Entry and Competition in Local Hospital Markets

There has been considerable consolidation in the hospital industry in recent years. Over 900 deals occurred from 1994-2000, and many local markets, even in large urban areas, have been reduced to monopolies, duopolies, or triopolies. This surge in consolidation has led to concern about competition in local markets for hospital services. We examine the effect of market structure on competition in local hospital markets -- specifically, does the hardness of competition increase with the number of firms? We extend the entry model developed by Bresnahan and Reiss to make use of quantity information, and apply it to data on the U.S. hospital industry. In the hospital markets we examine, entry leads to a quick convergence to competitive conduct. Entry reduces variable profits and increases quantity. Most of the effects of entry come from having a second and a third firm enter the market. The fourth entrant has little estimated effect. The use of quantity information allows us to infer that entry is consumer-surplus-increasing.

Biochemical aspects of Tourette's Syndrome

Kynurenine (KYN) is the first stable metabolite of the kynurenine pathway, the major route of tryptophan. (TRP) metabolIsm. In the liver, cortisol-inducible tIyptophan-2,3-dioxygenase (TDO) is the first enzyme and rate limiting step. In extrahepatic tissues, it is superceded by indoleamine-2,3-dioxygenase (IDO), an enzyme with a wider substrate specificity. Earlier work in this research group has found substantial elevations in plasma KYN in fasting Tourette's Syndrome (TS) patients with normal TRP and neopterin. The aim of our initial pilot study was to confirm this increase in KYN in fasting human TS patients compared with normal controls, and to see how changes in diet :ay influence certain kynurenine pathway variables. However, we failed to detect a change in plasma KYN, TRP, kynurenic acid (KYNA), neopterin or cortisol between the fasting TS and control groups. Moreover, none of the variables was affected by dietary status, and thus candidates selected for the larger cross-sectional study were permitted to eat and drink freely on the day that blood samples were submitted, but were requested to avoid products containing caffeine, aspirin or nicotine. In the cross-sectional study, TS patients exhibited significantly higher plasma KYN concentrations than controls, although the magnitude of the change was much smaller than originally found. This may be due to differences in detection procedure and the seasonal fluctuation of some biochemical variables, notably cortisol. The generalised increase in neopterin in the TS subject group, suggests a difference in the activity of cytokine-inducible IDO as a likely source for this elevated KYN. Other kynurenine pathway metabolites, specifIcally TRP, 3-hydroxykynurenine (HKY), 3-hydroxyanthranilic acid (HAA) and KYNA were unchanged. In view of recent speculation of the potential therapeutic effects of nicotine in TS, the lower KYN concentrations observed in TS smokers, compared with non-smoking TS patients, was another interesting finding. Tic-like movements, such as head-shakes (HS), which occur in rodents both spontaneously and following diverse drug treatments, closely resemble tic behaviours in humans. The animal tic model was used to examine what effects nicotine may have on shaking behaviours and on selected TRP metabolites. Acute systemic administration of nicotine to mice, produced a dose-dependent reduction in HS frequency (induced by the 5-HT2A/2C agonist DOl), which appeared to be mediated via central nicotinic cholinergic receptors, since mecamylamine pretreatment abolished this effect. Conversely, twice daily subcutaneous injections of nicotine for 7 days, led to an increase in spontaneous and DOI-induced HS. Chronic nicotine also caused a significant elevation m plasma and whole brain KYN concentrations, but plasma TRP, HKY, HAA and KYNA were unaltered. In addition, no change in brain 5-HT or 5-HIAA concentrations or 5-HT turnover, was found. Despite contrasting results from human and animal studIes, a role for nicotine in the mediation of tic-like movements is indicated. The relevance of the kynurenine pathway to TS and the potential role played by nicotine in modifying tic-like behaviours is discussed

Can governments do it better? Merger mania and hospital outcomes in the English NHS

Working Pape

Understanding Sustainability through Traditional Maasai Pastoral Systems in Southern Kenya

In the developed world, we tend to think of sustainability as a newly articulated solution to challenges of environmental resource degradation and issues of social and economic injustice. However, pastoralism, as traditionally practiced by the Maasai of southern Kenya, is intimately tied to the land and responds to climatic variation of the region. As a result of a shift toward privatization of land tenure, traditional pastoral systems are no longer viable. While studying abroad with The School For Field Studies, we became aware of the struggle many Maasai face as they attempt to continue pastoralism in an increasingly hostile environment. Ultimately, development efforts in the region should focus not on implementing exogenous concepts of ‘sustainability’ but rather on supporting and adapting systems that are already in place

