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PubMed2000

Evaluation of analytical and clinical performance of a dual-probe phenotyping method for CYP2D6 polymorphism and CYP3A4 activity screening.

A bioanalytical method for the determination of dextromethorphan (DEX) and its metabolites dextrorphan (DTX), 3-methoxymorphinan (3MM), and 3-hydroxymorphinan (3HM) in human urine was developed for CYP2D6 phenotyping and CYP3A4 activity measurements in clinical pharmacology studies using dextromethorphan administered in a drinking solution as substrate. The method was evaluated by thorough conventional validation and by a cross-validation of the method with a previously applied method for dextromethorphan and dextrorphan only (CYP2D6 phenotyping). Cross-validation with the former method showed no significant differences in measured concentrations of volunteer samples. This guaranteed the consistency of epidemiologic data in the database collected from two methods. For the CYP2D6 and CYP3A4 evaluations, the clinical parameters are ratios of concentrations. It appeared that severe variance in individual concentrations generally did not influence the variance of ratios significantly, because experimental errors in concentrations of two analytes proved to correlate considerably. For CYP2D6 values around the antimodes, the chance of a misclassification is very small. The chance of classifying an extensive metabolizer as a poor metabolizer or vice versa is negligible. For CYP3A4 activity determinations it was concluded that in general a change in dextromethorphan/3-methoxymorphinan (DEX/3MM) ratios of 10% or more as detected with the current method, is a significant increase or decrease in the activity of CYP3A4. The authors concluded that they had obtained an analytically valid and clinically reliable bioanalytical method for the determination of dextromethorphan and its metabolites dextrorphan, 3-methoxymorphinan, and 3-hydroxymorphinan in human urine for CYP2D6 phenotyping and CYP3A4 activity measurements for clinical pharmacology studies.

Cytochrome P-450 CYP2D6↗
PubMed1989

Long-term effects of triethylenemelamine exposure on mouse testis cells and sperm chromatin structure assayed by flow cytometry.

The toxic and potentially mutagenic actions of triethylenemelamine (TEM) on mouse body and testis weights, testicular cell kinetics, sperm production, sperm head morphology, and sperm chromatin structure were assessed in two experiments. The first experiment examined effects of four dose levels of TEM, assayed 1, 4, and 10 wk after toxic exposure. In the second study, effects from five dosage levels were measured at 1, 4, and 10 wk, and the highest dosage level was evaluated over 44 wk. TEM produced an expected dose related loss of spermatogenic activity and subsequent recovery as determined by dual-parameter (DNA, RNA) flow cytometry (FCM) measurements of testicular cells. Both testicular weights and caudal sperm reserves remained generally below controls after 44 wk recovery following exposure to the highest (1.0 mg/kg daily x 5) dosage. Chromatin structure alterations, defined as increased susceptibility to DNA denaturation in situ, and sperm head morphology were highly correlated (.87-.93, P less than .001) with dose and with each other. Data obtained from the sperm chromatin structure essay (SCSA) on fresh sperm was highly correlated with measurements of aliquots of the same sample collected over 44 wk, frozen, and then measured on the same day. Sperm head morphology and sperm chromatin structure remained abnormal at 44 wk for the 1.0 mg/kg TEM dosage, suggesting that the abnormalities, present long after the initial toxic response, may be a result of mutation. This study demonstrates that flow cytometry provides a unique, rapid, and efficient means to measure effects of reproductive toxins and potential mutagens.

Animals↗
PubMed2025

Prediction of personalized antiseizure medications response based on clinical signatures in epilepsy.

