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The performance of administrative and self-reported measures for risk adjustment of Veterans Affairs expenditures.

OBJECTIVE: To evaluate the performance of different prospective risk adjustment models of outpatient, inpatient, and total expenditures of veterans who regularly use Veterans Affairs (VA) primary care. DATA SOURCES: We utilized administrative, survey and expenditure data on 14,449 VA patients enrolled in a randomized trial that gave providers regular patient health assessments. STUDY DESIGN: This cohort study compared five administrative data-based, two self-report risk adjusters, and base year expenditures in prospective models. DATA EXTRACTION METHODS: VA outpatient care and nonacute inpatient care expenditures were based on unit expenditures and utilization, while VA expenditures for acute inpatient care were calculated from a Medicare-based inpatient cost function. Risk adjusters for this sample were constructed from diagnosis, medication and self-report data collected during a clinical trial. Model performance was compared using adjusted R2 and predictive ratios. PRINCIPAL FINDINGS: In all expenditure models, administrative-based measures performed better than self-reported measures, which performed better than age and gender. The Diagnosis Cost Groups (DCG) model explained total expenditure variation (R2=7.2 percent) better than other models. Prior outpatient expenditures predicted outpatient expenditures best by far (R2=42 percent). Models with multiple measures improved overall prediction, reduced over-prediction of low expenditure quintiles, and reduced under-prediction in the highest quintile of expenditures. CONCLUSIONS: Prediction of VA total expenditures was poor because expenditure variation reflected utilization variation, but not patient severity. Base year expenditures were the best predictor of outpatient expenditures and nearly the best for total expenditures. Models that combined two or more risk adjusters predicted expenditures better than single-measure models, but are more difficult and expensive to apply.

Aged↗

Lipoprotein oxidation and progression of carotid atherosclerosis.

BACKGROUND: Epidemiological studies and animal experiments have provided evidence supporting the role of lipid peroxidation in atherogenesis and cardiovascular diseases. Direct evidence linking lipid oxidation to atherosclerotic progression in humans, however, has been lacking. We investigated the association of lipid oxidation products with the progression of early carotid atherosclerosis in hypercholesterolemic men from eastern Finland. METHODS AND RESULTS: Twenty subjects with a fast progression and 20 with no progression of carotid atherosclerosis in 3 years were selected from > 400 participants in the Kuopio Atherosclerosis Prevention Study. Progression of carotid atherosclerosis was assessed by high-resolution B-mode ultrasonography. Serum 7 beta-hydroxycholesterol, a major oxidation product of cholesterol in membranes and lipoproteins, and seven other cholesterol oxidation products were measured by isotope dilution-mass spectrometry, lipid hydroperoxides in LDL fluorometrically as thiobarbituric acid-reactive substances (TBARS) and oxidation susceptibility of LDL and VLDL kinetically. High concentrations of serum 7 beta-hydroxycholesterol (beta = 47, P = .0005), cigarette smoking (beta = .35, P = .0167), and LDL TBARS (beta = .23, P = .0862) and an increased oxidation susceptibility of VLDL + LDL (beta = .22 P = .1114) were the strongest predictors of a 3-year increase in carotid wall thickness of more than 30 variables tested in step-up least-squares regression models. A 10-variable model explained 60% of the atherosclerotic progression. In a multivariate logistic model, the risk of experiencing a fast progression increased by 80% (P = .013) per unit (microgram/L) of 7 beta-hydroxycholesterol. CONCLUSIONS: The findings of this study provide further evidence to support an association between lipid oxidation and atherogenesis in humans.

Arteriosclerosis↗

A pacific culture among wild baboons: its emergence and transmission.

Reports exist of transmission of culture in nonhuman primates. We examine this in a troop of savanna baboons studied since 1978. During the mid-1980s, half of the males died from tuberculosis; because of circumstances of the outbreak, it was more aggressive males who died, leaving a cohort of atypically unaggressive survivors. A decade later, these behavioral patterns persisted. Males leave their natal troops at adolescence; by the mid-1990s, no males remained who had resided in the troop a decade before. Thus, critically, the troop's unique culture was being adopted by new males joining the troop. We describe (a) features of this culture in the behavior of males, including high rates of grooming and affiliation with females and a "relaxed" dominance hierarchy; (b) physiological measures suggesting less stress among low-ranking males; (c) models explaining transmission of this culture; and (d) data testing these models, centered around treatment of transfer males by resident females.

