Maintaining clearance in peritoneal dialysis

Numerous studies have now established that there is a strong association between small solute clearance and improved outcomes in peritoneal dialysis (PD) patients. Preservation of both renal and peritoneal clearances is therefore of paramount importance, although very few trials have satisfactorily addressed this critical issue. Observational studies have suggested that the groups most at risk of loss of residual renal function are women, non-whites, diabetic patients, patients with congestive cardiac failure, patients who experience frequent episodes of peritonitis and, possibly, patients treated with automated PD (APD). There have been no controlled trials of renoprotective therapies in PD patients, but reasonable strategies for preventing renal functional decline include avoidance of nephrotoxins and infection, maintenance of adequate blood pressure, abstinence from smoking and possibly administration of angiotensin-converting enzyme inhibitors and/or calcium channel blockers. In contrast, peritoneal small solute removal can be maximized by augmenting fill volume, increasing exchange frequency and using either long-dwell continuous ambulatory PD (CAPD) or short-dwell (APD) therapies to suit individual patients' transport characteristics. Tidal PD may additionally increase solute clearance, although studies have reported conflicting findings. Preservation of membrane function may be achieved by minimizing episodes of peritonitis and avoiding hypertonic glucose exchanges. Newer peritoneal dialysates, such as icodextrin, amino acids, bicarbonate-buffered solutions and aldehyde-poor fluids, are more biocompatible in experimental models of PD, but their long-term clinical safety and efficacy have not yet been established by clinical trials. Moreover, no trials have demonstrated an independent effect of peritoneal clearance on patient outcomes. Further studies determining the relative value of renal and peritoneal clearances are therefore urgently required in order to optimize dialytic adequacy for PD patients.

Analysis of thermodynamic non-ideality in terms of protein solvation

The effects of thermodynamic non-ideality on the forms of sedimentation equilibrium distributions for several isoelectric proteins have been analysed on the statistical-mechanical basis of excluded volume to obtain an estimate of the extent of protein solvation. Values of the effective solvation. parameter delta are reported for ellipsoidal as well as spherical models of the proteins, taken to be rigid, impenetrable macromolecular structures. The dependence of the effective solvated radius upon protein molecular mass exhibits reasonable agreement with the relationship calculated for a model in which the unsolvated protein molecule is surrounded by a 0.52-nm solvation shell. Although the observation that this shell thickness corresponds to a double layer of water molecules may be of questionable relevance to mechanistic interpretation of protein hydration, it augurs well for the assignment of magnitudes to the second virial coefficients of putative complexes in the quantitative characterization of protein-protein interactions under conditions where effects of thermodynamic non-ideality cannot justifiably be neglected. (C) 2001 Elsevier Science B.V. All rights reserved.

Studies of solute self-association by sedimentation equilibrium: allowance for effects of thermodynamic non-ideality beyond the consequences of nearest-neighbor interactions

A sedimentation equilibrium study of a-chymotrypsin self-association in acetate-chloride buffer, pH 4.1 I 0.05, has been used to illustrate determination of a dimerization constant under conditions where thermodynamic non-ideality is manifested beyond the consequences of nearest-neighbor interactions. Because the expressions for the experimentally determinable interaction parameters comprise a mixture of equilibrium constant and excluded volume terms, the assignment of reasonable magnitudes to the relevant virial coefficients describing non-associative cluster formation is essential for the evaluation of a reliable estimate of the dimerization constant. Determination of these excluded volume parameters by numerical integration over the potential-of-mean-force is shown to be preferable to their calculation by approximate analytical solutions of the integral for this relatively small enzyme monomer with high net charge (+ 10) under conditions of low ionic strength (0.05 M). (C) 2001 Elsevier Science B.V. All rights reserved.

