Prioritizing genomic applications for action by level of evidence: a horizon-scanning method.

As evidence accumulates on the use of genomic tests and other health-related applications of genomic technologies, decision makers may increasingly seek support in identifying which applications have sufficiently robust evidence to suggest they might be considered for action. As an interim working process to provide such support, we developed a horizon-scanning method that assigns genomic applications to tiers defined by availability of synthesized evidence. We illustrate an application of the method to pharmacogenomics tests.

Public health action in genomics is now needed beyond newborn screening.

For decades, newborn screening was the only public health program in the US focused on reducing morbidity, mortality and disability in people affected by genetic conditions. The landscape has changed, however, as evidence-based recommendations are now available for several other genomic applications that can save lives now in the US. Many more such applications are expected to emerge in the next decade. An action plan, based on evidence, provides the impetus for a new paradigm for public health practice in genomics across the lifespan using established multilevel processes as a guide. These include policy interventions, education, clinical interventions, and surveillance. Applying what we know today in hereditary breast/ovarian cancer, Lynch syndrome and familial hypercholesterolemia has the potential to affect thousands of people in the US population every year. Enhanced partnerships between genetic and nongenetic providers of clinical medicine and public health are needed to overcome the challenges for implementing genomic medicine applications both now and in the future.

Quasielastic light scattering study of the living human lens as a function of age.

PURPOSE: To determine contributions of molecular scattering elements to the increase with age in the light scattered from the human ocular lens in vivo. METHODS: We used quasielastic light scattering to measure autocorrelation functions of the intensity of light scattered in vivo from three locations (anterior, nuclear and posterior) along the optic axis in ocular lenses of 225 subjects, ranging from 17 to 63 years of age. We deduced probability distributions of key parameters (Is, If, Ii, IT), which describe contributions of slowly diffusing (Is), rapidly diffusing (If) and relatively immobile (Ii) scattering elements to the total light intensity (IT) scattered into the collection optics. We deduced characteristic time tau s and tau f that describe the Brownian motion of scattering elements. RESULTS: Probability distributions for each age decile show clearly defined shifts in key parameters with age. IT at the nucleus increases by a factor of three from age 20 to 60 years. This increase is produced principally by an approximate five-fold increase is Is. IT and Is and can be detected with an accuracy of approximately +/- 10%. We estimate threshold values for IT, which mark the boundary beyond which clinical cataract becomes manifest. This boundary represents 6 to 8 times the light scattering efficiency expected from the newborn lens. CONCLUSIONS: This methodology permits a sensitive, quantitative, clinically useful representation of the pre-cataractous molecular changes associated with aging in the living human lens.

Multilayer fluorescent immunoassay technique.

We describe a new multilayer immunoassay element for the determination of haptens in undiluted serum and plasma. Polysaccharide layers are coated onto a plastic base. The signal layer contains an immobilized antibody and a fluorescent-labeled hapten. A second layer, containing a pigment, acts as an optical screen. Sample spreading is achieved by a molded grid in contact with the upper layer of the immunoassay element. After sample is added to the element, endogenous analyte competes with the labeled hapten for the binding sites of the immobilized antibody; equilibrium is reached in 4-12 min. Because of the relative liquid-holding capacities of the layers and the grid, only a small amount of the free components remains in the signal layer. The signal is measured by front-surface fluorimetry. This technology has been applied to theophylline and thyroxin assays. Within- and between-run CVs range from 3% to 6%. Comparisons with fluorescent polarization immunoassays (Abbott TDx) showed excellent correlation (theophylline: r = 0.98, slope = 1.07, intercept = 0.3; thyroxin: r = 0.97, slope = 0.91, intercept = 0.8). The new method requires only one pipetting step (sample delivery) and is potentially applicable to a wide range of analytes.

Calcium pyrophosphate deposition in nonhuman primates.

Naturally occurring deposition of calcium pyrophosphate has been identified in six rhesus monkeys following acute episodes of trauma and various septicemias. Scanning electron microscopy with energy-dispersive X-ray analytical system and single crystal electron diffraction studies were used to identify the crystals within the articular cartilage. The osteoarthritis grading system was used to determine the degree of cartilage degenerative changes.

Prolapse of the amniotic sac ("hourglass membranes"): ultrasound appearance.

Prolapse of the amniotic sac through the partially dilated cervical os in pregnancy is called "hourglass membranes." Ultrasonography may be useful in identifying the presenting fetal or intra-uterine parts within the bulging membranes.