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Prognostic significance of unexplained elevated amniotic fluid alpha-fetoprotein.

OBJECTIVE: To compare the prognostic values of unexplained elevated amniotic fluid alpha-fetoprotein (AF AFP > or = 2.0 multiples of the median [MoM]) and unexplained elevated maternal serum alpha-fetoprotein (MSAFP > or = 2.5 MoM). METHODS: We accessed a data base containing the results of MSAFP screening tests, genetic amniocenteses, and pregnancy outcome data on all women undergoing second-trimester genetic amniocentesis from October 1988 through August 1994. After excluding all patients whose elevated AFP levels had any identifiable cause (positive AF acetylcholinesterase, AF blood contamination, fetal malformation or aneuploidy, multiple gestation, etc), 5743 cases were analyzed. Relative risks (RR) for selected pregnancy complications were determined. RESULTS: Elevated MSAFP, with any AF AFP, was associated with fetal growth restriction (RR 2.5, 95% confidence interval [CI] 1.4-4.4), stillbirth (RR 3.5, 95% CI 1.4-8.3), preeclampsia (RR 2.8, 95% CI 1.1-7.0), and preterm delivery (RR 2.8, 95% CI 2.3-3.4). Elevated AF AFP, with any MSAFP, was associated with preeclampsia (RR 4.4, 95% CI 2.0-10.0) and preterm delivery (RR 1.7, 95% CI 1.3-2.4). Elevation of both AF AFP and MSAFP was associated with preterm delivery (RR 4.0, 95% CI 2.8-5.7). When elevated AF AFP was found in association with a normal MSAFP, the RR to develop preeclampsia was 4.6 (95% CI 1.9-11.2). CONCLUSION: Maternal serum alpha-fetoprotein is a better predictor of late pregnancy complications than AF AFP. However, unexplained elevated AF AFP appears to be especially predictive of preeclampsia.

Amniotic Fluid↗

Using the Very Large Array (VLA) and other radio telescopes to perform a parasitic Search for Extraterrestrial Intelligence (SETI).

This paper describes several attempts to utilize various radio telescopes in a manner that we term "parasitic," that is in a manner that does not interrupt or seriously impact the standard astronomical observing programs in progress at the radio observatories. In the extreme case, only recorded astronomical data are accessed off-line, after the fact, without any burden on the observatory at all.

Astronomy↗

Fluorescence analysis of the interaction between ganglioside GM1-containing phospholipid vesicles and the B subunit of cholera toxin.

Binding of cholera toxin B protomer (CT-B) to a pyrene-labeled analogue of its ganglioside GM1 receptor (pyrene-GM1) in the absence and presence of phosphatidylcholine vesicles was monitored using steady-state fluorescence spectroscopy. CT-B association with pyrene-GM1 micelles induces changes in the fluorescence properties of this ganglioside analogue that are consistent with its conversion from an excimer to a monomer form. Incubation of pyrene-GM1 with preformed vesicles of phosphatidylcholine (PC) results in complete conversion of pyrene-GM1 to its monomer form, however, unlike with CT-B binding, incorporation of pyrene-GM1 into PC vesicles occurs with a concomitant loss of fluorescence quenching by the small polar quenching agent acrylamide. Subsequent binding of CT-B to the PC-GM1 composite vesicles causes no further change in the pyrene fluorescence emission spectrum but does appear to increase acrylamide accessibility. These data lead to the conclusion that cholera toxin binding to a cell membrane alters membrane packing at the site of attachment. Furthermore, this phenomenon appears to be influenced by environmental conditions such as pH. A pH of about 4.0 or less causes acrylamide quenching to decrease to approximately the levels observed in the absence of CT-B. These results may be useful in describing the dynamics of the interaction between cholera toxin and target cell membranes. Moreover, these data could provide clues to the mechanism by which the toxic portion of CT is able to enter the cytoplasm of target cells.

Acrylamide↗

A C-language program for the computation of power spectra on a laboratory microcomputer.

A computer program is described which performs power-spectral analyses on time-domain data. The program is written in the C language and incorporates an algorithm for the fast Fourier transform translated from BASIC into C. Sequential segments of time-domain data are accessed by the program, transformed to the frequency domain, and ensemble-averaged to generate smoothed spectra. Specific application of the program to the detection of high-frequency oscillations in the phrenic neurogram of the cat is addressed. Thus, 100 successive 512-point fast Fourier transforms were found to accurately reveal the relative strength (power) and frequency position (spectrum) of multiple peaks in this respiratory motor pathway. Because C language programs are very transportable, this program should run on machines other than our LSI 11/23, provided a C-compiler is available.

