The Medicare Care Choices Model was associated with reductions in disparities in the use of hospice care for Medicare beneficiaries with terminal illness.

OBJECTIVE: To assess the effects of the Medicare Care Choices Model (MCCM) on disparities in hospice use and quality of end-of-life care for Medicare beneficiaries from underserved groups-those from racial and ethnic minority groups, dually eligible for Medicare and Medicaid, or living in rural areas. DATA SOURCES AND STUDY SETTING: Medicare enrollment and claims data from 2013 to 2021 for terminally ill Medicare fee-for-service beneficiaries nationwide. STUDY DESIGN: Through MCCM, terminally ill enrolled Medicare beneficiaries received supportive and palliative care services from hospice providers concurrently with curative treatments. Using a matched comparison group, we estimated subgroup-specific effects on hospice use, days at home, and aggressive treatment and multiple emergency department visits in the last 30 days of life. DATA COLLECTION/EXTRACTION METHODS: The sample included decedent Medicare beneficiaries enrolled in MCCM and a matched comparison group from the same geographic areas who met model eligibility criteria at time of enrollment: having a diagnosis of cancer, congestive heart failure, chronic obstructive pulmonary disease, or HIV/AIDS; living in the community; not enrolled in the Medicare hospice benefit in the previous 30 days; and having at least one hospital stay and three office visits in the previous 12 months. PRINCIPAL FINDINGS: Eligible beneficiaries from underserved groups were underrepresented in MCCM. MCCM increased enrollees' hospice use and the number of days at home and reduced aggressive treatment among all subgroups analyzed. MCCM also reduced disparities in hospice use by race and ethnicity and dual eligibility by 4.1 (90% credible interval [CI]: 1.3-6.1) and 2.4 (90% CI: 0.6-4.4) percentage points, respectively. It also reduced disparities in having multiple emergency department visits for rural enrollees by 1.3 (90% CI: 0.1-2.7) percentage points. CONCLUSIONS: MCCM increased hospice use and quality of end-of-life care for model enrollees from underserved groups and reduced disparities in hospice use and having multiple emergency department visits.

Medicare Care Choices Model Improved End-Of-Life Care, Lowered Medicare Expenditures, And Increased Hospice Use.

The Medicare Care Choices Model (MCCM) tested a new option for eligible Medicare beneficiaries to receive conventional treatment for terminal conditions along with supportive and palliative care from participating hospice providers. Using claims data, we estimated differences in average outcomes from enrollment to death between deceased MCCM enrollees and matched comparison beneficiaries who received usual services covered by original Medicare. Enrollees were 15 percentage points less likely to receive an aggressive life-prolonging treatment at the end of life and spent more than five more days at home. MCCM also reduced net Medicare expenditures by 13 percent, decreased inpatient admissions by 26 percent, reduced outpatient emergency department visits by 12 percent, and increased hospice use by 18 percentage points. Although the Centers for Medicare and Medicaid Services did not expand the model, given concerns about generalizability, these results provide evidence that MCCM is a promising approach to transforming care delivery at the end of life.

Muonic atom spectroscopy with microgram target material.

Muonic atom spectroscopy-the measurement of the x rays emitted during the formation process of a muonic atom-has a long standing history in probing the shape and size of nuclei. In fact, almost all stable elements have been subject to muonic atom spectroscopy measurements and the absolute charge radii extracted from these measurements typically offer the highest accuracy available. However, so far only targets of at least a few hundred milligram could be used as it required to stop a muon beam directly in the target to form the muonic atom. We have developed a new method relying on repeated transfer reactions taking place inside a 100 bar hydrogen gas cell with an admixture of 0.25% deuterium that allows us to drastically reduce the amount of target material needed while still offering an adequate efficiency. Detailed simulations of the transfer reactions match the measured data, suggesting good understanding of the processes taking place inside the gas mixture. As a proof of principle we demonstrate the method with a measurement of the 2p-1s muonic x rays from a 5  µ g gold target.

Mindfulness-Based Cognitive Therapy as Migraine Intervention: a Randomized Waitlist Controlled Trial.

