Parents’ role in adolescents’ leisure time use: From goals to parenting practices

Inspired by Ann Swidler’s toolkit theory, this qualitative study aims to achieve a better understanding of social class differences in parenting practices and, in turn, in young people’s leisure time use. To that end, 32 semi-structured face-to-face interviews with parents from middle- and working-class families were conducted in a small city in Belgium. An inductive thematic analysis revealed substantial social class differences with respect to three parenting practices: (1) setting an example, (2) resolving conflicts and (3) facilitating leisure activities. The interviews showed that these differences were mainly linked to social class differences in parents’ resources: working-class parents more often lacked flexible time, financial resources, an extensive social network on which they could rely and the institutionally required attitudes, skills and experience to engage in the above-mentioned parenting practices. We conclude that young people’s (continued) institutional leisure participation puts high requirements on parents and not all (working-class) parents are able to live up to such requirements. In that way, contemporary leisure settings reproduce rather than mitigate inequality in the use of leisure time

Shallow whole-genome sequencing of plasma cell-free DNA accurately differentiates small from non-small cell lung carcinoma

Background Accurate lung cancer classification is crucial to guide therapeutic decisions. However, histological subtyping by pathologists requires tumor tissue-a necessity that is often intrinsically associated with procedural difficulties. The analysis of circulating tumor DNA present in minimal-invasive blood samples, referred to as liquid biopsies, could therefore emerge as an attractive alternative. Methods Concerning adenocarcinoma, squamous cell carcinoma, and small cell carcinoma, our proof of concept study investigates the potential of liquid biopsy-derived copy number alterations, derived from single-end shallow whole-genome sequencing (coverage 0.1-0.5x), across 51 advanced stage lung cancer patients. Results Genomic abnormality testing reveals anomalies in 86.3% of the liquid biopsies (16/20 for adenocarcinoma, 13/16 for squamous cell, and 15/15 for small cell carcinoma). We demonstrate that copy number profiles from formalin-fixed paraffin-embedded tumor biopsies are well represented by their liquid equivalent. This is especially valid within the small cell carcinoma group, where paired profiles have an average Pearson correlation of 0.86 (95% CI 0.79-0.93). A predictive model trained with public data, derived from 843 tissue biopsies, shows that liquid biopsies exhibit multiple deviations that reflect histological classification. Most notably, distinguishing small from non-small cell lung cancer is characterized by an area under the curve of 0.98 during receiver operating characteristic analysis. Additionally, we investigated how deeper paired-end sequencing, which will eventually become feasible for routine diagnosis, empowers tumor read enrichment by insert size filtering: for all of the 29 resequenced liquid biopsies, the tumor fraction could be increased in silico, thereby "rescuing" three out of five cases with previously undetectable alterations. Conclusions Copy number profiling of cell-free DNA enables histological classification. Since shallow whole-genome sequencing is inexpensive and often fully operational at routine molecular laboratories, this finding has current diagnostic potential, especially for patients with lesions that are difficult to reach

Comparative study of antioxidant defence mechanisms in marine fish fed variable levels of oxidised oil and vitamin E

The aim of the study was to compare the antioxidant systems in juvenile marine fish of commercial importance in European aquaculture, namely turbot (Scophthalmus maximus), halibut (Hippoglossus hippoglossus) and gilthead sea bream (Sparus aurata). The present dietary trial was specifically designed to investigate the antioxidant effects of vitamin E under moderate oxidising conditions, including high dietary levels of highly unsaturated fatty acids and the feeding of oxidised oils. The objective was to induce a stressful pro-oxidant status to enable characterisation of the biochemical responses to peroxidative stress without causing unnecessary suffering to the experimental animals or high mortalities during the trials. Both sea bream and turbot showed excellent growth, whereas growth was poorer in halibut. Dietary oxidised oil significantly reduced growth in turbot and especially in halibut, but not in sea bream. Vitamin E improved growth in sea bream fed oxidised oil but not in turbot or halibut. However, vitamin E supplementation appeared to improve survival in all three species. In sea bream and turbot, liver antioxidant defence enzyme activities were generally increased by feeding peroxidised oil and reduced by vitamin E. Conversely, in halibut, the liver antioxidant defence enzyme activities were not increased by feeding peroxidised oil and only superoxide dismutase was reduced by feeding vitamin E. Consistent with these data, feeding oxidised oil increased lipid peroxidation products in halibut, but generally not in sea bream or turbot. Furthermore, lipid peroxidation products were generally reduced by dietary vitamin E in both sea bream and turbot, but not in halibut. Therefore, halibut liver antioxidant defence enzymes did not respond to dietary oxidised oil or vitamin E as occurred in turbot and, especially sea bream. This resulted in increased levels of lipid peroxides in halibut compared to turbot and sea bream in fish given dietary oxidised oil. In addition, supplemental vitamin E did not reduce lipid peroxides in halibut as it did in turbot and sea bream. The increased peroxidation stress in halibut may account for their poorer growth and survival in comparison to turbot and especially sea bream. Halibut were reared at a lower temperature, although relatively high for halibut, than either turbot or sea bream but they were also slightly younger/smaller fish and possibly, therefore, more developmentally immature, and either or all of these factors may be important in the lack of response of the liver enzymes in halibut

Definitions of disease burden across the spectrum of metastatic castration-sensitive prostate cancer: comparison by disease outcomes and genomics

