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PubMed1991

Turn around or pull the plug? Lessons in hospital diversification.

Diversification has reached a crossroad. Ventures that are profitable or break even are likely to continue as such. For those which are not, management can divest through sale or liquidation or choose the "turnaround" route, which entails carefully and objectively appraising each diversification activity or entity. The initial step in a turnaround is to review the original strategic diversification objectives to determine if they remain valid. Next is a strategic overview and appraisal of the system's diversification activities. Specific, measurable objectives and action plans are necessary to guide the turnaround process. But even with the best turnaround plan, managers must anticipate the possibility of failure by establishing a "pull-the-plug" threshold. This is the point at which a venture's operating losses exceed the value of profits. Experience with successful turnarounds shows that corporate managers must consider the following steps: (1) the specialized skills and experience of the diversification activities' managers, (2) market-based volume and revenue projections, (3) downsizing space allocations, sharing space, or adding new services, (4) ways to keep from drowning in overhead, (5) appropriate organizational controls, (6) ways to improve patient access, (7) employee incentives, (8) use of equity capital, (9) effective management information systems, and (10) "sticking to the knitting."

Decision Making↗
PubMed1987

Hospital diversification: how to involve the pharmacy.

Participation by hospital pharmacy departments in planning and development of diversified services is described. Diversification requires market planning. Seven basic marketing steps are identification of mission, goals, and objectives; identification of growth strategies (market penetration, market development, product development, and diversification); market analysis of external factors (size, growth, and logistics; reimbursement and financial considerations; competition; regulatory issues; and legal issues); market analysis of internal factors (departmental organization and reporting lines, demographics of the institution, and costs and productivity associated with the new service); program development and design; implementation; and evaluation. Hospitals can diversify by expanding acute-care services through management contracts and mergers; developing new services to include long-term-care, ambulatory-care, occupational-health, and wellness programs; starting other health-care ventures, such as consulting, continuing medical education, and continuing education for nurses; and expanding into non-health-care businesses. Vertical diversification is finding new markets for existing services; horizontal diversification is development of new services for new markets. To diversify, an institution may need to change its corporate structure; it may form a family of corporations that includes a university, nonprofit hospitals, holding companies, for-profit corporations, joint ventures, and service organizations. Through diversification, institutions and pharmacy departments can create alternative sources of funding and offer more comprehensive services to patients.

Hospital Administration↗
PubMed1998

Multiple sites of V lambda diversification in cattle.

Ig repertoire diversification in cattle was studied in the ileal Peyer's patch (IPP) follicles of young calves and in the spleens of late first-trimester bovine fetuses. To investigate follicular diversification, individual IPP follicles were isolated by microdissection; VA diversity was examined by RT-PCR and subsequent cloning and sequencing. When 52 intrafollicular sequences from a 4-wk-old calf were determined and compared, two major groups, one of 23 members and the other of 25, could be delineated. An examination of these groups revealed clear genealogic relationships that implicated in situ diversification of V lambda sequences within the confines of an IPP follicle. V lambda expression was also examined in early (95 and 110 gestational day) fetal bovine spleens. Although earlier studies in cattle and sheep implicated the IPP as a likely site of Ab diversification, a close investigation of V lambda sequences in late first-trimester fetal calves revealed that diversity appears in the early fetal spleen before the establishment of a diverse repertoire in the ileum. When the sequences for the fetal spleen were compared with an existing pool of germline sequences, we found evidence of possible gene conversion events and possible untemplated point mutations occurring in sequences recovered from fetal spleens. We conclude that IPP is not the sole site of VA diversification in cattle. Also, as suggested for rabbits, cattle may use both gene conversion and untemplated somatic point mutation to diversify their primary VA repertoire.

Animals↗
PubMed2025

Isolation by distance promotes strain diversification in the wild mouse gut microbiota.

