Defining the buffering process by a triprotic acid without relying on stewart-electroneutrality considerations

Upon the addition of protons to an aqueous solution, a component of the H+ load will be bound i.e. buffered. In an aqueous solution containing a triprotic acid, H+ can be bound to three different states of the acid as well as to OH- ions that are derived from the auto-ionization of H2O. In quantifying the buffering process of a triprotic acid, one must define the partitioning of H+ among the three states of the acid and also the OH- ions in solution in order to predict the equilibrium pH value. However, previous quantitative approaches that model triprotic acid titration behaviour and used to predict the equilibrium pH rely on the mathematical convenience of electroneutrality/charge balance considerations. This fact has caused confusion in the literature, and has led to the assumption that charge balance/electroneutrality is a causal factor in modulating proton buffering (Stewart formulation). However, as we have previously shown, although charge balance can be used mathematically as a convenient tool in deriving various formulae, electroneutrality per se is not a fundamental physicochemical parameter that is mechanistically involved in the underlying buffering and proton transfer reactions. The lack of distinction between a mathematical tool, and a fundamental physicochemical parameter is in part a reason for the current debate regarding the Stewart formulation of acid-base analysis. We therefore posed the following question: Is it possible to generate an equation that defines and predicts the buffering of a triprotic acid that is based only on H+ partitioning without incorporating electroneutrality in the derivation? Towards this goal, we derived our new equation utilizing: 1) partitioning of H+ buffering; 2) conservation of mass; and 3) acid-base equilibria. In validating this model, we compared the predicted equilibrium pH with the measured pH of an aqueous solution consisting of Na2HPO4 to which HCl was added. The measured pH values were in excellent agreement with the predictions of our equation. Our results provide further important evidence that one can mathematically model the chemistry of acid-base phenomenology without relying on electroneutrality (Stewart formulation) considerations

Knowledge, attitude and skills before and after a module on pharmaceutical promotion in a Nepalese medical school

<p>Abstract</p> <p>Background</p> <p>Pharmaceutical promotion is widespread and can impact prescribing by health professionals. Little research has been conducted on interactions between medical students and the pharmaceutical industry. Teaching about pharmaceutical promotion is inadequate. A survey showed that many schools spend only about two hours teaching this important topic while others spend around six hours. Recently a manual on understanding and responding to promotion has been published by Health Action International (HAI) and the World Health Organization (WHO). From April to August 2011 the department of Clinical Pharmacology at KIST Medical College, Lalitpur, Nepal conducted a module on pharmaceutical promotion for second year students based on the manual. The module used active learning strategies such as brainstorming sessions, role plays and group activities. The study worked on the hypothesis that a module on pharmaceutical promotion will be effective in improving the knowledge, attitude and skills of medical students regarding pharmaceutical promotion. The impact of the module on knowledge, attitude and skills was tested using a retrospective-pre questionnaire. The scores according to gender and method of financing of medical education before and after the module were compared using appropriate non-parametric tests.</p> <p>Results</p> <p>Eighty-seven of the 100 second year students (87%) participated in the study. 47 were females (54%) and 39 (44.83%) were males and one did not state the gender. Seventy-seven students (88.5%) were self-financing while 9 were scholarship students. The median knowledge, attitude and skills score before the module were 9, 13 and 6 respectively while the overall score was 28. The scores increased significantly to 16, 15 and 14 respectively after the module while the overall score increased to 45. The median attitude scores and total scores were significantly higher among females both before and after the module. The scores did not vary with method of financing of medical education. All scores increased significantly at the end of the module.</p> <p>Conclusions</p> <p>The nine hour module held over a period of four months was effective in improving respondents' knowledge, attitudes and skills about pharmaceutical promotion. The module was not resource intensive and used resources already available in the institution. Similar modules can be considered in other medical and health profession schools in Nepal, South Asia and other developing countries.</p

Variable selection for large p small n regression models with incomplete data: Mapping QTL with epistases

<p>Abstract</p> <p>Background</p> <p>Identifying quantitative trait loci (QTL) for both additive and epistatic effects raises the statistical issue of selecting variables from a large number of candidates using a small number of observations. Missing trait and/or marker values prevent one from directly applying the classical model selection criteria such as Akaike's information criterion (AIC) and Bayesian information criterion (BIC).</p> <p>Results</p> <p>We propose a two-step Bayesian variable selection method which deals with the sparse parameter space and the small sample size issues. The regression coefficient priors are flexible enough to incorporate the characteristic of "large <it>p </it>small <it>n</it>" data. Specifically, sparseness and possible asymmetry of the significant coefficients are dealt with by developing a Gibbs sampling algorithm to stochastically search through low-dimensional subspaces for significant variables. The superior performance of the approach is demonstrated via simulation study. We also applied it to real QTL mapping datasets.</p> <p>Conclusion</p> <p>The two-step procedure coupled with Bayesian classification offers flexibility in modeling "large p small n" data, especially for the sparse and asymmetric parameter space. This approach can be extended to other settings characterized by high dimension and low sample size.</p

Multiple ITS Copies Reveal Extensive Hybridization within Rheum (Polygonaceae), a Genus That Has Undergone Rapid Radiation

