Site Plan of 78 U.S. Route 1, Cumberland, Maine, 2013

78 US Route 1 Site Plan, Cumberland, Maine was created by Florence Nightingale Corp. in 2013. Scale 1 =30\u27.https://digitalmaine.com/cumberland_plans/1227/thumbnail.jp

Ethical, legal and social issues in diversifying genomic data: literature review and synthesis

Advances in technology have resulted in the ability to sequence entire human genomes as a routine, relatively inexpensive, investigation in healthcare. This offers many promises of personalising, stratifying, and targeting healthcare with an understanding of genetic susceptibility to particular diseases or conditions. However, research collections (databases, biobanks etc) that underpin these developments are significantly skewed towards populations of European ancestry meaning that our understanding of genetic susceptibility (or indeed of genetic protection to disease) is less good for many other populations in the world. Just as a dermatology text book skewed towards skin problems on white skin may be less useful to black populations, so genomic knowledge derived from one particular ancestry means it may be less useful to people with different ancestries. The need to diversify genomic data, to improve the evidence base for genomic medicine for all ancestries, is well recognised, but is more complex than simply increasing the collection of data from people from a range of ancestries. We reviewed the literature to understand the challenges of diversifying genomic data to identify key ethical, legal and social issues. Our findings were: 1. Many research practices are exclusionary and need to change. Examples include approaches to recruitment or data collection that do not consider the cultural setting in which potential participants are situated. Research also often lacks reflexivity about diversity on the part of researchers and research institutions. 2. Co-design is key to identifying and avoiding potential problems around data diversification. This requires an understanding of the concerns of underserved individuals and communities regarding exploitation and stigmatisation, as well as issues of data ownership and sovereignty. Without attention to group as well as individual concerns, participant engagement may become tokenistic which in turn risks exacerbating existing, as well as creating new, inequalities. 3. There are wider structural issues that influence researchers’ and participants’ attempts to generate diverse data. For example, (a) some researchers view data as neutral, but this ignores the social construction of data and technologies, and their tendencies to reflect societal inequalities. (b). Efforts to diversify data should be contextualised within the historical trajectory of structural racism and legacies of colonialism. (c) Classification and categorisation of populations have political consequences and need to be closely interrogated. These findings show that deliberation between researchers and participants, during all stages of research from planning and recruitment through to analysis, interpretation and dissemination is key to successful diversification

ILC2-modulated T cell-to-MDSC balance is associated with bladder cancer recurrence.

Non-muscle-invasive bladder cancer (NMIBC) is a highly recurrent tumor despite intravesical immunotherapy instillation with the bacillus Calmette-Guérin (BCG) vaccine. In a prospective longitudinal study, we took advantage of BCG instillations, which increase local immune infiltration, to characterize immune cell populations in the urine of patients with NMIBC as a surrogate for the bladder tumor microenvironment. We observed an infiltration of neutrophils, T cells, monocytic myeloid-derived suppressor cells (M-MDSCs), and group 2 innate lymphoid cells (ILC2). Notably, patients with a T cell-to-MDSC ratio of less than 1 showed dramatically lower recurrence-free survival than did patients with a ratio of greater than 1. Analysis of early and later time points indicated that this patient dichotomy existed prior to BCG treatment. ILC2 frequency was associated with detectable IL-13 in the urine and correlated with the level of recruited M-MDSCs, which highly expressed IL-13 receptor α1. In vitro, ILC2 were increased and potently expressed IL-13 in the presence of BCG or tumor cells. IL-13 induced the preferential recruitment and suppressive function of monocytes. Thus, the T cell-to-MDSC balance, associated with a skewing toward type 2 immunity, may predict bladder tumor recurrence and influence the mortality of patients with muscle-invasive cancer. Moreover, these results underline the ILC2/IL-13 axis as a targetable pathway to curtail the M-MDSC compartment and improve bladder cancer treatment

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Notes on Nursing: What It Is, and What It Is Not

Includes index.Mode of access: Internet.Advertisements laid in.Blue embossed cloth hard cover binding; gilt title and medal (given to Nightingale by Queen Victoria for her nursing work during the Crimean War) embossed on cover.ACQ: 35669; Janice B. Longone; Gift; 6/21/2001

Miss Florence Nightingale-ovy Kniha o ošetřování nemocných

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