Nursing home prices and quality of care - Evidence from administrative data.

There is widespread concern about the quality of care in nursing homes. On the basis of administrative data of a large health insurance fund, we investigate whether nursing home prices are associated with relevant quality of care indicators at the resident level. Our results indicate negative associations between price and both inappropriate and psychotropic medication. In contrast, we do not find any relationship between the price and impairments of physical health.

Precision Measurement of the p(e,e

New results are reported from a measurement of π^{0} electroproduction near threshold using the p(e,e^{'}p)π^{0} reaction. The experiment was designed to determine precisely the energy dependence of s- and p-wave electromagnetic multipoles as a stringent test of the predictions of chiral perturbation theory (ChPT). The data were taken with an electron beam energy of 1192 MeV using a two-spectrometer setup in Hall A at Jefferson Lab. For the first time, complete coverage of the ϕ_{π}^{*} and θ_{π}^{*} angles in the pπ^{0} center of mass was obtained for invariant energies above threshold from 0.5 up to 15 MeV. The 4-momentum transfer Q^{2} coverage ranges from 0.05 to 0.155 (GeV/c)^{2} in fine steps. A simple phenomenological analysis of our data shows strong disagreement with p-wave predictions from ChPT for Q^{2}>0.07 (GeV/c)^{2}, while the s-wave predictions are in reasonable agreement.

Self-perceived job insecurity and the demand for medical rehabilitation: does fear of unemployment reduce health care utilization?

An inverse relationship between job insecurity and sickness absence has been established in the literature, which is explained by employees avoiding to send signals of both poor health and uncooperative behavior towards the employer. In this paper, we focus on whether the same mechanism applies to the demand for medical rehabilitation measures. This question has recently gained much interest in the context of the current public debate on presenteeism. Using county-level unemployment rates as instrument for the employees' fear of job loss on the individual level, we find that an increase in subjective job insecurity substantially decreases the probability of participating in medical rehabilitation.

Activation barriers of oxygen transformation at the active site of [FeFe] hydrogenases.

Oxygen activation at the active sites of [FeFe] hydrogenases has been proposed to be the initial step of irreversible oxygen-induced inhibition of these enzymes. On the basis of a first theoretical study into the thermodynamics of O2 activation [Inorg. Chem. 2009, 48, 7127] we here investigate the kinetics of possible reaction paths at the distal iron atom of the active site by means of density functional theory. A sequence of steps is proposed to either form a reactive oxygen species (ROS) or fully reduce O2 to water. In this reaction cascade, two branching points are identified where water formation directly competes with harmful oxygen activation reactions. The latter are water formation by O-O bond cleavage of a hydrogen peroxide-bound intermediate competing with H2O2 dissociation and CO2 formation by a putative iron-oxo species competing with protonation of the iron-oxo species to form a hydroxyo ligand. Furthermore, we show that proton transfer to activated oxygen is fast and that proton supply to the active site is vital to prevent ROS dissociation. If sufficiently many reduction equivalents are available, oxygen activation reactions are accelerated, and oxygen reduction to water becomes possible.

Theoretical 57Fe Mössbauer spectroscopy for structure elucidation of [Fe] hydrogenase active site intermediates.

[Fe] hydrogenase is a hydrogen activating enzyme that features a monoiron active site, which can be well characterized by Mössbauer spectroscopy. Mössbauer spectra have been measured of the CO and CN(-) inhibited species as well as under turnover conditions [Shima, S. et al., J. Am. Chem. Soc., 2005, 127, 10430]. This study presents calculated Mössbauer parameters for various active-site models of [Fe] hydrogenase to provide structural information about the species observed in experiment. Because theoretical Mössbauer spectroscopy requires the parametrization of observables from first-principles calculations (i.e., electric-field gradients and contact densities) to the experimental observables (i.e., quadrupole splittings and isomer shifts), nonrelativistic and relativistic density functional theory methods are parametrized against a reference set of Fe complexes specifically selected for the application to the Fe center in [Fe] hydrogenase. With this methodology, the measured parameters for the CO and CN(-) inhibited complexes can be reproduced. Evidence for the protonation states of the hydroxyl group in close proximity to the active site and for the thiolate ligand, which could participate in proton transfer, is obtained. The unknown resting state measured in the presence of the substrate and under pure H2 atmosphere is identified to be a water-coordinated complex. Consistent with previous assignments based on infrared and X-ray absorption near-edge spectroscopy, all measured Mössbauer data can be reproduced with the active site's iron atom being in oxidation state +2.