BACKGROUND: Several definitions have attempted to stratify metastatic castrate-sensitive prostate cancer (mCSPC) into low and high-volume states. However, at this time, comparison of these definitions is limited. Here we aim to compare definitions of metastatic volume in mCSPC with respect to clinical outcomes and mutational profiles. METHODS: We performed a retrospective review of patients with biochemically recurrent or mCSPC whose tumors underwent somatic targeted sequencing. 294 patients were included with median follow-up of 58.3 months. Patients were classified into low and high-volume disease per CHAARTED, STAMPEDE, and two numeric (≤3 and ≤5) definitions. Endpoints including radiographic progression-free survival (rPFS), time to development of castration resistance (tdCRPC), and overall survival (OS) were evaluated with Kaplan-Meier survival curves and log-rank test. The incidence of driver mutations between definitions were compared. RESULTS: Median OS and tdCRPC were shorter for high-volume than low-volume disease for all four definitions. In the majority of patients (84.7%) metastatic volume classification did not change across all four definitions. High volume disease was significantly associated with worse OS for all four definitions (CHAARTED: HR 2.89; p < 0.01, STAMPEDE: HR 3.82; p < 0.01, numeric ≤3: HR 4.67; p < 0.01, numeric ≤5: HR 3.76; p < 0.01) however, were similar for high (p = 0.95) and low volume (p = 0.79) disease across all four definitions. Those with discordant classification tended to have more aggressive clinical behavior and mutational profiles. Patients with low-volume disease and TP53 mutation experienced a more aggressive course with rPFS more closely mirroring high-volume disease. CONCLUSIONS: The spectrum of mCSPC was confirmed across four different metastatic definitions for clinical endpoints and genetics. All definitions were generally similar in classification of patients, outcomes, and genetic makeup. Given these findings, the simplicity of numerical definitions might be preferred, especially when integrating metastasis directed therapy. Incorporation of tumor genetics may allow further refinement of current metastatic definitions

Two-Photon Imaging of Cortical Surface Microvessels Reveals a Robust Redistribution in Blood Flow after Vascular Occlusion

A highly interconnected network of arterioles overlies mammalian cortex to route blood to the cortical mantle. Here we test if this angioarchitecture can ensure that the supply of blood is redistributed after vascular occlusion. We use rodent parietal cortex as a model system and image the flow of red blood cells in individual microvessels. Changes in flow are quantified in response to photothrombotic occlusions to individual pial arterioles as well as to physical occlusions of the middle cerebral artery (MCA), the primary source of blood to this network. We observe that perfusion is rapidly reestablished at the first branch downstream from a photothrombotic occlusion through a reversal in flow in one vessel. More distal downstream arterioles also show reversals in flow. Further, occlusion of the MCA leads to reversals in flow through approximately half of the downstream but distant arterioles. Thus the cortical arteriolar network supports collateral flow that may mitigate the effects of vessel obstruction, as may occur secondary to neurovascular pathology

Unraveling the genomic underpinnings of advanced prostate cancer

Metastatic hormone-sensitive prostate cancer (mHSPC) is a highly heterogeneous malignancy with varied outcomes observed across patients. Genomic features have been associated with differential clinical characteristics and treatment outcomes, but it is not yet clear to what degree these features should guide clinical decision-making in mHSPC. Precision medicine in mHSPC care is today confounded by the multifocality and molecular heterogeneity often seen in PCa. In this thesis, we aim to resolve the genomic drivers of mHSPC disease and dissect the tumor heterogeneity with an ultimate goal of enhancing the integration of genomics in cancer practice. In a first phase, a thorough review of the literature to summarize the current understanding of genomic alterations in mHSPC in terms of both the prevalence of alterations involving specific pathways and the relationship of these alterations with clinical features was performed. This study showed that genomic alterations may have prognostic and predictive implications. Another key finding of this study was that genomic data from mHSPC patients varied greatly in terms of the clinical states of patients and the source of material, and that the current study designs, in which only one sample from the resected tumor is sequenced, are not optimized for the study of multifocality. In a second phase, we assessed the prognostic and predictive ability of a genomic signature to risk stratify outcomes for patients with oligometastatic PCa recurrences, by pooling the only two prospective randomized trials, STOMP and ORIOLE, of metastasis-directed therapy (MDT) versus observation in oligometastatic HSPC. In this study, we observed a high-risk mutational signature consisting of pathogenic alterations in ATM, BRCA1/2, Rb1 and TP53 that is highly prognostic and predictive in this patient population suggesting that future trials should integrate these biomarkers to better understand their role in patient selection. Next, we investigated whether lung involvement should be considered as a proxy of more indolent disease in patients with presenting with lung recurrences. To address this question, we determined the genomic alterations that characterize lung-recurrent mHSPC (i.e. patients with lung metastases after curative-intent treatment for PCa) through multi-region profiling of both primary and metastatic lung samples. We found that the presence of lung recurrences associates with clinical and genomic indolence, proposing the site of metastatic recurrence as stratification factor for future predictive models in mHPSC. A second aim was to develop a practical strategy to reliably genotype patients with metastases at first diagnosis of prostate cancer, which is known as de novo mHSPC. First, we explored the extent to which a single diagnostic biopsy captures the metastatic genotype in synchronous metastatic tissue/ctDNA. Clinically relevant alterations were often missed in these single-biopsy approaches due to the heterogeneity within the primary and metastases. Exploration of the relationship between primary and metastatic tumors revealed little genomic evolution in lung-recurrent mHSPC patients, whereas we found extensive polyclonal seeding in a significant proportion of the de novo mHSPC patients