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Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

PDF file - 131K, Generation of Trp53+/- mice; Human samples; Virus preparation; HCMV in situ hybridization; HCMV DNA PCR and RT-PCR; Other statistical analysis

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PDF file - 60K, Analysis for MCMV DNA and RNA in muscle and connective tissue in mice infected with MCMV at 4 weeks of age.

PDF file - 600K, Control IHC and additional HCMV IHC in human RMS

Fungi are abundant in the environment, causing our lungs to be constantly exposed to a diverse range of species. While the majority of these are cleared effectively in healthy individuals, constant exposure to spores (especiallyAspergillusspp.) can lead to the development of allergic inflammation that underpins and worsen diseases such as asthma. Despite this, the precise mechanisms that underpin the development of fungal allergic disease are poorly understood. Innate immune cells, such as macrophages (MΦs) and dendritic cells (DCs), have been shown to be critical for mediating allergic inflammation to a range of different allergens. This review will focus on the crucial role of MΦ and DCs in mediating antifungal immunity, evaluating how these immune cells mediate allergic inflammation within the context of the lung environment. Ultimately, we aim to highlight important future research questions that will lead to novel therapeutic strategies for fungal allergic diseases.

Abrogating synaptotoxicity in age-related neurodegenerative disorders is an extremely promising area of research with significant neurotherapeutic implications in tauopathies including Alzheimer’s disease (AD). Our studies using human clinical samples and mouse models demonstrated that aberrantly elevated phospholipase D1 (PLD1) is associated with amyloid beta (Aβ) and tau-driven synaptic dysfunction and underlying memory deficits. While knocking out the lipolytic PLD1 gene is not detrimental to survival across species, elevated expression is implicated in cancer, cardiovascular conditions and neuropathologies, leading to the successful development of well-tolerated mammalian PLD isoform-specific small molecule inhibitors. Here, we address the importance of PLD1 attenuation, achieved using repeated 1 mg/kg of VU0155069 (VU01) intraperitoneally every alternate day for a month in 3xTg-AD mice beginning only from ~11 months of age (with greater influence of tau-driven insults) compared to age-matched vehicle (0.9% saline)-injected siblings. A multimodal approach involving behavior, electrophysiology and biochemistry corroborate the impact of this pre-clinical therapeutic intervention. VU01 proved efficacious in preventing in later stage AD-like cognitive decline affecting perirhinal cortex-, hippocampal- and amygdala-dependent behaviors. Glutamate-dependent HFS-LTP and LFS-LTD improved. Dendritic spine morphology showed the preservation of mushroom and filamentous spine characteristics. Differential PLD1 immunofluorescence and co-localization with Aβ were noted.

Background Intradialytic exercise (IDE) may improve physical function and health-related quality of life. However, incorporating IDE into standard hemodialysis care has been slow due to feasibility challenges. We conducted a multicenter qualitative feasibility study to identify potential barriers and enablers to IDE and generate potential solutions to these factors. Methods We conducted 43 semistructured interviews with healthcare providers and patients across 12 hospitals in Ontario, Canada. We used the Theoretical Domains Framework and directed content analysis to analyze the data. Results We identified eight relevant domains (knowledge, skills, beliefs about consequences, beliefs about capabilities, environmental context and resources, goals, social/professional role and identity, and social influences) represented by three overarching categories: knowledge, skills and expectations: lack of staff expertise to oversee exercise, uncertainty regarding exercise risks, benefits and patient interest, lack of knowledge regarding exercise eligibility; human, material and logistical resources: staff concerns regarding workload, perception that exercise professionals should supervise IDE, space, equipment and scheduling conflict concerns; and social dynamics of the unit: local champions and patient stories contribute to IDE sustainability. We developed a list of actionable solutions by mapping barriers and enablers to behavior change techniques. We also developed a feasibility checklist of 47 questions identifying key factors to address prior to IDE launch. Conclusions Evidence-based solutions to identified barriers to and enablers of IDE and a feasibility checklist may help recruit and support units, staff and patients and address key challenges to the delivery of IDE in diverse clinical and research settings.

