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Comorbidity of fibromyalgia and posttraumatic stress disorder symptoms in a community sample of women.

OBJECTIVE: To test alternative explanations for the comorbidity between fibromyalgia (FM), a medically unexplained syndrome involving widespread pain, and posttraumatic stress disorder (PTSD). In contrast to a default "risk factor" hypothesis, tested hypotheses were that: A) The association is due to a sampling bias introduced by the study of care-seeking individuals; B) FM is an additive burden that strains coping resources when confronting life stress; and C) Arousal symptoms of PTSD and FM are confounded. DESIGN: Community-dwelling women in the New York/New Jersey metropolitan area (N=1,312) completed a telephone survey regarding FM-like symptoms prior to September 11, 2001. Approximately 6 months after the World Trade Center terrorist attacks, they again completed the survey, to which questions regarding PTSD symptoms were added. RESULTS: The odds of probable PTSD were more than three times greater in women with FM-like symptoms, both assessed after 9/11. The odds ratio was not reduced by controlling for FM-like symptoms before 9/11 or for the potentially confounded symptoms of PTSD specifically related to arousal. CONCLUSIONS: These findings lead us to reject alternate explanations for the comorbidity between FM and PTSD. Speculations that FM and PTSD share psychobiological risk factors remain plausible.

Adult↗

Research applications of ultrasonic imaging in reproductive biology.

In the short time that transrectal ultrasonic imaging of the reproductive tract has been used as a research tool, many discoveries have resulted, some of which would otherwise have escaped detection for many years. Ultrasonography provides a wide array of morphologic information without invading or disturbing the tissues. Examinations can be done repeatedly over many days, or a dynamic event (e.g., ovulation) can be monitored in its entirety by continuous observation (e.g., 30 min). Inclusion of ultrasonic examinations in experimental protocols affords the opportunity to associate changing morphology with hormonal and other functional changes. If experimental testing is expected to involve changing morphology, ultrasonic imaging should be considered. End points can be measured or ranked and therefore data can be statistically analyzed for conventional hypothesis testing. The research potential of this technology and its adaptability for computer-assisted assessment go far beyond simplistic determination of ovulation, luteal formation, and pregnancy diagnosis. It is the authors' opinion that ultrasonic imaging is a revolutionary advance in reproductive research that is destined to rival the impact of other technologic breakthroughs, including radioimmunoassay.

Animals↗

Reliability and validity of the Food Pyramid Self Efficacy Scale: use in coronary artery bypass patients.

Inappropriate dietary intake is associated with 5 of the 10 leading causes of U.S. death; coronary artery disease (CAD) ranks highest regardless of gender in people over the age of 65. Of the modifiable risk factors for CAD, two of four pertain to food choices. Although lifestyle habits can enhance or impair health, people's beliefs that they can motivate and regulate their own behavior (self efficacy) plays a crucial role in whether they even consider changing detrimental health habits. The Food Pyramid Self Efficacy Scale (FPSES) is an instrument to measure an elder's confidence in his/her ability to choose healthy food items in a variety of situations. The purpose of this study was to determine the reliability and validity of the FPSES. Thirty postoperative CABG patients participated (mean age 70.4). FPSES test-retest (r = 0.78, p = 0.008); coefficient alpha = 0.92. Six content experts judged the FPSES (content validity index [CVI] = 0.85). Construct validity of the instrument was achieved through hypothesis testing, supporting the statement that the higher the nutritional risk, the greater the functional decline (r = 0.37, p = 0.05). As many of the health problems associated with the elderly are preventable or controllable through health promotion, it is vital that measures exist to determine a person's confidence that one believes in the capability to change to healthy eating behaviors.

Activities of Daily Living↗

Multifactorial analysis of family data ascertained through truncation: a comparative evaluation of two methods of statistical inference.

