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PubMedDate not supplied

Shifting perspectives: gero-oncology nursing research.

PURPOSE/OBJECTIVES: To analyze the development of gero-oncology research through a critical review of nursing and other relevant research as well as the present state of practice. DATA SOURCES: Journal articles, book chapters, and personal experience. DATA SYNTHESIS: Cancer in older adults is viewed through two investigative perspectives. The assumptions, questions, theoretical frames, and research design that follow from these investigative perspectives do not adequately meet the need to examine the interplay of responses to aging, cancer, and nursing practice. The mismatch of need, knowledge, and resources marks older adults with cancer as a special population in need of far more sophisticated research. With the synthesis of a new perspective, gero-oncology nursing research becomes age focused, more precisely shaping theoretical, methodologic, and analytic approaches. CONCLUSIONS: Uniform attachment of chronologic age or other simple age-related variables to investigations, which is the primary consideration of age-related research, is irrelevant for older adults who are diagnosed with, treated for, live with, survive, and die from cancer. Shaping the next phase of gero-oncology research with a focus on age precisely integrates theoretical, methodologic, and analytic approaches through language specific to older adults and cancer. IMPLICATIONS FOR NURSING: Shifting perspectives in gero-oncology nursing research will better inform future practice.

Aged↗
PubMed2006

Bias arising from missing data in predictive models.

OBJECTIVE: The purpose of this study is to determine the effect of three common approaches to handling missing data on the results of a predictive model. STUDY DESIGN AND SETTING: Monte Carlo simulation study using simulated data was used. A baseline logistic regression using complete data was performed to predict hospital admission, based on the white blood cell count (WBC) (dichotomized as normal or high), presence of fever, or procedures performed (PROC). A series of simulations was then performed in which WBC data were deleted for varying proportions (15-85%) of patients under various patterns of missingness. Three analytic approaches were used: analysis restricted to cases with complete data, missing data assumed to be normal (MAN), and use of imputed values. RESULTS: In the baseline analysis, all three predictors were all significantly associated with admission. Using either the MAN approach or imputation, the odds ratio (OR) for WBC was substantially over- or underestimated depending on the missingness pattern, and there was considerable bias toward the null in the OR estimates for fever. In the CC analyses, OR for WBC was consistently biased toward the null, OR for PROC was biased away from the null, and the OR for fever was biased toward or away from the null. Estimates for overall model discrimination were substantially biased using all analytic approaches. CONCLUSIONS: All three methods of handling large amounts of missing data can lead to biased estimates of the OR and of model performance in predictive models. Predictor variables that are measured inconsistently can affect the validity of such models.

Adolescent↗
PubMed2006

Gene expression profiling on lung cancer outcome prediction: present clinical value and future premise.

DNA microarray has been widely used in cancer research to better predict clinical outcomes and potentially improve patient management. The new approach provides accurate tumor classification and outcome predictions, such as tumor stage, metastatic status, and patient survival, and offers some hope for individualized medicine. However, growing evidence suggests that gene-based prediction is not stable and little is known about the prediction power of gene expression profiles compared with well-known clinical and pathologic predictors. This review summarized up-to-date publications in microarray-based lung cancer clinical outcome prediction and conducted secondary analyses for those with sufficient sample sizes and associated clinical information. Among the most commonly used analytic approaches, unsupervised clustering mainly recaptures tumor histology and provides variable degrees of prediction for tumor stage, lymph node status, or survival. Overall, most studies lack an independent validation. Supervised learning and testing generally offer a better prediction. Noted is that when conventional predictors of age, gender, stage, cell type, and tumor grade are considered collectively, the predictive advantage of the gene expression profiles diminishes. We conclude that outcome prediction from gene expression signatures selected by current analytic approaches can be mostly explained by well-known conventional predictors, particularly histologic subtype and grade of differentiation. A strategy for establishing independent or more accurate signatures is commented.

Cell Differentiation↗
PubMed2007

Physical approach to analytic simulation of Fresnel integrals.

