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The yeast Kluyveromyces marxianus offers unique potential for industrial biotechnology because of useful features like rapid growth, thermotolerance and a wide substrate range. As an emerging alternative platform, K. marxianus requires the development and validation of metabolic engineering strategies to best utilise its metabolism as a basis for bio-based production. To illustrate the synthetic biology strategies to be followed and showcase its potential, we describe a comprehensive approach to rationally engineer a metabolic pathway in K. marxianus. We use the phenylalanine biosynthetic pathway both as a prototype and because phenylalanine is a precursor for commercially valuable secondary metabolites. First, we modify and overexpress the pathway to be resistant to feedback inhibition so as to overproduce phenylalanine de novo from synthetic minimal medium. Second, we assess native and heterologous means to increase precursor supply to the biosynthetic pathway. Finally, we eliminate branch points and competing reactions in the pathway and rebalance precursors to redirect metabolic flux to a specific product, 2-phenylethanol (2-PE). As a result, we are able to construct robust strains capable of producing over 800mg L 2-PE from minimal medium. The strains we constructed are a promising platform for the production of aromatic amino acid-based biochemicals, and our results illustrate challenges with attempting to combine individually beneficial modifications in an integrated platform. The strains we constructed are a promising platform for the production of aromatic amino acid-based biochemicals, and our results illustrate challenges with attempting to combine individually beneficial modifications in an integrated platform. Designing public health policies to target the needs of specific places requires highly granular data. When geographic health statistics from official sources are absent or lacking in spatial detail, Sanitary Vulnerability metrics derived from Census and other georeferenced public data can be used to identify areas in particular need of attention. With that aim, a Vulnerability Map was developed, identifying areas with a substantial deficit in its population health coverage. As a result a novel methodology for measuring Sanitary Vulnerability is presented, that can potentially be applied to different time periods or geographies. Census, official listings of public health facilities and crowdsourced georeferenced data are used. https://www.selleckchem.com/products/tideglusib.html The Vulnerability Index is built using dimensionality reduction techniques such as Autoencoders and Non-parametric PCA. The high resolution map shows the geographical distribution of a Sanitary Vulnerability Index, produced using official and crowdsourced open data sources, overcoming the lack of official sources on health indicators at the local level. The Sanitary Vulnerability Map's value as a tool for place specific policymaking was validated by using it to predict local health related metrics such as health coverage. Further lines of work contemplate using the Map to study the interaction between Sanitary Vulnerability and the prevalence of different diseases, and also applying its methodology in the context of other public services such as education, security, housing, etc. The Sanitary Vulnerability Map's value as a tool for place specific policymaking was validated by using it to predict local health related metrics such as health coverage. Further lines of work contemplate using the Map to study the interaction between Sanitary Vulnerability and the prevalence of different diseases, and also applying its methodology in the context of other public services such as education, security, housing, etc. In Kenya, pre-exposure prophylaxis (PrEP) for HIV prevention is almost exclusively delivered at HIV clinics. Developing novel PrEP delivery models is important for increasing the reach of PrEP. Delivery of PrEP through pharmacies is one approach utilized in the US to improve accessibility. Retail pharmacies are commonly used as a first-line access point for medical care in Kenya, but have not been utilized for PrEP delivery. We conducted a collaborative consultative meeting of stakeholders to develop a care pathway for pharmacy-based PrEP delivery in Kenya. In January 2020, we held a one-day meeting in Nairobi with 36 stakeholders from PrEP regulatory, professional, healthcare service delivery, civil society, and research organizations. Attendees reviewed a theory of change model, results from formative qualitative research with pharmacy providers and clients, and anticipated core components of pharmacy-based PrEP delivery counseling, HIV testing, prescribing, and dispensing. Stakeholders participated in for pilot testing that has the potential to expand PrEP delivery options in Kenya and other similar settings. PrEP delivery stakeholders in Kenya were strongly supportive of developing and testing a model for pharmacy-based PrEP delivery to increase PrEP access. We collaboratively developed a care pathway for pilot testing that has the potential to expand PrEP delivery options in Kenya and other similar settings. The Revised Short McGill Pain Questionnaire Version-2 (SF-MPQ-2) is a multidimensional outcome measure designed to capture, evaluate and discriminate pain from neuropathic and non-neuropathic sources. A recent systematic review found insufficient psychometric data with respect to musculoskeletal (MSK) health conditions. This study aimed to describe the reproducibility (test-retest reliability and agreement) and internal consistency of the SF-MPQ-2 for use among patients with musculoskeletal shoulder pain. Eligible patients with shoulder pain from MSK sources completed the SF-MPQ-2 at baseline (n = 195), and a subset did so again after 3-7days (n = 48), if their response to the Global Rating of Change (GROC) scale remained unchanged. Cronbach alpha (α) and intraclass correlation coefficient (ICC ), and their related 95% CI were calculated. Standard error of measurement (SEM), group and individual minimal detectable change (MDC90), and Bland-Altman (BA) plots were used to assess agreement. Cronbach α ranged from 0.
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