A Multi-Strategy Adaptive Comprehensive Learning PSO Algorithm and Its Application.

In this paper, a multi-strategy adaptive comprehensive learning particle swarm optimization algorithm is proposed by introducing the comprehensive learning, multi-population parallel, and parameter adaptation. In the proposed algorithm, a multi-population parallel strategy is designed to improve population diversity and accelerate convergence. The population particle exchange and mutation are realized to ensure information sharing among the particles. Then, the global optimal value is added to velocity update to design a new velocity update strategy for improving the local search ability. The comprehensive learning strategy is employed to construct learning samples, so as to effectively promote the information exchange and avoid falling into local extrema. By linearly changing the learning factors, a new factor adjustment strategy is developed to enhance the global search ability, and a new adaptive inertia weight-adjustment strategy based on an S-shaped decreasing function is developed to balance the search ability. Finally, some benchmark functions and the parameter optimization of photovoltaics are selected. The proposed algorithm obtains the best performance on 6 out of 10 functions. The results show that the proposed algorithm has greatly improved diversity, solution accuracy, and search ability compared with some variants of particle swarm optimization and other algorithms. It provides a more effective parameter combination for the complex engineering problem of photovoltaics, so as to improve the energy conversion efficiency.

Complete Genome Sequence of Campylobacter jejuni Strain 12567, a Livestock-Associated Clade Representative.

We report here the complete genome sequence of Campylobacter jejuni strain 12567, a member of a C. jejuni livestock-associated clade that expresses glycoconjugates associated with improved gastrointestinal tract persistence.

Complete Genome Sequences of Three Campylobacter jejuni Phage-Propagating Strains.

Bacteriophage therapy can potentially reduce Campylobacter jejuni numbers in livestock, but it requires a detailed understanding of phage-host interactions. C. jejuni strains readily infected by certain phages are designated as phage-propagating strains. Here, we report the complete genome sequences of three such strains, NCTC 12660, NCTC 12661, and NCTC 12664.

Adenomas with high-grade dysplasia and early adenocarcinoma are more likely to be sessile in the proximal colon.

AIM: Size and the sessile morphology of an adenoma may explain why colonoscopy is less effective in preventing proximal colonic cancer than distal cancers. We wanted to determine if advanced polypoid neoplasms (APNs, i.e. adenoma with high-grade dysplasia or early adenocarcinoma) are more likely to be sessile and/or smaller in the proximal colon. METHOD: We searched our institution's pathology database from 2004 to 2012 and identified patients with APNs. Polyps were categorized by size, morphology and location in the colon. Average polyp size and morphology were determined for each location. RESULTS: During the study period, 564 patients with APNs were identified. Of these, adenocarcinoma was noted in 21.6% and high-grade dysplasia in 78.4%. The average patient age was 64.4 years and 54.9% were men. The proportion of APNs that were ≤ 5 mm was 1.7%, ≤ 10 mm 19.3% and ≤ 15 mm 39%. APNs in the proximal colon were larger than those in the distal colon, but the difference was not statistically significant (27 vs 24 mm; P = 0.06). Eighty-three per cent of APNs in the proximal colon were sessile vs 57% in the distal colon (P = 0.001). APNs in the proximal colon were almost four times more likely to be sessile than in the distal colon (OR = 3.7). A similar association was noted for polyps ≤ 20 mm or polyps with high-grade dysplasia. CONCLUSION: APNs in the proximal colon were almost four-times more likely to be sessile than those in the distal colon. No difference in the size of polyps was noted.