A pragmatic cluster-randomized trial (CRT) is a research design that may be used to efficiently test promising interventions that directly inform dialysis care. While the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials provides general ethical guidance for CRTs, the dialysis setting raises additional considerations. In this paper we outline ethical issues raised by pragmatic CRTs in dialysis facilities. These issues may be divided into seven key domains: justifying the use of cluster randomization; adopting randomly allocated individual-level interventions as a facility standard of care; conducting benefit-harm analyses; gatekeepers and their responsibilities; obtaining informed consent from research participants; patient notification; and including vulnerable participants. We describe existing guidelines relevant to each domain, illustrate how they were considered in the Time to Reduce Mortality in End-Stage Renal Disease (TiME) trial (a prototypical pragmatic hemodialysis CRT), and highlight remaining areas of uncertainty. The following is the first step in an interdisciplinary, mixed-methods research project to guide the design and conduct of pragmatic CRTs in dialysis facilities. Subsequent work will expand on these concepts, and where possible, argue for a preferred solution.

Earth's millennial climate cycle has been studied by scientists for decades, but its cause has been lacking. It warms the Earth for several hundred years and melts some of the ice sheets in Greenla...

Hemodialysis is a life-sustaining treatment for persons with kidney failure. However, those on hemodialysis still face a poor quality of life and a short life expectancy. High-quality research evidence from large randomized controlled trials is needed to identify interventions that improve the experiences, outcomes, and health care of persons receiving hemodialysis. With the support of the Canadian Institutes of Health Research and its Strategy for Patient-Oriented Research, the Innovative Clinical Trials in Hemodialysis Centers initiative brought together Canadian and international kidney researchers, patients, health care providers, and health administrators to participate in a workshop held in Toronto, Canada, on June 2 and 3, 2018. The workshop served to increase knowledge and awareness about the conduct of innovative, pragmatic, cluster-randomized registry trials embedded into routine hemodialysis care and provided an opportunity to discuss and build support for new trial ideas. The workshop content included structured presentations, facilitated group discussions, and expert panel feedback. Partnerships and promising trial ideas borne out of the workshop will continue to be developed to support the implementation of future large-scale trials.L’hémodialyse constitue un traitement essentiel au maintien de la vie pour les personnes atteintes d’insuffisance rénale. Les patients hémodialysés voient cependant leur qualité et leur espérance de vie réduites. Des données de recherches probantes, provenant de vastes essais cliniques contrôlés à répartition aléatoire, sont nécessaires pour améliorer l’expérience, les résultats et les soins des patients hémodialysés. Grâce au soutien des Instituts de recherche en santé du Canada (IRSC) et de leur Stratégie de recherche axée sur le patient (SRAP), l’initiative sur les essais cliniques novateurs (ECN) en centres d’hémodialyse a réuni divers intervenants en santé rénale (chercheurs, patients, fournisseurs de soins et administrateurs), du Canada et de partout dans le monde, lors d’un colloque qui s’est tenu à Toronto les 2 et 3 juin 2018. Ce colloque a permis d’accroître la sensibilisation et les connaissances sur la conduite d’essais cliniques novateurs, répartis en grappes, pragmatiques et intégrés aux soins d’hémodialyse de routine. Cette rencontre a également fourni une occasion de discuter de nouvelles idées d’essais cliniques et de susciter les appuis nécessaires à leur réalisation. Le colloque s’est déroulé sous forme de présentations structurées, de discussions animées en groupe et de rétroaction de la part d’un comité d’experts. Les idées de recherche prometteuses et les partenariats issus de ce colloque continueront d’être développés pour soutenir la réalisation d’essais cliniques futurs de grande envergure.

