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PubMed2006

Stereospecificity in metallocene catalyzed acrylate polymerizations: the chiral orientation of the growing chain selects its own chain end enantioface.

The mechanism of stereocontrol in the site-controlled stereospecific polymerization of methyl methacrylate (MMA) with C2- and CS-symmetric zirconocenes is investigated with a DFT based approach. Our model explains the experimentally observed isospecificity in MMA polymerization with the C2-symmetric rac-C2H4(Ind)2Zr-based system as well as the experimentally observed syndiospecificity in MMA polymerization with the CS-symmetric Me2C(Cp)(Flu)Zr-based system. In both cases, the chiral metallocene induces a chiral orientation of the ester enolate growing chain. In turn, the chirally oriented growing chain selects its own enantioface. Comparison with the mechanism of stereocontrol operative in the case of propene polymerization by the same zirconocenes is performed to stress similarities and differences. Although analogies are expected, surprising differences also exist. The most peculiar is that the in the case of 1-olefins, the enantioselective event is selection between the enantiofaces of the prochiral monomer. Instead, in the case of acrylates, the enantioselective event is selection between the enantiofaces of the prochiral growing chain.

Catalysis↗

PubMed1999

6-Substituted benzopyrans as potassium channel activators: synthesis, vasodilator properties, and multivariate analysis.

During the last 10 years compounds have been discovered which can activate or block KATP channels. In particular, K channel activators (KCA) have been found to be smooth muscle relaxants with their main utility in hypertension and bronchodilation. In this paper we describe the synthesis of new KCA of the benzopyran type with a fixed 4-substituent and a systematic variation in the 6-position. The relaxant potency in rat aorta and trachea was used for biological characterization of the benzopyrans. In both biological test systems, they exhibit potency ranges of more than 3 log units. Structure-activity relationships are investigated by principal component analysis (PCA) and partial least-squares (PLS) analysis. Most striking outliers in an initial PLS analysis of the entire database were the unsubstituted 6-H compound 13 as well as 34 and 35. For the remaining set of 31 compounds, a 3-component PLS model explains the variance in biological activity to 81% in the aortic and to 82% in the tracheal test system. 6-Substituents influence affinity by a direct (presumably dipolar) interaction with the receptor site. According to the 2D-plot of the partial PLS weights, a strong electronegativity as well as high values for the integy moment and for the heat of formation in water dominate the first component; low values for substituent size (as defined by globularity or surface) are in addition favorable for high potency. High lipophilicity and low minimum energies of interaction dominate the second component. Chemical descriptors for the biological potency of the test set in rat aorta and rat trachea are very similar according to the almost identical projection of the Y-variables onto the X-component space.

Animals↗

PubMed2004

TOPS-MODE approach for the prediction of blood-brain barrier permeation.

The blood-brain barrier permeation has been investigated by using a topological substructural molecular design approach (TOPS-MODE). A linear regression model was developed to predict the in vivo blood-brain partitioning coefficient on a data set of 119 compounds, treated as the logarithm of the blood-brain concentration ratio. The final model explained the 70% of the variance and it was validated through the use of an external validation set (33 compounds of the 119, MAE = 0.33), a leave-one-out crossvalidation (q(2) = 0.65, S(press) = 0.43), fivefold full crossvalidation (removing 28 compounds in each cycle, MAE = 33, RMSE = 0.43) and the prediction of +/- values for an external test set (85.7% of good prediction). This methodology evidenced that the hydrophobicity increase the blood-brain barrier permeation, while the polar surface and its interaction with the atomic mass of compounds decrease it; suggesting the capacity of the TOPS-MODE descriptors to estimate brain penetration potential of new drug candidates. Finally, by the present approach, positive and negative substructural contributions to the brain permeation were identified, and their possibilities in the lead generation and optimization processes were evaluated.

Blood-Brain Barrier↗

PubMedDate not supplied

Objectively measured boar sperm motility parameters correlate with the outcomes of on-farm inseminations: results of two fertility trials.