Aggression↗

Notch in vertebrates--molecular aspects of the signal.

Notch is a receptor consisting of a single path transmembrane protein which is essential for stem cell regulation in both vertebrates and invertebrates. We have investigated the function of Notch signaling and found that ligands of the Notch receptor (Delta and Serrate) sometimes act as receptor modulators in a cell autonomous manner; the balance of their activity as ligands explains satisfactorily 'lateral inhibition' as well as 'lateral specification'. This model explains not only fly morphogenesis, but also the general regulation of stem cells. In vertebrates, members of a novel family of genes which encode small secretory proteins, CCN, were demonstrated to bind to Notch and stimulate signaling. This is not a ligand type binding, but rather a modifier of the protein structure of Notch, so as to form a macromolecular complex. This association may open up novel perspectives on Notch signaling, for instance in the movement of cells involved in somite segmentation or angiogenesis. Thus, a well-conserved signal such as Notch seems to have changed in function during the evolution of vertebrates.

Animals↗

Modeling pesticide volatilization from turf.

Pesticide volatilization models are typically based on equilibrium partitioning of the chemical into solid, liquid, and gaseous phases in the soil environment. In turf systems direct vaporization from vegetation surfaces is a more likely source, and it is difficult to apply equilibrium methods to plant material due to the uncertainties of solid-liquid-gas partitioning. An alternative approach is to assume that pesticide volatilization is governed by the same processes that affect water evaporation. A model was developed in which evapotranspiration values, as determined by the Penman equation, were adjusted to chemical vaporization using ratios of water and chemical saturated vapor pressures and latent heats of vaporization. The model also assumes first-order degradation of pesticide on turf vegetation over time. The model was tested by comparisons of predictions with measurements of volatilization for eight pesticides measured during 3 to 7 d in 11 field experiments. Measured volatilization fluxes ranged from 0.1 to 22% of applied chemical. Pesticides were divided into two groups based on saturated vapor pressures and organic C partition coefficients. One pesticide was selected from each group to calibrate the model's volatilization constant for the group, and the remaining pesticides were used for model testing. Testing results indicated that the model provides relatively conservative estimates of pesticide volatilization. Predicted mean losses exceeded observations by 20%, and the model explained 67% of the observed variation in volatilization fluxes. The model was most accurate for those chemicals that exhibited the largest volatilization losses.

Air Pollutants↗

Cutaneous leishmaniasis in the Peruvian Andes: risk factors identified from a village cohort study.

Risk factors for cutaneous leishmaniasis were identified from a comparative study of transmission rates in 27 villages in the Departments of Lima, Ancash, and Piura in Peru. To evaluate regression analysis as a tool for the incrimination of sand fly vectors in the absence of other biologic evidence, univariate and multivariate logistic regression analyses were used to identify which of 14 variables (the abundance of nine sand fly species, four social factors, and region) predicted transmission rates in villages (incidence, active prevalence, or cumulative prevalence). In general, suspected or proven vectors (e.g., Lutzomyia peruensis) had the strongest associations with transmission rate, indicating that regression is a useful supplementary method of incriminating vectors. Regression was then used to quantify the importance of suspected risk factors. Transmission rate increased with the abundance of Lu. peruensis, Lu. ayacuchensis, Lu. noguchii, and, to a lesser extent, Lu. verrucarum and transmission was higher among villagers who slept more frequently in temporary shelters in crop areas. There were also weak effects of the number of dogs/ person (negative) and the number of persons/household (positive). Linear regressions failed to detect a threshold sand fly density below which transmission ceases. The minimal adequate multiple regression model explained 82% of the variance in village incidence rates. This model was used to predict the effect on incidence of reducing each of the four suspected vectors in northern and southern Peru. The results indicate that vector control programs in the south should aim at Lu. peruensis, Lu. verrucarum, and Lu. noguchii, but focus on Lu. ayacuchensis in the north.

Analysis of Variance↗

Managers' leadership and critical care nurses' intent to stay.

