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Detection of cytomegalovirus antibody by enzyme immunoassay and lack of evidence for an effect resulting from strain heterogeneity.

A total of 259 serum samples from random blood donors were assayed by an enzyme immunoassay for antibody to cytomegalovirus (CMV) with antigens prepared from eight genetically unrelated clinical isolates of CMV and the laboratory-adapted strains AD169 and Towne. A total of 144 serum samples were reactive against all 10 strains, and 115 serum samples lacked immunoglobulin against all 10 strains. The results support the continued use of the AD169 strain of human CMV as the reference antigen for CMV serologic testing.

Antibodies, Viral↗

Analysis and assessment of heavy metal pollution in suspended solids and sediments of the river Danube.

The Joint Danube Survey (JDS)--a comprehensive monitoring survey to assess the environmental pollution status of the river Danube--was carried out in 2001. Samples were taken at 74 positions along the river from Neu-Ulm (River-km 2589) down to the Danube Delta at the Black Sea (River-km 0) and in 24 main tributaries and anabranches. Besides other biological and chemical parameters, concentrations of Al, As, Cd, Cr, Cu, Fe, Pb, Mn, Hg, Ni, and Zn were determined in sediments and suspended solids. Lowest heavy metal concentrations were measured around River-km 1800. After an increase down to River-km 1000 (the Irongate Reservoir), a constant level or a slight decrease could be found down to and in the Danube Delta. Very high element concentrations were determined at only a few stations of the river Danube and in some tributaries. An evaluation of the pollution status of the river was carried out by enrichment factors (EFs) calculated using adapted background concentrations of heavy metals. Except single sampling sites and some tributaries, the pollution of the river Danube by As, Cr, Cu, Pb, Hg, Ni, and Zn can be regarded as rather low. However, elevated concentrations of Cd were found in both investigated matrices, particularly in the lower stretch of the river Danube beginning at the Irongate.

Environmental Monitoring↗

Gay men with AIDS: perceptions of social support and adaptational outcome.

Using a multivariate design, this study examined social support as a mediating variable between the stressor of AIDS and adaptational outcome in a culturally and socioeconomically diverse sample of 60 urban gay men with AIDS. Whereas earlier studies have suggested that social support for gay men with AIDS is often lacking or ineffective, findings in this study indicated that family of origin and friends may provide more support to gay men with AIDS than has been generally recognized. Both family of origin and friend support were strongly correlated with positive outcomes, indicating that social support was not only forthcoming but was also effective. The relationship between family of origin support and positive outcomes was particularly strong.

Acquired Immunodeficiency Syndrome↗

Sequential equivalence testing and repeated confidence intervals, with applications to normal and binary responses.

We propose group sequential tests of the equivalence of two treatments based on ideas related to repeated confidence intervals. These tests adapt readily to unpredictable group sizes, to the possibility of continuing even though a boundary has been crossed, and to nonnormal observations. In comparing two binomial distributions, the required sample size depends strongly on the average success probability and an adaptive choice of group size is needed to produce an efficient test meeting specified error probability constraints. A special case is the experiment where interim analyses are performed, not for the purpose of early termination but simply to adjust the sample size so that nominal error rates will be guaranteed, despite the presence of a nuisance parameter.

Binomial Distribution↗

Family influences on adaptive development in young children with Down syndrome.

In this study we investigated the extent to which the family environment predicted differences in trajectories of adaptive development in young children with Down syndrome. The sample was comprised of 54 children with Down syndrome and their families who were studied from infancy through the age of 5 years as part of a longitudinal study of children with disabilities. Hierarchical linear modeling (HLM) was used to estimate the parameters of hierarchical growth models in domains of adaptive development. Results indicated that growth in communication, daily living skills, and socialization domains were predicted by measures of the family environment (i.e., family cohesion and mother-child interaction) above and beyond that predicted by maternal education. Further, Bayley MDI measures during infancy did not predict changes in adaptive development in any of the domains. The results are discussed in terms of implications for service provision and for expanding theoretical frameworks to include the development of children with disabilities.

Adaptation, Psychological↗

Genetic Adaptation to Brackish Water and Spawning Season in European Cisco.