Fresnel integrals continue to find new applications in various areas of human activity, including technology and music. However, performing calculations with them is often hindered by a mathematical peculiarity of these integrals, which is the rapidly oscillating functions of the basic variable. This circumstance complicates the numerical calculations when these integrals need additional integral transformation: convolution, Fourier transform, etc. The suggested solution of the problem consists of replacement of the complex Fresnel integral by a single rational function that simulates this integral in the entire area of its existence with an accuracy up to 10(-6). The advantages of the suggested approach are confirmed by the concrete example.

Journal Article↗
PubMedDate not supplied

Mass spectrometry for detection of 4-hydroxy-trans-2-nonenal (HNE) adducts with peptides and proteins.

Despite the great technical advancement of mass spectrometry, this technique has contributed in a limited way to the discovery and quantitation of specific/precocious markers linked to free radical-mediated diseases. Unsaturated aldehydes generated by free radical-induced lipid peroxidation of polyunsaturated fatty acids, and in particular 4-hydroxy-trans-2 nonenal (HNE), are involved in the onset and progression of many pathologies such as cardiovascular (atherosclerosis, long-term complications of diabetes) and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and cerebral ischemia). Most of the biological effects of HNE are attributed to the capacity of HNE to react with the nucleophilic sites of proteins and peptides (other than nucleic acids), to form covalently modified biomolecules that can disrupt important cellular functions and induce mutations. By considering the emerging role of HNE in several human diseases, an unequivocal analytical approach as mass spectrometry to detect/elucidate the structure of protein-HNE adducts in biological matrices is strictly needed not only to understand the reaction mechanism of HNE, but also to gain a deeper insight into the pathological role of HNE. This with the aim to provide intermediate diagnostic biomarkers for human diseases. This review sheds focus on the "state-of-the-art" of mass spectrometric applications in the field of HNE-protein adducts characterization, starting from the fundamental early studies and discussing the different MS-based approaches that can provide detailed information on the mechanistic aspects of HNE-protein interaction. In the last decade, the increases in the accessible mass ranges of modern instruments and advances in ionization methods have made possible a fundamental improvement in the analysis of protein-HNE adducts by mass spectrometry, and in particular by matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) tandem mass spectrometry. The recent developments and uses of combined analytical approaches to detect and characterize the type/site of interaction have been highlighted, and several other aspects, including sample preparation methodologies, structure elucidation, and data analysis have also been considered.

Aldehydes↗
PubMed1994

In vitro heart valve testing: steady versus pulsatile flow.

The design of artificial heart valves has traditionally been based on the development of a prototype device which was then subjected to extensive laboratory testing in order to confirm its suitability for clinical use. In the past the in vitro assessment of a valve's performance was based principally on the measurement of parameters such as pressure difference, regurgitation and, more recently, energy losses. Such measurements can be defined as being at the 'macro' level and rarely show any clinically significant differences amongst currently available prostheses. The analytical approach to flow through heart valves has previously been hampered by difficulties experienced in solving the relevant equations of flow particularly in the case of pulsatile conditions. Computational techniques are now available which enable appropriate solutions to be obtained for these problems and consequently provide an opportunity for detailed examination of the 'micro' level of flow disturbances exhibited by the different valves. This present preliminary study is designed to illustrate the use of such an analytical approach to the flow through prosthetic valves. A single topic has been selected for this purpose which is the comparative value of steady versus pulsatile flow testing. A bileaflet valve was chosen for the analysis and a mathematical model of this valve in the aortic position of the Sheffield Pulse Duplicator was created. The theoretical analysis was carried out using a commercially available Computational Fluid Dynamics package, namely, FIDAP, on a SUN MICROSYSTEMS 10-30 workstation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗
PubMed1999

Sub-grouping non-melancholic major depression using both clinical and aetiological features.

