Mycobacterium leprae in Armadillo Tissues from Museum Collections, United States

We examined armadillos from museum collections in the United States using molecular assays to detect leprosy-causing bacilli. We found Mycobacterium leprae bacilli in samples from the United States, Bolivia, and Paraguay; prevalence was 14.8% in nine-banded armadillos. US isolates belonged to subtype 3I-2, suggesting long-term circulation of this genotype

A cyclic peptide inhibitor of HIF-1 heterodimerization that inhibits hypoxia signaling in cancer cells

Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival and progression of tumors. Here we report cyclo-CLLFVY, identified from a library of 3.2 million cyclic hexapeptides using a genetically encoded high-throughput screening platform, as an inhibitor of the HIF-1α/HIF-1β protein-protein interaction in vitro and in cells. The identified compound inhibits HIF-1 dimerization and transcription activity by binding to the PAS-B domain of HIF-1α, reducing HIF-1-mediated hypoxia response signaling in a variety of cell lines, without affecting the function of the closely related HIF-2 isoform. The reported cyclic peptide demonstrates the utility of our high-throughput screening platform for the identification of protein-protein interaction inhibitors, and forms the starting point for the development of HIF-1 targeted cancer therapeutics

The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis

The lungs are generated by branching morphogenesis as a result of reciprocal signalling interactions between the epithelium and mesenchyme during development. Mutations that disrupt formation of either the correct number or shape of epithelial branches affect lung function. This, in turn, can lead to congenital abnormalities such as cystadenomatoid malformations, pulmonary hypertension or lung hypoplasia. Defects in lung architecture are also associated with adult lung disease, particularly in cases of idiopathic lung fibrosis. Identifying the signalling pathways which drive epithelial tube formation will likely shed light on both congenital and adult lung disease. Here we show that mutations in the planar cell polarity (PCP) genes Celsr1 and Vangl2 lead to disrupted lung development and defects in lung architecture. Lungs from Celsr1Crsh and Vangl2Lp mouse mutants are small and misshapen with fewer branches, and by late gestation exhibit thickened interstitial mesenchyme and defective saccular formation. We observe a recapitulation of these branching defects following inhibition of Rho kinase, an important downstream effector of the PCP signalling pathway. Moreover, epithelial integrity is disrupted, cytoskeletal remodelling perturbed and mutant endoderm does not branch normally in response to the chemoattractant FGF10. We further show that Celsr1 and Vangl2 proteins are present in restricted spatial domains within lung epithelium. Our data show that the PCP genes Celsr1 and Vangl2 are required for foetal lung development thereby revealing a novel signalling pathway critical for this process that will enhance our understanding of congenital and adult lung diseases and may in future lead to novel therapeutic strategies

Histoire de l’art et potlatch : regards croisés entre la France et le Canada

Le présent débat vise à interroger les relations entre l’histoire de l’art et le potlatch sous un nouveau jour. Il est en effet convenu, dans le champ de l’histoire de l’art, de voir dans cette institution cérémonielle en usage chez les Premières Nations de la côte nord-ouest de l’Amérique avant tout une activité d’échanges somptuaires et de destruction ostentatoire de la richesse. C’est Georges Bataille, dans son texte de 1933 « La notion de dépense », repris et augmenté en 1949 dans La part..

Lalakenis/All Directions : A Journey of Truth and Unity

"The catalogue offers visual documentation of the belongings that were gathered together and displayed in the Gallery during the Lalakenis exhibition, along with images from the two journeys that culminated in copper-breaking ceremonies: Awalaskenis I (February 2013) beginning in Quatsino and ending in Victoria, BC and Awalaskenis II (July 2014) which saw Beau Dick and 21 companions setting out from UBC for Ottawa." -- Publisher's website

Widening participation – recruitment methods in mental health randomised controlled trials: a qualitative study

Background: Barriers to mental health research participation are well documented including distrust of services and research; and stigma surrounding mental health. They can contribute to a lack of diversity amongst participants in mental health research, which threatens the generalisability of knowledge. Given the recent widespread use of the internet in medical research, this study aimed to explore the perspectives of key partners on the use of online (e.g. social media) and offline (e.g. in-person) recruitment as an approach to improving diversity in mental health randomised controlled trials (RCTs).Methods: Face-to-face and online interviews/focus groups with researchers working in mental health and Patient and Public Involvement partners in the United Kingdom. Recordings were transcribed and analysed using a combination of inductive and deductive thematic analysis.Results: Three focus groups and three interviews were conducted with a total N=23 participants. Four overarching themes were identified: (1) recruitment reach; (2) Demographic factors that affect selection of recruitment method; (3) safety of technology, and; (4) practical challenges. Five main factors were identified that affect the choice of recruitment method: age, complexity of mental health problem and stigma, cultural and ethnicity differences and digital divide. The use of online methods was considered more accessible to people who may feel stigmatised by their mental health condition and with a benefit of reaching a wider population. However, a common view amongst participants was that online methods require closer data monitoring for quality of responders, are not fully secure and less trustworthy compared to offline methods that enable participants to build relationships with health providers. Funding, staff time and experience, organisational support, and technical issues such as spam or phishing emails were highlighted as practical challenges facing online recruitment. All participants agreed that using a hybrid approach tailored to the population under study is paramount.Conclusions: This study highlighted the importance of offering a flexible and multifaceted recruitment approach by integrating online with offline methods to support inclusivity and widening participation in mental health research. The findings will be used to develop considerations for researchers designing RCTs to improve recruitment in mental health research

Does device matter? Impacts of food-specific inhibition training on food choice, liking and approach bias when delivered by smartphone or computer.

