Methods: Performed mathematical and statistical analysis of the cross-sectional estimator of HIV incidence to evaluate bias and variance. Developed probability models to evaluate impact of long tails of the window period distribution on accuracy.

Results: The standard cross-sectional estimate of HIV incidence rate is estimating a time-lagged incidence where the lag time, called the shadow, depends on the mean and the coefficient of variation of window periods. Equations show how the shadow increases with the mean and the coefficient of variation. We find with an assay such as

BED capture enzyme immunoassay, if only 0.5% are elite controllers who remain in the window until death, then the shadow is over 2.5 years, implying that estimates reflect HIV incidence more than 2 years in the past rather than current levels. If even 5% of AIDS cases are unrecognized and not excluded from the numbers in the window, then

the shadow is more than 2.2 years.

Conclusions: Small perturbations to the tail of the window period distribution can have large effects on the accuracy of current HIVincidence estimates. The shadow and mean window period are usefulfor comparing the accuracy of assays. The results help explaindifferences reported between cohort and cross-sectional HIVincidence estimates. Screening out elite or viremic controllers by RNA polymerase chain reaction testing, and persons with advancedHIV disease (with AIDS or on antiretrovirals) may considerablyimprove the accuracy of HIV incidence estimates based on BED or similar assays.

Design: Considered the Hargrove and McDougal adjustment procedures that adjust biomarker estimates of HIV incidence rates for misclassification with respect to the timing of infections.

Methods: Performed mathematical and statistical analysis of the adjustment formulas. Evaluated sources of error in cohort studies of incidence that could also explain discrepancies between cohort and biomarker estimates.

Results: The McDougal adjustment has no net effect on the estimate of HIV incidence because false positives exactly counterbalance false negatives. The Hargrove adjustment has a mathematical error that can cause significant underestimation of HIV incidence rates especially if there is a large pool of prevalent long standing infections.

Conclusion: The two adjustment procedures of biomarker incidence estimates evaluated here that purport to correct for misclassification, do not increase accuracy and in some situations can introduce significant bias. Instead, the accuracy of biomarker estimates can be increased through improvements in the estimates of the mean window period of the populations under study and the representativeness of the cross-sectional samples. Cohort estimates of incidence are also subject to important sources of error and should not blindly be considered the gold standard for assessing the validity of biomarker estimates.

The article is dedicated to the memory of Blake Charvat

Methods We identified all studies in the peer review literature that reported age-specific incidence rates for AD. We modeled the logarithm of the incidence rate as a linear function of age. We used both fixed effects models and random effects models to account for interstudy variation.

Results AD incidence rates exponentially increase with increasing age. The overall estimate of the doubling time was 5.5 years. The doubling times from studies performed in North America and Europe were 6.0 and 5.8, respectively; whereas the doubling times in all other parts of the world were 5.0. There was no significant geographic differences in doubling times (P = .3). Although the doubling times were slightly longer for men (6.5 years) than for women (5.4 years), the difference was not significant (P = .3).

Conclusions Doubling times of AD incidence rates are not statistically significantly different among populations throughout the world. The risk of AD grows exponentially with age, doubling approximately every 5 to 6 years. Although the shapes of the incidence curves are similar, there is considerable variation in absolute incidence rates throughout the world. Currently, there are limited epidemiologic data at the oldest ages, and further study is needed to accurately define the incidence curve above age 90.

Objective: To estimate HIV incidence in the United States.

Design, Setting, and Patients : Remnant diagnostic serum specimens from patients 13 years or older and newly diagnosed with HIV during 2006 in 22 states were tested with the BED HIV-1 capture enzyme immunoassay to classify infections as recent or long-standing. Information on HIV cases was reported to the Centers for Disease Control and Prevention through June 2007. Incidence of HIV in the 22 states during 2006 was estimated using a statistical approach with adjustment for testing frequency and extrapolated to the United States. Results were corroborated with back-calculation of HIV incidence for 1977-2006 based on HIV diagnoses from 40 states and AIDS incidence from 50 states and the District of Columbia.

Main Outcome Measure : Estimated HIV incidence.

Results: An estimated 39 400 persons were diagnosed with HIV in 2006 in the 22 states. Of 6864 diagnostic specimens tested using the BED assay, 2133 (31%) were classified as recent infections. Based on extrapolations from these data, the estimated number of new infections for the United States in 2006 was 56 300 (95% confidence interval [CI], 48 200-64 500); the estimated incidence rate was 22.8 per 100 000 population (95% CI, 19.5-26.1). Forty-five percent of infections were among black individuals and 53% among men who have sex with men. The back-calculation (n = 1.230 million HIV/AIDS cases reported by the end of 2006) yielded an estimate of 55 400 (95% CI, 50 000-60 800) new infections per year for 2003-2006 and indicated that HIV incidence increased in the mid-1990s, then slightly declined after 1999 and has been stable thereafter.

Conclusions: This study provides the first direct estimates of HIV incidence in the United States using laboratory technologies previously implemented only in clinic-based settings. New HIV infections in the United States remain concentrated among men who have sex with men and among black individuals.

METHODS: The numbers of individuals in the United States with Alzheimer's disease and the numbers of newly diagnosed cases that can be expected over the next 50 years were estimated from a model that used age-specific incidence rates summarized from several epidemiological studies, US mortality rates, and US Bureau of the Census projections.

RESULTS: in 1997, the prevalence of Alzheimer's disease in the United States was 2.32 million (range: 1.09 to 4.58 million); of these individuals, 68% were female. It is projected that the prevalence will nearly quadruple in the next 50 years, by which time approximately 1 in 45 Americans will be afflicted with the disease. Currently, the annual number of new incident cases in 360,000. If interventions could delay onset of the disease by 2 years, after 50 years there would be nearly 2 million fewer cases than projected; if onset could be delayed by 1 year, there would be nearly 800,000 fewer prevalent cases.

CONCLUSIONS: As the US population ages, Alzheimer's disease will become an enormous public health problem. interventions that could delay disease onset even modestly would have a major public health impact.

On October 2, 2001 a sixty-three-year-old Florida man who worked as a photo editor at a media publishing company was admitted to an emergency department complaining of nausea, vomiting, and fever. His symptoms began four days earlier on a recreational trip to North Carolina. The man died shortly thereafter. An astute clinician quickly made the surprising diagnosis of inhalational anthrax, which is a serious and deadly disease. The diagnosis was surprising because inhalational anthrax is extremely rare; only 18 cases were reported in the United States between 1900 and 1978. Public health officials at first believed that the Florida case was an isolated, rare event that might have gone unnoticed except for the heightened state of public health vigilance and alert following the catastrophic events of September 11, 2001. However, when a second case occurred in a seventy-three-year-old man who worked at the same Florida media publishing company and delivered mail to the first man, the coincidence seemed remarkable. Employees of the media publishing company reported seeing a suspicious letter on or about September 19, 2001, although that letter was never found. Public health officials theorized that a letter contaminated with deadly finely milled anthrax spores was the source of the disease. Thus began the 2001 anthrax outbreak in the United States caused by the intentional release of anthrax spores, an act of bioterrorism.