Determinants of longitudinal health-related quality-of-life change in children with asthma from low-income families: a report from the PROMIS® Pediatric Asthma Study.

BACKGROUND: How the longitudinal asthma control status and other socio-demographic factors influence the changes of health-related quality of life (HRQOL) among asthmatic children, especially from low-income families, has not been fully investigated. OBJECTIVES: This study aimed to describe the trajectories of asthma-specific HRQOL over 15 months and examine the effect of asthma control status on HRQOL by taking socio-demographic factors into consideration. METHODS: A total of 229 dyads of asthmatic children and their parents enroled in public insurance programs were recruited for assessing asthma control status and HRQOL over four time points of assessment. Asthma control status was measured using the Asthma Control and Communication Instrument, and asthma-specific HRQOL was assessed using the Patient-Reported Outcomes Measurement Information System's Pediatric Asthma Impact Scale. Latent growth models (LGMs) were applied to examine the trajectory of HRQOL and the factors contributing to the changes of HRQOL. RESULTS: Unconditional LGM revealed that HRQOL was improved over time. Conditional LGM suggested that accounting for asthma control and participants' socio-demographic factors, the variation in the initial level of HRQOL was significant, yet the rate of change was not. Conditional LGM also revealed that poorly controlled asthma status was associated with poor HRQOL at each time point (P's < 0.05). Lower parental education was associated with lower baseline HRQOL (P < 0.05). Hispanic children had a larger increase in HRQOL over time (P < 0.01) than non-Hispanic White children. CONCLUSIONS: Vulnerable socio-demographic characteristics and poorly controlled asthma status affect HRQOL in children. This finding encourages interventions to improve asthma control status and HRQOL in minority children.

Rotationally symmetric formulation of the wave propagation method-application to the straylight analysis of diffractive lenses.

We introduce a modified formulation of the wave propagation method for the efficient simulation of rotationally symmetric micro-optical components. The reformulated algorithm provides an increased computational performance of approximately two orders of magnitude and strongly reduced memory requirements, in comparison to the original formulation. This enables the efficient wave optical simulation of extended micro-optical structures beyond the common thin-element approximation. As a prototypical example, we assess the modified algorithm for the evaluation of straylight induced by diffractive lenses. We find an excellent accuracy, while comparing to rigorous simulations, which justifies the ability to overcome the limitations of the thin-element approximation.

Wave-optical modeling beyond the thin-element-approximation.

The optical design and analysis of modern micro-optical elements with high index contrasts and large numerical apertures is still challenging, as fast and accurate wave-optical simulations beyond the thin-element-approximation are required. We introduce a modified formulation of the wave-propagation-method and assess its performance in comparison to different beam-propagation-methods with respect to accuracy, required sampling densities, and computational performance. For typical micro-optical components, the wave-propagation-method is found to be considerably faster and more accurate at even lower sampling densities compared to the different beam-propagation-methods. This enables realistic wave-optical simulations beyond the thin-element-approximation for micro-optical components. As an example, the modified wave-propagation-method is applied for in-line holographic measurements of strongly diffracting objects. From a direct comparison of experimental results and corresponding simulations, the geometric parameters of a test object could be retrieved with high accuracy.

Image formation properties and inverse imaging problem in aperture based scanning near field optical microscopy.

Aperture based scanning near field optical microscopes are important instruments to study light at the nanoscale and to understand the optical functionality of photonic nanostructures. In general, a detected image is affected by both the transverse electric and magnetic field components of light. The discrimination of the individual field components is challenging as these four field components are contained within two signals in the case of a polarization resolved measurement. Here, we develop a methodology to solve the inverse imaging problem and to retrieve the vectorial field components from polarization and phase resolved measurements. Our methodology relies on the discussion of the image formation process in aperture based scanning near field optical microscopes. On this basis, we are also able to explain how the relative contributions of the electric and magnetic field components within detected images depend on the chosen probe. We can therefore also describe the influence of geometrical and material parameters of individual probes within the image formation process. This allows probes to be designed that are primarily sensitive either to the electric or magnetic field components of light.

Prior myocardial infarction and presence of upper gastrointestinal conditions among patients with venous thromboembolism: prevalence, associated comorbidities and burden.

