Valence Force Fields as a Tool in Vibrational Spectroscopy and Molecular Mechanics

Force field calculations on conjugated molecules are discussed. The discussion is based on the experience of a series of overlay calculations, recently carried out, where the transferability of force constants was thoroughly studied. Successful applications as well as limitations of the constructed force field are described. The effects of nonbonded interactions are recognized as the most serious restriction of the transferability of valence force fields, and it is suggested that the molecular mechanics method, where the nonbonded interactions are taken explicitly into account, would be advantageous. The treatment of potential energy in the molecular mechanics method is briefly described and theconnections between valence force constants and potential energy parameters in this method are discussed

Conversion of ab-initio force fields and structures to molecular mechanics energy functions

The rapid development of computers in recent years has brought increasingly complex compounds into the range of high level ab-initio calculations. Such calculations produce valuable results which in many cases would be difficult or even impossible to obtain, with comparable accuracy, in any other way (Fogarasi & Pulay, Annu. Rev. Phys. Chem. 35, 191, 1984). Thus, it is highly desirable to be able to utilize these results in the construction of potential energy functions used in molecular mechanics (MM), molecular dynamics and Monte-Carlo calculations. For instance, the significance of quadratic cross terms in MM energy functions is still insufficiently explored (Lii & Allinger, J. Am. Chem. Soc. 111, 8566, 1989). In order to make possible the complete utilization of ab-initio results in MM calculations, we have developed a method by which scaled ab-initio (or empirical) force fields and structures can be directly converted to MM potential energy parameters, without sacrificing any of the original accuracy with regard to vibrational frequencies or structure. Here we briefly outline the conversion procedure, a more complete analysis being published separately.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29587/1/0000676.pd

Optimization of parameters of nonbonded interactions in a spectroscopically determined force field

A procedure is given by which parameters of nonbonded interactions in a molecular mechanics energy function can be optimized for maximum compatibility with ab initio force fields and structures. The method is based on a previously derived transformation of ab initio valence parameters to the molecular mechanics formalism. Explicit analytical expressions for the derivatives of the molecular mechanics force constants and reference geometry parameters with respect to the parameters of the nonbonded interactions are derived. The form of the goodness-of-fit function is discussed. A first application to a set of alanine dipeptides is described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30924/1/0000594.pd

Utilization of overlay and AB initio force fields in the construction of empirical potential energy functions for conjugated molecules

The optimization of the parameters in the molecular mechanics method is discussed. The utilization of spectroscopic force fields is described, and the advantages of utilizing molecular symmetry in the optimization of the parameters on the vibrational frequencies are stressed. The development of the potential functions for the benzene ring and for the vinyl group is briefly described, and the the application of these functions to calculate the geometry of the styrene molecule is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28713/1/0000534.pd

Response rates and selection problems, with emphasis on mental health variables and DNA sampling, in large population-based, cross-sectional and longitudinal studies of adolescents in Norway

Background Selection bias is a threat to the internal validity of epidemiological studies. In light of a growing number of studies which aim to provide DNA, as well as a considerable number of invitees who declined to participate, we discuss response rates, predictors of lost to follow-up and failure to provide DNA, and the presence of possible selection bias, based on five samples of adolescents. Methods We included nearly 7,000 adolescents from two longitudinal studies of 18/19 year olds with two corresponding cross-sectional baseline studies at age 15/16 (10th graders), and one cross-sectional study of 13th graders (18/19 years old). DNA was sampled from the cheek mucosa of 18/19 year olds. Predictors of lost to follow-up and failure to provide DNA were studied by Poisson regression. Selection bias in the follow-up at age 18/19 was estimated through investigation of prevalence ratios (PRs) between selected exposures (physical activity, smoking) and outcome variables (general health, mental distress, externalizing problems) measured at baseline. Results Out of 5,750 who participated at age 15/16, we lost 42% at follow-up at age 18/19. The percentage of participants who gave their consent to DNA provision was as high as the percentage that consented to a linkage of data with other health registers and surveys, approximately 90%. Significant predictors of lost to follow-up and failure to provide DNA samples in the present genetic epidemiological study were: male gender; non-western ethnicity; postal survey compared with school-based; low educational plans; low education and income of father; low perceived family economy; unmarried parents; poor self-reported health; externalized symptoms and smoking, with some differences in subgroups of ethnicity and gender. The association measures (PRs) were quite similar among participants and all invitees, with some minor discrepancies in subgroups of non-western boys and girls. Conclusions Lost to follow-up had marginal impact on the estimated prevalence ratios. It is not likely that the invitation to provide DNA influenced the response rates of 18/19 year olds. Non-western ethnicity, male gender and characteristics related to a low social class and general and mental health problems measured at baseline are associated with lost to follow-up and failure to provide DNA