Bacterial species within the mammalian gut microbiota exhibit considerable strain diversity associated with both geography and host genetic ancestry. However, because geography and host ancestry are typically confounded, disentangling their contributions to the diversification of gut bacterial strains has remained challenging. Here, we show through joint profiling of gut bacterial and mitochondrial genomes from wild-living populations of deer mice (Peromyscus maniculatus) sampled across the United States that isolation by distance (IBD) drives gut bacterial strain diversification independently of the effects of host ancestry. Analyses revealed significant IBD in 27 predominant gut bacterial species, including members of the Muribaculaceae and Lachnospiraceae, but limited evidence for co-inheritance of gut bacterial genomes with mitochondria during the diversification of extant mouse populations. Gut bacterial species capable of forming spores exhibited reduced IBD independently of phylogenetic history, indicating that adaptations facilitating bacterial dispersal can mitigate the geographic structuring of strain diversity. These results show that the diversification of gut bacterial strains within rodent species has been mediated by geographic separation of host populations rather than host genealogical divergence.

biogeography↗
PubMed1999

MtDNA phylogeography and recent intra-island diversification among Canary Island Calathus beetles.

The genus Calathus Bonelli comprises 24 species on the Canary Islands. Sequences of 927 and 687 bp of the mitochondrial cytochrome oxidase I and II genes, respectively, as well as the intervening tRNA leu gene in 21 of the 24 species, have identified three genetically divergent and unequivocally monophyletic groupings. A phylogeographic analysis is presented for the major monophyletic group comprising all the species of Gran Canaria, La Gomera, and El Hierro, and two Tenerifean species. A distance-based phylogenetic analysis and maximum parsimony analysis have clearly shown that this clade is composed of four distinct lineages. DNA sequence data suggest a recent origin for this clade and that lineages have not evolved at the same rate. Compared with diversification patterns observed in other Coleoptera on the Canary Islands, diversification has been recent relative to the time of colonization within the islands of Gran Canaria and La Gomera. Calathus diversification on La Gomera has been greater than on Gran Canaria. The influences of geological and ecological history are discussed in relation to Calathus diversification.

Animals↗
PubMedDate not supplied

Preventing diversification of malignant tumor cells during therapy.

One of the most difficult problems arising during cancer therapy is the emergence of unique tumor cell subpopulations that express altered malignant and therapeutic properties. In model tumor systems cytotoxic therapies that eliminate all but a few tumor cells seem to stimulate cell diversification to yield heterogeneous cell populations with divergent properties. Clinically the use of repeated cycles of cytotoxic therapies followed by intervening recovery periods often results in the eventual emergence of highly resistant and increasingly malignant tumor cells. To circumvent tumor cell diversification during therapeutic recovery periods we suggest that cytostatic agents might be employed. Although cytostatic agents such as differentiation modulators, hormones, growth factors, vitamins, and other natural products are unlikely to be effective therapeutic agents if used alone, they could be used during therapeutic recovery periods to modulate the diversification of surviving tumor cells so that these periods might be characterized by less extensive tumor cell diversification. At the end of recovery periods after the removal of cytostatic agents, surviving tumor cells could be briefly restimulated by growth factors, hormones or mitogens, just prior to initiation of new cycles of therapy using cytotoxic agents.

Cell Division↗
PubMed1999

Diversification pattern of the HMG and SOX family members during evolution.

From a database containing the published HMG protein sequences, we constructed an alignment of the HMG box functional domain based on sequence identity. Due to the large number of sequences (more than 250) and the short size of this domain, several data sets were used. This analysis reveals that the HMG box superfamily can be separated into two clearly defined subfamilies: (i) the SOX/MATA/TCF family, which clusters proteins able to bind to specific DNA sequences; and (ii) the HMG/UBF family, which clusters members which bind non specifically to DNA. The appearance and diversification of these subfamilies largely predate the split between the yeast and the metazoan lineages. Particular emphasis was placed on the analysis of the SOX subfamily. For the first time our analysis clearly identified the SOX subfamily as structured in six groups of genes named SOX5/6, SRY, SOX2/3, SOX14, SOX4/22, and SOX9/18. The validity of these gene clusters is confirmed by their functional characteristics and their sequences outside the HMG box. In sharp contrast, there are only a few robust branching patterns inside the UBF/HMG family, probably because of the much more ancient diversification of this family than the diversification of the SOX family. The only consistent groups that can be detected by our analysis are HMG box 1, vertebrate HMG box 2, insect SSRP, and plant HMG. The various UBF boxes cannot be clustered together and their diversification appears to be extremely ancient, probably before the appearance of metazoans.