WHAT IS KNOWN AND OBJECTIVES: Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a serious, life-threatening condition that often complicates treatment of individuals who are already ill and increases in risk with age. The comorbidity burden of VTE can complicate treatment; therefore, treatment should be influenced by the presence of comorbidities (Kearon 2012). The prevalence of common conditions in the VTE population is, therefore, an important subject of research. Prevalence of two common comorbid burdens, prior myocardial infarction (MI) and upper gastrointestinal (GI) conditions, was studied among survey respondents who reported DVT or PE. METHODS: Responses to the 2010 wave of the National Health and Wellness Survey (NHWS), a self-administered, internet-based questionnaire from a nationwide, demographically representative sample of adults, were evaluated. RESULTS AND DISCUSSION: Among the 814 participants reporting a history of VTE, 9·7% (n = 60) of the DVT subpopulation and 13·2% (n = 39) of the PE subpopulation also reported prior MI. In respondents with prior MI, cardiovascular, urological, and pain comorbidities were each reported as additional comorbidities by at least two thirds of respondents in both the PE and DVT subpopulations, with cardiovascular and urological conditions reported significantly (P < 0·05) more often than among respondents with no prior MI. Among the respondents reporting VTE, 48·9% (n = 302) of the subpopulation reporting DVT and 52·2% (n = 154) of those reporting PE also reported upper GI comorbidities. Cardiovascular and pain conditions in the respondents reporting upper GI comorbidities were each reported by more than three quarters of VTE patients in both the DVT and PE subpopulations and were significantly more common (P < 0·05) than among their counterparts without upper GI comorbidities. WHAT IS NEW AND CONCLUSION: The results of the NHWS indicate that VTE patients who have either of two common comorbid burdens, prior MI and concomitant upper GI conditions, also showed high levels of additional, concurrent comorbidities and generally poor health status. Clinicians must be aware of the total comorbidity profile of their patients who have experienced VTE in order to best manage them and prescribe appropriate therapy.

[Medical care unit -- a suitable instrument for ambulatory patient-adequate care and performance-related remuneration]. / Medizinisches Versorgungszentrum - geeignetes Instrument der ambulanten patientenadäquaten Versorgung und leistungsgerechten Vergütung.

BACKGROUND: The question of whether a medical care unit is an appropriate tool for outpatient care has been discussed for a long time. Our aim is to investigate whether the MCU is an effective instrument for outpatient care and adequate performance-related remuneration. MATERIAL AND METHODS: This retro- and prospective overview of the work included statements on legal foundations for medical care units, for reimbursement of services in medical care units, the development of medical care centres in Germany and a listing of the specific advantages and disadvantages of an MCU. This article focuses on the generally applicable facts and complements them with examples from general, visceral and vascular surgery. The main quantitative data on medical centre statistics come from different publications of the National Association of Statutory Health Insurance for Physicians. RESULTS: From a legal point of view the instrument MCU allows the participating of ambulatory and stationary care in the framework of medical care contracts. This has been especially extended for stationary applications, including the spectrum of possibilities that can contribute under certain circumstances for the provision of medical care in underdeveloped regions. Freelancers can benefit primarily from financial risk and minimising bureaucratic routine. The remuneration for services performed in the MCU is analogous to that of other ambulatory care providers. Basically, there are no disadvantages, but a greater design freedom and opportunities for the generation of aggregates are visible. The number of MCU in Germany has quadrupled in the last five years, indicating an establishment of an outpatient care landscape. MCU offers from the patient's perspective, providers and policy specific advantages and disadvantages. Indeed the benefits outweigh the disadvantages, but this is not yet verified by qualitative studies. CONCLUSION: The question of the appropriateness of medical care units as outpatient care instrumentation must be considered differentially. Under current conditions it appears suitable for ensuring the MCU and the supplement of care supply. Whether a value can be generated in the quality of care of patients, however, has to be examined separately, as there are no valid data so far. The same applies to economic assessments of costs and benefits from an economic perspective.

Modeling of line roughness and its impact on the diffraction intensities and the reconstructed critical dimensions in scatterometry.