OBJECTIVE: In previous papers we have considered the extent to which two contrasting analytic approaches, examining reported clinical symptom variables alone and aetiological variables alone, assist definition of subgroups of non-melancholic major depression. Here, we address the same objective but combine both sets of variables, and contrast the combined solution with each of the contributing ones. METHOD: We study a sample of 185 subjects with a putative non-melancholic major depressive disorder, with analyses involving 13 aetiological and 38 symptom variables. RESULTS: A four-class subgrouping was derived by use of a cluster analytic technique, with 'neurotic depression', non-anxious 'depressed', 'situational' and 'residual' groups. The largest group comprised 'neurotic depression' subjects, with characteristics compatible with a spectrum disorder encompassing both clinical features as well as an underlying temperament and personality style marked by anxiety. CONCLUSIONS: Comparative advantages and properties of the three differing analytic approaches to defining 'meaningful' non-melancholic major depressive subgroupings are considered. As a 'neurotic depressive' class has been consistently identified across those three approaches, but with quite varying numbers of subjects circumscribed, it is clearly a 'fuzzy' entity which may benefit from a dimensional approach to its measurement. As many of the non-melancholic groupings appear secondary to a substantive predisposing factor such as anxiety or disordered personality functioning, the clinical importance and treatment utility in identifying and circumscribing such classes are clearly supported.

Adult↗
PubMed2006

Cortical network modeling: analytical methods for firing rates and some properties of networks of LIF neurons.

The circuitry of cortical networks involves interacting populations of excitatory (E) and inhibitory (I) neurons whose relationships are now known to a large extent. Inputs to E- and I-cells may have their origins in remote or local cortical areas. We consider a rudimentary model involving E- and I-cells. One of our goals is to test an analytic approach to finding firing rates in neural networks without using a diffusion approximation and to this end we consider in detail networks of excitatory neurons with leaky integrate-and-fire (LIF) dynamics. A simple measure of synchronization, denoted by S(q), where q is between 0 and 100 is introduced. Fully connected E-networks have a large tendency to become dominated by synchronously firing groups of cells, except when inputs are relatively weak. We observed random or asynchronous firing in such networks with diverse sets of parameter values. When such firing patterns were found, the analytical approach was often able to accurately predict average neuronal firing rates. We also considered several properties of E-E networks, distinguishing several kinds of firing pattern. Included were those with silences before or after periods of intense activity or with periodic synchronization. We investigated the occurrence of synchronized firing with respect to changes in the internal excitatory postsynaptic potential (EPSP) magnitude in a network of 100 neurons with fixed values of the remaining parameters. When the internal EPSP size was less than a certain value, synchronization was absent. The amount of synchronization then increased slowly as the EPSP amplitude increased until at a particular EPSP size the amount of synchronization abruptly increased, with S(5) attaining the maximum value of 100%. We also found network frequency transfer characteristics for various network sizes and found a linear dependence of firing frequency over wide ranges of the external afferent frequency, with non-linear effects at lower input frequencies. The theory may also be applied to sparsely connected networks, whose firing behaviour was found to change abruptly as the probability of a connection passed through a critical value. The analytical method was also found to be useful for a feed-forward excitatory network and a network of excitatory and inhibitory neurons.

Action Potentials↗
PubMed1997

11C-diprenorphine binding in Huntington's disease: a comparison of region of interest analysis with statistical parametric mapping.