Animals↗
PubMed1998

HLA class II phenotype controls diversification of the autoantibody response in primary Sjögren's syndrome (pSS).

The coexistence of anti-La (SS-B) and anti-Ro (SS-A) autoantibodies in pSS is probably explained by intermolecular spreading of autoimmunity toward different components of the La/Ro ribonucleoprotein (RNP). In order to evaluate the role of the HLA class II phenotype in controlling diversification of this autoantibody response, 80 patients with pSS were typed by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) at the HLA class II loci DRB1, DQA1 and DQB1. Serum samples were examined for anti-La and anti-Ro by counterimmunoelectrophoresis and by ELISA using purified recombinant La and 60-kD Ro proteins. Patient sera were classified according to the extent of diversification of the anti-La, anti-Ro response including the presence or absence of precipitating anti-La antibodies. Immunogenic characteristics of these stratified groups were then studied. All patients with pSS, with or without autoantibodies to Ro and La, were found to have at least one of the HLA-DRB1 types DR2, DR3 or DR5. The HLA DR3-DQA1*0501-DQB1*02 (DR3-DQ2) haplotype was primarily associated with a diversified La/Ro RNP response containing precipitating autoantibodies to La (P<0.001); whereas the haplotype HLA DR2-DQA1*0102-DQB1*0602 (DR2-DQ1) was associated with a less diversified La/Ro RNP response containing non-precipitating (restricted epitope) anti-La autoantibodies (P<0.001). Anti-La-positive patients lacking both HLA-DR2 and HLA-DR3 all expressed the HLA-DQA1*0501 allele, which was present at increasing frequency with greater diversification of the anti-La/Ro autoantibody response. The association of distinct HLA haplotypes with different degrees of autoantibody diversification in patients with pSS suggests a model of HLA-restricted presentation of La/Ro peptide determinants to autoreactive helper T cells. We propose that non-precipitating anti-La responses are driven by limited intermolecular help from DR2-DQ1-restricted T helper cells recognizing Ro determinants. On the other hand, we speculate that the more diversified, precipitating anti-La responses obtain more efficient cognate T help from DR3-DQ2-restricted T helper cells recognizing La determinants, where HLA-DQA1*0501 may be a critical determinant for antigen presentation.

Alleles↗
PubMed1998

Age and rate of diversification of the Hawaiian silversword alliance (Compositae).

Comparisons between insular and continental radiations have been hindered by a lack of reliable estimates of absolute diversification rates in island lineages. We took advantage of rate-constant rDNA sequence evolution and an "external" calibration using paleoclimatic and fossil data to determine the maximum age and minimum diversification rate of the Hawaiian silversword alliance (Compositae), a textbook example of insular adaptive radiation in plants. Our maximum-age estimate of 5.2 +/- 0.8 million years ago for the most recent common ancestor of the silversword alliance is much younger than ages calculated by other means for the Hawaiian drosophilids, lobelioids, and honeycreepers and falls approximately within the history of the modern high islands (</=5.1 +/- 0.2 million years ago). By using a statistically efficient estimator that reduces error variance by incorporating clock-based estimates of divergence times, a minimum diversification rate for the silversword alliance was estimated to be 0.56 +/- 0.17 species per million years. This exceeds average rates of more ancient continental radiations and is comparable to peak rates in taxa with sufficiently rich fossil records that changes in diversification rate can be reconstructed.

