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Plasma protein profiling for diagnosis of pancreatic cancer reveals the presence of host response proteins.

Plasma protein profiling using separations coupled to matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) has great potential in translational research; it can be used for biomarker discovery and contribute to disease diagnosis and therapy. Previously reported biomarker searches have been done solely by MS protein profiling followed by bioinformatics analysis of the data. To add to current methods, we tested an alternative strategy for plasma protein profiling using pancreatic cancer as the model. First, offline solid-phase extraction is done with 96-well plates to fractionate and partially purify the proteins. Then, multiple profiling and identification experiments can be conducted on the same protein fractions because only 5% of the fractions are used for MALDI MS profiling. After MALDI MS analysis, the mass spectra are normalized and subjected to a peak detection algorithm. Over three sets of mass spectra acquired using different instrument variables, approximately 400 unique ion signals were detected. Classification schemes employing as many as eight individual peaks were developed using a training set with 123 members (82 cancer patients) and a blinded validation set with 125 members (57 cancer patients). The sensitivity of the study was 88%, but the specificity was significantly lower, 75%. The reason for the low specificity becomes apparent upon protein identification of the ion signals used for the classification. The identifications reveal only common serum proteins and components of the acute phase response, including serum amyloid A, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and inter-alpha-trypsin inhibitor.

Acute-Phase Proteins↗

Health status and access to care for children with special health care needs.

BACKGROUND: About 11-14% of children with special health care needs (CSHCN) have unmet needs during a given year. Little is known about the determinants of unmet health care needs for CSHCN. AIMS OF THE STUDY: The objective of this study was to explore the association between access to care (unmet needs) among CSHCN and their caregivers' mental health status as well as children's mental health status. METHODS: We surveyed a random sample of 1,088 caregivers of CSHCN who resided in the District of Columbia during the summer and fall of 2002. In the survey, we collected information on children's unmet needs mental health status (PARS) and their caregivers' mental health status (CES-D). We estimated the association between mental health status determinants of unmet needs adjusting for selection bias associated with plan choice (partially capitated managed care versus FFS) with an instrumental variables probit estimation technique. We used caregivers' preferences about physicians and hospitals networks, and whether the caregiver and child had the same last name to identify the plan choice equation. RESULTS: We found that caregivers with symptoms of depression were 26.3% more likely to report any unmet need, 67.6% more likely to report unmet hospital and physician need, 66.1% more likely to report unmet mental health care need and 38.8% more likely to report unmet need for other health care services. Caregivers of children with poor psychological adjustment were 26.3% more likely to report their child had an unmet need and 92.3% more likely to report an unmet mental health care need. DISCUSSION: Our analyses show that children whose caregivers experience symptoms of depression are significantly more likely to encounter difficulties obtaining needed medical and mental health care services. Furthermore, the findings reported here indicate that children with poor psychological adjustment are significantly more likely to experience unmet needs for medical and mental health care services. Our study has some limitations. First, most of the children in our sample are African-American, so these findings may differ for children of other races. Second, these findings may not be applicable to CSHCN who reside in rural areas. Third, we recognize the possibility that child and caregiver mental health is potentially endogenous. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The mental health status of CSHCN and their caregivers are barriers to care. IMPLICATIONS FOR HEALTH POLICIES: Policymakers should be concerned about the mental health status of children with special health care needs and their caregivers as such problems appear to be barriers to obtaining care. Therefore, to adequately address the access problems of children with special health care needs, policy must address the mental health problems of children and their caregivers. Providing mental health care for caregivers and children has the potential for improving overall access for CSHCN. IMPLICATION FOR FURTHER RESEARCH: Future research should determine the causal relationship between mental health problems of CSHCN and their caregivers and the level unmet health care needs.

Adolescent↗

A systematic review of relations between neighborhoods and mental health.

