Optimization of Time- and Code-Division-Multiplexed Readout for Athena X-IFU.

Readout of a large, spacecraft-based array of superconducting transition-edge sensors (TESs) requires careful management of the layout area and power dissipation of the cryogenic-circuit components. We present three optimizations of our time- (TDM) and code-division-multiplexing (CDM) systems for the X-ray Integral Field Unit (X-IFU), a several-thousand-pixel-TES array for the planned Athena-satellite mission. The first optimization is a new readout scheme that is a hybrid of CDM and TDM. This C/TDM architecture balances CDM's noise advantage with TDM's layout compactness. The second is a redesign of a component: the shunt resistor that provides a dc-voltage bias to the TESs. A new layout and a thicker Pd-Au resistive layer combine to reduce this resistor's area by more than a factor of 5. Third, we have studied the power dissipated by the first-stage SQUIDs (superconducting quantum-interference devices) and the readout noise versus the critical current of the first-stage SqUIDs. As a result, the X-IFU TDM and C/TDM SQUIDs will have a specified junction critical current of 5 µA. Based on these design optimizations and TDM experiments described by Durkin, et al. (these proceedings), TDM meets all requirements to be X-IFU's backup-readout option. Hybrid C/TDM is another viable option that could save spacecraft resources.

Demonstration of Athena X-IFU Compatible 40-Row Time-Division-Multiplexed Readout.

Time-division multiplexing (TDM) is the backup readout technology for the X-ray Integral Field Unit (X-IFU), a 3,168-pixel X-ray transition-edge sensor (TES) array that will provide imaging spectroscopy for ESA's Athena satellite mission. X-0IFU design studies are considering readout with a multiplexing factor of up to 40. We present data showing 40-row TDM readout (32 TES rows + 8 repeats of the last row) of TESs that are of the same type as those being planned for X-IFU, using measurement and analysis parameters within the ranges specified for X-IFU. Singlecolumn TDM measurements have best-fit energy resolution of (1.91 ± 0.01) eV for the Al Kα complex (1.5 keV), (2.10 ± 0.02) eV for Ti Kα (4.5 keV), (2.23 ± 0.02) eV for Mn Kα (5.9 keV), (2.40 ± 0.02) eV for Co Kα (6.9 keV), and (3.44 ± 0.04) eV for Br Kα (11.9 keV). Three-column measurements have best-fit resolution of (2.03 ± 0.01) eV for Ti Kα and (2.40 ± 0.01) eV for Co Kα. The degradation due to the multiplexed readout ranges from 0.1 eV at the lower end of the energy range to 0.5 eV at the higher end. The demonstrated performance meets X-IFU's energy-resolution and energy-range requirements. True 40-row TDM readout, without repeated rows, of kilopixel scale arrays of X-IFU-like TESs is now under development.

Antibody to human endogenous retrovirus peptide in urine of human immunodeficiency virus type 1-positive patients.

Human endogenous retrovirus (HERV)-like sequences are normal inherited elements that constitute several hundredths of the human genome. The expression of genes located within these elements can occur as a consequence of several different events, including persistent inflammation or genotoxic events. Antibodies to endogenous retroviral gene products have been found in a number of infectious, chronic, and malignant diseases, suggesting a role in disease initiation and progression. We studied human immunodeficiency virus type 1 (HIV-1)-infected patients for evidence of urine antibody to a HERV peptide and investigated correlates with clinical and laboratory parameters. Forty-three HIV-1-infected patients in documented asymptomatic, symptomatic, or AIDS stages of disease and 21 age- and gender-matched, uninfected controls were tested for antibody to HERV-related peptide 4.1. Urine specimens were examined in a blinded fashion with the Calypte Biomedical Corp. experimental enzyme immunoassay for antibody to peptide 4.1. Results were compared with demographic data, medical history, clinical state of disease, and results of other laboratory tests. Thirty-six percent of the asymptomatic (Centers for Disease Control and Prevention [CDC] category A) and 81.3% of both the symptomatic (CDC category B) and AIDS (CDC category C) patients were positive for antibody to HERV-related peptide 4.1. None of the controls were positive. In this study, antibodies to HERV-related peptide 4.1 were found more frequently in patients with advanced stages (categories B and C) of HIV-1 disease than in those patients with an earlier stage (category A) of HIV disease. In HIV patients, severe immunosuppression, defined as having had at least one opportunistic infection, correlated with the expression of antibody to a HERV-related peptide.

Sarcoidosis: a primary care review.

