The Effects Of Medicare Payment Changes On Nursing Home Staffing

In light of persistent shortcomings in nursing home care quality and evidence that lower nurse staffing levels could be harmful to residents, we examine whether staffing levels are affected by changes in Medicare reimbursement rates. We exploit a 2006 change in Medicare’s methodology for adjusting provider payments for geographic differences in costs, a change that generated plausibly exogenous variation in nursing facility reimbursement rates. Our method compares facilities with higher and lower shares of Medicare resident days, which were differentially exposed to the payment changes we examine. Using panel data on US nursing homes from 2003 through 2009, we find that higher Medicare payments increased nurse staffing hours per resident day. Additional results suggest that changes in Medicare payments did not affect other measures of quality

Coastal ocean wind fields gauged against the performance of an ocean circulation model

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 31 (2004): L14303, doi:10.1029/2003GL019261.Atmosphere model-derived flux fields are used to force coastal ocean models. Coarse resolution and incomplete boundary layer dynamics limit the accuracy of these forcing fields and hence the performance of the ocean models. We address this limitation for the west Florida shelf using optimal interpolation to blend winds measured in situ with winds produced by model analyses. By improving the coastal wind field we improve the fidelity between currents modeled and currents observed. Comparisons between momentum analyses performed independently from the model and the data demonstrate the fidelity to be of a correct dynamical basis. We conclude that the primary limitation to coastal ocean model performance lies with the boundary conditions.Support was provided by the Office of Naval Research, Grant #s N00014-98-1-0158 and N00014-02-1-0972

Novel 2-amino-isoflavones exhibit aryl hydrocarbon receptor agonist or antagonist activity in a species/cell-specific context

The aryl hydrocarbon receptor (AhR) mediates the induction of a variety of xenobiotic metabolism genes. Activation of the AhR occurs through binding to a group of structurally diverse compounds, most notably dioxins, which are exogenous ligands. Isoflavones are part of a family which include some well characterised endogenous AhR ligands. This paper analysed a novel family of these compounds, based on the structure of 2-amino-isoflavone. Initially two luciferase-based cell models, mouse H1L6.1c2 and human HG2L6.1c3, were used to identify whether the compounds had AhR agonistic and/or antagonistic properties. This analysis showed that some of the compounds were weak agonists in mouse and antagonists in human. Further analysis of two of the compounds, Chr-13 and Chr-19, was conducted using quantitative real-time PCR in rat H4IIE and human MCF-7 cells. The results indicated that Chr-13 was an agonist in rat but an antagonist in human cells. Chr-19 was shown to be an agonist in rat but more interestingly, a partial agonist in human. Luciferase induction results not only revealed that subtle differences in the structure of the compound could produce species-specific differences in response but also dictated the ability of the compound to be an AhR agonist or antagonist. Substituted 2-amino-isoflavones represent a novel group of AhR ligands that must differentially interact with the AhR ligand binding domain to produce their species-specific agonist or antagonist activity and future ligand binding analysis and docking studies with these compounds may provide insights into the differential mechanisms of action of structurally similar compounds

Data assimilative hindcast of the Gulf of Maine coastal circulation

Author Posting. © American Geophysical Union, 2005. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 110 (2005): C10011, doi:10.1029/2004JC002807.A data assimilative model hindcast of the Gulf of Maine (GOM) coastal circulation during an 11 day field survey in early summer 2003 is presented. In situ observations include surface winds, coastal sea levels, and shelf hydrography as well as moored and shipboard acoustic Doppler D current profiler (ADCP) currents. The hindcast system consists of both forward and inverse models. The forward model is a three-dimensional, nonlinear finite element ocean circulation model, and the inverse models are its linearized frequency domain and time domain counterparts. The model hindcast assimilates both coastal sea levels and ADCP current measurements via the inversion for the unknown sea level open boundary conditions. Model skill is evaluated by the divergence of the observed and modeled drifter trajectories. A mean drifter divergence rate (1.78 km d−1) is found, demonstrating the utility of the inverse data assimilation modeling system in the coastal ocean setting. Model hindcast also reveals complicated hydrodynamic structures and synoptic variability in the GOM coastal circulation and their influences on coastal water material property transport. The complex bottom bathymetric setting offshore of Penobscot and Casco bays is shown to be able to generate local upwelling and downwelling that may be important in local plankton dynamics.This work was supported by CSCOR/COP/ NOAA as part of NOAA MERHAB program. DJM gratefully acknowledges support from JPL through the ocean vector wind science team. DRL and KWS acknowledge support of NOAA/COP ECOHAB program

