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East Africa and India have recently been proposed as places of origin for leprosy, based primarily on the geographical mapping of sixteen single-nucleotide polymorphism subtypes (snps). When comparing these data with historical texts, however, obstacles become apparent for both interpretations. Large population movements, a lack of divergence date ranges for some snp subtypes, and the discovery of a second strain of leprosy further complicate the geography of the disease. Dated skeletons with snp subtypes and molecular data, along with the informed collaboration of historical evidence, are key to determining the place of origin for both leprosy species.

\"Explore Twisted, the Python-based event-driven networking engine, and review several of its most popular application projects. It is written by community leaders who have contributed to many of the projects covered, and share their hard-won insights and experience.Expert Twisted starts with an introduction to event-driven programming, explaining it in the context of what makes Twisted unique. It shows how Twisted's design emphasizes testability as a solution to common challenges of reliability, debugging, and start-to-finish causality that are inherent in event-driven programming. It also explains asynchronous programming, and the importance of functions, deferreds, and coroutines. It then uses two popular applications, treq and klein, to demonstrate calling and writing Web APIs with Twisted./The second part of the book dives into Twisted projects, in each case explaining how the project fits into the Twisted ecosystem and what it does, and offers several examples to bring readers up to speed, with pointers to additional resources for more depth. Examples include using Twisted with Docker, as a WSGI container, for file sharing, and more.\"-- Provided by publisher

For over a century, it has been widely accepted that leprosy did not exist in the Americas before the arrival of Europeans. This proposition was based on a combination of historical, paleopathological, and representational studies. Further support came from molecular studies in 2005 and 2009 that four Mycobacterium leprae single-nucleotide polymorphisms (SNPs) and then 16 SNP subtypes correlated with general geographic regions, suggesting the M. leprae subtypes in the Americas were consistent with European strains. Shortly thereafter, a number of studies proposed that leprosy first came to the Americas with human migrations around 12,000 or 13,000 years ago. These studies are based primarily on subsequent molecular data, especially the discovery of a new leprosy species Mycobacterium lepromatosis and its close association with diffuse lepromatous leprosy, a severe, aggressive form of lepromatous leprosy, which is most common in Mexico and the Caribbean Islands. A review of these and subsequent molecular data finds no evidence for either leprosy species in the Americas before the arrival of Europeans, and strains of both species of leprosy found in eastern Mexico, Caribbean Islands, and Brazil came from Europe while strains found in western Mexico are consistent with their arrival via direct voyages from the Philippines.

In this report, the CSIS Harold Brown Chair in Defense Policy Studies analyzes the types of capabilities necessary across the range of military operations, and compares that with the characteristics of amphibious ships, as well as those in the Combat Logistics Fleet, Maritime Prepositioning Force, and others. Resulting shortfalls in key capability areas suggest some degree of risk. The study then describes how amenable those risks may be to mitigation and some of the associated implications. This report provides a framework for policymakers to understand those areas in which alternative platforms might be most useful, where risks associated with their employment are most significant, and how readily broadening platforms beyond the uses for which they were designed might be accomplished. -- Amazon.

DNA repair mechanisms in human primary cells, including error-free repair, and, recurrent nuclease cleavage events, remain largely uncharacterised. We elucidate gene-editing related repair processes using Cleavage and Lesion Evaluation via Absolute Real-time dPCR (CLEAR-time dPCR), an ensemble of multiplexed dPCR assays that quantifies genome integrity at targeted sites. Utilising CLEAR-time dPCR we track active DSBs, small indels, large deletions, and other aberrations in absolute terms in clinically relevant edited cells, including HSPCs, iPSCs, and T-cells. By quantifying up to 90% of loci with unresolved DSBs, CLEAR-time dPCR reveals biases inherent to conventional mutation screening assays. Furthermore, we accurately quantify DNA repair precision, revealing prevalent scarless repair after blunt and staggered end DSBs and recurrent nucleases cleavage. This work provides one of the most precise analyses of DNA repair and mutation dynamics, paving the way for mechanistic studies to advance gene therapy, designer editors, and small molecule discovery. Quantifying genomic aberrations resulting from designer nucleases activity is essential for gene therapy clinical translation. Here, the authors present a modular digital PCR technique that profiles DNA repair precision and cut-repair cycles at the edited loci, exposing current evaluation biases.

Our perspectives on aortic stenosis (AS) are changing. Evolving from the traditional thought of a passive degenerative disease, developing a greater understanding of the condition’s mechanistic underpinning has shifted the paradigm to an active disease process. This advancement from the ‘wear and tear’ model is a result of the growing economic and health burden of AS, particularly within industrialised countries, prompting further research. The pathophysiology of calcific AS (CAS) is complex, yet can be characterised similarly to that of atherosclerosis. Progressive remodelling involves lipid-protein complexes, with lipoprotein(a) being of particular interest for diagnostics and potential future treatment options.There is an unmet clinical need for asymptomatic patient management; no pharmacotherapies are proven to slow progression and intervention timing varies. Novel approaches are developing to address this through: (1) screening with circulating biomarkers; (2) development of drugs to slow disease progression and (3) early valve intervention guided by medical imaging. Existing biomarkers (troponin and brain natriuretic peptide) are non-specific, but cost-effective predictors of ventricular dysfunction. In addition, their integration with cardiovascular MRI can provide accurate risk stratification, aiding aortic valve replacement decision making. Currently, invasive intervention is the only treatment for AS. In comparison, the development of lipoprotein(a) lowering therapies could provide an alternative; slowing progression of CAS, preventing left ventricular dysfunction and reducing reliance on surgical intervention.The landscape of AS management is rapidly evolving. This review outlines current understanding of the pathophysiology of AS, its management and future perspectives for the condition’s assessment and treatment.