Low rates of cardiovascular preventive therapy with statin medications is a significant public health problem in Canada. There is a pressing need for public health interventions to increase the use of statin medications, especially among high-risk patients. In this article, we present the results of a quality assurance pilot program to provide laboratory-reported Framingham Risk Score (FRS) to physicians. This work was performed in a mixed urban and rural setting in southern Alberta. We provided FRSs and, for high-risk patients, statin treatment recommendations in conjunction with laboratory lipid panel requests. Adhesive labels were supplied to primary care physicians, and space was provided for information necessary for the calculation of the FRS by a laboratory information system. In total, 16 physicians from 4 different clinics participated in the pilot program. Data were collected from October 25, 2014-November 5, 2015, during which time 1266 patients had FRSs from the laboratory. Three hundred twenty-four individuals were identified as high risk for coronary heart disease (≥ 20% 10-year risk) and received a recommendation for treatment with a statin medication in the laboratory result report. These individuals had a 26% relative and a 6.4% absolute increase in statin prescriptions compared with before the pilot program. The laboratory-based provision of FRSs with statin treatment recommendations for high-risk individuals has the potential to significantly increase the use of statin drugs.

This article is about the learning and reflections of six professors who gathered together as a community of scholars to discuss ways of enriching the learning experiences of our students by attempting to build community in the classroom. The first part of the article defines the essence of pedagogical community. The article suggests that pedagogical community is important in the classroom because it contributes to learning and to students’ formation as future leaders of church communities. The second part examines the barriers to pedagogical community, namely, diversity and lack of commitment to community. The final part presents the implications of our findings for pedagogical community and sets forth best practices for the classroom by considering the attitude of the professor, the role of students, and the classroom environment.

This paper discusses aspects of the process design approach used for the Delta House production facility (Mississippi Canyon 254 "A"). Specifically, the challenges associated with the disposition of NGL's (considering constraints imposed by export pipeline requirements and the desire to maximize liquids sales volumes) are addressed. Delta House's process system was initially designed assuming a reservoir composition similar to an analogous nearby well. Based on this composition, liquids from compressor scrubbers were to be routed to production separators with lower operating pressures. This philosophy is very common for offshore facilities and caused minimal liquid recycle and a negligible increase in compression requirements. Subsequent to this initial process design, a well sample phase behavior (PVT) analysis became available. The PVT data was believed to be representative of the majority of the production associated with Delta House. The PVT data indicated that the reservoir had an approximate stock tank gas-to-oil ratio (GOR) of 2100 and 38° API crude oil gravity. These PVT results represented a significant change from the initially assumed composition. Additionally, the reservoir fluid was very rich with condensate, particularly propanes (C3's), butanes (C4's), and pentanes (C5's). A significant liquid recycle and a drastic increase in compression requirements were observed when the compositional basis of the reservoir was entered into the steady-state process simulator. In addition, meeting the oil pipeline Reid Vapor Pressure (RVP) specification became a significant challenge due to the rich nature of the crude. The current liquid handling philosophy no longer appeared suitable, and various options were quickly investigated and evaluated. The two most practical options were direct injection of the condensate into the gas pipeline and a full crude stabilizer. It was determined that a hybrid (a Condensate Stabilization System) of the two options was the most economical option due to the ability to recombine the stabilized condensate with the crude oil for sales. This paper addresses the reasons, benefits, and methodology of installing a Condensate Stabilization System on the Delta House Floating Production System (FPS). It also discusses the process equipment that composes the system, the intended operating conditions, as well as the effects of seasonal variables (oil pipeline RVP specification and ambient temperatures). A Condensate Stabilization System provides a means to optimize facility production and allows for better RVP control. This is achieved by controlling the reboiler temperature which correlates to the amount of light ends that are recycled to the bulk separation train. It also greatly reduces compression and horsepower requirements. Finally, a condensate stabilization system affords operators the ability to achieve greater margins by providing the flexibility to move liquids from the gas processing and sales system to the oil system.

