Leadership development programs for health care middle managers: An exploration of the top management team member perspective.

BACKGROUND: Hospitals throughout the United States establish leadership and management programs for their middle managers. Despite their pervasiveness and an increased emphasis on physician leadership, there is limited research regarding the development programs designed for clinical and nonclinical health care middle managers. PURPOSE: Using two theoretical lenses, signaling and institutional theory, this exploratory study investigates mid-sized hospital development programs from the perspective of top management team (TMT) members. Our objective is to find out what types of programs hospitals have, how they are developed, and how they are evaluated. METHODOLOGY/APPROACH: We conducted semistructured interviews with 13 TMT members in six purposefully selected hospitals and matched these interviews with program curricula. Careful coding of the data allowed us not only to show our data in a meaningful visual representation but also to show the progression of the data from raw form to aggregate themes in the qualitative research process. FINDINGS: We identified four types of development programs used in the selected hospitals: (a) ongoing series, (b) curriculum-based, (c) management orientation, and (d) mentoring. Challenges existed in aligning the need for the program with program content. Communication occurred both through direct messaging regarding policies and procedures and through hidden signals. TMT members referenced other programs for guidance but were not always clear about what it is they wanted the programs to accomplish. Finally, there was limited program outcome measurement. PRACTICE IMPLICATIONS: Our small sample indicates that specific, structured, and comprehensive programs perform best. The better programs were always trying to improve but that most needed better accountability of tracking outcomes. In setting up a program, a collaborative approach among TMT members to establish what the needs are and how to measure outcomes worked well. Successful programs also tied in their leadership development with overall employee development.

Gtpbp2 is a positive regulator of Wnt signaling and maintains low levels of the Wnt negative regulator Axin.

BACKGROUND: Canonical Wnt signals, transduced by stabilized ß-catenin, play similar roles across animals in maintaining stem cell pluripotency, regulating cell differentiation, and instructing normal embryonic development. Dysregulated Wnt/ß-catenin signaling causes diseases and birth defects, and a variety of regulatory processes control this pathway to ensure its proper function and integration with other signaling systems. We previously identified GTP-binding protein 2 (Gtpbp2) as a novel regulator of BMP signaling, however further exploration revealed that Gtpbp2 can also affect Wnt signaling, which is a novel finding reported here. RESULTS: Knockdown of Gtpbp2 in Xenopus embryos causes severe axial defects and reduces expression of Spemann-Mangold organizer genes. Gtpbp2 knockdown blocks responses to ectopic Wnt8 ligand, such as organizer gene induction in ectodermal tissue explants and induction of secondary axes in whole embryos. However, organizer gene induction by ectopic Nodal2 is unaffected by Gtpbp2 knockdown. Epistasis tests, conducted by activating Wnt signal transduction at sequential points in the canonical pathway, demonstrate that Gtpbp2 is required downstream of Dishevelled and Gsk3ß but upstream of ß-catenin, which is similar to the previously reported effects of Axin1 overexpression in Xenopus embryos. Focusing on Axin in Xenopus embryos, we find that knockdown of Gtpbp2 elevates endogenous or exogenous Axin protein levels. Furthermore, Gtpbp2 fusion proteins co-localize with Dishevelled and co-immunoprecipitate with Axin and Gsk3b. CONCLUSIONS: We conclude that Gtpbp2 is required for canonical Wnt/ß-catenin signaling in Xenopus embryos. Our data suggest a model in which Gtpbp2 suppresses the accumulation of Axin protein, a rate-limiting component of the ß-catenin destruction complex, such that Axin protein levels negatively correlate with Gtpbp2 levels. This model is supported by the similarity of our Gtpbp2-Wnt epistasis results and previously reported effects of Axin overexpression, the physical interactions of Gtpbp2 with Axin, and the correlation between elevated Axin protein levels and lost Wnt responsiveness upon Gtpbp2 knockdown. A wide variety of cancer-causing Wnt pathway mutations require low Axin levels, so development of Gtpbp2 inhibitors may provide a new therapeutic strategy to elevate Axin and suppress aberrant ß-catenin signaling in cancer and other Wnt-related diseases.

Leveraging remote behavioral health interventions to improve medical outcomes and reduce costs.

OBJECTIVE: The dramatic rise in healthcare expenditures calls for innovative and scalable strategies to achieve measurable, near-term improvements in health. Our objective was to determine whether a remotely delivered behavioral health intervention could improve medical health, reduce hospital admissions, and lower cost of care for individuals with a recent cardiovascular event. STUDY DESIGN: This retrospective observational cohort study included members of a commercial health plan referred to participate in AbilTo's Cardiac Health Program. AbilTo is a national provider of telehealth, behavioral change programs for high risk medical populations. METHODS: The program is an 8-week behavioral health intervention delivered by a licensed clinical social worker and a behavioral coach via phone or secure video. RESULTS: Among the 201 intervention and 180 comparison subjects, the study found that program participants had significantly fewer all-cause hospital admissions in 6 months (293 per 1000 persons/year vs 493 per 1000 persons/year in the comparison group) resulting in an adjusted percent reduction of 31% (P = .03), and significantly fewer total hospital days (1455 days per 1000 persons/year vs 3933 per 1000 persons/year) with an adjusted percent decline of 48% (P = .01). This resulted in an overall savings in the cost of care even after accounting for total program costs. CONCLUSIONS: Successful patient engagement in a national, remotely delivered behavioral health intervention can reduce medical utilization in a targeted cardiac population. A restored focus on tackling barriers to behavior change in order to improve medical health is an effective, achievable population health strategy for reducing health costs in the United States.

