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At least 523 records · Page 29Linked to original sources

Synthesis of short RNA fragments by the benzotriazolyl phosphotriester approach.

Analytical and experimental evidence will be presented to show that addition of a slight excess of 2-chlorophenyl-0,0-bis[1-benzotriazolyl]phosphate to a properly 2',5'-protected ribonucleoside gives an intermediate 3'-phosphotriester, which, after addition of a 2'-protected ribonucleoside, affords a dimer containing solely a 3'-5'-internucleotide linkage. The above phosphorylation procedure has been used in the synthesis of the pentamer UpApCpGpC.

Base Sequence↗

Approaches to observational study designs and analytical options to evaluate the safety of multi-dose vaccines: a systematic review.

INTRODUCTION: Observational studies require careful considerations when evaluating the safety of multidose vaccines. We reviewed design and analytical approaches in observational studies evaluating the safety of multidose vaccines in the post-licensure phase. METHODS: EMBASE, MEDLINE, Web of Science, and Scopus (2018-2022) were searched for hypothesis-testing studies evaluating the safety of multidose vaccines. Key features from frequently used designs were extracted. RESULTS: Among 123 eligible studies, cohort (46%) and self-controlled case series (SCCS)/self-controlled risk interval (SCRI) (40%) followed by case-control (12%) were the most common designs, and 15% of studies used multiple designs. Among cohort studies evaluating multiple doses, vaccination date (36%) and cohort entry with time-updated exposure status (32%) were frequent approaches used to define time zero. Twenty-eight percent of cohort studies did not report time zero; all but one evaluated COVID-19 vaccine effect on post-delivery and fertility-related outcomes. For SCCS/SCRI, 64% of studies accounted for event-dependent exposures, mainly by including pre-exposure periods (53%) and modified SCCS model (48%), while 20% employed multiple correction strategies. Among studies using multiple designs, 68% reached consistent conclusions. CONCLUSIONS: SCCS/SCRI and cohort designs dominate multidose vaccine safety studies. Clear reporting on time zero in pregnancy and fertility-related cohort studies, and on addressing event-dependent exposures in SCCS/SCRI studies is needed, along with guidance on interpreting results from multiple designs.

Humans↗

A new look at information retrieval evaluation: proposal for solutions.

This is the fourth and the final in the series of the papers on an application of the systems analytic approach to evaluation of information retrieval (IR). In the previous papers terminological and evaluation problems associated with IR were identified and discussed, and it was proposed that the systems analytic approach could provide solutions to these problems. A review of existing systems analytic approaches in IR was given, and a conceptual framework and two models of IR were presented. This paper discusses how the proposed conceptual framework and the models can be used to improve terminology of IR, to analyze the relevance-based method of recall and precision, and to propose new approaches to evaluate relevance relationships and search engines. The proposed evaluation approaches are compared amongst each other and with the existing methods. The paper is concluded by a summary of the contributions of the research and an identification of the directions for a future research in IR evaluation.

Canada↗

The teaching of Blissymbols as a bridge into literacy for children with cognitive impairments: a comparison of two training approaches.

This study compares the learning of Blissymbols by six mildly cognitively impaired children by means of a global and an analytic approach. Training consisted of two stages. The first was the training of eight compound symbols and the second the training of seven single configuration symbols. The study concludes that Blissymbols as an entrance into literacy can be taught successfully to cognitively impaired individuals by means of either an analytic or a global approach. The analytic approach seems to have greater long-term benefits, as the subjects instructed by the analytic approach consistently performed better in the generalization and re-evaluation procedures. The analytic approach, however, was much more time consuming than the global approach in terms of the length of training required. The implications for literacy development and augmentative and alternative communication systems are discussed.

Child↗

Calcitriol and the parathyroid hormone-ionized calcium curve: a comparison of methodologic approaches.