During adaptive radiation events, characters can arise multiple times due to parallel evolution, but transfer of traits through hybridization provides an alternative explanation for the same character appearing in apparently non-sister lineages. The signature of hybridization can be detected in incongruence between phylogenies derived from different markers, or from the presence of two divergent versions of a nuclear marker such as ITS within one individual.In this study, we cloned and sequenced ITS regions for 30 species of the genus Rheum, and compared them with a cpDNA phylogeny. Seven species contained two divergent copies of ITS that resolved in different clades from one another in each case, indicating hybridization events too recent for concerted evolution to have homogenised the ITS sequences. Hybridization was also indicated in at least two further species via incongruence in their position between ITS and cpDNA phylogenies. None of the ITS sequences present in these nine species matched those detected in any other species, which provides tentative evidence against recent introgression as an explanation. Rheum globulosum, previously indicated by cpDNA to represent an independent origin of decumbent habit, is indicated by ITS to be part of clade of decumbent species, which acquired cpDNA of another clade via hybridization. However decumbent and glasshouse morphology are confirmed to have arisen three and two times, respectively.These findings suggested that hybridization among QTP species of Rheum has been extensive, and that a role of hybridization in diversification of Rheum requires investigation

Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women

Endometriosis is a disorder that affects 5% of the normal population but is present in up to 40% of women with pelvic pain and/or infertility. Recent evidence suggests that the endometrium of women with endometriosis exhibits progesterone insensitivity. One endometrial protein that fluctuates in response to progesterone is the estrogen receptor-alpha (ER alpha), being down-regulated at the time of peak progesterone secretion during the window of implantation. Here we demonstrate that the biomarker of uterine receptivity, beta 3 integrin subunit, is reduced or absent in some women with endometriosis and that such defects are accompanied by inappropriate over-expression of ER alpha during the mid-secretory phase. Using a well-differentiated endometrial cell line we showed that the beta 3 integrin protein is negatively regulated by estrogen and positively regulated by epidermal growth factor (EGF). By competing against estrogen with various selective estrogen receptor modulators (SERMs) and estrogen receptor agonists and antagonists, inhibition of expression of the beta 3 integrin by estrogen can be mitigated. In conclusion, we hypothesize that certain types of uterine receptivity defects may be caused by the loss of appropriate ER alpha down-regulation in the mid-secretory phase, leading to defects in uterine receptivity. Such changes might be effectively treated by timely administration of the appropriate anti-estrogens to artificially block ER alpha and restore normal patterns of gene expression. Such treatments will require further clinical studies

Lattice Boltzmann simulations of soft matter systems

This article concerns numerical simulations of the dynamics of particles immersed in a continuum solvent. As prototypical systems, we consider colloidal dispersions of spherical particles and solutions of uncharged polymers. After a brief explanation of the concept of hydrodynamic interactions, we give a general overview over the various simulation methods that have been developed to cope with the resulting computational problems. We then focus on the approach we have developed, which couples a system of particles to a lattice Boltzmann model representing the solvent degrees of freedom. The standard D3Q19 lattice Boltzmann model is derived and explained in depth, followed by a detailed discussion of complementary methods for the coupling of solvent and solute. Colloidal dispersions are best described in terms of extended particles with appropriate boundary conditions at the surfaces, while particles with internal degrees of freedom are easier to simulate as an arrangement of mass points with frictional coupling to the solvent. In both cases, particular care has been taken to simulate thermal fluctuations in a consistent way. The usefulness of this methodology is illustrated by studies from our own research, where the dynamics of colloidal and polymeric systems has been investigated in both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures, 76 page

The Beck Cognitive Insight Scale (BCIS): translation and validation of the Taiwanese version

<p>Abstract</p> <p>Background</p> <p>Over the last few decades, research concerning the insight of patients with schizophrenia and its relationships with other clinical variables has been given much attention in the clinical setting. Since that time, a series of instruments assessing insight have been developed. The purpose of this study was to examine the reliability and validity of the Taiwanese version of the Beck Cognitive Insight Scale (BCIS). The BCIS is a self-administered instrument designed to evaluate cognitive processes that involves reevaluating patients' anomalous experiences and specific misinterpretations.</p> <p>Methods</p> <p>The English language version of the BCIS was translated into Taiwanese for use in this study. A total of 180 subjects with and without psychosis completed the Taiwanese version of the BCIS and additional evaluations to assess researcher-rated insight scales and psychopathology. Psychometric properties (factor structures and various types of reliability and validity) were assessed for this translated questionnaire.</p> <p>Results</p> <p>Overall, the Taiwanese version of the BCIS showed good reliability and stability over time. This translated scale comprised a two-factor solution corresponding to reflective attitude and certain attitude subscales. Following the validation of the internal structure of the scale, we obtained an R-C (reflective attitude minus certain attitude) index of the translated BCIS, representing the measurement of cognitive insight by subtracting the score of the certain attitude subscale from that of the reflective attitude subscale. As predicted, the differences in mean reflective attitude, certain attitude and R-C index between subjects with and without psychosis were significant. Our data also demonstrated that psychotic patients were significantly less reflective, more confident in their beliefs, and had less cognitive insight compared with nonpsychotic control groups.</p> <p>Conclusions</p> <p>In light of these findings, we believe that the Taiwanese version of BCIS is a valid and reliable instrument for the assessment of cognitive insight in psychotic patients.</p