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies., Wellcome Trust (London, England) (Core Award 090532/Z/09/Z), Wellcome Trust (London, England) (Senior Investigator Award 095552/Z/11/Z ), Wellcome Trust (London, England) (WT095908), Wellcome Trust (London, England) (WT109497), Wellcome Trust (London, England) (WT098051), Wellcome Trust (London, England) (WT086084/Z/08/Z), Wellcome Trust (London, England) (WT100956/Z/13/Z ), Wellcome Trust (London, England) (WT097307), Wellcome Trust (London, England) (WT0855322/Z/08/Z ), Wellcome Trust (London, England) (WT090770/Z/09/Z ), Wellcome Trust (London, England) (Major Overseas program in Vietnam grant 089276/Z.09/Z), Medical Research Council (Great Britain) (grant G0801823), Biotechnology and Biological Sciences Research Council (Great Britain) (grant BB/I02593X/1), Biotechnology and Biological Sciences Research Council (Great Britain) (grant BB/I021213/1), Zhongguo ke xue ji shu qing bao yan jiu suo. Office of 863 Programme of China (2012AA02A201), National Basic Research Program of China (2011CB809201), National Basic Research Program of China (2011CB809202), National Basic Research Program of China (2011CB809203), National Natural Science Foundation of China (31161130357), Shenzhen Municipal Government of China (grant ZYC201105170397A), Canadian Institutes of Health Research (grant 136855), Quebec Ministry of Economic Development, Innovation, and Exports (PSR-SIIRI-195), Germany. Bundesministerium für Bildung und Forschung (0315428A), Germany. Bundesministerium für Bildung und Forschung (01GS08201), Germany. Bundesministerium für Bildung und Forschung (BMBF-EPITREAT grant 0316190A), Deutsche Forschungsgemeinschaft (Emmy Noether Grant KO4037/1-1), Beatriu de Pinos Program (2006 BP-A 10144), Beatriu de Pinos Program (2009 BP-B 00274), Spanish National Institute for Health (grant PRB2 IPT13/0001-ISCIII-SGEFI/FEDER), Japan Society for the Promotion of Science (fellowship number PE13075), Marie Curie Actions Career Integration (grant 303772), Fonds National Suisse del la Recherche, SNSF, Scientifique (31003A_130342), National Center for Biotechnology Information (U.S.) (U54HG3067), National Center for Biotechnology Information (U.S.) (U54HG3273), National Center for Biotechnology Information (U.S.) (U01HG5211), National Center for Biotechnology Information (U.S.) (U54HG3079), National Center for Biotechnology Information (U.S.) (R01HG2898), National Center for Biotechnology Information (U.S.) (R01HG2385), National Center for Biotechnology Information (U.S.) (RC2HG5552), National Center for Biotechnology Information (U.S.) (U01HG6513), National Center for Biotechnology Information (U.S.) (U01HG5214), National Center for Biotechnology Information (U.S.) (U01HG5715), National Center for Biotechnology Information (U.S.) (U01HG5718), National Center for Biotechnology Information (U.S.) (U01HG5728), National Center for Biotechnology Information (U.S.) (U41HG7635), National Center for Biotechnology Information (U.S.) (U41HG7497), National Center for Biotechnology Information (U.S.) (R01HG4960), National Center for Biotechnology Information (U.S.) (R01HG5701), National Center for Biotechnology Information (U.S.) (R01HG5214), National Center for Biotechnology Information (U.S.) (R01HG6855), National Center for Biotechnology Information (U.S.) (R01HG7068), National Center for Biotechnology Information (U.S.) (R01HG7644), National Center for Biotechnology Information (U.S.) (DP2OD6514), National Center for Biotechnology Information (U.S.) (DP5OD9154), National Center for Biotechnology Information (U.S.) (R01CA166661), National Center for Biotechnology Information (U.S.) (R01CA172652), National Center for Biotechnology Information (U.S.) (P01GM99568), National Center for Biotechnology Information (U.S.) (R01GM59290), National Center for Biotechnology Information (U.S.) (R01GM104390), National Center for Biotechnology Information (U.S.) (T32GM7790), National Center for Biotechnology Information (U.S.) (R01HL87699), National Center for Biotechnology Information (U.S.) (R01HL104608), National Center for Biotechnology Information (U.S.) (T32HL94284), National Center for Biotechnology Information (U.S.) (HHSN268201100040C), National Center for Biotechnology Information (U.S.) (HHSN272201000025C), Lundbeck Foundation (grant R170-2014-1039, Simons Foundation (SFARI award SF51), National Science Foundation (U.S.) (Research Fellowship DGE-1147470)