Journal Article↗
PubMed2002

Analysis of histone acetyltransferase and histone deacetylase families of Arabidopsis thaliana suggests functional diversification of chromatin modification among multicellular eukaryotes.

Sequence similarity and profile searching tools were used to analyze the genome sequences of Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans and Drosophila melanogaster for genes encoding three families of histone deacetylase (HDAC) proteins and three families of histone acetyltransferase (HAT) proteins. Plants, animals and fungi were found to have a single member of each of three subfamilies of the GNAT family of HATs, suggesting conservation of these functions. However, major differences were found with respect to sizes of gene families and multi-domain protein structures within other families of HATs and HDACs, indicating substantial evolutionary diversification. Phylogenetic analysis identified a new class of HDACs within the RPD3/HDA1 family that is represented only in plants and animals. A similar analysis of the plant-specific HD2 family of HDACs suggests a duplication event early in dicot evolution, followed by further diversification in the lineage leading to Arabidopsis. Of three major classes of SIR2-type HDACs that are found in animals, fungi have representatives only in one class, whereas plants have representatives only in the other two. Plants possess five CREB-binding protein (CBP)-type HATs compared with one to two in animals and none in fungi. Domain and phylogenetic analyses of the CBP family proteins showed that this family has evolved three distinct types of CBPs in plants. The domain architecture of CBP and TAF(II)250 families of HATs show significant differences between plants and animals, most notably with respect to bromodomain occurrence and their number. Bromodomain-containing proteins in Arabidopsis differ strikingly from animal bromodomain proteins with respect to the numbers of bromodomains and the other types of domains that are present. The substantial diversification of HATs and HDACs that has occurred since the divergence of plants, animals and fungi suggests a surprising degree of evolutionary plasticity and functional diversification in these core chromatin components.

Acetyltransferases↗
PubMed1999

Patterns of genetic diversification within the Adh gene family in the grasses (Poaceae).

We investigated the evolutionary dynamics of the Adh gene family within the grasses (Poaceae), with the goal of using molecular evolutionary tools to understand the process of gene family diversification. We analyzed 21 Adh sequences representing a broad array of grasses. Phylogenetic analyses suggested that Adh duplicated into Adh1 and Adh2 before the radiation of the grasses roughly 65 MYA. Gene structure, including intron length, has varied little over this period. Conservation of intron length prompted investigation into the dynamics of intron evolution, particularly the ability of intron sequences to form secondary structures. Intron sequences did not have an extremely high or low minimum free energy of folding relative to permuted sequences, suggesting that individual Adh introns do not evolve under secondary structural constraints. For coding sequences, the diversification of Adh1 and Adh2 was marked by a shift in third-position G + C content. This shift may reflect differential selection for codon use. Diversification between Adh1 and Adh2 was also typified by a shift in nonsynonymous nucleotide substitution rates, but there was no evidence that relatively fast nonsynonymous nucleotide substitution rates in the Adh2 clade were a product of diversifying selection. Gene conversion may have played a role in retarding diversification of Adh1 and Adh2 in rice, but there is no evidence of gene conversion between paralogs in other taxa. Although the reasons for retention of two functional Adh genes remain obscure, we propose that a shift in gene expression was important for the retention of the two Adh gene copies within the grasses.

Alcohol Dehydrogenase↗
PubMed1984

Hospital diversification and financial management.

Hospital diversification and its impact on the operating ratio are studied for 62 New York hospitals during the period 1974-1979. Diversification and operating ratio are modeled in a two-stage least squares (TSLS) framework as being jointly dependent. Institutional diversification is found to yield better financial position, and the better operating ratio allows the institution the wherewithal to diversify. The impact of external government planning and hospital competition are also measured. An institution life cycle hypothesis is advanced to explain hospital behavior: boom and bust, diversification and divestiture, occasionally leading to closure or merger. These results should not be generalized beyond the New York State context. Restructuring of the organization, unrelated business ventures, and transactions with related organizations were not a problem in this sample. However, in 1983, many a new corporation is set up whose revenues do not become part of the hospital's and whose complex transactions conceal unallowable costs and maximize reimbursement. A number of hypotheses are advanced concerning hospital administrator's attitude toward risk.