We compare region of interest (ROI) analytical approaches with statistical parametric mapping (SPM) of 11C-diprenorphine positron emission tomography findings in five patients with Huntington's disease (HD) and nine age-matched controls. The ROI were placed on caudate, putamen, and an occipital reference area. Ratios of striatal-occipital uptake from averaged static images centered at 60 minutes showed a mean 20% reduction in caudate (P = 0.034) and 15% reduction in putamen (P = 0.095) receptor binding in the HD patients. Dynamic data from caudate and putamen ROI, together with a plasma tracer input function, were analyzed using spectral analysis to give regional impulse response functions. Regional data at 60 minutes after impulse showed a mean 29% decrease in caudate (P = 0.006) and 23% decrease in putamen (P = 0.029) opioid binding in the HD cohort. Parametric images of tracer binding also were produced with spectral analysis on a voxel basis. The images of the unit impulse response function at 60 minutes showed a mean 31% decrease in caudate (P = 0.005) and a 26% decrease in putamen binding (P = 0.011) in HD. The voxel-based parametric images were transformed into standard stereotactic space, and a between-group comparison (patient versus controls) was performed with SPM. This approach revealed symmetrical decreases in caudate (peak 40% decrease, z score = 4.38) and putamen opioid binding (peak 24% decrease, z score = 4.686) with additional nonhypothesized changes in cingulate, prefrontal, and thalamic areas. The significance and precision of changes measured with spectral analysis applied to dynamic data sets were superior to ROI-based ratio analysis on static images. The SPM replicated the striatal reductions in opioid binding in HD and detected additional nonpredicted changes. This study suggests that SPM is a valid alternative to conventional ROI analytical approaches for determining binding changes with positron emission tomography and may have advantages over region-based analyses in exploratory studies.

Adult↗
PubMed2002

Technical and analytical advances in pulmonary ventilation SPECT with xenon-133 gas and Tc-99m-Technegas.

This paper describes the recent advances in technical and analytical methods in pulmonary ventilation SPECT studies, including a respiratory-gated image acquisition of Technetium-99m (99mTc)-labeled Technegas SPECT, a fusion image between Technegas SPECT and chest CT images created by a fully automatic image registration algorithm, and a three-dimensional (3D). display of xenon-133 (133Xe) gas SPECT data, and new analytical approaches by means of fractal analysis or the coefficient of variations of the pixel counts for Technegas SPECT data. The respiratory-gated image acquisition can partly eliminate problematic effects of the SPECT images obtained during non-breath-hold. The fusion image is available for routine clinical use, and provides complementary information on function and anatomy. The 3D displays of dynamic 133Xe SPECT data are helpful for accurate perception of the anatomic extent and locations of impaired ventilation, and the assessment of the severity of ventilation abnormalities. The new analytical approaches facilitate the objective assessment of the degrees of ventilation abnormalities.

Adult↗
PubMed1997

Alternative approaches to analytical designs in occupational injury epidemiology.

In this paper, we discuss the theoretical framework upon which observational studies of occupational injuries are based. Following a general description of how causal effects are estimated, the challenges faced by researchers working in this area are outlined, with an emphasis on case-control studies. These challenges include defining the at-risk period for workers whose tasks change over time and whose hazard period may be very brief, evaluating the underreporting of both exposures and injuries, and considering the effects of multiple injuries per individual on study design and data analysis. We review both the theoretical and practical considerations in the design and conduct of traditional case-control studies, based on the collection of individual level data, as well as other approaches, such as using information culled from administrative and descriptive databases, and case-control studies in which the plant or work site is the unit of analysis. The case-crossover design is also reviewed and its utility for reducing confounding due to differences between individuals by self-matching is highlighted. While this design has not yet been applied to the work setting, its potential for increasing our understanding of the causes of acute-onset occupational injuries seems promising. Finally, a variety of hybrid designs are discussed, including combinations of case-control, case-crossover, and cohort designs.

Accidents, Occupational↗
PubMed2001

Reconsideration of the backscatter components in the intermediate cavity theory for photon beams.

Cavity theories are used to relate the dose in a medium to the dose in a cavity. No satisfactory analytical approach exists for the case of intermediate cavities, such as TLDs, when interface effects are important. Burlin proposed a general cavity theory that accounts for the cavity size but which ignores interface effects between cavity material and the surrounding materials. Horowitz modified Burlin's theory to include a more systematic account for the contribution of electrons generated in the cavity. Both Kearsley and Haider proposed new models that consider backscattering effects at cavity interfaces. However, these last models introduce additional parameters whose values are not easily available. By using a pure analytical approach, higher orders of backscatter terms were considered and a photon cavity expression was derived. The proposed formula depends on backscattering and attenuation coefficients of the cavity material and the surrounding media as well as the size of the cavity and angular effects. This expression has the Burlin and Bragg-Gray formulae as limiting cases and follows better the pattern of Ogunleye's experimental results.