When family data are ascertained through single selection based on truncation, a prevailing method of analysis is to condition the likelihood function on the proband's actual phenotypic value. An alternative method conditions the likelihood function on the event that the proband's measurement lies in the truncation region. Both methods are contrasted here by using Monte Carlo simulations; identical sets of data were analyzed using both methods. The results suggest that, under either method, (1) parameter estimates are nearly unbiased and (2) likelihood-ratio tests of null hypotheses are approximately distributed as chi 2. However, conditioning on the proband's actual phenotypic value yields considerably less efficient estimates and reduced power for hypothesis tests. A corresponding result also holds under complete ascertainment. It is argued, therefore, that whenever sufficient information is available on the nature of truncation, the alternative approach should be used.

Computer Simulation↗

Cardiac mechanical performance in circulatory shock: a critical review of methods and results.

The article reviews studies which have focused upon the changes in cardiac contractile behavior induced by shock states. The major hypothesis tested experimentally was that cardiac contractility is depressed by shock states. The conclusions drawn by the cited articles are diverse, equally divided between confirming and rejecting the above hypothesis. The thesis of this article is that these diverse conclusions may have been caused by the limitations of the methods employed to assess cardiac contractility. The concepts of cardiac function curves, cardiac work and efficiency, parameters of shortening and the analysis of the end systolic pressure volume relationship (EES) are examined for their suitability to determine changes in cardiac contractility during shock states. Only the EES methodology appears to be able to assess cardiac contractility in shock states due to its insensitivity to altered conditions of cardiac contraction.

Animals↗

Symptoms of chronic vaginal infection and microscopic condyloma in women.

The purpose of this study was to determine if women who self-reported symptoms of chronic vaginal infection might be at risk for microscopic condyloma and, therefore, in need of colposcopic examinations. The hypothesis tested was that women who report yeast-type symptom chronicity and who have yeast-negative laboratory studies will have a significant incidence of microscopic vulvar condyloma. The hypothesis was supported by the results. Findings show a need to broaden the use of the colposcope to detect condyloma in women with a chronicity of unexplained yeast-type symptoms.

Adolescent↗

Leukocytic pyrogen: a major mediator of the acute phase reaction.

The acute phase reaction is initiated and regulated by leukocytic pyrogen which is released by activated host phagocytes at inflammatory sites during inflammatory reactions of any etiology. The physiological alterations which follow include, in addition to the characteristic acute phase protein changes, fever, granulocytosis, fall in serum iron and zinc, metabolic stimulation of blood granulocytes, activation of T-cell function and doubtless other effects as yet unrecognized. These responses are mediated by free or by protein-bound LP molecules and reflect both direct receptor coupled effects and more indirect mechanisms such as release of secondary mediators from cells or body fluids and involvement of neural or neurohumoral pathways. This unitarian hypothesis implies a functional interrelationship between the component parts, and allows a model for critical examination and new hypothesis testing. The wider availability of pure preparations of LP and of possible subtypes of LP and of a sensitive immunoassay would help us to prove or to expand this hypothesis and to advance our understanding of this important phase of acute inflammation. Earlier in this conference we heard that the mediator derepresses a message: I'd like to put forward the idea that in the acute phase reaction the mediator is the message.

Acute Disease↗

Characteristics of replicated single-nucleotide polymorphism genotypes from COGA: Affymetrix and Center for Inherited Disease Research.

Genetic Analysis Workshop 14 provided re-genotyped single-nucleotide polymorphism (SNP) data. Specifically, both Center for Inherited Disease Research (CIDR) and Affymetrix genotyped the same 11,560 SNPs from the Affymetrix GeneChip Mapping 10K Array marker set on the same 184 individuals from the Collaborative Study on the Genetics of Alcoholism database. While the inconsistency rate between CIDR and Affymetrix (two different genotypes for the same subject) was low (0.2%), the non-replication rate (two different genotypes for the same subject or one identified genotype and one missing genotype) was substantial (9.5%). The missing data could be from no-call regions, which is inconsistent with recent recommendations about the use of no-call regions in association tests. In addition, no-call regions would suggest that the actual inconsistency rate is higher than reported. A high inconsistency rate has significant impact on power in related hypothesis tests. In addition, the data are consistent with assumptions made in a recently proposed likelihood ratio test of association for re-genotyped data.