Historic 2005 toxic bloom of Alexandrium fundyense in the western Gulf of Maine : 2. Coupled biophysical numerical modeling

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 113 (2008): C07040, doi:10.1029/2007JC004602.A coupled physical/biological modeling system was used to hindcast a massive Alexandrium fundyense bloom that occurred in the western Gulf of Maine in 2005 and to investigate the relative importance of factors governing the bloom's initiation and development. The coupled system consists of a state-of-the-art, free-surface primitive equation Regional Ocean Modeling System (ROMS) tailored for the Gulf of Maine (GOM) using a multinested configuration, and a population dynamics model for A. fundyense. The system was forced by realistic momentum and buoyancy fluxes, tides, river runoff, observed A. fundyense benthic cyst abundance, and climatological nutrient fields. Extensive comparisons were made between simulated (both physical and biological) fields and in situ observations, revealing that the hindcast model is capable of reproducing the temporal evolution and spatial distribution of the 2005 bloom. Sensitivity experiments were then performed to distinguish the roles of three major factors hypothesized to contribute to the bloom: (1) the high abundance of cysts in western GOM sediments; (2) strong ‘northeaster' storms with prevailing downwelling-favorable winds; and (3) a large amount of fresh water input due to abundant rainfall and heavy snowmelt. Model results suggest the following. (1) The high abundance of cysts in western GOM was the primary factor of the 2005 bloom. (2) Wind-forcing was an important regulator, as episodic bursts of northeast winds caused onshore advection of offshore populations. These downwelling favorable winds accelerated the alongshore flow, resulting in transport of high cell concentrations into Massachusetts Bay. A large regional bloom would still have happened, however, even with normal or typical winds for that period. (3) Anomalously high river runoff in 2005 resulted in stronger buoyant plumes/currents, which facilitated the transport of cell population to the western GOM. While affecting nearshore cell abundance in Massachusetts Bay, the buoyant plumes were confined near to the coast, and had limited impact on the gulf-wide bloom distribution.Research support was provided through the Woods Hole Center for Oceans and Human Health, National Science Foundation (NSF) grant OCE-0430723 and National Institute of Environmental Health Science (NIEHS) grant 1-P50-ES012742-01, ECOHAB program through NSF grant OCE-9808173 and NOAA grant NA96OP0099, and GOMTOX program through NOAA grant NA06NOS4780245

Read-Across of 90-day Rat Oral Repeated-Dose Toxicity: A Case Study for Selected n-Alkanols

n-Alkanols provide an excellent example where a category-approach to read-across may be used to estimate the repeated-dose endpoint for a number of untested derivatives (target chemicals) using experimental data for tested derivatives (source chemicals). n-Alkanols are non-reactive and exhibit the unspecific, reversible simple anaesthesia or non-polar narcosis mode of toxic action in that the metabolic products of the parent alcohols do not contribute to the toxic endpoint evaluated. In this case study, the chemical category is limited to the readily bioavailable (C5 to C13) analogues. The toxicokinetic premise includes rapid absorption via the gastrointestinal tract, distribution in the circulatory system, and first-pass metabolism in the liver resulting in metabolism via oxidation to CO2 and with minor elimination of oxidative intermediate as glucuronides. Two analogues have experimental 90-day oral repeated-dose toxicity data which exhibit qualitative and quantitative consistency. Typical findings include decreased body weight, slightly increased liver weight which, in some cases, is accompanied by clinical chemical and haematological changes but generally without concurrent histopathological effects at the Lowest Observed Effect Level (LOEL). Chemical similarity between the analogues is readily defined by a variety of structure-related properties; data uncertainty associated with toxicokinetic and toxicodynamic similarities is low. Uncertainty associated with mechanistic relevance and completeness of the read-across is reduced by the concordance of in vivo and in vitro results, as well as high throughput and in silico methods data. As shown in detail, the 90-day oral repeated-dose toxicity No Observed Effect Level (NOEL) value of 1000 mg/kg bw/d for 1-pentanol and 1-hexanol based on LOEL of very low systemic toxicity can be read across to fill the data gaps of the untested analogues in this category with acceptable uncertainty

Microcephaly, intellectual impairment, bilateral vesicoureteral reflux, distichiasis, and glomuvenous malformations associated with a 16q24.3 contiguous gene deletion and a Glomulin mutation