Animals↗

A creative method for determining the immunization status of a community hospital medical staff.

During 1985 and 1986, 191 of the 212 (90%) medical staff members in active private practice, who were surveyed responded to a one-page report regarding the status of their immunity and immunization to important infectious illnesses. Response rates were improved by including the survey form with the hospital privilege-renewal form that was required to be returned to the medical staff office. Of the respondents 96% reported prior history of chickenpox and 95% reported prior immunization to tetanus; of the 42 who reported prior bacille Calmette-Guérin (BCG) vaccination, only 17 reported a positive tuberculin skin test. An additional 32 medical staff members had a history of a positive tuberculin skin test with no prior BCG vaccination. Only 2 (1%) reported prior history of hepatitis B, and only 15 (8%) reported hepatitis B vaccination begun or completed at the time of the survey. This survey allows targeting of infection control activities, such as implementation of the hepatitis B vaccine promotion program and serologic testing of those with a negative history of chickenpox, to be developed for the medical staff. It allows the hospital infection control team instant access to data that can be simply obtained and updated regularly when information is needed about the immunization status of selected medical staff members during an outbreak situation.

Data Collection↗

Managing data quality through automation.

Traditional definitions of data quality deal primarily with individual data sets and the data collection process. Today's standards for ensuring data quality have not changed with respect to the desired results, but have simply been expanded to take advantage of modern technology. Computers are used to acquire, review, store, analyze, and report data. Because each of these steps can be automated, the need for human intervention and manual review is minimized. As a result, the potential for invalid data to reach the data analysis stage has increased significantly. To reduce this potential, efforts must be devoted to developing automated procedures that cover every conceivable validation possibility. Relationships between data and data sets must be well defined [1], and data base support that facilitates ready access to the data for the purpose of analysis must be provided. For small data sets, automation may therefore be impractical; but for large, interrelated data sets, automation is highly desirable. Computer automation has therefore expanded the traditional concept of ensuring data quality to include a complex array of interrelated tasks that must be properly managed to achieve the desired results.

Animals↗

General practitioners' decision making for mental health problems: outcomes and ecological validity.

A major problem in the field of medical decision making is the ecological (external) validity of the results. In a Judgement Analysis study on mental health, vignettes were used to capture the decision strategies of 28 General Practitioners (GPs). Two different decision strategies for mental health problems could be distinguished. Although the results were statistically satisfactory and met the assumptions of Judgement Analysis, it was considered necessary to determine the ecological validity of the vignettes. Video tapes (n = 90) of GP consultations were scored in terms of the units of information (cues) which had been used in the vignette study. Additional data gave access to the judgements of the GPs, which were comparable to the judgements obtained in the vignette study. Results showed that the weights given to the different cues in the vignette study were situated within the confidence interval of the weights from the video study. Thus indicating that the results obtained from the vignette study have ecological validity.

Cues↗

The diagnosis of polycythemia vera: new tests and old dictums.

Pathogenetically fundamental observations have identified polycythemia vera (PV) as a clonal stem cell disease with bone marrow histological and other biological features that distinctly differentiate it from other causes of 'increased' hematocrit. However, relatively little attention has been given to the effective utilization of pathology and laboratory markers of clonal myeloproliferation as diagnostic tools in PV. In contrast, the diagnostic use of red cell mass (RCM) measurement in PV stemmed from the accidental endorsement, as 'diagnostic criteria', of 'study eligibility criteria' that were formulated for clinical trials. It has since become evident that RCM measurement is a tedious procedure that is fraught with multiple-level imprecision, as well as suboptimal diagnostic accuracy. Therefore, it is reasonable to consider dispensing with RCM measurement as a diagnostic test for PV and instead utilize a diagnostic algorithm that combines clinical information with easily accessible laboratory data, including serum erythropoietin level and bone marrow histology. Recent discoveries of myeloproliferative-disease-specific molecular markers, including the JAK2 V617F tyrosine kinase mutation that is found in the majority of patients with PV, provide further support for such a measure.

Algorithms↗

EEG background activity described by a large computerized database.