Development of a reference material for analysing naturally occurring radioactive material from the steel industry.

Accurate measurement of naturally occurring radionuclides in blast furnace slag, a by-product of the steel industry, is required for compliance with building regulations where it is often used as an ingredient in cement. A matrix reference blast furnace slag material has been developed to support traceability in these measurements. Raw material provided by a commercial producer underwent stability and homogeneity testing, as well as characterisation of matrix constituents, to provide a final candidate reference material. The radionuclide content was then determined during a comparison exercise that included 23 laboratories from 14 countries. Participants determined the activity per unit mass for 226Ra, 232Th and 40K using a range of techniques. The consensus values obtained from the power-moderated mean of the reported participant results were used as indicative activity per unit mass values for the three radionuclides: A0(226Ra) = 106.3 (34) Bq·kg-1, A0(232Th) = 130.0 (48) Bq·kg-1 and A0(40K) = 161 (11) Bq·kg-1 (where the number in parentheses is the numerical value of the combined standard uncertainty referred to the corresponding last digits of the quoted result). This exercise helps to address the current shortage of NORM industry reference materials, putting in place infrastructure for production of further reference materials.

Molecular identification and microbiological evaluation of isolates from equipments and food contact surfaces in a hospital Food and Nutrition Unit.

The hygienic and sanitary control in Food and Nutrition Units (FNU) is considered a standard procedure to produce adequate meals and reduce the risk of foodborne diseases and hospital infections. This study aimed to evaluate the isolation and identification of bacteria from equipment and food contact surfaces in a hospital FNU as well as to evaluate the sanitary condition. Likewise, it was analyzed the adhesion of the microorganisms on polyethylene cutting boards. The presence of aerobic mesophilic microorganisms, yeasts, molds, coagulase-positive staphylococci, coliform and fecal coliform, and Escherichia coli were analyzed on eating tables, countertop surfaces and cutting boards used for meat or vegetable handling, and equipment such as microwaves and refrigerators. The molecular identification it was done by 16S rRNA gene sequencing. The adhesion of the microorganisms (biofilm formation) on meat and vegetable cutting boards was also evaluated by scanning electron microscopy. The results showed high numbers of all microorganisms, except for E. coli , which was not observed in the samples. The molecular analysis identified species of the Enterobacteriaceae family and species of the Pseudomonadaceae family. Scanning electron microscopy analyses revealed bacterial adhesion on the cutting board surfaces. The results obtained in this study indicated that the hygienic conditions of surfaces like plastic cutting boards and equipment in this hospital FNU were inadequate. The achievement and application of standard operating procedures could positively help in the standardization of sanitary control, reducing the microbial contamination and providing a safe food to hospitalized patients.

New Evidence on Employment Effects of Informal Care Provision in Europe.

OBJECTIVE: To estimate how labor force participation is affected when adult children provide informal care to their parents. DATA SOURCE: Survey of Health, Ageing and Retirement in Europe from 2004 to 2013. STUDY DESIGN: To offset the problem of endogeneity, we exploit the availability of other potential caregivers within the family as predictors of the probability to provide care for a dependent parent. Contrary to most previous studies, the dataset covers the whole working-age population in the majority of European countries. Individuals explicitly had to opt for or against the provision of care to their care-dependent parents, which allows us to more precisely estimate the effect of caregiving on labor force participation. PRINCIPAL FINDINGS: Results reveal a negative causal effect that indicates that informal care provision reduces labor force participation by 14.0 percentage points (95 percent CI: -0.307, 0.026). Point estimates suggest that the effect is larger for men; however, this gender difference is not significantly different from zero at conventional levels. CONCLUSIONS: Results apply to individuals whose consideration in long-term care policy is highly relevant, that is, children whose willingness to provide informal care to their parents is altered by available alternatives of family caregivers.