How species adapt to diverse environmental conditions is essential for understanding evolution and the maintenance of biodiversity. The European cisco (Coregonus albula) is a salmonid that occurs in both fresh and brackish water, and this together with the presence of sympatric spring- and autumn-spawning lacustrine populations provides an opportunity for studying the genetics of adaptation in relation to salinity and timing of reproduction. Here, we present a high-quality reference genome of the European cisco based on PacBio HiFi long read sequencing and HiC-directed scaffolding. We generated low-coverage whole-genome sequencing data from 336 individuals across 12 population samples to explore population structure and genetics of ecological adaptation. We found a major subdivision between two groups of populations most likely reflecting colonisation from different glacial refugia. Within the two major groups, we detected further genetic differentiation between spring- and autumn-spawning populations and between populations from freshwater lakes, rivers and brackish water (Bothnian Bay). A genome-wide screen for genetic differentiation among populations identified a set of outlier SNPs strongly correlated with spawning timing and salinity. Several of the genes associated with spawning time, including BHLHE40, TIMELESS and CPT1A, have previously been shown to have a role in circadian rhythm biology. As many as 17 loci were associated with genetic differentiation between populations reproducing in fresh and brackish water. This study provides insights into the genomic basis of ecological adaptation in European cisco with implications for sustainable fishery management.

Animals↗

Sampling local respiratory tract sites for inflammation.

Although host defense mechanisms protect the health of the respiratory tract, deficiencies or excessive host responses such as inflammation can create sino-nasal and pulmonary illnesses. Analysis of expectorated secretions (sputum) is traditional, but selective site specific samples (surface washing) seem more applicable for studying illnesses such as rhinitis, bronchitis, or aveolitis. Regional samples should contain representative components (cells and proteins) that ideally reflect changes in adjacent tissue; however, biopsy of contiguous mucosa and lung parenchyma is required for a comprehensive analysis that can link surface samples and tissue pathology. Clinical strategies must be flexible so that maximal information about the host can be obtained through investigation of healthy normals, volunteer-patients with latent illness that can be induced locally and observed in situ, and patients with active illness. Implicit in studying inflammation is the adaptation of new analytic methods to surface or topical samples such as nasal, bronchial and bronchoalveolar lavage (BALF). More correlations between respective components in nasal fluids, bronchial and BAL specimens seem indicated, so that more readily available samples can be used for clinical monitoring. Moreover, further correlations between bronchial and BAL cells and immunohistochemical analysis of tissue for cells are needed.

Bronchoalveolar Lavage↗

Cutaneous sensory receptors in the rat foot.

1. A total of 574 cutaneous afferent units in the sural and plantar nerves supplying the skin of the rat foot was examined: 399 A beta-units, 55 A delta-units, and 120 C-units. Their receptive-field (RF) properties were similar to those described in other mammals. However, the receptor type composition of units was different between the two nerves. 2. The sural A beta-fiber sample (n = 160) consisted of G-hair (41%), field (11%), rapidly adapting (RA; 6%), slowly adapting type I (SA-I; 7%), and type II (SA-II; 35%) mechanoreceptors. The plantar A beta-fiber sample (n = 239) was composed of G-hair (3%), RA (35%), SA-I (30%), SA-II (24%), and Pacinian corpuscle (PC; 8%) mechanoreceptors. 3. The RFs of SA-II units were located on both hairy and glabrous skin overlying the foot joints. Many of the SA-II units responded to movement of the foot joints. The RFs of both SA-I and RA units were small in size and located in high density on the toe tips and footpads. PC units were very sensitive to vibration and had extremely large RFs as in other species, although they were rare and found only in the plantar nerve. Field units were similar to SA-II units in response properties and RF distribution. 4. The sural A delta-fiber sample (n = 44) included nociceptors (68%), D-hair (27%), and cold (5%) receptors. All sampled plantar A delta-fibers (n = 11) were nociceptors. Of A delta-nociceptor units, A delta-mechanical nociceptors (73%) were dominant. 5. The sural C-fiber sample (n = 85) included nociceptors (44%), C-mechanoreceptors (33%), and cold receptors (21%). The plantar C-fiber sample (n = 35) included nociceptors (77%) and cold receptors (23%). No warm units were found among either the sural or plantar nerve fibers. Of C-nociceptors, C-mechanoheat nociceptors (80%) were dominant. 6. The results indicate that all well-known types of cutaneous receptors, except warm receptors, exist in the foot skin of the rat. On the basis of the fact that RFs of RA and SA-I units are in high density on the toe tips and footpads, it is suggested that those regions may have a spatial discriminating capacity. It is also suggested that SA-II receptors may play a role in proprioception, because they have RFs on the skin over foot joints and respond to joint movement.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Temperament and vagal tone in boys with fragile X syndrome.