BACKGROUND: Cyclical fluctuations in turnover of critical care nurses are a large and complex problem. Managers' leadership characteristics may be a determinant of critical care nurses' intent to stay in the job. OBJECTIVE: To examine the direct and indirect effects of nurse-managers' characteristics of power, influence, and leadership style on critical care nurses' intent to stay in the nurses' employment positions. METHODS: The sample was 255 staff nurses in intensive care units at 4 urban hospitals. Established instruments with sound reliability and validity were used to assess the predictor, intervening, and outcome variables. Path analysis was used to examine the relationships in a conceptual model of intent to stay. RESULTS: The model explained 52% of the variance in intent to stay, and managers' characteristics were significant at each stage. Managers' position power and influence over work coordination had a direct link to intent to stay; structuring expectations and consideration contributed indirectly through the variables of instrumental communication, autonomy, and group cohesion. Instrumental communication, autonomy, and group cohesion decreased job stress and thus increased job satisfaction. Job satisfaction was directly linked with intent to stay. CONCLUSIONS: Inclusion of nurse-managers' characteristics explained more variance in intent to stay than did previous models. Managers with leadership styles that seek and value contributions from staff, promote a climate in which information is shared effectively, promote decision making at the staff nurse level, exert position power, and influence coordination of work to provide a milieu that maintains a stable cadre of nurses.

Adult↗

A cell-based model of hemostasis.

Based on our work and that of many other workers, we have developed a model of coagulation in vivo. Many workers have demonstrated mechanisms by which cells can influence the coagulation process. Nonetheless, the prevailing view of hemostasis remains that the protein coagulation factors direct and control the process with cells serving primarily to provide a phosphatidylserine containing surface on which the procoagulant complexes are assembled. By contrast, we propose a model in which coagulation is regulated by properties of cell surfaces. This model emphasizes the importance of specific cellular receptors for the coagulation proteins. Thus, cells with similar phosphatidylserine content can play very different roles in hemostasis depending on their complement of surface receptors. We propose that coagulation occurs not as a "cascade", but in three overlapping stages: 1) initiation, which occurs on a tissue factor bearing cell; 2) amplification, in which platelets and cofactors are activated to set the stage for large scale thrombin generation; and 3) propagation, in which large amounts of thrombin are generated on the platelet surface. This cell based model explains some aspects of hemostasis that a protein-centric model does not.

Animals↗

Patients' perspectives of a spinal cord injury unit.

The purpose of this study is to provide an ethnographic description of the subculture of a spinal cord injury (SCI) unit. The research method was qualitative, combining ethnographic interviews, participant observation, and document review. A 30 bed SCI facility on the west coast was selected as the setting for this ethnographic description. The developmental research sequence model (Spradley, 1980) and grounded theory (Glaser & Strauss, 1967) were used for data analysis. Findings indicate optimal rehabilitation is a creative and individualized process of reintegration. Reintegration prepares the individual for coping with physical limitations, architectural barriers, and societal prejudices while simultaneously making the person feel intact and valued. Successful reintegration promotes a "fit" between the newly injured spinal cord patient and the home environment. The patient learns to compensate for the physical limitations of the spinal cord injury in a manner that promotes safety, comfort, and personal worth. Successful reintegration assures the newly injured SCI patient returns to a viable occupation, feels physically attractive, participates in a rich, full social life, and maintains family ties. Four phases of reintegration emerged: buffering, transcending, toughening, and launching. Buffering is the nurturing and protective process of lessening, absorbing, or protecting the newly injured SCI patient against the shock of multiple ramifications of the injury and the indignities of being a patient; Transcending is the process of helping SCI patients recognize and rise above culturally imposed limitations and negative beliefs about people with disabilities. The "toughening up" process focuses on compensating for physical limitations, gaining independence, and maintaining social interactions without "using the disability." Launching is the process of (1) exposing rehabilitation patients to the real world, (2) exploring the range of options for living in the community, (3) promoting patient autonomy and decision making, and (4) facilitating the ejection of the patient from the rehabilitation program. The study is significant because it offers a new perspective for viewing a spinal cord injury unit. The proposed theoretical model explains patients' attitudes, beliefs, and behavior on SCI units. This model provides a framework for designing a prototype therapeutic milieu in SCI.

Adaptation, Psychological↗

Decreased interstitial apolipoprotein A-I levels in IDDM patients with diabetic nephropathy.

