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.

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.

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.

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.

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.

The mesodermal expression of rolling stone (rost) is essential for myoblast fusion in Drosophila and encodes a potential transmembrane protein.

In homozygous rolling stone embryos, the fusion of myoblasts to syncytial myotubes is diminished. Nevertheless, the visceral mesoderm, the heart mesoderm, and few somatic muscles are properly formed. Thus, we postulate a central role of rolling stone for the fusion process within the somatic mesoderm. We have cloned the rolling stone gene, and the deduced protein sequence is in accordance with a transmembrane protein, which agrees with the enrichment of Rost in the membrane fraction of Drosophila embryos. No homologous genes have been described so far. rolling stone is expressed in the embryonic nervous system and cells of the somatic mesoderm, most notable in muscle founder cells. To elucidate the function of rolling stone for myoblast fusion, we applied a knock-out strategy. The expression of an antisense rolling stone transcript specifically within the mesoderm of wild-type embryos results in fusion defects of myoblasts, proving that the rolling stone expression in the mesoderm is responsible for the rolling stone phenotype. We suggest that rolling stone is a member of a group of genes that are necessary for the fusion process during myogenesis.

Specific heat and thermal conductivity of solid fullerenes.

Evidence is presented that the lattice vibrations of compacted C(60)/C(70) fullerite microcrystals consist predominantly of localized modes. Vibrational motions of the rigid molecules ("buckyballs") have been identified as well as their internal vibrations. Debye waves play only a relatively minor role, except below approximately 4 kelvin. By comparison with other crystalline materials, for these materials the Einstein model of the specific heat and thermal conductivity of solids, which is based on the assumption of atoms (in this case, buckyballs) vibrating with random phases, is in much better agreement with the measurements than the Debye model, which is based on collective excitations.

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.

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.

The initiator element of the Drosophila beta2 tubulin gene core promoter contributes to gene expression in vivo but is not required for male germ-cell specific expression.

The tissue-specific expression of the Drosophila beta 2 tubulin gene ( B2t ) is accomplished by the action of a 14-bp activator element (beta2UE1) in combination with certain regulatory elements of the TATA-less, Inr-containing B2t core promoter. We performed an in vivo analysis of the Inr element function in the B2t core promoter using a transgenic approach. Our experiments demonstrate that the Inr element acts as a functional cis -regulatory element in vivo and quantitatively regulates tissue-specific reporter expression in transgenic animals. However, our mutational analysis of the Inr element demonstrates no essential role of the Inr in mediating tissue specificity of the B2t promoter. In addition, a downstream element seems to affect promoter activity in combination with the Inr. In summary, our data show for the first time the functionality of the Inr element in an in vivo background situation in Drosophila.

Cytochrome P-450-dependent xenobiotic metabolizing activity in Zymbal's gland, a specialized sebaceous gland of rodents.

Homogenates of Zymbal's glands from beta-naphthoflavone-treated rats and mice have 7-ethoxycoumarin O-deethylase activity, while those from rats also have aryl hydrocarbon hydroxylase activity. Measured concentrations of cytochrome P-450 in microsomes from Zymbal's glands of beta-naphthoflavone-treated rats are not higher than those from untreated rats. Studies of inhibitors of 7-ethoxycoumarin O-deethylation and aryl hydrocarbon hydroxylation in homogenates of Zymbal's glands from beta-naphthoflavone-treated rats suggest that these enzyme activities are catalyzed by cytochrome P-450. These findings indicate that reactive metabolites of chemical carcinogens may be formed in Zymbal's gland, a target organ for chemical carcinogenesis.

Essential genes for myoblast fusion in Drosophila embryogenesis.

In Drosophila, as in vertebrates, each muscle is a syncytium and arises from mesodermal cells by successive fusion. This requires cell-cell recognition, alignment, formation of prefusion complexes, followed by electron-dense plaques and membrane breakdown. Because muscle development in Drosophila is rapid and well-documented, it has been possible to identify several genes essential for fusion. Molecular analysis of two of these genes revealed the importance of cytoplasmic components. One of these, Myoblast city, is expressed in several tissues and is homologous to the mammalian protein DOCK180. Myoblast city is presumably involved in cell recognition and cell adhesion. Blown fuse, the second cytoplasmic component, is selectively expressed in the mesoderm and essential in order to proceed from the prefusion complex to electron-dense plaques at opposed membranes between adjacent myoblasts. The rolling stone gene is transiently expressed during myoblast fusion. The Rost protein is located in the membrane and thus might be a key component for cell recognition. The molecular characterization of further genes relevant for fusion such as singles bar and sticks and stones will help to elucidate the mechanism of myoblast fusion in Drosophila.