Physiological hyperarousal, an elevated state of physiological arousal and poor modulation, has been postulated to be a significant source of behavior problems in children with fragile X syndrome (FXS). Temperament has been associated with behavior problems and may also reflect biological reactivity. Young boys with FXS display poorly modulated and low levels of vagal tone (Roberts, Dev Psychobiol 2001;39:107-123) and high activity, poor attention, low adaptability, poor persistence, and low intensity when compared with a reference sample of typically developing (Hatton, Dev Med Child Neurol 1991;41:625-632). In this study, we integrated physiological indices of vagal tone with temperament ratings and compared a sample of 29 young boys with FXS to 31 typically developing boys matched on chronological age and ethnicity. Boys with FXS were more active, less adaptable, and less persistent than the comparison group. Boys with FXS also showed lower baseline levels and less suppression of vagal tone in response to changing task demands. A relationship between baseline vagal tone and persistence was shown across both groups. However, group differences in temperament dimensions did not appear to be mediated or moderated by vagal tone.

Arousal↗

Stress, symptom proneness, and general adaptational distress during pregnancy.

Symptom proneness (SP), the 20 psychiatric items of the Cornell Medical Index, here called the Cornell Psychiatric Items (CPI), and a test developed partially from the Schedule of Recent Experiences called the Utah Stress Scales (STRESS) were used to predict general adaptational distress (GAD) symptoms during pregnancy on a sample of 1306 primigravidas. The causal model explored in seven path analyses developed for months 3-9 of pregnancy is that SP and STRESS affect CPI, and that SP, STRESS, and CPI directly affect GAD symptoms. Results suggest that CPI is most predictive of GAD symptoms until the ninth month when SP and STRESS become more predictive. It is suggested that GAD pregnancy symptoms are affected by situational stress, symptom proneness, and level of psychological upset and that this system of relations changes over the course of pregnancy. This information should have important implications for anticipating potential problems and improving the quality of nursing care of pregnant women.

Adaptation, Psychological↗

Establishment of a simple cleanup procedure and bioassay for determining 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents of environmental samples.

The study was aimed at establishing a bioassay for the determination of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents (TEQs) in environmental samples. Specifically, development of a rapid cleanup procedure adapted to the needs of the bioassay and simplification of the measurement of its endpoint, the induction of 7-ethoxyresorufin O-deethylase (EROD) in rat H4IIEC3/T hepatoma cells, were desired. The results indicate that a single "sandwich" column suffices to remove substances that may interfere with the bioassay from extracts of various environmental matrices such as sewage sludge, compost, soil, sediment, fly ash, tissue filter dust, and fire residue. The cumbersome conventional in vitro assay for EROD activity on cells exposed to the test material in culture plates could readily be replaced by a simple assay on intact cells grown and treated in 96-well microtiter plates. TEQ values obtained from the bioassays were consistently higher than those derived from chemical analysis of dibenzo-p-dioxins/furans and biphenyls by a factor of 1.5-3.0 depending on the matrix used. The results indicate that this bioassay, which combines a simple cleanup and a rapid procedure for measuring biological effects, offers a cost- and time-effective alternative to chemical analysis when screening large numbers of samples from complex environmental matrices.

Animals↗

Randomization in substance abuse clinical trials.