Investigations of the effects of calcitriol on the inverse sigmoidal relationship between parathyroid hormone (PTH) and ionized calcium (iCa) have yielded contradictory conclusions, possibly because of variations in experimental and analytical approaches. To clarify the existing literature, PTH-iCa curves were constructed by inducing hypo- and hypercalcemia through alterations in dialysate calcium concentration in eight hemodialysis patients with mild to moderate secondary hyperparathyroidism. The effects of low (metabolic acidosis) versus normal bicarbonate dialysis were compared before and after 4 wk of intravenous calcitriol, in a cross-over design. The PTH-iCa curves were primarily evaluated by using a four-parameter model. In addition, a variety of alternative published analytic approaches were examined and PTH-iCa curve slopes were further evaluated after normalization by (maximum - minimum PTH). The latter partially corrects for gland mass and cell-secretory capacity, and therefore yields a purer measure of the sensitivity of secretory activity to changes in iCa. The results of the study indicate that calcitriol decreased basal, maximal, and minimal PTH and non-normalized slope (all P < 0.05), but did not affect set point or normalized slope, independent of the specific analytic approach. Acute metabolic acidosis did not affect the PTH-iCa curve. Thus, intravenous calcitriol appears to decrease parathyroid gland functional mass, as reflected by decreases in maximal and minimal PTH levels, but does not affect the sensitivity of the parathyroid gland to changes in iCa, as set point and normalized slope were unaffected.

Adult↗

Cotinine analytical workshop report: consideration of analytical methods for determining cotinine in human body fluids as a measure of passive exposure to tobacco smoke.

A two-day technical workshop was convened November 10-11, 1986, to discuss analytical approaches for determining trace amounts of cotinine in human body fluids resulting from passive exposure to environmental tobacco smoke (ETS). The workshop, jointly sponsored by the U.S. Environmental Protection Agency and Centers for Disease Control, was attended by scientists with expertise in cotinine analytical methodology and/or conduct of human monitoring studies related to ETS. The workshop format included technical presentations, separate panel discussions on chromatography and immunoassay analytical approaches, and group discussions related to the quality assurance/quality control aspects of future monitoring programs. This report presents a consensus of opinion on general issues before the workshop panel participants and also a detailed comparison of several analytical approaches being used by the various represented laboratories. The salient features of the chromatography and immunoassay analytical methods are discussed separately.

Animals↗

Characterization of mannooligosaccharide caps in mycobacterial lipoarabinomannan by capillary electrophoresis/electrospray mass spectrometry.

A new analytical approach based on capillary electrophoresis-electrospray mass spectrometry (CE/ESI-MS) has provided new insight into the characterization of mannooligosaccharide caps from lipoarabinomannans (LAMs), which are key molecules in the immunopathogenesis of tuberculosis. This analytical approach requires oligosaccharide labeling with the fluorophore 1-aminopyrene-3,6,8-trisulfonate (APTS) by reductive amination at the reducing termini. Optimization of the separation and ionization conditions, such as the choice of capillary electrophoresis (CE) electrolyte buffers, is presented and discussed. Anionic separation of the mono and oligosaccharide APTS derivatives was finally achieved with aqueous triethylammonium formate buffer. It was found that in contrast to the triethylammonium phosphate buffer, the triethylammonium formate buffer was appropriate for CE/ESI-MS coupling analysis of APTS-carbohydrate derivatives. In this case, negative ESI-mass spectra of APTS-carbohydrate adducts showed mainly (M-2H)2-pseudomolecular ions and some sequence fragment ions allowing their non-ambiguous structural characterization at the picomolar level. This analytical approach was successfully applied to more complex mixtures of carbohydrates released by mild acid hydrolysis of the lipoarabinomannans from Mycobacterium bovis BCG. The APTS-mannooligosaccharide cap adducts were separated by CE and their structural characterization achieved by CE/ESI-MS analyses. Mannooligosaccharide caps were routinely analyzed by capillary electrophoresis-laser induced fluorescence (CE-LIF) from 50 fmol of lipoarabinomannans with mannosyl capping (ManLAMs) but sensitivity was about 50 times lower using ESI-MS detection.

