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BACKGROUNDWe aimed to characterize factors associated with the under-studied complication of cognitive decline in aging people with long-duration type 1 diabetes (T1D).METHODSJoslin \"Medalists\" (n = 222; T1D ≥ 50 years) underwent cognitive testing. Medalists (n = 52) and age-matched nondiabetic controls (n = 20) underwent neuro- and retinal imaging. Brain pathology (n = 26) was examined. Relationships among clinical, cognitive, and neuroimaging parameters were evaluated.RESULTSCompared with controls, Medalists had worse psychomotor function and recall, which associated with female sex, lower visual acuity, reduced physical activity, longer diabetes duration, and higher inflammatory cytokines. On neuroimaging, compared with controls, Medalists had significantly lower total and regional brain volumes, equivalent to 9 years of accelerated aging, but small vessel disease markers did not differ. Reduced brain volumes associated with female sex, reduced psychomotor function, worse visual acuity, longer diabetes duration, and higher inflammation, but not with glycemic control. Worse cognitive function, lower brain volumes, and diabetic retinopathy correlated with thinning of the outer retinal nuclear layer. Worse baseline visual acuity associated with declining psychomotor function in longitudinal analysis. Brain volume mediated the association between visual acuity and psychomotor function by 57%. Brain pathologies showed decreased volumes, but predominantly mild vascular or Alzheimer's-related pathology.CONCLUSION To our knowledge, this is the first comprehensive study of cognitive function, neuroimaging, and pathology in aging T1D individuals demonstrated that cognitive decline was related to parenchymal rather than neurovascular abnormalities, unlike type 2 diabetes, suggestive of accelerated aging in T1D. Improving visual acuity could perhaps be an important preventive measure against cognitive decline in people with T1D.FUNDINGThe Beatson Foundation, NIH/NIDDK grants 3P30DK036836-34S1 and P30DK036836-37, and Mary Iacocca fellowships.

Background Modeling the cell-division cycle has been practiced for many years. As time has progressed, this work has gone from understanding the basic principles to addressing distinct biological problems, e.g., the nature of the restriction point, how checkpoints operate, the nonlinear dynamics of the cell cycle, the effect of localization, etc. Most models consist of coupled ordinary differential equations developed by the researchers, restricted to deal with the interactions of a limited number of molecules. In the future, cell-cycle modeling--and indeed all modeling of complex biologic processes--will increase in scope and detail. Results A framework for modeling complex cell-biologic processes is proposed here. The framework is based on two constructs: one describing the entire lifecycle of a molecule and the second describing the basic cellular machinery. Use of these constructs allows complex models to be built in a straightforward manner that fosters rigor and completeness. To demonstrate the framework, an example model of the mammalian cell cycle is presented that consists of several hundred differential equations of simple mass action kinetics. The model calculates energy usage, amino acid and nucleotide usage, membrane transport, RNA synthesis and destruction, and protein synthesis and destruction for 33 proteins to give an in-depth look at the cell cycle. Conclusions The framework presented here addresses how to develop increasingly descriptive models of complex cell-biologic processes. The example model of cellular growth and division constructed with the framework demonstrates that large structured models can be created with the framework, and these models can generate non-trivial descriptions of cellular processes. Predictions from the example model include those at both the molecular level--e.g., Wee1 spontaneously reactivates--and at the system level--e.g., pathways for timing-critical processes must shut down redundant pathways. A future effort is to automatically estimate parameter values that are insensitive to changes.

Objective. We assessed the validity of selected items on the 2003 revised U.S. Standard Certificate of Live Birth to understand the accuracy of new and existing items. Methods. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of select variables reported on the birth certificate using the medical record as the gold standard for a representative sample of live births in New York City (n=603) and Vermont (n=664) in 2009. Results. In both sites, sensitivity was excellent (>90%) for Medicaid coverage at delivery, any previous live births, and current method of delivery; sensitivity was moderate (70%-90%) for gestational diabetes; and sensitivity was poor (<70%) for premature rupture of the membranes and gestational hypertension. In both sites, PPV was excellent for Medicaid coverage, any previous live births, previous cesarean delivery, and current method of delivery, and poor for premature rupture of membranes. In both sites, almost all items had excellent (>90%) specificity and NPV. Conclusion. Further research is needed to determine how best to improve the quality of data on the birth certificate. Future revisions of the birth certificate may consider removing those items that have consistently proven difficult to report accurately.