A rare case series of concomitant inflammatory bowel disease, sporadic adenomas, and serrated polyposis syndrome.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) involving the colon is associated with an increased risk of colon cancer. Patients may develop sporadic adenomas further increasing their risk of colorectal cancer. Current knowledge of IBD with concomitant serrated polyposis syndrome (SPS) is limited. We describe four patients with both IBD and SPS. METHODS: Four patients with inflammatory bowel disease and hyperplastic polyps referred to Beth Israel Deaconess Medical Center meeting the World Health Organization (WHO) criteria for SPS were identified. RESULTS: Four patients with long standing IBD involving the colon were identified. All of these patients' IBD were in clinical remission. Additionally, 2 of the 4 patients were also noted to have sporadic adenomas. Each patient was also found to have multiple sessile serrated adenomas and hyperplastic polyps meeting the WHO criteria for SPS. Two of the patients had colonoscopy with chromoendoscopy which improved polyp detection. Discussions were held with each patient regarding the potentially increased risk of colorectal cancer with the combination of IBD and SPS. Patients were advised that colectomy would be the safest method to reduce the risk of cancer. None of the patients opted for colectomy and instead planned on a repeat colonoscopy with chromoendoscopy at 3-12 month intervals. CONCLUSION: Serrated polyposis syndrome develops in patients with IBD. It is unclear how high the risk of colon cancer is in patients who have both IBD and SPS and what the recommendations should be regarding the frequency of surveillance or surgery. Further studies are necessary to identify the optimal management of these patients.

Use of an improved atpA amplification and sequencing method to identify members of the Campylobacteraceae and Helicobacteraceae.

UNLABELLED: Emerging Campylobacter and Arcobacter spp. have been increasingly isolated from human clinical samples, food, veterinary samples and the environment. Unambiguous species identification of such organisms is of obvious importance in epidemiological studies, but is also necessary to accurately assess their host range and determine their prevalence in the food chain and in the environment. Species identification methods for the Campylobacteraceae have been described; however, some with high resolving power are limited to a small number of taxa, while other broader-range methods cannot distinguish between closely related species. We present in this study a novel species identification method, based on amplification and sequencing of a portion of the atpA gene. This method, which uses a single primer pair, was able to amplify and accurately identify all current taxa within Campylobacter and Arcobacter as well as several members of the Helicobacteraceae, although unambiguous identification of the Camp. fetus subspecies could not be achieved. In addition, five putative novel Campylobacter taxa were recognized, making this new species identification method valuable in the characterization of novel epsilonproteobacteria. Thus, a single-locus method that can accurately identify multiple epsilonproteobacterial species will prove important in the characterization of emerging organisms and those associated with illness. SIGNIFICANCE AND IMPACT OF THE STUDY: The atpA-based species identification method described here uses a single primer pair to amplify DNA from all current validly-described Campylobacter and Arcobacter taxa, as well as multiple members of the Helicobacteraceae. This method unambiguously identified all taxa tested, although it could not discriminate the subspecies of Camp. fetus. Furthermore, five putative novel Campylobacter taxa were observed following testing of environmental campylobacters with this method. The scope and resolution of this method make it an important addition to studies of epsilonproteobacterial epidemiology and evolution.

Milk-induced wheezing in children with asthma

Background: Food allergy has been gaining increasing attention, mostly as causing gastrointestinal and cutaneous reactions. Its role in asthma seems to be under-recognised. Objectives: This study's aim is to explore the frequency of involvement of a common food, namely cow's milk, in childhood asthma.Methods32 children (5 months to 11 years; median 24 months; mean 34 months) with asthma and a suspected history of cow's milk allergy were studied. They underwent skin prick testing (SPT) and specific IgE (sIgE) testing to whole cow's milk (WCM), casein, α-lactalbumin, and β-lactoglobulin, followed by single-blind oral milk challenge. Results: Reactions to milk challenge occurred in 12 (37.5%) including wheezing in 5 (41.7%, or 15.6% of the whole group). Children who developed wheezing at the time of challenge were younger than those who had negative challenge (23.0 months vs. 34.8 months). Challenge was positive in 33.3% of subjects who had a positive SPT, and SPT was positive in 50% of challenge-positive subjects. Regarding sIgE, challenge was positive in 26.7% of sIgE-positive subjects, and sIgE was positive in 33.3% of challenge positive subjects. Skin or serum testing with individual protein fractions did not seem to add significant advantage over testing with WCM alone. Conclusion: This study shows that cow's milk can cause wheezing in children with asthma. Although SPT seemed to be more reliable than sIgE testing, both had suboptimal reliability. It is worth considering possible milk allergy in children with asthma, particularly when poorly controlled in spite of proper routine management (AU)

Endovascular catheter for magnetic navigation under MR imaging guidance: evaluation of safety in vivo at 1.5T.

