Personalizing Breast Cancer Screening Based on Polygenic Risk and Family History

_Background:_ We assessed the clinical utility of a first-degree breast cancer family history and polygenic risk score (PRS) to inform screening decisions among women aged 30-50 years. _Methods:_ Two established breast cancer models evaluated digital mammography screening strategies in the 1985 US birth cohort by risk groups defined by family history and PRS based on 313 single nucleotide polymorphisms. Strategies varied in initiation age and interval. The benefits and harms were compared with those seen with 3 established screening guidelines. _Results:_ Women with a breast cancer family history who initiated biennial screening at age 40 years had a 36% increase in life-years gained and 20% more breast cancer deaths averted, but 21% more overdiagnoses and 63% more false positives. Screening tailored to PRS vs biennial screening from50 to 74 years had smaller positive effects on life-years gained and breast cancer deaths averted but also smaller increases in overdiagnoses and false positives. Combined use of family history and PRS vs biennial screening from 50 to 74 years had the greatest increase in life-years gained and breast cancer deaths averted. _Conclusions:_ Our results suggest that breast cancer family history and PRS could guide screening decisions before age 50 years among women at increased risk for breast cancer but expected increases in overdiagnoses and false positives should be expected

The Origin, Early Evolution and Predictability of Solar Eruptions

Coronal mass ejections (CMEs) were discovered in the early 1970s when space-borne coronagraphs revealed that eruptions of plasma are ejected from the Sun. Today, it is known that the Sun produces eruptive flares, filament eruptions, coronal mass ejections and failed eruptions; all thought to be due to a release of energy stored in the coronal magnetic field during its drastic reconfiguration. This review discusses the observations and physical mechanisms behind this eruptive activity, with a view to making an assessment of the current capability of forecasting these events for space weather risk and impact mitigation. Whilst a wealth of observations exist, and detailed models have been developed, there still exists a need to draw these approaches together. In particular more realistic models are encouraged in order to asses the full range of complexity of the solar atmosphere and the criteria for which an eruption is formed. From the observational side, a more detailed understanding of the role of photospheric flows and reconnection is needed in order to identify the evolutionary path that ultimately means a magnetic structure will erupt

Controlling injection: regulation of type III secretion in enterohaemorrhagic <i>Escherichia coli</i>

Type III secretion (T3S) systems enable the injection of bacterial proteins through membrane barriers into host cells, either from outside the host cell or from within a vacuole. This system is required for colonization of their ruminant reservoir hosts by enterohaemorrhagic &lt;i&gt;Escherichia coli&lt;/i&gt; (EHEC) and might also be important for the etiology of disease in the incidental human host. T3S systems of &lt;i&gt;E. coli&lt;/i&gt; inject a cocktail of proteins into epithelial cells that enables bacterial attachment and promotes longer-term colonization in the animal. Here, we review recent progress in our understanding of the regulation of T3S in EHEC, focusing on the induction and assembly of the T3S system, the co-ordination of effector protein expression, and the timing of effector protein export through the apparatus. Strain variation is often associated with differences in bacteriophages encoding the production of Shiga toxin and in multiple cryptic prophage elements that can encode effector proteins and T3S regulators. It is evident that this repertoire of phage-related sequences results in the different levels of T3S demonstrated between strains, with implications for EHEC epidemiology and strain evolution

Comparison of Access Policies for Replica Placement in Tree Networks

In this paper, we discuss and compare several policies to place replicas in tree networks sub ject to server capacity. The client requests are known beforehand, while the number and location of the servers are to be determined. The standard approach in the literature is to enforce that all requests of a client be served by a single server in the tree (Single). One major contribution of this paper is to assess the impact of a new policy in which requests of a given client can be processed by multiple servers (Multiple), thus distributing the processing of requests over the platform. We characterize problem instances for which Multiple cannot be more than two times better than the optimal Single solution, if this latter exists. For such instances, we provide a procedure which builds a Single solution with a guarantee on its cost. This is a very interesting result for applications which do not accept multiple servers for a given client, since it might be more difficult to implement such a complex strategy