The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima.

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.

Gtpbp2 is required for BMP signaling and mesoderm patterning in Xenopus embryos.

Smad proteins convey canonical intracellular signals for activated receptors in the TGFß superfamily, but the activity of Smads and their impact on target genes are further regulated by a wide variety of cofactors and partner proteins. We have identified a new Smad1 partner, a GTPase named Gtpbp2 that is a distant relative of the translation factor eEf1a. Gtpbp2 affects canonical signaling in the BMP branch of the TGFß superfamily, as morpholino knockdown of Gtpbp2 decreases, and overexpression of Gtpbp2 enhances, animal cap responses to BMP4. During Xenopus development, gtpbp2 transcripts are maternally expressed and localized to the egg animal pole, and partitioned into the nascent ectodermal and mesodermal cells during cleavage and early gastrulation stages. Subsequently, gtpbp2 is expressed in the neural folds, and in early tadpoles undergoing organogenesis gtpbp2 is expressed prominently in the brain, eyes, somites, ventral blood island and branchial arches. Consistent with its expression, morpholino knockdown of Gtpbp2 causes defects in ventral-posterior germ layer patterning, gastrulation and tadpole morphology. Overexpressed Gtpbp2 can induce ventral-posterior marker genes and localize to cell nuclei in Xenopus animal caps, highlighting its role in regulating BMP signaling in the early embryo. Here, we introduce this large GTPase as a novel factor in BMP signaling and ventral-posterior patterning.

Conservation and evolutionary divergence in the activity of receptor-regulated smads.

BACKGROUND: Activity of the Transforming growth factor-ß (TGFß) pathway is essential to the establishment of body axes and tissue differentiation in bilaterians. Orthologs for core pathway members have been found in all metazoans, but uncertain homology of the body axes and tissues patterned by these signals raises questions about the activities of these molecules across the metazoan tree. We focus on the principal canonical transduction proteins (R-Smads) of the TGFß pathway, which instruct both axial patterning and tissue differentiation in the developing embryo. We compare the activity of R-Smads from a cnidarian (Nematostella vectensis), an arthropod (Drosophila melanogaster), and a vertebrate (Xenopus laevis) in Xenopus embryonic assays. RESULTS: Overexpressing NvSmad1/5 ventralized Xenopus embryos when expressed in dorsal blastomeres, similar to the effects of Xenopus Smad1. However, NvSmad1/5 was less potent than XSmad1 in its ability to activate downstream target genes in Xenopus animal cap assays. NvSmad2/3 strongly induced general mesendodermal marker genes, but weakly induced ones involved in specifying the Spemann organizer. NvSmad2/3 was unable to induce a secondary trunk axis in Xenopus embryos, whereas the orthologs from Xenopus (XSmad2 and XSmad3) and Drosophila (dSmad2) were capable of doing so. Replacement of the NvSmad2/3 MH2 domain with the Xenopus XSmad2 MH2 slightly increased its inductive capability, but did not confer an ability to generate a secondary body axis. CONCLUSIONS: Vertebrate and cnidarian Smad1/5 have similar axial patterning and induction activities, although NvSmad1/5 is less efficient than the vertebrate gene. We conclude that the activities of Smad1/5 orthologs have been largely conserved across Metazoa. NvSmad2/3 efficiently activates general mesendoderm markers, but is unable to induce vertebrate organizer-specific genes or to produce a secondary body axis in Xenopus. Orthologs dSmad2 and XSmad3 generate a secondary body axis, but activate only low expression of organizer-specific genes that are strongly induced by XSmad2. We suggest that in the vertebrate lineage, Smad2 has evolved a specialized role in the induction of the embryonic organizer. Given the high level of sequence identity between Smad orthologs, this work underscores the functional importance of the emergence and fixation of a few divergent amino acids among orthologs during evolution.

Whole genome duplications and expansion of the vertebrate GATA transcription factor gene family.