BACKGROUND: Based on promising effects seen in a pilot study evaluating a generic mindfulness-based program for migraine, we developed a migraine-specific adaptation of the Mindfulness-Based Cognitive Therapy (MBCT) program. The aim of this study was to evaluate this program for feasibility and effectiveness in a randomized controlled trial. METHOD: Fifty-four patients suffering from migraine were randomly allocated to either waitlist or the adapted MBCT. Outcomes were migraine-related parameters as well as variables of psychological functioning and coping. Assessment took place at baseline and post-intervention, for the intervention group also at follow-up (7 months). The effects of the intervention were analyzed by the use of ANCOVAs and linear mixed models. RESULTS: With respect to migraine parameters we did not find a significant group difference in the primary outcome (headache-related impairment), but the intervention resulted in a significant reduction of headache frequency (p = .04). In the analysis of secondary outcomes, MBCT showed superiority in four out of eight psychological parameters (perceived stress, anxiety, rumination, catastrophizing) with small to medium effect sizes. The intervention proved to be feasible and participants reported high degrees of contentment and achievement of personal goals. CONCLUSIONS: The migraine-specific MBCT program did not result in improvements with regard to headache-related impairment but showed a reduction in headache frequency as well as improved psychological functioning in secondary outcomes. TRIAL REGISTRATION: This trial was registered in the German Trial Registry "Deutsches Register Klinischer Studien" (ID: DRKS00007477), which is a WHO-listed primary trial register.

The effect of accidents on labor market outcomes: Evidence from Chile.

We estimate the causal effect of accidents on employment and earnings among Chilean men using event study methods and monthly administrative data. An accident of any type reduces the probability of being employed by 8.4 percentage points in the first year, by 11.2 percentage points in the second year, and by 14.8 percentage points in the third year after the accident. On average, over the three years after the accident, employment declines by 14%, relative to the pre-accident mean. In addition, accidents reduce monthly earnings by around 11% in the first year, 17% in the second year, and 22% in the third year after the accident. On average, monthly earnings fall by 16%, relative to the pre-accident average. Thus, we estimate persistent and increasing labor market effects of accidents over time. These effects vary by individuals' age, education, and industry and by severity of the accident. Our findings imply that the economic consequences of health shocks go beyond direct medical expenses.

Medical innovation, education, and labor market outcomes of cancer patients.

Innovations in cancer treatment have lowered mortality, but little is known about their economic benefits. We assess the effect of two decades of improvement in cancer treatment options on the labor market outcomes of breast and prostate cancer patients. In addition, we compare this effect across cancer patients with different levels of educational attainment. We estimate the effect of medical innovation on cancer patients' labor market outcomes employing tax return and cancer registry data from Canada and measuring medical innovation by using the number of approved drugs and a quality-adjusted patent index. We find that innovations in cancer treatment during the 1990s and 2000s reduced the negative employment effects of cancer by 63% to 70%, corresponding to a reduction in the economic costs of prostate and breast cancer diagnoses by 13,500 and 5800 dollars per year, respectively. The benefits of medical innovation are limited to cancer patients with postsecondary education.

Morphology of single picosecond pulse subsurface laser-induced modifications of sapphire and subsequent selective etching.

The effect of 1030nm single picosecond pulsed laser-induced modification of the bulk of crystalline sapphire using a combined process of laser amorphization and selective wet chemical etching is studied. Pulse durations of more than 1 picosecond are not commonly used for this subsurface process. We examine the effect of 7 picosecond pulses on the morphology of the unetched, as well as etched, single pulse modifications, showing the variation of shape and size when varying the pulse energy and the depth of processing. In addition, a qualitative analysis of the material transformation after irradiation is provided as well as an analysis of cracking phenomena. Finally, a calculated laser intensity profile inside sapphire, using the Point Spread Function (PSF), is compared to the shape of the modifications. This comparison is employed to calculate the intensity threshold leading to amorphization, which equals 2.5⋅1014 ± 0.4⋅1014 W/cm2.

Picosecond-pulsed laser ablation of zinc: crater morphology and comparison of methods to determine ablation threshold.

