The English are healthier than the Americans: really?

Background: When comparing the health of two populations, it is not enough to compare the prevalence of chronic diseases. The objective of this study is therefore to propose a metric of health based on domains of functioning to determine whether the English are healthier than the Americans. Methods: We analysed representative samples aged 50 to 80 years from the 2008 wave of the Health and Retirement Study (N?=?10?349) for the US data, and wave 4 of the English Longitudinal Study of Ageing (N?=?9405) for English counterpart data. We first calculated the age-standardized disease prevalence of diabetes, hypertension, all heart diseases, stroke, lung disease, cancer and obesity. Second, we developed a metric of health using Rasch analyses and the questions and measured tests common to both surveys addressing domains of human functioning. Finally, we used a linear additive model to test whether the differences in health were due to being English or American. Results: The English have better health than the Americans when population health is assessed only by prevalence of selected chronic health conditions. The English health advantage disappears almost completely, however, when health is assessed with a metric that integrates information about functioning domains. Conclusions: It is possible to construct a metric of health, based on data directly collected from individuals, in which health is operationalized as domains of functioning. Its application has the potential to tackle one of the most intractable problems in international research on health, namely the comparability of health across countries

Chemotherapy of Metastatic Renal Adenocarcinoma with a Five- Drug Regimen*

In the past, chemotherapy of renal adenocarcinoma has been relatively unsuccessful. The progestational agent, medroxy progesterone acetate (MPA), has been the most effective single agent, even though the response rate probably does not exceed 12%. This report describes the results of a program of combination therapy with MPA, cyclophosphamide, hydroxyurea, vinblastine and prednisone that was used on 42 patients, ten of whom had received prior MPA therapy. One complete remission and seven partial remissions were observed, oniyone of whom had received prior MPA therapy. Treatment of metastatic renal adenocarcinoma with combination chemotherapy should probably include MPA and adriamycin. The role of estrogen receptor (ER) and progesterone receptor (PR) as predictions of response to hormonal therapy in this disease looks encouraging, but the results reported to date have been limited

The English are healthier than the Americans: really?

Background: When comparing the health of two populations, it is not enough to compare the prevalence of chronic diseases. The objective of this study is therefore to propose a metric of health based on domains of functioning to determine whether the English are healthier than the Americans. Methods: We analysed representative samples aged 50 to 80 years from the 2008 wave of the Health and Retirement Study (N = 10 349) for the US data, and wave 4 of the English Longitudinal Study of Ageing (N = 9405) for English counterpart data. We first calculated the age-standardized disease prevalence of diabetes, hypertension, all heart diseases, stroke, lung disease, cancer and obesity. Second, we developed a metric of health using Rasch analyses and the questions and measured tests common to both surveys addressing domains of human functioning. Finally, we used a linear additive model to test whether the differences in health were due to being English or American. Results: The English have better health than the Americans when population health is assessed only by prevalence of selected chronic health conditions. The English health advantage disappears almost completely, however, when health is assessed with a metric that integrates information about functioning domains. Conclusions: It is possible to construct a metric of health, based on data directly collected from individuals, in which health is operationalized as domains of functioning. Its application has the potential to tackle one of the most intractable problems in international research on health, namely the comparability of health across countrie

Mechanical response of random heteropolymers

We present an analytical theory for heteropolymer deformation, as exemplified experimentally by stretching of single protein molecules. Using a mean-field replica theory, we determine phase diagrams for stress-induced unfolding of typical random sequences. This transition is sharp in the limit of infinitely long chain molecules. But for chain lengths relevant to biological macromolecules, partially unfolded conformations prevail over an intermediate range of stress. These necklace-like structures, comprised of alternating compact and extended subunits, are stabilized by quenched variations in the composition of finite chain segments. The most stable arrangements of these subunits are largely determined by preferential extension of segments rich in solvophilic monomers. This predicted significance of necklace structures explains recent observations in protein stretching experiments. We examine the statistical features of select sequences that give rise to mechanical strength and may thus have guided the evolution of proteins that carry out mechanical functions in living cells.Comment: 10 pages, 6 figure