Three-dimensional orthotropic viscoelastic finite element model of a human ligament

Ligaments undergo finite strain displaying hyperelastic behaviour as the initially tangled fibrils present straighten out, combined with viscoelastic behaviour (strain rate sensitivity). In the present study the anterior cruciate ligament of the human knee joint is modelled in three dimensions to gain an understanding of the stress distribution over the ligament due to motion imposed on the ends, determined from experimental studies. A three dimensional, finite strain material model of ligaments has recently been proposed by Pioletti in Ref. [2]. It is attractive as it separates out elastic stress from that due to the present strain rate and that due to the past history of deformation. However, it treats the ligament as isotropic and incompressible. While the second assumption is reasonable, the first is clearly untrue. In the present study an alternative model of the elastic behaviour due to Bonet and Burton (Ref. [4]) is generalized. Bonet and Burton consider finite strain with constant modulii for the fibres and for the matrix of a transversely isotropic composite. In the present work, the fibre modulus is first made to increase exponentially from zero with an invariant that provides a measure of the stretch in the fibre direction. At 12% strain in the fibre direction, a new reference state is then adopted, after which the material modulus is made constant, as in Bonet and Burton's model. The strain rate dependence can be added, either using Pioletti's isotropic approximation, or by making the effect depend on the strain rate in the fibre direction only. A solid model of a ligament is constructed, based on experimentally measured sections, and the deformation predicted using explicit integration in time. This approach simplifies the coding of the material model, but has a limitation due to the detrimental effect on stability of integration of the substantial damping implied by the nonlinear dependence of stress on strain rate. At present, an artificially high density is being used to provide stability, while the dynamics are being removed from the solution using artificial viscosity. The result is a quasi-static solution incorporating the effect of strain rate. Alternate approaches to material modelling and integration are discussed, that may result in a better model.

Diet, lifestyle and the risk of Type 2 Diabetes Mellitus in women

Background Previous studies have examined individual dietary and lifestyle factors in relation to type 2 diabetes, but the combined effects of these factors are largely unknown. Methods We followed 84,941 female nurses from 1980 to 1996; these women were free of diagnosed cardiovascular disease, diabetes, and cancer at base line. Information about their diet and lifestyle was updated periodically. A low-risk group was defined according to a combination of five variables: a body-mass index (the weight in kilograms divided by the square of the height in meters) of less than 25; a diet high in cereal fiber and polyunsaturated fat and low in trans fat and glycemic load (which reflects the effect of diet on the blood glucose level); engagement in moderate-to-vigorous physical activity for at least half an hour per day; no current smoking; and the consumption of an average of at least half a drink of an alcoholic beverage per day. Results During 16 years of follow-up, we documented 3300 new cases of type 2 diabetes. Overweight or obesity was the single most important predictor of diabetes. Lack of exercise, a poor diet, current smoking, and abstinence from alcohol use were all associated with a significantly increased risk of diabetes, even after adjustment for the body-mass index. As compared with the rest of the cohort, women in the low-risk group (3.4 percent of the women) had a relative risk of diabetes of 0.09 (95 percent confidence interval, 0.05 to 0.17). A total of 91 percent of the cases of diabetes in this cohort (95 percent confidence interval, 83 to 95 percent) could be attributed to habits and forms of behavior that did not conform to the low-risk pattern. Conclusions Our findings support the hypothesis that the majority of cases of type 2 diabetes could be prevented by the adoption of a healthier lifestyle.

Attachment style and coping resources as predictors of coping strategies in the transition to parenthood

The relations among adult attachment style, coping resources, appraised strain, and coping strategies were examined in a prospective study of married couples having their first child (N = 92). Attachment and coping resources were measured during the second trimester of pregnancy, and parenting strain and coping strategies were assessed when the babies were about 6 weeks old. Results supported a theoretical model proposing that attachment is predictive of coping resources and appraised strain, and that attachment, resources, and strain are predictive of coping strategies. Results also highlighted the complexity of associations among attachment, stress, and coping: Gender differences in mean scores and predictive associations were obtained, and some interactions were found between resources and strain in predicting coping strategies. The findings support the utility of integrating theories of attachment and coping in explaining couples' adjustment to important developmental transitions.