The risk of cardiovascular morbidity and mortality is highly increased in patients with diabetic nephropathy. Postulating that the generalized vasculopathy observed in these patients may enhance transcapillary filtration of lipids and lipoproteins resulting in a more atherogenic interstitial lipid profile, we set out to analyze the composition of their interstitial fluid. We studied healthy control subjects (n = 9), normoalbuminuric insulin-dependent diabetes mellitus (IDDM) patients (n = 16), and IDDM patients with diabetic nephropathy (n = 11) matched for age, body mass index, smoking habits, duration of diabetes, and metabolic control. Interstitial fluid was collected after an overnight fast by applying mild suction (200 mmHg) to the skin. Interstitial apolipoprotein A-I (apoA-I) levels were significantly lower in patients with nephropathy (0.18 +/- 0.10 milligram [mean +/- SD]) compared with normoalbuminuric diabetic patients (0.29 +/- 0.08 milligram) and healthy control subjects (0.30 +/- 0.09 milligram). Interstitial apolipoprotein B:apoA-I ratios tended to be higher in patients with diabetic nephropathy. In these patients, normal interstitial low-density lipoprotein cholesterol concentrations were observed in the presence of lower apoA-I levels. Transcapillary filtration of apoA-I was significantly lower in patients with diabetic nephropathy. Furthermore, an altered multiple regression model explaining interstitial apoA-I levels was observed in diabetic nephropathy. In this model, transcapillary protein (IgG) filtration and serum apoA-I levels no longer explained interstitial apoA-I levels. If we assume that interstitial apoA-I is involved in reverse cholesterol transport, these data suggest a more atherogenic interstitial lipoprotein profile in IDDM patients with nephropathy.

Adult↗

Community-based mental health care: to what extent are service costs associated with clinical, social and service history variables?

BACKGROUND: The growing movement in many European countries towards capitation-based systems for financing mental health care has generated increasing interest in developing appropriate models capitation formulae. The aims of the study were: to detect and compare any differences in service costs between patients with different diagnoses; and to analyse the associations between patient characteristics and service costs. METHODS: All patients in contact with the South-Verona Community Mental Health Service during the last quarter of 1996 were included in the study. Clinical and service-related variables were collected at first index contact; 3 months later, patients were interviewed using the Client Services Recipient Interview. For those who completed both the clinical assessments and the services receipt schedule (N = 339), 1-year psychiatric and non-psychiatric direct care costs were calculated. Weighted backward regression analyses were performed. RESULTS: The most significant variables associated with psychiatric costs were: admission to hospital in the previous year; intensity and duration of previous contacts with South-Verona CMHS; being unemployed; having a diagnosis of affective disorder; and, Global Assessment of Functioning score. The final model explained 66% of the variation in costs of psychiatric care and 13 % of variation in non-psychiatric medical costs. CONCLUSIONS: The model presented in this study explains a higher degree of cost variance than previously published studies. In community-based services more resources are targeted towards the most disabled patients. Previous psychiatric history (number of admissions in the previous year and intensity of psychiatric contacts lifetime) is strongly associated with psychiatric costs.

Adult↗

The relationship of somatization and depression to experimental pain response in women with temporomandibular disorders.

OBJECTIVE: Patients with temporomandibular pain disorders (TMD) have greater experimental pain perception when compared with pain-free controls. Common psychological features of TMD include somatization and depression. The impact of depression on experimental pain perception has received considerable attention. However, the role of somatization on experimental pain in a chronic pain population has not been explored. METHODS: Fifty-six women with TMD and 59 pain-free controls underwent three experimental pain procedures, including palpation at fixed amounts of pressure, pressure pain thresholds, and an ischemic pain task. Levels of depression and somatization were assessed using the Research Diagnostic Criteria for TMD. Multiple regression analyses were performed to determine the extent to which depression and somatization were associated with experimental pain response. RESULTS: After controlling for characteristic pain intensity and depression, somatization explained a significant proportion of variance in numbers of masticatory sites rated as painful (R2 change = 6.7%, p = .046) with the full model explaining 16.4% of the variance (p = .024). This did not meet an adjusted level of statistical significance (p = .008). After controlling for characteristic pain, only depression added significantly to the model predicting ischemic pain threshold and tolerance. The full models including characteristic pain and depression explained 49% and 20% of the variance in ischemic pain threshold and tolerance, respectively. CONCLUSIONS: These findings suggest that depression and somatization are associated with different measures of experimental pain. Somatization may be related to more attentional and perceptual measures of clinically relevant pain while depression may be related to more behavioral measures of pain.

