Recommended Revisions to the National SEP‐1 Sepsis Quality Measure: A commentary by the Society of Infectious Diseases Pharmacists on the Infectious Diseases Society of America Position Paper

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154912/1/phar2384.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154912/2/phar2384_am.pd

Pervasive lesion segregation shapes cancer genome evolution

Cancers arise through the acquisition of oncogenic mutations and grow through clonal expansion. Here we reveal that most mutagenic DNA lesions are not resolved as mutations within a single cell-cycle. Instead, DNA lesions segregate unrepaired into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterise this process in mutagen-induced mouse liver tumours and show that DNA replication across persisting lesions can produce multiple alternative alleles in successive cell divisions, thereby generating both multi-allelic and combinatorial genetic diversity. The phasing of lesions enables the accurate measurement of strand biased repair processes, quantification of oncogenic selection, and fine mapping of sister chromatid exchange events. Finally, we demonstrate that lesion segregation is a unifying property of exogenous mutagens, including UV light and chemotherapy agents in human cells and tumours, which has profound implications for the evolution and adaptation of cancer genomes.This work was supported by: Cancer Research UK (20412, 22398), the European Research Council (615584, 682398), the Wellcome Trust (WT108749/Z/15/Z, WT106563/Z/14/A, WT202878/B/16/Z), the European Molecular Biology Laboratory, the MRC Human Genetics Unit core funding programme grants (MC_UU_00007/11, MC_UU_00007/16), and the ERDF/Spanish Ministry of Science, Innovation and Universities-Spanish State Research Agency/DamReMap Project (RTI2018-094095-B-I00)

Nondense mammographic area and risk of breast cancer

Introduction The mechanisms underlying the strong association between percentage dense area on a mammogram and the risk of breast cancer are unknown. We investigated separately the absolute dense area and the absolute nondense area on mammograms in relation to breast cancer risk. Methods We conducted a nested case-control study on prediagnostic mammographic density measurements and risk of breast cancer in the Nurses\u27 Health Study and the Nurses\u27 Health Study II. Premenopausal mammograms were available from 464 cases and 998 controls, and postmenopausal mammograms were available from 960 cases and 1,662 controls. We used a computer-assisted thresholding technique to measure mammographic density, and we used unconditional logistic regression to calculate OR and 95% CI data. Results Higher absolute dense area was associated with a greater risk of breast cancer among premenopausal women (ORtertile 3 vs 1 = 2.01, 95% CI = 1.45 to 2.77) and among postmenopausal women (ORquintile 5 vs 1 = 2.19, 95% CI = 1.65 to 2.89). However, increasing absolute nondense area was associated with a decreased risk of breast cancer among premenopausal women (ORtertile 3 vs 1 = 0.51, 95% CI = 0.36 to 0.72) and among postmenopausal women (ORquintile 5 vs 1 = 0.46, 95% CI = 0.34 to 0.62). These associations changed minimally when we included both absolute dense area and absolute nondense area in the same statistical model. As expected, the percentage dense area was the strongest risk factor for breast cancer in both groups. Conclusions Our results indicate that absolute dense area is independently and positively associated with breast cancer risk, whereas absolute nondense area is independently and inversely associated with breast cancer risk. Since adipose tissue is radiographically nondense, these results suggest that adipose breast tissue may have a protective role in breast carcinogenesis

The Public Playground Paradox: "Child’s Joy" or Heterotopia of Fear?

Literature depicts children of the Global North withdrawing from public space to“acceptable islands”. Driven by fears both of and for children, the publicplayground – one such island – provides clear-cut distinctions between childhoodand adulthood. Extending this argument, this paper takes the original approach oftheoretically framing the playground as a heterotopia of deviance, examining –for the first time – three Greek public playground sites in relation to adjacentpublic space. Drawing on an ethnographic study in Athens, findings show fear tounderpin surveillance, control and playground boundary porosity. Normativeclassification as “children’s space” discourages adult engagement. However, in anovel and significant finding, a paradoxical phenomenon sees the playground’spresence simultaneously legitimizing playful behaviour in adjacent public spacefor children and adults. Extended playground play creates alternate orderings andnegotiates norms and hierarchies, suggesting significant wider potential toreconceptualise playground-urban design for an intergenerational public realm

An optimistic outlook on the use of evidence syntheses to inform environmental decision-making