MetScore: Site of Metabolism Prediction Beyond Cytochrome P450 Enzymes.

The metabolism of xenobiotics by humans and other organisms is a complex process involving numerous enzymes that catalyze phase I (functionalization) and phase II (conjugation) reactions. Herein we introduce MetScore, a machine learning model that can predict both phase I and phase II reaction sites of drugs in a single prediction run. We developed cheminformatics workflows to filter and process reactions to obtain suitable phase I and phase II data sets for model training. Employing a recently developed molecular representation based on quantum chemical partial charges, we constructed random forest machine learning models for phase I and phase II reactions. After combining these models with our previous cytochrome P450 model and calibrating the combination against Bayer in-house data, we obtained the MetScore model that shows good performance, with Matthews correlation coefficients of 0.61 and 0.76 for diverse phase I and phase II reaction types, respectively. We validated its potential applicability to lead optimization campaigns for a new and independent data set compiled from recent publications. The results of this study demonstrate the usefulness of quantum-chemistry-derived molecular representations for reactivity prediction.

Site of Metabolism Prediction Based on ab†initio Derived Atom Representations.

Machine learning models for site of metabolism (SoM) prediction offer the ability to identify metabolic soft spots in low-molecular-weight drug molecules at low computational cost and enable data-based reactivity prediction. SoM prediction is an atom classification problem. Successful construction of machine learning models requires atom representations that capture the reactivity-determining features of a potential reaction site. We have developed a descriptor scheme that characterizes an atom's steric and electronic environment and its relative location in the molecular structure. The partial charge distributions were obtained from fast quantum mechanical calculations. We successfully trained machine learning classifiers on curated cytochrome P450 metabolism data. The models based on the new atom descriptors showed sustained accuracy for retrospective analyses of metabolism optimization campaigns and lead optimization projects from Bayer Pharmaceuticals. The results obtained demonstrate the practicality of quantum-chemistry-supported machine learning models for hit-to-lead optimization.

Human transitional cell carcinoma in the NMRI-nu/nu mouse bladder: a new animal model for the in vivo use of monoclonal antibodies and cytotoxic agents.

Human transitional cell carcinoma of the bladder was successfully transplanted into the bladder of the NMRI-nu/nu mouse. Transplantation of a single-cell suspension from a human Grade II transitional cell carcinoma had an acceptance rate of 33%. The tumors showed invasive growth and could be identified by an anti-human monoclonal antibody. This tumor model can be valuable as an in vivo test system for the local use of cytotoxic agents and monoclonal antibodies in diagnosis of and therapy for human bladder carcinoma.

Selective killing of human bladder cancer cells by combined treatment with A and B chain ricin antibody conjugates.

The monoclonal antibody 486P 3-12-1 raised against transitional bladder carcinoma cells was coupled to either the ricin A or B chain. The toxicity of A chain conjugates could be enhanced by addition of either free ricin B chain or by ricin B chain coupled to 486P 3-12-1 or to antibodies conjugated to ricin B and directed against the mouse monoclonal antibody. Using a two-step procedure where the A and B chains of ricin were delivered separately, the appropriate target cells 486P and 647V were killed, while the pancreatic cell line QGP-1 was not affected. The efficiency of killing by immunotoxin was independent whether free or coupled B chain was used, but B chain was essential for mediating the toxicity of the A chain. The two-step procedure enhances the selectivity of immunotoxin treatment by reducing nonspecific toxicity. Such a procedure could be applicable in vivo by direct administration to the bladder cavity.

Monoclonal antibody-defined human pancreatic cancer-associated antigens.