We investigate the impact of line-edge and line-width roughness (LER, LWR) on the measured diffraction intensities in angular resolved extreme ultraviolet (EUV) scatterometry for a periodic line-space structure designed for EUV lithography. LER and LWR with typical amplitudes of a few nanometers were previously neglected in the course of the profile reconstruction. The two-dimensional (2D) rigorous numerical simulations of the diffraction process for periodic structures are carried out with the finite element method providing a numerical solution of the 2D Helmholtz equation. To model roughness, multiple calculations are performed for domains with large periods, containing many pairs of line and space with stochastically chosen line and space widths. A systematic decrease of the mean efficiencies for higher diffraction orders along with increasing variances is observed and established for different degrees of roughness. In particular, we obtain simple analytical expressions for the bias in the mean efficiencies and the additional uncertainty contribution stemming from the presence of LER and/or LWR. As a consequence this bias can easily be included into the reconstruction model to provide accurate values for the evaluated profile parameters. We resolve the sensitivity of the reconstruction from this bias by using simulated data with LER/LWR perturbed efficiencies for multiple reconstructions. If the scattering efficiencies are bias-corrected, significant improvements are found in the reconstructed bottom and top widths toward the nominal values.

North Central Cancer Treatment Group (NCCTG) N0432: phase II trial of docetaxel with capecitabine and bevacizumab as first-line chemotherapy for patients with metastatic breast cancer.

BACKGROUND: Docetaxel (T; Taxotere) with capecitabine (X) is active against metastatic breast cancer (MBC); bevacizumab (BV) has demonstrated efficacy with taxanes in the first-line setting. This study was conducted to assess the safety and efficacy of TX-BV in patients with MBC. PATIENTS AND METHODS: In this single-arm, multicenter phase II study, patients received first-line bevacizumab 15 mg/kg and docetaxel 75 mg/m(2) on day 1 and capecitabine 825 mg/m(2) twice per day on days 1-14 every 21 days. Primary and secondary end points were tumor response rate (RR), overall survival (OS), progression-free survival (PFS), and toxicity. RESULTS: A total of 45 assessable patients received TX-BV for a median of seven cycles. Two complete and 20 partial responses were observed (overall RR 49%); nine patients had stable disease >6 months, for a clinical benefit rate of 69%. Median response duration was 11.8 months. Median OS and PFS were 28.4 and 11.1 months, respectively. Grade 3/4 adverse events included hand-foot syndrome (29%), fatigue (20%), febrile neutropenia (18%), and diarrhea (18%). In cycles 3-10, median dose levels of docetaxel and capecitabine were 60 mg/m(2) and 660 mg/m(2), respectively. CONCLUSION: TX-BV demonstrated significant activity; dose modifications were required to manage drug-related toxic effects.

Freeze-fracturing in ultrahigh vacuum at -196 degrees C.

Conventional freeze-etching is carried out in a vacuum of approximately 10(-6) torr and at a specimen temperature of -100 degrees C. The relatively poor topographic resolution of most freeze-etch replicas, and the lack of complementarity of morphological details in double replicas have been thought to be caused by structural distortions during fracturing, and radiation damage during replication. Both phenomena can be reduced by lowering the specimen temperature. To prevent condensation of residual gases (especially H2O) on the fracture faces at lower specimen temperature, an improved vacuum is required. Therefore, an ultrahigh vacuum freeze-fracture apparatus has been developed which allows fracturing and Pt/C-shadowing of specimens at -196 degrees C while maintaining a vacuum of 10(-9) torr. It consists of a modified Balzers BA 350 ultrahigh vacuum (UHV) unit, equipped with an airlock which enables the input of nonhoar-frosted specimens directly into the evacuated bell jar. A comparison of the paracrystalline plasmalemma structure in yeast cells portrayed by the conventional technique and by UHV-freeze-fracturing at -196 degrees C shows the improved topographic resolution which has been achieved with the new technique. The improvement is explained by less structural distortions during fracturing at lower temperatures. The particles of the paracrystalline regions on the P face are more regularly arranged and exhibit a craterlike substructure which corresponds with a ringlike depression in the E face. The optical diffraction patterns of these paracrystalline regions demonstrate the improvement of the structural record by showing well-defined third- and fourth-order spots.