Adolescent↗

Dipolar modelling of the scalp evoked potentials to painful contact heat stimulation of the human skin.

Contact heat evoked potentials (CHEPs) were collected in 12 healthy subjects by stimulating the forearm skin with a couple of thermodes at a painful intensity. The stimulated area was 628 mm(2) and the repetition rate was 0.1 Hz. The electroencephalogram was recorded by 31 electrodes placed on the scalp according to an extended 10-20 System. A dipolar model explaining the scalp CHEP distribution was built by using the brain electrical source analysis. The model includes two dipoles located bilaterally in the perisylvian region, one dipole in the deep midline region and two dipoles located bilaterally in the deep temporal lobe. This dipolar model is very similar to that previously described to explain the topography of evoked potentials to radiant heat stimulation by laser pulses. Since laser stimuli activate the nociceptive fibres, the strong similarity of the cerebral dipoles activated by contact heat stimuli and by laser pulses suggests that only nociceptive inputs are involved in the scalp painful CHEP building. Therefore, CHEP recording can be useful for clinical examination of the nociceptive system.

Adult↗

Validation and predictive power of Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis classes for malignant glioma patients: a report using RTOG 90-06.

PURPOSE: The recursive partitioning analysis (RPA) classes for malignant glioma patients were previously established using data on over 1500 patients entered on Radiation Therapy Oncology Group (RTOG) clinical trials. The purpose of the current analysis was to validate the RPA classes with a new dataset (RTOG 90-06), determine the predictive power of the RPA classes, and establish the usefulness of the database norms for the RPA classes. PATIENTS AND METHODS: There are six RPA classes for malignant glioma patients that comprise distinct groups of patients with significantly different survival outcome. RTOG 90-06 is a randomized Phase III study of 712 patients accrued from 1990 to 1994. The minimum potential follow-up is 18 months. The treatment arms were combined for the purpose of this analysis. There were 84, 13, 105, 240, 150, and 23 patients in the RPA Classes I-VI from RTOG 90-06, respectively. RESULTS: The median survival times (MST) and 2-year survival rates for the six RPA classes in RTOG 90-06 are compared to those previously published. The MST and 2-year survival rates for the RTOG RPA classes were within 95% confidence intervals of the 90-06 estimates for Classes I, III, IV, and V. The RPA classes explained 43% of the variation (squared error loss). By comparison, a Cox model explains 30% of the variation. The RPA classes within RTOG 90-06 are statistically distinct with all comparisons exceeding 0.0001, except those involving Class II. A survival analysis from a prior RTOG study indicated that 72.0 Gy had superior outcome to literature controls; analysis of this data by RPA classes indicates the survival results were not superior to the RTOG database norms. CONCLUSION: The validity of the model is verified by the reliability of the RPA classes to define distinct groups with respect to survival. Further evidence is given by prediction of MST and 2-year survival for all classes except Class II. The RPA classes explained a good portion of the variation in survival outcome in the data. Lack of correlation in RPA Class II between datasets may be an artifact of the small sample size or an indication that this class is not distinct. The validation of the RPA classes attests to their usefulness as historical controls for the comparison of future Phase II results.

Dose Fractionation, Radiation↗

Nanoenzymology of the 20S proteasome: proteasomal actions are controlled by the allosteric transition.

The proteasome is a major cytosolic proteolytic assembly, essential for the physiology of eukaryotic cells. Both the architecture and enzymatic properties of the 20S proteasome are relatively well understood. However, despite longstanding interest, the integration of structural and functional properties of the proteasome into a coherent model explaining the mechanism of its enzymatic actions has been difficult. Recently, we used tapping mode atomic force microscopy (AFM) in liquid to demonstrate that the alpha-rings of the proteasome imaged in a top-view position repeatedly switched between their open and closed conformations, apparently to control access to the central channel. Here, we show with AFM that the molecules in a side-view position acquired two stable conformations. The overall shapes of the 20S particles were classified as either barrel-like or cylinder-like. The relative abundance of the two conformers depended on the nature of their interactions with ligands. Similarly to the closed molecules in top view, the barrels predominated in control or inhibited molecules. The cylinders and open molecules prevailed when the proteasome was observed in the presence of peptide substrates. Based on these data, we developed the two-state model of allosteric transitions to explain the dynamics of proteasomal structure. This model helps to better understand the observed properties of the 20S molecule, and sets foundations for further studies of the structural dynamics of the proteasome.