Ablation of bulk polycrystalline zinc in air is performed with single and multiple picosecond laser pulses at a wavelength of 1030 nm. The relationships between the characteristics of the ablated craters and the processing parameters are analyzed. Morphological changes of the ablated craters are characterized by means of scanning electron microscopy and confocal laser scanning microscopy. Chemical compositions of both the treated and untreated surfaces are quantified with X-ray photoelectron spectroscopy. A comparative analysis on the determination of the ablation threshold using three methods, based on ablated diameter, depth and volume is presented along with associated incubation coefficients. The single pulse ablation threshold value is found to equal 0.21 J/cm2. Using the calculated incubation coefficients, it is found that both the fluence threshold and energy penetration depth show lesser degree of incubation for multiple laser pulses.

Spatial hole burning in thin-disk lasers and twisted-mode operation.

Spatial hole burning prevents single-frequency operation of thin-disk lasers when the thin disk is used as a folding mirror. We present an evaluation of the saturation effects in the disk for disks acting as end mirrors and as folding mirrors, explaining one of the main obstacles toward single-frequency operation. It is shown that a twisted-mode scheme based on a multi-order quarter-wave plate combined with a polarizer provides an almost complete suppression of spatial hole burning and creates an additional wavelength selectivity that enforces efficient single-frequency operation.

Health and work in the family: Evidence from spouses' cancer diagnoses.

Using Canadian administrative data from multiple sources, we provide the first nationally representative estimates for the effect of spouses' cancer diagnoses on individuals' employment and earnings and on family income. Our identification strategy exploits unexpected health shocks and combines matching with individual fixed effects in a generalized difference-in-differences framework to control for observable and unobservable heterogeneity. While the effect of spousal health shocks on labor supply is theoretically ambiguous, we find strong evidence for a decline in employment and earnings of individuals whose spouses are diagnosed with cancer. We interpret this result as individuals reducing their labor supply to provide care to their sick spouses and to enjoy joint leisure. Family income substantially declines after spouses' cancer diagnoses, suggesting that the financial consequences of such health shocks are considerable.

Active fiber-based retroreflector providing phase-retracing anti-parallel laser beams for precision spectroscopy.

We present an active fiber-based retroreflector providing high quality phase-retracing anti-parallel Gaussian laser beams for precision spectroscopy of Doppler sensitive transitions. Our design is well-suited for a number of applications where implementing optical cavities is technically challenging and corner cubes fail to match the demanded requirements, most importantly retracing wavefronts and preservation of the laser polarization. To illustrate the performance of the system, we use it for spectroscopy of the 2S-4P transition in atomic hydrogen and demonstrate an average suppression of the first order Doppler shift to 4 parts in 106 of the full collinear shift. This high degree of cancellation combined with our cryogenic source of hydrogen atoms in the metastable 2S state is sufficient to enable determinations of the Rydberg constant and the proton charge radius with competitive uncertainties. Advantages over the usual Doppler cancellation based on corner cube type retroreflectors are discussed as well as an alternative method using a high finesse cavity.

Hepatitis C virus dynamics and cellular gene expression in uPA-SCID chimeric mice with humanized livers during intravenous silibinin monotherapy.

Legalon SIL (SIL) is a chemically hydrophilized version of silibinin, an extract of milk thistle (Silybum marianum) seeds that has exhibited hepatoprotective and antiviral effectiveness against hepatitis C virus (HCV) in patients leading to viral clearance in combination with ribavirin. To elucidate the incompletely understood mode of action of SIL against HCV, mathematical modelling of HCV kinetics and human hepatocyte gene expression studies were performed in uPA-SCID-chimeric mice with humanized livers. Chronically HCV-infected mice (n = 15) were treated for 14 days with daily intravenous SIL at 469, 265 or 61.5 mg/kg. Serum HCV and human albumin (hAlb) were measured frequently, and liver HCV RNA was analysed at days 3 and 14. Microarray analysis of human hepatocyte gene expression was performed at days 0, 3 and 14 of treatment. While hAlb remained constant, a biphasic viral decline in serum was observed consisting of a rapid 1st phase followed by a second slower phase (or plateau with the two lower SIL dosings). SIL effectiveness in blocking viral production was similar among dosing groups (median ε = 77%). However, the rate of HCV-infected hepatocyte decline, δ, was dose-dependent. Intracellular HCV RNA levels correlated (r = 0.66, P = 0.01) with serum HCV RNA. Pathway analysis revealed increased anti-inflammatory and antiproliferative gene expression in human hepatocytes in SIL-treated mice. The results suggest that SIL could lead to a continuous second-phase viral decline, that is potentially viral clearance, in the absence of adaptive immune response along with increased anti-inflammatory and antiproliferative gene expression in human hepatocytes.