Two fertility trials were undertaken to evaluate the relationship between boar semen quality and fertility (conception rate and litter size) after on-farm artificial insemination (AI). Trial 1 included 98 ejaculates from 27 boars, and trial 2 included 72 ejaculates from 26 boars. The semen quality was measured by computer-assisted semen analysis (CASA) using the Hobson Sperm Tracker. Boar semen was diluted in a standard extender (Beltsville Thawing Solution, BTS), dispensed into 75 ml allquots each containing 1.5 x 10(9) spermatozoa and dispatched to farms by overnight mail for use by their normal AI procedures. Randomly selected 75 ml aliquots of semen from each boar were also sent to the institute of Zoology for CASA measurement. Prior to CASA analysis, the spermatozoa were recovered from the BTS using Percoll gradients, resuspended in trisbuffered saline media containing 40 mM Ca++, and incubated at 39 degrees C. Parameters of sperm motion were measured after 0, 2, 4, and 6 hours of incubation. Various multiple regression models based on measured motion parameters could account for up to 24% of the variation in litter size. Using logistic regression, highly significant (P < 0.0001) models explaining conception rate in terms of sperm motion were derived for trial 2 only. The change in sperm velocity during the first 2 hours of incubation and the magnitude of the velocity parameters after 2 hours were identified as the most consistent indicators of fertility. Other attributes of sperm quality, i.e., frequency of spontaneous acrosome reactions (AR) and ARs induced by ionophore A23187 or solubilized pig zona pellucida, were also examined. When the "within-trial" median litter size was used as a way of allocating ejaculates to "high" or "low" litter-size groups, higher litter size was associated with lower frequency of both spontaneous and induced AR. These results demonstrate that fertility information can be derived from the CASA analysis of boar semen provided it is combined with a period of incubation in capacitating conditions.

Animals↗

PubMed1995

Wavelengths for laser treatment of port wine stains and telangiectasia.

BACKGROUND AND OBJECTIVE: This report presents analytical modelling of the influence of wavelength on the amount of volumetric rate of heat produced in dermal blood vessels by millisecond laser radiation. STUDY DESIGN/MATERIALS AND METHODS: A new anatomical model is proposed that represents port wine stains as well as telangiectatic lesions. It consists of a target blood vessel, representing the deepest dermal blood vessel that requires irreversible injury, and a layer of whole blood, representing all other dermal blood vessels above the target vessel. The laser light that interacts with the blood vessels is assumed to be diffuse. Selective photothermolysis is the basis for the analysis. We consider wavelengths between 577 nm and 600 nm, the argon laser wavelengths at 488/515 nm, and the frequency doubled Nd:YAG laser wavelength at 532 nm. RESULTS: The rate of volumetric heat production of absorbed laser light in the target blood vessel is expressed analytically as a function of blood absorption, the concentration of additional dermal blood, and the depth of the target vessel. CONCLUSION: The model explains why 585 nm is a good compromise for treating port wine stains that vary widely in number of dermal blood vessels. It predicts that wavelengths between 577 nm and 582 nm are excellent for the treatment of port wine stains in young children, and it suggests a possible explanation as to why the argon laser is sometimes said to be capable of treating dark mature port wine stains. The copper vapour laser wavelength at 578 nm, and the frequency doubled Nd:YAG laser wavelength at 532 nm, are predicted to be suitable for the treatment of port wine stains that contain, respectively, a small to moderate and a moderate number of dermal blood vessels. When laser beam spotsize becomes smaller, the best wavelength for producing maximal rate of heat in the target vessel is predicted to shift to 577 nm.

Animals↗

PubMed1995

Evolutionary origin of expandable G-C-rich triplet repeat DNA sequences.