Decoration of specific sites on freeze-fractured membranes.

Fracturing under ultrahigh vacuum (UHV, P less than or equal to 10(-9) Torr) produces membrane fracture faces devoid of contamination. Such clean surfaces are a prerequisite for studies of interactions between condensing gases and distinct regions of a surface. For the study of water condensation, a device has been developed which enables production of pure water vapor and controlled variation of its partial pressure in an UHV freeze-fracture apparatus. Experiments with yeast plasmalemma fracture faces, produced at -196 degrees C and exposed to pure water vapor before replication, resulted in a "specific decoration" with ice crystals of those pits in the extraplasmic face where the corresponding particles of the plasmic face had been removed. Because water condenses as discrete ice crystals which resemble intramembrane particles, ice crystals might easily be misinterpreted as actual membrane structures. At low specimen temperature (T less than or equal to 110 degrees C) the structural features of membrane fracture faces produced under high vacuum (P approximately 10(-6) Torr) should, therefore, be interpreted with caution.

Single bacteriorhodopsin molecules revealed on both surfaces of freeze-dried and heavy metal-decorated purple membranes.

The flat sheets of the purple membrane from Halobacterium halobium contain only a single protein (bacteriorhodopsin) arranged in a hexagonal lattice. After freeze-drying at -80 degrees C (a method that is superior to air-drying), shadowing with tantalum/tungsten, and image processing, structural details on both surfaces are portrayed in the range of 2 nm. One surface is rough and lattice lines are clearly visible, whereas the other is smooth and the hexagonal order seems to be absent. The optical diffraction patterns, however, indicate a hexagonal lattice for both surfaces. In addition, these diffraction patterns are characteristic and easily distinguished. The orientation of the two surfaces was identified by silver decoration: partial condensation of silver on purple membranes enabled the smooth surface to be identified as the plasmatic and the rough surface as the exoplasmic surface. After image processing, the exoplasmic surface shows a triplet structure which exactly fits the projected structure determined by Unwin and Henderson (1975. Nature(Lond.). 257:28-32) at molecular resolution, whereas, on the plasmatic surface, four image details per unit cell are visible. Three of them match the arrangement of bacteriorhodopsin, whereas the fourth must be located over a lipidic array. Summarizing these results, it is possible to show the part of each single bacteriorhodopsin protein that is present in the surfaces of the purple membrane. By "shadowing" the membranes perpendicularly, we prove that these components of the surfaces are mainly portrayed by a decoration effect of the tantalum/tungsten condensate.

Image reconstructions of microtubules decorated with monomeric and dimeric kinesins: comparison with x-ray structure and implications for motility.

We have decorated microtubules with monomeric and dimeric kinesin constructs, studied their structure by cryoelectron microscopy and three-dimensional image reconstruction, and compared the results with the x-ray crystal structure of monomeric and dimeric kinesin. A monomeric kinesin construct (rK354, containing only a short neck helix insufficient for coiled-coil formation) decorates microtubules with a stoichiometry of one kinesin head per tubulin subunit (alpha-beta-heterodimer). The orientation of the kinesin head (an anterograde motor) on the microtubule surface is similar to that of ncd (a retrograde motor). A longer kinesin construct (rK379) forms a dimer because of the longer neck helix forming a coiled-coil. Unexpectedly, this construct also decorates the microtubule with a stoichiometry of one head per tubulin subunit, and the orientation is similar to that of the monomeric construct. This means that the interaction with microtubules causes the two heads of a kinesin dimer to separate sufficiently so that they can bind to two different tubulin subunits. This result is in contrast to recent models and can be explained by assuming that the tubulin-kinesin interaction is antagonistic to the coiled-coil interaction within a kinesin dimer.

Structure of the mitochondrial creatine kinase octamer: high-resolution shadowing and image averaging of single molecules and formation of linear filaments under specific staining conditions.