In our effort to develop high-affinity ligands for the dopamine transporter which might find potential use as cocaine medication, a polar hydroxy substituent was introduced into the piperidine ring of one of our disubstituted lead analogues derived from 1-[2-(diphenylmethoxy)-ethyl]-4-(3-phenylpropyl)piperazine (GBR 12935). Both cis- and trans-3-hydroxy derivatives were synthesized and the racemic trans isomer, (+/-)-5, was further resolved into two enantiomers. Newly synthesized compounds were characterized for their binding affinity at the dopamine, serotonin, and norepinephrine transporter systems in rat brain. The two enantiomers (+)-5 and (-)-5 exhibited marked differential affinities at the dopamine transporter with (+)-5 being 122-fold more potent than (-)-5 in inhibiting radiolabeled cocaine analogue binding (IC(50); 0.46 vs 56.7 nM) and 9-fold more active for inhibiting dopamine uptake (IC(50); 4.05 vs 38.0 nM). Furthermore, the most active (+)-5 was 22-fold more potent at the dopamine transporter compared to the standard GBR 12909. Absolute configuration of one of the enantiomers was determined unambiguously by X-ray structural analysis. In in vivo locomotor activity studies, the enantiomer (+)-5 and the racemic (+/-)-5, but not (-)-5, exhibited stimulant activity with a long duration of effect. All three compounds, (+)-5, (-)-5, and (+/-)-5, within the dose range tested, partially (50%) but incompletely (80%) produced cocaine-like responses in mice trained to discriminate 10 mg/kg ip cocaine from vehicle. Compound (-)-5 was distinctive in this regard in that, unlike (+)-5 and (+/-)-5, it did not affect locomotor activity yet, but similar to them, was able to engender (albeit incompletely) cocaine-like responses.

The figures shown in this chapter are 100 % computer visualizations and consequently have been kept separate from the digitally augmented plates in the previous chapter. The simulations are illustrated in a double-page spread format, with the left page being sunrise and the right side sunset. In all these figures, north will be towards the top, east to the left, and west to the right – in other words an SCT type of image. Image scales may vary, but you can compare these with the craters in the plates in the previous chapter. The title numbering system corresponds to the map sheet numbers from last chapter. In all cases the simulated images are each separated 3° apart in terms of their selenographic colongitude, or approximately 6 h difference in Earth time. The sub-solar point has been kept fixed at 0° latitude, and the libration has been set to be on the lunar equator on a meridian line of 0° latitude (Fig. 4.1).

In order to evaluate the long-term results of patients treated conservatively for plantar heel pain, a telephone follow-up survey was conducted. After eliminating those patients with worker's compensation-related complaints and those with documented inflammatory arthritides, data on 100 patients (58 females and 42 males) were available for review. The average patient was 48 years old (range 20–85 years). The average follow-up was 47 months (24–132 months). Clinical results were classified as good (resolution of symptoms) for 82 patients, fair (continued symptoms but no limitation of activity or work) for 15 patients, and poor (continued symptoms limiting activity or changing work status) in 3 patients. The average duration of symptoms before medical attention was sought was 6.1, 18.9, and 10 months for the three groups, respectively. The three patients with poor results all had bilateral complaints, but had no other obvious risk factors predictive of their poor result. Thirty-one patients stated that, even with the understanding that surgical treatment carries significant risk, they would have seriously considered it at the time medical attention was sought; twenty-two of these patients eventually had resolution of symptoms. Although the treatment of heel pain can be frustrating due to its indolent course, a given patient with plantar fasciitis has a very good chance of complete resolution of symptoms. There is a higher risk for continued symptoms in overweight patients, patients with bilateral symptoms, and those who have symptoms for a prolonged period before seeking medical attention.