Three pancreatic cancer-associated antigens were characterized by use of monoclonal antibodies in immunobinding studies with various cellular and soluble target antigens, in immunoprecipitation, and in immunoperoxidase staining. C54-0 represents a tumor-associated Mr 122,000 antigen, which appears to be widely distributed on various epithelial tumors and to a lower extent on normal tissue. C1-N3 antigen exhibited a more restricted distribution, reacting with pancreatic and various gastrointestinal tract tumors as well as with chronically inflamed pancreatic tissue. The most specific antigen expression was observed for C1-P83 antigen, found on all exocrine tumors of the pancreas, but not on normal or chronically inflamed pancreatic tissue.

Chromatographic study on the specificity of bis-p-nitrophenylphosphate in vivo. Identification of labelled proteins of rat liver after intravenous injection of bis-p-nitro[14C]phenylphosphate as carboxylesterases and amidases.

The procedure established to isolate the carboxylesterases E1, E2 and EA from rat liver (Arndt, R. and Krisch, K. (1972) Hoppe-Seyler's Z. Physiol. Chem. 353, 589-598) was applied to characterize in vivo bis-p-nitro[14C]-phenyl-P-labelled proteins. The peaks of radioactivity and of residual enzyme activities (hydrolysing methylbutyrate, p-nitrophenylacetate and acetanilide) were found in the same peaks after column chromatography and could be related to the well-defined esterases E1, E2 and EA. There is no indication of a nonspecific binding of bis-p-nitrophenyl-P or of one of its metabolites. The relative quantitative amounts of E1, E2 and EA were calculated to represent 40, 14 and 46%, respectively, of the total carboxylesterase content of rat liver. The relative amount of bound (not dialysable) radioactivity in rat liver depended on the survival time. During purification, the yield of enzyme activities corresponded to that of bound radioactivity, confirming the specificity of bis-p-nitrophenyl-P in vivo. Hence the radioactive metabolites of the inhibitor obviously do not possess binding affinities of quantitative importance to the rat liver proteins.

Voltage-clamp experiments on oxidized cholesterol membranes modified with excitability-inducing material and comparison with a model.

The conductance of oxidized cholesterol membranes modified with excitability-inducing material was observed in membranes containing either single conductance channels or 100-1000 channels. Membranes containing single channels have several conductance states for each voltage polarity, and the current through membranes containing manychannels decays with at least two, and probably three, time constants following a step change in voltage (voltage-clamp). The time constants differ by about an order of magnitude. The multi-state behavior seems more pronounced in membranes made from highly oxidized cholesterol. Although a given conductance state could occur at either positive or negative voltages, each state was much more frequent at one polarity or the other. The most frequently observed single-channel conductance states in 0.1 M NaCl are about 0.3, 0.1, 0.03, and 0.0 n-1 for negative voltages and 0.25, 0.05, 0.03, and 0.0 n-1 for positive voltages. The current following a voltage clamp decays to a quasi-steady state within 1 min for positive voltages and 1-15 min for negative voltages. When the holding voltage is --20 mV, the decay constants and quasi-steady state conductances as functions of clamping voltage are reasonably well described by either a three-state model of the conductance or a two-state model applied independently at negative and positive voltages. However, for high voltages, the quasi-steady state does not appear to approach a state in which all the channels are in a low conductance state.

The singing vortex.

Marine propellers display several forms of cavitation. Of these, propeller-tip vortex cavitation is one of the important factors in propeller design. The dynamic behaviour of the tip vortex is responsible for hull vibration and noise. Thus, cavitation in the vortices trailing from tips of propeller blades has been studied extensively. Under certain circumstances cavitating vortices have been observed to have wave-like disturbances on the surfaces of vapour cores. Intense sound at discrete frequencies can result from a coupling between tip vortex disturbances and oscillating sheet cavitation on the surfaces of the propeller blades. This research article focuses on the dynamics of vortex cavitation and more in particular on the energy and frequency content of the radiated pressures.

Who responds to financial incentives for weight loss? Evidence from a randomized controlled trial.