Randomised comparison of provisional side branch stenting versus a two-stent strategy for treatment of true coronary bifurcation lesions involving a large side branch: the Nordic-Baltic Bifurcation Study IV

Background It is still uncertain whether coronary bifurcations with lesions involving a large side branch (SB) should be treated by stenting the main vessel and provisional stenting of the SB (simple) or by routine two-stent techniques (complex). We aimed to compare clinical outcome after treatment of lesions in large bifurcations by simple or complex stent implantation.Methods The study was a randomised, superiority trial. Enrolment required a SB >= 2.75 mm, >= 50% diameter stenosis in both vessels, and allowed SB lesion length up to 15 mm. The primary endpoint was a composite of cardiac death, non-procedural myocardial infarction and target lesion revascularisation at 6 months. Two-year clinical follow-up was included in this primary reporting due to lower than expected event rates.Results A total of 450 patients were assigned to simple stenting (n = 221) or complex stenting (n=229) in 14 Nordic and Baltic centres. Two-year follow-up was available in 218 (98.6%) and 228 (99.5%) patients, respectively. The primary endpoint of major adverse cardiac events (MACE) at 6 months was 5.5% vs 2.2% (risk differences 3.2%, 95% CI -0.2 to 6.8, p=0.07) and at 2 years 12.9% vs 8.4% (HR 0.63, 95% CI 0.35 to 1.13, p = 0.12) after simple versus complex treatment. In the subgroup treated by newer generation drug-eluting stents, MACE was 12.0% vs 5.6% (HR 0.45, 95% CI 0.17 to 1.17, p = 0.10) after simple versus complex treatment.Conclusion In the treatment of bifurcation lesions involving a large SB with ostial stenosis, routine two-stent techniques did not improve outcome significantly compared with treatment by the simpler main vessel stenting technique after 2 years

Social inequalities in changes in health-related behaviour among Slovak adolescents aged between 15 and 19: A longitudinal study

<p>Abstract</p> <p>Background</p> <p>Lower socioeconomic position is generally associated with higher rates of smoking and alcohol consumption and lower levels of physical activity. Health-related behaviour is usually established during late childhood and adolescence. The aim of this study is to explore changes in health-related behaviour in a cohort of adolescents aged between 15 and 19, overall and by socioeconomic position.</p> <p>Methods</p> <p>The sample consisted of 844 first-year students (42.8% males, baseline in 1998 – mean age 14.9, follow-up in 2002 – mean age 18.8) from 31 secondary schools located in Kosice, Slovakia. This study focuses on changes in adolescents' smoking, alcohol use, experience with marijuana and lack of physical exercise with regard to their socioeconomic position. Four indicators of socioeconomic position were used – adolescents' current education level and employment status, and the highest education level and highest occupational status of their parents. We first made cross tabulations of HRB with these four indicators, using McNemar's test to assess differences. Next, we used logistic regression to assess adjusted associations, using likelihood ratio tests to assess statistical significance.</p> <p>Results</p> <p>Statistically significant increases were found in all health-related behaviours. Among males, the most obvious socioeconomic gradient was found in smoking, both at age 15 and at 19. Variations in socioeconomic differences in health-related behaviour were more apparent among females. Although at age 15, almost no socioeconomic differences in health-related behaviour were found, at age 19 differences were found for almost all socioeconomic indicators. Among males, only traditional socioeconomic gradients were found (the lower the socioeconomic position, the higher the prevalence of potentially harmful health-related behaviour), while among females reverse socioeconomic gradients were also found.</p> <p>Conclusion</p> <p>We confirmed an increase in unhealthy health-related behaviour during adolescence. This increase was related to socioeconomic position, and was more apparent in females.</p

