Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies.

Recently our group and others have identified DDX41 mutations both as germ line and acquired somatic mutations in families with multiple cases of late onset myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML), suggesting that DDX41 acts as a tumor suppressor. To determine whether novel DDX41 mutations could be identified in families with additional types of hematologic malignancies, our group screened two cohorts of families with a diverse range of hematologic malignancy subtypes. Among 289 families, we identified nine (3%) with DDX41 mutations. As previously observed, MDS and AML were the most common malignancies, often of the erythroblastic subtype, and 1 family displayed early-onset follicular lymphoma. Five novel mutations were identified, including missense mutations within important functional domains and start-loss and splicing mutations predicted to result in truncated proteins. We also show that most asymptomatic mutation carriers have normal blood counts until malignancy develops. This study expands both the mutation and phenotypic spectra observed in families with germ line DDX41 mutations. With an increasing number of both inherited and acquired mutations in this gene being identified, further study of how DDX41 disruption leads to hematologic malignancies is critical.

Nudges or mandates? The ethics of mandatory flu vaccination.

According to the CDC report for the 2012-2013 influenza season, there was a modest increase in the vaccination coverage rate among healthcare workers from 67% in 2011-2012, to 72% in 2012-2013 to the current 75% coverage. This is still far from reaching the US National Healthy People 2020 goal of 90% hospitals vaccination rates. The reported increase in coverage is attributed to the growing number of healthcare facilities with vaccination requirements with average rates of 96.5%. However, a few other public health interventions stir so much controversy and debate as vaccination mandates. The opposition stems from the belief that a mandatory flu shot policy violates an individual right to refuse unwanted treatment. This article outlines the historic push to achieve higher vaccination rates among healthcare professionals and a number of ethical issues arising from attempts to implement vaccination mandates. It then turns to a review of cognitive biases relevant in the context of decisions about influenza vaccination (omission bias, ambiguity aversion, present bias etc.) The article suggests that a successful strategy for policy-makers and others hoping to increase vaccination rates is to design a "choice architecture" that influences behavior of healthcare professionals without foreclosing other options. Nudges incentivize vaccinations and help better align vaccination intentions with near-term actions.