Despite the increasing number of available antiseizure medications (ASMs), optimal medical therapy is still a process of trial and error. We aimed to predict the responsiveness of various ASMs based on initial tests using artificial intelligence. The study consisted of 2586 patients fulfilling the following criteria: (1) first visit to the epileptologists from 2008 to 2017, (2) a diagnosis of epilepsy, and 3) ≥ three years of follow-up duration. The clinical characteristics, ASM history, seizure frequency, laboratory, EEG, and MRI results, were collected. Machine algorithms were utilized to predict the responsiveness of specific regimens. Valproate showed the highest area under curve (AUC), 0.636. The AUCs of levetiracetam, oxcarbazepine, and lamotrigine were 0.614, 0.633, and 0.674. The AUCs of common dual regimens were 0.543 for levetiracetam + oxcarbazepine, 0.454 for levetiracetam + valproate, and 0.583 for levetiracetam + lamotrigine. Levetiracetam + carbamazepine showed the highest AUC, 0.686. In Shapley Additive exPlanations analysis, seizure type significantly impacted prediction performance for valproate responsiveness, and onset age and disease duration for lamotrigine. The prediction performances for the response based on initial data differ according to ASMs. An enormous dataset from a multicenter would improve the prediction power of ASM responsiveness in the future.

Humans↗
PubMed2000

A survey of resident selection procedures in oral and maxillofacial surgery.

PURPOSE: This study was conducted to analyze the current procedures used in oral and maxillofacial surgery resident selection, to compare these selection procedures with those used 2 decades ago, to determine whether any differences exist in the selection procedures between 4-year certificate programs and programs that offer formal medical education, and to provide criteria to assist in the counseling of dental students on the application process for oral and maxillofacial surgery residencies. SUBJECTS AND METHODS: Questionnaires were sent to the 106 oral and maxillofacial surgery graduate training programs accredited by the American Dental Association. To provide for a more direct comparison to the study completed in 1976, the current questionnaire was developed, using the original survey as a model. It was divided into 5 sections: general information, information obtained from the formal application and letters of recommendation, the interview, the decision process, and a retrospective view of past decisions. The results were tabulated and the Pearson chi-square test was used to determine statistical significance when comparing the 4-year certificate programs to the programs that offer formal medical education. RESULTS: Seventy-one responses (75.5%) from nonmilitary programs were returned and analyzed. Thirty-nine responses represented dual-degree (MD) programs. Factors that were considered very important when judging a candidate's written application included dental school class rank (76.1%), dental school basic science grades (70.4%), and dental school clinical grades (63.4%). Dual-degree programs placed a greater emphasis on predental basic science grades (P < .01) and dental national board scores (P < .05). When asked about prior resident selection, 86.7% of the respondents said they would select 80% of their former residents again. In addition, 89.9% of the respondents were satisfied with their current selection process. CONCLUSIONS: The procedures used to select oral and maxillofacial surgery residents are relatively constant among programs. Although the dual-degree and 4-year certificate programs use the same criteria for resident selection, the dual-degree programs place greater emphasis on predental academic performance and on the results of the national dental boards. Criteria used 22 years ago to select residents are still applicable, but there has been a shift in the importance of some variables.

Certification↗
PubMed1996

Ecology of weaning among nomadic Turkana pastoralists of Kenya: maternal thinking, maternal behavior, and human adaptive strategies.

Weaning of human children is a complex process involving the introduction of non-breast-milk foods, reduction in suckling activity, and eventual termination of breast feeding. Because the choice of strategies for each component of the weaning process depends on the operating environmental constraints, reproductive demands on women, and prevailing levels of infant and weanling mortality, it is appropriate to examine weaning practices as human adaptive strategies. Here, I examine the structure of weaning and maternal attitudes toward weaning among nomadic Turkana pastoralists from the perspective of human adaptation. Using retrospective and prospective data on breast feeding, the use of non-breast-milk foods, and the cessation of breast feeding. I identify ideal strategies as those defined by Turkana women. Real behavior in relation to weaning, however, deviates considerably from the ideal, and this deviation reflects adaptive responses to nutritional and disease risks to infants. Particular attention is given to problematic aspects of weaning practices in Turkana, such as premature introduction of non-breast-milk foods and abrupt termination of breast feeding, which have been shown to contribute to high infant and weanling mortality in populations in developing countries. These practices have evolved from the dual caretaking and childbearing role of women and the necessity of reconciling the needs of the breast-feeding child with the demands of the next pregnancy. As such, they represent rational strategies for enhancing reproductive success in this and other similarly stressful environments.