Alcoholism↗

Work and depression among women in the Federal Republic of Germany.

A study was carried out to test the association between workplace stress and depression among working women and men in the Federal Republic of Germany (FRG). The data are from the 1984 German national health survey. The sample (N = 795) was composed of 319 working women and 476 working men. The hypothesis tested was that depression is related to high job demands and low job decision latitude. Correlation and multiple regression analyses supported the hypothesis for both women and men. However, the mean level of decision latitude was lower for women than men, as was the level of job demands. The mean depression score was higher for women, and correlations between depression and high job demands/low decision latitude were stronger for women than men. It was concluded that low decision latitude combined with high job demands, a condition experienced frequently by working women, contributes to depression among working women in the FRG. Study findings shed light on the health of employed women in the FRG and may also have implications for working women in other Western industrialized countries.

Decision Making↗

Global gene mining and the pharmaceutical industry.

Worldwide efforts are ongoing in optimizing medical treatment by searching for the right medicine at the right dose for the individual. Metabolism is regulated by polymorphisms, which may be tested by relatively simple SNP analysis, however requiring DNA from the test individuals. Target genes for the efficiency of a given medicine or predisposition of a given disease are also subject to population studies, e.g., in Iceland, Estonia, Sweden, etc. For hypothesis testing and generation, several bio-banks with samples from patients and healthy persons within the pharmaceutical industry have been established during the past 10 years. Thus, more than 100,000 samples are stored in the freezers of either the pharmaceutical companies or their contractual partners at universities and test institutions. Ethical issues related to data protection of the individuals providing samples to bio-banks are several: nature and extent of information prior to consent, coverage of the consent given by the study person, labeling and storage of the sample and data (coded or anonymized). In general, genetic test data, once obtained, are permanent and cannot be changed. The test data may imply information that is not beneficial to the patient and his/her family (e.g., employment opportunities, insurance, etc.). Furthermore, there may be a long latency between the analysis of the genetic test and the clinical expression of the disease and wide differences in the disease patterns. Consequently, information about some genetic test data may stigmatize patients leading to poor quality of life. This has raised the issue of 'genetic exceptionalism' justifying specific regulation of use of genetic information. Discussions on how to handle sampling and data are ongoing within the industry and the regulatory sphere, the European Agency for the Evaluation of Medicinal Products (EMEA) having issued a position paper, the Council for International Organizations of Medical Sciences (CIOMS) having a working group on this issue, and the European Society of Human Genetics preparing background paper on 'Polymorphic sequence variants in medicine: Technical, social, legal and ethical issues. Pharmacogenetics as an example'. Within the European project Privacy in Research Ethics and Law (PRIVIREAL), recommendations for common European guidelines for membership in research ethical committees have been discussed, balancing the interests and assuring independence and legal competence. Good decision making, assuring legality of protocols and assessment of data protection is suggested to be part of any evaluation of protocols.

Drug Industry↗

Accounting for coalescent stochasticity in testing phylogeographical hypotheses: modelling Pleistocene population structure in the Idaho giant salamander Dicamptodon aterrimus.

