Life in lockdown:A longitudinal study investigating the impact of the UK COVID-19 lockdown measures on lifestyle behaviours and mental health.

BACKGROUND: The COVID-19 pandemic led to the UK government enforcing lockdown restrictions to control virus transmission. Such restrictions present opportunities and barriers for physical activity and healthy eating. Emerging research suggests that in the early stages of the pandemic, physical activity levels decreased, consumption of unhealthy foods increased, while levels of mental distress increased. Our aims were to understand patterns of diet, physical activity, and mental health during the first lockdown, how these had changed twelve-months later, and the factors associated with change. METHODS: An online survey was conducted with UK adults (N = 636; 78% female) during the first national lockdown (May–June 2020). The survey collected information on demographics, physical activity, diet, mental health, and how participants perceived lifestyle behaviours had changed from before the pandemic. Participants who provided contact details were invited to complete a twelve-month follow-up survey (May–June 2021), 160 adults completed the survey at both time-points. Descriptive statistics, T-tests and McNemar Chi Square statistics were used to assess patterns of diet, physical activity, and mental health at baseline and change in behaviours between baseline and follow-up. Linear regression models were conducted to explore prospective associations between demographic and psycho-social variables at baseline with change in healthy eating habit, anxiety, and wellbeing respectively. RESULTS: Between baseline and follow-up, healthy eating habit strength, and the importance of and confidence in eating healthily reduced. Self-rated health (positively) and confidence in eating healthily (negatively) were associated with change in healthy eating habit. There were no differences between baseline and follow-up for depression or physical activity. Mean anxiety score reduced, and wellbeing increased, from baseline to follow-up. Living with children aged 12–17 (compared to living alone) was associated with an increase in anxiety, while perceiving mental health to have worsened during the first lockdown (compared to staying the same) was associated with reduced anxiety and an increase in mental wellbeing. CONCLUSIONS: While healthy eating habits worsened in the 12 months since the onset of the pandemic, anxiety and mental wellbeing improved. However, anxiety may have increased for parents of secondary school aged children. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-13888-1

Genetic Variation in an Individual Human Exome

There is much interest in characterizing the variation in a human individual, because this may elucidate what contributes significantly to a person's phenotype, thereby enabling personalized genomics. We focus here on the variants in a person's ‘exome,’ which is the set of exons in a genome, because the exome is believed to harbor much of the functional variation. We provide an analysis of the ∼12,500 variants that affect the protein coding portion of an individual's genome. We identified ∼10,400 nonsynonymous single nucleotide polymorphisms (nsSNPs) in this individual, of which ∼15–20% are rare in the human population. We predict ∼1,500 nsSNPs affect protein function and these tend be heterozygous, rare, or novel. Of the ∼700 coding indels, approximately half tend to have lengths that are a multiple of three, which causes insertions/deletions of amino acids in the corresponding protein, rather than introducing frameshifts. Coding indels also occur frequently at the termini of genes, so even if an indel causes a frameshift, an alternative start or stop site in the gene can still be used to make a functional protein. In summary, we reduced the set of ∼12,500 nonsilent coding variants by ∼8-fold to a set of variants that are most likely to have major effects on their proteins' functions. This is our first glimpse of an individual's exome and a snapshot of the current state of personalized genomics. The majority of coding variants in this individual are common and appear to be functionally neutral. Our results also indicate that some variants can be used to improve the current NCBI human reference genome. As more genomes are sequenced, many rare variants and non-SNP variants will be discovered. We present an approach to analyze the coding variation in humans by proposing multiple bioinformatic methods to hone in on possible functional variation

Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration

Acknowledgements We are indebted to Jim Humphries, JennyCorrigan, LizDarley, Elizabeth Joynson, Natalie Walters, Sara Wells and the whole necropsy, histology, genotyping and MLC ward 6 teams at MRC Harwell for excellent technical assistance. We thank the staff of the WTSI Illumina Bespoke Team for the RNA-seq data, the Sanger Mouse Genetics Project for the initial mouse characterization and Dr David Adams for critical reading of the manuscript. We also thank KOMP for the mouse embryonic stem cells carrying the knockout first promoter-less allele (tm1a(KOMP)Wtsi) within Zfp016. Conflict of Interest statement. None declared. Funding This work was funded by the UK Medical Research Council (MRC) to A.A.-A. and a Motor Neurone Disease Association (MNDA) project grant to A.A.-A. and EMCF. D.L.H.B. is a Wellcome Trust Senior Clinical Scientist Fellow and P.F. is a MRC/MNDA Lady Edith Wolfson Clinician Scientist Fellow. Funding to pay the Open Access publication charges for this article was provided by the MRC grant number: MC_UP_A390_1106.Peer reviewedPublisher PD

Droplet Generation by Disintegration of Oil Films at the Rim of a Rotating Disk

ABSTRACT A fundamental study has been performed to examine oil film disintegration mechanisms at the rim of a rotating disk. The configuration investigated is an abstraction of one of the droplet generation sources in an aero-engine bearing compartment. The paper aims to contribute to both the determination of directly applicable droplet characteristics and the establishment of a data-base that can be used for the development of droplet generation models. The near-term objectives of the study are (i) to identify disintegration modes relevant with respect to aeroengine bearing compartment operating conditions, (ii) to determine droplet sizes under those operating conditions, and (iii) to measure individual droplet diameter/velocity relationships. The long-term objective is to incorporate this information into advanced CFD-based design tools. The disintegration modes identified here were similar to previously reported flow regimes generated by rotary atomizer

Scar-like lesion on dorsal nose (cellular neurothekeoma)

Neurothekeomas are tumors of neural differentiation and of unknown origin that occur in females at the 2nd and 3rd decades of life. They usually affect the face with an unspecific clinical aspect. The histological features include cellular or mixoid differentiation and immunohistochemistry can be positive for protein s-100, vimentin and epithelilal membrane antigen (EMA)

A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal

The classification of neuroendocrine neoplasms (NENs) differs between organ systems and currently causes considerable confusion. A uniform classification framework for NENs at any anatomical location may reduce inconsistencies and contradictions among the various systems currently in use. The classification suggested here is intended to allow pathologists and clinicians to manage their patients with NENs consistently, while acknowledging organ-specific differences in classification criteria, tumor biology, and prognostic factors. The classification suggested is based on a consensus conference held at the International Agency for Research on Cancer (IARC) in November 2017 and subsequent discussion with additional experts. The key feature of the new classification is a distinction between differentiated neuroendocrine tumors (NETs), also designated carcinoid tumors in some systems, and poorly differentiated NECs, as they both share common expression of neuroendocrine markers. This dichotomous morphological subdivision into NETs and NECs is supported by genetic evidence at specific anatomic sites as well as clinical, epidemiologic, histologic, and prognostic differences. In many organ systems, NETs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, and/or the presence of necrosis; NECs are considered high grade by definition. We believe this conceptual approach can form the basis for the next generation of NEN classifications and will allow more consistent taxonomy to understand how neoplasms from different organ systems inter-relate clinically and genetically

Functional polymorphisms in the promoter regions of MMP2 and MMP3 are not associated with melanoma progression