BACKGROUND: A well designed randomized clinical trial rates as the highest level of evidence for a particular intervention's efficacy. Randomization, a fundamental feature of clinical trials design, is a process invoking the use of probability to assign treatment interventions to patients. In general, randomization techniques pursue the goal of providing objectivity to the assignment of treatments, while at the same time balancing for treatment assignment totals and covariate distributions. Numerous randomization techniques, each with varying properties of randomness and balance, are suggested in the statistical literature. This paper reviews common randomization techniques often used in substance abuse research and an application from a National Institute on Drug Abuse (NIDA)-funded clinical trial in substance abuse is used to illustrate several choices an investigator faces when designing a clinical trial. RESULTS: Comparisons and contrasts of randomization schemes are provided with respect to deterministic and balancing properties. Specifically, Monte Carlo simulation is used to explore the balancing nature of randomization techniques for moderately sized clinical trials. Results demonstrate large treatment imbalance for complete randomization with less imbalance for the urn or adaptive scheme. The urn and adaptive randomization methods display smaller treatment imbalance as demonstrated by the low variability of treatment allocation imbalance. For all randomization schemes, covariate imbalance between treatment arms was small with little variation between adaptive schemes, stratified schemes and unstratified schemes given that sample sizes were moderate to large. CONCLUSION: We develop this paper with the goal of reminding substance abuse researchers of the broad array of randomization options available for clinical trial designs. There may be too quick a tendency for substance abuse researchers to implement the fashionable urn randomization schemes and other highly adaptive designs. In many instances, simple or blocked randomization with stratification on a major covariate or two will accomplish the same objectives as an urn or adaptive design, and it can do so with more simply implemented schedules and without the dangers of overmatching. Furthermore, the proper analysis, fully accounting for the stratified design, can be conducted.

Humans↗

Vanadium levels in French and Californian wines: influence on vanadium dietary intake.

An accurate and reproducible method for direct determination of vanadium (V) in wine using graphite furnace atomic absorption spectrometry (GFAAS) is described. This method gave results insignificantly different from those obtained using dry mineralization of wine samples, with a detection limit of 42 pg. A total of 68 wine samples from different regions of France and California were analysed. Vanadium levels ranged from 7.0 to 90.0 micrograms/l in red and from 6.6 to 43.9 micrograms/l in white wines. The method was also adapted to the determination of vanadium levels in 12 grape samples from different varieties after acid mineralization. Vanadium content varied from 2 to 17 micrograms/kg for white and from 5 to 11 micrograms/kg for red varieties. Our data indicate that wine storage conditions may increase vanadium content. The contribution of wine consumption to daily vanadium dietary intake of the French population was estimated to be 11 micrograms/day per individual.

Canada↗

Acid adaptation does not promote survival or growth of Listeria monocytogenes on fresh beef following acid and nonacid decontamination treatments.

The objective of this study was to evaluate the survival and growth of acid-adapted and nonadapted Listeria monocytogenes inoculated onto fresh beef subsequently treated with acid or nonacid solutions. Beef slices (2.5 by 5 by 1 cm) from top rounds were inoculated with acid-adapted or nonadapted L. monocytogenes (4.6 to 5.0 log CFU/cm2) and either left untreated (control) or dipped for 30 s in water at 55 degrees C, water at 75 degrees C, 2% lactic acid at 55 degrees C, or 2% acetic acid at 55 degrees C. The beef slices were vacuum packaged and stored at 4 or 10 degrees C and were analyzed after 0, 7, 14, 21, and 28 days of storage. Dipping in 75 degrees C water, lactic acid, and acetic acid resulted in immediate pathogen reductions of 1.4 to 2.0, 1.8 to 2.6, and 1.4 to 2.4 log CFU/cm2, respectively. After storage at 10 degrees C for 28 days, populations of L. monocytogenes on meat treated with 55 degrees C water increased by ca. 1.6 to 1.8 log CFU/cm2. The pathogen remained at low population levels (1.6 to 2.8 log CFU/cm2) on acid-treated meat, whereas populations on meat treated with 75 degrees C water increased rapidly, reaching levels of 3.6 to 4.6 log CFU/cm2 by day 14. During storage at 4 degrees C, there was no growth of the pathogen for at least 21 days in samples treated with 55 and 75 degrees C water, and periods of no growth were longer for acid-treated samples. There were no differences between acid-adapted and nonadapted organisms across treatments with respect to survival or growth. In conclusion, the dipping of meat inoculated with L. monocytogenes into acid solutions reduced and then inhibited the growth of the pathogen during storage at 4 and 10 degrees C, while dipping in hot water allowed growth despite initial reductions in pathogen contamination. The results of this study indicate a residual activity of acid-based decontamination treatments compared with water-based treatments for refrigerated (4 degrees C) or temperature-abused (10 degrees C) lean beef tissue in vacuum packages, and these results also indicate that this activity may not be counteracted by prior acid adaptation of L. monocytogenes.