A van-mounted ruby lidar system has been developed for the remote single-ended measurement of smoke plume transmittance at ranges of 150–500 m. The measurement of transmittance is obtained by comparing the clear air lidar return from the near side of the plume with that from the far side. The system performance has been tested using synthetic targets of known transmittance, and its aclidar curacy limitation has been found to be photomultiplier tube afterpulsing. Results from these target tests as well as field tests using real power plant smoke plumes where comparison telephotometer measurements were made are discussed in terms of accuracy for the determination of plume transmittance.

We examined the effects of rosiglitazone: 1) on glucose homeostasis, insulin action, beta-cell function, and plasma adiponectin and TNF-alpha (TNF-alpha) levels; and 2) the expression of adipose tissue TNF-alpha and adiponectin mRNA in African Americans with parental history of type 2 diabetes and with varying degrees of glucose intolerance.The study groups comprised 11 African Americans with normal glucose tolerance and six with diabetes and impaired glucose tolerance. The glucose-intolerant subjects received rosiglitazone (4-8 mg/day) every morning for 12 weeks. They underwent oral glucose tolerance test (OGTT) and subcutaneous adipose tissue biopsy (under local anesthesia) before and after 12 weeks of rosiglitazone therapy. Beta cell function and insulin resistance were calculated by using homeostasis model assessment (HOMA). Adipose tissue gene expression (mRNA) was measured by real-time polymerase chain reaction in both groups.Rosiglitazone monotherapy improved both fasting and two-hour serum glucose levels during OGTT in the glucose-intolerant group. However, mean serum insulin and C-peptide levels did not change when compared with baseline. Rosiglitazone monotherapy improved insulin resistance but not overall beta-cell secretion. Mean adiponectin levels at fasting and two hours after oral glucose ingestion were significantly (50%) lower in the glucose-intolerant group than in the control group. Rosiglitazone monotherapy significantly increased plasma adiponectin levels at fasting and two hours after oral challenge by two-fold in the glucose-intolerant group. Mean plasma TNF-alpha levels were not significantly different at fasting and after two hours during OGTT. Rosiglitazone had no significant effect on plasma TNF-alpha levels during OGTT. No significant differences were seen in the expression of adipose tissue TNF-alpha and adiponectin mRNA in the groups at baseline. Rosiglitazone did not significantly change the adipose tissue adiponectin and TNF-alpha mRNA. Rosiglitazone was well tolerated, without experiencing weight gain, edema, and liver function test abnormality in the glucose intolerant subjects.Rosiglitazone improved glucose homeostasis and insulin resistance in high-risk African Americans. We found that adiponectin was lower in the glucose-intolerant group, while TNF-alpha was similar. While rosiglitazone increased plasma adiponectin, it had no effect on adipose tissue adiponectin mRNA. In addition, rosiglitazone had no effect on plasma TNF-alpha and adipose tissue TNF-alpha mRNA. We conclude that the metabolic effects of rosiglitazone could be mediated by adiponectin but not TNF-alpha in African Americans with glucose intolerance. Our study demonstrates that: 1) the role of adipocytokines in the etiology of type 2 diabetes in African Americans is complex; and 2) that adiponectin, but not TNF-alpha, could mediate the metabolic benefits of thiazolidinediones in African Americans with glucose intolerance.

