The European Common Variable Immunodeficiency Disorders registry was started in 1996 to define distinct clinical phenotypes and determine overlap within individual patients. A total of 7 centers contributed patient data, resulting in the largest cohort yet reported. Patients (334), validated for the diagnosis, were followed for an average of 25.6 years (9461 patientyears). Data were used to define 5 distinct clinical phenotypes: no complications, autoimmunity, polyclonal lymphocytic infiltration, enteropathy, and lymphoid malignancy. A total of 83% of patients had only one of these phenotypes. Analysis of mortality showed a considerable reduction in the last 15 years and that different phenotypes were associated with different survival times. Types of complications and clinical phenotypes varied significantly between countries, indicating the need for large, international registries. Ages at onset of symptoms and diagnosis were shown to have a Gaussian distribution, but were not useful predictors of phenotype. The only clinical predictor was polyclonal lymphocytic infiltration, which was associated with a 5-fold increased risk of lymphoid malignancy. There was widespread variation in the levels of serum immunoglobulin isotypes as well as in the percentages and absolute numbers of B cells, confirming the heterogeneity of these conditions. Higher serum IgM and lower circulating CD8 proportions were found to be predictive markers for polyclonal lymphocytic infiltration and autoimmunity, respectively. (Blood. 2008;112:277-286)

Vignettes are a valid tool for measuring the quality of clinical practice. They can be used for diverse clinical settings, diseases, physician types, and situations in which case-mix variation is a concern. They are inexpensive and easy to use. Vignettes are particularly useful for comparing quality among and within sites and may be useful for longitudinal evaluations of interventions intended to change clinical practice.

Although testosterone levels and muscle mass decline with age, many older men have serum testosterone level in the normal range, leading to speculation about whether older men are less sensitive to testosterone. We determined the responsiveness of androgen-dependent outcomes to graded testosterone doses in older men and compared it to that in young men. The participants in this randomized, double-blind trial were 60 ambulatory, healthy, older men, 60-75 yr of age, who had normal serum testosterone levels. Their responses to graded doses of testosterone were compared with previous data in 61 men, 19-35 yr old. The participants received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate weekly for 20 wk. Fat-free mass, fat mass, muscle strength, sexual function, mood, visuospatial cognition, hormone levels, and safety measures were evaluated before, during, and after treatment. Of 60 older men who were randomized, 52 completed the study. After adjusting for testosterone dose, changes in serum total testosterone (change, -6.8, -1.9, +16.1, +49.5, and +101.9 nmol/liter at 25, 50, 125, 300, and 600 mg/wk, respectively) and hemoglobin (change, -3.6, +9.9, +20.9, +12.6, and +29.4 g/liter at 25, 50, 125, 300, and 600 mg/wk, respectively) levels were dose-related in older men and significantly greater in older men than young men (each P < 0.0001). The changes in FFM (-0.3, +1.7, +4.2, +5.6, and +7.3 kg, respectively, in five ascending dose groups) and muscle strength in older men were correlated with testosterone dose and concentrations and were not significantly different in young and older men. Changes in fat mass correlated inversely with testosterone dose (r = -0.54; P < 0.001) and were significantly different in young vs. older men (P < 0.0001); young men receiving 25- and 50-mg doses gained more fat mass than older men (P < 0.0001). Mood and visuospatial cognition did not change significantly in either group. Frequency of hematocrit greater than 54%, leg edema, and prostate events were numerically higher in older men than in young men. Older men are as responsive as young men to testosterone's anabolic effects; however, older men have lower testosterone clearance rates, higher increments in hemoglobin, and a higher frequency of adverse effects. Although substantial gains in muscle mass and strength can be realized in older men with supraphysiological testosterone doses, these high doses are associated with a high frequency of adverse effects. The best trade-off was achieved with a testosterone dose (125 mg) that was associated with high normal testosterone levels, low frequency of adverse events, and significant gains in fat-free mass and muscle strength.

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Abstract-We report the results of high-resolution, analytical and scanning transmission electron microscopy (STEM), including intensive element mapping, of severely thermally modified dust from comet 81P/Wild 2 caught in the silica aerogel capture cells of the Stardust mission. Thermal interactions during capture caused widespread melting of cometary silicates, Fe-Ni-S phases, and the aerogel. The characteristic assemblage of thermally modified material consists of a vesicular, silicarich glass matrix with abundant Fe-Ni-S droplets, the latter of which exhibit a distinct core-mantle structure with a metallic Fe,Ni core and a iron-sulfide rim. Within the glassy matrix, the elemental distribution is highly heterogeneous. Localized amorphous "dust-rich" patches contain Mg, Al, and Ca in higher abundances and suggest incomplete mixing of silicate progenitors with molten aerogel. In some cases, the element distribution within these patches seems to depict the outlines of ghost mineral assemblages, allowing the reconstruction of the original mineralogy. A few crystalline silicates survived with alteration limited to the grain rims. The Fe-and CI-normalized bulk composition derived from several sections show CI-chondrite relative abundances for Mg, Al, S, Ca, Cr, Mn, Fe, and Ni. The data indicate a 5 to 15% admixture of fine-grained chondritic comet dust with the silica glass matrix. These strongly thermally modified samples could have originated from a finegrained primitive material, loosely bound Wild 2 dust aggregates, which were heated and melted more efficiently than the relatively coarse-grained material of the crystalline particles found elsewhere in many of the same Stardust aerogel tracks (Zolensky et al. 2006).

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5 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Sunday, June, 2, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.

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