The combination of high-resolution tantalum/tungsten (Ta/W) shadowing at very low specimen temperature (-250 degrees C) under ultrahigh vacuum (less than 2 x 10(-9) mbar) with circular harmonic image averaging revealed details on the surface structure of mitochondrial creatine kinase (Mi-CK) molecules with a resolution less than 2.5 nm. Mi-CK octamers exhibit a cross-like surface depression dividing the square shaped projection of 10 x 10 nm into four equally sized subdomains, which correspond to the four dimers forming the octameric Mi-CK molecule. By a combination of positive staining (with uranyl acetate) and heavy metal shadowing, internal structures as well as the surface relief of Mi-CK were visualized at the same time at high resolution. Computational image analysis revealed only a single projection class of molecules, but the ability of Mi-CK to form linear filaments, as well as geometrical considerations concerning the formation of octamers by four equal, asymmetric dimers, suggest the existence of at least two distinct faces on the molecule. By image processing of Mi-CK filaments a side view of the octamer differing from the top-bottom projections of single molecules became evident showing a funnel-like access each form the top and bottom of the octamer connected by a central channel. The general structure of the Mi-CK octamer described here is relevant to the localization of the molecule at the inner-outer mitochondrial contact sites and to the function of Mi-CK as an "energy channeling" molecule.

Luminescence of apollo 11 lunar samples.

Luminescence measurements were made of four lunar rocks, two terrestrial rocks (granite and gabbro), and one terrestrial mineral (willemite) by comparing the spectral curves with the curve of a barium sulfate standard. Efficiencies with 3000 angstrom excitation were < 6 x 10(-5) for the lunar samples, < 8 x 10(-5) for gabbro of very similar composition to the lunar samples, approximately 10(-4) for granite, and approximately 2 X 10(-2) for willemite. If these are typical values for other ultraviolet excitation wavelengths, the Apollo 11 site appears to contribute little to the observed lunar luminescence.

Scanning tunneling microscopy of recA-DNA complexes coated with a conducting film.

A link between scanning tunneling microscopy (STM) and conventional transmission electron microscopy has been established for biological material by applying STM on freeze-dried recA-DNA complexes coated with a conducting film. The topography of the complexes observed by means of STM revealed a right-handed single helix composed of about six recA monomers per helical turn.

Scanning tunneling microscopy of uncoated recA-DNA complexes.

Uncoated recA-DNA complexes were imaged with the scanning tunneling microscope (STM). The images, which reveal the right-handed helical structure of the complexes with subunits clearly resolved, are comparable in quality to STM images of metal-coated specimens. Possible conduction mechanisms that allow STM imaging of biological macromolecules are discussed.

Oxidized low density lipoproteins induce apoptosis in human lymphocytes: involvement of mitogen-activated protein kinases.

Oxidized low density lipoproteins (oxLDL), macrophages and T-lymphocytes are present in atherosclerotic lesions. We and others have shown that oxLDL is cytotoxic for macrophages, endothelial, smooth muscle and activated T-lymphocytes and induce apoptosis. Here we demonstrate that (i) oxidized LDL (oxLDL), oxidized VLDL (oxVLDL) and hydrogen peroxide (H2O2) induce apoptosis in human T-lymphocytes and (ii) mitogen-activated protein kinases are involved in this process. Apoptosis was monitored by immunofluorescence microscopy and flow cytometry for annexin V binding, Apo 2.7 expression, the TUNEL reaction and caspase 3 activity. In the presence of oxLDL (100 microg/ml), oxVLDL (50 microg/ml) and H2O2 (5 mM), the fraction of apoptotic cells increased within 6 hours to more than 70%. Preincubation of lymphocytes with the MAPKK inhibitor PD-98059 and the p38MAPK inhibitor SB-203580 almost completely abolished these effects. Furthermore, oxLDL and H2O2 but not native LDL strongly enhanced phosphorylation of JNK, p38MAPK and p42/44MAPK. The results suggest that in the resting lymphocyte apoptosis triggered by oxidized lipoproteins and oxidative stress depends on the activation of p44/42MAPK and p38MAPK cascades.

Significant changes in physical activity among pregnant women in the UK as assessed by accelerometry and self-reported activity.