Matrix Development in Self-Assembly of Articular Cartilage

Articular cartilage is a highly functional tissue which covers the ends of long bones and serves to ensure proper joint movement. A tissue engineering approach that recapitulates the developmental characteristics of articular cartilage can be used to examine the maturation and degeneration of cartilage and produce fully functional neotissue replacements for diseased tissue.This study examined the development of articular cartilage neotissue within a self-assembling process in two phases. In the first phase, articular cartilage constructs were examined at 1, 4, 7, 10, 14, 28, 42, and 56 days immunohistochemically, histologically, and through biochemical analysis for total collagen and glycosaminoglycan (GAG) content. Based on statistical changes in GAG and collagen levels, four time points from the first phase (7, 14, 28, and 56 days) were chosen to carry into the second phase, where the constructs were studied in terms of their mechanical characteristics, relative amounts of collagen types II and VI, and specific GAG types (chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, and hyaluronan). Collagen type VI was present in initial abundance and then localized to a pericellular distribution at 4 wks. N-cadherin activity also spiked at early stages of neotissue development, suggesting that self-assembly is mediated through a minimization of free energy. The percentage of collagen type II to total collagen significantly increased over time, while the proportion of collagen type VI to total collagen decreased between 1 and 2 wks. The chondroitin 6- to 4- sulfate ratio decreased steadily during construct maturation. In addition, the compressive properties reached a plateau and tensile characteristics peaked at 4 wks.The indices of cartilage formation examined in this study suggest that tissue maturation in self-assembled articular cartilage mirrors known developmental processes for native tissue. In terms of tissue engineering, it is suggested that exogenous stimulation may be necessary after 4 wks to further augment the functionality of developing constructs

Effect of Systemic Hypertension With Versus Without Left Ventricular Hypertrophy on the Progression of Atrial Fibrillation (from the Euro Heart Survey).

Hypertension is a risk factor for both progression of atrial fibrillation (AF) and development of AF-related complications, that is major adverse cardiac and cerebrovascular events (MACCE). It is unknown whether left ventricular hypertrophy (LVH) as a consequence of hypertension is also a risk factor for both these end points. We aimed to assess this in low-risk AF patients, also assessing gender-related differences. We included 799 patients from the Euro Heart Survey with nonvalvular AF and a baseline echocardiogram. Patients with and without hypertension were included. End points after 1 year were occurrence of AF progression, that is paroxysmal AF becoming persistent and/or permanent AF, and MACCE. Echocardiographic LVH was present in 33% of 379 hypertensive patients. AF progression after 1 year occurred in 10.2% of 373 patients with rhythm follow-up. In hypertensive patients with LVH, AF progression occurred more frequently as compared with hypertensive patients without LVH (23.3% vs 8.8%, p = 0.011). In hypertensive AF patients, LVH was the most important multivariably adjusted determinant of AF progression on multivariable logistic regression (odds ratio 4.84, 95% confidence interval 1.70 to 13.78, p = 0.003). This effect was only seen in male patients (27.5% vs 5.8%, p = 0.002), while in female hypertensive patients, no differences were found in AF progression rates regarding the presence or absence of LVH (15.2% vs 15.0%, p = 0.999). No differences were seen in MACCE for hypertensive patients with and without LVH. In conclusion, in men with hypertension, LVH is associated with AF progression. This association seems to be absent in hypertensive women