OBJECTIVE: To show how our newly developed software for classification and storage of visually routinely assessed EEGs are used to evaluate the general background activity (GBA) and the alpha rhythm (AR) in a large number of prospective EEGs. METHODS: EEGs from 4651 consecutive patients were visually assessed using a computerized description system connected to an EEG database. The AR and the GBA apart from the AR were described separately for frequency and amplitude. RESULTS: AR frequencies declined from the age of 45 years and slowed with increasing age independently of non-AR pathology and gender. Females had higher AR frequencies than males. EEGs with non-GBA pathology had lower GBA frequencies and higher GBA amplitudes. Higher GBA amplitudes were associated with lower GBA frequencies in normal EEGs for all age groups. EEG interpretations by 4 independent electroencephalographers showed the same trends, but differed in exact assessment of frequencies and amplitudes. CONCLUSIONS: EEG interpretations stored in a categorized database with easy access to data have successfully been used to evaluate interobserver variation and other quality control measurements. Statistical analysis of the data has at the same time produced new information regarding the development of AR and GBA throughout life.

Adolescent↗

Financial incentives and health coaching to improve glycemic outcomes among young adults with type 1 diabetes: A factorial randomized trial (SweetGoals).

AIM: This study aimed to improve glycemic control among young adults with type 1 diabetes (T1D), an at-risk and understudied population. METHOD: N = 300 young adults with T1D recruited nationally were randomized to the factorial combination of (1) financial incentives targeting glucose checking and mealtime behaviors and (2) web health coaching focused on increasing motivation and goal setting for self-management behaviors. All received a smartphone app that accessed device data and provided weekly goal feedback. The intervention lasted 6 months. HbA1c (A1c) was assessed at baseline, +6 months, and +12 months. The mean number of glucose checking and mealtime goals met per week during the intervention were tested as mediators of intervention effects on A1c at 12 months. RESULTS: A1c was significantly reduced from baseline to +12 months across all participants. Indirect effects of both incentives and coaching on A1c reductions were significant and partially mediated by mealtime but not glucose checking goal achievement. There was no synergistic (interaction) effect of incentives and coaching. CONCLUSION: Incentives and coaching both improved critical mealtime behavior but through different strategies. These results suggest that either intervention would be suitable for future testing and dissemination, and that lower cost of incentives may favor their prioritization.

Adolescent↗

Decreased survival in diabetic patients with heart failure due to systolic dysfunction.

BACKGROUND: Prognosis of patients with heart failure (HF) has improved in recent years due to advances in therapy. Whether this is also true for diabetic subjects with HF in clinical practice has not been studied in a prospective manner. METHODS: All patients with HF and left ventricular systolic dysfunction attending the outpatient clinic at our Veteran's Hospital between October 1999 and November 2000 were enrolled in our study and followed prospectively. Electronic medical records were accessed for data on comorbid conditions, medications, echocardiogram results and mortality information. Mean follow-up was 2.7 years. RESULTS: Of 495 patients with HF due to systolic dysfunction enrolled in the study, 293 (59%) had diabetes. Prevalence of hypertension, diuretic use and angiotensin converting enzyme inhibitor use was higher among diabetics. Beta-blocker usage was equal and high in both groups (60%). On follow-up, 109/273 (37%) patients in the diabetic group died, compared with 49/202 (24%) in the non-diabetic group. Independent predictors of death were diabetes (p<0.005, OR=1.73), age at enrollment (p<0.0001, OR=1.06), serum creatinine (p<0.01, OR=1.44) and diuretic use (p=0.038, OR=1.85). Beta-blocker use was associated with a decreased risk of death on univariate analysis only. CONCLUSIONS: Our results show that diabetic patients with HF continue to have higher mortality than non-diabetic patients with HF despite advances in therapy.

Aged↗

The modular xylanase Xyn10A from Rhodothermus marinus is cell-attached, and its C-terminal domain has several putative homologues among cell-attached proteins within the phylum Bacteroidetes.

Until recently, the function of the fifth domain of the thermostable modular xylanase Xyn10A from Rhodothermus marinus was unresolved. A putative homologue to this domain was however identified in a mannanase (Man26A) from the same microorganism which raised questions regarding a common function. An extensive search of all accessible data-bases as well as the partially sequenced genomes of R. marinus and Cytophaga hutchinsonii showed that homologues of this domain were encoded by multiple genes in microorganisms in the phylum Bacteroidetes. Moreover, the domain occurred invariably at the C-termini of proteins that were predominantly extra-cellular/cell attached. A primary structure motif of three conserved regions including structurally important glycines and a proline was also identified suggesting a conserved 3D fold. This bioinformatic evidence suggested a possible role of this domain in mediating cell attachment. To confirm this theory, R. marinus was grown, and activity assays showed that the major part of the xylanase activity was connected to whole cells. Moreover, immunocytochemical detection using a Xyn10A-specific antibody proved presence of Xyn10A on the R. marinus cell surface. In the light of this, a revision of experimental data present on both Xyn10A and Man26A was performed, and the results all indicate a cell-anchoring role of the domain, suggesting that this domain represents a novel type of module that mediates cell attachment in proteins originating from members of the phylum Bacteroidetes.