Practitioners and policymakers working in environmental arenas make decisions that can have large impacts on ecosystems. Basing such decisions on high‐quality evidence about the effectiveness of different interventions can often maximize the success of policy and management. Accordingly, it is vital to understand how environmental professionals working at the science‐policy interface view and use different types of evidence, including evidence syntheses that collate and summarize available knowledge on a specific topic to save time for decision‐makers. We interviewed 84 senior environmental professionals in Canada working at the science‐policy interface to explore their confidence in, and use of, evidence syntheses within their organizations. Interviewees value evidence syntheses because they increase confidence in decision‐making, particularly for high‐profile or risky decisions. Despite this enthusiasm, the apparent lack of available syntheses for many environmental issues means that use can be limited and tends to be opportunistic. Our research suggests that if relevant, high quality evidence syntheses exist, they are likely to be used and embraced in decision‐making spheres. Therefore, efforts to increase capacity for conducting evidence syntheses within government agencies and/or funding such activities by external bodies have the potential to enable evidence‐based decision‐making.Additional co-authors: Karen E. Smokorowski, Steven M. Alexander, Steven J. Cook

Factors associated with testicular self-examination among unaffected men from multiple-case testicular cancer families

<p>Abstract</p> <p>Background</p> <p>The lifetime testicular cancer (TC) risk in the general population is relatively low (~1 in 250), but men with a family history of TC are at 4 to 9 times greater risk than those without. Some health and professional organizations recommend consideration of testicular self-examination (TSE) for certain high-risk groups (e.g. men with a family history of TC). Yet little is known about factors associated with TSE behaviors in this at-risk group.</p> <p>Methods</p> <p>We collected information on this subject during an on-going NCI multidisciplinary, etiologically-focused, cross-sectional Familial Testicular Cancer (FTC) study. We present the first report specifically targeting TSE behaviors among first- and second-degree relatives (n = 99) of affected men from families with ≥ 2 TC cases. Demographic, medical, knowledge, health belief, and psychological factors consistent with the Health Belief Model (HBM) were evaluated as variables related to TSE behavior, using chi-square tests of association for categorical variables, and t-tests for continuous variables.</p> <p>Results</p> <p>For men in our sample, 46% (n = 46) reported performing TSE regularly and 51% (n = 50) reported not regularly performing TSE. Factors associated (p < .05) with regularly performing TSE in multivariate analysis were physician recommendation and testicular cancer worry. This is the first study to examine TSE in unaffected men from FTC families.</p> <p>Conclusion</p> <p>The findings suggest that, even in this high-risk setting, TSE practices are sub-optimal. Our data provide a basis for further exploring psychosocial issues that are specific to men with a family history of TC, and formulating intervention strategies aimed at improving adherence to TSE guidelines.</p

Working relationships between obstetric care staff and their managers: a critical incident analysis

Background Malawi continues to experience critical shortages of key health technical cadres that can adequately respond to Malawi’s disease burden. Difficult working conditions contribute to low morale and frustration among health care workers. We aimed to understand how obstetric care staff perceive their working relationships with managers. Methods A qualitative exploratory study was conducted in health facilities in Malawi between October and December 2008. Critical Incident Analysis interviews were done in government district hospitals, faith-based health facilities, and a sample of health centres’ providing emergency obstetric care. A total of 84 service providers were interviewed. Data were analyzed using NVivo 8 software. Results Poor leadership styles affected working relationships between obstetric care staff and their managers. Main concerns were managers’ lack of support for staff welfare and staff performance, lack of mentorship for new staff and junior colleagues, as well as inadequate supportive supervision. All this led to frustrations, diminished motivation, lack of interest in their job and withdrawal from work, including staff seriously considering leaving their post. Conclusions Positive working relationships between obstetric care staff and their managers are essential for promoting staff motivation and positive work performance. However, this study revealed that staff were demotivated and undermined by transactional leadership styles and behavior, evidenced by management by exception and lack of feedback or recognition. A shift to transformational leadership in nurse-manager relationships is essential to establish good working relationships with staff. Improved providers’ job satisfaction and staff retentionare crucial to the provision of high quality care and will also ensure efficiency in health care delivery in Malawi

Sustainable care for children with cancer: a Lancet Oncology Commission.

We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020-50 would be four times greater than the cumulative treatment costs of$594 billion, producing a net benefit of $1986 billion on the global investment: a net return of$3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths

Beta cell function and ongoing autoimmunity in long-standing, childhood onset type 1 diabetes.

This study aimed to determine the frequency of residual beta cell function in individuals with long-standing type 1 diabetes who were recruited at diagnosis, and relate this to baseline and current islet autoantibody profile.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site