Several theoretical studies have demonstrated the importance of accounting for coalescent stochasticity in phylogeographical studies, however, there are few empirical examples that do so in the context of explicit hypothesis testing. Here, we provide an example from the Idaho giant salamander (Dicamptodon aterrimus) using 118 mtDNA sequences, nearly 2 kb in length. This species is endemic to mesic forests in northern and central Idaho, and several a priori hypotheses have been erected based both on palaeoclimatic grounds and from phylogeographical studies of codistributed amphibians. Phylogenetic analysis of the D. aterrimus data suggests an expansion from a single refugium south of the Salmon River, whereas the inference from nested clade analysis is one of expansion from a single refugium in the Clearwater drainage. Explicit testing of these hypotheses, using geographically structured coalescent simulations to erect null distributions, indicates we can reject expansion from the Clearwater drainage (pCLW = 0.089), but not expansion from the South Fork of the Salmon drainage (pSAL = 0.329). Furthermore, data from codistributed amphibians suggest that there may have been two refugia, and an amova shows that most of the molecular variance partitioned between the Clearwater and the Salmon drainages (54.40%; P < 0.001) and within drainages (43.61%; P < 0.001). As a result, we also tested three a priori hypotheses which predicted that both the Clearwater and Salmon drainages functioned as refugia during the late Pleistocene; we could reject (PCORD = 0.019) divergence dates during the Cordilleran glacial maxima [c. 20 000 years before present (ybp)], during the Sangamon interglacial (c. 35 000 ybp; pSANG = 0.032), as well as pre-Pleistocene divergence (c. 1.7 Ma; ppP < 0.001). Mismatch distributions and Tajima's D within the individual drainages provide further support to recent population expansion. This work demonstrates coalescent stochasticity is an important phenomenon to consider in testing phylogeographical hypotheses, and suggests that analytical methods which fail to sufficiently quantify this uncertainty can lead to false confidence in the conclusions drawn from these methods.

Animals↗

The analysis of repeated measures designs in medical research.

Medical researchers can employ repeated measures designs to study the effects of a treatment over time or when each subject receives all treatments. Univariate F tests and multiple comparison procedures for comparing means constitute the methods to test for the presence of treatment effects. For validity, however, these tests must satisfy the sphericity assumption. To circumvent the biasing effects of non-sphericity, this paper shows the applicability of the Greenhouse and Geisser three stage approach for univariate omnibus hypothesis testing in repeated measures designs containing any number of repeated factors. In addition, we present a multiple comparison procedure which provides a valid or robust test and thus controls the overall probability of a Type I error.

Research Design↗

New approaches to understanding p53 gene tumor mutation spectra.

The first p53 gene mutation arising in a human tumor was described a decade ago by Baker et al. [S.J. Baker, E.R. Fearon, J.M. Nigro, S.R. Hamilton, A.C. Preisinger, J.M. Jessup, P. van Tuinen, D.H. Ledbetter, D.F. Barker, Y. Nakamura, R. White, B. Vogelstein, Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas, Science 244 (1989) 217-221]. There are now over 10,000 mutations extracted from the published literature in the IARC database of human p53 tumor mutations [P. Hainaut, T. Hernandez, A. Robinson, P. Rodriguez-Tome, T. Flores, M. Hollstein, C.C. Harris, R. Montesano, IARC database of p53 gene mutations in human tumors and cell lines: updated compilation, revised formats and new visualization tools, Nucleic Acids Res. 26 (1998) 205-213; Version R3, January 1999]. A large and diverse collection of tumor mutations in cancer patients provides important information on the nature of environmental factors or biological processes that are important causes of human gene mutation, since xenobiotic mutagens as well as endogenous mechanisms of genetic change produce characteristic types of patterns in target DNA [J.H. Miller, Mutational specificity in bacteria, Annu. Rev. Genet. 17 (1983) 215-238; T. Lindahl, Instability and decay of the primary structure of DNA, Nature 362 (1993) 709-715; S.P. Hussain, C.C. Harris, Molecular epidemiology of human cancer: contribution of mutation spectra studies of tumor suppressor genes, Cancer Res. 58 (1998) 4023-4037; P. Hainaut, M. Hollstein, p53 and human cancer: the first ten thousand mutations, Adv. Cancer Res. 2000]. P53 gene mutations in cancers can be compared to point mutation spectra at the HPRT locus of human lymphocytes from patients or healthy individuals with known exposure histories, and accumulated data indicate that mutation patterns at the two loci share certain general features. Hypotheses regarding specific cancer risk factors can be tested by comparing p53 tumor mutations typical of a defined patient group against mutations generated experimentally in rodents or in prokaryotic and eukaryotic cells in vitro. Refinements of this approach to hypothesis testing are being explored that employ human p53 sequences introduced artificially into experimental organisms used in laboratory mutagenesis assays. P53-specific laboratory models, combined with DNA microchips designed for high through-put mutation screening promise to unmask information currently hidden in the compilation of human tumor p53 mutations.