H3K79 methylation directly precedes the histone-to-protamine transition in mammalian spermatids and is sensitive to bacterial infections.

In both mammalian and Drosophila spermatids, the completely histone-based chromatin structure is reorganized to a largely protamine-based structure. During this histone-to-protamine switch, transition proteins are expressed, for example TNP1 and TNP2 in mammals and Tpl94D in Drosophila. Recently, we demonstrated that in Drosophila spermatids, H3K79 methylation accompanies histone H4 hyperacetylation during chromatin reorganization. Preceding the histone-to-protamine transition, the H3K79 methyltransferase Grappa is expressed, and the predominant isoform bears a C-terminal extension. Here, we show that isoforms of the Grappa-equivalent protein in humans, rats and mice, that is DOT1L, have a C-terminal extension. In mice, the transcript of this isoform was enriched in the post-meiotic stages of spermatogenesis. In human and mice spermatids, di- and tri-methylated H3K79 temporally overlapped with hyperacetylated H4 and thus accompanied chromatin reorganization. In rat spermatids, trimethylated H3K79 directly preceded transition protein loading on chromatin. We analysed the impact of bacterial infections on spermatid chromatin using a uropathogenic Escherichia coli-elicited epididymo-orchitis rat model and showed that these infections caused aberrant spermatid chromatin. Bacterial infections led to premature emergence of trimethylated H3K79 and hyperacetylated H4. Trimethylated H3K79 and hyperacetylated H4 simultaneously occurred with transition protein TNP1, which was never observed in spermatids of mock-infected rats. Upon bacterial infection, only histone-based spermatid chromatin showed abnormalities, whereas protamine-compacted chromatin seemed to be unaffected. Our results indicated that H3K79 methylation is a histone modification conserved in Drosophila, mouse, rat and human spermatids and may be a prerequisite for proper chromatin reorganization.

Is the proton radius a player in the redefinition of the International System of Units?

It is now recognized that the International System of Units (SI units) will be redefined in terms of fundamental constants, even if the date when this will occur is still under debate. Actually, the best estimate of fundamental constant values is given by a least-squares adjustment, carried out under the auspices of the Committee on Data for Science and Technology (CODATA) Task Group on Fundamental Constants. This adjustment provides a significant measure of the correctness and overall consistency of the basic theories and experimental methods of physics using the values of the constants obtained from widely differing experiments. The physical theories that underlie this adjustment are assumed to be valid, such as quantum electrodynamics (QED). Testing QED, one of the most precise theories is the aim of many accurate experiments. The calculations and the corresponding experiments can be carried out either on a boundless system, such as the electron magnetic moment anomaly, or on a bound system, such as atomic hydrogen. The value of fundamental constants can be deduced from the comparison of theory and experiment. For example, using QED calculations, the value of the fine structure constant given by the CODATA is mainly inferred from the measurement of the electron magnetic moment anomaly carried out by Gabrielse's group. (Hanneke et al. 2008 Phys. Rev. Lett. 100, 120801) The value of the Rydberg constant is known from two-photon spectroscopy of hydrogen combined with accurate theoretical quantities. The Rydberg constant, determined by the comparison of theory and experiment using atomic hydrogen, is known with a relative uncertainty of 6.6×10(-12). It is one of the most accurate fundamental constants to date. A careful analysis shows that knowledge of the electrical size of the proton is nowadays a limitation in this comparison. The aim of muonic hydrogen spectroscopy was to obtain an accurate value of the proton charge radius. However, the value deduced from this experiment contradicts other less accurate determinations. This problem is known as the proton radius puzzle. This new determination of the proton radius may affect the value of the Rydberg constant . This constant is related to many fundamental constants; in particular, links the two possible ways proposed for the redefinition of the kilogram, the Avogadro constant N(A) and the Planck constant h. However, the current relative uncertainty on the experimental determinations of N(A) or h is three orders of magnitude larger than the 'possible' shift of the Rydberg constant, which may be shown by the new value of the size of the proton radius determined from muonic hydrogen. The proton radius puzzle will not interfere in the redefinition of the kilogram. After a short introduction to the properties of the proton, we will describe the muonic hydrogen experiment. There is intense theoretical activity as a result of our observation. A brief summary of possible theoretical explanations at the date of writing of the paper will be given. The contribution of the proton radius puzzle to the redefinition of SI-based units will then be examined.