BACKGROUND: The relationship between neighborhood characteristics and resident mental health has been widely investigated in individual studies in recent years, but this literature is not adequately reviewed. AIMS OF THE STUDY: To systematically review relevant individual research of the relation between neighborhoods and adult mental health by identifying and synthesizing all relevant studies in this literature. METHODS: We conducted an electronic search with PubMed and PsycINFO, and manual reference-checking, resulting in 8,562 screened studies of which 29 were selected. Studies were included in the main synthesis if they (i) were published in English in peer reviewed journals; (ii) had relevant definitions and measures of neighborhood characteristics; (iii) utilized standardized measures of adult mental health; (iv) controlled for individual characteristics; (v) reported quantitative results; and, (vi) studied a population in a developed country. We focused on two key areas within this literature: the methodologies utilized to study neighborhood effects and quantitative results. With regard to the former, we examined five major issues: (i) definitions and measures of neighborhoods; (ii) definitions and measures of mental health; (iii) controls for individual level characteristics; (iv) conceptual models; and (v) analytical models. As for quantitative results, the relation was reviewed by types of neighborhood characteristics. We summarized general quantitative findings and drew common conclusions across groups of studies. RESULTS: 27/29 studies found statistically significant association between mental health and at least one measure of neighborhood characteristics, after adjusting for individual factors. This association was evident for all types of neighborhood features, varying from sociodemographic characteristics to physical environment, and from objective to subjective measures. Neighborhood effects were weakened when adding individual-level characteristics into the regression models, and were generally modest relative to individual effects. DISCUSSION AND LIMITATIONS: Although the evidence is highly consistent across studies, detailed evaluation of each individual study reveals a complex reality. The included studies used various study designs and measures of mental health and neighborhoods, making generalization of their relationships less meaningful. It is not possible to conclude that studies with weaker controls for individual characteristics found stronger association between neighborhoods and mental health and vice versa. As only two studies used randomized and controlled trials, causal effects must be interpreted with caution. Formal meta-analysis techniques cannot be used due to large heterogeneity across the included studies. Efficient methods for quantitative analysis remain a great challenge. IMPLICATIONS FOR HEALTH POLICY: The current evidence suggests that efforts to improve mental health may be limited if only individual-level interventions are implemented. The calculation of the costs and benefits of neighborhood-level interventions deserves more attention. Moreover, policy makers may want to incorporate mental health as a measure for evaluating neighborhood improvement programs. IMPLICATIONS FOR FUTURE RESEARCH: There are not enough replicated or comparable studies in this literature to make more precise quantitative conclusions of this relation. Key aspects of study design and analyses could be improved to better understand the true nature of causal relationships. The data resolution of neighborhood characteristics needs to better match with the scale of neighborhood definition that is hypothesized to affect the residents' mental health. As experimental designs are rare in this area, thoughtful use of panel data, instrumental variable (IV) techniques, and other non-experimental approaches deserves further exploration.

Adult↗

Steps in reviewing literature.

Reviewing the literature is an important part of the research process. Systematic steps to follow when evaluating the literature include critiquing the following: title, abstract, problem, purpose, theoretical or conceptual framework or model, implications for nursing, review of literature, hypotheses or research questions, variables, instruments, subjects, ethical concerns, research designs, results, conclusions, recommendations, and future studies. Frequently, the reader must search for these topics since few studies list the above as separate headings; however, it is important to evaluate each to determine a study's relevance to the reader's research needs.

Humans↗

Problems in measuring role strains and social functioning in relation to psychological symptoms.

The problems that people experience in social roles can be regarded as either causes or consequences of psychological symptoms. To reflect one of these possibilities, Pearlin et al. (1981) developed measures of "role strains" which are considered sources of psychopathology. To reflect the other position, Dohrenwend et al. (1981) constructed measures of "role functioning" which are seen as consequences of psychopathology. We show that the measures developed by these two teams of investigators are similar in content and show substantial empirical overlap despite the different meanings attributed to them. In an effort to understand whether these highly correlated measures assess, "role strain" or "role functioning," we conduct an exploratory analysis of marital and housework role problems, using a small panel sample of New York City residents. Specifically, we use instrumental variables to identify reciprocal effects between psychological distress and each role area. We find that the relationship between housework role problems and distress is more consistent with Pearlin et al.'s interpretation, whereas the relationship between marital problems and distress is more consistent with that of Dohrenwend et al. Investigators interested in measuring either role strain or role functioning must bear in mind the strong possibility of contamination from the other construct.