Adaptation, Psychological↗
PubMed2026

Exploring Professional Experiences in Caring for Vulnerable Migrants in an Italian Rural Reception Centre: A Qualitative Study Using Multidimensional Textual Analysis-Professional Experiences in Rural Migrant Care.

AIM: This study aims to explore the experiences, strengths, challenges, and potential improvements for professionals in managing the complex needs of vulnerable migrants (VM) in an Italian rural reception centre. METHODS: A qualitative study using semi-structured interviews was conducted in April 2024. Data were analysed using the Automatic Analysis of Textual Data, based on Fraire's seven-step model for Exploratory Multidimensional Data Analysis. DATA SOURCES: Data were collected from 16 professionals working in a rural reception centre in southern Italy. Interviews were conducted and analysed using AATD in April 2024. FINDINGS: The analysis identified two main dimensions of professionals' roles: balancing systemic responsibilities with personal engagement and managing immediate needs versus long-term integration goals. Professionals face significant challenges, such as resource scarcity, bureaucratic inefficiencies, and emotional fatigue, which impact their well-being and the quality of care provided to migrants. Resilience, adaptability, and multidisciplinary collaboration were identified as key strengths. CONCLUSION: The study highlights the dual nature of professionals' work in reception centres, requiring them to balance operational tasks with emotional involvement in migrant care. Targeted interventions and systemic reforms are necessary to support professionals and enhance the quality of care for vulnerable migrants, particularly in resource-constrained rural settings. IMPLICATIONS FOR PRACTICE AND/OR PATIENT CARE: This study underscores the importance of providing targeted support to professionals working in reception centres, including training in intercultural competence, stress management, and coping strategies. Policies should address systemic challenges and provide resources to enhance healthcare delivery and social integration programs. REPORTING METHOD: This study adhered to the EQUATOR guidelines for reporting qualitative research (COREQ). The findings were reported in compliance with these guidelines, ensuring methodological rigour and transparency. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study highlights the critical need for targeted support and training for professionals working in reception centres, particularly in rural settings. To improve care for vulnerable migrants, professionals should receive training in intercultural competence, stress management, and coping strategies to better navigate the complex challenges they face. Furthermore, systemic changes are necessary to alleviate the pressures on reception centres, such as streamlining bureaucratic processes and enhancing healthcare infrastructure, particularly in rural areas where resources are limited. By addressing these needs, we can improve the well-being of both the professionals and the migrants they serve, fostering more effective support systems and better care outcomes. Additionally, fostering multidisciplinary collaboration and community engagement can contribute to more comprehensive and sustainable care models. PROTOCOL REGISTRATION: The Ethics Committee of the University of Rome Tor Vergata approved this study on 07/07/2021 (protocol registration number 160.21).

Humans↗
PubMed2006

Sex differences in bone size and bone mineral density exist before puberty. The Copenhagen School Child Intervention Study (CoSCIS).

BACKGROUND: The aim of this study was to provide normative data of bone mineral density (BMD; g/cm(2)) of the forearm and the calcaneus, evaluated by peripheral dual X ray absorbtiometry (DXA), in children aged 6 to 7 years of age and to evaluate the association with anthropometrics and sex. MATERIAL AND METHODS: 368 boys and 326 girls with a mean age of 6.7 +/- 0.4 years participated. BMD was measured by DXA in the forearms and the os calcanei, with average values presented in this report. Measurements of weight, height, skinfolds, the width of distal radius and ulna, and the femur condyles were collected and body composition estimated from skinfolds measurements. RESULTS: There was no difference in calcaneus BMD when comparing boys and girls, whereas the boys had 4.5% (0.013 g/cm(2)) higher forearm BMD than the girls (P < 0.001). Calcaneal BMD (mean 0.318 g/cm(2)) was 11% higher than forearm BMD (mean 0.283 g/cm(2)). Linear relationship was found between calcaneus BMD and weight (partial r = 0.50), Fat free mass (FFM) (partial r = 0.50), Fat mass (FM) (partial r = 0.45), % body fat (partial r = 0.29) and knee width (partial r = 0.46), all P < 0.000 respectively. Adjusted for weight the relationship between calcaneus BMD and FFM, FM, %body fat and knee width disappeared. There were significant relationships between the forearm BMD and weight (partial r = 0.37), FFM (partial r = 0.39), FM (partial r = 0.28), %body fat (partial r = 0.14) and wrist width (partial r = 0.24), all P < 0.000 respectively. Adjusted for body weight, the relationship remained between forearm BMD and FFM (r = 0.10), FM (R = -0.10) and % body fat (r = -0.12), all P < 0.000 respectively. Children measured in the spring had 3.5% (P < 0.01) higher calcaneus BMD than children measured in the winter. CONCLUSION: Seven year old boys have higher BMD in the forearm but not in the calcaneus in comparison with girls of a similar age. Body weight is the best predictor of calcaneus BMD, accounting for 25% of the variance whereas body weight and FFM are the best predictors of forearm BMD, each accounting for 17% of the variance, respectively.