Animals↗

Effectiveness of a group exercise program in a long-term care facility: a randomized pilot trial.

OBJECTIVE: The purpose of this pilot was to determine whether a strength and flexibility program in frail long-term care facility (LTC) residents would result in improved function. DESIGN: A prospective, randomized, controlled, semicrossover trial was designed with participants assigned either to group exercise (EX) or recreational therapy (C). In the EX group, the intervention continued for 1 year. In the C group, recreation continued for 6 months; these controls were then crossed over to the same exercise intervention as the EX group and followed for an additional 6 months. Functional outcomes were measured at baseline and 3, 6, 9, and 12 months for both groups. SETTING: A LTC facility, which included both assisted living (AL) and nursing home (NH) residents. PARTICIPANTS: Twenty frail residents (5 from NH, 15 from AL) aged 75 to 99 years at one LTC facility. INTERVENTION: After random group assignment, the EX group met 1 hour three times per week. An exercise physiologist and LTC staff conducted sessions which included seated range of motion (ROM) exercises and strength training using simple equipment such as elastic resistance bands (therabands) and soft weights. The C group met three times per week and participated in activities such as painting during the first 6 months, before crossing over to exercise. MEASUREMENTS AND METHODS: Objective measures of physical and cognitive function were obtained at baseline and 3, 6, 9, and 12 months using the timed get-up-and-go test (TUG), Berg balance scale, physical performance test (PPT), and mini-mental status exam (MMSE). Because we were interested in the impact of exercise on multiple endpoints and to protect the type I error rate, a global hypothesis test was used. RESULTS: There was a significant overall impact across the four measures of the exercise intervention (P = 0.013). Exercise benefit as indicated by the difference between exercise and control conditions showed exercise decreased TUG by 18 seconds, which represents an effect size (in standard deviation units) of 0.50, increased PPT scores by 1.3, with effect size = 0.40, increased Berg scores by 4.8, with effect size of 0.32, and increased MMSE by 3.1, with effect size = 0.54. Except for the Berg, 90% confidence intervals on these exercise effects excluded 0. CONCLUSION: Frail elderly in a LTC facility were able to participate and benefit from a strength training program. The program was delivered with low-cost equipment by an exercise physiologist and LTC staff. The advantage of such a program is that it provides recreational and therapeutic benefits.

Activities of Daily Living↗

Transport of airborne particles within a room.

The objective of this study is to test a technique used to analyze contaminant transport in the wake of a bluff body under controlled experimental conditions for application to aerosol transport in a complex furnished room. Specifically, the hypothesis tested by our work is that the dispersion of contaminants in a room is related to the turbulence kinetic energy and length scale. This turbulence is, in turn, determined by the size and shape of furnishings within the room and by the ventilation characteristics. This approach was tested for indoor dispersion through computational fluid dynamics simulations and laboratory experiments. In each, 3 mum aerosols were released in a furnished room with varied contaminant release locations (at the inlet vent or under a desk). The realizable k approximately epsilon model was employed in the simulations, followed by a Lagrangian particle trajectory simulation used as input for an in-house FORTRAN code to compute aerosol concentration. For the experiments, concentrations were measured simultaneously at seven locations by laser photometry, and air velocity was measured using laser Doppler velocimetry. The results suggest that turbulent diffusion is a significant factor in contaminant residence time in a furnished room. This procedure was then expanded to develop a simplified correlation between contaminant residence time and the number of enclosing surfaces around a point containing the contaminant. Practical Implications The work presented here provides a methodology for relating local aerosol residence time to properties of room ventilation and furniture arrangement. This technique may be used to assess probable locations of high concentration by knowing only the particle release location, furniture configuration, inlet and outlet locations, and air speeds, which are all observable features. Applications of this method include development of 'rules of thumb' for first responders entering a room where an agent has been released and selection of sampler locations to monitor conditions in sensitive areas.