Educational Status↗

The measurement of oxygen tension in tissue.

Delivery of oxygen to cells is critical to biochemical and metabolic processes and is particularly important during conditions of illness and recovery. However, accurate measurement of perfusion and tissue oxygen tension, determinants of cellular oxygen supply, has been problematic. Technologic advancements offer promise for the assessment of these significant variables. Instruments utilizing polarographic electrodes have been commonly used for the measurement of tissue oxygen tension. Recently, optical fluorescence has been employed to measure the partial pressure of oxygen. These predominant methods for determining tissue oxygen tension are described and applications for research are discussed.

Blood Gas Monitoring, Transcutaneous↗

Computer-assisted microfluorometry.

The paper describes an automated microscope fluorometer, based on a Leitz MPV compact system. Automation of the system was provided by an Apple II personal computer thus greatly simplifying operating procedures and increasing measuring speed. The computer system was programmed in BASIC supplemented by a few assembly-level subroutines, necessary for the on-line visualization of results and key-touch control of plot features. Automation resulted in enhancement of measuring precision, due to the greater number of cells that could be analyzed within reasonable time, and to standardization of the measuring procedure itself. Moreover, computer-controlled acquisition made it possible to exploit fast averaging data detection thus enabling the signal-to-noise ratio to be increased and the part of coefficient of variation due to instrumental variability to be diminished. A program for cytophotometric measurements on two separate cell populations from the same slide is described.

Cytophotometry↗

Statistical methods for growth allometric studies.

Simple least square regression analysis, major axis regression, and reduced major axis regression have been advocated for straight line fitting to the logarithmically transformed data pairs in bivariate allometric studies. As all these techniques are based on rigid a priori assumptions on the error structure, their application may lead to considerable biases in slope estimation if these requirements are not met. A different mathematical model, the linear functional relationship, allows to remove the bias by estimating the error structure from grouped empirical data. The model is applicable to interspecific and cross-sectional growth allometric studies where natural grouping criteria are available (species, age). The technique is illustrated by growth allometry of myocardial cells and capillaries in the late postnatal period (after weaning) in 33 normal male Wistar rats (group 1: 5 weeks, group 2: 7 weeks, group 3: 13 weeks, group 4: 52 weeks). In left ventricular myocardium fixed by vascular perfusion, length and volume densities of myocardial cells and capillaries were estimated by stereological techniques at the light and electron microscopic level. Total capillary length and total myocardial cell volume were scaled to total myocardial cell length. A comparison of the scaling methods showed an underestimation of the slope and its confidence interval by all regression techniques, which would have led to the erroneous conclusion that the myocardial cell does not remain geometrically similar throughout the normal growth process. Linear functional relationship and the technique of instrumental variables led to nearly identical results and were both compatible with geometric similarity of the myocardial cell during growth. Positive allometry of total capillary length to total myocardial cell length (b = 1.674) demonstrates continuous neoformation of capillaries. The intensity of capillary proliferative activity during growth was intermediate between the reactions observed in myocardial hypertrophy due to pressure overload and that due to physical training. This agrees with the fact that both systemic arterial pressure and cardiac output increase during maturation. The study is designed as a worked example which should enable the practicing researcher to treat data from cross-sectional growth allometric studies with a simple and unbiased statistical method.

Animals↗

Effects of characteristics of the survey instrument on response rates to a mail survey of community hospitals.