A model explaining properties exhibited by fragile-X DNA systems arises from observations that time-dependent base substitutions are expressed at G-C sites but not at A-T sites (Biochem. Genet. 32:383, 1994). [CGG]n sequences are classified as most sensitive to evolutionary base substitution processes involving time-dependent populating of G-C sites with enol-imine states having enhanced stability. Increased density of these states in oocyte DNA would introduce a ground-state collapse double-helix of reduced energy that would inhibit strand separation by the replicase. Evolutionarily altered G' in CG'G triplets allows CG'G to be transcribed as CTG, an initiation codon. And this will cause reinitiation of DNA synthesis, thereby adding additional CGG units to the collapsed double helix. This situation would not occur in slower-evolving male haploid DNA that replicates frequently.

Base Composition↗

PubMed1999

The interpretation of Mg(2+) binding isotherms for nucleic acids using Poisson-Boltzmann theory.

Magnesium ions play a crucial role in the structural integrity and biological activity of nucleic acids. Experimental thermodynamic descriptions of Mg(2+) interactions with nucleic acids in solution have generally relied on the analyses of binding polynomials to estimate the energetic contributions of diffuse and site-bound ions. However, since ion binding is dominated by long-range electrostatic forces, such models provide only a phenomenological description of the experimental Mg(2+) binding data and provide little insight into the actual mechanism of the binding equilibria. Here, we present a rigorous theoretical framework based on the non-linear Poisson-Boltzmann (NLPB) equation for understanding diffuse ion interactions that can be used to interpret experimental Mg(2+) binding isotherms. As intuitively expected, in the NLPB model binding is simply the total accumulation of the ion around the nucleic acid. Comparing the experimental data to the calculated curves shows that the NLPB equation provides a remarkably accurate description of Mg(2+) binding to linear polynucleotides like DNA and poly(A x U) without any fitted parameters. In particular, the NLPB model explains two general features of magnesium binding; the strong dependence on univalent salt concentration, and its substantial anticooperativity. Each of these effects can be explained by changes in the Mg(2+) distribution around the polyion under different solution conditions. In order to more fully understand these different aspects of magnesium binding, the free energy of Mg(2+) binding, DeltaGMg, is calculated and partitioned into several salt-dependent contributions: the change in the electrostatic interaction free energy of the charges, DeltaDeltaGE.D (including Mg(2+)-phosphate, Mg(2+)-Mg(2+), Mg(2+)-Na(+), Na(+)-Na(+), Na(+)-phosphate interactions, and similar contributions for Cl(-)) and the cratic free energies of (re)organizing the MgCl2 and NaCl atmospheres, DeltaG(Mg)org and DeltaDeltaG(Na)org, respectively. For the systems studied here, DeltaGMg is strongly influenced by entropic free energy changes in the distributions of both NaCl and MgCl2, DeltaG(Mg)org and DeltaDeltaG(Na)org. From this analysis, we also raise the possibility that coions added with the magnesium salt might play an important role in the overall stability of nucleic acids under some conditions.

Binding, Competitive↗

PubMed1997

Exercise testing in the preoperative evaluation of patients with bronchogenic carcinoma.

The aim of this study was to evaluate which parameters of preoperative spirometry and cardiopulmonary exercise test are the best predictors of postoperative morbidity and mortality in patients with bronchogenic carcinoma. Ninety seven patients were prospectively and consecutively examined. All patients had preoperative maximal exercise test and dynamic spirometry. Postoperative complications and causes of death were registered. Logistic regression was used and models explaining the relationship between preoperative variables and postoperative complications and deaths were constructed. We found significant differences in preoperative maximal workload and carbon dioxide output between groups, with and without cardiopulmonary-related complications, but not in spirometry variables. Logistic regression showed maximal workload to be the only predictor of cardiopulmonary complications. Maximal oxygen uptake was predictive of cardiopulmonary deaths. Maximal oxygen uptake and forced expiratory volume were predictive of postoperative complications. A maximal oxygen uptake <50% predicted was associated with high risk of death from cardiopulmonary causes. Kaplan-Meier survival curves showed that maximal oxygen uptake was correlated to long-term survival, while spirometric variables were not. Exercise testing can be used in the preoperative evaluation of patients with nonmetastatic bronchogenic carcinoma. A combination of the results of variables from spirometry and exercise testing is proposed to be used as a preoperative criterion for operability.