BACKGROUND AND PURPOSE: Endovascular navigation under MR imaging guidance can be facilitated by a catheter with steerable microcoils on the tip. Not only do microcoils create visible artifacts allowing catheter tracking, but also they create a small magnetic moment permitting remote-controlled catheter tip deflection. A side product of catheter tip electrical currents, however, is the heat that might damage blood vessels. We sought to determine the upper boundary of electrical currents safely usable at 1.5T in a coil-tipped microcatheter system. MATERIALS AND METHODS: Alumina tubes with solenoid copper coils were attached to neurovascular microcatheters with heat shrink-wrap. Catheters were tested in carotid arteries of 8 pigs. The catheters were advanced under x-ray fluoroscopy and MR imaging. Currents from 0 mA to 700 mA were applied to test heating and potential vascular damage. Postmortem histologic analysis was the primary endpoint. RESULTS: Several heat-mitigation strategies demonstrated negligible vascular damage compared with control arteries. Coil currents ≤300 mA resulted in no damage (0/58 samples) compared with 9 (25%) of 36 samples for > 300-mA activations (P = .0001). Tip coil activation ≤1 minute and a proximal carotid guide catheter saline drip > 2 mL/minute also had a nonsignificantly lower likelihood of vascular damage. For catheter tip coil activations ≤300 mA for ≤1 minute in normal carotid flow, 0 of 43 samples had tissue damage. CONCLUSIONS: Activations of copper coils at the tip of microcatheters at low currents in 1.5T MR scanners can be achieved without significant damage to blood vessel walls in a controlled experimental setting. Further optimization of catheter design and procedure protocols is necessary for safe remote control magnetic catheter guidance.

Milk-induced wheezing in children with asthma.

BACKGROUND: Food allergy has been gaining increasing attention, mostly as causing gastrointestinal and cutaneous reactions. Its role in asthma seems to be under-recognised. OBJECTIVES: This study's aim is to explore the frequency of involvement of a common food, namely cow's milk, in childhood asthma. METHODS: 32 children (5 months to 11 years; median 24 months; mean 34 months) with asthma and a suspected history of cow's milk allergy were studied. They underwent skin prick testing (SPT) and specific IgE (sIgE) testing to whole cow's milk (WCM), casein, α-lactalbumin, and ß-lactoglobulin, followed by single-blind oral milk challenge. RESULTS: Reactions to milk challenge occurred in 12 (37.5%) including wheezing in 5 (41.7%, or 15.6% of the whole group). Children who developed wheezing at the time of challenge were younger than those who had negative challenge (23.0 months vs. 34.8 months). Challenge was positive in 33.3% of subjects who had a positive SPT, and SPT was positive in 50% of challenge-positive subjects. Regarding sIgE, challenge was positive in 26.7% of sIgE-positive subjects, and sIgE was positive in 33.3% of challenge positive subjects. Skin or serum testing with individual protein fractions did not seem to add significant advantage over testing with WCM alone. CONCLUSION: This study shows that cow's milk can cause wheezing in children with asthma. Although SPT seemed to be more reliable than sIgE testing, both had suboptimal reliability. It is worth considering possible milk allergy in children with asthma, particularly when poorly controlled in spite of proper routine management.

GB toxicity reassessed using newer techniques for estimation of human toxicity from animal inhalation toxicity data: new method for estimating acute human toxicity (GB).