The leisure satisfaction of people with psychiatric disabilities

Leisure plays a dynamic role in peoples' lives and it would be useful to know how the satisfaction gained from leisure choices relates to personal and social adjustment, mental health and life satisfaction for people with psychiatric ability. Lloyd et al identify the extent of satisfaction derived from leisure activities for people with a mental illness and determine whether or not a standardized measure of leisure satisfaction can be applied to a population of people with mental illness.

Gender stereotypes and drinking cognitions as indicators of moderate and high risk drinking among young women and men

The study examined differences in gender stereotypes, restrained drinking and self-efficacy for alcohol refusal between moderate and high risk drinkers among a university sample of 301 women and 118 men. Both female and male high risk drinkers displayed a response conflict, typified by high scores on restrained drinking but low scores on self-efficacy. This pattern of response conflict was more pronounced for high risk drinking women, who also identified poorly with feminine trails (e.g. 'nurturing', 'love children', 'appreciative'). The findings are discussed in relation to society's double standard that accepts intoxication in men but condemns it in women. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Aluminophosphate-based mesoporous molecular sieves: Synthesis and characterization of TAPOs

Mesoporous Ti-substituted aluminophosphates (AlPOs) with a hexagonal, cubic and lamellar pore structure, characteristic of MCM-41, MCM-48, and MCM-50, respectively, were synthesized. The stability of these mesophases upon template removal was studied. The pore structures, surface properties, and local atom environments of Al, P, and Ti of the hexagonal and cubic Ti-containing mesoporous products were extensively characterized using X-ray diffraction, magic angle spinning nuclear magnetic resonance, AAS, XPS, ultraviolet–visible, and adsorption of nitrogen and water vapor techniques while the lamellar mesophase was not further characterized due to its very poor thermal stability. Ti-containing mesoporous AlPO materials show a reasonable thermal stability upon template removal, a hydrophilic surface property, and high porosity showing application potentials in catalytic oxidation of hydrocarbons.

The validity of an Australian modification of the AUDIT questionnaire

The Alcohol Use Disorders Identification Test (AUDIT) has been used widely and is reported to be superior to conventional questionnaires in detection of current hazardous and harmful alcohol use. We assessed the validity of an Australian modification of the AUDIT (the AusAUDIT), which has been employed widely in Australian and New Zealand early intervention programmes. We used a cross-sectional study of 370 subjects from the follow-up phase of a randomized controlled trial of early intervention to reduce hazardous alcohol consumption. Scores on the AusAUDIT were compared against 12-month ICD-10 diagnoses of harmful alcohol use and dependence, as determined by the Composite International Diagnostic Interview, and against self-report of alcohol consumption exceeding Australian National Health and Medical Research Council (NH&MRC) recommended limits. AusAUDIT had good internal consistency and discriminated significantly between persons meeting criteria for ICD-10 alcohol use disorders, and drinkers who did not. At currently recommended cut-off scores, AusAUDIT detected more than 85% of people meeting criteria for ICD-10 alcohol use disorders, or drinking over NH&MRC recommended limits, but its specificity was limited (29% in men, and 58% in women for drinking over NH&MRC limits). No subset of questions performed as well as the full AusAUDIT in detection of drinking problems, but the alcohol consumption items provided a reasonable screen for drinking over NH&MRC limits. We conclude that AusAUDIT is effective in detecting problematic drinking, but positive cases should be confirmed by clinical assessment. The findings illustrate the need for validation of questionnaire modifications, and the difficulty in increasing test sensitivity without reducing specificity.