Carcinoma, Bronchogenic↗

PubMed2005

Adult height and pubertal growth in Turner syndrome after treatment with recombinant growth hormone.

OBJECTIVE: The objective of this study was to evaluate factors affecting adult height (AH) in patients with Turner syndrome treated with GH. DESIGN: The study design was a population-based cohort study. SETTING: The setting was The StaTur Study, a register of patients treated in France between 1986 and 1997, followed for a mean of 9.3 yr. PATIENTS: We followed 704 of the 891 eligible patients (79%) to AH. INTERVENTION: GH (0.8 +/- 0.2 IU/kg.wk; 0.26 +/- 0.06 mg/kg.wk; mean +/- sd) was administered for 5.0 +/- 2.2 yr. Puberty was classified as spontaneous (10%), spontaneous with secondary estrogens (13%), or induced (77%). Estrogen treatment was initiated at 15.0 +/- 1.9 yr of age in those with induced puberty. MAIN OUTCOME MEASURE: The main outcome measure was multivariate analysis of AH after grouping potential predictors. RESULTS: The mean AH was 149.9 +/- 6.1 cm, 8.5 cm above projected height. The model explained 90% of the variance, with major effects of age at initiation and duration of treatment. Other factors included birth length, target height, bone age delay and weight at initiation of treatment, age at pubertal onset, GH dose, and number of injections per week. Age at introduction of estrogens was not a predictor, and the use of percutaneous vs. oral estrogens was associated with greater height (+2.1 cm; 95% confidence interval, 1.00-3.25). CONCLUSIONS: Our results support the early initiation of GH treatment and induction of puberty at a physiological age to achieve optimal AH. They suggest that GH should be injected daily, and percutaneous estrogens used. These results should be considered in the context of the lack of demonstrable influence of AH on psycho-social outcomes, uncertainties regarding long-term safety, and treatment cost.

Adolescent↗

PubMed2004

Female preference for multiple condition-dependent components of a sexually selected signal.

Theoretical models explain the evolution of multi-cue mate-choice decisions from a trade-off between benefits owing to improved assessment of potential mates and costs linked to the use of multiple signals. However, empirical support for these basic assumptions is lacking. In field crickets (Gryllus campestris) we experimentally investigated the female preference to variation in two key components of the male calling song: carrier frequency and chirp rate. Previous studies have revealed carrier frequency and chirp rate as reliable indicators of male quality that reflect past condition and current condition, respectively. In a two-way choice experiment, females significantly preferred test songs of lower carrier frequency and higher chirp rate, but prioritized the carrier frequency over the chirp rate. Hence, the static long-term indicator of mate quality was weighted more than the dynamic short-term one. Our results thus indicate that females integrate information from independent condition-dependent cues to discriminate between available males in mate-choice decisions.

Acoustic Stimulation↗

PubMed1995

Understanding the factors behind the decision to purchase varying coverage amounts of long-term care insurance.

OBJECTIVE: This article examines the factors related to an individual's decision to purchase a given amount of long-term care insurance coverage. DATA SOURCE AND STUDY SETTING: Primary data analyses were conducted on an estimation sample of 6,545 individuals who had purchased long-term care (LTC) insurance policies in late 1990 and early 1991, and 1,248 individuals who had been approached by agents but chose not to buy such insurance. Companies contributing the two samples represented 45 percent of total sales during the study year. STUDY DESIGN: A two-stage logit-OLS (ordinary least squares) choice-based sampling model was used to examine the relationship between the expected value of purchased coverage and explanatory variables that included: demographic traits, attitudes, risk premium, nursing home bed supply, and Medicaid program configurations. DATA COLLECTION: Mail surveys were used to collect information about individuals' reasons for purchase, attitudes about long-term care, and demographic characteristics. Through an identification code, information on the policy designs chosen by these individuals was linked to each of the returned mail surveys. The response rate to the survey was about 60 percent. PRINCIPAL FINDINGS: The model explains about 47 percent of the variance in the dependent variable-expected value of policy coverage. Important variables negatively associated with the dependent variable include advancing age, being married, and having less than a college education. Variables positively related include being male, having more income, and having increasing expected LTC costs. Medicaid program configuration also influences the level of benefits purchased: state reimbursement rates and the presence of comprehensive estate recovery programs are both positively related to the expected value of purchased benefits. Finally, as the difference between the premium charged and the actuarially fair premium increases, individuals buy less coverage. CONCLUSIONS: An important finding with implications for policymakers is that changes in Medicaid policy affect the decisions of consumers regarding the acquisition of private LTC policies as well as the level of protection chosen. This is particularly important to states interested in pursuing public-private partnerships in long-term care financing.