Carbohydrate Sequence↗

Relationships among multiple task asymmetries. I. A critical review.

Previous multiple-task experiments examining relationships among lateral difference measures have been interpreted as supporting (a) both global and local relationships or (b) local relationships only. The evidence from principle components, correlational, and factor analytic approaches is reviewed with the aim of reconciling the literature. Although a principle component has been reported to which all asymmetries correlate positively, it may not reflect existing null and negative correlations between pairs of measures. All three literatures make clear that such correlations exist, calling into question the reality of a global relationship. In contrast, all three approaches find evidence supporting the reality of local relationships. Factor analytic approaches most fully develop local relationships and permit interpretation in terms of hemispheric processes, but they need to (a) use larger sample sizes, (b) prescreen measures for reliability, and (c) make publicly available the underlying correlational matrices.

Auditory Perception↗

Effective potential analytic continuation approach for real time quantum correlation functions involving nonlinear operators.

We apply the effective potential analytic continuation (EPAC) method to the calculation of real time quantum correlation functions involving operators nonlinear in the position operator q. For a harmonic system the EPAC method provides the exact correlation function at all temperature ranges, while the other quantum dynamics methods, the centroid molecular dynamics and the ring polymer molecular dynamics, become worse at lower temperature. For an asymmetric anharmonic system, the EPAC correlation function is in very good agreement with the exact one at t = 0. When the time increases from zero, the EPAC method gives good coincidence with the exact result at lower temperature. Finally, we propose a simplified version of the EPAC method to reduce the computational cost required for the calculation of the standard effective potential.

Journal Article↗

The pterional-transsylvian approach: an analytical study.

OBJECTIVE: Splitting of the sylvian fissure (SF) improves exposure with the pterional (PT) approach. Traditionally, the choice of whether or not to split the SF and how far to open it has depended on the neurosurgeon's experience and preference rather than on quantifiable data. We undertook this study to evaluate the effects of progressive splitting of the SF on surgical exposure with the PT approach. METHODS: A PT craniotomy was performed on nine sides of cadaver heads. Splitting the SF was divided into four steps: 1) dissection of the basal cisterns, 2) dissection of the sphenoidal compartment, 3) dissection of the operculoinsular compartment to the anterior ascendant ramus, and 4) dissection progressing 2.0 cm distal to the anterior ascendant ramus. The degree of the retraction and the relative position of the brain retractors were kept constant. After each step, we used a computerized tracking system to measure the area of surgical exposure of the circle of Willis, the angles of approach to the carotid bifurcation, and the distance between the frontal lobe and skull base. RESULTS: Exposure of the circle of Willis, angles of approach to the carotid bifurcation, and linear distance between the frontal lobe and skull base all increased significantly as splitting of the SF progressed from Steps 1 to 2 and from Steps 2 to 3. There was no significant difference between Steps 3 and 4. CONCLUSION: Exposure of the basal cisterns and circle of Willis by the PT approach is optimized when dissection of the SF reaches the anterior ascendant ramus. Further splitting of the SF provides no additional gain.

Cadaver↗

The economics of optimal health and productivity in smallholder livestock systems in developing countries.