OBJECTIVE: Research on the impact of maternal physical activity on pregnancy outcomes has often employed subjective measures of physical activity obtained by diary or questionnaire. This study investigates the feasibility of using accelerometry as an objective measure of physical activity of pregnant women compared with subjective data obtained via activity recall among pregnant women. DESIGN: Activity data were collected prospectively on 57 women at 12, 16, 25, 34 and 38 weeks of gestation. Total daily physical activity was assessed by ambulatory accelerometer and activity interview (self-report). Maternal personality variables (health value, extroversion) were assessed by established scales. SETTING: Leicestershire, UK. SUBJECTS: Pregnant women were recruited by voluntary participation via antenatal booking clinics. In all, 64 pregnant women with low-risk pregnancy were enrolled onto the study, of whom 57 completed the study. RESULTS: Mean 24 h physical activity levels (PAL) decreased significantly from second to third trimester as assessed by self-report interview (1.51-1.29 Metabolic Equivalent TEE-h/day, P<0.01) and accelerometry (200.05-147.42 counts/min, P<0.01). The correlation between the two measures declined as pregnancy progressed (r value ranging from 0.55 to 0.08). Compliance with the accelerometers declined from 90% at 12 weeks to 47% at 34 weeks (P<0.01). Compliance with the self-report interviews was 100%. Those who fully complied with the accelerometry demonstrated a significantly higher health value (P<0.05) and a significantly greater level of extroversion (P<0.05) than those who did not. CONCLUSIONS: Accelerometers and self-reported activity interviews both indicated a significant decline in PAL during pregnancy. Although subjects showed a willingness to use both methods, accelerometers resulted in variable compliance with 72 h monitoring. Both techniques may be limited by the need to measure low levels of physical activity during the third trimester. SPONSORSHIP: Cambridge Neurotechnology Ltd, UK, assisted with the provision of Actiwatch accelerometers.

The first phytoplasma RNase P RNA provides new insights into the sequence requirements of this ribozyme.

A high variability of RNase P RNA structures is seen among members of the Mycoplasma group. To gain further insight into the structure-function relations of this ribozyme, we have searched for the RNase P RNA gene from more distant relatives, the phytoplasmas. These mycoplasma-like organisms are the aetiological agents of many severe plant diseases. We report the sequence and catalytic properties of RNase P RNA from the phytoplasma causing apple proliferation disease. The primary and postulated secondary structure of this 443 nt long RNA are most similar to those of Acholeplasma, supporting the phylogenetic position of this pathogen. Remarkably, the extremely AT-rich (73.6%) phytoplasma RNA differs from the known bacterial consensus sequence by a single base pair, which is positioned close to the substrate cleavage site in current three-dimensional models. Phytoplasma RNase P RNA functions as an efficient ribozyme in vitro. Conversion of its sequence to the full consensus and kinetic analysis of the resulting mutant RNAs suggests that neither the sequence alone, nor the type of pairing at this position is crucial for substrate binding or catalysis by the RNase P ribozyme. These results refine the bacterial consensus structure close to the catalytic core and thus improve our understanding of RNase P RNA function.

Triplex forming oligonucleotide targeted to 3'UTR downregulates the expression of the bcl-2 proto-oncogene in HeLa cells.

The bcl-2 proto-oncogene is overexpressed in a variety of human cancers and plays an important role in programmed cell death. Recent reports implied that the 3'-untranslated region (3'UTR) functions effectively in the regulation of gene expression. Here, we attempt to assay the ability of triplex forming oligonucleotides (TFOs) to inhibit expression of a target gene in vivo and to examine the potential of the 3'UTR of the bcl-2 proto-oncogene in the regulation of bcl-2 gene expression. To do this, we have developed a novel cellular system that involves transfection of a Doxycyclin inducible expression plasmid containing the bcl-2 ORF and the 3'UTR together with a TFO targeted to the 3'UTR of the bcl-2 proto-oncogene. Phosphorothioate-modified TFO targeted to the 3'UTR of the bcl-2 gene significantly downregulated the expression of the bcl-2 gene in HeLa cells as demonstrated by western blotting. Our results indicate that blocking the functions of the 3'UTR using the TFO can downregulate the expression of the targeted gene, and suggest that triplex strategy is a promising approach for oligonucleotide-based gene therapy. In addition, triplex-based sequence targeting may provide a useful tool for studying the regulation of gene expression.