Financial Management↗
PubMed2007

How does resource supply affect evolutionary diversification?

The availability of different resources in the environment can affect the outcomes of evolutionary diversification. A unimodal distribution of diversity with resource supply has been widely observed and explained previously in the context of selection acting in a spatially heterogeneous environment. Here, we propose an alternative mechanism to explain the relationship between resource supply and diversification that is based on selection for exploitation of different resources. To test this mechanism, we conducted a selection experiment using the bacterium Pseudomonas fluorescens in spatially homogeneous environments over a wide range of resource supply rates. Our results show that niche diversification peaks at intermediate levels of resource availability. We suggest that this unimodal relationship is due to evolutionary diversification that is driven by competition for resources but constrained by the ecological opportunity represented by different resource types. These processes may underlie some general patterns of diversity, including latitudinal gradients in species richness and the effects of anthropogenic enrichment of the environment.

Adaptation, Biological↗
PubMed2003

Diversification in sexual and asexual organisms.

Sexual reproduction has long been proposed as a major factor explaining the existence of species and species diversity. Yet, the importance of sex for diversification remains obscure because of a lack of critical theory, difficulties of applying universal concepts of species and speciation, and above all the scarcity of empirical tests. Here, we use genealogical theory to compare the relative tendency of strictly sexual and asexual organisms to diversify into discrete genotypic and morphological clusters. We conclude that asexuals are expected to display discrete clusters similar to those found in sexual organisms. Whether sexuals or asexuals display stronger clustering depends on a number of factors, but in at least some scenarios asexuals should display a stronger pattern. Confounding factors aside, the only explanation we identify for stronger patterns of diversification in sexuals than asexuals is if the faster rates of adaptive change conferred by sexual reproduction promote greater clustering. Quantitative comparisons of diversification in related sexual and asexual taxa are needed to resolve this issue. The answer should shed light not only on the importance of the different stages leading to diversification, but also on the adaptive consequences of sex, still largely unexplored from a macroevolutionary perspective.

Adaptation, Biological↗
PubMed1998

Diversification of rabbit VH genes by gene-conversion-like and hypermutation mechanisms.

Where, when and how does VH diversification occur in the rabbit? Early diversification by gene-conversion and somatic hypermutation in rabbit appendix and chicken bursa of Fabricius are similar processes; the chicken bursa and the rabbit appendix have homologous functions. However, diversification in bursa starts during embryonic development whereas it starts in rabbit appendix about 2 weeks after birth in the presence of antigens and superantigens that may contribute to positive and negative selection, affect B-cell expansion and mold the repertoire. The biochemical steps leading to diversification by gene conversion are unknown. However elevated levels of RAD51 mRNA in both chicken bursa and young rabbit appendix suggest that repair of double strand breaks may be involved. The base changes found in expressed rabbit VH sequences derived from rearrangement of known germline VH genes followed by one or more gene conversions occur with frequencies similar to those found in analyses of somatic hypermutation. The Ser codons in CDR1 and CDR2 of rabbit VH1 genes are all AGY rather than TCN, suggesting that they may represent intrinsic hotspots for hypermutation comparable to those described in human and mouse VH. Somatic hypermutation may further refine antibody affinities in rabbit germinal centers.

Animals↗
PubMed1989

Rearrangement and diversification of immunoglobulin light-chain genes in lymphoid cells transformed by reticuloendotheliosis virus.