Amino Acid Sequence↗

Ambulatory healthcare information system: a conceptual framework.

Despite the tremendous amount of data collected in the field of ambulatory care, political authorities still lack synthetic indicators to provide them with a global view of health services utilization and costs related to various types of diseases. Moreover, public health indicators fail to provide useful information for physicians' accountability purposes. The approach is based on the Swiss context, which is characterized by the greatest frequency of medical visits in Europe, the highest rate of growth for care expenditure, poor public information but a lot of structured data (new fee system introduced in 2004). The proposed conceptual framework is universal and based on descriptors of six entities: general population, people with poor health, patients, services, resources and effects. We show that most conceptual shortcomings can be overcome and that the proposed indicators can be achieved without threatening privacy protection, using modern cryptographic techniques. Twelve indicators are suggested for the surveillance of the ambulatory care system, almost all based on routinely available data: morbidity, accessibility, relevancy, adequacy, productivity, efficacy (from the points of view of the population, people with poor health, and patients), effectiveness, efficiency, health services coverage and financing. The additional costs of this surveillance system should not exceed Euro 2 million per year (Euro 0.3 per capita).

Ambulatory Care↗

Self-reported data from patients with bipolar disorder: impact on minimum episode length for hypomania.

OBJECTIVE: Some investigators have suggested decreasing the minimum hypomania episode length criterion from 4 days, as in the DSM-IV, to 2 days. Using daily self-reported mood ratings, we studied the impact of changing the length requirement on the number of hypomanic episodes in patients with bipolar disorder. METHOD: 203 patients (135 bipolar I and 68 bipolar II by DSM-IV criteria) recorded mood daily using ChronoRecord software (30,348 total days, mean 150 days). Episodes of hypomania and days of hypomania outside of episodes were determined. RESULTS: Decreasing the minimum duration criterion for an episode of hypomania from 4 to 2 days doubled the mean percent of days in a hypomanic episode for each patient (4% to 8%), doubled the number of patients with a hypomanic episode (44 to 96) and increased the number of hypomanic episodes for all patients about three-fold (129 to 404). With a minimum episode length of 4 days, bipolar I patients were more likely to report hypomania outside episodes than bipolar II patients (p=0.010), but with a length of 2 or 3 days there was no significant difference in the distribution of hypomania outside of episodes by diagnosis. With a 2-day length, about one-third (36%) of hypomania remained outside of an episode. LIMITATIONS: Self-reported data, computer access, relatively short length, fewer bipolar II than bipolar I patients. CONCLUSION: As the minimum length for an episode of hypomania decreases, there was a large increase in both the number of episodes and number of patients with episodes. One-day hypomania outside of episodes occurs frequently in both bipolar I and bipolar II disorder.

Adult↗

Self-reported data from patients with bipolar disorder: frequency of brief depression.

OBJECTIVE: Patients with bipolar disorder often report depressive symptoms that do not meet the DSM-IV criteria for an episode. Using daily self-reported mood ratings, we studied how changing the length requirement to that typical of recurrent brief depression (2-4 days) would impact the number of depressed episodes. METHOD: 203 patients (135 bipolar I and 68 bipolar II by DSM-IV criteria) recorded mood daily using ChronoRecord software on a home computer (30,348 total days; mean 150 days). Episodes of depression and days of depression outside of episodes were determined. Symptom intensity (mild versus moderate or severe) was investigated within and outside of depressive episodes. RESULTS: Decreasing the minimum duration criterion for an episode of depression to 2 days increased the number of patients with a depressed episode two and a half times (52 to 131), and quadrupled both the number of depressed episodes per patient (0.62 to 2.88) and the number of depressed episodes for all patients (125 to 584). With a 2-day episode length, 34% of days of depression remained outside an episode. The ratio of days with severe symptoms within episodes remained consistent (about 25%) in spite of decreasing the episode length to 2 days. Considering only days with severe symptoms, about 25% remained outside of episodes even with a 2-day length. None of the results distinguished bipolar I from bipolar II disorder. LIMITATIONS: Self-reported data, computer access required, relatively short study length, no control group. CONCLUSION: Brief depressive episodes and single days of depression outside of episodes occur frequently in both bipolar I and bipolar II disorder. Moderate or severe symptoms occur during brief episodes at a ratio similar to that for episodes that meet the DSM-IV criteria.