Absorptiometry, Photon↗
PubMed2001

Food web implications of delta13C and delta15N variability over 370 km of the regulated Colorado River USA.

Dual stable isotope analysis in the regulated Colorado River through Grand Canyon National Park, USA, revealed a food web that varied spatially through this arid biome. Down-river enrichment of delta13C data was detected across three trophic levels resulting in shifted food webs. Humpack chub delta13C and delta15N values from muscle plugs and fin clips did not differ significantly. Humpback chub and rainbow trout trophic position is positively correlated with standard length indicating an increase in piscivory by larger fishes. Recovery of the aquatic community from impoundment by Glen Canyon Dam and collecting refinements for stable isotope analysis within large rivers are discussed.

Animals↗
PubMed2002

Frame size, ethnicity, lifestyle, and biologic contributors to areal and volumetric lumbar spine bone mineral density in Indian/Pakistani and American Caucasian premenopausal women.

Published data on the spinal bone mineral density (BMD) of premenopausal women originating from the Indian subcontinent (Indian/Pakistani) are few. We compared anteroposterior (AP) and lateral areal BMD (aBMD) using dual X-ray absorptiometry and calculated volumetric BMD (vBMD) in Indian/Pakistani (n = 47) vs American (n = 47) women with dissimilar statures and skeletal sizes. To account for differences, we "adjusted" lumbar aBMD separately for vertebral size (aBMD/the square root of the projected area), height (aBMD/height), and hip skeletal width (aBMD/hip width). We "corrected" bone mineral content (BMC), aBMD, and vBMD for frame size, collectively using height, hip width, and vertebral size. Unadjusted mean aBMD values for AP lumbar (L1-L4, p = 0.0086; L3-L4, p = 0.044) spine were higher in Americans than Indians/Pakistanis,whereas lateral vBMD (p = 0.56) or aBMD (p = 0.060) values were not different. After adjusting for height, hip width, or vertebral size, or correcting for frame size, differences in aBMD disappeared. Regression analyses indicated that the best measures to correct for frame size were: vertebral area for BMC, hip width for aBMD, and vertebral width for lateral vBMD. Height was not significant in any model. In correcting for frame size, we accounted for 73-85% of the variability in BMC, 22-28% in aBMD, and 27% in lateral vBMD. After frame size was corrected, we accounted for 34% of the variability in AP BMC and aBMD, in contrast with 6-9% in the lateral models. Five significant biologic and lifestyle factors remained in AP models; only body weight remained for lateral spine. Upon accounting for frame size using regression, much variability in BMD, aBMD, and vBMD was explained by lifestyle and biologic factors, not by ethnicity.

Absorptiometry, Photon↗
PubMed2005

Excipient effects on gastrointestinal transit and drug absorption in beagle dogs.