Sarcoidosis is a multisystemic disorder of unknown etiology that most commonly affects adults between 20 and 40 years of age. Patients with sarcoidosis frequently present with bilateral hilar lymphadenopathy and pulmonary infiltration, and often with ocular and skin lesions. The diagnosis is established when clinical and radiographic findings are supported by histologic evidence of non-caseating epithelioid cell granulomas found on tissue biopsy. Diagnosis of sarcoidosis requires exclusion of other causes of granuloma formation. Sarcoidosis is also characterized by distinctive laboratory abnormalities, including hyperglobulinemia, an elevated serum angiotensin converting enzyme level, evidence of depressed cellular immunity manifested by cutaneous anergy and, occasionally, hypercalcemia and hypercalciuria. Glucocorticoids remain the mainstay of therapy when treatment is required, although other anti-inflammatory agents are being used increasingly often.

Implementation of a proficiency testing program for Lyme disease in New York State.

Nine proficiency test events for Lyme disease (Borrelia burgdorferi) antibody were carried out from October 1988 to January 1992 by the New York State Department of Health, Albany, Overall sensitivity for the 846 participants averaged 95.4%, with varying sensitivities of 98.7% for users (71 laboratories) of immunofluorescence assays, 97.4% for users (144 laboratories) of solid-phase fluorescence immunoassays, and 94.6% for users (631 laboratories) of enzyme immunoassays. Thirty percent of the enzyme immunoassay laboratories tested at greater than or equal to 98.4% sensitivity by the DiaMedix test kit (DiaMedix Corp, Miami, Fla) and MarDx test kit (MarDx Diagnostics Inc, Scotch Plains, NJ), while 7% tested at less than or equal to 83% by the Access test kit (Access Medical Systems Inc, Branford, Conn) and the Cambridge BioScience test kit (Cambridge BioScience, Worcester, Mass). Overall specificity was 98.8%, with specificities greater than 99% for both solid-phase fluorescence immunoassay and enzyme immunoassay users and 92.9% for immunofluorescence assay users. Cross-reactivity with Treponema pallidum antibody was high for the Hillcrest (Hillcrest Biologicals, Cypress, Calif) (30%) and Wampole (Wampole Laboratories, Cranbury, NJ) (25%) immunofluorescence assay test kit users and for the MarDx (30%) and 3M (3M Diagnostics Systems Inc, Santa Clara, Calif) (24%) enzyme immunoassay test kit users. Laboratories that tested by the Wampole immunofluorescence assay test kit had also high cross-reactivity (25%) against heterophile antibody.

HIV infection among women entering the New York State correctional system.

Human immunodeficiency virus infection is the leading medical problem among prison inmates in several states. In 1988 a blinded seroprevalence study was conducted on 480 New York female prison entrants to determine the prevalence of and risk factors for HIV infection in this population. Ninety (18.8 percent) women were HIV-seropositive. Seroprevalence was highest among women ages 30-39 (25.0 percent) and varied by ethnicity (Hispanics, 29.4 percent; Blacks, 14.4 percent; Whites, 7.1 percent) and residence (New York City, 23.8 percent; Upstate, 5.1 percent). Nearly half (44.9 percent) of the 136 acknowledged intravenous drug users and one-third (33.8 percent) of the 71 women with a positive syphilis serology were HIV-seropositive. There was no difference in fertility histories between seropositive and seronegative women, and two of 21 pregnant women were seropositive. This study led to increased clinical and prevention services for this high-risk population.

Feed restriction of turkey breeder hens--a review.

Past research on feed restriction methods with turkey breeder hens has involved the feeding of 1) high-fiber or low-energy diets, 2) low dietary protein, 3) limited quantities of feed, 4) rations on a skip-a-day program, 5) distasteful compounds, or 6) combinations of these methods. In general, feed-restricted turkey breeder hens showed a reduction in BW and a delay in sexual maturity at time of lay with no effect on fertility, hatchability of fertile eggs, and hatchability of all eggs set. Egg weight was unaffected in 13 studies, but decreases and increases were reported for two and three studies, respectively. The results on egg production and feed efficiency (number of eggs/unit of feed) were more variable. Egg production decreased, increased, or had no effect in 6, 2, and 14 of the feed restriction programs, respectively. Feed efficiency of restricted hens either was poorer (two reports), improved (three studies), or had no effect (six studies). The larger parent-stock breeder candidate of today may not respond to these feed restriction programs in the same manner as the breeder hens of the 1970s and early 1980s. Most likely, more severe feed restriction programs will have to be designed to lower the BW of these larger hens.