Power of the joint segregation analysis method for testing mixed major-gene and polygene inheritance models of quantitative traits

Understanding the genetic architecture of quantitative traits can greatly assist the design of strategies for their manipulation in plant-breeding programs. For a number of traits, genetic variation can be the result of segregation of a few major genes and many polygenes (minor genes). The joint segregation analysis (JSA) is a maximum-likelihood approach for fitting segregation models through the simultaneous use of phenotypic information from multiple generations. Our objective in this paper was to use computer simulation to quantify the power of the JSA method for testing the mixed-inheritance model for quantitative traits when it was applied to the six basic generations: both parents (P-1 and P-2), F-1, F-2, and both backcross generations (B-1 and B-2) derived from crossing the F-1 to each parent. A total of 1968 genetic model-experiment scenarios were considered in the simulation study to quantify the power of the method. Factors that interacted to influence the power of the JSA method to correctly detect genetic models were: (1) whether there were one or two major genes in combination with polygenes, (2) the heritability of the major genes and polygenes, (3) the level of dispersion of the major genes and polygenes between the two parents, and (4) the number of individuals examined in each generation (population size). The greatest levels of power were observed for the genetic models defined with simple inheritance; e.g., the power was greater than 90% for the one major gene model, regardless of the population size and major-gene heritability. Lower levels of power were observed for the genetic models with complex inheritance (major genes and polygenes), low heritability, small population sizes and a large dispersion of favourable genes among the two parents; e.g., the power was less than 5% for the two major-gene model with a heritability value of 0.3 and population sizes of 100 individuals. The JSA methodology was then applied to a previously studied sorghum data-set to investigate the genetic control of the putative drought resistance-trait osmotic adjustment in three crosses. The previous study concluded that there were two major genes segregating for osmotic adjustment in the three crosses. Application of the JSA method resulted in a change in the proposed genetic model. The presence of the two major genes was confirmed with the addition of an unspecified number of polygenes.

Role of cytokine gene polymorphisms in acute rejection and renal impairment after liver transplantation

Although immunosuppressive regimens are effective, rejection occurs in up to 50% of patients after orthotopic liver transplantation (OLT), and there is concern about side effects from long-term therapy. Knowledge of clinical and immunogenetic variables may allow tailoring of immunosuppressive therapy to patients according to their potential risks. We studied the association between transforming growth factor-beta, interleukin-10, and tumor necrosis factor alpha (TNF-alpha) gene polymorphisms and graft rejection and renal impairment in 121 white liver transplant recipients. Clinical variables were collected retrospectively, and creatinine clearance was estimated using the formula of Cockcroft and Gault. Biallelic polymorphisms were detected using polymerase chain reaction-based methods. Thirty-seven of 121 patients (30.6%) developed at least 1 episode of rejection. Multivariate analysis showed that Child-Pugh score (P =.001), immune-mediated liver disease (P =.018), normal pre-OLT creatinine clearance (P =.037), and fewer HLA class 1 mismatches (P =.038) were independently associated with rejection, Renal impairment occurred in 80% of patients and was moderate or severe in 39%, Clinical variables independently associated with renal impairment were female sex (P =.001), pre-OLT renal dysfunction (P =.0001), and a diagnosis of viral hepatitis (P =.0008), There was a significant difference in the frequency of TNF-alpha -308 alleles among the primary liver diseases. After adjustment for potential confounders and a Bonferroni correction, the association between the TNF-alpha -308 polymorphism and graft rejection approached significance (P =.06). Recipient cytokine genotypes do not have a major independent role in graft rejection or renal impairment after OLT, Additional studies of immunogenetic factors require analysis of large numbers of patients with appropriate phenotypic information to avoid population stratification, which may lead to inappropriate conclusions.