Previous work has shown that polyethylene glycol 400 (PEG 400) has an accelerating effect on gastrointestinal transit and a modulating influence on drug absorption in humans. The aim of this study was to assess the impact of various excipients, PEG 400, propylene glycol, d-alpha-tocopheryl-polyethylene glycol-1000 succinate (TPGS) and Labrasol on gastrointestinal transit and drug absorption in four beagle dogs using scintigraphy. Each dog received, on five separate occasions, water (control) or a dose of excipient equivalent to 1 g PEG 400, 2 g propylene glycol, 1 g TPGS or 2 g Labrasol dissolved in water and administered in the form of two capsules. The model drugs ampicillin (200mg) and antipyrine (100mg) were co-administered in the capsules. The capsule solutions were radiolabelled with technetium-99m to follow their transit using a dual-headed gamma camera, and blood samples were collected to determine drug pharmacokinetics. On a separate occasion, the drugs were dissolved in saline and given intravenously. The capsules rapidly disintegrated in the stomach liberating their liquid contents. The mean small intestinal transit times for the different treatments (control, PEG 400, propylene glycol, TPGS and Labarasol) were 183, 179, 195, 168 and 154 min, respectively. The corresponding mean absolute oral bioavailability figures were 36, 32, 39, 42 and 32% for ampicillin and 76, 74, 85, 73 and 74% for antipyrine, respectively. The transit and bioavailability data for the excipient treatments were not significantly different from the control. In summary, these excipients, at the doses administered, have limited influence on gastrointestinal transit and drug in beagle dogs.

Ampicillin↗
PubMed1994

Epidemic of herpes zoster following HIV epidemic in Manipur, India.

Since 1989, injecting drug use (IDU) related HIV infection has affected thousands of young adults in Manipur, a north eastern state of India bordering Myanmar following a similar kind of epidemic in adjoining countries like Thailand and Myanmar. During a clinical surveillance of a group of HIV positive IDUs for a natural history study at Manipur, herpes zoster (HZ) emerged as the most specific early HIV related illness (positive predictive value of 100%) in patients belonging to the age group of 12-45 years. Data collected from the dermatology departments of the two main hospitals of the state revealed that there had been an epidemic of HZ since 1990 (rate of 1990 being 11.3/1000 compared to 6.5/1000 in 1989, P value < 0.0001) among males of 12-45 years. The epidemic of HZ has been attributed to the preceding epidemic of IDU related HIV in the same age and gender group occurring 1 year earlier. HZ should be recognised as a marker condition similar to tuberculosis indicating the necessity of screening for HIV in regions where the dual problem of IDU and HIV exist in young adults.

AIDS-Related Opportunistic Infections↗
PubMed1982

The aminopyrine breath test as a measure of liver function. A quantitative description of its metabolic basis in normal subjects.

The APBT is used widely as a measure of liver function. The development of the APBT into a liver function test of greater diagnostic value requires quantitative information on the processes involved in aminopyrine disposition and metabolism in man and on how APBT values reflect changes in these processes. A dual-isotope kinetic study of aminopyrine disposition and metabolism has been carried out on five normal adult subjects. Oral administration of 13C-aminopyrine (2 mg/kg) accompanied by simultaneous intravenous injection of 14C-aminopyrine was followed by serial measurements of aminopyrine and monomethylaminopyrine in plasma and urine over 6 hr. Timed collections of respiratory CO2 were analyzed for the content of excess 13CO2 and for 14CO2. On separate days, an intravenous bolus of 13C-labeled NaHCO3 was administered to obtain estimates of the kinetic parameters of CO2 elimination in each subject. These data were fitted simultaneously to a multicompartmental model that, in addition to providing hitherto unavailable quantitative information, has revealed that (1) demethylation is the major elimination pathway for aminopyrine; (2) a major alternative pathway not involving demethylation exists for monomethylaminopyrine; and (3) only 50% of the labeled carbon generated by demethylation eventually is oxidized to HCO3-. The sensitivity of seven types of APBT scores to 50% reductions in the rates of aminopyrine absorption, metabolism of monomethylaminoantipyrine, intermediate carbon metabolism, and bicarbonate kinetics was evaluated with breath test curves simulated using the APBT model. Every APBT score currently in use was affected by variations in both gastrointestinal output of aminopyrine and bicarbonate kinetics. There is a need for further development of selective scoring methods in the aminopyrine breath test.

Adult↗
PubMed1995

Evolution of spinal bone loss and biochemical markers of bone remodeling after menopause in normal women.

