezolizumab (anti-PD-L1) therapy as first-line treatment for non-small-cell lung cancer (NSCLC). CITYSCAPE is a phase 2, randomised, double-blind, placebo-controlled trial. Patients with chemotherapy-naive, PD-L1-positive (defined as a tumour proportion score of ≥1% by 22C3 immunohistochemistry pharmDx assay; Dako, Agilent Technologies, Santa Clara, CA, USA) recurrent or metastatic NSCLC with measurable disease, Eastern Cooperative Oncology Group performance status of 0 or 1, and no EGFR or ALK alterations were enrolled from 41 clinics in Europe, Asia, and the USA. Patients were randomly assigned (1:1), via an interactive voice or web-based response system, to receive tiragolumab (600 mg) plus atezolizumab (1200 mg) or placebo plus atezolizumab intravenously once every 3 weeks. Investigators and patients were masked to treatment assignment. The co-primary endpoints were investigator-assessed objective response rate and progression-free survival as per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population, analysed after approximately 80 progression-free survival events had been observed in the primary population. Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03563716, and is ongoing. Patients were enrolled between Aug 10, 2018, and March 20, 2019. At data cutoff for the primary analysis (June 30, 2019), 135 of 275 patients assessed for eligibility were randomly assigned to receive tiragolumab plus atezolizumab (67 [50%]) or placebo plus atezolizumab (68 [50%]). In this primary analysis, after a median follow-up of 5·9 months (4·6–7·6, in the intention-to-treat population, 21 patients (31·3% [95% CI 19·5–43·2]) in the tiragolumab plus atezolizumab group versus 11 patients (16·2% [6·7–25·7]) in the placebo plus atezolizumab group had an objective response (p=0·031). Median progression-free survival was 5·4 months (95% CI 4·2–not estimable) in the tiragolumab plus atezolizumab group versus 3·6 months (2·7–4·4) in the placebo plus atezolizumab group (stratified hazard ratio 0·57 [95% CI 0·37–0·90], p=0·015). 14 (21%) patients receiving tiragolumab plus atezolizumab and 12 (18%) patients receiving placebo plus atezolizumab had serious treatment-related adverse events. The most frequently reported grade 3 or worse treatment-related adverse event was lipase increase (in six [9%] patients in the tiragolumab plus atezolizumab group vs two [3%] in the placebo plus atezolizumab group). Two treatment-related deaths (of pyrexia and infection) occurred in the tiragolumab plus atezolizumab group. Tiragolumab plus atezolizumab showed a clinically meaningful improvement in objective response rate and progression-free survival compared with placebo plus atezolizumab in patients with chemotherapy-naive, PD-L1-positive, recurrent or metastatic NSCLC. Tiragolumab plus atezolizumab was well tolerated, with a safety profile generally similar to that of atezolizumab alone. These findings demonstrate that tiragolumab plus atezolizumab is a promising immunotherapy combination for the treatment of previously untreated, locally advanced unresectable or metastatic NSCLC. F Hoffmann-La Roche and Genentech.

In a randomized trial involving patients with previously untreated advanced non–small-cell lung cancer, pembrolizumab was associated with a higher response rate, longer progression-free and overall survival, and fewer adverse events than was platinum-based chemotherapy. Approximately 23 to 28% of patients with advanced non–small-cell lung cancer (NSCLC) have a high level of programmed death ligand 1 (PD-L1) expression, which is defined as membranous PD-L1 expression on at least 50% of tumor cells, regardless of the staining intensity (i.e., a PD-L1 tumor proportion score of 50% or greater). 1 , 2 Data from the phase 1 KEYNOTE-001 and phase 3 KEYNOTE-010 studies indicated that patients with advanced NSCLC and a PD-L1 tumor proportion score of 50% or greater were more likely than those with lower tumor proportion scores to have a response to pembrolizumab, a highly selective, humanized . . .

Patients with resectable lung cancer were assigned to neoadjuvant pembrolizumab or placebo plus chemotherapy and adjuvant pembrolizumab or placebo. Two-year event-free survival was 62.4% with pembrolizumab and 40.6% with placebo.