Possible typhus-group infection in New York State: presentation of four suspect cases.

Epidemiologic investigations were recently conducted on four cases which were reported in New York State in 1986 and 1987, three of which were within one family. These included hospital chart reviews, case or family interviews, animal trappings, and ectoparasite surveys. Serologic tests and immunoblots were performed on blood samples obtained from these patients. All four patients had acute febrile illnesses; two required hospitalization and one died. Microimmunofluorescence test results using Rickettsia typhi and R. prowazekii antigens showed a greater than or equal to 4-fold increase in titer with paired sera from three patients. The remaining patient had a single serum titer of 4096 with both antigens. In addition, sera from all patients reacted with R. typhi in the immunoblot test and, from the three patients for whom sera were available, also with R. prowazekii. Results suggest that the four patients were exposed to the typhus-group rickettsiae or to an organism which shares a common epitope(s).

Fluoroimmunoassay studies with solubilized antigens from Borrelia burgdorferi.

Sodium deoxycholate-solubilized Borrelia burgdorferi antigen was prepared for use in a solid-phase fluoroimmunoassay (FIA-L) to detect antibodies in Lyme disease. Serum specimens were tested by FIA-L and by a microimmunofluorescence test. The FIA-L results are comparable to those of the standard microimmunofluorescence test. The overall agreement was 0.98. Moreover, the FIA-L procedure is simple and rapid; fluorescence is objectively determined and is proportional to antibody titer.

Monitoring human immunodeficiency virus type 1-infected patients by ratio of antibodies to gp41 and p24.

Antibody responses of 85 patients to human immunodeficiency virus type 1 antigens were quantitated by densitometric analysis of Western blot (immunoblot) assays. All patients had been classified into the following three clinical categories: asymptomatic (ASY), acquired immunodeficiency syndrome (AIDS)-related complex (ARC), or AIDS. Fifty of the patients were monitored for 6 to 29 months. The gp41/p24 antibody ratio was examined in three studies. In the first study, initial specimens from each patient were analyzed. The mean gp41/p24 antibody ratios were 1.5 (ASY), 3.2 (ARC), and 5.4 (AIDS). Of ASY patients, 79% had antibody ratios of less than 2.0. In contrast, 72% of patients with AIDS had ratios of greater than or equal to 2.0. In the second study, serially obtained specimens from ASY, ARC, and AIDS patients were analyzed. These patients were further grouped according to progression of their clinical condition. Of ASY patients whose clinical condition progressed to ARC, 80% consistently had ratios of greater than or equal to 2.0. Of ARC patients whose clinical condition progressed to AIDS, 71% consistently had ratios of greater than or equal to 2.0. Of AIDS patients who died during the study, 100% consistently had ratios of greater than or equal to 2.0. No patients were treated with azidothymidine during the first two studies. In the third study, AIDS patients were monitored before and during treatment with azidothymidine. During treatment, ratios stabilized or improved transiently in five of seven patients. In these three studies, a gp41/p24 antibody ratio of less than 2.0 correlated with a benign clinical state and a ratio of greater than or equal to 2.0 correlated with AIDS or progression to AIDS.

Densitometric analysis of Western blot (immunoblot) assays for human immunodeficiency virus antibodies and correlation with clinical status.

Western blot assays for antibodies directed against components of human immunodeficiency virus (HIV) associated with acquired immunodeficiency syndrome (AIDS) were examined with a densitometer and integrator. Antibody responses to seven HIV proteins were determined from the areas under the peaks of bands on blots from 430 seropositive individuals. Antibody responses corresponded qualitatively and quantitatively with clinical status. The Western blot assays examined were done on single specimens from individuals in one of four clinical states: asymptomatic with no risk factor identified, asymptomatic with risk factor(s) identified, AIDS-related complex, and AIDS. The ratios of gp41 antibody to p24 antibody and of gp41 antibody to total HIV antibodies increased, and the number of total HIV antibodies decreased progressively in these populations. Parameters were assigned to characterize the typical response found in AIDS: gp41 antibody/p24 antibody ratio, greater than or equal to 2.0; gp41 antibody/total HIV antibodies ratio, greater than or equal to 0.30; and number of total HIV antibodies, less than or equal to 25.0 signal units. Parameter match increased with progression of clinical status. These parameters were applied in a brief follow-up study of 34 HIV-infected asymptomatic individuals who developed AIDS-related complex or AIDS. Initial specimens showed a stronger correlation than our population data base had predicted, suggesting that the parameters have prognostic value. Densitometric analysis of antibody responses on Western blot assays of single or serial specimens should prove useful to physicians in staging and monitoring HIV-infected individuals and in predicting which individuals will progress to AIDS.

