Accountable Care Organizations and Transaction Cost Economics

Using a Transaction Cost Economics (TCE) approach, this paper explores which organizational forms Accountable Care Organizations (ACOs) may take. A critical question about form is the amount of vertical integration that an ACO may have, a topic central to TCE. We posit that contextual factors outside and inside an ACO will produce variable transaction costs (the non-production costs of care) such that the decision to integrate vertically will derive from a comparison of these external versus internal costs, assuming reasonably rational management abilities. External costs include those arising from environmental uncertainty and complexity, small numbers bargaining, asset specificity, frequency of exchanges, and information impactedness. Internal costs include those arising from human resource activities including hiring and staffing, training, evaluating (i.e., disciplining, appraising, or promoting), and otherwise administering programs. At the extreme, these different costs may produce either total vertical integration or little to no vertical integration with most ACOs falling in between. This essay demonstrates how TCE can be applied to the ACO organization form issue, explains TCE, considers ACO activity from the TCE perspective, and reflects on research directions that may inform TCE and facilitate ACO development

Clustered and Distinct: A Taxonomy of Local Multihospital Systems

Despite their prevalence and power in markets throughout the United States, local multihospital systems (LMSs)—also referred to as hospital-based “clusters”—remain an understudied organizational form, with studies instead primarily focusing either upon individual hospitals or viewing hospital systems collectively without distinguishing the local “sub-systems” that comprise larger regional or national hospital chains. To better understand these organizational forms, we develop a taxonomy specifically devoted to LMSs, applying taxonomic analysis methods to a sample of LMSs in six U.S. states while accounting for LMSs’ geographic arrangements and non-hospital-based service locations. Our analysis identifies five distinct LMS categories, with forms clearly distinguished according to their varying degrees of differentiation and integration. The study’s results accentuate the importance of accounting for hospital systems’ activities and arrangements in local markets—including their non-hospital-based sites—and highlight differences in systems’ achievement of integration and coordination across services and locations, providing considerations in light of U.S. health system reform as well as international patterns of regional system formation

Foreign medical graduates and U.S. physician supply: old issues and new questions

Recent increases in the number of foreign medical graduates (FMGs) in U.S. hospital-training positions raise new questions about the future role of FMGs in U.S. medicine. Despite an historical surplus of physicians, forces such as greater demand for resident house officers, stabilization in undergraduate medical education enrollment, increase in demand for medical services, growth in both the number of women in medicine and physician employment in group practices, and continuing imbalances in the distribution of physicians favor FMG migration to the United States. Health system reform must be sensitive to the historical, current, and future role FMGs play in medical care delivery, especially in regard to service in underserved areas, specialties, and employment settings.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30654/1/0000296.pd

Strategic Activity and Financial Performance of U.S. Rural Hospitals: A National Study, 1983 to 1988

This study examines the effect of 13 strategic management activities on the financial performance of a national sample of 797 U.S. rural hospitals during the period of 1983-1988. Controlled for environment-market, geographic-region, and hospital-related variables, the results show almost no measurable effect of strategic adoption on rural hospital profitability and liquidity. Where statistically significant relationships existed, they were more often negative than positive. These findings were not expected; it was hypothesized that positive effects across a broad range of strategies would emerge, other things being equal. Discussed are possible explanations for these findings as well as their implication for a rural health policy relying on individual rural hospital strategic adaptation to environmental change.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72301/1/j.1748-0361.1994.tb00225.x.pd

CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold

The CD8 co-receptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR)-binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~10-fold). In this study, we used a panel of MHCI mutants with altered CD8-binding properties to show that TCR-mediated antigen specificity is delimited by a pMHCI/CD8 affinity threshold. Our findings suggest that CD8 can be engineered within certain biophysical parameters to enhance the therapeutic efficacy of adoptive T-cell transfer irrespective of antigen specificity

CD8+ T-­cell specificity is compromised at a defined major histocompatibility complex class I/CD8 affinity threshold

The CD8 co-receptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR)-binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~10-fold). In this study, we used a panel of MHCI mutants with altered CD8-binding properties to show that TCR-mediated antigen specificity is delimited by a pMHCI/CD8 affinity threshold. Our findings suggest that CD8 can be engineered within certain biophysical parameters to enhance the therapeutic efficacy of adoptive T-cell transfer irrespective of antigen specificity

CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold

The CD8 coreceptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR) binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~ 1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~ 10-fold). In this study, we used a panel of MHCI mutants with altered CD8 binding properties to show that TCR-mediated antigen specificity is delimited by a pMHCI/CD8 affinity threshold. Our findings suggest that CD8 can be engineered within certain biophysical parameters to enhance the therapeutic efficacy of adoptive T-cell transfer irrespective of antigen specificity. The pMHCI/CD8 interaction controls specificit

Psychiatric gene discoveries shape evidence on ADHD\u27s biology

A strong motivation for undertaking psychiatric gene discovery studies is to provide novel insights into unknown biology. Although attention-deficit hyperactivity disorder (ADHD) is highly heritable, and large, rare copy number variants (CNVs) contribute to risk, little is known about its pathogenesis and it remains commonly misunderstood. We assembled and pooled five ADHD and control CNV data sets from the United Kingdom, Ireland, United States of America, Northern Europe and Canada. Our aim was to test for enrichment of neurodevelopmental gene sets, implicated by recent exome-sequencing studies of (a) schizophrenia and (b) autism as a means of testing the hypothesis that common pathogenic mechanisms underlie ADHD and these other neurodevelopmental disorders. We also undertook hypothesis-free testing of all biological pathways. We observed significant enrichment of individual genes previously found to harbour schizophrenia de novo non-synonymous single-nucleotide variants (SNVs; P=5.4 x 10-4) and targets of the Fragile X mental retardation protein (P=0.0018). No enrichment was observed for activity-regulated cytoskeleton-associated protein (P=0.23) or N-methyl-D-aspartate receptor (P=0.74) post-synaptic signalling gene sets previously implicated in schizophrenia. Enrichment of ADHD CNV hits for genes impacted by autism de novo SNVs (P=0.019 for non-synonymous SNV genes) did not survive Bonferroni correction. Hypothesis-free testing yielded several highly significantly enriched biological pathways, including ion channel pathways. Enrichment findings were robust to multiple testing corrections and to sensitivity analyses that excluded the most significant sample. The findings reveal that CNVs in ADHD converge on biologically meaningful gene clusters, including ones now established as conferring risk of other neurodevelopmental disorders

Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

The Pancreas Is Altered by In Utero Androgen Exposure: Implications for Clinical Conditions Such as Polycystic Ovary Syndrome (PCOS)

Using an ovine model of polycystic ovary syndrome (PCOS), (pregnant ewes injected with testosterone propionate (TP) (100 mg twice weekly) from day (d)62 to d102 of d147 gestation (maternal injection – MI-TP)), we previously reported female offspring with normal glucose tolerance but hyperinsulinemia. We therefore examined insulin signalling and pancreatic morphology in these offspring using quantitative (Q) RT-PCR and western blotting. In addition the fetal pancreatic responses to MI-TP, and androgenic and estrogenic contributions to such responses (direct fetal injection (FI) of TP (20 mg) or diethylstilbestrol (DES) (20 mg) at d62 and d82 gestation) were assessed at d90 gestation. Fetal plasma was assayed for insulin, testosterone and estradiol, pancreatic tissue was cultured, and expression of key β-cell developmental genes was assessed by QRT-PCR. In female d62MI-TP offspring insulin signalling was unaltered but there was a pancreatic phenotype with increased numbers of β-cells (