A novel insulin formulation with a more rapid onset of action.

AIMS/HYPOTHESIS: This study evaluates the pharmacodynamic and pharmacokinetic properties of the novel ultra-fast insulin product VIAject, a formulation of human soluble insulin and generally recognised as safe ingredients designed to increase the rate of absorption. METHODS: We performed five euglycaemic glucose clamps (Biostator; target blood glucose 5 mmol/l) in ten healthy volunteers. Using a crossover design with a fixed treatment order, 12 IU human soluble insulin, 12 U insulin lispro and 12 IU ultra-fast insulin were injected s.c. in the abdominal region on three study days. On the other two study days, 6 and 3 IU ultra-fast insulin were injected. RESULTS: Subcutaneous injection of 12 IU ultra-fast insulin resulted in a time-action profile characterised by an even more rapid onset of action and maximal metabolic activity than insulin lispro: time to early half-maximal activity was 33 +/- 17 min (mean +/- SD) vs insulin lispro 51 +/- 13 min vs human soluble insulin 66 +/- 15 min (p < 0.05 ultra-fast insulin

Acoustic properties of amorphous silica between 1 and 500 mK.

We have made reliable measurements of the sound velocity delta v/v(0) and internal friction Q(-1) in vitreous silica at 1.03, 3.74, and 14.0 kHz between 1 mK and 0.5 K. In contrast with earlier studies that did not span as wide a temperature and frequency range, our measurements of Q(-1) reveal a crossover (as T decreases) only near 10 mK from the T(3) dependence predicted by the standard tunneling model to a T dependence predicted if interactions are accounted for. We find good fits at all frequencies using a single interaction parameter, the prefactor of the interaction-driven relaxation rate, in contrast to earlier claims of a frequency dependent power law. We also show that the discrepancy in the slopes d(delta v/v(0))/d(log(10)T) below and above the sound velocity maximum (1: -1 observed, 1: -2 predicted) can be resolved by assuming a modified distribution of tunneling states.

Effect of age on diurnal changes of 24-hour QT interval variability.

QT interval on the surface electrocardiogram (ECG) reflects the time for repolarization of myocardium and prolongation of QTc is strongly associated with sudden cardiac death. Studies using novel techniques on beat-to-beat QT interval variability (QTV) have shown that it is influenced by the autonomic nervous system and is a predictor of sudden cardiac death. In this study, we examined the awake and sleep changes in QTV in 39 normal adults (mean age, 35 years) and 10 children (mean age, 11 years) using 24-hour ECG records. We obtained eight 5-minute segments of ECG sampled at 1000 Hz from the 24-hour records. Our results show that there is a diurnal variation of QTvm, detrended QT interval variance corrected for mean QT, and QTvi, an index of QTvm divided by heart rate variability corrected for mean heart rate. There was a significant increase in mean QT during sleep, whereas there was a significant decrease in QTvm and QTvi. QTvi significantly increased during the early morning hours. There were significant but modest correlations between the average 24-hour and awake QTvi and age (p < 0.01). There were also decreased low-frequency and high-frequency powers of QT during sleep. Coherence between heart rate and QT interval fluctuations in the range of 0-0.5 Hz, and especially in the high-frequency range (0.15-0.5 Hz), was significantly lower in adults than in children (p < 0.0002). These findings demonstrate diurnal fluctuations in ventricular repolarization lability. We speculate that these effects may relate to changes in cardiac autonomic function and may contribute to the well-known diurnal variation in the incidence of ventricular arrhythmias.