Lightweight, low compression aircraft diesel engine

The feasibility of converting a spark ignition aircraft engine to the diesel cycle was investigated. Procedures necessary for converting a single cylinder GTS10-520 are described as well as a single cylinder diesel engine test program. The modification of the engine for the hot port cooling concept is discussed. A digital computer graphics simulation of a twin engine aircraft incorporating the diesel engine and Hot Fort concept is presented showing some potential gains in aircraft performance. Sample results of the computer program used in the simulation are included

PyMT-Maclow: A novel, inducible, murine model for determining the role of CD68 positive cells in breast tumor development

CD68+ tumor-associated macrophages (TAMs) are pro-tumorigenic, pro-angiogenic and are associated with decreased survival rates in patients with cancer, including breast cancer. Non-specific models of macrophage ablation reduce the number of TAMs and limit the development of mammary tumors. However, the lack of specificity and side effects associated with these models compromise their reliability. We hypothesized that specific and controlled macrophage depletion would provide precise data on the effects of reducing TAM numbers on tumor development. In this study, the MacLow mouse model of doxycycline-inducible and selective CD68+ macrophage depletion was crossed with the murine mammary tumor virus (MMTV)-Polyoma virus middle T antigen (PyMT) mouse model of spontaneous ductal breast adenocarcinoma to generate the PyMT-MacLow line. In doxycycline-treated PyMT-MacLow mice, macrophage numbers were decreased in areas surrounding tumors by 43%. Reducing the number of macrophages by this level delayed tumor progression, generated less proliferative tumors, decreased the vascularization of carcinomas and down-regulated the expression of many pro-angiogenic genes. These results demonstrate that depleting CD68+ macrophages in an inducible and selective manner delays the development of mammary tumors and that the PyMT-MacLow model is a useful and unique tool for studying the role of TAMs in breast cancer

Assessment of Maternal Vascular Remodeling During Pregnancy in the Mouse Uterus.

The placenta mediates the exchange of factors such as gases and nutrients between mother and fetus and has specific demands for supply of blood from the maternal circulation. The maternal uterine vasculature needs to adapt to this temporary demand and the success of this arterial remodeling process has implications for fetal growth. Cells of the maternal immune system, especially natural killer (NK) cells, play a critical role in this process. Here we describe a method to assess the degree of remodeling of maternal spiral arteries during mouse pregnancy. Hematoxylin and eosin-stained tissue sections are scanned and the size of the vessels analysed. As a complementary validation method, we also present a qualitative assessment for the success of the remodeling process by immunohistochemical detection of smooth muscle actin (SMA), which normally disappears from within the arterial vascular media at mid-gestation. Together, these methods enable determination of an important parameter of the pregnancy phenotype. These results can be combined with other endpoints of mouse pregnancy to provide insight into the mechanisms underlying pregnancy-related complications.This work was funded by The Wellcome Trust [094073/Z/10/Z], The Centre for Trophoblast Research and The British Heart Foundation.This is the author accepted manuscript. The final version is available from JOVE via http://dx.doi.org/10.3791/5353

MHC-dependent inhibition of uterine NK cells impedes fetal growth and decidual vascular remodelling.

NK cells express variable receptors that engage polymorphic MHC class I molecules and regulate their function. Maternal NK cells accumulate at the maternal-fetal interface and can interact with MHC class I molecules from both parents. The relative contribution of the two sets of parental MHC molecules to uterine NK cell function is unknown. Here we show that, in mice, maternal and not paternal MHC educates uterine NK cells to mature and acquire functional competence. The presence of an additional MHC allele that binds more inhibitory than activating NK cell receptors results in suppressed NK cell function, compromised uterine arterial remodelling and reduced fetal growth. Notably, reduced fetal growth occurs irrespectively of the parental origin of the inhibitory MHC. This provides biological evidence for the impact of MHC-dependent NK inhibition as a risk factor for human pregnancy-related complications associated with impaired arterial remodelling.This work was supported by the Wellcome Trust, the Medical Research Council, the Centre for Trophoblast Research and the British Heart Foundation.This is the final version of the article. It first appeared from Nature Publishing Group at http://dx.doi.org/10.1038/ncomms4359