Allosteric Regulation↗

Equivalence of the mixed and regressive models for genetic analysis. I. Continuous traits.

The mixed model of segregation analysis specifies major gene effects and partitions the residual variance into polygenic and environmental components. The model explains familial correlations essentially in terms of genetic causation. The regressive model, on the other hand, is constructed by successively conditioning on ancestral phenotypes and major genes. Familial patterns of dependence are described in terms of correlations without necessarily introducing a particular scheme of causal relationship. These two approaches are compared both theoretically and numerically through computer simulations for the case of continuous traits on nuclear families. The class D regressive model, which is characterized by equal sib-sib correlations, is mathematically and numerically equivalent to the mixed model. The simpler class A regressive model, which is also characterized by equal sib-sib correlations determined in this case by the common parentage, provides good estimates of the mixed model parameters: major gene parameters and residual polygenic heritability, derived from the parent-offspring correlation. However, in the absence of a major gene, the restriction imposed by the class A model on the sibling correlation can affect the conclusions of segregation analysis: False inference of a major gene was observed in two out of ten replicates. Our simulations also indicate that the mixed model allowing for different heritabilities in adults and children leads to correct estimates of the major gene parameters and residual familial correlations (parent-offspring and sib-sib) as specified by the class A model. For all the models studied, major gene effects, when present, are correctly detected and estimated.

Adult↗

Transcriptional autoregulation by phosphorylated and non-phosphorylated KaiC in cyanobacterial circadian rhythms.

Cyanobacteria are the simplest organisms known to exhibit circadian rhythms, which is the fundamental process of homeostasis adapting to daily environmental changes. The cyanobacterial clock gene products, KaiA, KaiB, and KaiC interact with each other, and regulate KaiC phosphorylation and kaiBC expression in a circadian fashion. Molecular genetic study recently proposed that KaiC protein may enhance and repress transcription of clock genes depending on KaiC's phosphorylation status, however, the precise mechanism is still unknown. We developed a mathematical model for the dynamics of cyanobacterial circadian rhythms focusing on the transcriptional regulation by KaiC. We investigated the model using numerical methods, and predicted the transcriptional regulation mechanism by KaiC. We searched for conditions for generating circadian oscillation and concluded that only two mechanisms of the transcriptional regulation are the possible pictures. One is the Transcriptional Repression Model where KaiC represses transcription of the clock genes after phosphorylation, and the other is the Transcriptional Activation Model where KaiC induces transcription after phosphorylation. The Transcriptional Repression Model includes self-repression similarly to the circadian oscillator models that have been proposed previously, and dynamical oscillation is easy to understand. However, the Transcriptional Activation Model does not include any direct repression in its interactive circuit, and is distinct from the previous ideas for circadian clocks. Subsequent computer simulation showed that the Transcriptional Activation Model explains most of the observed mutant phenotypes, and the Transcriptional Repression Model realizes only a half of them. It was also revealed that oscillations in the Transcriptional Activation Model is much more robust against the disruption by cell division or cell elongation than the Transcriptional Repression Model. It suggests that the Transcriptional Activation Model may reflect the essence of the actual transcriptional mechanism of the kai oscillator in cyanobacteria.

Bacterial Proteins↗

Adaptive branching in evolution and epigenesis.

We describe one of the simplest models that exhibit an adaptive branching behaviour. It is analysed both experimentally and formally, and its successive bifurcations provide a good model of what R. Thom called 'generalized catastrophes'. Two theorems on the stochastic adaptivity of the algorithm to very general shapes of target are given. The model further displays the phenomenon of abortive branching: each macroscopic branching appears after a burst of microscopic branchings that stop growing after a very short time. The mathematical analysis of the model explains why and how this behaviour occurs. Possible applications of these models to Evolution (natural and artificial) and Epigenesis are briefly mentioned, and a higher dimensional version is applied to growing a tree in a space of shapes in the context of a database of medical images.

Adaptation, Physiological↗