There is a paucity of evidence on the heterogeneous impacts of financial incentives on weight loss. Between March 2010 and January 2012, in a randomized controlled trial, we assigned 700 obese persons to three experimental arms. We test whether particular subgroups react differently to financial incentives for weight loss. Two treatment groups obtained a cash reward (€150 and €300 with 237 and 229 participants, respectively) for achieving an individually-assigned target weight within four months; the control group (234 participants) was not incentivized. Participants and administrators were not blinded to the intervention. We find that monetary rewards effectively induced obese individuals to reduce weight across all subgroups. However, there is no evidence for treatment-effect heterogeneity for those groups that were incentivized. Among those who were in the €300 group, statistically significant and large weight losses were observed for women, singles, and those who are not working (all above 4 kg in four months). In addition, the magnitude of the reward matters only for women and migrants. The effectiveness of financial incentives to reduce weight nevertheless raises sensitive ethical issues that should be taken into consideration by policymakers.

Serological reactivity of recombinant 1D autoantigen and its expression in human thyroid and eye muscle tissue: a possible autoantigenic link in Graves' patients.

Thyroid-associated ophthalmopathy (TAO) is a potentially severe autoimmune disease, in and around the orbit, usually accompanied by Graves' disease. It was the goal of this study to develop a serological indicator for TAO and to characterize its expression in human thyroid and eye muscle tissue. Thus, we have recloned the full-length 1D-complementary DNA and assessed its expression levels in 90 healthy and diseased human thyroids. Only Graves' patients suffering from TAO (n = 29) displayed a significant, 2.1-fold increase of 1D expression levels (P = 0.029), compared with normal controls (n = 9), as assessed using the Mann-Whitney U-test for paired, nonnormally distributed samples. In contrast, a decrease of 1D expression (to 40% of control normal values) was confined to thyroid autonomy (n = 19, P = 0.032). In all other diseased human thyroids, including Graves' thyroids from patients not suffering from clinically overt TAO (n = 9), 1D expression levels were not different from the healthy controls. 1D gene expression was demonstrated in both healthy (n = 10) and diseased (n = 10) eye muscle tissues. Furthermore, a recombinant protein derived from baculovirus-infected Sf9 insect cells was purified under both nondenaturing and denaturing conditions. While under nondenaturing conditions, the molecular mass of recombinant 1D was determined to be 85 kDa; denaturing isolation yielded the expected 64-kDa protein. Autoantibodies against denatured 1D protein were not detectable in sera of diseased or healthy subjects. Immunoreactivity against the 85-kDa, nondenatured protein, evaluated in a panel of 222 different human sera, showed that 82% of Graves' patients suffering from TAO had autoantibodies against recombinant 1D, whereas only 5% of the healthy controls were positive for antibodies against 1D. Taken together, our results demonstrate a high disease sensitivity and specificity of recombinant, nondenatured 1D, to distinguish Graves' disease with or without TAO from other forms of thyroid and/or eye disease. Prospective studies will have to show whether autoantibodies against 1D can also be used as a prognosticator of TAO.

Strategy for typing human papillomaviruses by RFLP analysis of PCR products and subsequent hybridization with a generic probe.

Genital human papillomaviruses (HPV) were detected by PCR using L1 consensus primers MY09 and MY11. To determine the underlying HPV type(s). PCR products were subsequently analyzed employing a combination of restriction fragment length polymorphism (RFLP) and hybridization with a generic oligonucleotide probe that binds to a conserved region located close to the MY11-binding site within the PCR products. Using computer-assisted sequence analysis, the lengths of the corresponding BamHI, DdeI, HaeIII, HinfI and PstI restriction fragments hybridizing with the generic probe were calculated, revealing distinct patterns for each of the 45 mucosal HPV types. This method is superior to RFLP analysis since it is not impaired by large amounts of restriction fragments resulting from nonspecific PCR products. Moreover, considering clinical specimens containing two or three different HPV types, direct sequencing of PCR products will be inconclusive, and the increased number of restriction fragments will complicate interpretation of RFLP patterns. Subsequent hybridization with the generic probe, however, results in the appearance of, at most, 2 or 3 bands per restriction enzyme digest and thus facilitates identification of the underlying HPV types.