Estimated human inhalation toxicity values for Sarin (GB) were calculated using a new two independent (concentration, exposure time), one dependent (toxic response), non-linear dose response (toxicity) model combined with re-evaluated allometric equations relating to animal and human respiration. Historical animal studies of GB toxicity containing both exposure and fractional animal response data were used to test the new process. The final data set contained 6621 animals, 762 groups, 37 studies and 7 species. The toxicity of GB for each species was empirically related to exposure concentration (C; mg m(-3)) and exposure time (T; min) through the surface function Y = b0 + b1 Log10C + b2 Log10T or Y = b0 + b2 Log10C(n)T where Y is the Normit, b0, b1 and b2 are constants and n is the 'toxic load exponent' (Normit is PROBIT - 5). Between exposure times of 0.17 and 30 min, the average value for n in seven species was 1.35 +/- 0.15. The near parallel toxic load equations for each species and the linear relationship between minute volume/body weight ratio and the inhalation toxicity (LCt50) for GB were used to create a pseudo-human data set and then an exposure time/toxicity surface for the human. The calculated n for the human was 1.40. The pseudo-human data had much more variability at low exposure times. Raising the lower exposure limit to 1 min, did not change the LCt50 but did result in lower variability. Raising the lower value to 2 min was counterproductive. Based on the toxic load model for 1-30 min exposures, the human GB toxicities (LCt01, LCt05, LCt50 and LCt95) for 70 kg humans breathing 15 l min(-1) were estimated to be 11, 16, 36 and 83; 18, 25, 57 and 132 and 24, 34, 79 and 182 mg x min m(-3) for 2, 10 and 30 min exposures, respectively. These values are recommended for general use for the total human population. The empirical relationships employed in the calculations may not be valid for exposure times >30 min.

Allometric respiration/body mass data for animals to be used for estimates of inhalation toxicity to young adult humans.

The relationship between body weight (BW) and respiratory minute volume (V(m)) was reviewed by collecting a database from the literature. The data were separated into anaesthetized and non-anaesthetized groups. Only young adult terrestrial mammals were included in the final data set. This database is the largest to be reported to date, is the first to separate the anaesthetized and non-anaesthetized groups and is matched to the target population of young, fit adult humans. The data set of non-anaesthetized animals contained 142 studies representing 2616 animals and 18 species from mice at 12 g body weight to horses and a giraffe at ca. 500 kg body weight. Analysis of the data indicated a power law (allometric) relationship between the minute volume and body weight. The resulting allometric equations for the empirical relationship between minute volume and body weight are: log(10)V()(m)= -0.302 + 0.809 log(10)BW and V(m) = 0.499 BW(0.809)where V(m) is the minute volume (l min(-1)) and BW is the body weight (kg). From these equations, a minute volume of 15.5 lmin(-1)was obtained for a 70 kg human in the same physiological and/or emotional state as the animals. The results of the analyses were compared to other empirical studies in the literature, the more recent of which also indicated a scaling factor of 0.8. The relationship between minute volume and body weight is recommended for use in estimating the inhalation toxicity to young adult humans (military personnel), because this is the first study to use a large database focused exclusively upon non-anaesthetized young adult terrestrial mammals.

An impact-effect mathematical model incorporating the influence of exposures to fluctuating concentrations in a dispersing plume of pollutant in the atmosphere.

The statistical properties of the impact or toxic load (pollutant concentration raised to an exponent and multiplied by exposure duration), obtained from fluctuating concentrations in a plume dispersing in the atmosphere, are investigated both analytically and experimentally. A general expression for the kth order moment of the impact is derived in terms of the k-time point joint moment of the nth power of the fluctuating plume concentration field. Special cases of this general relationship are treated explicitly: (i) a simple model for the ensemble-mean impact (or equivalently, the ensemble-mean impact ratio) is derived on the basic hypothesis that the higher moments of concentration can be adequately modelled using an exponential probability density function (PDF), and this hypothesis is shown to give results that agree remarkably well with an extensive new set of concentration fluctuation measurements; and (ii) a model for the integral time scale of the process obtained by raising the concentration to the nth power is formulated using Gifford's meandering plume model, and the latter is subsequently used to derive a simple expression for estimating the impact variance for all exposure times, given the mean and mean-square concentrations and the plume concentration integral time scale only. The results of this model for impact variance are favorably compared with some data from full-scale field experiments. The impact PDF is found to be reasonably well-characterized by a clipped-normal PDF for exposure times, t(e), of practical interest (e.g., t(e) approximately >5 s). The implications of these results, for determining the fraction of an exposed population that will experience a specified level of effect from a random impact arising from exposure to a fluctuating plume of pollutant, are discussed briefly.

