An increased risk of cardiovascular death in Cytomegalovirus (CMV)-infected individuals remains unexplained, although it might partly result from the fact that CMV infection is closely associated with the accumulation of CD28null T-cells, in particular CD28null CD4 T-cells. These cells can directly damage endothelium and precipitate cardiovascular events. However, the current paradigm holds that the accumulation of CD28null T-cells is a normal consequence of aging, whereas the link between these T-cell populations and CMV infection is explained by the increased prevalence of this infection in older people. Resolving whether CMV infection or aging triggers CD28null T-cell expansions is of critical importance because, unlike aging, CMV infection can be treated.Methods: We used multi-color flow-cytometry, antigen-specific activation assays, and HLA-typing to dissect the contributions of CMV infection and aging to the accumulation of CD28null CD4 and CD8 T-cells in CMV+ and CMV- individuals aged 19 to 94 years. Linear/logistic regression was used to test the effect of sex, age, CMV infection, and HLA-type on CD28null T-cell frequencies.Results: The median frequencies of CD28null CD4 T-cells and CD28null CD8 T-cells were >12-fold (p=0.000) but only approximately 2-fold higher (p=0.000), respectively, in CMV+ (n=136) compared with CMV- individuals (n=106). The effect of CMV infection on these T-cell subsets was confirmed by linear regression. Unexpectedly, aging contributed only marginally to an increase in CD28null T-cell frequencies, and only in CMV+ individuals. Interestingly, the presence of HLA-DRB1*0301 led to an approximately 9-fold reduction of the risk of having CD28null CD4 T-cell expansions (OR=0.108, p=0.003). Over 75% of CMV-reactive CD4 T-cells were CD28null.Conclusion: CMV infection and HLA type are major risk factors for CD28null CD4 T-cell-associated cardiovascular pathology. Increased numbers of CD28null CD8 T-cells are also associated with CMV infection, but to a lesser extent. Aging, however, makes only a negligible contribution to the expansion of these T-cell subsets, and only in the presence of CMV infection. Our results open up new avenues for risk assessment, prevention, and treatment.

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Enabling Dedicated Path Protection (DPP) in Filterless Optical Networks (FONs) poses specific design challenges, as FONs require dividing the network topology in non-overlapping fiber trees, and lightpaths cannot cross from one tree to another unless additional devices are installed. In this study, we consider the possibility to deploy three type of devices, namely Inter-Tree Transceivers (ITTs), Wavelength Blockers (WBs) and Colored Passive Filters (CPFs) to achieve DPP in FON, and we compare the three resulting DPP strategies, called P-ITT, P-WB and P-WBC. More specifically, we formulate three Integer Linear Programming (ILP) models for DPP in FON with the objective to minimize additional device cost and minimize total wavelength consumption. Numerical results over two realistic topologies show that P-WBC achieves cost savings up to 33% in comparison to P-WB and up to 97% in comparison to P-ITT. However, even if it is the costliest approach, P-ITT ensures up to 7% savings in wavelength consumption and up to 23% savings in resource overbuild compared to P-WB and P-WBC, making it a possible candidate in spectrum-scarce deployments.

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