Arbitration Agreements and Your Malpractice Coverage

With new legislation and favorable case law developments, many providers of health care services are turning to binding arbitration agreements as a partial solution to the medical malpractice crisis. Existing data indicate tremendous advantages can be gained from the use of such agreements, if they are carefully drawn to comply with new law, tailored to the particular situation in which they will be used and coupled with appropriate procedures to secure the intended benefits.Arbitration is not a substitute for insurance, but if a provider has taken the calculated risk of forgoing insurance he should not be without a carefully drawn binding arbitration agreement.     

Purification and some properties of the phosphoprotein from rat incisors.

The phosphoprotein of rat incisors has been purified by successive gel and ion-exchange chromatography. The product gave a single band on polyacrylamide gel electrophoresis and contained approximately 34% phosphoserine and 32% aspartic acid. Alkaline elimination experiments showed all the phosphate to be present as phosphoserine. Ultraviolet spectra in the presence or absence of ATP showed that the phosphoprotein did not contain an nucleotide moiety as suggested by Veis, A., Spector, A. R. and Zamoscianyk, H. ((1972) Biochim. Biophys. Acta 257, 404-413) for bovine dentin phosphoprotein.     

The effect of a myelin apoprotein on lipid structure: a spin probe study.

Spin probes, stable free radical derivatives of stearic acid and cholestanone, were used to observe the effects of the "Folch-Lees" protein isolated from the white matter of bovine brain on the organization and motion of lipid molecules. The incorporation of the organic solvent soluble form of this protein decreased the tendency of a variety of lipid molecules with zero, positive or negative net charges to arrange themselves close to the normal to the lipid bilayer. The aqueous form of the protein also had a profound chaotropic effect on the molecular geometry of the lipid, but only if the lipids had a net negative charge (the protein has a net positive charge in the pH range investigated). Examination of the ESR spectra indicated that this protein altered the geometry of the lipid structure without causing major changes in the mobility of the individual lipid molecules.     

Uridine diphosphoglucose dehydrogenase in the intervertebral disc

Synopsis Intervertebral discs of an old sheep and a young pig were examined for the presence of cells containing the enzyme uridine diphosphoglucose dehydrogenase. In the sheep, the inner anulus had a higher proportion of active cells than the outer anulus; in the pig, there was no difference. From a consideration of cell numbers, it is suggested that there is an accumulation of glycosaminoglycans in the centre of the disc rather than an increased production rate. Notochordal cells in the pig disc contain uridine diphosphoglucose dehydrogenase and are capable of producing glycosaminoglycans.     

Parents exposed to warming produce offspring lower in weight and condition

The parental environment can alter offspring phenotypes via the transfer of non‐genetic information. Parental effects may be viewed as an extension of (within‐generation) phenotypic plasticity. Smaller size, poorer physical condition, and skewed sex ratios are common responses of organisms to global warming, yet whether parental effects alleviate, exacerbate, or have no impact on these responses has not been widely tested. Further, the relative non‐genetic influence of mothers and fathers and ontogenetic timing of parental exposure to warming on offspring phenotypes is poorly understood. Here, we tested how maternal, paternal, and biparental exposure of a coral reef fish (Acanthochromis polyacanthus) to elevated temperature (+1.5°C) at different ontogenetic stages (development vs reproduction) influences offspring length, weight, condition, and sex. Fish were reared across two generations in present‐day and projected ocean warming in a full factorial design. As expected, offspring of parents exposed to present‐day control temperature that were reared in warmer water were shorter than their siblings reared in control temperature; however, within‐generation plasticity allowed maintenance of weight, resulting in a higher body condition. Parental exposure to warming, irrespective of ontogenetic timing and sex, resulted in decreased weight and condition in all offspring rearing temperatures. By contrast, offspring sex ratios were not strongly influenced by their rearing temperature or that of their parents. Together, our results reveal that phenotypic plasticity may help coral reef fishes maintain performance in a warm ocean within a generation, but could exacerbate the negative effects of warming between generations, regardless of when mothers and fathers are exposed to warming. Alternatively, the multigenerational impact on offspring weight and condition may be a necessary cost to adapt metabolism to increasing temperatures. This research highlights the importance of examining phenotypic plasticity within and between generations across a range of traits to accurately predict how organisms will respond to climate change.     

Identifying control ensembles for information processing within the cortico-basal ganglia-thalamic circuit

In situations featuring uncertainty about action-reward contingencies, mammals can flexibly adopt strategies for decision-making that are tuned in response to environmental changes. Although the cortico-basal ganglia thalamic (CBGT) network has been identified as contributing to the decision-making process, it features a complex synaptic architecture, comprised of multiple feed-forward, reciprocal, and feedback pathways, that complicate efforts to elucidate the roles of specific CBGT populations in the process by which evidence is accumulated and influences behavior. In this paper we apply a strategic sampling approach, based on Latin hypercube sampling, to explore how variations in CBGT network properties, including subpopulation firing rates and synaptic weights, map to variability of parameters in a normative drift diffusion model (DDM), representing algorithmic aspects of information processing during decision-making. Through the application of canonical correlation analysis, we find that this relationship can be characterized in terms of three low-dimensional control ensembles within the CBGT network that impact specific qualities of the emergent decision policy: responsiveness (a measure of how quickly evidence evaluation gets underway, associated with overall activity in corticothalamic and direct pathways), pliancy (a measure of the standard of evidence needed to commit to a decision, associated largely with overall activity in components of the indirect pathway of the basal ganglia), and choice (a measure of commitment toward one available option, associated with differences in direct and indirect pathways across action channels). These analyses provide mechanistic predictions about the roles of specific CBGT network elements in tuning the way that information is accumulated and translated into decision-related behavior.     