The distribution of serum albumin in the rat testis, studied by electron microscope immunocytochemistry on ultrathin frozen sections.

The distribution of serum albumin is of interest in the rat testis because this protein is the principal carrier for testosterone in the plasma and interstitial fluid of this species. We have localized extravascular serum albumin in the rat testis at the electron microscope level, using gold particle immunocytochemistry on ultrathin frozen sections of tissue fixed lightly by perfusion. The same localization was obtained with three different antisera. Preabsorption and normal rabbit serum controls were negative, and Western blots of testis extracts showed major activity only at the molecular weight of albumin. Serum albumin occurred in substantial concentration throughout extracellular space in the interstitial tissue, as well as in the space between the boundary layer and the base of the seminiferous epithelium. Immunoreactivity extended between Sertoli cells, as well as around spermatogonia and early primary spermatocytes (to stage 11), but did not traverse the Sertoli-Sertoli junctions that comprise the blood-testis barrier. Macrophages in the interstitial tissue showed some endocytic activity. If perfusion fixation was carried out in a manner that flushed most of the albumin from the interstitial space, then a layer of albumin remained on the surface of Leydig cells and many macrophages but was minimal or absent on the surface of other cell types that are normally in contact with albumin, such as Sertoli cells, spermatogonia, myoid cells, lymphatic endothelium, fibroblasts, or cells of blood vessels.

Evaluation of an enzyme-linked immunosorbent assay for treponemal antibody.

A new enzyme-linked immunosorbent assay with Treponema pallidum antigen bound to ferrous metal beads (Syphilis Bio-EnzaBead; Litton Bionetics Laboratory Products) was compared with the standard fluorescent treponemal antibody-absorption test for syphilis. Bio-EnzaBead and fluorescent treponemal antibody-absorption tests were done on 218 specimens from documented cases of syphilis, on 315 sera from individuals with diseases other than syphilis, and on sera submitted to a public health laboratory for premarital (304 specimens) or diagnostic (501 specimens) tests for syphilis. Agreement between the Bio-EnzaBead and reference tests ranged from 93.0% for sera for the diagnostic test to 99.5% for sera from patients with syphilis. The overall agreement among the 1,338 sera tested was 96.3%. The reproducibility of the Bio-EnzaBead test with 60 coded sera of graded reactivity was 97%. The test is easy to perform, the indicator results are clear and unequivocal, and the findings are comparable to those of the fluorescent treponemal antibody-absorption test.

Solid-phase fluoroimmunoassay for treponemal antibody.

An objective, solid-phase fluoroimmunoassay for treponemal antibody was developed with a lysate of virulent Treponema pallidum (Nichols strain) adsorbed on cellulose acetate disks. A probe containing both the antigen and control disks is inserted successively into a serum specimen dilution, a buffer rinse, fluoroscein isothiocyanate-conjugated goat anti-human immunoglobulin G, and a second buffer rinse. Fluorescence signal units are measured with a fluorometer. To establish test calibration curves, the corrected fluorescence values (antigen disk minus control) of reference sera are plotted against indirect fluorescent treponemal antibody test titers. The corrected fluorescence values obtained for 62 sera reactive in the fluorescent treponemal antibody absorption test ranged from 64 to 178; values for 66 nonreactive sera ranged from 20 to 46. Thus, the solid-phase fluoroimmunoassay for treponemal antibody clearly separated specimens from patients with documented primary, secondary, or latent disease from fluorescent treponemal antibody absorption-nonreactive sera. The test is technically simple and produces an objective quantitative result.

Tolerance to rectal ketamine in paediatric anaesthesia.

The use of rectal ketamine as the sole anaesthetic for short, minor procedures in young children is discussed. A case in which 18 anaesthetics were administered by this route, to facilitate radiotherapy, is reported and the subsequent development of tolerance and its possible mechanisms are discussed.

Evaluation of a charcoal particle test for rheumatoid factor.

A rheumatoid factor charcoal card test was compared with a rheumatoid factor latex slide and tube agglutination test. Qualitative findings with 280 of 290 selected sera were the same. Quantitative results converted to standard rheumatoid factor units were similar.