Food-specific inhibition training (FSIT) requires users to inhibit responses to energy-dense (ED) food stimuli within a reaction time game. FSIT reduces choice and liking of ED foods. Research with the public shows larger effects when FSIT is delivered by computer versus smartphone. This pre-registered study is the first to compare computer-FSIT versus smartphone-FSIT in a controlled setting. Three-hundred-and-thirty-one adults were randomised to computer-FSIT, smartphone-FSIT or non-food control training (computer-delivered). In session 1, participants completed baseline measures of impulsive food choice, food approach bias (approach/avoid implicit association test), and food liking ratings, before completing eight minutes of FSIT/control training. In session 2, participants repeated the same training task, followed by the same measures of food choice, approach bias and liking. We hypothesised that FSIT groups would show healthier food choices, lower ED food liking, and reduced ED food approach bias at post-training compared to control. We expected no statistically significant differences between the two FSIT groups. Post-exclusions, data for 259 participants was analysed. Contrary to predictions, there was no evidence of significant group differences on any of the outcome measures. Baseline measures suggest participants already showed high approach to healthy foods, which may explain these null results

Assessing Integration Methodology (AIM): A Handbook for Measuring and Assessing the Integration of Family Planning and Other Reproductive Health Services

Several international statements over the past two decades have endorsed the integration of family planning (FP) services with other reproductive health (RH) services as a means of expanding availability and access for potential users. Many rationales underlie the move toward integrating FP with other services. First is that it provides benefits to the client and the program. Moreover, there is the expectation that the costs to the health system of configuring two or more services will cost less than providing them independently. However, there is still little empirical evidence available about integration of services. Over time, a number of methodologies for undertaking health facility assessments of service delivery have been developed and field-tested, but none focus specifically on measurement of the integration of services. This handbook presents a methodology that seeks to address this gap. It has been developed from experience gained by the Population Council in undertaking assessments of various combinations of integrated services in many developing countries, mostly undertaken through the FRONTIERS program

Opportunities and challenges of delivering digital clinical trials: lessons learned from a randomised controlled trial of an online behavioural intervention for children and young people

Background: Despite being the gold standard of research to determine effectiveness, randomised controlled trials (RCTs) often struggle with participant recruitment, engagement and retention. These issues may be exacerbated when recruiting vulnerable populations, such as participants with mental health issues. We aimed to update understanding of the scope of these problems in trials of health technology, and identify possible solutions through reflecting on experiences from an exemplar trial (Online Remote Behavioural Intervention for Tics; ORBIT).Method: We extracted anonymised data on recruitment, retention and requests for more funding and time from trials funded by the largest funder of health technology trials in the UK (the National Institute of Health Research Health Technology Assessment) between 2010-2020, and compared these with data from a recent, successful trial (ORBIT). ORBIT aimed to assess the clinical- and cost-effectiveness of blended online and human behavioural therapy for tics in young people. Many of the trial procedures, including recruitment, the intervention and data collection, were undertaken online. Results: Data were extracted on 51 trials conducted between 2010 and 2020. 60% of trials failed to reach their original recruitment target and only 44% achieved their follow-up in the specified time frame. In contrast, ORBIT recruited to target and achieved 90% follow up. We posit that these achievements are related to a) judicious use of digital technology for trial procedures and b) adequate numbers of highly trained and motivated trial staff. We provide details of both these to help other research teams plan and cost for successful trials. Conclusion: An approach combining human and online methods may be advantageous in facilitating trial delivery, particularly in paediatric mental health services. Given the importance of successful clinical trials in advancing healthcare delivery and the waste of human and economic resources associated with unsuccessfully delivered trials, it is imperative that trials are appropriately costed and future research focusses on improving trial design and delivery. Trial registration: The ORBIT Trial is registered with ISRTCN (ISRCTN70758207) and clinicaltrials.gov (NCT03483493)

The art of indigeneity: Aesthetics and competition in Mexican economies of culture

On the basis of ethnographic research with woodcarvers in Oaxaca, Mexico, this paper investigates the role that aesthetic practices play in economic competition in cultural markets. I explain how one family has become the most successful artisans in their village by aesthetically referencing the indigenous art that is highly sought after by the North American ethnic art market. By reformulating Bourdieu's analysis of artistic fields, I argue that aesthetic competition should be theorised at the level of genres, which allow insight into how individual aesthetic innovations may transform the fields in which art is produced and circulated. I show that by referencing indigeneity, this successful family not only accesses a new market but also renders their work more authoritative than the carvings of their neighbours, which aesthetically reference Mexican ‘artesanías’ (craftwork). In so doing, they not only earn more money but also change the ways that Oaxacan woodcarvings are valued in general