Comparative analysis defines a broader FMRFamide-gated sodium channel family and determinants of neuropeptide sensitivity

FMRFamide (Phe-Met-Arg-Phe-amide, FMRFa) and similar neuropeptides are important physiological modulators in most invertebrates, but the molecular basis of FMRFa activity at its receptors is unknown. We therefore sought to identify the molecular determinants of FMRFa potency against one of its native targets, the excitatory FMRFa-gated sodium channel (FaNaC) from gastropod mollusks. Using molecular phylogenetics and electrophysiological measurement of neuropeptide activity, we identified a broad FaNaC family that includes mollusk and annelid channels gated by FMRFa, FVRIamides, and/or Wamides (or myoinhibitory peptides). A comparative analysis of this broader FaNaC family and other channels from the overarching degenerin (DEG)/epithelial sodium channel (ENaC) superfamily, incorporating mutagenesis and experimental dissection of channel function, identified a pocket of amino acid residues that determines activation of FaNaCs by neuropeptides. Although this pocket has diverged in distantly related DEG/ENaC channels that are activated by other ligands but enhanced by FMRFa, such as mammalian acid-sensing ion channels, we show that it nonetheless contains residues that determine enhancement of those channels by similar peptides. This study thus identifies amino acid residues that determine FMRFa neuropeptide activity at FaNaC receptor channels and illuminates the evolution of ligand recognition in one branch of the DEG/ENaC superfamily of ion channels.     

Proteomic identification of the cerebral cavernous malformation signaling complex

Cerebral cavernous malformations (CCM) are sporadic or inherited vascular lesions of the central nervous system characterized by dilated, thin-walled, leaky vessels. Linkage studies have mapped autosomal dominant mutations to three loci: ccm1 (KRIT1), ccm2 (OSM), and ccm3 (PDCD10). All three proteins appear to be scaffolds or adaptor proteins, as no enzymatic function can be attributed to them. Our previous results demonstrated that OSM is a scaffold for the assembly of the GTPase Rac and the MAPK kinase kinase MEKK3, for the hyperosmotic stress-dependent activation of p38 MAPK. Herein, we show that the three CCM proteins are members of a larger signaling complex. To define this complex, epitope-tagged wild type OSM or OSM harboring the mutation of F217-->A, which renders the OSM phosphotyrosine binding (PTB) domain unable to bind KRIT1, were stably introduced into RAW264.7 mouse macrophages. FLAG-OSM or FLAG-OSMF217A and the associated complex members were purified by immunoprecipitation using anti-FLAG antibody. OSM binding partners were identified by gel-based methods combined with electrospray ionization-MS or by multidimensional protein identification technology (MudPIT). Previously identified proteins that associate with OSM including KRIT1, MEKK3, Rac, and the KRIT1-binding protein ICAP-1 were found in the immunoprecipitates. In addition, we show for the first time that PDCD10 binds to OSM and is found in cellular CCM complexes. Other prominent proteins that bound the CCM complex include EF1A1, RIN2, and tubulin, with each interaction disrupted with the OSMF217A mutant protein. We further show that PDCD10 binds phosphatidylinositol di- and triphosphates and OSM binds phosphatidylinositol monophosphates. The findings define the targeting of the CCM complex to membranes and to proteins regulating trafficking and the cytoskeleton.     

Developing a vision for improved monitoring and reporting of riparian restoration projects

Representatives from agencies involved in natural resource management in the Murray‐Darling Basin gathered for a workshop in November 2010 to develop a vision for improved monitoring and reporting of riparian restoration projects. The resounding message from this workshop was that the effectiveness of riparian restoration depends on having sound, documented and agreed evidence on the ecological responses to restoration efforts. Improving our capacity to manage and restore riparian ecosystems is constrained by (i) a lack of ecological evidence on the effects of restoration efforts, and (ii) short‐termism in commitment to restoration efforts, in funding of monitoring and in expected time spans for ecosystem recovery. Restoration at the effective spatial scope will invariably require a long‐term commitment by researchers, funding agencies, management agencies and landholders. To address the knowledge gaps that constrain riparian restoration in the Basin, participants endorsed four major fields for future research: the importance of landscape context to restoration outcomes; spatio‐temporal scaling of restoration outcomes; functional effects of restoration efforts; and developing informative and effective indicators of restoration. To improve the monitoring and restoration of riparian zones throughout the Basin, participants advocated an integrated approach: a hierarchical adaptive management framework that incorporates long‐term ecological research.