Adult↗

The influence of geological factors on indoor radon concentrations in Norway.

Indoor radon levels in 1618 Norwegian dwellings located in different geological settings are compared with geological information. The results show a significant correlation between indoor radon levels and geological factors. Radium content and permeability of the building ground have been found to be useful indicators of indoor radon concentrations. Based on easily accessible geological data, an assessment of the radon potential of an area can be given. Areas of high radon risk in Norway include: (a) exposed bedrock with elevated levels of radium; and (b) highly permeable unconsolidated sediments derived from all rock types and moderately permeable sediments derived from rock types rich in radium. A comparison of indoor radon with house construction characteristics and ventilation habits suggests that radon concentrations in Norwegian dwellings are also influenced by ventilation system, aeration habits and floor level of the room where the measurements were carried out. The significant correlation between indoor radon levels and geological factors observed in the present investigation indicates that it is possible to outline areas of high radon risk in Norway based on geological information.

Air Pollution, Indoor↗

Model-based analysis of assembly kinetics for virus capsids or other spherical polymers.

The assembly of virus capsids or other spherical polymers--empty, closed structures composed of hundreds of protein subunits--is poorly understood. Assembly of a closed spherical polymer is unlike polymerization of a filament or crystal, examples of open-ended polymers. This must be considered to develop physically meaningful analyses. We have developed a model of capsid assembly, based on a cascade of low-order reactions, that allows us to calculate kinetic simulations. The behavior of this model resembles assembly kinetics observed in solution (Zlotnick, A., J. M. Johnson, P. W. Wingfield, S. J. Stahl, and D. Endres. 1999. Biochemistry. 38:14644-14652). We exhibit two examples of this general model describing assembly of dodecahedral and icosahedral capsids. Using simulations based on these examples, we demonstrate how to extract robust estimates of assembly parameters from accessible experimental data. These parameters, nucleus size, average nucleation rate, and average free energy of association can be determined from measurement of subunit and capsid as time and concentration vary. Mathematical derivations of the analyses, carried out for a general model, are provided in an Appendix. The understanding of capsid assembly developed in this paper is general; the examples provided can be readily modified to reflect different biological systems. This enhanced understanding of virus assembly will allow a more quantitative analysis of virus stability and biological or antiviral factors that affect assembly.

Biophysical Phenomena↗

Single-molecule microscopy on model membranes reveals anomalous diffusion.

The lateral mobility of lipids in phospholipid membranes has attracted numerous experimental and theoretical studies, inspired by the model of Singer and Nicholson (1972. Science, 175:720-731) and the theoretical description by Saffman and Delbrück (1975. Proc. Natl. Acad. Sci. USA. 72:3111-3113). Fluorescence recovery after photobleaching (FRAP) is used as the standard experimental technique for the study of lateral mobility, yielding an ensemble-averaged diffusion constant. Single-particle tracking (SPT) and the recently developed single-molecule imaging techniques now give access to data on individual displacements of molecules, which can be used for characterization of the mobility in a membrane. Here we present a new type of analysis for tracking data by making use of the probability distribution of square displacements. The potential of this new type of analysis is shown for single-molecule imaging, which was employed to follow the motion of individual fluorescence-labeled lipids in two systems: a fluid-supported phospholipid membrane and a solid polymerstabilized phospholipid monolayer. In the fluid membrane, a high-mobility component characterized by a diffusion constant of 4.4 microns2/s and a low-mobility component characterized by a diffusion constant of 0.07 micron2/s were identified. It is proposed that the latter characterizes the so-called immobile fraction often found in FRAP experiments. In the polymer-stabilized system, diffusion restricted to corrals of 140 nm was directly visualized. Both examples show the potentials of such detailed analysis in combination with single-molecule techniques: with minimal interference with the native structure, inhomogeneities of membrane mobility can be resolved with a spatial resolution of 100 nm, well below the diffraction limit.

Diffusion↗