A 4-factor, 16-cell experimental design was used to investigate the relationship between response rates of community hospitals to a survey conducted by the American Hospital Association (AHA) and 4 characteristics of the survey instrument, each varied dichotomously: the perceived length of the questionnaire, the order of questions, the orientation of the appeal made in the cover letter, and the presence or absence of a promise to share the results of the study with respondents. Response rate variations between the various cells were examined and multiple logistic regression was used to analyze the significance of the association between response rates and each of the four survey instrument variables while controlling for the effect of the others. At the same time, control was also maintained for the effects of five institutional characteristics of hospitals which a previous study had shown to have a significant relationship to response: bed size, location within or outside a standard metropolitan statistical area, AHA membership status, type of ownership, and form of control. The perceived length of the questionnaire and the order of questions were found to have a significant effect on response rates, but the orientation of the cover letter and a promise to share the results of the study with the respondents were found to be insignificant.

American Hospital Association↗

The impact of "parent care" on female labor supply decisions.

Data from the 1986-1988 Survey of Income and Program Participation panels were used to analyze how informal caregiving of disabled elderly parents affected female labor supply. Instrumental variables analyses suggested that coresidence with a disabled parent leads to a large, significant reduction in work hours, due primarily to withdrawal from the labor force. Although the impact of nonhousehold member caregiving was insignificant, evidence of an effect was stronger when commitment of caregiving time was greater. Projections of female labor force participation rates should account for potential increases in caregiving demand due to the aging of the U.S. population.

Adult↗

Assessing the linkages between low body mass index and morbidity in adults: evidence from four developing countries.

The study explores the relationship between low BMI and illness patterns in four developing countries. Using probit analysis, the study finds small but statistically significant effect of low BMI on proneness to morbidity in Pakistan and Kenya but none in the Philippines and Ghana. The circularity of causation between low BMI and illness was addressed by using the instrumental variable approach. The study also finds that the threshold at which morbidity begins to rise is not consistent with the suggested cut-off of BMI 18.5 kg/m2. The cut-offs were meaningful only in the case of Pakistan, but even here, the sizes of relationships are quite small although statistically significant.

Adolescent↗

[Prostatic-vesical inflammation and sexual problems].

With the purpose of investigating the relationship between prostatico-vesical inflammation and sexual disturbances, two groups of 15 patients with uncomplicated BPH were treated with mepartricin 150,000 U/die for 60 days. The two groups differed from each other for the presence of sexual disturbances only present in group A. The relationship between BPH and sexual picture was studied on the grounds of both the symptomatic and instrumental variables habitually adopted in the presence of the pathology in question and of a specific method for the quantitative evaluation of dynamic erection. The examination of the results obtained confirmed BPH clinical implications on sexuality as well as mepartricin excellent manageability, confirmed by the fact that never were sexual disturbances brought about by the drug. On the other hand the erectile activity index measured in the two groups, underwent a qualitative improvement even in the absence of changes in the quantitative datum.

Adult↗

Method development strategy for the analysis of anionic solutes by capillary electrophoresis.

A systematic approach to the development of methodology for the analysis of anionic solutes by capillary electrophoresis (CE) has been implemented. The strategy allows a rapid optimization of the experimental conditions and is based on the following steps: 1) A near optimum pH is chosen by inspection of the effective mobility versus pH curves of the sample components. The optimum pH lies in a region where the differences in the mobilities of all solutes are maximal. 2) An electrolyte system is selected by comparing the effective mobility of the electrolyte with the effective mobility of the primary components of the studied mixture. The appropriate electrolyte has a mobility as similar as possible to the mobility of the major components of the sample. 3) An initial experiment is run with the selected electrolyte system adjusted to the chosen pH and input values for other instrumental variables and electrolyte characteristics. 4) Depending on the degree of resolution obtained in the initial run, two important variables, the applied voltage and the electrolyte concentration, are then tuned in the proper direction, favoring the achievement of the highest resolution at the lowest possible analysis time. The proposed method development strategy was validated experimentally with a mixture of short-chained carboxylic acids and inorganic anions.

Anions↗

The impact of child support on cognitive outcomes of young children.