Livestock kept or produced in smallholder farming systems are an important component of the agricultural economy in the developing world. The role of livestock on smallholder farms varies widely, providing draught power for crop production or as a production activity for subsistence needs or market sale under systems ranging from extensive pastoralist to intensive, peri-urban feeder and dairy systems. A set of unique conditions and features characterise smallholder systems, and these need to be appreciated when assessing the strategies that have evolved for managing animal health in smallholder systems, and evaluating opportunities for improving disease control strategies. To provide a framework for discussing animal health issues and analytical methodogies, a typology of smallholder livestock and crop/livestock systems is developed. The typology considers livestock systems both in terms of the degree of intensification, as measured by market orientation and intensity of factor use, and in terms of importance within the household economy, as measured by contribution to household income. A number of characteristics are identified that distinguish smallholder systems from the commercialised systems of developed countries, including the multiple functions livestock serve, the integrated nature of livestock activities, multiple objectives of producers and lower capacity to bear risk at the household level, as well as poor infrastructure, markets, and access to information at the community level. Three representative smallholder livestock systems from Africa are described in detail, highlighting the relevant characteristics and the implications for analysing disease control strategies. Smallholder dairy systems in Kenya demonstrate the role of individual producer decision-making for animal health management in intensive, market-oriented systems, placing emphasis on farm-level risk and production management aspects of disease control. In extensive pastoralist systems where epidemic disease are still important and infrastructure is poor, disease control primarily involves managing communal natural resources, requiring a different analytical approach. Finally, in crop farming systems using draught cattle, the livestock activity is an integrated component of crop production and this must be reflected in the approach used to evaluate draught animal health management. Continued development of analytical approaches and decision-support tools for disease control strategies adapted to the special characteristics of these systems will be needed as smallholder systems continue to intensify in areas with good market access, and those in marginal areas face increasing pressures to optimally manage the natural resource base.

Africa↗

Mathematical modeling of electrical activity of the heart.

This paper reviews the literature on mathematical models of cardiac activation and evaluates these approaches against an analytical approach that includes both structure and membrane properties. The advantages and disadvantages of each methodology are described and directions for future research suggested.

Animals↗

Constrained spin-dynamics description of random walks on hierarchical scale-free networks.

We study a random walk problem on the hierarchical network which is a scale-free network grown deterministically. The random walk problem is mapped onto a dynamical Ising spin chain system in one dimension with a nonlocal spin update rule, which allows an analytic approach. We show analytically that the characteristic relaxation time scale grows algebraically with the total number of nodes N as T--N(z). From a scaling argument, we also show the power-law decay of the autocorrelation function C(sigma)(t)--t(-alpha), which is the probability to find the Ising spins in the initial state sigma after t time steps, with the state-dependent nonuniversal exponent alpha. It turns out that the power-law scaling behavior has its origin in a quasiultrametric structure of the configuration space.

Journal Article↗

Influence of individually estimated portion size on the assessment of nutritional risk in colorectal cancer in Portugal.

We evaluated the influence of individually estimated portion sizes on the estimate of nutrient related risk of colorectal cancer, using data from a Portuguese hospital based case-control study on diet and colorectal cancer. A total of 100 patients with colorectal adenocarcinoma (aged 15-92 years) and 211 controls (aged 36-89 years) were included. Two data sets were created for nutrient analysis, the first one allowed estimates of food intake using data on portion size as collected with visual aids during the interview. The second estimate substituted respondents' estimate with a standard portion size, as used in the semi-quantitative (SQ) food frequency approach. The two analytic approaches yielded similar energy and nutrient intakes in cases and controls. The percent range of concordance is acceptable, in the same quartile varying from 44 to 82% (mean: 56%) and very good in the same or adjacent (+/-1) quartile (mean: 91%, range: 85-97%). The two estimates lead to a similar pattern of multivariate odd's ratio, however the SQ estimates resulted in more significant findings. We conclude that little extra information is gained by including individual portion size information when assessing diet-related risk of colorectal cancer.

Adenocarcinoma↗

Methods for the analysis and assessment of clinical databases: the clinician's perspective.

Innovative approaches to analysing clinical databases can be considered from a perspective of innovations that improve the analytical approach or from a more global perspective in which clinical databases themselves are evaluated as a technology. The analytic approach for using a database to estimate risk can be considered as a matrix of three methodologic concerns: the predictive method; the assessment of the quality of the predictions; and the assessment of the validity or generalizability of the predictions. Considering databases as a technology places in perspective the merit of clinical databases and defines their potential value to the health care system. An awareness of both the clinical and analytic problem encourages innovation and can lead to creative solutions to the many problems present in the analysis of clinical databases.