BACKGROUND: GATA transcription factors influence many developmental processes, including the specification of embryonic germ layers. The GATA gene family has significantly expanded in many animal lineages: whereas diverse cnidarians have only one GATA transcription factor, six GATA genes have been identified in many vertebrates, five in many insects, and eleven to thirteen in Caenorhabditis nematodes. All bilaterian animal genomes have at least one member each of two classes, GATA123 and GATA456. RESULTS: We have identified one GATA123 gene and one GATA456 gene from the genomic sequence of two invertebrate deuterostomes, a cephalochordate (Branchiostoma floridae) and a hemichordate (Saccoglossus kowalevskii). We also have confirmed the presence of six GATA genes in all vertebrate genomes, as well as additional GATA genes in teleost fish. Analyses of conserved sequence motifs and of changes to the exon-intron structure, and molecular phylogenetic analyses of these deuterostome GATA genes support their origin from two ancestral deuterostome genes, one GATA 123 and one GATA456. Comparison of the conserved genomic organization across vertebrates identified eighteen paralogous gene families linked to multiple vertebrate GATA genes (GATA paralogons), providing the strongest evidence yet for expansion of vertebrate GATA gene families via genome duplication events. CONCLUSION: From our analysis, we infer the evolutionary birth order and relationships among vertebrate GATA transcription factors, and define their expansion via multiple rounds of whole genome duplication events. As the genomes of four independent invertebrate deuterostome lineages contain single copy GATA123 and GATA456 genes, we infer that the 0R (pre-genome duplication) invertebrate deuterostome ancestor also had two GATA genes, one of each class. Synteny analyses identify duplications of paralogous chromosomal regions (paralogons), from single ancestral vertebrate GATA123 and GATA456 chromosomes to four paralogons after the first round of vertebrate genome duplication, to seven paralogons after the second round of vertebrate genome duplication, and to fourteen paralogons after the fish-specific 3R genome duplication. The evolutionary analysis of GATA gene origins and relationships may inform understanding vertebrate GATA factor redundancies and specializations.

The evolution of protostome GATA factors: molecular phylogenetics, synteny, and intron/exon structure reveal orthologous relationships.

BACKGROUND: Invertebrate and vertebrate GATA transcription factors play important roles in ectoderm and mesendoderm development, as well as in cardiovascular and blood cell fate specification. However, the assignment of evolutionarily conserved roles to GATA homologs requires a detailed framework of orthologous relationships. Although two distinct classes, GATA123 and GATA456, have been unambiguously recognized among deuterostome GATA genes, it has been difficult to resolve exact orthologous relationships among protostome homologs. Protostome GATA genes are often present in multiple copies within any one genome, and rapidly evolving gene sequences have obscured orthology among arthropod and nematode GATA homologs. In addition, a lack of taxonomic sampling has prevented a stepwise reconstruction of protostome GATA gene family evolution. RESULTS: We have identified the complete GATA complement (53 genes) from a diverse sampling of protostome genomes, including six arthropods, three lophotrochozoans, and two nematodes. Reciprocal best hit BLAST analysis suggested orthology of these GATA genes to either the ancestral bilaterian GATA123 or the GATA456 class. Using molecular phylogenetic analyses of gene sequences, together with conserved synteny and comparisons of intron/exon structure, we inferred the evolutionary relationships among these 53 protostome GATA homologs. In particular, we resolved the orthology and evolutionary birth order of all arthropod GATA homologs including the highly divergent Drosophila GATA genes. CONCLUSION: Our combined analyses confirm that all protostome GATA transcription factor genes are members of either the GATA123 or GATA456 class, and indicate that there have been multiple protostome-specific duplications of GATA456 homologs. Three GATA456 genes exhibit linkage in multiple protostome species, suggesting that this gene cluster arose by tandem duplications from an ancestral GATA456 gene. Within arthropods this GATA456 cluster appears orthologous and widely conserved. Furthermore, the intron/exon structures of the arthropod GATA456 orthologs suggest a distinct order of gene duplication events. At present, however, the evolutionary relationship to similarly linked GATA456 paralogs in lophotrochozoans remains unclear. Our study shows how sampling of additional genomic data, especially from less derived and interspersed protostome taxa, can be used to resolve the orthologous relationships within more divergent gene families.

Ectoderm- and endomesoderm-specific GATA transcription factors in the marine annelid Platynereis dumerilli.

The GATA family of transcription factors appears to retain conserved roles in early germ layer patterning in most, if not all, animals; however, the number and structure of GATA factor genes varies substantially when different animal genomes are compared. Thus, the origin and relationships of invertebrate and vertebrate GATA factors, and their involvement in animal germ layer evolution, are unclear. We identified two highly conserved GATA factor genes in a marine annelid, the polychaete Platynereis dumerilii. A phylogenetic analysis indicates that the two Platynereis GATA factors are orthologous to the GATA1/2/3 and GATA4/5/6 subfamilies present in vertebrates. We also identified conserved motifs within each GATA class, and assigned the divergent Caenorhabditiselegans and Drosophila melanogaster GATA factor genes to the vertebrate classes. Similar to their vertebrate homologs, PdGATA123 mRNA expression was restricted to ectoderm, whereas PdGATA456 was detected only in endomesoderm. Finally, we identified in genome databases one GATA factor gene in each of two distantly related cnidarians that include motifs from both bilaterian GATA factor classes. Our results show that distinct orthologs of the two vertebrate GATA factor classes exist in a protostome invertebrate, suggesting that bilaterian GATA factors originated from GATA1/2/3 and 4/5/6 ancestral orthologs. Moreover, our results indicate that the GATA gene duplication and the functional divergence that led to these two ancestral GATA factor genes occurred after the split of the bilaterian stem group from the cnidarians.