Spatio-temporal dynamics of quantum-well excitons

We investigate the lateral transport of excitons in ZnSe quantum wells by using time-resolved micro-photoluminescence enhanced by the introduction of a solid immersion lens. The spatial and temporal resolutions are 200 nm and 5 ps, respectively. Strong deviation from classical diffusion is observed up to 400 ps. This feature is attributed to the hot-exciton effects, consistent with previous experiments under cw excitation. The coupled transport-relaxation process of hot excitons is modelled by Monte Carlo simulation. We prove that two basic assumptions typically accepted in photoluminescence investigations on excitonic transport, namely (i) the classical diffusion model as well as (ii) the equivalence between the temporal and spatial evolution of the exciton population and of the measured photoluminescence, are not valid for low-temperature experiments.Comment: 8 pages, 6 figure

Single Molecule Statistics and the Polynucleotide Unzipping Transition

We present an extensive theoretical investigation of the mechanical unzipping of double-stranded DNA under the influence of an applied force. In the limit of long polymers, there is a thermodynamic unzipping transition at a critical force value of order 10 pN, with different critical behavior for homopolymers and for random heteropolymers. We extend results on the disorder-averaged behavior of DNA's with random sequences to the more experimentally accessible problem of unzipping a single DNA molecule. As the applied force approaches the critical value, the double-stranded DNA unravels in a series of discrete, sequence-dependent steps that allow it to reach successively deeper energy minima. Plots of extension versus force thus take the striking form of a series of plateaus separated by sharp jumps. Similar qualitative features should reappear in micromanipulation experiments on proteins and on folded RNA molecules. Despite their unusual form, the extension versus force curves for single molecules still reveal remnants of the disorder-averaged critical behavior. Above the transition, the dynamics of the unzipping fork is related to that of a particle diffusing in a random force field; anomalous, disorder-dominated behavior is expected until the applied force exceeds the critical value for unzipping by roughly 5 pN.Comment: 40 pages, 18 figure

Quantitative multi-modality imaging analysis of a fully bioresorbable stent: a head-to-head comparison between QCA, IVUS and OCT

The bioresorbable vascular stent (BVS) is totally translucent and radiolucent, leading to challenges when using conventional invasive imaging modalities. Agreement between quantitative coronary angiography (QCA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) in the BVS is unknown. Forty five patients enrolled in the ABSORB cohort B1 study underwent coronary angiography, IVUS and OCT immediately post BVS implantation, and at 6 months. OCT estimated stent length accurately compared to nominal length (95% CI of the difference: −0.19; 0.37 and −0.15; 0.47 mm2 for baseline and 6 months, respectively), whereas QCA incurred consistent underestimation of the same magnitude at both time points (Pearson correlation = 0.806). IVUS yielded low accuracy (95% CI of the difference: 0.77; 3.74 and −1.15; 3.27 mm2 for baseline and 6 months, respectively), with several outliers and random variability test–retest. Minimal lumen area (MLA) decreased substantially between baseline and 6 months on QCA and OCT and only minimally on IVUS (95% CI: 0.11; 0.42). Agreement between the different imaging modalities is poor: worst agreement Videodensitometry-IVUS post-implantation (ICCa 0.289); best agreement IVUS-OCT at baseline (ICCa 0.767). All pairs deviated significantly from linearity (P < 0.01). Passing-Bablok non-parametric orthogonal regression showed constant and proportional bias between IVUS and OCT. OCT is the most accurate technique for measuring stent length, whilst QCA incurs systematic underestimation (foreshortening) and solid state IVUS incurs random error. Volumetric calculations using solid state IVUS are therefore not reliable. There is poor agreement for MLA estimation between all the imaging modalities studied, including IVUS-OCT, hence their values are not interchangeable

Single-molecule experiments in biological physics: methods and applications

I review single-molecule experiments (SME) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SME it is possible to: manipulate molecules one at a time and measure distributions describing molecular properties; characterize the kinetics of biomolecular reactions and; detect molecular intermediates. SME provide the additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SME it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level emphasizing the importance of SME to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SME from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOT), magnetic tweezers (MT), biomembrane force probe (BFP) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation), proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SME to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.Comment: Latex, 60 pages, 12 figures, Topical Review for J. Phys. C (Cond. Matt