Electrons↗
PubMedDate not supplied

Cardiac disease in chronic uremia: can it explain the reverse epidemiology of hypertension and survival in dialysis patients?

Definitive randomized trials are rare in the dialysis literature. Treatment decisions are often based on extrapolation from trials in other populations and observational studies in dialysis patients. "Reverse epidemiology" is a term increasingly applied to classic cardiovascular risk factors in studies of dialysis patients. The term is used when outcome associations are the opposite of those seen in general population studies. Hypertension is an archetypal example, with several studies showing inverse associations with mortality. As a term, "reverse epidemiology" is intellectually unsatisfactory because validation of the real direction of an association is only possible with experimental designs. In contrast, blood pressure (BP) is associated with typical association patterns for outcomes other than death, including left ventricular hypertrophy and cardiac failure, which are dominant entities in dialysis populations. There is a strong suspicion that current analytical approaches may partly explain the paradox. For example, it is possible that unmeasured comorbidities are associated with lower BP levels. In addition, few studies use BP as a time-integrated parameter, which is problematic given the variability of this parameter. Several recent studies suggest that using pulse pressure as a BP parameter may normalize associations with mortality. BP, extracellular blood volume, residual renal function, and vasoactive medications are interlinked. Time-integrated analysis that examines all these parameters concurrently makes sense, but has rarely been attempted. A large burden of cardiac disease and insensitive analytical approaches may go a long way toward explaining the reverse epidemiology of hypertension and survival in dialysis patients.

Blood Pressure↗
PubMed2003

Determination of firing times for the stochastic Fitzhugh-Nagumo neuronal model.

We present for the first time an analytical approach for determining the time of firing of multicomponent nonlinear stochastic neuronal models. We apply the theory of first exit times for Markov processes to the Fitzhugh-Nagumo system with a constant mean gaussian white noise input, representing stochastic excitation and inhibition. Partial differential equations are obtained for the moments of the time to first spike. The observation that the recovery variable barely changes in the prespike trajectory leads to an accurate one-dimensional approximation. For the moments of the time to reach threshold, this leads to ordinary differential equations that may be easily solved. Several analytical approaches are explored that involve perturbation expansions for large and small values of the noise parameter. For ranges of the parameters appropriate for these asymptotic methods, the perturbation solutions are used to establish the validity of the one-dimensional approximation for both small and large values of the noise parameter. Additional verification is obtained with the excellent agreement between the mean and variance of the firing time found by numerical solution of the differential equations for the one-dimensional approximation and those obtained by simulation of the solutions of the model stochastic differential equations. Such agreement extends to intermediate values of the noise parameter. For the mean time to threshold, we find maxima at small noise values that constitute a form of stochastic resonance. We also investigate the dependence of the mean firing time on the initial values of the voltage and recovery variables when the input current has zero mean.

Models, Neurological↗
PubMed2001

What is the evidence for a reduced risk of local recurrence with age among older patients treated by breast conserving therapy?