Air Movements↗

Methods for pooling results from multi-center studies.

A multi-center study is one conducted simultaneously in several participating centers following an agreed protocol, where the randomization has been carried out independently within each center. The main consideration for pooling the data from the individual centers is the choice between a weighted analysis, which weights centers relative to the number of patients in them, or an unweighted analysis as the primary statistical method. The unweighted analysis is used to investigate whether there was an interaction between the centers and study groups. Another issue is whether a fixed- or random-effects model should be used. There is unresolved controversy among statisticians about whether to use a weighted (type II) or unweighted analysis (type III), since there are advantages and disadvantages to the use of either method. The weighted analysis provides the most powerful test of the treatment contrast if there is no interaction between treatment and center. If there is an interaction, the unweighted analysis leads to unbiased estimates. Although, from an estimation and hypothesis testing standpoint, there is no need to balance the number of patients between the sites, it is sensible to avoid major imbalances among the study sites. There is agreement among statisticians that a fixed-effects model should be used.

Data Interpretation, Statistical↗

The precision of fit at the implant prosthodontic interface.

STATEMENT OF PROBLEM: Percussion, visual observation, and conventional periapical radiographs are the methods most frequently used clinically to evaluate the accuracy of implant component assemblies, whereas methods to measure the precision of fit are limited. PURPOSE: In this study the Periotest instrument was used to evaluate the stability of the interfaces between the implant and the abutment, along with the abutment and the gold cylinder under a series of assembly conditions. The hypothesis tested is that a more negative Periotest value (PTV) would indicate an accurate fit and a more positive value PTV would correlate with an inaccurate fit. MATERIAL AND METHODS: To investigate this hypothesis in vitro, two bovine ribs were used as patient simulation models. Each model contained three self-tapping Brånemark implants placed approximately 7 to 10 mm apart and arranged in a reasonable curvature. A series of component assembly conditions were created as accurate and inaccurate with thickness gauges of 25.4 microns, 50.8 microns, and 101.6 microns. RESULTS: The mean Periotest values and SDs for accurately assembled abutments and gold cylinders were -6.0 +/- 0.32 and -3.4 +/- 0.68, respectively. Periotest value data of the assembly conditions were statistically analyzed with multiple regression analysis. The misfit in the implant to abutment interface resulted in a more negative Periotest value trend (r = 0.54) with increases in gauge thickness. However, the same magnitudes of misfit at the abutment to gold cylinder interface produced a more positive Periotest value trend (r = 0.72). CONCLUSION: The PTV trends were consistent with increased stability at the abutment to implant interface from the increasing magnitude of misfit created with the thickness gauges. In contrast, the measurement trends observed for the abutment to gold cylinder interface were consistent with decreased stability with each increase in gauge thickness inserted at the interface.

Acceleration↗

A log-normal model for individual bioequivalence.

A log-normal model is developed for testing pi 1, the probability that a subject's response will fall within given bioequivalence limits. The model is a parametric analog of Anderson and Hauck's TIER rule. Confidence intervals and hypothesis tests are derived. Statistical power is compared with the that of the TIER rule. The probability of demonstrating mean bioequivalence is shown to greatly exceed that of showing individual bioequivalence.

Humans↗