Evidence-Informed Case Rates: Paying for Safer, More Reliable Care

Compares estimated payments to providers using evidence-informed case rates -- which combine global fees with allowances for complications and performance incentives -- with fee-for-service payments in myocardial infarction and diabetes cases

Sustaining the Medical Home: How PROMETHEUS Payment Can Revitalize Primary Care

Argues for reforming the current fee-for-service payment system on the PROMETHEUS model of budgeting for a comprehensive episode of care for a condition. Analyzes the implications for a sustainable patient-centered medical home model of care delivery

Extensive craniospinal dissemination of extraventricular neurocytoma: A case report and review of literature

Central neurocytomas (CNCs) are benign intraventricular neoplasms seen in children and young adults. Rarely, neoplasms that are similar in histopathological appearance arise in the brain parenchyma and are termed as extra-ventricular neurocytoma (EVNC). These EVNCs commonly present as epilepsy and behave more aggressively than CNCs with poorer long-term outcome. Here, we present a case of EVNCs in a male child with multiple recurrences, aggressive behavior and extensive craniospinal dissemination. Keywords: Central neurocytoma, Extra-ventricular neurocytoma, Craniospinal disseminatio

Disability for Function: Loss of Ca²⁺-Binding Is Obligatory for Fitness of Mammalian βγ-Crystallins

Vertebrate βγ-crystallins belonging to the βγ-crystallin superfamily lack functional Ca²⁺-binding sites, while their microbial homologues do not; for example, three out of four sites in lens γ-crystallins are disabled. Such loss of Ca²⁺-binding function in non-lens βγ-crystallins from mammals (e.g., AIM1 and Crybg3) raises the possibility of a trade-off in the evolutionary extinction of Ca²⁺-binding. We test this hypothesis by reconstructing ancestral Ca²⁺-binding motifs (transforming disabled motifs into the canonical ones) in the lens γB-crystallin by introducing minimal sets of mutations. Upon incorporation of serine at the fifth position in the N/D-N/D-X-X-S/T(5)-S motif, which endowed a domain with microbial characteristics, a decreased domain stability was observed. Ca²⁺ further destabilized the N-terminal domain (NTD) and its serine mutants profoundly, while the incorporation of a C-terminal domain (CTD) nullified this destabilization. On the other hand, Ca²⁺-induced destabilization of the CTD was not rescued by the introduction of an NTD. Of note, only one out of four sites is functional in the NTD of γB-crystallins responsible for weak Ca²⁺ binding, but the deleterious effects of Ca²⁺ are overcome by introduction of a CTD. The rationale for the onset of cataracts by certain mutations, such as R77S, which have not been clarified by structural means, could be explained by this work. The findings presented here shed light on the evolutionary innovations in terms of the functional loss of Ca²⁺-binding and acquisition of a bilobed domain, besides imparting additional advantages (e.g., protection from light) required for specialized functions