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BackgroundRestraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan.MethodsUsing Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture.ResultsWe developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo.ConclusionsOur method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors.

Following publication of the original article [1], the authors reported two errors in Fig. 1B and Fig. 2B. 1. The two EP + siGLO and DS + siGLO brightfield/β-gal images from Fig. 2A were accidentally duplicated in Fig. 1B. The images in Fig. 2A are correct. The images in Fig. 1B are replaced with representative images of untransfected EP and DS cells. The incorrect and the correct figure are given below. The incorrect Fig. 1: (Figure presented.) The correct Fig. 1: (Figure presented.) The replacement of these images does not change any of the other data in this figure, nor the conclusion of this figure. 2. The authors also noticed that the panels in Fig. 2B labelled with “DS” were incorrectly labelled. The bar charts and figure legend correctly state that these images are “DS + siGLO” images. These panels are now relabelled as “DS + siGLO”. This proposed relabelling does not change any of the other data in this figure, nor the conclusion of Fig. 2B. The incorrect and the correct figure are given below. The incorrect Fig. 2: (Figure presented.) The correct Fig. 2: (Figure presented.) In both instances, these errors do not change any data associated with these figures, nor do they change the conclusions of the corresponding figures and the paper.

In comparison to the efforts required to bring a new drug or formulation to the clinic, bestowing a name on a medicine is relatively simple. However, if the name we choose causes confusion—by making its contents ambiguous or if it is too alike another drug—it can precipitate clinical errors. This prompted the World Health Organization to set up the International Nonproprietary Naming Committee in the 1970s to select unambiguous names for drugs. Unfortunately, multidrug products—which are becoming increasingly popular—do not fall under the remit of conventional International Non‐proprietary Nomenclature. We have identified 26 combination formulations that have been historically named with the co‐drug format in the United Kingdom. Most of them have also been prescribed in the United Kingdom in the past year, and although several of them are not prescribed very often, 11 were prescribed more than 2000 times. In this paper, we have explored the literature to identify prescribing errors with co‐drug products and found several idiosyncrasies that have caused drug errors in the past. We advocate for a standard nomenclature (state the international nonproprietary name [INN] of each component followed by dose information in the x + y format) for these products on the box and in prescribing resources. We hope that this will enhance clarity and safety during prescribing and administration, particularly for high‐volume drugs like paracetamol + codeine (co‐codamol), amoxicillin + clavulanic acid (co‐amoxiclav) and trimethoprim + sulfamethoxazole (co‐trimoxazole). [ABSTRACT FROM AUTHOR]

Law enforcement organizations invest in ongoing education of employees on various topics concerning diversity, equity and accountability. Such education is designed to ensure the highest levels of performance and to earn the trust of the public. Traditional approaches to education, however, have proved challenging. The effectiveness of what passes as "training" is unregulated, and negative attitudes and beliefs about mandatory educational programs themselves may sabotage any possible benefits for policing. Utilizing a 2-wave, pre-/post-education panel design (N = 263), we demonstrate significant, even dramatic attitude and belief change among members of a police department concerning the value and importance of implicit bias education. That the program succeeded in promoting positive attitudes and beliefs offers a possible path forward given that law enforcement desires a rational, science-based approach to improving professional conduct and police-community relations, and given increased demands for implicit bias education as a component of police reform. Self-reported attitude change is most emphatically not an indication of reduction in bias in the trenches of policing. Nevertheless, positive shifts in attitudes and beliefs about bias education is a notable step forward as it likely reduces resistance to procedures and policies for individual and institutional reform that might otherwise remain elusive. [ABSTRACT FROM AUTHOR]

The ideology of native speakerism and its effects on the professional lives of 'native' and 'non-native speakers' in English language teaching (ELT) have been widely documented. Nevertheless, little is known about the impact native speakerism might have on the selection of plenary speakers for ELT conferences. Hence, through the analysis of plenary line-ups of seven conferences in the EU and interviews with their organisers, this study aimed to explore whether 'native' and 'non-native speakers' were represented equally as plenary speakers. The results show that overall only 25 per cent of the 416 analysed plenary speaker line-ups were given by 'non-native speakers'. At some conferences, over 80 per cent of all plenary speakers were 'native speakers'. Apart from one conference organiser who highlighted that steps had been taken to ensure a more equal balance of speakers, the other organisers seemed not to place much importance on equal balance of 'native' and 'non-native speakers' when inviting plenary speakers, preferring a 'colourblind' approach. This study suggests native-speakerism impacts the choice of plenary speakers at certain ELT conferences, and that conscious efforts must be made to alter this balance. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that social identities are an important determinant of adaptation following traumatic life experiences. In this paper, we analyse accounts of people who experienced child sexual abuse. Using publicly available talk of people who waived their right to anonymity following successful conviction of perpetrators, we conducted a thematic analysis focusing on trauma‐related changes in their social identities. Analysis of these accounts highlighted two themes. The first highlights the acquisition in these accounts of unwanted and damaging identity labels. The second presents child sexual abuse as a key destructive force in terms of important identity work during childhood. Discussion of this analysis centres on the pathological consequences of social identity change. Both the loss of valued identities and the acquisition of aberrant and isolating identities are experienced and constructed as devastating by those affected by child sexual abuse. This has important implications, not only for those impacted by child sexual abuse but for how abuse is discussed in society, and how it is approached by policy makers, educators and individuals working with survivors and their families. [ABSTRACT FROM AUTHOR]