Clinical Medicine↗

Use of multiple headspace solid-phase microextraction and pervaporation for the determination of off-flavours in wine.

The occurrence of off-flavours in wines and especially the so-called "cork taint defect" represents one of the most serious problem in wine industry in which 2,4,6-trichloroanisole has been blamed as the main responsible. The development of analytical methods for haloanisoles determination in wine/cork represent a challenge, mainly due to food matrix complexity and low taste and odour (T&O) threshold levels which are generally beyond the sensitivity of the analytical systems. In this work, a method based on the combined use of the recently developed multiple headspace solid-phase microextraction (MHS-SPME) and gas chromatography-ion-trap mass spectrometry has been optimised for the determination of haloanisoles in wines. This powerful analytical methodology is compared with several analytical approaches based on pervaporation, an innovative membrane-based technique similar to dynamic headspace. Analytical features of the methods assayed reveal their suitability for the appraisal of haloanisoles in this matrix in which threshold odor concentrations are in the range 4-40 ng l(-1). The analytical approaches have been applied to the analysis of haloanisoles in different Spanish white and red wines, in which spiking experiments showed good recoveries for the methodologies assayed.

Anisoles↗

Selecting methodologies for the evaluation of differences in time to response between antidepressants.

BACKGROUND: The delay in the therapeutic effect of antidepressants is a considerable impediment to their successful clinical use, and attention has recently been focused on antidepressant drugs that may have a faster onset of action. DATA SYNTHESIS: Several methodologies exist for evaluating differences in time to response between antidepressants including the identification of the timepoint at which statistically or clinically significant differences between treatment groups emerge, pattern analysis, and survival analytical approaches. All have conceptual as well as practical advantages and disadvantages. CONCLUSION: The survival analytical approach is generally considered to be the most rigorous and sensitive in detecting differences in the speed of response of antidepressants, but the other methodologies provide useful information.

Antidepressive Agents↗

Applicability of bioanalysis of multiple analytes in drug discovery and development: review of select case studies including assay development considerations.

The development of sound bioanalytical method(s) is of paramount importance during the process of drug discovery and development culminating in a marketing approval. Although the bioanalytical procedure(s) originally developed during the discovery stage may not necessarily be fit to support the drug development scenario, they may be suitably modified and validated, as deemed necessary. Several reviews have appeared over the years describing analytical approaches including various techniques, detection systems, automation tools that are available for an effective separation, enhanced selectivity and sensitivity for quantitation of many analytes. The intention of this review is to cover various key areas where analytical method development becomes necessary during different stages of drug discovery research and development process. The key areas covered in this article with relevant case studies include: (a) simultaneous assay for parent compound and metabolites that are purported to display pharmacological activity; (b) bioanalytical procedures for determination of multiple drugs in combating a disease; (c) analytical measurement of chirality aspects in the pharmacokinetics, metabolism and biotransformation investigations; (d) drug monitoring for therapeutic benefits and/or occupational hazard; (e) analysis of drugs from complex and/or less frequently used matrices; (f) analytical determination during in vitro experiments (metabolism and permeability related) and in situ intestinal perfusion experiments; (g) determination of a major metabolite as a surrogate for the parent molecule; (h) analytical approaches for universal determination of CYP450 probe substrates and metabolites; (i) analytical applicability to prodrug evaluations-simultaneous determination of prodrug, parent and metabolites; (j) quantitative determination of parent compound and/or phase II metabolite(s) via direct or indirect approaches; (k) applicability in analysis of multiple compounds in select disease areas and/or in clinically important drug-drug interaction studies. A tabular representation of select examples of analysis is provided covering areas of separation conditions, validation aspects and applicable conclusion. A limited discussion is provided on relevant aspects of the need for developing bioanalytical procedures for speedy drug discovery and development. Additionally, some key elements such as internal standard selection, likely issues of mass detection, matrix effect, chiral aspects etc. are provided for consideration during method development.

Animals↗