The association between Chance fractures and intra-abdominal injuries is reported to be as high as 89 per cent. Because prior studies were small series or case reports, we conducted a multicenter review to learn the true association between Chance fractures and intra-abdominal injuries as well as diagnostic trends. Trauma registry data, medical records, and radiology reports from 7 trauma centers were used to characterize 79 trauma patients with Chance fractures. Initial methods of abdominal assessment were computed tomography (CT) scan (79%), clinical examination (16%), and diagnostic peritoneal lavage (DPL) (5%). Twenty-six (33%) patients had intraabdominal injuries of which hollow viscus injuries predominated (22%). Twenty patients (25%) underwent laparotomy. The presence of an abdominal wall contusion and automobile restraint use were highly predictive of intra-abdominal injury and the need for laparotomy. The association between a Chance fracture and intra-abdominal injury is not as high as previously reported. CT scan has become the primary modality to assess the abdominal cavity of patients with Chance fractures, whereas the role of DPL has diminished.

Three porous ceramic bone graft materials were compared with regard to their ability to heal a 2.5 cm defect created surgically in a bilateral canine radius model. The ceramic materials were analyzed at 12 and 24 weeks after surgery and included tricalcium phosphate, hydroxyapatite, and collagen hydroxyapatite, which contained a mixture of 35% tricalcium phosphate and 65% hydroxyapatite with added collagen. Each material was evaluated alone and with added bone marrow aspirate. All the implants were compared with a graft of autogenous cancellous bone in the contralateral radius. Biomechanical testing and radiographic evaluation revealed that the addition of bone marrow aspirate was essential for tricalcium phosphate and hydroxyapatite to achieve results comparable with those of cancellous bone. Collagen hydroxyapatite performed well without the addition of bone marrow, although the addition of marrow did have a positive effect. Further qualitative radiographic and histological analysis demonstrated that tricalcium phosphate was the only ceramic that showed any sign of degradation at 24 weeks. This observed degradation proved to be an important factor in evaluating radiographs because the radiodensity of collagen hydroxyapatite and hydroxyapatite interfered with the determination of radiographic union. At 24 weeks, tricalcium phosphate with bone marrow was the material that performed most like cancellous bone. In this study, the biomechanical and radiographic parameters of tricalcium phosphate with bone marrow were roughly comparable with those of cancellous bone at 12 and 24 weeks. Tricalcium phosphate was the only implant that showed significant evidence of degradation at 24 weeks by both histological and radiographic evaluations, and this degradation took place only after a degree of mechanical competence necessary for weight-bearing was achieved.

As chief of three pediatric services in three quite different cities—New Haven, Brooklyn, and Rochester, New York—I have been involved in studies related to quality assurance issues. Although the studies have been hospital based, some inpatient and some outpatient, I believe that extrapolations to the office practice of pediatrics are legitimate. A review of some of these and related studies by others of the quality of the medical care of children; some highlighting of major problems and thus challenges for future pediatric care; and some recommendations will be the subjects of this report. Major underlying theses will be (1) that there is a serious gap between what we know should be done for children and what we do, (2) that this has serious quality and cost consequences, and (3) that we are not using modern information processing and analysis techniques to assist in improving the quality of care in either hospital or office settings. Finally, I will make some suggestions about how the knowledge-performance gap might be reduced.

We studied the clinical and pathologic features of 22 cases of granulomas of the conjunctiva or eyelids. All cases showed the histologic features of the Splendore-Hoeppli phenomenon, that is, a giant cell and eosinophil granulomatous reaction to an antigen-antibody precipitate originally described in relation to parasites or fungi. In four of seven typical cases selected for detailed description unidentified nematodes were found to be the cause of the condition. In light of these findings together with a review of similar "allergic granulomas" reported both in ocular tissues and elsewhere in the body, we considered the cause in the remaining cases. All 22 cases may have been caused by nematodes, as seems, probable in 14 of them, or the causative antigens may have been of widely different kinds. Although in our cases all ocular granulomas had an identical histology, this study did not resolve the problem of those cases where no causative agent was found. Thorough investigation of such cases in the future and the demonstration of their cause may elucidate the wider problem of nonocular allergic granulomas.