Mining wheat germplasm collections for yield enhancing traits

The material in genebanks includes valuable traditional varieties and landraces, non-domesticated species, advanced and obsolete cultivars, breeding lines and genetic stock. It is the wide variety of potentially useful genetic diversity that makes collections valuable. While most of the yield increases to date have resulted from manipulation of a few major traits (such as height, photoperiodism, and vernalization), meeting future demand for increased yields will require exploitation of novel genetic resources. Many traits have been reported to have potential to enhance yield, and high expression of these can be found in germplasm collections. To boost yield in irrigated situations, spike fertility must be improved simultaneously with photosynthetic capacity. CIMMYT's Wheat Genetic Resources program has identified a source of multi-ovary florets, with up to 6 kernels per floret. Lines from landrace collections have been identified that have very high chlorophyll concentration, which may increase leaf photosynthetic rate. High chlorophyll concentration and high stomatal conductance are associated with heat tolerance. Recent studies, through augmented use of seed multiplication nurseries, identified high expression of these traits in bank accessions, and both traits were heritable. Searches are underway for drought tolerance traits related to remobilization of stem fructans, awn photosynthesis, osmotic adjustment, and pubescence. Genetic diversity from wild relatives through the production of synthetic wheats has produced novel genetic diversity.

Helping the female partners of men abusing alcohol: a comparison of three treatments

Aim. To evaluate the effectiveness of three approaches to assisting the female partners of male problem drinkers with the stress imposed by the male's drinking. Design. Participants were assigned randomly via random number tables to one of three treatment conditions: supportive counselling, stress management or alcohol-focused couples therapy. Setting. The intervention took place at the Behaviour Research and Therapy Centre (BRTC), The University of Queensland. This research and training centre offers outpatient psychology services to the community. Participants. Sixty-one married women whose husbands drank heavily. Participants reported protracted alcohol problems, severe impact of alcohol on social functioning and severe marital distress. Measurement. The women's stress, alcohol consumption by the male, and relationship functioning were assessed at pre- and post-treatment and at 6-month follow-up. Interventions. All three treatments involved 15 1-hour sessions with the woman. In the alcohol-focused couple therapy, attempts were made to engage the man in these sessions. Results. Contrary to our predictions, there were few differences between the treatments. All three treatments were associated with reductions in the women's reported stress, with trends for somewhat greater reduction in the women's stress in the stress management and alcohol-focused couples therapy conditions than for supportive counselling. None of the treatments produced clinically significant reductions in men's drinking or relationship distress. Conclusion. The treatments ease stresses and burden but do not improve drinking or relationships. Limited power in the design restricted the capacity to detect differential treatment effects.

A cross-sectional study of the association between Heberden's nodes, radiographic osteoarthritis of the hands, grip strength, disability and pain

Objective: To describe the associations between hand osteoarthritis (OA), pain and disability in males and females and to further validate the Australian/Canadian CA hand index (AUSCAN LK3.0). Design: Cross-sectional study of 522 subjects from 101 Tasmanian families (males N=174, females N=348). Hand OA was assessed by two observers using the Altman atlas for joint space narrowing and osteophytes at distal interphalangeal and first carpometacarpal joints as well as a score for Heberden's nodes based on hand photography. Hand pain and function were assessed by the AUSCAN LK3.0 and grip strength by dynamometry in both hands on two occasions. Results: The prevalence of hand CA was high in this sample at 44-71% (depending on site). Pain and dysfunction increased with age while grip strength decreased (all P <0.001). All three measures were markedly worse in women, even after taking the severity of arthritis into account. Hand CA explained 5.7-10% of the variation in function, grip strength and pain scores, even after adjustment for age and sex. Further adjustment suggested that the osteoarthritic associations with function and grip strength were largely mediated by pain. Severity of disease was more strongly associated with these scores than presence or absence. Lastly, the AUSCAN LK3.0 showed a comparable association to grip strength with structural damage providing further evidence of index validity. Conclusions: Hand CA at these two sites makes substantial contributions to hand function, strength and pain. The associations with function and strength measures appear mediated by pain. Gender differences in all three measures persist after adjustment for variation in age and CA severity indicating that factors apart from radiographic disease are responsible. (C) 2001 OsteoArthritis Research Society International.