Avian lymphoid cells transformed by reticuloendotheliosis virus (REV-T) serve as a model to analyze the mechanism by which B-cell differentiation and antibody diversification occur in birds. Immunoglobulin light-chain gene rearrangements, diversification, and expression were analyzed in 72 independently derived REV-T-transformed cell lines. Lymphoid cells transformed as the result of expression of the v-rel oncogene were divided into two distinct groups based on light-chain gene rearrangements. The status of the light-chain gene loci in these REV-T-transformed cell lines was determined in part by the ages of the chickens whose spleen cells were transformed. In embryonic spleen cell lines transformed by the v-rel oncogene, rearrangements were not detected, even after prolonged culture in vitro, indicating that these cells are arrested in B-cell differentiation. REV-T transformants derived from spleens obtained from chickens 2 weeks old or older, however, had at least one light-chain allele rearranged. All of the cell lines analyzed which exhibited rearranged light-chain genes contained light-chain transcripts, and most of the REV-T-transformed cells which displayed light-chain rearrangements expressed immunoglobulin protein. REV-T, therefore, transforms B-lymphoid cells at phenotypically different stages of development. Many REV-T-transformed cells undergo immunoglobulin chain gene rearrangements during prolonged propagation in vitro. Most of the cell lines which rearrange their light-chain alleles also undergo diversification during cultivation in vitro. Light-chain diversification occurs during or after the rearrangement event.

Aging↗
PubMed1998

Predictors of crop diversification: a survey of tobacco farmers in North Carolina (USA).

OBJECTIVE: To assess the attitudes and behaviours of North Carolina tobacco farmers around crop diversification. DESIGN: Cross-sectional telephone survey. PARTICIPANTS: Active tobacco farmers in 14 North Carolina counties (n = 1236), interviewed between January and April 1997 (91% response rate). OUTCOME MEASURES: Interest in, experience with, and perceived barriers to diversification. RESULTS: Most farmers (95%) grew/raised a commodity other than tobacco (mean = 2.8). A total of 60% of farmers expressed interest in trying other on-farm activities to supplement their tobacco and 60% reported taking action in the past year around supplementation. Younger age and college education were positively associated with interest. College education, off-farm income, and larger farm size were associated with the number of actions taken. For perceived external barriers to diversification, use of tobacco, percent income from tobacco, lack of college education, and younger age were most strongly associated with the number of barriers. For internal barriers (personal factors), percent income from tobacco, use of tobacco, and lack of college education were most strongly associated with the number of barriers. CONCLUSIONS: Most farmers were involved in diverse operations and expressed interest in continuing to diversify, although the breadth of diversification was narrow. Farmers noted many barriers to diversifying. If conventional production and marketing techniques are employed for non-tobacco alternatives, these alternatives may not provide the sustainable profitability that tobacco has afforded. Competition from foreign tobacco growers is the primary threat to the future of American growers and tobacco dependent communities.

Adult↗
PubMed1998

Organizational diversification in the American hospital.

This paper outlines a conceptual framework of organizational diversification and assesses the state of empirical research on hospital organizational change. The literature on economic organization of hospitals, one of the most developed branches of health services research, still has only weak ties to economic theory. Evolving physician-hospital organizations do not fit into existing frameworks based on horizontal integration, vertical integration, or diversification. Empirical research has primarily focused on horizontal integration, and cause-effect relationships are often obscured by models that depart from economic theory and lack controls for self-selection bias. Recent empirical studies indicate that hospital mergers had moderate, rather than dramatic, effects on the rate of change in operating costs, staffing, and scale. Mergers rarely resulted in hospital closure, but were as likely to result in acute care consolidation and restructuring as in conversion to non-acute inpatient uses. While administrative costs were higher in for-profit than non-profit system hospitals, total costs were similar. System hospitals had lower marginal and average costs per stay than independent hospitals. Hospital vertical integration into subacute care was largely an artifact of the governmental uniform pricing system, which encouraged vertical integration. Hospitals that shared governance or financial risks with physicians outperformed those with high levels of physician governance and financial integration (e.g. stock ownership). Formal physician-hospital organizational arrangements often served to coordinate managed care contracting or to forge links with primary care group practices. Hospital diversification into related services improved short-term financial performance over unrelated diversification, although long-term performance was similar.

Delivery of Health Care, Integrated↗