During Drosophila embryogenesis the beta 1 tubulin gene is specifically expressed in the nervous system and the apodemes.

We determined the in vivo distribution of the beta 1 tubulin from D. melanogaster using isotype specific antibodies. Maternally expressed beta 1 tubulin is incorporated into mitotic spindles. Later in development a strong expression in the CNS is observed. Furthermore, all chordotonal organs and the apodemes are marked by beta 1 tubulin. Nuclear run-on assays and stage specific in vitro transcription showed a zygotic expression of the beta 1 tubulin gene from the extended germ-band stage onwards. Using the P-element system, we identified several elements; upstream between -2.2 kb and the transcription initiation site, elements for low level expression in the CNS are present. In the intron between +0.44 kb and +2.5 kb enhancer elements are located that drive the expression in the chordotonal organs and the apodemes. Between the start site and +0.44 kb (273 bp) and +2.5 kb and the second exon (315 bp), maternal and CNS enhancers result in full level expression of a lacZ-beta 1 reporter gene. We show, that the beta 1 tubulin gene is very early effector gene starting its expression shortly after the commitment of neuroblast cell fate. This gene offers an excellent model system for the identification of neural and apodeme specific transcription factors.

The Drosophila don juan (dj) gene encodes a novel sperm specific protein component characterized by an unusual domain of a repetitive amino acid motif.

We identified and characterized the don juan gene (dj) of Drosophila melanogaster. The don juan gene codes for a sperm specific protein component with an unusual repetitive six amino acid motif (DPCKKK) in the carboxy-terminal part of the protein. The expression of Don Juan is limited to male germ cells where transcription of the dj gene is initiated during meiotic prophase. But Western blot experiments indicate that DJ protein occurs just postmeiotically. Examination of transgenic flies bearing a dj-promoter-lacZ reporter construct revealed lacZ mRNA distribution resembling the expression pattern of the endogenous dj mRNA in the adult testes, whereas beta-galactosidase expression is exclusively present in postmeiotic germ cells. Thus, these observations strongly suggest that dj transcripts are under translational repression until in spermiogenesis. To study the function and subcellular distribution of DJ in spermiogenesis we expressed a chimaeric dj-GFP fusion gene in the male germline exhibiting strong GFP fluorescence in the liver testes, where only elongated spermatids are decorated. With regard to the characteristic expression pattern of DJ protein and its conspicuous repeat units possible functional roles are discussed.

Somatic mesoderm differentiation and the development of a subset of pericardial cells depend on the not enough muscles (nem) locus, which contains the inscuteable gene and the intron located gene, skittles.

Not enough muscles (nem) mutants of Drosophila reveal defects in the development of embryonic muscles, a subset of pericardial cells, the CNS and derivatives of the PNS (Burchard, S., Paululat, A., Hinz, U. and Renkawitz-Pohl, R. (1995) The mutant not enough muscles (nem) reveals reduction of the Drosophila embryonic muscle pattern. J. Cell. Sci. 108, 1443-1454). The molecular analysis of the nem locus shows a complex genomic structure. One transcription unit was identified as inscuteable (insc). Within the first intron of insc we find another independent gene, skittles (sktl), which is not affected in nem mutants. insc transcripts are localised apically in neuroblasts and may prefigure the localisation of the protein. The skittles mRNA is ubiquitously distributed during early embryogenesis due to maternal contribution. Later, some enrichment of sktl is observed in the nervous system and the mesoderm. The muscle phenotype shows deletions as well as duplication of specific muscles which is reflected in a change of even-skipped (eve) and Krüppel (Kr) expressing cells. Our data suggest a role for insc in the specification process of a subset of muscle progenitors/founders. Furthermore, in insc mutants the eve expressing pericardial cells of the developing heart are significantly reduced in numbers.