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Background The online BeUpstanding™ program is an eight-week workplace-delivered intervention for desk-based workers to raise awareness of the benefits of sitting less and moving more and build a supportive culture for change. A workplace representative (the “champion”) delivers the program, which includes a workshop where teams collectively choose their sit less/move more strategies. A toolkit provides the champion with a step-by-step guide and associated resources to support program uptake, delivery, and evaluation. Here we report on the main findings from the Australian national implementation trial of BeUpstanding. Methods Recruitment (12/06/2019 to 30/09/2021) was supported by five policy and practice partners, with desk-based work teams from across Australia targeted. Effectiveness was measured via a single arm, repeated-measures trial. Data were collected via online surveys, toolkit analytics, and telephone calls with champions. The RE-AIM framework guided evaluation, with adoption/reach (number and characteristics); effectiveness (primary: self-reported workplace sitting time); implementation (completion of core components; costs); and, maintenance intentions reported here. Linear mixed models, correcting for cluster, were used for effectiveness, with reach, adoption, implementation, and maintenance outcomes described. Results Of the 1640 website users who signed-up to BeUpstanding during the recruitment period, 233 were eligible, 198 (85%) provided preliminary consent, and 118 (50.6%) champions consented and started the trial, with 94% ( n  = 111 champions) completing. Trial participation was from across Australia and across industries, and reached 2,761 staff, with 2,248 participating in the staff survey(s): 65% female; 64% university educated; 17% from a non-English speaking background. The program effectively changed workplace sitting (-38.5 [95%CI -46.0 to -28.7] minutes/8-hour workday) and all outcomes targeted by BeUpstanding (behaviours and culture), with small-to-moderate statistically-significant effects observed. All participating teams ( n  = 94) completed at least 5/7 core steps; 72.4% completed all seven. Most champions spent $0 (72%) or >$0-$5 (10%) per team member; most (67/70 96%) intended to continue or repeat the program. Conclusions BeUpstanding can be adopted and successfully implemented by a range of workplaces, reach a diversity of staff, and be effective at creating a supportive culture for teams of desk-based workers to sit less and move more. Learnings will inform optimisation of the program for longer-term sustainability. Trial registration ACTRN12617000682347.

Stuart MacGregor and colleagues report the results of a genome-wide association study for melanoma susceptibility in an Australian population. They identify a new melanoma susceptibility locus on chromosome 1. We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R , ASIP and MTAP – CDKN2A . We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10 −11 , OR in combined replication cohorts of 0.89 (95% CI 0.85–0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10 −8 ). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1 . Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.

Whole-genome sequencing identifies a novel germline variant in the oncogene MITF , which is associated with the development of melanoma. MITF , a melanoma predisposition gene Two papers in this issue of Nature demonstrate that missense substitutions in the gene encoding for microphthalmia-associated transcription factor (MITF) are associated with susceptibility to melanoma and renal cell carcinoma. Functional analysis shows that the variant has impaired sumoylation that leads to differential regulation of several MITF targets, and promotes tumour cell clonogenicity, migration and invasion. So far, two genes associated with familial melanoma have been identified, accounting for a minority of genetic risk in families. Mutations in CDKN2A account for approximately 40% of familial cases 1 , and predisposing mutations in CDK4 have been reported in a very small number of melanoma kindreds 2 . Here we report the whole-genome sequencing of probands from several melanoma families, which we performed in order to identify other genes associated with familial melanoma. We identify one individual carrying a novel germline variant (coding DNA sequence c.G1075A; protein sequence p.E318K; rs149617956) in the melanoma-lineage-specific oncogene microphthalmia-associated transcription factor ( MITF ). Although the variant co-segregated with melanoma in some but not all cases in the family, linkage analysis of 31 families subsequently identified to carry the variant generated a log of odds (lod) score of 2.7 under a dominant model, indicating E318K as a possible intermediate risk variant. Consistent with this, the E318K variant was significantly associated with melanoma in a large Australian case–control sample. Likewise, it was similarly associated in an independent case–control sample from the United Kingdom. In the Australian sample, the variant allele was significantly over-represented in cases with a family history of melanoma, multiple primary melanomas, or both. The variant allele was also associated with increased naevus count and non-blue eye colour. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets. These data indicate that MITF is a melanoma-predisposition gene and highlight the utility of whole-genome sequencing to identify novel rare variants associated with disease susceptibility.

Brown et al . report results of a genome-wide association study for melanoma. Their screen, which used a pooling strategy, identified common variants on 20q11.22 associated with melanoma susceptibility. In two separate studies, Sulem et al . and Gudbjartsson et al . report that the same region on 20q11.22, near ASIP , influences pigmentation and confers risk of cutaneous melanoma and basal cell carcinoma. We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 × 10 −15 ). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases.

The web-based BeUpstanding Champion Toolkit was developed to support work teams in addressing the emergent work health and safety issue of excessive sitting. It provides a step-by-step guide and associated resources that equip a workplace representative-the champion-to adopt and deliver the 8-week intervention program (BeUpstanding) to their work team. The evidence-informed program is designed to raise awareness of the benefits of sitting less and moving more, build a supportive culture for change, and encourage staff to take action to achieve this change. Work teams collectively choose the strategies they want to implement and promote to stand up, sit less, and move more, with this bespoke and participative approach ensuring the strategies are aligned with the team's needs and existing culture. BeUpstanding has been iteratively developed and optimized through a multiphase process to ensure that it is fit for purpose for wide-scale implementation. The study aimed to describe the current version of BeUpstanding, and the methods and protocol for a national implementation trial. The trial will be conducted in collaboration with five Australian workplace health and safety policy and practice partners. Desk-based work teams from a variety of industries will be recruited from across Australia via partner-led referral pathways. Recruitment will target sectors (small business, rural or regional, call center, blue collar, and government) that are of priority to the policy and practice partners. A minimum of 50 work teams will be recruited per priority sector with a minimum of 10,000 employees exposed to the program. A single-arm, repeated-measures design will assess the short-term (end of program) and long-term (9 months postprogram) impacts. Data will be collected on the web via surveys and toolkit analytics and by the research team via telephone calls with champions. The Reach, Effectiveness, Adoption, Implementation, and Maintenance Framework will guide the evaluation, with assessment of the adoption/reach of the program (the number and characteristics of work teams and participating staff), program implementation (completion by the champion of core program components), effectiveness (on workplace sitting, standing, and moving), and maintenance (sustainability of changes). There will be an economic evaluation of the costs and outcomes of scaling up to national implementation, including intervention affordability and sustainability. The study received funding in June 2018 and the original protocol was approved by institutional review board on January 9, 2017, with national implementation trial consent and protocol amendment approved March 12, 2019. The trial started on June 12, 2019, with 48 teams recruited as of December 2019. The implementation and multimethod evaluation of BeUpstanding will provide the practice-based evidence needed for informing the potential broader dissemination of the program. Australian New Zealand Clinical Trials Registry ACTRN12617000682347; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372843&isReview=true. DERR1-10.2196/15756.