Two hereditary syndromes, lymphedema‐distichiasis (LD) syndrome and blepharo‐chelio‐dontic (BCD) syndrome include the aberrant growth of eyelashes from the meibomian glands, known as distichiasis. LD is an autosomal dominant syndrome primarily characterized by distichiasis and the onset of lymphedema usually during puberty. Mutations in the forkhead transcription factor FOXC2 are the only known cause of LD. BCD syndrome consists of autosomal dominant abnormalities of the eyelid, lip, and teeth, and the etiology remains unknown. In this report, we describe a proband that presented with distichiasis, microcephaly, bilateral grade IV vesicoureteral reflux requiring ureteral re‐implantation, mild intellectual impairment and apparent glomuvenous malformations (GVM). Distichiasis was present in three generations of the proband's maternal side of the family. The GVMs were severe in the proband, and maternal family members exhibited lower extremity varicosities of variable degree. A GLMN (glomulin) gene mutation was identified in the proband that accounts for the observed GVMs; no other family member could be tested. TIE2 sequencing revealed no mutations. In the proband, an additional submicroscopic 265 kb contiguous gene deletion was identified in 16q24.3, located 609 kb distal to the FOXC2 locus, which was inherited from the proband's mother. The deletion includes the C16ORF95 , FBXO31 , MAP1LC3B , and ZCCHC14 loci and 115 kb of a gene desert distal to FOXC2 and FOXL1 . Thus, it is likely that the microcephaly, distichiasis, vesicoureteral, and intellectual impairment in this family may be caused by the deletion of one or more of these genes and/or deletion of distant cis ‐regulatory elements of FOXC2 expression. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90599/1/35229_ftp.pd

Transcriptional interaction-assisted identification of dynamic nucleosome positioning

<p>Abstract</p> <p>Background</p> <p>Nucleosomes regulate DNA accessibility and therefore play a central role in transcription control. Computational methods have been developed to predict static nucleosome positions from DNA sequences, but nucleosomes are dynamic in vivo.</p> <p>Results</p> <p>Motivated by our observation that transcriptional interaction is discriminative information for nucleosome occupancy, we developed a novel computational approach to identify dynamic nucleosome positions at promoters by combining transcriptional interaction and genomic sequence information. Our approach successfully identified experimentally determined nucleosome positioning dynamics available in three cellular conditions, and significantly improved the prediction accuracy which is based on sequence information alone. We then applied our approach to various cellular conditions and established a comprehensive landscape of dynamic nucleosome positioning in yeast.</p> <p>Conclusion</p> <p>Analysis of this landscape revealed that the majority of nucleosome positions are maintained during most conditions. However, nucleosome occupancy at most promoters fluctuates with the corresponding gene expression level and is reduced specifically at the phase of peak expression. Further investigation into properties of nucleosome occupancy identified two gene groups associated with distinct modes of nucleosome modulation. Our results suggest that both the intrinsic sequence and regulatory proteins modulate nucleosomes in an altered manner.</p

Male gynecomastia and risk for malignant tumours – a cohort study

BACKGROUND: Men with gynecomastia may suffer from absolute or relative estrogen excess and their risk of different malignancies may be increased. We tested whether men with gynecomastia were at greater risk of developing cancer. METHODS: A cohort was formed of all the men having a histopathological diagnosis of gynecomastia at the Department of Pathology, University of Lund, following an operation for either uni- or bilateral breast enlargement between 1970–1979. All possible causes of gynecomastia were accepted, such as endogenous or exogenous hormonal exposure as well as cases of unknown etiology. Prior to diagnosis of gynecomastia eight men had a diagnosis of prostate carcinoma, two men a diagnosis of unilateral breast cancer and one had Hodgkin's disease. These patients were included in the analyses. The final cohort of 446 men was matched to the Swedish Cancer Registry, Death Registry and General Population Registry. RESULTS: At the end of the follow up in December 1999, the cohort constituted 8375.2 person years of follow-up time. A total of 68 malignancies versus 66.07 expected were observed; SIR = 1.03 (95% CI 0.80–1.30). A significantly increased risk for testicular cancer; SIR = 5.82 (95% CI 1.20–17.00) and squamous cell carcinoma of the skin; SIR = 3.21 (95% CI 1.71–5.48) were noted. The increased risk appeared after 2 years of follow-up. A non-significantly increased risk for esophageal cancer was also seen while no new cases of male breast cancer were observed. However, in the prospective cohort, diagnostic operations for gynecomastia may substantially have reduced this risk CONCLUSIONS: There is a significant increased risk of testicular cancer and squamous cell carcinoma of the skin in men who have been operated on for gynecomastia