NF-kappaB activation is required for human endothelial survival during exposure to tumor necrosis factor-alpha but not to interleukin-1beta or lipopolysaccharide.

In the presence of a protein synthesis inhibitor, cycloheximide, tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1beta), or lipopolysaccharide (LPS) induces human umbilical vein endothelial cells (HUVECs) to undergo apoptosis, suggesting that constitutive or inducible cytoprotective pathways are required for cell survival. We studied the correlation between nuclear factor-kappaB (NF-kappaB) activation and cell death induced by TNF-alpha, IL-1beta, or LPS. Adenovirus-mediated overexpression of a dominant-negative IkappaBalpha (inhibitor of kappaB) mutant blocked NF-kappaB activation by gel shift assay and blocked induction of vascular cell adhesion molecule-1 protein by TNF-alpha, IL-1beta, and LPS, a NF-kappaB-dependent response. In cells overexpressing the IkappaBalpha mutant, TNF-alpha induced cell death, whereas IL-1beta or LPS did not. We conclude that cell survival following TNF-alpha stimulation is NF-kappaB-dependent but that a constitutive or inducible NF-kappaB-independent pathway(s) protects IL-1beta- or LPS-treated HUVECs from cell death.

Quantitation of human haptoglobin: comparative ELISA studies using adsorption and capture methods.

Three ELISA methods for the quantitation of haptoglobin (Hp) in plasma and albumin are described: a polystyrene direct adsorption method and capture methods with antibody and hemoglobin. Hp aggregates generated by 60 degrees C heating showed as much as a hundred-fold higher response by polystyrene adsorption compared to the two capture methods, while unheated Hp showed comparable responses by the three methods.

Lipopolysaccharide induces the antiapoptotic molecules, A1 and A20, in microvascular endothelial cells.

The effect of lipopolysaccharide (LPS) on endothelial cells is a key component of the inflammatory response seen in Gram-negative sepsis. LPS does not cause death of cultured human endothelial cells. However, when the expression of new proteins is inhibited by cycloheximide, microvascular endothelial cells in culture undergo apoptosis. This finding suggests that LPS induces apoptotic and antiapoptotic pathways, with the antiapoptotic response being dependent on the synthesis of new proteins. Concurrent activation of apoptotic and antiapoptotic pathways has previously been documented for tumor necrosis factor (TNF). In the case of TNF, the antiapoptotic signal has been attributed to at least two cytoprotective proteins: the Bcl-2 homologue, A1, and the zinc-finger protein, A20. In this study, we demonstrate that both these molecules are induced in microvascular endothelial cells by LPS. Enforced overexpression of either A1 or A20 inhibits LPS and cycloheximide-initiated apoptosis. Induction of A1 and A20 does not require synthesis of intermediary proteins, but is dependent on the presence of soluble CD14. In addition, we show that inhibition of signaling by the transcription factor, NF-kappaB, blocks accumulation of A1 and A20 mRNA. Taken together, our findings suggest that LPS directly induces expression of the cytoprotective proteins, A1 and A20, via a CD14-dependent pathway requiring activation of NF-kappaB.

Nitric oxide inhibits lipopolysaccharide-induced apoptosis in pulmonary artery endothelial cells.