Background Laparoscopy is a minimally-invasive surgical procedure that uses long slender instruments that require much smaller incisions than conventional surgery. This leads to faster recovery times, fewer post-surgical wound infections and shorter hospital stays. For these reasons, laparoscopy could be particularly advantageous to patients in low to middle income countries (LMICs). Unfortunately, sterile processing departments in LMIC hospitals are faced with limited access to equipment and trained staff which poses an obstacle to safe surgical care. The reprocessing of laparoscopic devices requires specialised equipment and training. Therefore, when LMIC hospitals invest in laparoscopy, an update of the standard operating procedure in sterile processing is required. Currently, it is unclear whether LMIC hospitals, that already perform laparoscopy, have managed to introduce updated reprocessing methods that minimally invasive equipment requires. The aim of this study was to identify the laparoscopic sterile reprocessing procedures in rural India and to test the effectiveness of the sterilisation equipment. Methods We assessed laparoscopic instrument sterilisation capacity in four rural hospitals in different states in India using a mixed-methods approach. As the main form of data collection, we developed a standardised observational checklist based on reprocessing guidelines from several sources. Steam autoclave performance was measured by monitoring the autoclave cycles in two hospitals. Finally, the findings from the checklist data was supported by an interview survey with surgeons and nurses. Results The checklist data revealed the reprocessing methods the hospitals used in the reprocessing of laparoscopic instruments. It showed that the standard operating procedures had not been updated since the introduction of laparoscopy and the same reprocessing methods for regular surgical instruments were still applied. The interviews confirmed that staff had not received additional training and that they were unaware of the hazardous effects of reprocessing detergents and disinfectants. Conclusion As laparoscopy is becoming more prevalent in LMICs, updated policy is needed to incorporate minimally invasive instrument reprocessing in medical practitioner and staff training programmes. While reprocessing standards improve, it is essential to develop instruments and reprocessing equipment that is more suitable for resource-constrained rural surgical environments.

Grotesque and vulgar, the masked character Gongoli upends the codes of Mende decorum in his madcap pursuit of laughs. His impropriety goes so far as to allow his mask to fall, comically revealing the identity of his dancer and subverting the anonymity so elemental to his fellow spirits’ vaunted status. Yet despite such transgressions, he stands among the most beloved figures of Sierra Leone's rich performance traditions. Gongoli's popularity hinges on his irreverence towards the fundamental laws of masked dance, laws that also regulate the balance between individual agency and communal responsibility, between internal desire and external restraint. The only quality necessary to play Gongoli is shamelessness (ngufe baa), and the greatest performers are acrobats braving risks that are not physical, but social. This article follows Siloh, an itinerant performer whose celebrity inheres in his uncanny similarity to the Gongoli he often plays. The composite figure Siloh Gongoli exemplifies a comic aesthetic relished throughout Sierra Leone in storytelling, ritual, festivals, videos and radio shows. Although mobilized for different ends, each of these conventions undermines principles of self-effacement, gerontocratic privilege and esoteric power by shamelessly playing with and within the existential tensions between interior and exterior selves. Grotesque et vulgaire, le personnage masqué Gongoli bouleverse les codes de la bienséance mendé dans sa folle quête de faire rire. Son inconvenance va jusqu’à s'autoriser à baisser le masque, révélant de façon comique l'identité de son danseur et subvertissant l'anonymat si fondamental au statut de ses fameux esprits compagnons. Pourtant, malgré ces transgressions, il figure parmi les personnages les plus chéris des riches traditions du spectacle au Sierra Leone. La popularité de Gongoli repose sur son irrévérence vis-à-vis des lois fondamentales de la danse masquée, des lois qui régulent également l’équilibre entre action individuelle et responsabilité collective, entre désir interne et contrainte externe. La seule qualité nécessaire pour incarner Gongoli est l'impudence (ngufe baa), et les meilleurs artistes sont des acrobates qui bravent des risques non pas physiques mais sociaux. Cet article s'intéresse à Siloh, un artiste itinérant dont la célébrité tient à sa ressemblance troublante au Gongoli qu'il incarne souvent. Le personnage composite Siloh Gongoli exemplifie une esthétique comique appréciée partout au Sierra Leone, que ce soit dans les contes, les rituels, les festivals ou les programmes radiophoniques et télévisuels. Bien que ces conventions aient des finalités de mobilisation différentes, chacune d'elles ébranle les principes de l'effacement de soi et du privilège géroncratique, et masque le pouvoir en se jouant sans vergogne des tensions existentielles entre le soi intérieur et le soi extérieur.

Cheryl Ward recently proposed that the breaking down of Egyptian vessels evolved from the need to transport ships from the Nile to the Red Sea. Analysis of the Abydos BG10 boat and other data suggest that boat-wrights instead built vessels in this manner, with many standardised elements, primarily to conserve timber. An evaluation of the data supports the traditional interpretation that timber was indeed scarce in Ancient Egypt. Scarcity of timber and the centralisation of Egyptian society produced boat-wrights who were more innovative than boat-wrights of other ancient societies, as is evident in the construction of the symbolic BG 10 boat.