<p>Abstract</p> <p>Background</p> <p>The matrix metalloproteinases (MMPs) are enzymes that cleave various components of the extracellular matrix (ECM) and basement membranes. MMPs are expressed in melanocytes and their overexpression has been linked to tumor development, progression and metastasis. At the genetic level, the following functional promoter polymorphisms are known to modify the gene transcription: -1306 C/T and -735 C/T in the MMP2 gene, and -1171 5A/6A in the MMP3 gene. Functional polymorphisms in MMP genes' promoter regions may modulate the risk for melanoma progression.</p> <p>Methods</p> <p>We evaluated MMP2 and MMP3 germline polymorphisms in a group of 1002 melanoma patients using PCR-based methods, including fragment size analysis and melting temperature profiles. Two-sided Chi-Square, Cochran-Armitage tests for trend, Fisher's exact tests, and Kendall's Tau tests were performed to evaluate the associations between genotype and various clinical and epidemiologic factors. Multivariate analyses were conducted using logistic regression, adjusting for known melanoma confounders such as age, sex, phenotypic index, moles, freckles, and race. Survival estimates were computed using the Kaplan-Meier method and differences in survival were assessed using the log rank test.</p> <p>Results</p> <p>All genotypes were in Hardy-Weinberg equilibrium. After adjustment for age, sex and phenotypic characteristics of melanoma risk, no significant associations were identified with the clinical, pathological, and epidemiological variables studied. The melting profile for MMP2 -735 C/T identified a new change in one sample. A new PCR-amplification followed by direct sequencing confirmed a heterozygote G to A substitution at position -729.</p> <p>Conclusion</p> <p>This study does not provide strong evidence for further investigation into the role of the MMP2 and MMP3 variants in melanoma progression.</p

The Diploid Genome Sequence of an Individual Human

Presented here is a genome sequence of an individual human. It was produced from ∼32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb) of contiguous sequence with approximately 7.5-fold coverage for any given region. We developed a modified version of the Celera assembler to facilitate the identification and comparison of alternate alleles within this individual diploid genome. Comparison of this genome and the National Center for Biotechnology Information human reference assembly revealed more than 4.1 million DNA variants, encompassing 12.3 Mb. These variants (of which 1,288,319 were novel) included 3,213,401 single nucleotide polymorphisms (SNPs), 53,823 block substitutions (2–206 bp), 292,102 heterozygous insertion/deletion events (indels)(1–571 bp), 559,473 homozygous indels (1–82,711 bp), 90 inversions, as well as numerous segmental duplications and copy number variation regions. Non-SNP DNA variation accounts for 22% of all events identified in the donor, however they involve 74% of all variant bases. This suggests an important role for non-SNP genetic alterations in defining the diploid genome structure. Moreover, 44% of genes were heterozygous for one or more variants. Using a novel haplotype assembly strategy, we were able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploid nature of the genome. These data depict a definitive molecular portrait of a diploid human genome that provides a starting point for future genome comparisons and enables an era of individualized genomic information

Revision of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis Classification Schema for Melanocytic Lesions: A Consensus Statement

IMPORTANCE A standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose. OBJECTIVE To revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health-funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG). EVIDENCE REVIEW Practicing dermatopathologists recruited from 40 US states participated in the 2-year REMI study and provided feedback on the MPATH-Dx version 1.0 tool. Independently, member dermatopathologists participating in an IMPSG workshop dedicated to the MPATH-Dx schema provided additional input for refining the MPATH-Dx tool. A reference panel of 3 dermatopathologists, the original authors of the MPATH-Dx version 1.0 tool, integrated all feedback into an updated and refined MPATH-Dx version 2.0. FINDINGS The new MPATH-Dx version 2.0 schema simplifies the original 5-class hierarchy into 4 classes to improve diagnostic concordance and to provide more explicit guidance in the treatment of patients. This new version also has clearly defined histopathological criteria for classification of classes I and II lesions; has specific provisions for the most frequently encountered low-cumulative sun damage pathway of melanoma progression, as well as other, less common World Health Organization pathways to melanoma; provides guidance for classifying intermediate class II tumors vs melanoma; and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as neoplasms lacking criteria for melanoma. CONCLUSIONS AND RELEVANCE The implementation of the newly revised MPATH-Dx version 2.0 schema into clinical practice is anticipated to provide a robust tool and adjunct for standardized diagnostic reporting of melanocytic lesions and management of patients to the benefit of both health care practitioners and patients