Our group recently reported that cultured sheep pulmonary artery endothelial cells (SPAECs) became resistant to lipopolysaccharide (LPS)-induced apoptosis several days after constitutive synthesis of nitric oxide (NO) after adenoviral (Ad) transfer of inducible NO synthase (iNOS) or exposure to the NO donor S-nitroso-N-acetylpenicillamine (SNAP) (E. Tzeng, Y.-M. Kim, B. R. Pitt, A. Lizonova, I. Kovesdi, and T. R. Billiar. Surgery 122: 255-263, 1997). In the present study, we confirmed this observation by establishing stable transfectants after retroviral gene transfer [replication-deficient retrovirus (DFG)] of human iNOS (DFG-iNOS) SPAECs and then used all three approaches (Ad, DFG, and SNAP) to determine underlying mechanisms of this phenomenon. Continuous endogenous production of NO in itself did not cause apoptosis as assessed by phase-contrast microscopy, nuclear morphology, and internucleosomal DNA fragmentation. Prolonged (72-96 h) synthesis of NO, however, after DFG- or replication-deficient adenovirus (Ad. CMV)-iNOS or SNAP (100 microM, 96 h) inhibited LPS-induced apoptosis. The kinetics of such protection suggested that NO may be inducing other gene products. Ad-mediated transfer of manganese superoxide dismutase (MnSOD) decreased the sensitivity of wild-type SPAECs to LPS-induced apoptosis. MnSOD, however, was not induced in an NG-monomethyl-L-arginine (L-NMMA)-sensitive time-dependent fashion after Ad.CMV-iNOS. Other inducible genes that may be affected by NO and that may protect against potential oxidant-mediated LPS-induced apoptosis including 70-kDa heat shock protein, heme oxygenase-1, metallothionein, and Bcl-2 also were not elevated in an L-NMMA-sensitive, time-dependent fashion. Although the candidate gene product underlying NO-induced protection remains unclear, we did note that prolonged synthesis of NO inhibited LPS-induced activation of an interleukin-1beta-converting enzyme-like cysteine protease (cysteine protease protein-32-like) in a dithiothreitol-sensitive fashion, suggesting that S-nitrosylation of an important downstream target of convergence of apoptotic signals may contribute to the sensitivity of SPAECs to LPS.

Lipopolysaccharide-induced NF-kappaB activation in human endothelial cells involves degradation of IkappaBalpha but not IkappaBbeta.

We studied the signal transduction pathways involved in NF-kappaB activation and the induction of the cytoprotective A20 gene by lipopolysaccharide (LPS) in human umbilical vein endothelial cells (HUVEC). LPS induced human A20 mRNA expression with a maximum level 2 h after stimulation. The proteasome inhibitor N-acetyl-leucinyl-leucinyl-norleucinal-H (ALLN) and the tyrosine kinase inhibitor herbimycin A (HMA) blocked A20 mRNA expression and partially inhibited NF-kappaB DNA-binding activity induced by LPS treatment. LPS induced IkappaBalpha degradation at 30-60 min after treatment, but did not induce IkappaBbeta degradation up to 120 min. In contrast, TNF-alpha rapidly induced IkappaBalpha degradation within 5 min and IkappaBbeta degradation within 15 min. Cycloheximide did not prevent LPS-induced IkappaBalpha degradation, indicating that newly synthesized proteins induced by LPS were not involved in LPS-stimulated IkappaBalpha degradation. LPS-induced IkappaBalpha degradation was inhibited by ALLN, confirming that ALLN inhibits NF-kappaB activation by preventing IkappaBalpha degradation. Of note, HMA also inhibited LPS-induced IkappaBalpha degradation. However, tyrosine phosphorylation of IkappaBalpha itself was not elicited by LPS stimulation, suggesting that tyrosine phosphorylation of a protein(s) upstream of IkappaBalpha is required for subsequent degradation. We conclude that in HUVEC, LPS induces NF-kappaB-dependent genes through degradation of IkappaBalpha, not IkappaBbeta, and propose that this degradation is induced in part by HMA-sensitive kinase(s) upstream of IkappaBalpha.

A1 is a constitutive and inducible Bcl-2 homologue in mature human neutrophils.

During the process of terminal differentiation toward mature neutrophils, the anti-apoptotic proteins Bcl-2 and Bcl-x become down-regulated and eventually cease to be expressed, whereas the death-promoting Bcl-2 homologue, Bax, persists. Thus, the disappearance of anti-apoptotic homologues was thought to account for the early demise of mature neutrophils. However, although the survival of mature human neutrophils can be prolonged by a variety of factors, no anti-apoptotic Bcl-2 homologues have previously been identified. Human A1 is a Bcl-2 homologue previously shown to be present in endothelial cells and to convey anti-apoptotic function in vitro. We describe here that human A1 mRNA is constitutively expressed in mature neutrophils and is up-regulated by G-CSF and LPS, agonists that promote neutrophil survival. In addition, we show progressive A1 mRNA accumulation in HL-60 cells during all-trans retinoic acid-driven neutrophilic differentiation. Our findings suggest that A1 may have an important role in neutrophilic development and in modulating mature neutrophil survival.