Actuarial Analysis↗

PubMed2002

Elastic deformation of membrane bilayers probed by deuterium NMR relaxation.

In deuterium ((2)H) NMR spectroscopy of fluid lipid bilayers, the average structure is manifested in the segmental order parameters (S(CD)) of the flexible molecules. The corresponding spin-lattice relaxation rates (R(1Z) depend on both the amplitudes and the rates of the segmental fluctuations, and indicate the types of lipid motions. By combining (2)H NMR order parameter measurements with relaxation studies, we have obtained a more comprehensive picture of lipids in the liquid-crystalline (L(alpha)) state than formerly possible. Our data suggest that a lipid bilayer constitutes an ordered fluid, in which the phospholipids are grafted to the aqueous interface via their polar headgroups, whereas the fatty acyl chains are in effect liquid hydrocarbon. Studies of (2)H-labeled saturated lipids indicate their R(1Z) rates and S(CD) order parameters are correlated by a model-free, square-law functional dependence, signifying the presence of relatively slow bilayer fluctuations. A new composite membrane deformation model explains simultaneously the frequency (magnetic field) dependence and the angular anisotropy of the relaxation. The results imply the R(1Z) rates are due to a broad spectrum of 3-D collective bilayer excitations, together with effective axial rotations of the lipids. For the first time, NMR relaxation studies show that the viscoelastic properties of membrane lipids at megahertz frequencies are modulated by the lipid acyl length (bilayer thickness), polar headgroups (bilayer interfacial area), inclusion of a nonionic detergent (C(12)E(8)), and the presence of cholesterol, leading to a range of bilayer softness. Our findings imply the concept of elastic deformation is relevant on lengths approaching the bilayer thickness and less (the mesoscopic scale), and suggest that application of combined R(1Z) and S(CD) studies of phospholipids can be used as a simple membrane elastometer. Heuristic estimates of the bilayer bending rigidity kappa and the area elastic modulus K(a) enable comparison to other biophysical studies, involving macroscopic deformation of thin membrane lipid films. Finally, the bilayer softness may be correlated with the lipid diversity of biomembranes, for example, with regard to membrane curvature, repulsive interactions between bilayers, and lipid-protein interactions.

Cholesterol↗

PubMed2000

Socio-economic status and the utilisation of physicians' services: results from the Canadian National Population Health Survey.

This paper assesses the extent to which Canada's universal health care system has eliminated socio-economic barriers in the use of physician services by examining the role of socio-economic status in the differential use of specific, publicly-insured, primary and specialist care services. Data from the 1994 National Population Health Survey, a nationally representative survey, were analysed using multiple logistic regression. In order to control for the association between primary and specialist utilisation, a two-staged least squares method was used for models explaining specialist utilisation. Health need, as measured by perceived health status and number of health problems, was found to be consistently associated with increased physician utilisation, for both primary and specialist visits. Whereas the likelihood of an individual making at least one visit to a primary care physician was found to be independent of income, those with lower incomes were more likely to be frequent users of primary care, that is, make at least six visits to a primary care physician. Even after adjusting for the greater utilisation of primary care services by those in lower socio-economic groups, and, therefore, their higher exposure to the risk of referral, the utilisation of specialist visits was greater for those in higher socio-economic groups. Canadians lacking a regular medical doctor were less likely to receive primary and specialist care, even after adjustments for socio-economic variables such as income and education. Although financial barriers may not directly impede access to health care services in Canada, differential use of physician services with respect to socio-economic status persists. After adjusting for differences in health need, Canadians with lower incomes and fewer years of schooling visit specialists at a lower rate than those with moderate or high incomes and higher levels of education attained despite the existence of universal health care.