With the rising age of the population and the proposed extension of the breast screening programme to older women, increasing numbers of older patients are becoming eligible for breast conserving surgery and post-operative breast irradiation. Women over the age of 70 have traditionally been omitted from randomized controlled trials for assessing the role of breast radiotherapy after local surgery. The majority of trials suggest that local recurrence rates do decline with age. Similar conclusions are suggested by many non-randomized studies. Comparison of randomized and non-randomized studies is limited by differing extent of classifying tumour margins, nodal status, use of adjuvant systemic therapy, sample size, analytical approaches and duration of follow-up. Large randomized trials in older women are needed to assess whether, with careful attention to obtaining clear tumour margins, radiotherapy is required in low risk, ER positive, node negative breast cancer patients following wide excision and adjuvant tamoxifen. Within both randomized and non-randomized studies, only a few studies have failed to demonstrate an impact of age on recurrence rates following breast conserving treatment, with the majority finding a reduction in local recurrence rates with increasing age. Importantly for interpretation, no studies suggest that recurrence rates increase with age. The variation in analytical approaches and sample sizes are such that the variety of conclusions is not surprising. The results are compatible with a tendency for local recurrence rates to fall with age, but the variability is such that one cannot quantify this change with any precision.

Journal Article↗
PubMed2001

[Determination of 4-bromo-2,5-dimethoxyamphetamine (DOB) found in illicit tablets seized in Italy].

Some of the molecules belonging to the amphetamines group (4-bromo-2,5-dimethoxyamphetamine, DOB) or to the phenethylamines (4-bromo-2,5-dimethoxy-phenethylamine, 2C-B or Nexus) have closely related structures that make their identification quite difficult. The unambiguous identification is crucial in forensic responses. This paper describes the analytical approach used to achieve the identification of the main ingredient contained in tablets seized in the illicit market of Rome (Italy) and submitted to our laboratory by the Court of Law of Rome. The procedure entails the basic extraction of the main ingredient from the tablets with tert-butyl methyl ether followed by qualitative gas chromatographic mass-spectrometric (GC-MS) analysis using both electron impact detection (EI) and chemical ionization (CI). The examination of the mass spectra obtained from the native molecule and from its pentafluoropropionyl-derivative allows the structural identification of the side chain and the substitutions on the aromatic ring. This analytical approach can thus be useful to distinguish between amphetamine-like and phenetylamine-like compounds using instruments and techniques commonly available in the forensic toxicology laboratories.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed2001

Is there a "best" way to detect and minimize publication bias? An empirical evaluation.

Using 14 meta-analyses that included both published (n = 199) and unpublished (n = 50) randomized trials, we evaluated the utility of different analytical approaches to detect, assess robustness, and minimize publication bias in meta-analysis. The rank correlation and graphical tests indicated funnel plot asymmetry in 3 and 7 of the 14 meta-analyses, respectively. The file drawer number estimates using Iyengar-Greenhouse method were between 1.5 and 4.7 times smaller compared to Rosenthal's estimates. The median difference between the Trim and Fill estimates and the actual number of missing studies was 1 (range -4, 6). Weighted estimation methods adjusted for publication bias and provided estimates of intervention effect close to the reference standard, on average. We showed there are differences in the conclusions one would reach clinically based on the different analytical approaches dealing with publication bias. Our results also suggest that the appropriate use of these methods improves the reliability and accuracy of meta-analysis.

Humans↗
PubMed1996

Adaptive demands along the HIV disease continuum.

Our knowledge of the problems or adaptive demands associated with HIV infection has largely been derived from clinical history taking and qualitative research of persons with AIDS. This study uses a behaviour-analytic approach to systematically describe and quantify the specific adaptive demands encountered by persons with HIV across the disease continuum. Ninety six HIV-infected gay men and 33 seronegative comparison group participants were interviewed in depth. Participants were divided into three groups representing the disease continuum: seronegative, HIV asymptomatic and HIV symptomatic groups. Responses to a Problem Checklist were statistically and content analysed. Distressing emotions, relationship difficulties and HIV-related symptoms were the three most frequently endorsed problems and were also the three most frequently reported problems of most concern. Overall there was a trend for instrumental difficulties to increase with disease progression, whereas emotional and existential problems did not vary as a function of HIV stage. The behaviour-analytic approach to the specification of problems related to HIV infection has implications for both clinical and research endeavours. The specification of problems provided a means for accurately identifying common problems to target and could, therefore, provide the basis for developing suitably matched interventions for use with HIV-infected persons.

Adaptation, Psychological↗