Effect of low-level radiation on the low temperature acoustic behavior of a-SiO2.

We report on the mechanical behavior of an a-SiO2 84 kHz torsional oscillator operated between 100> or =T> or =1.0 mK. Below 10 mK we observed well-differentiated transient responses which we attribute to the interaction with low-level background radiation (gamma quanta and cosmic ray micro) and which can be modeled in terms of a change in the spring constant.

Pilot study with technosphere/PTH(1-34)--a new approach for effective pulmonary delivery of parathyroid hormone (1-34).

Sequential subcutaneous PTH injection therapy (repeated 14 days of PTH administration and a subsequent treatment pause for a few weeks) is known to increase bone mineral density in patients with osteopenic disorders. Alternative methods of drug delivery may be beneficial in increasing compliance. A pilot study was performed in 10 healthy volunteers (4 female/6-male, age: 25.6 +/- 3.5 years, BMI: 22.3 +/- 2.4 kg/m 2, mean +/- SD) to assess the pharmacokinetic profiles of 1600 IU of PTH(1 - 34) using the pulmonary Technosphere drug delivery system in comparison to a subcutaneous injection of 400 IU. The treatments were administered in the morning after an overnight fast and blood samples for measurement of PTH(1 - 34), PTH(1 - 84), and calcium and calcitonin were taken over a period of 6 hours. Both injection and pulmonary application of PTH(1 - 34) were well tolerated. After pulmonary administration of Technosphere/PTH(1 - 34), PTH(1 - 34) appeared in the serum with a faster concentration increase (T max: pulmonary 10 +/- 5 min vs. subcutaneous 28 +/- 8 min, p < 0.001) and with higher maximal concentrations (C max : pulmonary 309 +/- 215 pmol/l vs. subcutaneous 102 +/- 45 pmol/l, p < 0.05) as compared to the subcutaneous injection. The relative bioavailability of pulmonary Technosphere/PTH(1 - 34) was calculated to be 48 %. No differences were seen between pulmonary and subcutaneous application with regard to the PTH(1 - 84), calcitonin and calcium concentrations. In conclusion, pulmonary application of Technosphere/PTH(1 - 34) appears to be an effective and thus attractive candidate for PTH substitution therapy in osteoporosis and other conditions leading to a decrease in bone mineral density.

rolling pebbles (rols) is required in Drosophila muscle precursors for recruitment of myoblasts for fusion.

Mutations in the rolling pebbles (rols) gene result in severe defects in myoblast fusion. Muscle precursor cells are correctly determined, but myogenesis does not progress significantly beyond this point because recognition and/or cell adhesion between muscle precursor cells and fusion-competent myoblasts is disturbed. Molecular analysis of the rols genomic region reveals two variant transcripts of rols due to different transcription initiation sites, rols6 and rols7. rols6 mRNA is detectable mainly in the endoderm during differentiation as well as in malpighian tubules and in the epidermis. By contrast, rols7 expression is restricted to the mesoderm and later to progenitor descendants during somatic and pharyngeal muscle development. Transcription starts at the extended germ band stage when progenitor/founder cells are determined and persists until stage 13. The proteins encoded by the rols gene are 1670 (Rols6) and 1900 (Rols7) amino acids in length. Both forms contain an N-terminal RING-finger motif, nine ankyrin repeats and a TPR repeat eventually overlaid by a coiled-coil domain. The longer protein, Rols7, is characterized by 309 unique N-terminal amino acids, while Rols6 is distinguishable by 79 N-terminal amino acids. Expression of rols7 in muscle founder cells indicates a function of Rols7 in these cells. Transplantation assays of rols mutant mesodermal cells into wild-type embryos show that Rols is required in muscle precursor cells and is essential to recruit fusion-competent myoblasts for myotube formation.