We use the National Longitudinal Survey of Youth-Child data to address three questions. First, does the receipt of child support have beneficial effects for children with absent fathers apart from increasing income? Second, do the effects of child support differ when child-support awards and payments are made cooperatively as opposed to being court ordered? Third, are any positive effects of child support solely a product of unmeasured differences among fathers and families? Controlling for the socioeconomic characteristics of the child and family, we find some evidence that receipt of child support has a positive impact on children's cognitive test scores over and above its contribution to total income. However, the effects vary by test, by race, and by reason for father's absence. Our results also indicate that the distinction between cooperative and noncooperative awards is important. Finally, our instrumental variables estimates show that the effects of child support persist after we control for unobserved characteristics of fathers and families.

Achievement↗

Breath alcohol measurement variability associated with different instrumentation and protocols.

Breath alcohol measurement has variability resulting from instrumental, procedural and biological components. Reliable estimates of the standard deviation (S.D.) are necessary for calculating uncertainty in the form of confidence intervals. These estimates are concentration dependant and can be obtained from models derived from duplicate breath test data. Duplicate data from four state jurisdictions (Alabama using the Drager 7110, Minnesota using the Intoxilyzer 5000, Washington using the BAC Datamaster and Wisconsin using the Intoximeter EC/IR) were analyzed to derive predictive models for standard deviation as a function of concentration. All jurisdiction/instrument combinations yielded forensically acceptable variation while showing a general linear increase in standard deviation with concentration. This is consistent with a multiplicative error model. Jurisdictions using the same instruments but not performing duplicate analyses could also employ the straightforward models derived here to estimate standard deviations for their measurement results.

Alabama↗

Two kinds of items in quality of life instruments: 'indicator and causal variables' in the EORTC qlq-c30.

Two kinds of variables may be differentiated within instruments measuring health-related quality of life (HRQOL). Physical symptoms may be called causal variables because their occurrence can cause a change in HRQOL, but poor HRQOL need not necessarily imply that a patient suffers from these symptoms. Other items can be regarded as indicator variables. They reflect the level of HRQOL and a patient with a poor HRQOL is likely to have low scores on all indicator variables. The aim of this study was to test the relationship of the latent HRQOL construct to items and domains on the EORTC QLQ-C30. Confirmatory factor analysis was performed on EORTC QLQ-C30 data from 205 gastrointestinal cancer patients assessed one month after surgery. Functioning scales were established as variables indicating the level of HRQOL whereas all other subscales and items were established as variables causing a change in HRQOL. The model-data fit was satisfactory. Results support the hypothesis that two kinds of variables may be differentiated within HRQOL instruments. Further research should investigate whether both kinds of variables could be combined into a higher order, aggregate score for HRQOL.

Activities of Daily Living↗

Design and performance of a microchip electrophoresis instrument with sensitive variable-wavelength fluorescence detection.

A modular instrument for high-speed microchip electrophoresis (MCE) equipped with a sensitive variable-wavelength fluorescence detection system was developed and evaluated. The experimental setup consists mainly of a lamp-based epifluorescence microscope for variable-wavelength fluorescence detection and imaging and a programmable four-channel bipolar high-voltage source capable of delivering up to +/- 10 kV per channel. The optical unit was equipped with a high-sensitivity photomultiplier tube and an adjustable aperture. The system was applied to MCE separations of flurescein isothiocyanate (FITC)-labelled amines utilizing blue light (450-480 nm) for excitation as well as for the separation of rhodamines utilizing excitation light in the green spectral region (531-560 nm). At optimized conditions baseline separation of four FITC-labelled amines could be obtained in less than 50 s at a detection limit of 460 ppt (1 nM) with a signal-to-noise ratio of 3:1. Three rhodamines could be baseline-separated in less than 6 s at a detection limit of 240 ppt (500 pM). The relative standard deviations of absolute migration times determined in repetitive MCE separations of FITC-labelled amines were below 2.5% (n= 25). By the application of cyclodextrin-modified electrolytes, chiral separation of FITC-labelled amines could be performed in seconds demonstrating the potential of microchip electrophoresis for chiral high-throughput screening.

Cyclodextrins↗