The main objective of this study was to describe longitudinal patterns of spinal bone loss in normal women who undergo a natural menopause. The second objective was to determine if a proportion of women suffer excessively rapid postmenopausal bone loss from the spine. If this was the case it was the aim to devise a means of predicting the woman at excess risk; but if all women lost bone at similar rates, the aim was to document changing loss rates over the first 5-8 postmenopausal years. Responding women in six suburban general practices recalled for cervical smears who had their last menstrual period 9- 36 months previously were invited to participate in a longitudinal study of bone loss and the biochemical markers plasma osteocalcin and urinary hydroxyproline. Sixty-four subjects agreed to participate, a response rate of 80%. In the ensuing 5 years, six received hormone replacement therapy and are not reported on. The main outcome measures were rates of spinal bone loss over 5 years, measured by dual photon absorptiometry, and radial bone loss over the first 2 years measured to quantitative computed tomography. Spinal bone loss was similar between individuals, with 94% of the variability in the data being accounted for by a statistical model that assumed parallel rates of bone loss. A less restrictive model allowing women to have different rates of spinal bone loss accounted for 12% more of the remaining variance in the data than the previous model. However, rates of radial bone loss were more dissimilar between women than rates of spinal loss. The results of the biochemical data collected serially showed that the plasma osteocalcin rose slowly to a plateau at 5 years postmenopause; in contrast, the hydroxyproline fell progressively with time over the whole period of study. These results were interpreted as being consistent with diminishing rates of bone destruction which gradually reequilibrated with bone formation as time passed after menopause.

Absorptiometry, Photon↗
PubMed2006

Nepmucin, a novel HEV sialomucin, mediates L-selectin-dependent lymphocyte rolling and promotes lymphocyte adhesion under flow.

Lymphocyte trafficking to lymph nodes (LNs) is initiated by the interaction between lymphocyte L-selectin and certain sialomucins, collectively termed peripheral node addressin (PNAd), carrying specific carbohydrates expressed by LN high endothelial venules (HEVs). Here, we identified a novel HEV-associated sialomucin, nepmucin (mucin not expressed in Peyer's patches [PPs]), that is expressed in LN HEVs but not detectable in PP HEVs at the protein level. Unlike conventional sialomucins, nepmucin contains a single V-type immunoglobulin (Ig) domain and a mucin-like domain. Using materials affinity-purified from LN lysates with soluble L-selectin, we found that two higher molecular weight species of nepmucin (75 and 95 kD) were decorated with oligosaccharides that bind L-selectin as well as an HEV-specific MECA-79 monoclonal antibody. Electron microscopic analysis showed that nepmucin accumulates in the extended luminal microvillus processes of LN HEVs. Upon appropriate glycosylation, nepmucin supported lymphocyte rolling via its mucin-like domain under physiological flow conditions. Furthermore, unlike most other sialomucins, nepmucin bound lymphocytes via its Ig domain, apparently independently of lymphocyte function-associated antigen 1 and very late antigen 4, and promoted shear-resistant lymphocyte binding in combination with intercellular adhesion molecule 1. Collectively, these results suggest that nepmucin may serve as a dual-functioning PNAd in LN HEVs, mediating both lymphocyte rolling and binding via different functional domains.

Amino Acid Sequence↗
PubMed2006

Evidence of LAT as a dual substrate for Lck and Syk in T lymphocytes.

LAT is a linker protein essential for activation of T lymphocytes. Its rapid tyrosine-phosphorylation upon T cell receptor (TCR) stimulation recruits downstream signaling molecules for membrane targeting and activation. LAT is physically concentrated in cholesterol-enriched membrane microdomains and is known a substrate for Syk/Zap70 kinase. In this study, we demonstrate that LAT serves as a dual substrate for both Lck and Syk kinases. LAT phosphorylation is absent in Lck-deficient J.CaM1.6 cells and Lck is co-precipitated with LAT in pervanadate-activated Jurkat cells. Further, the in vitro kinase assay using purified Lck and LAT shows that Lck directly phosphorylates LAT. Both Lck and Syk, phosphorylate the ITAM-like motifs on LAT at Y171Y191, which is essential for induction of the interaction of LAT with downstream signaling molecules such as Grb2, PLC-gamma1 and c-Cbl, and for activation of MAPK-ERK. Collectively, our data indicate that LAT is an immediate substrate for Lck in one of the earliest events of T cell activation.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Pedal and knee loads using a multi-degree-of-freedom pedal platform in cycling.