Acetic Acid↗

A framework for two-stage adaptive procedures to simultaneously test non-inferiority and superiority.

In clinical trials it is often desirable to test for non-inferiority and for superiority simultaneously. For such a situation a two-stage adaptive procedure may be advantageous to a conventional single-stage procedure because a two-stage adaptive procedure allows the design of stage II, including the main study objective and sample size, to depend on the outcome of stage I. We propose a framework for designing two-stage adaptive procedures with a possible switch of the primary study objectives at the end of stage I between non-inferiority and superiority. The framework permits control of the type I error rate and specification of the unconditional powers and maximum sample size for each of non-inferiority and superiority objectives. The actions at the end of stage I are predetermined as functions of the stage I observations, thus making specification of the unconditional powers possible. Based on the results at the end of stage I, the primary objective for stage II is chosen, and sample sizes and critical values for stage II are determined.

Clinical Trials as Topic↗

Pupillary threshold as an index of population vitamin A status among children in India.

Two hundred seven vitamin A-deficient southern Indian children aged 1-7 y (mean age: 56.9 mo) underwent testing of dark-adapted visual and pupillary thresholds in their village setting according to a previously reported protocol. One hundred thirty (62.8%) of the children also underwent serum retinol testing, and 178 (86.0%) participated in a randomized, placebo-controlled vitamin A dosing trial with pre- and postdose testing of dark-adaptation threshold. Most subjects (184 of 207, 88.9%) were able to complete pupillary testing, an objective sign requiring minimal cooperation, including a high proportion of the youngest children (72.2% of subjects aged 2 y). The proportion of children completing visual threshold testing, which requires greater understanding and cooperation, was significantly smaller than that able to complete pupillary testing (131 of 207, 63.3%; P < 0.0001, chi square). At baseline (predosing), the mean serum retinol concentration declined in linear fashion with a higher pupillary threshold (0.73 mumol/L with a score < or = 4; 0.47 mumol/L with a score > or = 8; P < 0.01). The mean pupillary threshold for these highly vitamin A-deficient Indian children (-0.622 log cd/m2) was significantly higher than that for 136 more moderately deficient Indonesian children (-0.985 log cd/m2; P < 0.001, two-sample t test) and 56 normal American children (-1.335 log cd/m2; P < 0.0001, two-sample t test). The improvement in pupillary dark-adaptation testing was not significant for children receiving vitamin A or placebo, though there was a nonsignificant trend toward greater improvement in children receiving vitamin A (P = 0.2, two-sample t test). Pupillary threshold testing represents a new, noninvasive, practical, and seemingly valid approach to assessing the vitamin A status of a moderately to severely deficient preschool population.

Aging↗

Detection of Cryptosporidium parvum in raw milk by PCR and oligonucleotide probe hybridization.

Cryptosporidium spp. are potential contaminants of food. Suspected cases of food-borne cryptosporidiosis are rarely confirmed because of the limited numbers of oocysts in the samples and the lack of sensitive detection methods adaptable to food. PCR was investigated as a means of overcoming this problem. A PCR assay was designed for the specific amplification of a previously sequenced portion of an oocyst protein gene fragment of Cryptosporidium parvum (N. C. Lally, G. D. Baird, S. J. McQuay, F. Wright, and J. J. Oliver, Mol. Biochem. Parasitol. 56:69-78, 1992) and compared with the primer set of Laxer et al. (M. A. Laxer, B. K. Timblin, and R. J. Patel, Am. J. Trop. Med. Hyg. 45:688-694, 1991). The PCR products were hybridized with digoxigenin-labeled internal probes and detected by chemiluminescence to enhance sensitivity. The two sets of primers were compared with regard to their sensitivity and specificity by using a variety of human and animal isolates of C. parvum and related parasites. Both assays enabled the detection of 1 to 10 oocysts in 20 ml of artificially contaminated raw milk. The assay based on the PCR set and probe of Laxer et al. detected DNAs from Eimeria acervulina and Giardia intestinalis. The new assay has good specificity for C. parvum bovine isolates and hence has a better potential for monitoring the prevalence of C. parvum in raw milk and other environmental samples.

Animals↗