Fibroblast growth factor-2 inhibits endothelial cell apoptosis by Bcl-2-dependent and independent mechanisms.

Intact endothelium acts as a sensor and transducer of signals and also provides a nonthrombogenic surface at the blood-vascular wall interface. Hence, mechanisms that maintain the integrity of the endothelium are of interest in physiological and pathological states. In this study we show that apoptosis induced by growth factor and serum deprivation of endothelial cells occurs at all phases of the cell cycle and can be blocked by fibroblast growth factor-2 (FGF-2) independently of its mitogenic activity. As the Bcl-2 family of proteins plays a prominent role in regulating cell survival, we attempted to identify Bcl-2 homologues expressed in endothelial cells. Here we demonstrate that, in addition to the previously identified A1, four other members of the Bcl-2 family, Bcl-2, Mcl-1, Bcl-X(L), and Bax, are expressed in endothelial cells. Of these family members, only Bcl-2 is induced by FGF-2. Overexpression of Bcl-2, using a retroviral vector, protects endothelial cells from serum and growth factor deprivation. There is no difference in FGF-2-induced proliferation between Bcl-2-overexpressing cells and those transduced with the empty retroviral vector. At early time points Bcl-2 is not up-regulated, but FGF-2 still has a protective effect. However, FGF-2 protects only adherent endothelial cells but not those that are cultured in suspension. The early effect of FGF-2 is dependent on tyrosine phosphorylation but not on activation of the MAP kinase pathway. Thus, FGF-2 inhibits endothelial cell apoptosis by Bcl-2-dependent and independent mechanisms.

Preparing residents for managed care practice using an experience-based curriculum.

Many U.S. residency graduates will practice in various types of managed care organizations, where they will be expected to arrive skilled in managed care activities such as prescribing with formularies and adhering to preauthorization processes for procedures, referrals, and hospital admissions. Residency programs must prepare their trainees to negotiate for their patients' needs within such systems. This article describes a University of California, Los Angeles, UCLA School of Medicine curriculum that teaches managed care skills to residents in two internal medicine residency training programs. The residents in one program participate in a commercial health maintenance organization plan via a group-model faculty practice. Managed care activities for residents in this program were gradually introduced beginning in 1990. This reflected previous years' gradual yet enforced introduction of managed care activities that occurred for this program's faculty and most group practice physicians in California. Residents in the other program train at a public hospital where managed care practice is simulated. Managed care activities were not required by this program's institution but were voluntarily introduced for their educational value beginning in 1994. Responding to this program's trainee and faculty requests, these activities were rapidly implemented over two years with the goal of preparing residents for joining practices in a market with high managed care penetration. Since 1994, the centerpiece of the curriculum has been residents' participation in ambulatory utilization review and related activities. Residents learn managed care principles through problem-based learning, experiential exercises, and feedback on resource utilization. The curriculum has affected residents' attitudes toward managed care and changed their patterns of referrals and resource use. Residents trained with this curriculum perceive managed care practices as familiar and less intrusive. They submit fewer requests for referrals, perhaps with review in mind. However, precautions may be required to avoid undercare. The authors found that the reduction of referrals requested was greater than what they had expected. Residents may find scrutiny by colleagues intimidating. Also, this curriculum requires a substantial time commitment from residency training, with its already busy teaching agenda. The authors feel that initiating a managed care curriculum is an important investment in time for U.S. residency programs. Given that most graduates of residency programs will have their health care management decisions scrutinized while in practice, the authors feel it is important that residents' first exposure to managed care be while they are still in the supportive residency environment. They believe that early exposure will not only give residents the confidence to overcome the intimidation of colleague scrutiny, but may also give graduates the tools for involvement with the development of future managed care health policy.