To provide a scientific basis for the design of bicycle pedals which possibly alleviate over-use knee injuries, two hypotheses were tested in the present study. The two hypotheses were: (1) that the three-dimensional pedal constraint loads; and (2) that the three-dimensional intersegmental knee loads would be reduced more significantly by a foot/pedal platform allowing both adduction/abduction and inversion/eversion rotations simultaneously than by a platform which allowed either rotation individually. To test these hypotheses, pedal load and lower limb kinematic data were collected from 10 subjects who pedaled with four pedal platforms which allowed zero, one, and two degrees of freedom. A number of quantities describing both pedal loads and intersegmental knee loads was computed for each of the four pedal platforms using a previously reported biomechanical model. The quantities included the positive and negative extremes, averages, and areas, as well as the total absolute area and RMS. Quantities were compared using analysis of variance techniques. The key results were that there were significant reductions in the coupled nondriving moments at the pedal for the dual-rotation platform compared to each of the single-rotation cases. The significant reductions in the coupled moments at the pedal were not manifest at the knee. However, a general nonsignificant reduction in both coupled knee moments was evident. Also, the valgus knee moment was significantly reduced by the dual-rotation platform compared to the inversion/eversion only design. Although the axial knee moment was not significantly reduced by the dual-rotation platform over the adduction/abduction design, there was a general nonsignificant reduction. The lack of significance in knee load results occurred because of high intersubject variability. Accordingly, load reduction benefits made by introducing the second degree of freedom need to be considered individually.

Adult↗
PubMed2005

Gait variability: methods, modeling and meaning.

The study of gait variability, the stride-to-stride fluctuations in walking, offers a complementary way of quantifying locomotion and its changes with aging and disease as well as a means of monitoring the effects of therapeutic interventions and rehabilitation. Previous work has suggested that measures of gait variability may be more closely related to falls, a serious consequence of many gait disorders, than are measures based on the mean values of other walking parameters. The Current JNER series presents nine reports on the results of recent investigations into gait variability. One novel method for collecting unconstrained, ambulatory data is reviewed, and a primer on analysis methods is presented along with a heuristic approach to summarizing variability measures. In addition, the first studies of gait variability in animal models of neurodegenerative disease are described, as is a mathematical model of human walking that characterizes certain complex (multifractal) features of the motor control's pattern generator. Another investigation demonstrates that, whereas both healthy older controls and patients with a higher-level gait disorder walk more slowly in reduced lighting, only the latter's stride variability increases. Studies of the effects of dual tasks suggest that the regulation of the stride-to-stride fluctuations in stride width and stride time may be influenced by attention loading and may require cognitive input. Finally, a report of gait variability in over 500 subjects, probably the largest study of this kind, suggests how step width variability may relate to fall risk. Together, these studies provide new insights into the factors that regulate the stride-to-stride fluctuations in walking and pave the way for expanded research into the control of gait and the practical application of measures of gait variability in the clinical setting.

Journal Article↗
PubMed1978

From maximum security to secure treatment: organizational constraints.

This study focuses on an organization at the interface of the criminal justice and mental health systems. The institution examined was a maximum security mental hospital, primarily for incompetent felony defendants, as it was attempting to change from a custodial to a treatment orientation. Interest centered on whether structural factors in this type of organization place significant constraints on the ability of the organization to change in the intended direction. Data were collected at five points in time over a two-year period to test the impact of three substantial modifications in the organizational setting on the level of treatment. The latter was measured by patient/inmate responses on Prisonization and Favorableness Scales. Supporting the research hypotheses, there were some initial fluctuations in scle scores, but during the two periods of organizational stability no significant changes in either scale were evident. These findings are discussed in the context of technological constraints facing organizations, especially those providing mental health services in the criminal justice system, with the dual goals of custody and treatment.

Adult↗