Adolescent↗

PubMed2004

Reference values for insulin-like growth factor-binding protein-3 (IGFBP-3) and the ratio of insulin-like growth factor-I to IGFBP-3 throughout childhood and adolescence.

To facilitate the diagnosis of GH deficiency and monitor GH therapy, we constructed two reference models to allow comparison of serum IGF binding protein (IGFBP)-3 concentrations and IGF-I to IGFBP-3 ratios among children throughout childhood and adolescence. This report presents equations for determining the sd score of IGFBP-3 and IGF-I to IGFBP-3 measurements for individual patients. The data set contains serum values from 468 healthy children and adolescents (232 males, 236 females; ages 1.1-18.3 yr) whose height, weight, and body mass index were within +/- 3 sd of means. Puberty was classified according to breast development (B) and testicular volume into pre-, early, mid-, and late puberty. The values of IGFBP-3 and IGF-I to IGFBP-3 ratios were log transformed, and multiple linear regression analysis was used to identify models for converting serum concentrations into sd scores. The models include the variables of age, gender, and puberty and take into account the interactions among these variables. The best linear models explain 42% of the variation in serum IGFBP-3 concentrations and 50% of the variation in serum IGF-I to IGFBP-3 concentrations. The relationship between age and log(IGFBP-3) was positive for boys in pre-, early, and midpuberty. In late puberty, values were higher than earlier in puberty, and there was a negative relationship with age. For girls the relationship between age and log(IGFBP-3) also was positive in pre- and early puberty, with larger effect for girls older than 8 yr. Values for girls in midpuberty were relatively constant, and in late puberty values were higher than earlier in puberty, and there was a negative relationship with age. The relationship between age and log(IGF-I to IGFBP-3 ratio) was positive for boys in pre-, early, and early midpuberty (volume = 9-14 ml). In late midpuberty (volume = 15-19 ml), the relationship between age and IGF-I to IGFBP-3 ratio was negative. In late puberty, values were relatively constant and higher than earlier in puberty. For girls in prepuberty, the relationship with age was positive, with a larger effect in girls older than 8 yr. In early puberty, the girls' values were relatively constant. In early midpuberty (B = 3), log(IGF-I to IGFBP-3 ratio) values were higher for girls than boys of the same age. In late midpuberty (B = 4), the relationship with age was negative, and in late puberty values were relatively constant and higher than earlier in puberty.

Adolescent↗

PubMedDate not supplied

Do physicians do as they say? The case of mammography.

OBJECTIVE: To assess the utility of survey-based physician policy in predicting actual mammography ordering behavior, as measured by medical record abstraction. DESIGN: Cross-sectional survey of practicing community physicians. Responses were correlated with data abstracted from the medical records of patients in the practices of the participating physicians. PARTICIPANTS: Family and general practitioners in Washington State. Medical records of female patients aged 40 to 80 years provided data on actual mammography performance. MAIN OUTCOME MEASURES: The proportions of female patients aged 40 to 49 and 50 to 80 years who had received a screening mammogram within the previous 2 years. RESULTS: Of the more than 100 potential predictors available, only 4 were significantly associated with screening rates for women younger than 50 years and only 3 were associated with screening rates for older women. Regression models explained only 21% to 25% of the variance in screening rates. Physician estimates of screening rates were poorly correlated with actual screening rates. CONCLUSIONS: Practicing physicians do not know how well they screen their patients using mammography. Extensive survey data, including direct estimates of behavior, demographics, policy measures, and case scenario responses, were of limited use in predicting actual screening rates. Our results underscore the importance of using data rather than proxy measures to study physician performance.

Adult↗

PubMed2000

Fathers and child neglect.

