Characterizing web pornography consumption from passive measurements

Web pornography represents a large fraction of the Internet traffic, with thousands of websites and millions of users. Studying web pornography consumption allows understanding human behaviors and it is crucial for medical and psychological research. However, given the lack of public data, these works typically build on surveys, limited by different factors, e.g. unreliable answers that volunteers may (involuntarily) provide. In this work, we collect anonymized accesses to pornography websites using HTTP-level passive traces. Our dataset includes about $15\,000$ broadband subscribers over a period of 3 years. We use it to provide quantitative information about the interactions of users with pornographic websites, focusing on time and frequency of use, habits, and trends. We distribute our anonymized dataset to the community to ease reproducibility and allow further studies.Comment: Passive and Active Measurements Conference 2019 (PAM 2019). 14 pages, 7 figure

De novo mutations in regulatory elements in neurodevelopmental disorders

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordWe previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. Our findings represent a robust estimate of the contribution of de novo mutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasize the importance of combining functional and evolutionary evidence to identify regulatory causes of genetic disorders.Health Innovation Challenge FundWellcome TrustUK Department of HealthWellcome Trust Sanger Institut

Is Gly16Arg β₂ Receptor Polymorphism Related to Impulse Oscillometry in a Real-Life Asthma Clinic Setting?

PURPOSE: We evaluated whether Gly16Arg beta2-receptor genotype relates to impulse oscillometry (IOS) in a real-life clinic setting. METHODS: Patients with persistent asthma taking inhaled corticosteroid ± long-acting beta-agonist (ICS ± LABA) were evaluated. We compared genotype groups comprising either no Arg copies (i.e. GlyGly) versus one or two Arg copies (i.e. ArgArg or ArgGly). IOS outcomes included total airway resistance at 5 Hz (R5), central airway resistance at 20 Hz (R20), peripheral airway resistance (R5–R20), reactance at 5 Hz, area under reactance curve (AX) and resonant frequency (RF). In addition, we recorded ACQ-5 and salbutamol use. RESULTS: One hundred and twelve ICS-treated asthmatic patients (mean ICS dose 1238 µg/day), mean age 43 years, ACQ 2.34, FEV1 82 %, R5 177 % were identified—89 were also taking LABA. 61 patients were GlyGly, while 14 were ArgArg and 37 were ArgGly. There were no significant differences in IOS outcomes, ACQ or salbutamol use between the genotypes. The allelic risk (as odds ratio) for less well-controlled asthma (as ACQ > 1.5) was 1.1 (95 % CI 0.72–1.68) in relation to each Arg copy with a corresponding odds ratio for abnormal R5–R20 > 0.07kPA/l.s being 0.91 (95 % CI 0.57–1.44). 71 % of patients had an ACQ > 1.5 in the GlyGly group, versus 67 % in GlyArg/ArgArg group, with corresponding figures for abnormal R5–R20 > 0.07 kPa/l.s being 69 versus 73 %. CONCLUSION: In a real-life clinic setting for patients with poorly controlled persistent asthma taking ICS ± LABA, we found no evidence of any relationship of Gly16Arg to IOS, ACQ or salbutamol use

Characterizing Web Pornography Consumption from Passive Measurements

Web pornography represents a large fraction of the Internet traffic, with thousands of websites and millions of users. Studying web pornography consumption allows understanding human behaviors and it is crucial for medical and psychological research. However, given the lack of public data, these works typically build on surveys, limited by different factors, \eg unreliable answers that volunteers may (involuntarily) provide. In this work, we collect anonymized accesses to pornography websites using HTTP-level passive traces. Our dataset includes about 15,000 broadband subscribers over a period of 3 years. We use it to provide quantitative information about the interactions of users with pornographic websites, focusing on time and frequency of use, habits, and trends. We distribute our anonymized dataset to the community to ease reproducibility and allow further studies

Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders

How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark the fidelity of stem cell differentiation or cell programming, or interpret the pathogenicity of noncoding variation. Here, we study histone modifications across thirteen tissues during human organogenesis. We integrate the data with transcription to build an overview of how the human genome differentially regulates alternative organ fates including by repression. Promoters from nearly 20,000 genes partition into discrete states. Key developmental gene sets are actively repressed outside of the appropriate organ without obvious bivalency. Candidate enhancers, functional in zebrafish, allow imputation of tissue-specific and shared patterns of transcription factor binding. Overlaying more than 700 noncoding mutations from patients with developmental disorders allows correlation to unanticipated target genes. Taken together, the data provide a comprehensive genomic framework for investigating normal and abnormal human development

The development and validation of measures to assess cooking skills and food skills

BACKGROUND: With the increase use of convenience food and eating outside the home environment being linked to the obesity epidemic, the need to assess and monitor individuals cooking and food skills is key to help intervene where necessary to promote the usage of these skills. Therefore, this research aimed to develop and validate a measure for cooking skills and one for food skills, that are clearly described, relatable, user-friendly, suitable for different types of studies, and applicable across all sociodemographic levels. METHODS: Two measures were developed in light of the literature and expert opinion and piloted for clarity and ease of use. Following this, four studies were undertaken across different cohorts (including a sample of students, both 'Food preparation novices' and 'Experienced food preparers', and a nationally representative sample) to assess temporal stability, psychometrics, internal consistency reliability and construct validity of both measures. Analysis included T-tests, Pearson's correlations, factor analysis, and Cronbach's alphas, with a significance level of 0.05. RESULTS: Both measures were found to have a significant level of temporal stability (P < 0.001). Factor analysis revealed three factors with eigenvalues over 1, with two items in a third factor outside the two suggested measures. The internal consistency reliability for the cooking skills confidence measure ranged from 0.78 to 0.93 across all cohorts. The food skills confidence measure's Cronbach's alpha's ranged from 0.85 to 0.94. The two measures also showed a high discriminate validity as there were significant differences (P < 0.05 for cooking skills confidence and P < 0.01 for food skills confidence) between Food preparation novices' and 'Experienced food preparers.' CONCLUSIONS: The cooking skills confidence measure and the food skills confidence measure have been shown to have a very satisfactory reliability, validity and are consistent over time. Their user-friendly applicability make both measures highly suitable for large scale cross-sectional, longitudinal and intervention studies to assess or monitor cooking and food skills levels and confidence

Altered ureteric branching morphogenesis and nephron endowment in offspring of diabetic and insulin-treated pregnancy

<div><p>There is strong evidence from human and animal models that exposure to maternal hyperglycemia during <i>in utero</i> development can detrimentally affect fetal kidney development. Notwithstanding this knowledge, the precise effects of diabetic pregnancy on the key processes of kidney development are unclear due to a paucity of studies and limitations in previously used methodologies. The purpose of the present study was to elucidate the effects of hyperglycemia on ureteric branching morphogenesis and nephrogenesis using unbiased techniques. Diabetes was induced in pregnant C57Bl/6J mice using multiple doses of streptozotocin (STZ) on embryonic days (E) 6.5-8.5. Branching morphogenesis was quantified <i>ex vivo</i> using Optical Projection Tomography, and nephrons were counted using unbiased stereology. Maternal hyperglycemia was recognised from E12.5. At E14.5, offspring of diabetic mice demonstrated fetal growth restriction and a marked deficit in ureteric tip number (control 283.7±23.3 vs. STZ 153.2±24.6, mean±SEM, <i>p</i>&lt;0.01) and ureteric tree length (control 33.1±2.6 mm vs. STZ 17.6±2.7 mm, <i>p</i> = 0.001) vs. controls. At E18.5, fetal growth restriction was still present in offspring of STZ dams and a deficit in nephron endowment was observed (control 1246.2±64.9 vs. STZ 822.4±74.0, <i>p&lt;</i>0.001). Kidney malformations in the form of duplex ureter and hydroureter were a common observation (26%) in embryos of diabetic pregnancy compared with controls (0%). Maternal insulin treatment from E13.5 normalised maternal glycaemia but did not normalise fetal weight nor prevent the nephron deficit. The detrimental effect of hyperglycemia on ureteric branching morphogenesis and, in turn, nephron endowment in the growth-restricted fetus highlights the importance of glycemic control in early gestation and during the initial stages of renal development.</p> </div