To assess the validity of self-reported maternal and infant health indicators reported by mothers an average of 4 months after delivery. Three validity measures—sensitivity, specificity and positive predictive value (PPV)—were calculated for pregnancy history, pregnancy complications, health care utilization, and infant health indicators self-reported on the Pregnancy Risk Assessment Monitoring System (PRAMS) questionnaire by a representative sample of mothers delivering live births in New York City (NYC) (n = 603) and Vermont (n = 664) in 2009. Data abstracted from hospital records served as gold standards. All data were weighted to be representative of women delivering live births in NYC or Vermont during the study period. Most PRAMS indicators had >90 % specificity. Indicators with >90 % sensitivity and PPV for both sites included prior live birth, any diabetes, and Medicaid insurance at delivery, and for Vermont only, infant admission to the NICU and breastfeeding in the hospital. Indicators with poor sensitivity and PPV (<70 %) for both sites (i.e., NYC and Vermont) included placenta previa and/or placental abruption, urinary tract infection or kidney infection, and for NYC only, preterm labor, prior low-birth-weight birth, and prior preterm birth. For Vermont only, receipt of an HIV test during pregnancy had poor sensitivity and PPV. Mothers accurately reported information on prior live births and Medicaid insurance at delivery; however, mothers’ recall of certain pregnancy complications and pregnancy history was poor. These findings could be used to prioritize data collection of indicators with high validity.

Our society is increasingly reliant on systems and interoperating collections of systems, known as systems of systems (SoS). Our national security is built on SoS, such as Army brigades, airport security, and nuclear weapons security. These SoS are often subject to changing budgets, changing missions (e.g., nation building, arms-control treaties), changing threats (e.g., asymmetric warfare, terrorism, WMDs), and changing natural environments (e.g., climate, weather, natural disasters). Can vital SoS adapt to these changing landscapes effectively and efficiently? This paper describes research at Sandia National Laboratories to develop metrics for measuring the adaptability of SoS. We report that we could not find a single or absolute adaptability metric, in large part due to lack of general objectives or structures of SoS. However, we do report a set of metrics that can be applied relatively, plus a method for combining the metrics into an adaptability index, a single value that can be used to compare SoS designs. We show in a test case that these metrics can distinguish good and poor performance under a variable mission space and an uncertain threat environment. The metrics are intended to support a long-range goal of creating an analytic capability to assist in the design and operation of adaptable systems and SoS.

Today's fixed-income environment is challenging for insurers. With low yields and tight spreads, insurers have begun contemplating an investment strategy that includes both passive and active management of their portfolios. This modified total-return approach may be the most efficient way for insurers to generate meaningful returns. The first step in optimizing a portfolio is to complete a strategic asset allocation. One way for insurers to achieve potentially higher returns, without impacting overall portfolio risk, is to increase active fixed-income risk. Once the insurer determines that it is willing to take active risk (deviate from the benchmark), it should determine how much active risk it is willing to take. Once an insurer establishes the maximum amount of tracking error available from its guidelines and from the marketplace, it should determine the ultimate amount of tracking error it is willing to take, and, as importantly, the excess return it expects to generate by taking that risk.

The full-page photo (Sept. 13) showing the New York Fire Department raising the American flag amid the debris of...

Unlike the tone of McKenny's letter, I attempt to vote the most qualified person into office, not simply vote a political party into office.

There is a \"Framework Agreement\" between the OPP and the Timmins Police Service as in every other municipally policed community within Ontario, as mandated by the Police Services Act. This agreement specifies services will be provided by the signatories to the agreement in case of emergency at no cost to either service. There still exists today an excellent working relationship between members of the Timmins Police Service and the Ontario Provincial Police. This ensures citizens of the City of Timmins will continue to receive excellent policing from both the OPP and TPS. As to the comments that the Timmins Police at times works short handed, I wonder if Mr. [Clayton McAlpine] can provide dates and time when the TPS has worked short-handed due to illness, vacation leave or unforeseen circumstances?