OBJECTIVE: To examine the association between father involvement and child neglect. DESIGN: Cohort study. SETTING: Participants were recruited from an inner-city pediatric primary care clinic and a clinic for children at risk for human immunodeficiency virus infection in a teaching hospital. PARTICIPANTS: Mothers and fathers or father figures, and 244 five-year olds participating in a longitudinal study. MAIN OUTCOME MEASURES: Child neglect measured via home observation, a videotaped mother-child interaction, and child protective services reports. RESULTS: A father or father figure was identified for 72% of the children. Rates of neglect ranged between 11% and 30%. Father absence alone was not associated with neglect. However, in families with an identified and interviewed father, a longer duration of involvement (P<.01), a greater sense of parenting efficacy (P<.01), more involvement with household tasks (P<.05), and less involvement with child care (P<.05) were associated with less neglect. The overall model explained 26.5% of the variance in neglect. CONCLUSIONS: There is substantial involvement of fathers in a subset of this high-risk sample, although more than a quarter of the children lacked a father or father figure. The mere presence of a father did not significantly influence the neglect of the children; rather, the nature of his involvement did. Fathers who felt more effective as parents were less likely to have neglected their children. A greater sense of efficacy may reflect parenting skills and be important in enhancing the contribution of fathers to their children's well-being. Pediatric health care providers can play a valuable role in enhancing the involvement and skills of fathers.

Child Abuse↗

PubMed1989

A market analysis comparing the practices of psychiatrists and psychologists.

Data are analyzed that describe the clinical work of representative samples of psychiatrists and clinical psychologists who practiced in one of 62 markets for mental health services in the United States during 1982 and 1983. For psychiatrists, intensity of treatment (ie, mean face-to-face treatment minutes per patient per month) varied from 107 to 368 minutes vs 124 to 283 minutes for psychologists. Multiple regression models explain these variations somewhat differently for each provider group. Whereas the patient's severity or stage of illness is explanatory for both psychiatrists and psychologists, only psychologists appear to alter intensity of treatment in response to local economic conditions. Psychiatrists have large diversified practices, whereas psychologists tend to treat fewer persons and the bulk of these have less severe mental and emotional conditions. Neither practitioner group appeared to provide services in excess of their perceptions of patient need. These and other important similarities and differences are explored, and the advantages of local market focus for examining relevant public policy issues are discussed.

Female↗

PubMed1997

Traction fibre: toward a "tensegral" model of the spindle.

Most current hypotheses of mitotic mechanisms are based on the "PAC-MAN" paradigm in which chromosome movement is generated and powered by disassembly of kinetochore microtubules (k-MTs) by the kinetochore. Recent experiments demonstrate that this model cannot explain force generation for anaphase chromosome movement [Pickett-Heaps et al., 1996: Protoplasma 192:1-10]. Another such experiment is described here: a UV-microbeam cut several kinetochore fibres (k-fibres) in newt epithelial cells at metaphase and the half-spindle immediately shortened: in several cells, the remaining intact spindle fibres bowed outwards as they came under increased compression. Thus, severing of k-MTs can lead to increased tension between chromosomes and poles. This observation cannot be explained by models in which force is produced by motor molecules at the kinetochore actively disassembling k-MTs. Rather, we argue that tensile forces act along the whole k-fibre, which, therefore, can be considered as a classic "traction fibre." We suggest that anaphase polewards force is generated by MTs interacting with the spindle matrix and when k-MTs are severed, polewards force continues to act on the remaining kMT-stub; spindle MTs act as rigid struts concurrently resisting and being controlled by these forces. We suggest that the principles of "cellular tensegrity" [Ingber, 1993: J. Cell Sci. 104:613-627] derived from the behaviour and organization of the interphase cell apply to the spindle. In an evolutionary context, this argument further suggests that the spindle might originally have evolved as the mechanism by which a single tensegral unit (cytoplast) is divided into two cytoplasts; use of the spindle for segregating chromosomes might represent a secondary, more recent development of this primary function. If valid, this concept has implications for the way the spindle functions and for the spindle's relationship to cytokinesis.

Animals↗